Cardiology

Dr Linda Calabresi
Clinical Articles iconClinical Articles

This week’s valuable resource award is a little different to the usual. Rather than a handy algorithm or useful assessment tool, this is, in fact an article from a recent Australian Prescriber. It’s about all the potential complications and side effects that can potentially occur with amiodarone, that reasonably popular drug that tends to get started in patients with AF and ventricular arrhythmias. In fact, the list of potential side-effects is quite extensive and not all that intuitive, particularly in elderly patients, which is why having this article bookmarked somewhere to be able to access at a moment’s notice is such a good idea.

Dr Stephen Gordon
Monographs iconMonographs

This article summarises, in the light of recent research, the current benefits and disadvantages of prescribing low-dose aspirin.

Dr Linda Calabresi
Clinical Articles iconClinical Articles

To ablate, or not to ablate? That is the question. That’s what international researchers were investigating in two studies just published in The Journal of the American Medical Association. And the answer? As so often happens in medicine, the answer is: it depends. Looking at the two studies, patients with symptomatic atrial fibrillation had a greater improvement in their quality of life at the one year mark if they had undergone catheter ablation than if they had been treated with medical treatment alone. But not to diminish the importance of quality of life as a measure of success, other findings from the latest research are also worth noting. In the larger of the two studies, a randomised controlled controlled trial of over 2200  patients presenting with symptomatic AF, researchers found after four years of follow-up that there was no significant difference in mortality between the group who had received catheter ablation and those who were treated with drug therapy alone. Similarly, the rate of disabling stroke, serious bleeding and cardiac arrest were the same between the two groups. As one would expect there was a higher rate of AF recurrence among the drug therapy group as compared with the catheter ablation group (70% vs 50%), however that 50% recurrence rate among those who’d undergone the ablation procedure is still pretty high and overall among that intervention group 19.4% underwent a repeat procedure. But the study authors who came from 10 different countries did not seem too deflated by the result. While their study failed to show benefit for catheter ablation in any of the primary outcomes such as death or stroke they did find some advantage in terms of secondary outcomes, including quality of life. They also point to a trend toward benefit of the procedure even if that benefit wasn’t large enough to reach clinical significance. The other JAMA study involved just 155 patients who had symptomatic paroxysmal or persistent AF and who were randomised to receive either catheter ablation or drug therapy. The Scandinavian researchers were particularly assessing their symptoms and their quality of life. After four years, the catheter ablation group ‘produced 14% more patients who achieved complete or near complete relief from their AF symptoms.’ What’s more the quality of life improved for patients in both groups. However, the improvement was greater in the ablation group. So, what does it all mean? Firstly, it needs to be pointed out that, in keeping with the guidelines the majority of patients included in these trials were symptomatic – only 10% were asymptomatic. In other words, there have to be symptoms or another very good reason to consider ablation in a patient with AF. Secondly, overall, the ablation group was more successful than the drug therapy group in relieving those symptoms. As an accompanying editorial puts it: “For patients with symptoms, in whom quality of life is impaired by AF, catheter ablation can improve quality of life to a greater extent than drug therapy. However, patients who choose drug therapy will also likely experience significant improvements in quality of life and have no worse risk for the most concerning complications of AF, stroke and death. Thus, there is no mandate for these patients to undergo catheter ablation at this time.” And that’s where we’re at.

Reference:

Packer DL, Mark DB, Robb RA, Monahan KH, Bahnson TD, Poole JE, et al. Effect of Catheter Ablation vs Antiarrhythmic Drug Therapy on Mortality, Stroke, Bleeding, and Cardiac Arrest Among Patients With Atrial Fibrillation: The CABANA Randomized Clinical Trial. JAMA. 2019 Mar 15. DOI: 10.1001/jama.2019.0693 [Epub ahead of print] Mark DB, Anstrom KJ, Sheng S, Piccini JP, Baloch KN, Monahan KH, et al. Effect of Catheter Ablation vs Medical Therapy on Quality of Life Among Patients With Atrial Fibrillation: The CABANA Randomized Clinical Trial. JAMA. 2019 Mar 15. DOI: 10.1001/jama.2019.0692 [Epub ahead of print] Albert CM, Bhatt DL. Catheter Ablation for Atrial Fibrillation: Lessons Learned From CABANA. JAMA. 2019 Mar 15. DOI: 10.1001/jama.2018.17478 [Epub ahead of print] Blomström-Lundqvist C, Gizurarson S, Schwieler J, Jensen SM, Bergfeldt L, Kennebäck G, et al. Effect of Catheter Ablation vs Antiarrhythmic Medication on Quality of Life in Patients With Atrial Fibrillation: The CAPTAF Randomized Clinical Trial. JAMA. 2019 Mar 19; 321(11): 1059-68. DOI: 10.1001/jama.2019.0335
Dr Nelson Chong
Clinical Articles iconClinical Articles

