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Preference: Cardiology and Cardiac Surgery

99

Cardiac tamponade in undiagnosed systemic lupus erythematosus

A 22-year-old woman presented with a 3-day history of fever, retrosternal chest pain and exertional dyspnoea. Her heart rate was 130 bpm with a blood pressure level of 109/68 mmHg. Physical examination suggested tamponade: distended jugular veins, pulsus paradoxus and muffled heart tones. The chest radiography was notable for the characteristic water-bottle sign (Figure, A).1 Contrast-enhanced chest computed tomography demonstrated a massive pericardial effusion (Figure, B) associated with venous engorgement of the superior and inferior vena cava (SVC, IVC), prevascular space (arrows), and bilateral axillary veins (arrowheads). An emergency thoracoscopic pericardial window was performed and 620 mL of bloody fluid was drained.

The presence of anti-nuclear, anti-double-stranded DNA, anti-Smith antibodies and hypocomplementaemia supported the diagnosis of systemic lupus erythematosus.2 The patient recovered after 1 week of intravenous methylprednisolone pulse therapy. At an 8-month follow-up, there have been no recurrences.

Figure

A

B

How health technology helps promote cardiovascular health outcomes

Health technology in the hands of cardiac patients — helpful, hindrance, or hesitate to say?

Cardiovascular disease (CVD) is a leading cause of death and hospital admissions in Australia.1 Almost a third of patients will have a recurrence such as myocardial infarction (MI), stroke, heart failure and death within 5 years.2 Reductions of at least 80% in these events can be achieved through secondary prevention behaviours, including taking cardioprotective medications as prescribed, ceasing smoking, increasing physical activity and consuming a healthy diet.3 The most comprehensive and proven of strategies to support secondary prevention is cardiac rehabilitation. This is an evidence-based, cost-effective method to reduce CVD deaths, assist recovery and promote secondary prevention through reduction of cardiovascular risk factors.

The strength of secondary prevention success in cardiac rehabilitation ultimately depends on patients’ awareness, willingness and capacity to make lifestyle changes and to engage in the required behaviours. Patients must have a strong commitment to their health to sustain secondary prevention behaviours for the rest of their lives, often without direct evidence of benefit, as CVD is asymptomatic in the majority of cases.3 However, cardiac rehabilitation is widely underutilised, with less than a third of eligible patients attending the sessions and dropout rates estimated at 25%. In the absence of support, many patients struggle with sustaining the requisite behaviours.

Medications are a prime example of this struggle. Less than two-thirds of patients are reported to persist with all prescribed medications by 1 year following MI.4 The reasons given for discontinuation are largely self-determined, emphasising the importance of the patients’ understanding and engagement.5 Similar issues are present for most secondary prevention behaviours. At 6 months after MI, 27% of patients smoked, 26% consumed an unhealthy diet and 59% did not exercise enough.3 The key reasons identified for patients’ struggles are a lack of awareness that treatments must be long term to achieve effective prevention, and forgetting to follow recommendations.5 Patient education is necessary, but specialised support is often required for sustained behaviour change. Technology, particularly mobile technology, offers a solution for support for long term behaviour change and may also augment existing secondary prevention programs, such as cardiac rehabilitation.

Adoption of mobile technologies, such as mobile phones, smart phones and tablets that provide internet access, has been widespread in Australia.6 Rapid growth in popularity and technological advances have also occurred in wearable devices for tracking behaviours, such as fitness activities, that connect with mobile phones. These technologies and related applications can efficiently enable long term support for patients and provide memory prompts for behaviours. However, there has been such rapid evolution of technologies that we ask: are health technologies helpful, a hindrance, or should we hesitate to say?

Are health technologies helpful?

The evidence indicates that well designed and often simple technologies can improve patient outcomes in multiple cardiovascular risk factors.7 The most consistent evidence of benefit from health technologies is for coronary heart disease compared with other cardiovascular diseases.8 Simple short-message service (SMS) interventions delivered regularly can improve awareness and prompt actions, which may otherwise be forgotten. Text messages double the odds of adhering to medications and the Australian TEXT ME program has improved cardiovascular disease risk factor profiles.9 Emerging evidence indicates that many more risk factors may also be addressed through text messages and mobile phone apps, and potentially decrease dropout from cardiac rehabilitation.8,10 In addition, wearable activity trackers provide reliable information on steps and time spent in moderate to vigorous physical activity, which can be monitored, used for goal-setting and shared with treating doctors.11

There may be a temptation to assume that health technology is not applicable to cardiac patients because of their older age and lack of experience; however, such patients may be more ready and willing to use health technology than previously suspected. At least two-thirds of cardiac patients (67%) use the internet and at least half (50%) use mobile technologies for health, with higher rates of acceptance of health technology in cardiac rehabilitation participants (74%).12

Are health technologies a hindrance?

Several key issues hinder uptake and complicate recommendations for patient-facing technology in regular clinical practice. There is a proliferation of publicly available health technologies suitable for cardiac patients, particularly mobile phone apps, alongside a paucity of research-based evidence to support selection.7 Quality too is generally low, and popularity is a poor indicator. For instance, an evaluation of patient engagement, quality and safety of 1046 health care-related, patient-facing apps for chronic disease found that only 43% (iOS, Apple) and 27% (Android, Google) were actually likely to be useful.13 A recent review of mobile phone interventions for secondary prevention of cardiovascular disease did not identify any intervention that resulted in a negative impact, but six of the 28 interventions reviewed had no benefit.8 Owing to the poor quality of the studies included, it is difficult to distinguish the features that independently predict success; however, the use of text messaging, telemonitoring and interaction may have been important. In a similar way, popular weight loss apps do not incorporate successful behaviour change techniques and many have inaccurate content. The motivation of app developers must be carefully considered given the rise of pro-smoking apps disguised as educational games. At best, patients may experience no benefits from using health technology, and at worst, patients may question and disregard credible advice given by health professionals. Patients have few sources of advice for selection and use of health technologies, as physicians, like patients, have varying capacity and interest in using them. Previous experience, education, confidence and interaction with early adopters to understand how to interface with the health app and with the patient using the app are all required for success.14 Patients who are older, have little or no prior experience with technology and who have lower levels of education are less likely to be interested and have lower expectations of success or benefit from using technology for their health.12 The same could be argued for health professionals. This is important because, for health technologies that do prove useful, positive staff attitudes may offset the lower levels of expertise or interest present in older people and in those with lower education.

Should we hesitate to say?

The rapid advances in health technology, the mass of publicly available apps and programs, and the inability of research to keep pace are major factors affecting our ability to definitively determine whether health technologies are a help or a hindrance. These factors make it difficult to identify the technologies that are evidence-based and free from unintended negative consequences.15 However, there are a few shortcuts. For instance, there is no single repository for patient-based health technologies for cardiovascular secondary prevention, nor is there an accrediting or regulatory system for quality or effectiveness. There has been some attempt to catalogue apps, but the process is slow and apps are often modified by the time of publication. Regulation of health technologies, such as mobile phone apps, is poorly developed. A balance is needed between two polar possibilities: government regulation, as used for implanted medical devices, which is rigorous but slow and expensive; and self-regulation by technology companies through checklist certification, which is dependent on the company ethics.16 App stores such as those of Apple and Google currently vet apps sold in their stores, but the emphasis is on security, not on the quality or credibility of the app.17 Ultimately consumers must decide. One shortcut to ensuring credible content is to only use or recommend health technologies and health apps developed by reliable institutions, such as the Heart Foundations of Australia, Britain and Canada. However, the gains in credibility and time-saving from using this shortcut occur at a trade-off in diversity, innovation and personalisation for patients.

A principles-based approach may be more appropriate and feasible to discriminate the features of technology that encourage consumer uptake and promote appropriate behaviour change effectively. These principles have been highlighted for apps for the secondary prevention of CVD in a recent review12 and are relevant to most health technologies. Key elements to consider include simplicity, credibility of content, behaviour change components, real-time tracking, reward system, personalisation, social features and attention to privacy of data collected. A positive, but discerning attitude to patient-facing health technology is required, much the same as with any new health treatments, to maximise patient outcomes and ensure equitable access. Regular screening to identify effective health technology has become a necessary component of health professional life, equivalent to keeping up to date with effective medications and techniques. Evidence-based practice was introduced to medical curricula to help ensure the most effective treatment for an individual patient. Likewise, it is now time to introduce screening and selection systems for health technologies into health professional education.

In summary, the evidence suggests that mobile technologies will improve access to and participation in secondary prevention activities, but careful consideration is needed to ensure that the most effective and acceptable technologies are incorporated into patient care.

“Congenital heart health”: how psychological care can make a difference

An integrated approach incorporating both physical and mental health is critical to “congenital heart health”

Congenital heart disease (CHD) affects more than 2400 Australian babies each year. It is the most common cause of admission to paediatric intensive care in the neonatal period,1 a leading cause of infant death2 and one of the leading causes of disease-related disability in children under 5 years of age.3 In Australia and around the world, the landscape of CHD care is rapidly evolving. With advances in medicine, survival has markedly improved over the past two decades4 and the best estimates suggest that the total population, from newborns through to adults living with CHD, now represents well over 65 000 Australians.5 These gains in survival are a triumph, but paradoxically, they bring new challenges. Earlier diagnosis, more complex treatment choices, longer survivorship and a need for transition from paediatric to adult cardiac services lead us into new territory. Embedded in each of these challenges are a range of psychological complexities, foremost of which is how to best support the wellbeing of people with CHD across a lifetime. “Congenital heart health” requires an integrated, life course approach — with equal emphasis on the physical and the psychological — beginning before birth, through infancy to adulthood. This article presents the evidence for such an approach, highlighting the areas where evidence is lacking and calling for national standards of mental health care in CHD.

Beginning before birth: the mental health of expectant parents

Fetal diagnosis of CHD has changed clinical care. Half of all babies who need heart surgery in the first year of life are now diagnosed while in the womb.6 A major advantage of fetal diagnosis is that potentially unstable newborns can be delivered close to specialised paediatric cardiac services, reducing morbidity and improving survival.7,8 Fetal diagnosis also facilitates early family counselling regarding the nature of the baby’s heart abnormality and expected prognosis. But when a parent hears words such as “your baby has tetralogy of Fallot” their world stops. Fetal diagnosis of any abnormality, major or minor, precipitates an emotional crisis for expectant parents. Threats to the health of the fetus have long been recognised as an important risk factor for psychological disturbance during pregnancy, which in turn indicates a high risk of ongoing psychiatric disorders postpartum. Research has shown that one in three mothers and fathers of infants with complex CHD report symptoms that meet clinical criteria for depression, and about 50% of parents report severe stress reactions consistent with a need for clinical care up to 1 year after their baby’s diagnosis.9 These rates far exceed documented rates of perinatal depression and anxiety in the general community10 and as health care providers, we often markedly underestimate the severity and potential consequences of these symptoms.

There is now overwhelming evidence that depression and anxiety in the perinatal period (from conception to the end of the first postnatal year) can have devastating consequences, not only for the person experiencing it, but also for his or her children and family. Parents with high distress report poorer physical health,11 greater parenting burden,12 higher health service use13 and more suicidal ideation14 compared with parents of sick children with lower distress. At least 14 independent prospective studies have demonstrated a link between maternal antenatal stress and child neurocognitive, behavioural and emotional outcomes.15 Acknowledging these findings is not to blame parents — not in any way, not at all. But to not talk about this, to not address the significant emotional toll of CHD, is to not provide optimal care.

Early life experiences can have profound consequences

Diagnosis of a life-threatening illness during a child’s formative years can have far-reaching effects that ripple through the family and across a lifetime. Infants with complex CHD experience a range of uncommon and painful events, such as separation from their mother at birth, urgent transfer to specialised intensive care, frequent invasive medical procedures, feeding difficulties and withdrawal from narcotic pain relief. These early life experiences can have profound consequences for the developing child, shaping brain development, the body’s immune system and responses to stress. Studies of individuals exposed to high levels of stress early in life consistently show that the experience of early adversity is associated with disrupted child–parent attachment and with alterations in the developmental trajectories of networks in the brain associated with emotion and cognition.16

From a neurodevelopmental perspective, children with CHD experience greater difficulties compared with their healthy peers. The risk and severity of neurodevelopmental impairment increases with greater CHD complexity, the presence of a genetic disorder or syndrome, and greater psychological stress. During infancy, the most pronounced difficulties occur in motor functioning. By early childhood, studies show that children with complex CHD have an increased risk of neurodevelopmental impairment, characterised by difficulties in fine and gross motor skills, speech and language, attention, executive functioning, emotion regulation and behaviour.17 Emotionally, 15–25% of parents report significant internalising (eg, anxiety, depression, somatisation) or externalising (eg, aggression) difficulties in their child.18 Few studies have used validated clinical assessments, but those studies that have included a clinical assessment report psychiatric illness in more than 20% of adolescents and young adults with CHD. There is also a diagnostic rate of attention deficit and hyperactivity disorder up to four times higher than in the general population.18

Navigating the transitions of adolescence

Young people must not only navigate the typical transitions of adolescence and early adulthood, they also face the challenges that come with developing a sense of identity and autonomy in the context of CHD while, at the same time, breaking the bonds formed with their paediatric team and transitioning to adult cardiovascular care. Clinicians lose their “clinical hold” on so many patients during this process, with an alarmingly high proportion of adults with CHD (24–61%) not receiving the recommended cardiac care.5,19,20 This can have catastrophic health consequences,5 yet our understanding of the factors that influence transition is wanting. In 2013, the Cardiac Society of Australia and New Zealand published a statement outlining best practices in managing the transition from paediatric to adult CHD care.21 This statement recognises the role that psychological factors play in shaping young people’s capacity to manage their heart health care, in addition to clinical, familial and practical factors.

Living with CHD into adulthood

Our understanding of the psychology of adult CHD lags decades behind our knowledge of children’s experiences. While neurodevelopmental clinics have been established at several paediatric cardiac centres across Australia, little attention is paid to neurocognitive health in adult CHD care. Without effective intervention, hardships encountered during infancy and childhood can persist for years after diagnosis and treatment. It is also possible for difficulties to emerge for the first time in adulthood, with heart failure, atrial fibrillation, cardiac surgery and recurrent strokes increasing vulnerability to neurocognitive impairment in adults with CHD. A meta-analysis of 22 survey-based studies of emotional functioning in adolescents and adults with CHD found no differences from the norm;22 however, studies using clinical interviews have found that one in three adults with CHD report symptoms of anxiety or depression warranting intervention.23 The vast majority of these adults go untreated.