A stressful event, such as the death of a loved one, really can break your heart. In medicine, the condition is known as broken heart syndrome or takotsubo syndrome. It is characterised by a temporary disruption of the heart’s normal pumping function, which puts the sufferer at increased risk of death. It’s believed to be the reason many elderly couples die within a short time of each other. Broken heart syndrome has similar symptoms to a heart attack, including chest pain and difficulty breathing. During an attack, which can be triggered by a bereavement, divorce, surgery or other stressful event, the heart muscle weakens to the extent that it can no longer pump blood effectively. In about one in ten cases, people with broken heart syndrome develop a condition called cardiogenic shock where the heart can’t pump enough blood to meet the body’s needs. This can result in death.

Physical damage

It has long been thought that, unlike a heart attack, damage caused by broken heart syndrome was temporary, lasting days or weeks, but recent research suggest that this is not the case. A study by researchers at the University of Aberdeen provided the first evidence that broken heart syndrome results in permanent physiological changes to the heart. The researchers followed 52 patients with the condition for four months, using ultrasound and cardiac imaging scans to look at how the patients’ hearts were functioning in minute detail. They discovered that the disease permanently affected the heart’s pumping motion. They also found that parts of the heart muscle were replaced by fine scars, which reduced the elasticity of the heart and prevented it from contracting properly. In a recent follow-up study, the same research team reported that people with the broken heart syndrome have persistent impaired heart function and reduced exercise capacity, resembling heart failure, for more than 12 months after being discharged from hospital.

Long-term risk

A new study on the condition, published in Circulation, now shows that the risk of death remains high for many years after the initial attack. In this study, researchers in Switzerland compared 198 patients with broken heart syndrome who developed cardiogenic shock with 1,880 patients who did not. They found that patients who experienced cardiogenic shock were more likely to have had the syndrome triggered by physical stress, such as surgery or an asthma attack, and they were also significantly more likely to have died five years after the initial event. People with major heart disease risk factors, such as diabetes and smoking, were also much more likely to experience cardiogenic shock, as were people with atrial fibrillation (a type of heart arrythmia). A second study from Spain found similar results among 711 people with broken heart syndrome, 11% of whom developed cardiogenic shock. Over the course of a year, cardiogenic shock was the strongest predictor of death in this group of patients. These studies show that cardiogenic shock is not an uncommon risk factor in broken heart syndrome patients, and it is a strong predictor of death. They shed light on a condition that was previously thought to be less serious than it is. The evidence now clearly shows that the condition is not temporary and it highlights an urgent need to establish new and more effective treatments and careful monitoring of people with this condition.
A/Prof David Colquhoun
Monographs iconMonographs

This article discusses the importance of supplementary intake of marine omega-3 polyunsaturated fatty acids: (EPA) and (DHA) for patients post-acute myocardial infarction.

Dr Linda Calabresi
Clinical Articles iconClinical Articles

The physical health of mentally ill patients is a "massive problem and we are doing very badly at it,” psychiatrist Dr Matthew Warden told doctors at a recent Healthed evening seminar in Sydney. In particular, the prevalence of high cardiovascular risk among patients with a history of psychosis, means this population was a "ticking time bomb", said Dr Warden, who is the Director of Acute Inpatient Services for Mental Health at St Vincent’s Hospital in Melbourne. Even without antipsychotic medication, a disproportionate number of people with a history of psychosis are overweight or obese, do very little if any physical exercise and smoke. And it is well-known that the metabolic side-effects associated with antipsychotic medications increases this cardiovascular risk enormously. Consequently, there has been growing pressure on psychiatrists to assess, monitor and manage the physical health of their patients with psychosis, but Dr Warden said, realistically this needs to be also done by GPs as they will usually be managing these patients long-term and "they are better at it.” Baseline metabolic measurements need to be taken at first episode of psychosis, including weight, BMI, BP, lipid levels, fasting blood sugar and smoking status. Weight, in particular needs to be monitored carefully following the commencement of antipsychotic medication, as weight gain is extremely common, especially with olanzapine which, Australia-wide is the most commonly prescribed antipsychotic. In answer to a GP’s question following his talk, Dr Ward said it is extremely difficult to avoid or reverse this medication-induced weight gain with diet and exercise alone. In addition, weight loss pharmacotherapy such as phentermine is contraindicated in people with a history of psychosis. Key to managing the weight gain issue was to choose an antipsychotic with the least long-term side effects from the outset. Olanzapine and clozapine are associated with the greatest weight gain while lurasidone and the partial agonists, aripiprazole and ziprasidone have the least effect on weight. Alternatively, for patients who may have been started on olanzapine or similar, swap to a more weight-neutral medication at the first sign they were gaining weight or developing other metabolic side-effects. It is more likely that a person who as gained weight on olanzapine, will lose that weight if switched to another weight-neutral medication early. The longer that patient stays on olanzapine and the weight gain is sustained, the harder it will be to shift even if the medication is changed, Dr Warden said. In addition to managing weight gain in mentally ill patients, Dr Warden also encouraged GPs to offer smoking cessation advice and help. Even though this population were often considered among the most dependent and heaviest smokers, his own research had found a significant number of patients could successfully quit or at the least cut down given the right advice and assistance. While most smoking cessation pharmacotherapy could be used, Dr Warden suggested that varenicline (Champix) was probably best avoided in these patients. At St Vincent’s Hospital in Melbourne, patients receiving antipsychotic therapy have their metabolic markers assessed at admission and at regular intervals after that, including measuring their serum prolactin. “Hyperprolactinaemia is a significant problem and should be monitored every six months if it is elevated or increasing particularly if there are symptoms then either reduce the dose or change antipsychotic or add in low dose aripiprazole which will lower prolactin levels,” Dr Warden explained.   Dr Matthew Warden spoke on the “Management of Metabolic Dysregulation in Patients on Antipsychotics” at the Healthed, Mental Health in General Practice Evening Seminar held in Sydney in June, 2018.

Dr Linda Calabresi
Clinical Articles iconClinical Articles

Salt may have been unfairly targeted as a killer in the healthy heart stakes, according to newly published research. The observational study of over 90000 people in 300 communities across 18 countries, found that sodium consumption was not associated with an increase in health risks unless the average daily consumption was excessive – more than 5g/day or 2.5 teaspoons of salt. And, this average high daily sodium intake was mostly seen in China, with only about 15% of communities outside of China exceeding this 5g a day limit. As part of this ongoing Prospective Urban Rural Epidemiology (PURE) study, participants aged 35-70 were assessed initially at baseline and then followed for an average of 8.1 years, over which time the occurrence of any major cardiovascular events or death was recorded. What the researchers found was that the risk of hypertension and strokes was only increased in communities where the average daily sodium intake was greater than 5g. Perhaps unexpectedly, this higher sodium intake was actually found to be also associated with lower rates of myocardial infarction and total mortality. Furthermore, the research found that very low levels of sodium intake were harmful, being associated with an increased risk of cardiovascular disease and mortality. The findings fly in the face of the current WHO guidelines that recommend, as a global approach we should be aiming for populations to reduce their sodium intake to below 2g/day. However, no communities in the study came close to achieving this target. In fact, no communities in the study had an average sodium intake of less than 3g/day, based on morning fasting urine samples from the participants. “Sodium intake was associated with cardiovascular disease and strokes only in communities where mean intake was greater than 5g/day. A strategy of sodium reduction in these communities and countries but not in others might be appropriate,” the Canadian study authors said. But before we all go and stock up on our Saxa, an accompanying editorial sounds a word of caution. While acknowledging the findings that ‘normal’ salt intake appeared to be at least health-neutral if not beneficial, the editorial authors remind us that the study is observational and has not taken into consideration a number of potential confounders such as diet. Without taking these confounders into account, one can’t assume that just decreasing salt intake in people at high risk of stroke or increasing it in people at risk of a heart attack will work, they said. “Nevertheless the findings are exceedingly interesting and should be tested in a randomised controlled trial,” they concluded, adding that such a trial, to be conducted in a US federal prison population had been proposed.   Ref: Lancet Vol 392 No 10146 pp:496-506 Vol 392 No 10146 pp: 456-458