An integrated psychology service dedicated to CHD

In 2010, we established an integrated clinical psychology service dedicated to CHD. Located across the Sydney Children’s Hospitals Network, we provide a statewide mental health service for children and young people with all forms of heart disease and their families (Box). Evidence-based, psychologically informed care and a variety of interventions can prevent or relieve psychological morbidity.24 National (beyondblue, 2011) and international (International Marcé Society, 2013) authorities now recognise and endorse psychosocial assessment for depression and anxiety in the perinatal period as part of routine clinical care. Integrating psychosocial assessment within existing health services has been shown to improve treatment uptake, as well as mental health and parenting outcomes, up to at least 18 months postpartum.24 Indeed, integrating psychosocial assessment within a clinical setting with which families are already engaged is a key factor distinguishing successful and unsuccessful early mental health interventions. Providing tailored skills-based training and support to staff also has the potential to overcome a range of patient (eg, stigma, cost), provider (eg, limited awareness, low confidence), and health system (eg, cost, under-prioritisation) factors that can prevent access to care. Moreover, there are costs to not offering mental health care. In neonatal intensive care, for example, targeted interventions significantly reduce maternal depression and anxiety, increase positive parent–infant interactions, and reduce health service costs by reducing the length of stay at the neonatal intensive care unit and total hospital admission.25

A call for national standards of mental health care in CHD

While there may be deep sadness associated with many aspects of CHD, there may also be deep hope and, for many, good health. Early intervention can make a profound difference for families and influence a lifetime of outcomes for a child. To transition CHD to “congenital heart health”, equal emphasis must be placed on both physical and mental health so that the successes in physical care are not undermined by the absence of adequate emotional care. Across the CHD continuum, there are still huge gaps in access to mental health services. To start to address these gaps, we call for the formation of a multidisciplinary working group to develop national standards of mental health care in CHD. We also advocate strongly for more Australian research across the discovery-to-translation pipeline such that, from early life in the womb through to adulthood, we can better understand — and prevent or assuage — the difficulties that our patients and their families experience.

Box –
Integrated model of psychological care dedicated to congenital heart disease and based at the Heart Centre for Children

National Institute for Health and Care Excellence. Antenatal and postnatal mental health: clinical management and service guidance. NICE clinical guidelines, no. 192 (updated edition). London: NICE, 2014.

The clinical utility of new cardiac imaging modalities in Australasian clinical practice

Cardiac imaging is a rapidly evolving field, with improvements in the diagnostic capabilities of non-invasive cardiac assessment. In this article, we seek to introduce family physicians to the two main emerging technologies in cardiac imaging: computed tomography coronary angiography (CTCA) to evaluate chest symptoms consistent with ischaemia and exclude coronary artery disease; and cardiovascular magnetic resonance (CMR) imaging for evaluating cardiac morphology, function and presence of scar. These modalities are now in routine clinical practice for cardiologists in Australia and New Zealand. We provide a practical summary of the indications, clinical utility and limitations of these modern techniques to help familiarise clinicians with the use of these modalities in day-to-day practice. The clinical vignettes presented are cases that may be encountered in clinical practice. We searched the PubMed database to identify original papers and review articles from 2008 to 2016, as well as specialist society publications and guidelines (Society of Cardiovascular Computed Tomography, Society for Cardiovascular Magnetic Resonance, Cardiac Society of Australia and New Zealand, and Australian and New Zealand Working Group for Cardiovascular Magnetic Resonance), to formulate an evidence-based overview of new cardiac imaging techniques, as applied to clinical practice.

Part 1: Computed tomography coronary angiography for clinicians

CTCA is a non-invasive coronary angiogram, using electrocardiogram (ECG)-gated CT. The accuracy of CTCA has been well established in three large multicentre studies, with a negative predictive value approaching 100%, making it an excellent “rule out” test.1 This means that a normal CTCA showing no coronary plaque or stenosis accurately correlates to absence of disease on invasive angiography. Prognostic data have shown that a negative CTCA has very low event rate (< 1%), whereas increasing levels of disease seen on CTCA are associated with increasing risk of myocardial infarction and death over 5 years for both men and women.2

CTCA has been formally tested in randomised trials of chest pain in the emergency department, showing more rapid discharge and decreased health care costs, including in the Australian health system.3,4

The radiation dose for CTCA has decreased dramatically in recent years, with current generation scanners able to image the entire heart and coronary arteries for 2–3 mSv (equivalent to annual background radiation), and < 1 mSv in appropriate patients (similar to a mammogram). Thus, CTCA is gaining traction in clinical practice to rule out coronary artery disease (CAD) in a variety of clinical situations.

The primary use for CTCA is to exclude significant coronary artery stenosis in patients with symptoms consistent with coronary ischaemia due to potential stenotic CAD (harnessing the near 100% negative predictive value of CTCA). Application of the test in this manner is appropriate for patients with chest pain syndromes, with angina equivalent symptoms (eg, dyspnoea), to exclude graft stenosis in symptomatic patients after coronary artery bypass surgery, and also for patients with ongoing symptoms despite negative results from functional tests such as nuclear or echocardiography stress tests (as functional tests may return false-negative results). The Society of Cardiovascular Computed Tomography has published Appropriate Use Criteria,5 and the Cardiac Society of Australia and New Zealand has produced guidelines on non-invasive coronary imaging (Box 1).6

Clinical vignette 1: A 55-year-old woman presents to her general practitioner with dyspnoea on exertion, and risk factors of obesity and hypertension. A nuclear single-photon emission computed tomography myocardial perfusion scan is reported as positive for “mild apical ischaemia”. Computed tomography coronary angiography (CTCA) is performed to exclude significant coronary artery disease, demonstrating no significant stenosis in the major epicardial coronaries (left anterior descending, left circumflex or right coronary artery), but mild diffuse coronary atherosclerosis is present (with a calcium score of 370 Agatston units). She is commenced on medical therapy of aspirin and a statin, and is reassured that she does not have a stenosis requiring stent or bypass surgery, and that her chest symptoms are not due to coronary artery disease.

CTCA showing “clean” coronary arteries with no plaque or stenosis.

In Australia, Medicare reimbursement is available via specialist referral for three indications:

  • chest symptoms consistent with coronary ischaemia in low to intermediate risk patients;

  • evaluation of suspected coronary anomaly or fistula; or;

  • exclusion of CAD before heart transplant or valve surgery (non-coronary cardiac surgery).

Medicare-reimbursed indications do not cover asymptomatic patients with a strong family history of coronary artery disease (in which case, a coronary calcium score may suffice).7 When used appropriately, CTCA reduces the need for invasive coronary angiography, which is about five times more expensive, as a consequence of the reduced need for hospital admissions and different Medicare Benefits Schedule charges. Data suggest that use of CTCA is cost-effective and reduces downstream testing.8

Importantly, CTCA is not appropriate in patients with typical angina (defined as “constricting discomfort in the chest, which is precipitated by physical exertion, and relieved by rest or GTN”9) who have a high pre-test probability of obstructive disease and should proceed directly to invasive coronary angiography.

Evaluation after coronary artery stenting is limited to large diameter stents (> 3 mm) in proximal arteries and, in general, functional testing remains the clinical standard for reassessment of patients with known CAD.5 Conversely, assessment of graft patency following coronary artery bypass surgery can be well assessed by CTCA, without the risks of stroke or graft dissection from invasive engagement of the grafts during catheter angiography.5

The main weakness of CTCA is its modest positive predictive value, which varies from 60% to 90% depending on the prevalence of disease and the study. In clinical practice, this generally means that although coronary disease seen on CTCA is real, the percentage of stenosis generally appears more severe on CTCA compared with invasive coronary angiography. On the other hand, CTCA can visualise eccentric coronary plaques with positive vessel wall remodelling, which may be missed on invasive angiography (which only images the coronary lumen, and not the vessel wall itself).

An important factor in CTCA is heart rate control, which remains essential for good quality CTCA imaging. Ideal heart rates are in the 50–60 beats per minute range for optimal imaging, requiring pre-medication with β-blockers and/or ivabradine. Heart rate control is proportional to radiation dose, therefore low dose studies require a slow and steady heart rate. This improves the diagnostic accuracy of CTCA, but negative chronotropic medications may not be suitable for all patient groups, and atrial fibrillation remains a challenge. Newer high resolution and dual source scanners are able to image at higher heart rates, with algorithms to reconstruct cardiac motion, and are becoming more widely available.

Clinical vignette 2: A 38-year-old man presents to an emergency department with atypical central chest pain. Serial troponins are negative, and a 12-lead electrocardiogram shows non-specific T wave changes. He has ongoing pain, is not deemed suitable for an “accelerated diagnostic protocol” pathway, and early computed tomography coronary angiography (CTCA) is performed after 100 mg oral metoprolol with 10 mg ivabradine, to achieve a heart rate of 59 beats per minute, allowing a low dose (< 1 mSv) scan. CTCA shows a normal left coronary system, but an anomalous right coronary artery origin arising from the contralateral cusp, with an interarterial course and a slit-like origin.6 This is a potentially life-threatening anomaly due to potential compression between the aorta and pulmonary artery resulting in sudden death;10 however, this may not have been diagnosed on functional testing (eg, single-photon emission computed tomography). Cardiac CT is the reference test for the assessment of coronary anomalies and coronary fistulae.6


CTCA axial view showing the RCA origin adjacent to the left main sinus and with an interarterial course between the aorta and pulmonary artery (arrow). Ao = aorta. Cx = circumflex. LA = left atrium. LAD = left anterior descending artery. LCC = left coronary cusp. LMCA = left main coronary artery. NCC = non-coronary cusp. PA = pulmonary artery. RCA = right coronary artery. RCC = right coronary cusp.

Recent data from the PROMISE trial in 10 000 patients showed equivalence of a CTCA versus functional testing strategy in symptomatic patients, but with a reduced rate of “normal” invasive angiograms and decreased downstream testing in the CTCA group.11 Further, the SCOT-HEART trial recently demonstrated that adding CTCA to standard care reduced the need for additional stress testing, and was associated with a 38% reduction in fatal and non-fatal myocardial infarction.12

Future directions for CTCA

Rapid technological advancement in both CT hardware and post-processing reconstruction software algorithms are leading to further improvements in spatial and temporal resolution while minimising radiation exposure. CTCA has the ability to detect high risk vulnerable plaques,6,13 and statin therapy may help alter the natural history of atherosclerosis as imaged by CTCA.13 New developments enable functional assessment of a lesion on CTCA, allowing assessment of lesion-specific ischaemia at the same time as evaluating coronary anatomy. Adenosine stress perfusion cardiac CT allows functional assessment of myocardial perfusion in a similar manner to nuclear single-photon emission computed tomography (SPECT), and can be performed at the same time as CTCA with minimal additional radiation.14 Fractional flow reserve can be derived from static CTCA datasets, using computational fluid dynamics, and has been compared favourably with invasive haemodynamic assessment of fractional flow reserve during invasive coronary angiography.15 Overall, CTCA is a very useful tool to non-invasively assess the coronary arteries, with prognostic data now available to support its routine use in clinical practice.

Part 2: Cardiovascular magnetic resonance imaging for clinicians

CMR is a specialised form of magnetic resonance imaging (MRI), which employs specific MRI techniques with ECG gating to capture high resolution images of the heart and cardiac motion, in any imaging plane, without radiation.16 CMR is like a “super-echocardiogram” to assess heart function, but has the additional ability to quantitate vascular flow, myocardial oedema, cardiac perfusion, viability, and the presence of infiltrate or scar using gadolinium-based contrast agents. CMR improves diagnosis and risk stratification, predicts prognosis, and guides treatment decisions in many cardiac disorders.

Left and right ventricular function

Accurate quantitation of left and right ventricular function are essential to making decisions in clinical medicine, from commencement of drug therapy to implantation of costly devices such as automatic defibrillators. CMR is the gold standard for measurements of left ventricular mass, volume and ejection fraction and assessing the presence of regional wall motion abnormalities,17,18 and it is more reproducible than echocardiography.19

CMR offers particular advantages for conditions affecting the right ventricle, which is particularly difficult to assess using echocardiography. Assessment of right ventricular volume and wall motion by CMR are assigned as major criteria in the diagnosis of arrythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C), a genetic condition resulting in arrhythmias and sudden death.20 Right ventricular function is important in patients in pulmonary hypertension and with adult congenital heart disease,21 for which CMR is critical to decision making (eg, timing of surgery, replacement of cardiac valves). In patients with dilated right hearts, CMR is useful to detect the underlying causes, which may not be apparent on echocardiography (such as partial anomalous pulmonary venous drainage, or ARVD/C).

Viability and scar imaging

CMR can be used to confirm the diagnosis of myocardial infarction and assess viability before stenting or coronary artery bypass surgery, using gadolinium contrast agents to image scar tissue.

Clinical vignette 3: A 74-year-old man with a late-presentation ST-elevation myocardial infarction is shown to have an occluded left anterior descending artery during coronary angiography. Echocardiography shows an ejection fraction of 40%. Cardiovascular magnetic resonance (CMR) demonstrates that the anterior wall is akinetic, with full thickness infarction and no residual viable myocardium. Based on this information, he does not undergo stenting or coronary artery bypass graft surgery and is treated medically with heart failure therapy.


CMR imaging: two-chamber view showing a dilated left ventricle with akinetic anterior wall (A), and post-contrast imaging showing full thickness infarction of the entire anterior wall with no residual viable myocardium (B, arrows).

Infiltrative disorders traditionally requiring cardiac biopsy

CMR is a useful tool to diagnose infiltrative disorders which have traditionally required invasive cardiac biopsy, such as cardiac sarcoidosis, cardiac amyloidosis, and detection of fibrosis in hypertrophic cardiomyopathy.22–25 The EuroCMR registry of over 27 000 patients showed that using CMR improves diagnosis and changes clinical management in patients with cardiac conditions.26 Common indications and contraindications for CMR are shown in Box 2.27

Clinical vignette 4: A 26-year-old woman with palpitations has an echocardiogram showing a dilated right heart but with intact atrial and ventricular septum; the cause for right heart dilation was unclear. CMR showed a right ventricular volume index of 143 mL/m2 (moderate to severely dilated), and confirmed a diagnosis of partial anomalous pulmonary venous drainage of the right veins to the superior vena cava (significant intracardiac shunt: Qp:Qs, 2:1). She underwent minimally invasive cardiac surgical repair, with normalisation of right heart size at follow-up.

Myocardial fibrosis and iron overload

CMR is a “non-invasive microscope” of the heart, with techniques such as quantitative T1 mapping allowing non-invasive measurement of fibrosis and extracellular volume fraction.28 Cardiac iron overload occurs in haemochromatosis and thalassaemia, and is a significant cause of morbidity and mortality in these conditions.29 In the past, cardiac biopsy was the only means to assess myocardial iron overload. However, using iron-sensitive T2* imaging, CMR has been validated to quantitatively and non-invasively measure myocardial iron stores. Australian guidelines exist for using CMR to assess for iron overload, with T2* values of > 20 ms being normal, < 10–20 ms indicating moderate iron overload, and values of < 10 ms indicating severe iron overload warranting consideration for chelation therapy.29

Ventricular thrombus

CMR is the gold standard test for detection of ventricular thrombus after myocardial infarction and is superior to echocardiography, including microsphere contrast echocardiography (Box 3).30

Valvular dysfunction

Quantitation of valvular regurgitation is more reproducible by CMR than by echocardiography,31 and is particularly useful in assessing aortic and pulmonary regurgitation, which are difficult to quantitate echocardiographically. CMR has been allocated a Class I indication for use in patients with moderate or severe valve disorders and suboptimal or equivocal echocardiographic evaluation (Class I, Level of evidence B).31,32 CMR is validated for the direct planimetric assessment of aortic stenosis, which can be performed using steady-state free precession cine imaging without requiring contrast (this may be useful for patients with renal impairment, such as those being assessed for transcatheter aortic valve implantation).33 CMR is also superior to echocardiography for the assessment of mitral regurgitation after percutaneous mitral valve repair.34 In clinical practice, CMR is useful when a valve lesion is of indeterminate or equivocal severity by echocardiography, when quality echocardiographic images are suboptimal (eg, due to limited acoustic windows), or when the “downstream effect” of a lesion needs further quantitation, such as left ventricular dilation in severe but asymptomatic valve regurgitation.