Dr Linda Calabresi
Clinical Articles iconClinical Articles

Low density lipoprotein cholesterol is the well-known culprit in terms of cardiovascular risk. Courtesy of a large meta-analysis of statin trials done in 2010 (the Cholesterol Treatment Trialists Collaboration), we know that for people starting with higher LDL-C levels (approximately 3.4 mmol/L), they can lower their risk of having a major adverse vascular event by 22%, every time they lower their LDL-C level by 1mmol/L. But what happens once your LDL level is lower? Can you continue to increase your protection by lowering your LDL levels further? Or does the beneficial effect plateau at a certain level? Or, worse still can very low LDL levels actually cause harm? A new meta-analysis just published in JAMA Cardiology has gone some way in answering these questions. The researchers analysed data from the 26 statin studies in the CTTC as well as three large trials of non-statin, cholesterol-lowering therapy looking at those patients who had an LDL-C level of 1.8 mmol/L or less at baseline. They found the cardioprotective benefits continued as LDL-C levels declined to even lower levels. “We found consistent clinical benefit from further LDL-C lowering in patient populations starting as low as a median of 1.6 mmol/L and achieving levels as low as a median of 0.5 mmol/L”. What’s more, the incremental benefit was of an almost identical magnitude to that seen when the LDL-C levels were higher - 21% relative risk reduction per 1-mmol/L reduction in LDL-C through this range. “This relative risk reduction is virtually the same as the 22% reduction seen in the overall CTTC analysis in which the starting LDL-C was nearly twice as high,” they said. And even though very low cholesterol levels have been rumoured to be associated with everything from cancer to dementia, across all these studies there were no offsetting safety concerns with LDL-C lowering, even when extremely low levels were recorded, levels that were lower than those seen in newborns. Given the weight of benefit over risk, the study authors suggest the current targets for LDL-C could be lowered further, to even as low as 0.5 mmol/L to reduce cardiovascular risk. This suggestion is supported by an accompanying editorial, in which the author, Dr Antonio Gotto, a New York cardiologist, predicts the findings will be included as part of the revision of the American Heart Association National Cholesterol guidelines which is currently underway. He said the study findings would provide much needed evidence to help clinicians manage patients with these extremely low achieved cholesterol levels, that until recently have been very rare. “Whether one calls it a target or a threshold, practicing physicians need some guidance as they venture into achieved levels of LDL-C levels that are as foreign as travel to outer space. I have confidence that the new guidelines will be closer to a global positioning system map rather than just a compass and the stars”, he concluded. Ref: JAMA Cardiol. Published online August 1, 2018. doi:10.1001/jamacardio.2018.2258

Dr Linda Calabresi
Clinical Articles iconClinical Articles

Effectively treating depression in patients who have just experienced a heart attack will not only improve their quality of life, it could well improve their mortality, new research from Korea suggests. Among 300 patients who had recently experienced acute coronary syndrome and had depression as a comorbidity, those randomised to a 24-week course of escitalopram were 30% less likely to have a major adverse cardiac event over a median of eight years compared with those given placebo. In actual numbers, 40.9% (61)of the 149 patients given escitalopram had a major adverse event (including cardiac death, MI or PCI) over the period of follow-up compared with 53.6% (81) of the placebo group (151 patients), according to the study findings published in JAMA. It has long been known that depression is a common morbidity associated with acute coronary syndrome. It is also known that patients who have this comorbidity tend to have worse long-term cardiac outcomes than those who are depression-free. But what has yet to be proven is the benefit of treating this depression, at least in terms of mitigating this increased risk of a poor cardiac outcome. To date studies on the topic have yet to prove a significant benefit, with research providing conflicting results. According to the study authors, in this trial there was a significant correlation between improvement in the depression and better protection against major cardiac events. Even when they excluded those people who were still taking the antidepressant one year after the acute coronary syndrome, the protective effect was still present. Consequently, they hypothesised that the protection was more a reflection of the successfully treatment of the depression rather than the particular medication. This was consistent with a trend seen in previous research using different medications and treatments. However, the better result could be because escitalopram is more effective in treating acute coronary syndrome depression than other agents that were studied previously, the authors suggested. “Escitalopram may have modifying effects on disease prognosis in ACS-associated depressive disorder through reduction of depressive symptoms,” the study authors suggested. There were a number of caveats with regard this study that the authors said needed to be considered. These included the fact the cohort was entirely Korean which may have caused an ethnic bias, the depressive symptoms were less severe than in previous studies (though this was more likely to lead to the effect being an under-estimate) and also the severity of the underlying heart disease (namely heart failure) was relatively low. Nonetheless the researchers were able to conclude that among patients with depression who had had a recent acute coronary event, 24 weeks of treatment of escitalopram significantly reduced the risk of dying or having a further adverse cardiac event after a median of 8.1 years. How generalisable these findings are, will need to be the subject of further research. Ref: JAMA 2018;320 (4): 350-357. Doi: 10.1001/jama.2018.9422

Dr Linda Calabresi
Clinical Articles iconClinical Articles

All newly-diagnosed hypertensive patients should be screened for primary aldosteronism before they are started on treatment, Australian experts suggest in the latest issue of the MJA. “Primary aldosteronism is common, specifically treatable, and associated with significant cardiovascular morbidity and mortality,” say researchers Dr Jun Yang, Professor Peter Fuller and Professor Michael Stowasser. They refer to a recent systematic review of over 30 studies, that found among a cohort of people with severe or resistant hypertension (systolic BP >180mmHg and diastolic BP >110), 16.4% were found to have primary aldosteronism. Admittedly these studies were carried out in tertiary centres. There been far fewer studies on the issue conducted in primary care with somewhat mixed results, with one small Australian study suggesting 11.5% of people with significant hypertension in the general practice setting had primary aldosteronism. But its not only the patients with severe hypertension that need to be considered for primary aldosteronism screening, the authors suggest. They point to an Italian study including over 1600 GP patients selected randomly who were screened for primary aldosteronism and found a prevalence of 5.9%.  Importantly 45% of these had mild hypertension (BP 140-159/90-99mmHg). According to the article authors, these patients, because would have most likely remained undiagnosed if not for the study. And the effect of the untreated aldosterone excess would have most likely led to poor blood pressure control and increased cardiovascular, renal and metabolic morbidity long-term. In other words, identifying these patients early in the course of the disease could allow more appropriate treatment and ultimately avoid the end-organ damage that is more likely to occur if diagnosis is delayed until after the development of severe hypertension. “Targeted treatment of [primary aldosteronism] using surgery or mineralocorticoid receptor antagonists, such as spironolactone and eplerenone, rather than non-specific antihypertensive medications, can reverse the underlying cardiovascular pathology,” they said. The recommended biochemical screening tool for primary aldosteronism is the aldosterone to renin ratio which is elevated in this condition because plasma aldosterone is normal or elevated while renin is suppressed. The experts suggest screening prior to commencing antihypertensive therapy as many of these drugs, including beta blockers, calcium channel blockers, ACE inhibitors, ARBs and diuretics usually interfere with this aldosterone to renin ratio. The test isn’t perfect, they admit, as it can be influenced by a number of confounders including salt intake and age, but as a screening tool it has been proven, in trials both in Australia and internationally to be very useful, resulting in significantly increased numbers of patients diagnosed. Current Australian hypertension guidelines recommend clinicians consider primary aldosteronism in patients with hypertension particularly those with moderate to severe or treatment-resistant hypertension. But, as the article authors point out, given the prevalence of primary aldosteronism and the health burden associated with this cardiovascular risk factor both to the Australian population and the economy, maybe it is time to consider screening all newly-diagnosed hypertensive patients for this condition, before the commencement of non-specific antihypertensive therapy. “This diagnostic strategy should lead to significant individual and population health and economic impacts as a result of many patients with hypertension being offered the chance of curative or simpler treatment at an early stage of their disease.” Ref: MJA doi:10.5694/mja17.00783