Stress perfusion CMR

Stress perfusion testing can be performed with CMR and has superior spatial resolution to nuclear SPECT imaging without the exposure to radiation. A large, prospective comparative efficacy trial recently demonstrated that stress perfusion CMR was superior to SPECT for the diagnosis of myocardial ischaemia.35 CMR can also provide information on viability (scar) and the coronary arteries in the same non-invasive test, making it a “one-stop shop” that is increasingly being adopted in Europe and the United Kingdom for stress imaging in cardiology practice.26

Limitations of CMR

The main limitation of CMR is availability, with the technique mainly confined to reference expert centres owing to its complexity and the degree of training required to perform and report CMR. Guidelines exist from the Society of Cardiovascular Magnetic Resonance on the performance and reporting of CMR, and specific Australian and New Zealand guidelines are currently being formulated. The second major limitation is the lack of specific Medicare reimbursement for CMR. At present, two applications are before the Medical Services Advisory Committee (MSAC): one for stress perfusion/viability imaging and one for assessment of cardiomyopathies in patients with abnormal baseline echocardiography (MSAC application 1393: http://www.msac.gov.au/internet/msac/publishing.nsf/Content/1393-public).

While CMR provides superior diagnostic information than echocardiography in virtually all cardiac disorders, it is more resource intensive, time consuming and currently less available than echocardiography. CMR should be targeted for patients in whom echocardiography is inconclusive or non-diagnostic, or in specific circumstances where CMR is more appropriate than echocardiography (such as complex congenital heart disease, or the use of stress perfusion when it is clinically appropriate to assess ventricular function, viability and ischaemia in a single test).

Relative contraindications are present in patients with arrhythmias that affect ECG gating, claustrophobia, implantable devices, and severe renal impairment (if contrast imaging is required). Most modern pacemaker systems are MRI conditional at a field strength of 1.5 T, but are not compatible with 3 T systems.

Conclusions

Cardiac imaging is a rapidly evolving field, with improvements in the diagnostic capabilities of non-invasive cardiac assessment. CTCA is useful to exclude coronary artery disease non-invasively. CMR is useful to accurately quantitate left ventricular and right ventricular function and investigate cardiomyopathies, or patients with congenital heart disease. CTCA and CMR and are becoming routine clinical practice for cardiologists in Australia and New Zealand, with increasing use in both hospital and outpatient settings. General practitioners and general physicians should be familiar with the basic indications, clinical utility and limitations of these modern techniques to assist in their appropriate use and interpretation in day-to-day practice.

Box 1 –
Appropriate indications for computed tomography coronary angiography endorsed by the Cardiac Society of Australia and New Zealand6

  • Chest pain with low to intermediate pre-test probability of coronary artery disease (CAD)
  • Chest pain with uninterpretable or equivocal stress test or imaging results
  • Normal stress test results but continued or worsening symptoms
  • Suspected coronary or great vessel anomalies
  • Evaluation of coronary artery bypass grafts (with symptoms)
  • Exclude coronary artery disease in new onset left bundle branch block or heart failure

Box 2 –
Common indications and contraindications for cardiovascular magnetic resonance imaging25

Common indications

  • Myocardial viability (ischaemic cardiomyopathies)
  • Accurate assessment of left ventricular ejection fraction; eg, before device implantation (implantable cardioverter defibrillator and cardiac resynchronisation therapy)
  • Detection of interventricular thrombus
  • Interstitial fibrosis (dilated and infiltrative cardiomyopathies)
  • Congenital heart disease
  • Cardiac mass
  • Right ventricular quantification
  • Evaluation for arrythmogenic right ventricular dysplasia/cardiomyopathy
  • Post cardiac transplantation surveillance
  • Constrictive pericarditis
  • Quantification of valvular dysfunction
  • Aortic and vascular measurement
  • Iron overload quantification (T2*)

Contraindications

  • Absolute
    • Non-magnetic resonance compatible implantable devices
    • Severe claustrophobia
  • Relative
    • Magnetic resonance imaging conditional pacemakers (only 1.5 T field strength)
    • Arrythmias that affect electrocardiogram gating (atrial fibrillation and ectopy)
    • Severe renal impairment (risk of nephrogenic systemic fibrosis)

Box 3 –
Early post-contrast cardiovascular magnetic resonance image showing multiple thrombi in the mid-anterior wall and left ventricular apex (arrows)

Note: on microsphere contrast echocardiography, only the apical thrombus was seen; the thrombi adherent to the mid-anterior wall were not observed.

National Heart Foundation of Australia and Cardiac Society of Australia and New Zealand: Australian clinical guidelines for the management of acute coronary syndromes 2016

These clinical guidelines have been developed to assist in managing patients presenting with chest pain suspected to be caused by an acute coronary syndrome (ACS) and those with confirmed ACS. The development of these guidelines has been informed by reviews of the literature dealing with key aspects of chest pain assessment and ACS care, as well as broad consultation with local opinion leaders, stakeholder groups and the public. The recommendations focus on the core clinical and system-based components of care most associated with improved clinical outcomes. As such, these guidelines should be read in conjunction with the Acute coronary syndromes clinical care standard, developed by the Australian Commission on Safety and Quality in Health Care,1 and the Australian acute coronary syndromes capability framework, developed by the National Heart Foundation of Australia (NHFA).2 Guidance regarding both the strength of evidence supporting the recommendations and their potential impact on outcomes is provided to assist in informing clinical practice.3,4 Additional guidance regarding the timing and considerations informing the use of therapies and management strategies is given in the accompanying practice advice. A full version of the NHFA and Cardiac Society of Australia and New Zealand (CSANZ) Australian clinical guidelines for the management of acute coronary syndromes 2016 is available at: http://heartfoundation.org.au/for-professionals/clinical-information/acute-coronary-syndromes.

Methods

The NHFA, in partnership with the CSANZ, has undertaken an update to the NHFA/CSANZ Guidelines for the management of acute coronary syndromes 2006 and addenda of 2007 and 2011.5–7 The updated guideline will provide a synthesis of current evidence-based guidance for health professionals caring for patients with ACS.

The ACS Guideline Development Working Group comprised an Executive and the four writing groups of which it had oversight, covering the topics of chest pain, ST segment elevation myocardial infarction (STEMI), non-ST segment elevation ACS (NSTEACS) and secondary prevention. In addition, a Reference Group included representatives from stakeholder groups, potential endorsing organisations and regional experts. The Working Group comprised a broad mix of health professionals, including a general practitioner, general physician, cardiac surgeon, consumer representative, pathologist, ambulance service representative, cardiologists, emergency physicians, exercise physiologists and cardiac nurses.

The Working Group consulted state-based cardiac clinical networks and the Reference Group on the scope determination for the updated guideline. Based on this consultation, the expert Working Group generated clinical questions to inform the literature search of evidence required for the guideline’s development. The separate writing groups reviewed and graded the evidence, generated and graded recommendations, and produced draft sections for the four topic areas. The Executive group provided oversight for this process and approved the final document.

A draft of the guideline was open for a 30-day period of public consultation in April 2016 to capture stakeholder views and aid engagement with the guideline once completed. Attention has been paid to ensuring appropriate governance processes were in place, to ensure transparency, minimise bias, manage conflict of interest and limit other influences during guideline development.

Key evidence-based recommendations

Each recommendation is presented with a Grading of Recommendations Assessment, Development and Evaluation (GRADE) strength of recommendation (Appendix 1) and a National Health and Medical Research Council level of evidence (Level) (Appendix 2). Practice points (PPs) are also provided.

Assessment of possible cardiac causes of chest pain

  • It is recommended that a patient with acute chest pain or other symptoms suggestive of an ACS receives a 12-lead electrocardiogram (ECG), and this ECG is assessed for signs of myocardial ischaemia by an ECG-experienced clinician within 10 minutes of first acute clinical contact.8 GRADE: Strong; Level: IIIC

    • PP: Oxygen supplementation. The routine use of oxygen therapy among patients with a blood oxygen saturation (SaO2) level > 93% is not recommended, but its use when the SaO2 is below this level is advocated, despite the absence of clinical data.9,10 However, care should be exercised in patients with chronic obstructive pulmonary disease where the target SaO2 level is to be 88–92%.

    • PP: Initial aspirin therapy. In all patients with possible ACS and without contraindications, aspirin (300 mg orally, dissolved or chewed) should be given as soon as possible after presentation. Additional antiplatelet and anticoagulation therapy, or other therapies such as β-blockers, should not be given to patients without a confirmed or probable diagnosis of ACS.

  • A patient presenting with acute chest pain or other symptoms suggestive of an ACS should receive care guided by an evidence-based Suspected ACS Assessment Protocol (Suspected ACS-AP) that includes formal risk stratification.11 GRADE: Strong; Level: IA

    • PP: Selecting and implementing a Suspected ACS-AP. For hospitals using sensitive or highly sensitive troponin assays, the ADAPT or modified ADAPT protocol, respectively, identifies low risk patients (< 1% major adverse cardiac events [MACE] at 30 days) on the basis of negative troponin test results at both 0 and 2 hours, a Thrombolysis in Myocardial Infarction (TIMI) risk score of 0 (ADAPT) or 0 or 1 (modified ADAPT), and no ischaemic changes on ECG at both 0 and 2 hours.12,13

  • Using serial sampling, cardiac-specific troponin levels should be measured at hospital presentation and at clearly defined periods after presentation using a validated Suspected ACS-AP in patients with symptoms of possible ACS.14 GRADE: Strong; Level: IA

    • PP: Timing of troponin testing. Most patients with an underlying diagnosis of acute myocardial infarction (AMI) have elevated troponin levels within 3–6 hours of symptom onset, although some assays may not show elevated levels for up to 12 hours (Box 1). Validated rapid rule-in and rule-out algorithms for AMI incorporated into Suspected ACS-APs and/or using highly sensitive troponin assays may reduce the serial testing time to 1–2 hours after presentation.18,19,21,24,25 Incorporating sensitive or highly sensitive troponin assay results into the ADAPT or modified ADAPT protocol, respectively, allows early (2 hours after emergency department presentation) risk stratification.12,13

  • Non-invasive objective testing is recommended in intermediate risk patients, as defined by a validated Suspected ACS-AP, with normal serial troponin and ECG testing and who remain symptom free.26 GRADE: Weak; Level: IA

    • PP: Timing of testing. High risk patients require further objective testing during the index admission (Box 2). Intermediate risk patients may be safely accelerated for early inpatient testing or discharged for outpatient testing, ideally within 7 days but acceptable up to 14 days after presentation. Investigation before discharge from the emergency department is desirable among patients with characteristics associated with significant failure to re-attend for medical review, given the higher rates of MACE in such patients.27

  • Patients in whom no further objective testing for coronary artery disease is recommended are those at low risk, as defined by a validated Suspected ACS-AP: age < 40 years, symptoms atypical for angina, in the absence of known coronary artery disease, with normal troponin and ECG testing and who remain symptom free.26 GRADE: Weak; Level: III-3C

Diagnostic issues, risk stratification and acute management of ACS

  • The routine use of validated risk stratification tools for ischaemic and bleeding events (eg, GRACE score for ischaemic risk and CRUSADE score for bleeding risk) may assist in patient-centric clinical decision making in regards to ACS care.28–30 GRADE: Weak; Level: IIIB

    • PP: Choice of risk score. For ischaemic risk, the GRACE risk score is superior to the TIMI risk score in terms of discriminating between high risk and intermediate or low risk patients.28 However, estimating risk of death or recurrent myocardial infarction (MI) for an individual patient depends on local validation. For bleeding risk, the CRUSADE risk score is preferred, although it has limited validation in the Australian setting.31

Acute reperfusion and invasive management strategies for ACS

  • For patients with STEMI presenting within 12 hours of symptom onset, and in the absence of advanced age, frailty and comorbidities that influence the individual’s overall survival, emergency reperfusion therapy with either primary percutaneous coronary intervention (PCI) or fibrinolytic therapy is recommended.32,33 GRADE: Strong; Level: IA

    • PP: ECG interpretation. In situations where expertise in ECG interpretation may not be available, an electronic algorithm for ECG interpretation (coupled with review by an expert) can assist in diagnosing STEMI. Local or state care pathways should incorporate means for allowing expert ECG reading within 10 minutes of first contact, integrated with clinical decision making to enable timely reperfusion.

  • Primary PCI is preferred for reperfusion therapy in patients with STEMI if it can be performed within 90 minutes of first medical contact; otherwise, fibrinolytic therapy is preferred for those without contraindications.34–36 GRADE: Strong; Level: IA

    • PP: Strategies for reducing the time to reperfusion therapy. Coordinated protocols with planned decision making that incorporates ambulance services and paramedics, first-responder primary care physicians, and emergency and cardiology departments are critical for achieving acceptable reperfusion times. Strategies need to be tailored to the local community and the distribution of emergency services. Strategies that effectively shorten the time to reperfusion include: developing hospital networks with pre-determined management pathways for reperfusion; pre-hospital ECG and single call catheter laboratory activation; pre-hospital fibrinolytic therapy administered by suitably trained clinicians (eg, paramedics); the bypassing, where appropriate, of non-PCI-capable hospitals; and bypassing the emergency department on arrival in PCI-capable centres. Furthermore, an established capability for timely expert consultation for complex clinical scenarios is highly desirable. In the context of a system-based approach to reperfusion, the capacity for continuous audit and feedback is also advocated.

  • Among patients treated with fibrinolytic therapy who are not in a PCI-capable hospital, early or immediate transfer to a PCI-capable hospital for angiography, and PCI if indicated, within 24 hours is recommended.37 GRADE: Weak; Level: IIA

  • Among patients treated with fibrinolytic therapy, for those with ≤ 50% ST recovery at 60–90 minutes and/or with haemodynamic instability, immediate transfer for angiography with a view to rescue angioplasty is recommended.38 GRADE: Strong; Level: IB

    • PP: Hospital networks. Systems of care should be developed to provide advice and enable, when appropriate, immediate or early transfer for angiography of patients treated with fibrinolytic therapy who are not in a PCI-capable hospital.

  • Among high and very high risk patients with NSTEACS (except type 2 MI [secondary to ischaemia due to either increased oxygen demand or decreased supply]), a strategy of angiography with coronary revascularisation (PCI or coronary artery bypass grafting [CABG]), where appropriate, is recommended.39 GRADE: Strong; Level: IA

    • PP: Mode of revascularisation. Patient comorbidities, fitness for major surgery and coronary anatomy are the main determinants. Urgent revascularisation with CABG may be indicated for patients with failed PCI, cardiogenic shock or mechanical defects resulting from MI (eg, septal, papillary muscle or free-wall rupture). A combined Heart Team approach may provide the best consensus decision about the care of an individual patient.

    • PP: Invasive management for type 2 MI. Type 2 MI remains a challenging diagnosis, and no trials have examined the benefits of a routine invasive strategy in patients with type 2 MI. In the absence of any trial evidence, angiography with a view to revascularisation may be considered if there is ongoing ischaemia or haemodynamic compromise despite adequate treatment of the underlying acute medical problem that provoked the type 2 MI.

  • Patients with NSTEACS who have no recurrent symptoms and no risk criteria are considered at low risk of ischaemic events and can be managed with a selective invasive strategy guided by provocative testing for inducible ischaemia.39 GRADE: Strong; Level: IA

  • Very high risk patients: Among patients with NSTEACS with very high risk criteria (ongoing ischaemia, haemodynamic compromise, arrhythmias, mechanical complications of MI, acute heart failure, recurrent dynamic or widespread ST segment and/or T wave changes on ECG; Box 3), an immediate invasive strategy is recommended (ie, within 2 hours of admission).40 GRADE: Strong; Level: IIC

  • High risk patients: In the absence of very high risk criteria, for patients with NSTEACS with high risk criteria (GRACE score > 140, dynamic ST segment and/or T wave changes on ECG or rise and/or fall in troponin compatible with MI; Box 3), an early invasive strategy is recommended (ie, within 24 hours of admission).40 GRADE: Weak; Level: IC

  • Intermediate risk patients: In the absence of high risk criteria, for patients with NSTEACS with intermediate risk criteria (such as recurrent symptoms or substantial inducible ischaemia on provocative testing; Box 3), an invasive strategy is recommended (ie, within 72 hours of admission).40–42 GRADE: Weak; Level: IIC

Pharmacology for ACS

  • Aspirin 300 mg orally (dissolved or chewed) initially, followed by 100–150 mg/day, is recommended for all patients with ACS, in the absence of hypersensitivity.43 GRADE: Strong; Level: IA

  • Among patients with confirmed ACS at intermediate to very high risk of recurrent ischaemic events, use of a P2Y12 inhibitor (ticagrelor 180 mg orally, then 90 mg twice a day; or prasugrel 60 mg orally, then 10 mg daily; or clopidogrel 300–600 mg orally, then 75 mg daily) is recommended in addition to aspirin (ticagrelor or prasugrel preferred; see below).44–47 GRADE: Strong; Level: IA

    • PP: Choosing between P2Y12 inhibitors. Given their superior efficacy, ticagrelor and prasugrel are the preferred first-line P2Y12 inhibitors. Use of ticagrelor is advised for a broad spectrum of patients with STEMI or NSTEACS who are at intermediate to high risk of an ischaemic event, in the absence of atrioventricular conduction disorders (second and third degree atrioventricular block) and asthma or chronic obstructive pulmonary disease. Prasugrel may be considered for patients who have not received a P2Y12 antagonist and in whom PCI is planned, but it should not be used for patients > 75 years of age, of low bodyweight (< 60 kg) or with a history of transient ischaemic attack or stroke. Use of either prasugrel or ticagrelor, rather than clopidogrel, is also recommended for patients who have experienced recurrent events while taking clopidogrel or who have experienced stent thrombosis. Clopidogrel is recommended for patients who cannot receive ticagrelor or prasugrel, as an adjunctive agent with fibrinolytic therapy or for those requiring oral anticoagulation (refer to relevant prescribing information documentation). Ticagrelor or clopidogrel should be commenced soon after diagnosis, but due consideration should be given to ischaemic and bleeding risks, the likelihood of need for CABG (more likely in patients with extensive ECG changes, ongoing ischaemia or haemodynamic instability) and the delay to angiography. Prasugrel should be commenced immediately after diagnosis among patients undergoing primary PCI for STEMI, or after the coronary anatomy is known among those undergoing urgent PCI. Initiation of prasugrel before coronary angiography outside the context of primary PCI is not recommended.

    • PP: Combination of P2Y12 inhibition with long term anticoagulation. Among patients with an indication for oral anticoagulation, a careful assessment of thrombotic and bleeding risks is required, using CHA2DS2-VASc and HAS-BLED scores, respectively. The following advice is based on consensus opinion. In patients with a strong indication for long term anticoagulation (ie, mechanical heart valves, atrial fibrillation with CHA2DS2-VASc score ≥ 2), the anticoagulant should be continued at a reduced dose, and clopidogrel, rather than ticagrelor or prasugrel, should be used for these patients. The duration of triple therapy (ie, aspirin, clopidogrel and oral anticoagulation) should be determined by the bleeding risk.

  • Intravenous glycoprotein IIb/IIIa inhibition in combination with heparin is recommended at the time of PCI among patients with high risk clinical and angiographic characteristics or for treating thrombotic complications among patients with ACS.48 GRADE: Strong; Level: IB

  • Either unfractionated heparin or enoxaparin is recommended in patients with ACS at intermediate to high risk of ischaemic events.49,50 GRADE: Strong; Level: IA

    • PP: Choosing between indirect thrombin inhibitors. Enoxaparin may be preferred over unfractionated heparin as it does not require monitoring of partial thromboplastin time and is simpler to administer. Swapping between enoxaparin and unfractionated heparin has been shown to increase bleeding risk and is not recommended.

  • Bivalirudin (0.75 mg/kg intravenously with 1.75 mg/kg/h infusion) may be considered as an alternative to glycoprotein IIb/IIIa inhibition and heparin among patients with ACS undergoing PCI with clinical features associated with an increased risk of bleeding events.51 GRADE: Weak; Level: IIB

Discharge management and secondary prevention

  • Aspirin (100–150 mg/day) should be continued indefinitely unless it is not tolerated or an indication for anticoagulation becomes apparent.43 GRADE: Strong; Level: IA

  • Clopidogrel should be prescribed if aspirin is contraindicated or not tolerated. GRADE: Strong; Level: IA

  • Dual antiplatelet therapy with aspirin and a P2Y12 inhibitor (clopidogrel or ticagrelor) should be prescribed for up to 12 months in patients with ACS, regardless of whether coronary revascularisation was performed. The use of prasugrel for up to 12 months should be confined to patients receiving PCI. GRADE: Strong; Level: IA

  • Consider continuation of dual antiplatelet therapy beyond 12 months if ischaemic risks outweigh the bleeding risk of P2Y12 inhibitor therapy; conversely, consider discontinuation if bleeding risk outweighs ischaemic risks.52 GRADE: Weak; Level: IIC

  • Initiate and continue indefinitely, the highest tolerated dose of an HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase inhibitor (statin) for a patient following hospitalisation with ACS, unless contraindicated or there is a history of intolerance.53 GRADE: Strong; Level: IA

    • PP: Target cholesterol levels. There is additional benefit from progressive lowering of cholesterol levels, with no apparent lower limit. Within the context of an individualised care plan, a target low density lipoprotein cholesterol level of less than 1.8 mmol/L is suggested in the first instance.

  • Initiate treatment with vasodilatory β-blockers in patients with reduced left ventricular systolic function (left ventricular ejection fraction ≤ 40%) unless contraindicated.54 GRADE: Strong; Level: IIA

  • Initiate and continue angiotensin-converting enzyme inhibitors (or angiotensin receptor blockers) in patients with evidence of heart failure, left ventricular systolic dysfunction, diabetes, anterior MI or co-existent hypertension.55 GRADE: Strong; Level: IA

  • Attendance at cardiac rehabilitation or undertaking a structured secondary prevention service is recommended for all patients hospitalised with ACS.56,57 GRADE: Strong; Level: IA

    • PP: Individualisation of cardiac rehabilitation or secondary prevention service referral. A wide variety of prevention programs improve health outcomes in patients with coronary disease. After discharge from hospital, patients with ACS and, where appropriate, their companion(s) should be referred to an individualised preventive intervention according to their personal preference and values and the available resources. Services can be based in the hospital, primary care, the local community or the home.

System considerations

  • Continuous audit and feedback systems, integrated with work routines and patient flows, are strongly advocated to support quality assurance initiatives and provide data confirming continued, cost-efficient improvement in patient outcomes as a result of new innovations in care.

Box 1 –
Timing of troponin testing

Timing of sampling

Strategy*

Assays

0 hour (single sample)

Patients whose pain and symptoms resolved 12 hours prior to testing (cut points are the assay-specific 99th percentile

Both sensitive and highly sensitive (HS) assays

0 hour (single sample)

Patients with value < LoD of the specific assay (not > 99th percentile cut point) and symptom onset > 3 hours†15–17

HS assays

0 hour and 1 hour after presentation

Rule-in and rule-out AMI algorithms (cut points are assay-specific and not the 99th percentile)18–20

HS assays

0 and 2 hours after presentation

ADAPT protocol13

Sensitive assays

Modified ADAPT protocol12,21(cut points are the assay-specific 99th percentile)

HS assays

0 and ≥ 3 hours after presentation

Previous NHFA protocol7

HS assays

HEART Pathway22,23 (cut points are the assay-specific 99th percentile)

Both sensitive and HS assays

0 and ≥ 6–12 hours after presentation

Rule-in and rule-out AMI algorithms5 (cut points are the assay-specific 99th percentile)

Sensitive and point-of-care assays

ADAPT = 2-Hour Accelerated Diagnostic Protocol to Assess Patients with Chest Pain Symptoms Using Contemporary Troponins as the Only Biomarker. AMI = acute myocardial infarction. HEART = History, Electrocardiogram, Age, Risk factors and Troponin. LoD = limit of detection. NHFA = National Heart Foundation of Australia. * With concurrent clinical risk stratification. † Reports on the use and outcomes of the biomarker strategy in clinical practice are not currently available.

Box 2 –
Risk classification for possible cardiac causes of chest pain

High risk

  • Ongoing or recurrent chest discomfort despite initial treatment
  • Elevated cardiac troponin level
  • New ischaemic changes on electrocardiogram (ECG), such as persistent or dynamic ECG changes of ST segment depression ≥ 0.5 mm; transient ST segment elevation (≥ 0.5 mm) or new T wave inversion ≥ 2 mm in more than two contiguous leads; or ECG criteria consistent with Wellens syndrome
  • Diaphoresis
  • Haemodynamic compromise — systolic blood pressure < 90 mmHg, cool peripheries, Killip Class > I and/or new onset mitral regurgitation
  • Sustained ventricular tachycardia
  • Syncope
  • Known left ventricular systolic dysfunction (left ventricular ejection fraction ≤ 40%)
  • Prior acute myocardial infarction, percutaneous coronary intervention or coronary artery bypass grafting

Low risk

  • Age < 40 years
  • Symptoms atypical for angina
  • Remain symptom free
  • Absence of known coronary artery disease
  • Normal troponin level
  • Normal ECG

Intermediate risk

  • Neither high risk nor low risk criteria

Box 3 –
Markers of increased risk of mortality and recurrent events among patients with confirmed acute coronary syndrome

Risk classification

Clinical characteristic

Very high

  • Haemodynamic instability, heart failure, cardiogenic shock or mechanical complications of myocardial infarction (MI)
  • Life-threatening arrhythmias or cardiac arrest
  • Recurrent or ongoing ischaemia (ie, chest pain refractory to medical treatment) or recurrent dynamic ST segment and/or T wave changes, particularly with intermittent ST segment elevation, de Winter T wave changes or Wellens syndrome, or widespread ST segment elevation in two coronary territories

High

  • Rise and/or fall in troponin level consistent with MI
  • Dynamic ST segment and/or T wave changes with or without symptoms
  • GRACE score > 140

Intermediate

  • Diabetes mellitus
  • Renal insufficiency (glomerular filtration rate < 60 mL/min/1.73 m2)
  • Left ventricular ejection fraction ≤ 40%
  • Prior revascularisation: percutaneous coronary intervention or coronary artery bypass grafting
  • GRACE score > 109 and < 140

GRACE = Global Registry of Acute Coronary Events.

The uptake of coronary fractional flow reserve in Australia in the past decade

The use of coronary pressure wires (or fractional flow reserve [FFR]) has been shown to reduce the frequency of major adverse cardiac events and of unnecessary stent procedures, and to lower treatment costs in both the public and private sectors in Australia.1–3 FFR is a tool for assessing physiological ischaemia in coronary artery stenosis, measuring pre- and post-stenosis pressures during adenosine-induced hyperaemia. Because it is evidence-based and quantifiable, it may be discussed during the upcoming Medicare reform. Data on its uptake across Australia, however, have not been published.

We examined trends in FFR use after its addition to the Medicare Benefits Schedule 10 years ago. We analysed Australian Government Department of Human Services data on Medicare items for coronary flow reserve, coronary angiography and percutaneous coronary angiography.

A total of 14 160 FFR services were processed by Medicare during the past 10 years. FFR use grew during this period, with a mean annual increase of 55%, from 131 services in 2007 to 3869 in 2015 (non-parametric analysis, P = 0.004). Time series analysis identified a Gompertz non-linear trend of FFR against time, indicating that national FFR use is continuing to increase, although growth began to slow in 2014. Further, FFR use increased on a population basis by an average of 45% each year, from 1 per 100 000 in 2007 to 16 per 100 000 in 2015, when these figures were highest in New South Wales (23 per 100 000) and Queensland (19 per 100 000) (Box).

The national rate of FFR per coronary angiogram increased from 0.02% in 2006 to 4.8% in 2015 (P = 0.004), when the highest rate was in NSW (5.8%). The rate of FFR per percutaneous coronary intervention (PCI) increased from 0.1% in 2006 to 19.2% in 2015 (P = 0.004), when the highest rate was in Queensland (26.6%). In 2015, there were 5.2 PCIs per FFR used; the rate was not related to the population size of the state or territory (Spearman non-parametric correlation, ρS = 0.07; P = 0.87) or to total PCI use (ρS = 0.12, P = 0.78). There was marked variation between states and territories (Box), highlighting heterogeneity across Australia in the use of FFR.

The data summarised in the Box allow operators and hospitals to compare their use of FFR with state and national averages, and they facilitate more standardised care across Australia. Barriers to the uptake of FFR include operator and centre experience, availability and cost. It has been suggested that FFR is discouraged by the lower remuneration received if stenting is not performed.4 From a national perspective, however, there is a mean saving of $1200 per patient in the public sector and $5000 per patient in the private sector when FFR makes stenting unnecessary,2 representing a total annual saving of $4 million.4

The use of FFR across Australia is heterogeneous, but it has grown over the past decade, both in absolute numbers and as proportions of coronary angiograms and PCI.