Dr Vivienne Miller
Clinical Articles iconClinical Articles

How easy is it to say HFpEF and HFrEF?   The answer is… not very easy! However, heart failure has a new classification based on ejection fraction that doctors will need to know about. HFpEF stands for “heart failure with preserved ejection fraction.” This preserved ejection fraction is defined as greater than or equal to 50%. HFrEF stands for “heart failure with reduced ejection fraction.” This is the “classic” form of heart failure that doctors are familiar with. The ejection fraction in HRrEF is defined as less than or equal to 50%. Patients who have clinical signs of heart failure and a normal ejection fraction used to be diagnosed with diastolic heart failure.  They are now said, under the new classification, to have HFpEF. It should be noted that a patient may have diastolic dysfunction typically reported on echo, however if they do not have any clinical signs of heart failure they do NOT have HFpEF. In this situation, the diastolic dysfunction refers to the cardiac echo finding of impaired diastolic relaxation. This may be an age-related change or due to left ventricular hypertrophy, both of which may occur without necessarily causing symptoms and signs of heart failure. There is an additional group that some researchers refer to, and that is HFmEF, which stands for “heart failure with mid-range ejection fraction”. HFmEF is defined as an ejection fraction of between 40% and 50%. There is debate about the utility of the additional sub-classification of HFmEF. Most clinicians would consider HFmEF as simply mild HFrEF. Most agree that HFmEF simply identifies as subgroup of HFrEF for which there are fewer clinical trials or evidence for effective therapy, and so this highlights areas for future investigation and research. The utility of this new classification, particularly HFrEF versus HFpEF, is mainly to distinguish different pathophysiological processes, cardiac mechanics and treatment options. Presently, it is only HFrEF for which there exists medications that reduce mortality and improve survival. Additionally, device therapies such as implantable cardioverter defibrillators and biventricular pacemakers (now more commonly referred to as “cardiac resynchronisation therapies”) have only demonstrated benefit in HFrEF. For HFpEF, there are no medications or devices that have been shown to reduce mortality and improve survival. Typically, symptoms are managed with diuretic therapy. There is evidence to support a benefit from spironolactone, however the most recent trial (TOPCAT)1 failed to demonstrate a mortality benefit and it was plagued with disparities regarding the nature of recruitment in one of the large regions participating. Certainly, from a treatment viewpoint, the underlying causes contributing to HFpEF can often be managed. These typically include hypertension, diabetes, obesity and coronary artery disease. Not surprisingly, there are studies to show that patients with HFpEF do benefit from exercise, and from maintaining a healthy weight. But how best do we explain these definitions to the patient sitting in front of us? 'It can be very helpful to clarify the term [heart failure] and to explain that their heart has neither “failed”, nor has it “stopped working”, but that “it is just not working as well as normal”, said cardiologist, Dr Hendrik Zimmet. HFrEF can be explained as “the heart muscle not pumping as well as usual”. HFpEF can be explained as “the heart muscle being stiffer than usual, and not relaxing as well”. But no matter how the problem is explained to the patient, it is important to stress, as positively as possible, what can be done to help.
  1. Pfeffer, Marc et al. Regional Variation in Patients and Outcomes in the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT) Trial
Circulation. 2014; CIRCULATIONAHA.114.013255 Originally published November 18, 2014 https://doi.org/10.1161/CIRCULATIONAHA.114.013255 Based on an interview with cardiologist, Dr Hendrik Zimmet at the Annual Women and Children’s Health Update, Melbourne, March 2018

Dr Christopher Reid
Monographs iconMonographs

This article discusses the evidence for and role of aspirin in the secondary prevention of cardiovascular events following the clinical manifestation of atherosclerotic disease.