Box –
Summary of Medicare items for use of a coronary pressure wire (fractional flow reserve [FFR]) processed during 2015

Australia

NSW

Vic

Qld

SA

WA

Tas

ACT

NT

Total FFR services

3869

1764

688

944

146

225

77

11

14

FFR per 100 000 population

16

23

11

19

8

9

15

3

6

FFR per angiogram

1/21 (4.8%)

1/17 (5.8%)

1/28 (3.6%)

1/17 (5.7%)

1/30 (3.4%)

1/29 (3.5%)

1/21 (4.8%)

1/83 (1.2%)

1/38 (2.7%)

FFR per percutaneous coronary intervention

1/5.2 (19.2%)

1/4.6 (21.6%)

1/7.0 (14.3%)

1/3.8 (26.6%)

1/6.8 (14.7%)

1/7.7 (13.0%)

1/6.2 (16.2%)

1/34.1 (2.9%)

1/4.3 (23.3%)

Source: Australian Government Department of Human Services. Medicare Australia Statistics, medical item reports (http://medicarestatistics.humanservices.gov.au/statistics/mbs_item.jsp) for coronary flow reserve (item number, 38241), coronary angiogram (38215, 38218, 38220, 38222, 38225, 38228, 38231, 38234, 38237, 38240, 38246) and percutaneous coronary angiogram (38243, 38246).

Pre-hospital thrombolysis in ST-segment elevation myocardial infarction: a regional Australian experience

The known Pre-hospital thrombolysis in patients with ST-segment elevation myocardial infarction (STEMI) has been found to be an effective strategy in randomised controlled trials.

The new Pre-hospital thrombolysis is safe and effective in the real world setting, especially in a region where transport distances to the cardiac catheterisation laboratory are great.

The implications Pre-hospital thrombolysis can be implemented in regions where timely primary percutaneous coronary intervention for STEMI patients is not available.

Primary percutaneous coronary intervention (PCI), if performed in a timely manner, is the preferred reperfusion strategy for patients with an ST-segment elevation myocardial infarction (STEMI).1 However, physicians in regions geographically isolated from a primary PCI centre are unable to perform PCI rapidly, and the optimal reperfusion strategy is therefore undefined. Recent guidelines have highlighted the importance of systems-based approaches to STEMI management, taking into account regional characteristics.2 In Australia, many patients are a long way from a primary PCI centre, and these patients usually receive thrombolysis in hospitals that are not PCI-capable. However, if reperfusion with thrombolysis fails or a contraindication prevents its application, there can be long delays in reaching a cardiac catheterisation laboratory (CCL) for PCI.3 Further, a pharmaco-invasive (PI) strategy, including routine cardiac catheterisation within 24 hours of thrombolysis, was found to achieve better outcomes than ischemia-driven angiography.4 This strategy is especially relevant in areas where geographic access and logistical delays that increase the time to treatment (eg, rural areas, large urban areas with traffic congestion) may reduce some of the benefits of primary PCI in clinical practice.5

The international Strategic Reperfusion Early After Myocardial Infarction (STREAM) trial, in which STEMI patients who were unable to undergo primary PCI within one hour of presentation were randomised to either primary PCI or a PI strategy, confirmed that outcomes of the PI strategy at one year were not inferior to those of primary PCI.6,7 However, the STREAM trial did not include all patients who presented with STEMI; although most of those randomised underwent randomisation in the ambulance setting (81%), the patients included in the trial had presented within 3 hours of symptom onset (compared with 6–12 hours for the STEMI patients who were not included), and the median time from presentation to PCI in the PI arm was 10 hours, which may not be achievable in a real world setting. Similarly, geographical and logistical constraints that are important factors in different parts of the world, such as distance and regional resources, were not considered in the STREAM trial.

The case series described in this article was from the Hunter New England Local Health District (HNELHD), which has a complex geography and limited resources. The area it covers (130 000 km2) is comparable in size with England, but it has only one continuously operating CCL; it is located in one corner of the health district (in Newcastle), and patients with a STEMI may be as far as 600 km away (Box 1). In 2008, we implemented a system of care in HNELHD for providing rapid reperfusion to STEMI patients throughout this large district. Modelled on the Emergency Triage of Acute Myocardial Infarction study in the Northern Sydney Area Health Service, which achieved reduced delays and improved outcomes for patients with primary angioplasty,9 our system involved pre-hospital diagnosis and triage by paramedic staff, followed by their allocating the patients to either PHT or primary PCI according to their travel time to the CCL in our large regional health district. The analysis reported in this article compares the safety and effectiveness of pre-hospital assessment and allocation to pre-hospital thrombolysis (PHT) or primary angioplasty by paramedics.10

Methods

Study design

Hunter AMI was a prospective, non-randomised, consecutive, single-centre case series of STEMI patients who had been diagnosed on the basis of a pre-hospital ECG performed by paramedics. Data were collected electronically through the collaboration of the New South Wales Ambulance and the HNELHD, and data were independently analysed by the Clinical Research Design, IT and Statistical Support (CReDITSS) unit at the Hunter Medical Research Institute.

Study patients

For all patients with symptoms or signs suggesting myocardial infarction, paramedics recorded a 12-lead electrocardiogram (ECG; LIFEPAK 15 monitor system, Physio-Control Australia). Posterior and right-sided leads were not recorded by the paramedics for infero-posterior or right ventricular myocardial infarction. If the ECG indicated a possible STEMI according to the Glasgow algorithm,11,12 it was transmitted to the on-call cardiologist or cardiology advanced trainee at the John Hunter Hospital in Newcastle; the doctor and the paramedic then discussed the case, and reperfusion of the patient started. For patients who could reach a CCL within 60 minutes of first medical contact (FMC) or for whom there was any contraindication to thrombolysis (irrespective of FMC-to-CCL door time), reperfusion therapy consisted of primary PCI at the John Hunter Hospital. PHT (fibrinolysis with tenecteplase administered by paramedics) was administered by paramedics to patients for whom the FMC-to-CCL door time exceeded 60 minutes, and was followed by transfer to the PCI-capable centre (Appendix 1). All consecutive STEMI patients who had been diagnosed by pre-hospital ECG were included in our analysis.

FMC was defined as the first face-to-face contact made by paramedics with the patient. Total ischaemic time was defined as the time from symptom onset to balloon inflation for the primary PCI group, and to injection of tenecteplase for the PHT group. Hypertension was diagnosed if blood pressure greater than 140/90 mmHg was measured on two or more occasions in the hospital, or if the patient was already being treated with antihypertensive medication.13,14 Diabetes mellitus was diagnosed if two of the following applied: symptoms of hyperglycaemia; fasting sugar level > 7 mmol/L; 2-hour post-prandial sugar level > 11.1 mmol/L; HbA1c level > 6.5 mmol/mol.15 Cardiogenic shock was defined as persistent hypotension (systolic blood pressure < 90 mmHg or mean arterial pressure 30 mmHg lower than baseline).16 Left ventricular ejection fraction was recorded during the index hospitalisation by transthoracic echocardiography, using Simpson’s biplane method.

Study therapies

We present the outcomes of PHT and primary PCI performed according to our local guideline-based protocol, which includes concomitant dual antiplatelet and anticoagulant therapy. Adjunct administration of a glycoprotein IIb/IIIa antagonist was at the discretion of the intervening cardiologist. In the PHT arm, tenecteplase was administered at a weight-based dose (55 to < 60 kg, 30 mg; 60 to < 70 kg, 35 mg; 70 to < 80 kg, 40 mg; 80 to < 90 kg, 45 mg; ≥ 90 kg, 50 mg). The tenecteplase dose administered to patients aged 75 years or more has since been reduced by half. Anticoagulant therapy consisted of a 30 mg intravenous bolus of enoxaparin (omitted for patients aged 75 years or more) followed by subcutaneous injection of 1 mg/kg bodyweight (0.75 mg/kg for patients aged 75 years or more) twice each day. Antiplatelet therapy consisted of a 300 mg loading dose of clopidogrel (omitted for patients aged 75 years or more) followed by 75 mg daily, together with an initial 300 mg aspirin dose, immediately followed by 100 mg daily. Patients in the PHT arm with electrical or haemodynamic instability, ongoing ischaemic symptoms, or less than 50% ST-segment resolution within 90 minutes of thrombolysis underwent rescue PCI.

Primary endpoints

The primary efficacy endpoint was 12-month all-cause mortality. The primary safety endpoint was bleeding, categorised according to Thrombolysis in Myocardial Infarction (TIMI) study group criteria.17

Statistical analysis

Summary statistics for patient characteristics in each of the two groups are presented. Normality of distribution was assessed with the Shapiro–Wilk test. Between-group comparisons of continuous variables used independent sample t tests for parametric data and pairwise comparison median tests for non-parametric data. The Pearson χ2 test assessed differences between categorical variables. Nelson–Aalen survival distributions were estimated, and adjusted using Cox proportional hazards regression models. Predictors of 12-month mortality were assessed using logistic regression. All statistical analyses were conducted in Stata 14 (StataCorp) and SAS 9.4 (SAS Institute).

Ethics approval

The study protocol was approved by the Hunter New England Human Research Ethics Committee in August 2014 (reference, 14/06/18/5.09).

Results

From 1 August 2008 to 31 August 2013, 484 patients with STEMI diagnosed by pre-hospital ECG were allocated to PHT (150 patients) or primary PCI (334 patients) on the basis of estimated FMC-to-CCL door times or any contraindication to thrombolysis (Appendix 2). There were more patients in the primary PCI group with diabetes mellitus or hypertension, and fewer with hypercholesterolaemia (Box 2).

The median time from FMC to the start of reperfusion was 35 minutes (IQR, 28–43 min) for bolus tenecteplase and 130 minutes (IQR, 100–150 min) for balloon inflation (P = 0.001). The median time between symptom onset and treatment was correspondingly shorter in the PHT group (94 [IQR, 65–127] v 180 [IQR, 140–265] minutes) (Box 2). The median distance of patients in the PHT group from the CCL was 119 km (range, 8–483 km). The median time from symptom onset to angiography was thus longer in the PHT group than in the primary PCI group, with a delay of 4 hours for the 27% of patients who required rescue or urgent intervention, and of 49 hours for the other patients in this group. Significantly, more open vessels (TIMI flow grade of 2 or more) were found on first angiography in the PHT than in the primary PCI group (45% v 8%; P < 0.001) (Box 3).

There were three ischaemic strokes and two transient ischaemic attacks in the primary PCI group and none in the PHT group. Four of the five patients who suffered a transient ischaemic attack or stroke had atrial fibrillation, either before or detected during the admission. Bleeding was significantly more frequent in the PHT group than in the primary PCI group (9.3% v 5.1%; P = 0.001) with two (1.3%) TIMI major bleeds and one (0.7%) intracranial haemorrhage in the PHT group (Box 4).

Of the total cohort of 484 patients, 34 (7.0%) died within 12 months (the primary efficacy endpoint): 10 of 150 patients (6.7%) in the PHT group and 24 of 334 (7.2%) in the primary PCI group (relative risk in the PHT group, 0.93; 95% CI, 0.45–1.9; P = 0.84) (Box 5). Anterior STEMI, cardiogenic shock, and hypertension were independent predictors of mortality for the total cohort of 484 patients in the multivariate analysis (Box 6). Age, bleeding, ejection fraction and femoral access were significant only in the univariate analysis (data not shown).

Discussion

Our study produced several important findings. First, delivery of PHT by paramedics, based on algorithm assessment of 12-lead ECGs, is feasible and safe in regional Australia. Second, 12-month mortality for patients remote from a CCL who receive PHT and are then transferred to a PCI-capable centre is similar to that for patients near the CCL who receive primary PCI.

Our practice is to administer fibrinolysis to STEMI patients who are remote from the CCL if there is no contraindication, and to then assess clinical and ECG signs of reperfusion. If they were successfully reperfused, we did not mandate immediate cardiac catheterisation but instead brought them to the CCL as soon as convenient, provided they remained clinically stable in the meantime. Those for whom reperfusion was not successful or chest pain recurred were urgently transferred to the CCL for rescue PCI.

To place our findings in context, we compared them with the outcomes of the STREAM trial.7 Our PHT group had some notable differences from the STREAM PI group: our patients were older, if not statistically significantly (62 years [SD, 13] v 60 years [SD, 12]), and a greater proportion of our patients were aged 75 years or more (18% v 14%); we also had a higher proportion of patients with cardiogenic shock (5.3% v 0.1%). Sex balance, rates of diabetes, hypertension, and prior coronary artery bypass graft surgery, and symptom onset-to-treatment times were similar for our PHT patients and the STREAM fibrinolysis group. The median time to angiography for our PHT group was 28 hours, compared with 10 hours in the STREAM fibrinolysis arm. Despite these differences, which indicate a higher risk level for our patients, survival at 12 months in the two fibrinolysis groups was identical (93.3%).

All-cause mortality at 12 months was similar for both treatment groups in our study, but this was not a randomised controlled trial, so that conclusions about treatment efficacy should not be drawn. The safety of the pre-hospital assessment and treatment, on the other hand, is reassuring. As expected, there was a significantly higher bleeding complication rate in the PHT group, but only one intracranial haemorrhage. There was a higher stroke rate in the primary PCI group; most events occurred in association with atrial fibrillation, but this finding requires further follow-up assessment of potential contributors.

The optimal ECG algorithm for the detection of STEMI is unknown. For ease of use in the field, we chose to perform standard 12-lead ECGs without right ventricular or posterior leads. For their interpretation, we use the Glasgow algorithm because of its specificity.10 It remains unknown whether the addition of right ventricular or posterior leads, or the use of another algorithm, would improve the sensitivity or specificity of detection in this setting.

The transport times for the primary PCI group in our study were considerably longer than the 60-minute FMC-to-CCL goal. The decision to administer or withhold PHT was driven mainly by the estimated FMC-to-CCL time. In our protocol, the approximate time to the CCL is estimated by the paramedics, as their knowledge of prevailing weather and traffic conditions means they are in the best position to do so. Their decision is then discussed with the cardiologist or advanced trainee. There may be some bias towards underestimating transport times, but, more importantly, there are inherent difficulties in adhering to these guidelines. First, patients who had any contraindication to fibrinolysis underwent primary PCI, regardless of the estimated FMC-to-CCL time, and this would increase overall transport times for the primary PCI group. Second, clinical factors (eg, treatment of arrhythmias, resuscitation from cardiac arrest) sometimes interfere with transport, also prolonging transfer times. It is therefore important that actual transport times are reported, not just the goal transfer times. It is hoped that knowledge of both will help when devising systems of care for other Australian regions.

The long distances to the CCL for the patients in our PHT group underscore the importance of implementing systems of care in areas with complex geography that achieve optimal outcomes for STEMI patients. The median times from symptom onset to treatment in both our treatment groups were comparable with those of the STREAM groups. This finding suggests that total ischaemic time is the interval with the greatest prognostic impact, and that we should focus on reducing this period, not than just door-to-balloon times. While medical practitioners can influence treatment intervals after FMC, community education campaigns that encourage patients to call an ambulance as soon as they have chest pain are needed for reducing the time from symptom onset to FMC.

Our study had some important limitations. First, it was a non-randomised, consecutive case series study. We present the mortality associated with two therapies, but baseline and other differences between the two groups may have contributed to the different outcomes. Second, our study was underpowered for detecting small differences in mortality, so that our results should be interpreted with caution. It is nevertheless hoped that our data can inform systems of care for patients with STEMI throughout Australia.

In conclusion, our real world experience showed that PHT delivered by paramedics followed by early transfer to a PCI-capable centre is a safe and effective reperfusion strategy for patients remote from primary PCI centres.

Box 1 –
The Hunter New England Local Health District, about 600 km from north to south. The John Hunter Hospital is located in Newcastle, in the bottom right hand corner of the map*

* Adapted from: Eastwood et al (2010).8

Box 2 –
Baseline characteristics of the pre-hospital thrombolysis (PHT) and primary percutaneous coronary intervention (PCI) groups

All patients

PHT group

Primary PCI group

P

Total number

484

150

334

Age (years), mean (SD)

64 (13)

62 (13)

65 (13)

0.3

≥ 75 years

115 (24%)

27 (18%)

88 (26%)

0.05

Sex (males)

365 (75%)

114 (7%)

251 (75%)

0.8

Systolic blood pressure (mmHg), mean (SD)

130 (24)

125 (25)

131 (24)

0.1

Cardiogenic shock

30 (6.2%)

8 (5.3%)

22 (6.5%)

0.8

Anterior STEMI

188 (39%)

55 (37%)

133 (40%)

0.5

Cardiovascular history

Coronary artery disease

96 (20%)

28 (19%)

68 (20%)

0.9

Prior coronary artery bypass graft surgery

13 (2.7%)

2 (1.3%)

11 (3.3%)

0.2

Hypertension

267 (55%)

64 (43%)

203 (61%)

< 0.001

Diabetes mellitus

97 (20%)

20 (13%)

77 (23%)

0.01

Smoking

213 (44%)

67 (45%)

146 (44%)

0.8

Hypercholesterolaemia

198 (41%)

76 (51%)

122 (36%)

0.002

Body mass index (kg/m2), mean (SD)

29 (5)

28 (6)

29 (5)

0.08

First medical contact to treatment (min), median (IQR)

105 (49–140)

35 (28–43)

130 (100–150)

0.001

Symptom to treatment (min), median (IQR)

155 (107–235)

94 (65–127)

180 (140–265)

< 0.001

Symptom to first medical contact > 3 h

83 (17%)

14 (9.3%)

69 (21%)

0.002

Ejection fraction, mean (SD)

48% (8)(n = 332)

49% (10)(n = 236)

47% (7)(n = 96)

0.01

Peak troponin (ng/mL), mean (SD)

48 (32)

44 (28)

50 (35)

0.04

Haemoglobin (g/L), mean (SD)

144 (48)

145 (43)

143 (56)

0.2

Creatinine (μmol/L), mean (SD)

95 (31)

89 (20)

98 (34)

0.006

Length of stay (days), mean (SD)

4 (3)

4 (3)

4 (3)

1.0

STEMI = ST-segment elevation myocardial infarction.

Box 3 –
Angiographic characteristics of the pre-hospital thrombolysis (PHT) and primary percutaneous coronary intervention (PCI) groups

PHT group

Primary PCI group

P

Total number

150

334

Coronary angiography undertaken

138 (92%)

334 (100%)

< 0.001

Rescue PCI undertaken

37 (27%)

NA

—

Symptom onset to angiography (h), median (IQR)

28 (6–70)

3.5 (2.2–4.2)

< 0.001

Time to rescue PCI (h), median (IQR)

4 (3–5)

NA

—

Initial TIMI flow score ≥ 2

67 (45%)

27 (8.1%)

< 0.001

PCI/CABG undertaken

97 (65%)

307 (92%)

< 0.001

Femoral access

52 (38%)

153 (46%)

0.08

IIb/IIIa antagonist administered

7 (4.7%)

151 (45.2%)

0.004

CABG = coronary artery bypass graft surgery; NA = not applicable; TIMI = Thrombolysis in Myocardial Infarction study group.

Box 4 –
Primary efficacy and safety outcomes for the pre-hospital thrombolysis (PHT) and primary percutaneous coronary intervention (PCI) groups

PHT group

Primary PCI group

P

Primary efficacy outcome

12-month all-cause mortality

10 (6.7%)

24 (7.2%)

0.84

Primary safety outcomes

Intracranial haemorrhage

1 (0.7%)

0

—

Total bleeding (TIMI bleeding criteria)

14 (9.3%)

17 (5.1%)

0.001

TIMI major bleeding

2 (14%*)

0

—

TIMI minor bleeding

5 (36%*)

9 (53%*)

0.005

TIMI minimal bleeding

7 (50%*)

8 (47%*)

0.5

TIMI = Thrombolysis in Myocardial Infarction study group. * Percentage of all bleeding.

Box 5 –
Nelson–Aalen cumulative hazard estimates for patients receiving pre-hospital thrombolysis or primary percutaneous coronary intervention

Box 6 –
Independent predictors of mortality in 484 patients with ST-segment elevation myocardial infarction (multivariate analysis)

Odds ratio (95% CI)

P

Anterior STEMI

2.4 (1.2–4.8)

0.01

Cardiogenic shock

8.5 (3.4–21.3)

< 0.001

Hypertension

4.2 (1.8–10)

0.001

STEMI = ST-segment elevation myocardial infarction.

Time to bury “hypertension”

An absolute cardiovascular risk approach will better target patients who need pharmacotherapy

The publication of the Systolic Blood Pressure Intervention Trial (SPRINT), sponsored by the United States National Institutes of Health, has left physicians claiming that systolic blood pressure targets of < 120 mmHg are too low and unobtainable, and that the results are not generalisable to their “real” patients.1 Although it was ostensibly a “hypertension optimal treatment” trial, it was also, in effect, a quasi-trial of the treatment for elevated blood pressure in high risk individuals who would otherwise remain untreated. This can be argued because the study population were all high risk patients determined by age, clinical conditions or Framingham risk score, and the entry-level systolic blood pressure was 130 mmHg rather than the normal treatment threshold of 140 mmHg. The low entry level, with a mean systolic blood pressure of 139.7 mmHg, probably explains the low targets achieved in the intensive treatment group. The study demonstrated not only that the reduction of systolic blood pressure leads to benefits in decreasing the rates of all-cause mortality and cardiovascular morbidity and mortality, but also that this reduction could be achieved with relative safety, even for older patients, as there was no overall difference in serious adverse event rates between the intensive treatment group and the standard treatment group. This conclusion had also been arrived at in the Hypertension in the Very Elderly Trial, a randomised controlled study of blood pressure lowering in very old patients, where serious adverse events were actually lower in the treatment group compared with the placebo group.2 The accepted wisdom of “it only takes one broken hip to wipe out all that gain in cardiovascular risk” does not seem to hold true.3

The predictable criticism of the findings reflects the entrenched clinical concept of hypertension — that there is a magic figure above which you have the condition and below which you do not. SPRINT reinforces that lowering blood pressure to at least 120 mmHg may be beneficial for a high risk individual as no J-curve nadir was demonstrated. It is opportune to return elevated blood pressure to its continuous variable risk factor status rather than treat it as a dichotomous disease. After all, the very term “hypertension” is confusing to patients.4

Who should we treat with blood pressure-lowering drugs?

Initiation of pharmacotherapy should be reserved for those who will probably benefit in terms of preventing a major adverse cardiovascular event, and when this benefit clearly outweighs the potential harms of side effects and costs of treatment. Candidates are therefore those at moderate to high risk of such events in what is an asymptomatic condition. A simple algorithm populated by the most important determinants of cardiovascular disease risk is sufficient to identify the individuals who do not have a manifest disease. This is readily accessible with the Australian absolute cardiovascular risk calculator.5 Such an approach recognises that drug therapy should be considered in the context of the whole person, while acknowledging that action on risk stratification can be challenging and complex for many.

Implementing the absolute cardiovascular risk factor approach in Australian health care

Australian clinical practice has not yet widely adopted the absolute cardiovascular risk factor approach,6 despite the development of evidence-based guidelines by the National Vascular Diseases Prevention Alliance (NVDPA). These guidelines are the result of a collaboration of four peak bodies — Kidney Health Australia, the National Heart Foundation, the National Stroke Foundation and Diabetes Australia — and have the endorsement of the National Health and Medical Research Council (NHMRC).7,8 The NHMRC has also recently adopted the absolute cardiovascular risk approach as one of its priority cases for research translation.9

With such an approach, the recommended pharmacotherapy regimen will need to be changed for high risk “normotensive” patients and for low risk “hypertensive” patients. The first group comprises individuals who are at a high risk due to a clinical manifestation of cardiovascular disease or clustering of risk factors, but whose blood pressure has not crossed the 140/90 mmHg threshold. The National Prescribing Service, as part of its MedicineWise program, and the NVDPA have addressed this group through educational programs which use case vignettes of the unexpected fatal myocardial infarction of a late middle-aged male smoker who did not have hypertension or hypercholesterolaemia (http://www.nps.org.au/media-centre/media-releases/repository/latest-program-from-nps-medicinewise-targets-blood-pressure). SPRINT reinforces the benefits of treatment in this group.

The second group comprises those (often younger) patients with mildly elevated blood pressure, who are low risk but hypertensive and for whom drug treatment is not recommended. For this group, there is a concern that such individuals may be harmed due to a delay or absence of treatment, allowing irreversible pathological damage to occur, that is, to accrue adverse legacy effects. While research in this area is ongoing and has yet to demonstrate such effects, it does contrast with another clinical concern, that of overdiagnosis.10,11 Diagnosing an individual with a medical condition has adverse effects for those who have an asymptomatic condition where intermediate benefit is very unlikely; this also has opportunity costs to society because of the misdirection of limited resources. Such individuals do not remain untreated, just unmedicated, as attention is paid to adverse health behaviours, which, when addressed, have benefits beyond the cardiovascular system. In practice, such individuals are likely to delay rather than avoid drug therapy, as age is the most important determinant of risk; however, their years on therapy will be truncated without affecting their lifespan and quality of life. Evidence suggests that reassessment of risk is not required for most low to moderate risk individuals within 8–10 years of the diagnosis, with the exception of those close to treatment thresholds, for whom annual review is recommended.12

Given the limited uptake of the absolute risk approach to date, how can we encourage its increased use? One possible way is through the Pharmaceutical Benefits Scheme (PBS). The current PBS indication for blood pressure-lowering agents is hypertension, rather than a specified blood pressure threshold. Hence, prescribing would seem to be unimpeded by the absolute risk approach, given that such a definition is likely to be deferred to expert guidelines. Cholesterol-lowering agents, on the other hand, have a complex set of criteria for eligible prescribing on the scheme that are not solely based on a single serum cholesterol threshold (http://www.pbs.gov.au/info/healthpro/explanatory-notes/gs-lipid-lowering-drugs). To advance cardiovascular health care in Australia, the NHMRC Primary Health Care Steering Group recognised that uptake of the absolute risk approach could be enhanced by changing PBS criteria for statins from these criteria to one based more simply on an absolute risk threshold.9 To this end, the NHMRC is asking the Pharmaceutical Benefits Advisory Committee to consider aligning their prescribing conditions to the NHMRC-approved absolute cardiovascular disease risk guidelines.8 This would mean that all physicians would need to become familiar with the Australian cardiovascular risk calculator in order to access statins for their primary prevention patients. Once habituated, they may be more willing and able to apply it in the setting of treating elevated blood pressure.

With benefit demonstrated at lower thresholds and to lower targets, there is a greater imperative to move away from the hypertensive model of care as these thresholds and targets approach the ideal blood pressure of 115 mmHg,13 which would capture most of the population. Taking the absolute risk route will, on the other hand, target those who have a covert cardiovascular disease most likely to manifest clinically in the foreseeable future and, therefore, benefit from pharmacotherapy.

Appropriate use of serum troponin testing in general practice: a narrative review

In this article, we review the evidence regarding troponin testing in a community setting, particularly relating to new information on the utility of high sensitivity assays and within the context of contemporary guidelines for the management of chest pain and the acute coronary syndrome. For this review, we synthesised relevant evidence from PubMed-listed articles published between 1996 and 2016 and our own experience to formulate an evidence-based overview of the appropriate use of cardiac troponin assays in clinical practice. We included original research studies, focusing on high quality randomised controlled trials and prospective studies where possible, systematic and other review articles, meta-analyses, expert consensus documents and specialist society guidelines, such as those from the National Heart Foundation of Australia and Cardiac Society of Australia and New Zealand. This article reflects our understanding of current state-of-the-art knowledge in this area.

What is the purpose of the serum troponin assay?

The troponin assay was designed to assist in diagnosis and improve risk stratification for people presenting in the emergency setting with symptoms suggestive of an acute coronary syndrome.1,2 These symptoms include:

  • chest, jaw, arm, upper back or epigastric pain or pressure

  • nausea

  • vomiting

  • dyspnoea

  • diaphoresis

  • sudden unexplained fatigue.

As the troponin assay was not designed for use in clinical contexts outside that of a possible acute coronary syndrome, an elevated troponin level in a patient without this history, although of prognostic value, is not likely to be due to myocardial infarction unless it was caused by a clinically silent event. The troponin test result should always be interpreted with reference to symptoms, comorbidities, physical examination findings and the electrocardiogram (ECG). The degree of troponin elevation is also used for quantifying the size of myocardial infarction, although it is not well validated for this purpose.3,4

What are the causes of serum troponin elevation?

Unlike the earlier creatine kinase assay, which was not specific to cardiac muscle, troponins are structural proteins unique to cardiac myocytes, and any elevation represents cardiac muscle injury or necrosis. Most cardiac troponin is attached to the myofilaments, but about 5% is free in the cytosol. In acute myocardial infarction or following cardiac trauma, there is disruption of the sarcolemmal membrane of the cardiomyocyte and release of the troponin in the cytoplasmic pool. There is a delay in the appearance of troponin in serum of between 90 and 180 minutes,5–7 which means there is a requirement for serial testing of troponin levels in hospital emergency departments. Later, there is a prolonged release of troponin from the degradation of myofilaments over 10–14 days.

It is now clear that troponin may also be released under conditions of myocardial stress without cellular necrosis (including tachyarrhythmia, prolonged exercise, sepsis, hypotension or hypertensive crisis and pulmonary embolism)8,9 (Box 1), probably through the mechanism of stress-induced myocyte bleb formation10 and release of a small portion of the cytoplasmic troponin pool. Elevations of troponin seen in this context are sometimes erroneously referred to as “false positives”; this is incorrect because any troponin elevation is truly abnormal and is prognostic in many clinical states outside of the acute coronary syndrome.11

The serum troponin assay was designed to screen patients for spontaneous, usually atherothrombotic, myocardial infarction, but under the new classification of myocardial infarction (Box 2),12 troponin elevations associated with demand–supply imbalance have led to the new diagnostic category of type 2 myocardial infarction (which is more likely to be associated with reversible or minimal myocardial injury, rather than permanent myocardial necrosis). The prevalence of all types of myocardial infarction, particularly type 2, has been amplified by the new high sensitivity troponin assays. A rise and fall in serum troponin level is required to confirm an acute myocardial infarction, irrespective of the type of troponin assay used. Chronic stable elevations are seen in some conditions (eg, chronic heart failure) where the lack of change over time indicates that an acute process is not present. True instances of false-positive troponin elevation due to calibration errors, heterophile antibodies or interfering substances have been greatly reduced by improved analytical techniques, blocking reagents and the use of antibody fragments.

What is different about the new high sensitivity troponin assays?

The newly developed high sensitivity assays provide reliable detection of very low concentrations of troponin and therefore offer earlier risk stratification of patients with possible acute coronary syndrome (3 hours after an episode of chest pain).7 The high sensitivity assays are also presented in different units (ng/L, rather than the previous μg/L), enabling the reporting of whole numbers (eg, 40 ng/L is equivalent to the earlier assay report of 0.04 μg/L).

By expert consensus, the assay must have a coefficient of variance of < 10% at the 99th percentile value of a reference population,13 which is the cut-off used for elevation. The benefit of the improved precision of the new high sensitivity assays is that even small elevations above this cut-off can be considered a true elevation, rather than an artefact of the assay. Examples of cut-off for elevation (> 99th percentile of a reference population) include a high sensitivity troponin T (hsTnT; Roche Elecsys) level of 14 ng/L, and a high sensitivity troponin I (hsTnI; Abbott Architect) level of 26 ng/L (these values may differ between pathology laboratories). It has been suggested that sex-specific cut-off values should be provided,12 and, in Australia, laboratories reporting the hsTnI assay often use these differing cut-offs (female, 16 ng/L; male, 26 ng/L).

A study in an Australian hospital found that use of the high sensitivity assays was associated with significantly earlier diagnosis and less time spent in the emergency department, but did not change the revascularisation rate or reduce mortality.14 A recent meta-analysis demonstrated that about 5% of an asymptomatic community population had an elevated serum troponin level when tested using a high sensitivity assay,11 clearly different to the reference population (screened to exclude comorbidities) that was used to derive the assay cut-off. Even in this asymptomatic cohort, an elevated troponin level had prognostic significance and was associated with a threefold greater risk of adverse cardiac outcomes compared with people with normal troponin levels. This reflects a greater hazard than identified previously for those with elevated cholesterol (risk ratio [RR], 1.9) or diabetes, (RR, 1.7) or even from smoking (RR, 1.68).15

As older patients (aged ≥ 65 years) have a high prevalence of elevated troponin levels, a higher troponin cut-off has been proposed for this group.16,17 More than 50% of patients with heart failure have elevated high sensitivity troponin levels, and the level is correlated with prognosis.18 It has also been shown in a large cohort of patients with chronic atrial fibrillation who were taking anticoagulant therapy19 that troponin elevation was independently related to the long term risk of cardiovascular events and cardiac death.

When should a general practitioner measure serum troponin and what should be done if a high serum troponin level is found?

Patients who present with a history of a possible acute coronary syndrome, but have been symptom-free for between 24 hours and 14 days previously, and who have no high risk features (ongoing or recurrent pain, syncope, heart failure, abnormal ECG) could be assessed with a single serum troponin test. If patients have had ongoing symptoms within the preceding 24 hours, they should be referred immediately to an emergency department for assessment.20 For patients in whom a single troponin test is appropriate, the test should be labelled as urgent and, as the result has prognostic implications and may require an urgent action plan, a system must be in place to ensure medical notification of the result at any hour of the day or night. In this clinical context, even a small elevation in serum troponin level may indicate an acute coronary syndrome during the preceding 2 weeks, warranting urgent cardiac assessment and hospital referral.20 However, a negative serum troponin result in the absence of high risk features does not exclude a diagnosis of unstable angina, and urgent cardiac assessment would still be appropriate if the presenting symptoms are severe or repetitive.

When should a general practitioner not measure serum troponin?

Patients presenting with a possible acute coronary syndrome with symptoms occurring within the preceding 24 hours, or with possible acute coronary syndrome more than 24 hours previously and with high risk features such as heart failure, syncope or an abnormal ECG, require further investigations.20 These may include urgent angiography, serial troponin testing and further ECGs in a monitored environment where emergency reperfusion treatments are available. These patients should be referred and transported to a hospital emergency department by ambulance, as it is not appropriate to perform serial troponin testing of high risk patients in a community setting.20 High risk ECG abnormalities include tachyarrhythmia or bradyarrhythmia, any ST deviation, deep T wave inversion or left bundle branch block. Serial troponin testing is required to confirm a diagnosis of myocardial infarction, and these patients may require fibrinolysis or urgent angiography and revascularisation.

Measurement of troponin in asymptomatic people is not currently recommended as the result may be problematic, with multiple possible causes and no clearly effective investigative strategies or therapies, and has to be interpreted with respect to the entire clinical context.

Case reports of appropriate and inappropriate use of troponin testing

Patient 1

A 72-year-old woman with type 2 diabetes tells you that she had 2 hours of chest tightness 4 days ago, but has been feeling well since then. Her physical examination is unremarkable, and you think her ECG is normal. You arrange for her to have an urgent serum troponin test, and the result is significantly elevated (hsTnI, 460 ng/L; female reference interval [RI], < 16 ng/L). You call a cardiologist, who arranges her immediate admission to hospital. Echocardiography shows hypokinesis of the anterior wall and apex and a left ventricular ejection fraction of 48%. Angiography shows a severe proximal left anterior descending artery lesion, which is treated with coronary stenting, and minor disease of the other arteries. She is discharged and has a good outcome.

Comment

In this setting, measurement of troponin is reasonable, as her symptoms occurred 4 days previously and she has had no further symptoms and has no high risk features.

Patient 2

A 68-year-old man presents to your surgery with a history of severe chest tightness lasting for 2 hours that morning. It has now resolved and he is pain-free 5 hours later. He has no major cardiovascular risk factors and his physical examination and ECG are normal. You do not order any other tests and arrange ambulance transport to a hospital emergency department. Testing at the hospital shows that his hsTnI level is elevated (84 ng/L; male RI, < 26 ng/L), and angiography shows severe left main coronary artery disease. He undergoes coronary revascularisation and has a good outcome.

Comment

This patient has had possible acute ischaemic symptoms within the past 24 hours. Troponin testing in a general practice setting should therefore not be performed, and the actions taken in sending this patient for urgent assessment are appropriate.

Patient 3

A 62-year-old man with no relevant past medical history presents with a history of several episodes in the past week of dull central chest pain lasting 5–10 minutes; the latest episode was 3 days ago. His physical examination and ECG are considered normal. An urgent serum troponin assay is performed and the result is normal (hsTnI, 3 ng/L; male RI, < 26 ng/L). You are worried that his clinical presentation may still be consistent with unstable angina. You contact a cardiologist, who arranges a stress echocardiogram the following day, which is strongly positive. The patient is admitted and is found to have severe three-vessel coronary artery disease. He undergoes revascularisation, with a good outcome.

Comment

This patient presents with symptoms suggestive of unstable angina. In this setting, irrespective of any troponin values, further urgent assessment is required.

Patient 4

A 52-year-old obese man with controlled hypertension has had multiple episodes in the past 12 months of prolonged retrosternal burning pain. These have often lasted several hours and are particularly worse after meals and when recumbent. He has had no symptoms for the past 4 days. His physical examination and ECG are normal. A serum troponin test result is normal. You arrange a stress echocardiogram, which is normal, and an upper gastrointestinal endoscopy, which shows severe reflux oesophagitis. He commences taking proton pump inhibitors and has good control of his symptoms.

Comment

The symptoms of cardiac ischaemia are often atypical. In the absence of recent symptoms, consideration of a cardiac cause of this patient’s presentation is essential and, in the context of this case, a single troponin test is appropriate.

Patient 5

A 58-year-old formerly well woman presents to you immediately after a 1-hour episode of burning central chest discomfort, which resolved spontaneously. She has experienced minor chest pain episodically for the past 3 days. Her physical examination and ECG are normal. It is 7 pm; you order a serum troponin test and give her a referral for an upper gastrointestinal endoscopy. As you leave the surgery, you turn off your mobile phone so that you will not be interrupted, as you are going to the cinema. When you turn your phone on later that evening, you have two messages. The first message tells you that the troponin test result showed an elevated level (hsTnI, 43 ng/L; female RI, < 16 ng/L). The second message is from your patient’s husband, who says your patient developed severe chest pain at home and they were uncertain what to do. Upon calling her husband, he tearfully says that she had a cardiac arrest at home and did not survive.

Comment

A number of concerns arise in this case. First, the troponin test should not have been ordered as there was a significant clinical suspicion of an acute coronary syndrome and, with symptoms within the past 24 hours, the patient is considered potentially at high risk and should have been urgently referred to hospital, where serial ECGs, troponin testing and risk stratification could be performed in the safety of a fully equipped emergency department. Second, whenever troponin testing is used, systems must be in place for the result to be conveyed urgently to the medical practitioner21 and appropriate action taken.

Conclusions

Acute coronary syndrome remains a major cause of death and long term morbidity. For patients presenting to a general practice with possible acute coronary syndrome within the preceding 24 hours, including symptoms consistent with either unstable angina or high risk clinical features, a serum troponin test should not be ordered. Instead, these patients should be referred to an emergency department for evaluation in a monitored environment capable of offering defibrillation, urgent fibrinolysis or revascularisation. However, patients presenting with ischaemic symptoms that occurred more than 24 hours previously, who are now symptom-free and have no high risk features, may be assessed with a single troponin assay and referred urgently to hospital if the result is elevated. If the troponin result is negative, unstable angina is not excluded and urgent or semi-urgent cardiac referral may still be appropriate, depending on the timing and severity of symptoms. When troponin assays are used, systems must be in place for the result to be conveyed urgently to a medical practitioner so that appropriate action may be taken.

Future directions

Further refinement of strategies that use high sensitivity troponin assays may improve upon the current 3-hour rule-out time for acute myocardial infarction. Other methods of early risk stratification, including imaging techniques, are currently being evaluated. In the future, troponin levels may also prove to be useful in many clinical contexts, including gauging cardiotoxicity with chemotherapeutic agents, identifying cardiac allograft rejection or monitoring patients with heart failure. In addition, there is potential for troponin testing to be included in newer models of general cardiovascular risk stratification, but until further evaluation in prospective trials demonstrates a clinical benefit, troponin should not be measured in asymptomatic individuals.

Box 1 –
Causes of serum troponin level elevation

  • Acute myocardial infarction (see )
  • Coronary artery spasm (eg, due to cocaine or methamphetamine use)
  • Takotsubo cardiomyopathy
  • Coronary vasculitis (eg, systemic lupus erythematosus, Kawasaki disease)
  • Acute or chronic heart failure
  • Tachyarrhythmia or bradyarrhythmia
  • Frequent defibrillator shocks
  • Cardiac contusion or surgery
  • Rhabdomyolysis with cardiac involvement
  • Myocarditis or infiltrative diseases (eg, amyloidosis, sarcoidosis, haemochromatosis)
  • Cardiac allograft rejection
  • Hypertrophic cardiomyopathy
  • Cardiotoxic agents (eg, anthracyclines, trastuzumab, carbon monoxide poisoning)
  • Aortic dissection or severe aortic valve disease
  • Severe hypotension or hypertension (eg, haemorrhagic shock, hypertensive emergency)
  • Severe pulmonary embolism, pulmonary hypertension or respiratory failure
  • Dialysis-dependent renal failure
  • Severe burns affecting > 30% of the body surface
  • Severe acute neurological conditions (eg, stroke, cerebral bleeding or trauma)
  • Sepsis
  • Prolonged exercise or extreme exertion (eg, marathon running)

Box 2 –
The new classification of myocardial infarction (MI)12

Type

Clinical situation

Definition

1

Spontaneous

MI related to ischaemia from primary coronary event such as plaque rupture, erosion, fissuring or dissection

2

Demand–supply imbalance

MI related to secondary ischaemia due to myocardial oxygen supply–demand imbalance such as spasm, anaemia, hypotension or arrhythmia

3

Sudden death

Unexpected cardiac death, perhaps suggestive of MI, but occurring before blood samples can be obtained

4a

PCI

MI associated with PCI procedure

4b

Stent thrombosis

MI associated with stent thrombosis, as seen on angiography or autopsy

5

CABG

MI associated with CABG

CABG = coronary artery bypass grafting. PCI = percutaneous coronary intervention.

Guideline for the diagnosis and management of hypertension in adults — 2016

Blood pressure (BP) is an important common modifiable risk factor for cardiovascular disease. In 2014–15, 6 million adult Australians were hypertensive (BP ≥ 140/90 mmHg) or were taking BP-lowering medication.1 Hypertension is more common in those with lower household incomes and in regional areas of Australia (http://heartfoundation.org.au/about-us/what-we-do/heart-disease-in-australia/high-blood-pressure-statistics). Many Australians have untreated hypertension, including a significant proportion of Aboriginal and Torres Strait Islander people.1

Cardiovascular diseases are associated with a high level of health care expenditure.2 Controlled BP is associated with lower risks of stroke, coronary heart disease, chronic kidney disease, heart failure and death. Small reductions in BP (1–2 mmHg) are known to markedly reduce population cardiovascular morbidity and mortality.3,4

Method

The National Blood Pressure and Vascular Disease Advisory Committee, an expert committee of the National Heart Foundation of Australia, has updated the Guide to management of hypertension 2008: assessing and managing raised blood pressure in adults (last updated in 2010)5 to equip health professionals across the Australian health care system, especially those within primary care and community services, with the latest evidence to prevent, detect and manage hypertension.

International hypertension guidelines6–8 were reviewed to identify key areas for review. Review questions were developed using the patient problem or population, intervention, comparison and outcome(s) (PICO) framework.9 Systematic literature searches (2010–2014) of MEDLINE, Embase, CINAHL and the Cochrane Library were conducted by an external organisation, and the resulting evidence summaries informed the updated clinical recommendations. The committee also reviewed additional key literature relevant to the PICO framework up to December 2015.

Recommendations were based on high quality studies, with priority given to large systematic reviews and randomised controlled trials, and consideration of other studies where appropriate. Public consultation occurred during the development of the updated guideline. The 2016 update includes the level of evidence and strength of recommendation in accordance with National Health and Medical Research Council standards10 and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology.11 No level of evidence has been included where there was no direct evidence for a recommendation that the guideline developers agreed clearly outweighed any potential for harm.

Most of the major recommendations from the guideline are outlined below, together with background information and explanation, particularly in areas of change in practice. Key changes from the previous guideline are listed in Box 1. The full Heart Foundation Guideline for the diagnosis and management of hypertension in adults – 2016 is available at http://heartfoundation.org.au/for-professionals/clinical-information/hypertension. The full guideline contains additional recommendations in the areas of antiplatelet therapy, suspected BP variability, and initiating treatment using combination therapy compared with monotherapy.

Recommendations

Definition and classification of hypertension

Elevated BP is an established risk factor for cardiovascular disease. The relationship between BP level and cardiovascular risk is continuous, therefore the distinction between normotension and hypertension is arbitrary.12,13 Cut-off values are used for diagnosis and management decisions but vary between international guidelines. Current values for categorisation of clinic BP in Australian adults are outlined in Box 2.

Management of patients with hypertension should also consider absolute cardiovascular disease risk (where eligible for assessment) and/or evidence of end-organ damage. Several tools exist to estimate absolute cardiovascular disease risk. The National Vascular Disease Prevention Alliance developed a calculator for the Australian population, which can be found at http://www.cvdcheck.org.au.

Treatment strategies for individuals at high risk of a cardiovascular event may differ from those at low absolute cardiovascular disease risk despite similar BP readings. It is important to note that the absolute risk calculator has been developed using clinic BP, rather than ambulatory, automated office or home BP measures.

Some people are not suitable for an absolute risk assessment, including younger patients with uncomplicated hypertension and those with conditions that identify them as already at high risk.14

Blood pressure measurement

A comprehensive assessment of BP should be based on multiple measurements taken on several separate occasions. A variety of methods are available, each providing different but often complementary information. Methods include clinic BP, 24-hour ambulatory and home BP monitoring (Box 3).

Most clinical studies demonstrating effectiveness and benefits of treating hypertension have used clinic BP. Clinic, home and ambulatory BP all predict the risk of a cardiovascular event; however, home and ambulatory blood pressure measures are stronger predictors of adverse cardiovascular outcomes (Box 4).15,16

Automated office BP measurement involves taking repeated blood pressure measurements using an automated device with the clinician out of the room.17,18 This technique generally yields lower readings than conventional clinic BP and has been shown to have a good correlation with out-of-clinic measures.

The British Hypertension Society provides a list of validated BP monitoring devices.19 Use of validated and regularly maintained non-mercury devices is recommended as mercury sphygmomanometers are being phased out for occupational health and safety and environmental reasons.

Treatment thresholds

Although the benefits of lowering BP in patients with significantly elevated BP have been well established, the benefit of initiating drug therapy in patients with lower BP with or without comorbidities has been less certain. A meta-analysis of patients with uncomplicated mild hypertension (systolic BP range, 140–159 mmHg) indicated beneficial cardiovascular effects with reductions in stroke, cardiovascular death and all-cause mortality, through treatment with BP-lowering therapy.20 Corresponding relative reductions in 5-year cardiovascular disease risk were similar for all levels of baseline BP.21

Decisions to initiate drug treatment at less severe levels of BP elevations should consider a patient’s absolute cardiovascular disease risk and/or evidence of end-organ damage together with accurate blood pressure readings.

Treatment targets

Optimal blood pressure treatment targets have been debated extensively. There is emerging evidence demonstrating the benefits of treating to optimal BP, particularly among patients at high cardiovascular risk.17,20

The recent Systolic Blood Pressure Intervention Trial investigated the effect of targeting a higher systolic BP level (< 140 mmHg) compared with a lower level (< 120 mmHg) in people over the age of 50 years who were identified as having a cardiovascular 10-year risk of at least 20%.17 Many had prior cardiovascular events or mild to moderate renal impairment and most were already on BP-lowering therapy at the commencement of the study. Patients with diabetes, cardiac failure, severe renal impairment or previous stroke were excluded. The method of measurement was automated office BP,18 a technique that generally yields lower readings than conventional clinic BP. Patients treated to the lower target achieved a mean systolic BP of 121.4 mmHg and had significantly fewer cardiovascular events and lower all-cause mortality compared with the other treatment group, which achieved a mean systolic level of 136.2 mmHg. Older patients (> 75 years) benefited equally from the lower target BP. However, treatment-related adverse events increased in the more intensively treated patients, with more frequent hypotension, syncopal episodes, acute kidney injury and electrolyte abnormalities.

The selection of a BP target should be based on an informed, shared decision-making process between patient and doctor (or health care provider), considering the benefits and harms and reviewed on an ongoing basis.

Recommendations for treatment strategies and treatment targets for patients with hypertension are set out in Box 5.

Box 1 –
Key changes from previous guideline

  • Use of validated non-mercury sphygmomanometers that are regularly maintained is recommended for blood pressure (BP) measurement.
  • Out-of-clinic BP using home or 24-hour ambulatory measurement is a stronger predictor of outcome than clinic BP measurement.
  • Automated office blood pressure (AOBP) provides similar measures to home and ambulatory BP, and results are generally lower than those from conventional clinic BP measurement.
  • BP-lowering therapy is beneficial (reduced stroke, cardiovascular death and all-cause mortality) for patients with uncomplicated mild hypertension (systolic BP, 140–159 mmHg).
  • For patients with at least moderate cardiovascular risk (10-year risk, 20%), lower BP targets of < 120 mmHg systolic (using AOBP) provide benefit with some increase in treatment-related adverse effects.
  • Selection of a BP target should be based on informed, shared decision making between patients and health care providers considering the benefits and harms, and reviewed on an ongoing basis.

Box 2 –
Classification of clinic blood pressure in adults

Diagnostic category*

Systolic (mmHg)

Diastolic (mmHg)

Optimal

< 120

and

< 80

Normal

120–129

and/or

80–84

High-normal

130–139

and/or

85–89

Grade 1 (mild) hypertension

140–159

and/or

90–99

Grade 2 (moderate) hypertension

160–179

and/or

100–109

Grade 3 (severe) hypertension

≥ 180

and/or

≥ 110

Isolated systolic hypertension

> 140

and

< 90

Reproduced with permission from the National Heart Foundation of Australia. Guideline for the diagnosis and management of hypertension in adults — 2016. Melbourne: NHFA, 2016. * When a patient’s systolic and diastolic blood pressure levels fall into different categories, the higher diagnostic category and recommended actions apply.

Box 3 –
Criteria for diagnosis of hypertension using different methods of measurement

Method of measurement

Systolic (mmHg)

Diastolic (mmHg)

Clinic

≥ 140

and/or

≥ 90

ABPM daytime (awake)

≥ 135

and/or

≥ 85

ABPM night-time (asleep)

≥ 120

and/or

≥ 70

ABPM over 24 hours

≥ 130

and/or

≥ 80

HBPM

≥ 135

and/or

≥ 85

Reproduced with permission from the National Heart Foundation of Australia. Guideline for the diagnosis and management of hypertension in adults — 2016. Melbourne: NHFA, 2016. ABPM = ambulatory blood pressure monitoring. HBPM = home blood pressure monitoring.

Box 4 –
Recommendations for monitoring blood pressure (BP) in patients with hypertension or suspected hypertension

Method of measuring BP

Grade of recommendation*

Level of evidence†

If clinic BP is ≥ 140/90 mmHg or hypertension is suspected, ambulatory and/or home monitoring should be offered to confirm the BP level

Strong

I

Clinic BP measures are recommended for use in absolute cardiovascular risk calculators. If home or ambulatory BP measures are used in absolute cardiovascular disease risk calculators, risk may be inappropriately underestimated

Strong

–

Procedures for ambulatory BP monitoring should be adequately explained to patients. Those undertaking home measurements require appropriate training under qualified supervision

Strong

I

Finger and/or wrist BP measuring devices are not recommended

Strong

–

Reproduced with permission from the National Heart Foundation of Australia. Guideline for the diagnosis and management of hypertension in adults — 2016. Melbourne: NHFA, 2016. * Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology.11 † National Health and Medical Research Council standards;10 no level of evidence included where there was no direct evidence for a recommendation that the guideline developers agreed clearly outweighed any potential for harm.

Box 5 –Recommendations for treatment strategies and treatment targets for patients with hypertension, with grade of recommendation and level of evidence*

A healthy lifestyle, including not smoking, eating a nutritious diet and regular adequate exercise is recommended for all Australians including those with and without hypertension.

  • Lifestyle advice is recommended for all patients (grade: strong; level: –).
  • For patients at low absolute cardiovascular disease risk (5-year risk, < 10%) with persistent blood pressure (BP) ≥ 160/100 mmHg, antihypertensive therapy should be started (grade: strong; level: I).
  • For patients at moderate absolute cardiovascular disease risk (5-year risk, 10–15%) with persistent systolic BP ≥ 140 mmHg and/or diastolic ≥ 90 mmHg, antihypertensive therapy should be started (grade: strong; level: I).
  • Once decided to treat, patients with uncomplicated hypertension should be treated to a target of < 140/90 mmHg or lower if tolerated (grade: strong; level: I).
  • In selected high cardiovascular risk populations where a more intense treatment can be considered, aiming for a target of < 120 mmHg systolic BP can improve cardiovascular outcomes (grade: strong; level: II).
  • In selected high cardiovascular risk populations where a treatment is being targeted to < 120 mmHg systolic BP, close follow-up of patients is recommended to identify treatment-related adverse effects including hypotension, syncope, electrolyte abnormalities and acute kidney injury (grade: strong; level: II).
  • In patients with uncomplicated hypertension, angiotensin-converting enzyme (ACE) inhibitors or angiotensin-receptor blockers (ARBs), calcium channel blockers and thiazide diuretics are all suitable first-line antihypertensive drugs, either as monotherapy or in some combinations unless contraindicated (grade: strong; level: I).
  • The balance between efficacy and safety is less favourable for β-blockers than other first-line antihypertensive drugs. Thus β-blockers should not be offered as a first-line drug therapy for patients with hypertension that is not complicated by other conditions (grade: strong; level: I).
  • ACE inhibitors and ARBs are not recommended in combination due to an increased risk of adverse effects (grade: strong; level: I).

Treatment-resistant hypertension

Treatment-resistant hypertension is defined as a systolic BP ≥ 140 mmHg in a patient who is taking three or more antihypertensive medications, including a diuretic at optimal tolerated doses. Contributing factors may include variable compliance, white coat hypertension or secondary causes for hypertension.Few drug therapies specifically target resistant hypertension. Renal denervation is currently being investigated as a treatment option in this condition; however, to date, it has not been found to be effective in the most rigorous study conducted.22

  • Optimal medical management (with a focus on treatment adherence and excluding secondary causes) is recommended (grade: strong; level: II).
  • Percutaneous transluminal radiofrequency sympathetic denervation of the renal artery is currently not recommended for the clinical management of resistant hypertension or lower grades of hypertension (grade: weak; level: II).

Patients with hypertension and selected comorbidities

Stroke and transient ischaemic attack:

  • For patients with a history of transient ischaemic attacks or stroke, antihypertensive therapy is recommended to reduce overall cardiovascular risk (grade: strong; level: I).
  • For patients with a history of transient ischaemic attacks or stroke, any of the first-line antihypertensive drugs that effectively reduce BP are recommended (grade: strong; level: I).
  • For patients with hypertension and a history of transient ischaemic attacks or stroke, a BP target of < 140/90 mmHg is recommended (grade: strong; level: I).

Chronic kidney disease:

Most classes of BP-lowering drugs have a similar effect in reducing cardiovascular events and all-cause mortality in patients with chronic kidney disease (CKD). When treating with diuretics, the choice should be dependent on both the stage of CKD and the extracellular fluid volume overload in the patient. Detailed recommendations on how to manage patients with CKD are available.23

  • In patients with hypertension and CKD, any of the first-line antihypertensive drugs that effectively reduce BP are recommended (grade: strong; level: I).
  • When treating hypertension in patients with CKD in the presence of microalbuminuria or macroalbuminuria, an ARB or ACE inhibitor should be considered as first-line therapy (grade: strong; level: I).
  • In patients with CKD, antihypertensive therapy should be started in those with BP consistently > 140/90 mmHg and treated to a target of < 140/90 mmHg (grade: strong; level: I).
  • Dual renin-angiotensin system blockade is not recommended in patients with CKD (grade: strong; level: I).
  • For patients with CKD, aiming towards a systolic BP < 120 mmHg has shown benefit, where well tolerated (grade: strong; level: II).
  • In people with CKD, where treatment is being targeted to less than 120 mmHg systolic BP, close follow-up of patients is recommended to identify treatment-related adverse effects, including hypotension, syncope, electrolyte abnormalities and acute kidney injury (grade: strong; level: I).
  • In patients with CKD, aldosterone antagonists should be used with caution in view of the uncertain balance of risks versus benefits (grade: weak; level: –).

Diabetes:

  • Antihypertensive therapy is strongly recommended in patients with diabetes and systolic BP ≥ 140 mmHg (grade: strong; level: I).
  • In patients with diabetes and hypertension, any of the first-line antihypertensive drugs that effectively lower BP are recommended (grade: strong; level: I).
  • In patients with diabetes and hypertension, a BP target of < 140/90 mmHg is recommended (grade: strong; level: I).
  • A systolic BP target of < 120 mmHg may be considered for patients with diabetes in whom prevention of stroke is prioritised (grade: weak; level: –).
  • In patients with diabetes, where treatment is being targeted to < 120 mmHg systolic BP, close follow-up of patients is recommended to identify treatment-related adverse effects including hypotension, syncope, electrolyte abnormalities and acute kidney injury (grade: strong; level: –).

Myocardial infarction:

  • For patients with a history of myocardial infarction, ACE inhibitors and β-blockers are recommended for the treatment of hypertension and secondary prevention (grade: strong; level: II).
  • β-Blockers or calcium channel blockers are recommended for symptomatic patients with angina (grade: strong; level: II).

Chronic heart failure:

  • In patients with chronic heart failure, ACE inhibitors and selected β-blockers are recommended (grade: strong; level: II).
  • ARBs are recommended in patients who do not tolerate ACE inhibitors (grade: strong; level: I).

Peripheral arterial disease:

  • In patients with peripheral arterial disease, treating hypertension is recommended to reduce cardiovascular disease risk (grade: strong; level: –).
  • In patients with hypertension and peripheral arterial disease, any of the first-line antihypertensive drugs that effectively reduce BP are recommended (grade: weak; level: –).
  • In patients with hypertension and peripheral arterial disease, reducing BP to a target of < 140/90 mmHg should be considered and treatment guided by effective management of other symptoms and contraindications (grade: strong; level: –).

Older people:

  • Any of the first-line antihypertensive drugs that effectively reduce BP can be used in older patients with hypertension (grade: strong; level: I).
  • When starting treatment in older patients, drugs should be commenced at the lowest dose and titrated slowly as adverse effects increase with age (grade: strong; level: –).
  • For patients > 75 years of age, aiming towards a systolic BP of < 120 mmHg has shown benefit, where well tolerated, unless there is concomitant diabetes (grade: strong; level: II).
  • In older people whose treatment is being targeted to < 120 mmHg systolic BP, close follow-up is recommended to identify treatment-related adverse effects including hypotension, syncope, electrolyte abnormalities and acute kidney injury (grade: strong; level: II).
  • Clinical judgement should be used to assess benefit of treatment against risk of adverse effects in all older patients with lower grades of hypertension (grade: strong; level: –).

Adapted with permission from the National Heart Foundation of Australia. Guideline for the diagnosis and management of hypertension in adults – 2016. Melbourne: NHFA, 2016. * Grade of recommendation based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology;11 level of evidence according to the National Health and Medical Research Council standards10 — no level of evidence included where there was no direct evidence for a recommendation that the guideline developers agreed clearly outweighed any potential for harm.