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26th November 2021
Using sacubitril-valsartan in those experiencing an acute myocardial infarction (MI) and an ejection fraction lower then 40% appears to offer no mortality benefit over the use of ramipril alone. This was the conclusion of a trial by the PARADISE-MI researchers at the Cardiovascular Division, Brigham and Women’s Hospital, Boston, US.
The mortality benefits achieved from the use of angiotensin converting enzyme (ACE) inhibitors in randomised, placebo-controlled trials among patients with left-ventricular dysfunction or heart failure, is well established and is independent of age, sex, and baseline use of diuretics, aspirin, and beta-blockers. Moreover, the beneficial effects of ACE inhibitors also extents to the angiotensin-receptor blocker drugs such as valsartan.
Neprilysin is an enzyme that contributes to the breakdown of the biologically active natriuretic peptides and several other vasoactive compounds which have a favourable effect on the pathogenesis of heart failure. Inhibition of neprilysin with sacubitril, therefore maintains natriuretic peptides and the combination of sacubitril-valsartan has been approved for the management of patients with chronic heart failure and a reduced ejection fraction.
Nevertheless, whether this combination would be effective among patients suffering an acute MI without prior heart failure but with a reduced ejection fraction was the subject of the present study by the US team. They conducted the Prospective ARNI versus ACE Inhibitor Trial to Determine Superiority in Reducing Heart Failure Events after Myocardial Infarction (PARADISE-MI), which was an international, randomised, double-blind, active comparator trial, comparing sacubitril-valsartan with ramipril alone. The trial recruited patients with a spontaneous MI within 0.5 to 7 days before presentation in association with a reduced ejection fraction (< 40%), pulmonary congestion or both. Included patients were randomised 1:1 to sacubitril-valsartan or ramipril 5mg, both given twice daily in addition to any recommended therapy. The composite primary outcome was death from cardiovascular causes or incident heart failure.
A total of 5661 patients with an average age of 63.7 years (24.1% women) and a mean ejection fraction of 36%, were randomised to either therapy and followed up for a median duration of 22 months. There were 338 (11.9%) primary outcome events in the sacubitril-valsartan group and 373 (13.2%)in the ramipril group and this difference was non-significant (hazard ratio, HR = 0.90, 95% CI 0.78 – 1.04, p = 0.17). Similarly, death due to cardiovascular causes was also not different (HR = 0.91, 95% CI 0.78 – 1.07), as was hospitalisation for heart failure or outpatient heart failure (HR = 0.84, 95% CI 0.70 – 1.02) and death due to any cause (HR = 0.88, 95% CI 0.73 – 1.05).
The authors concluded that sacubitril-valsartan offered no benefit survival benefit among those with an acute MI and a reduced ejection fraction.
Pfeffer MA. et al. Angiotensin Receptor–Neprilysin Inhibition in Acute Myocardial Infarction. N Eng J Med 2021
6th September 2021
Coronary heart diseases are the leading global cause of death and responsible for an estimated 17.9 million lives lost each year. The idea that influenza might contribute to the development of myocardial infarction (MI) and subsequent death, comes from autopsy studies of patients who died during influenza epidemics. In fact, a recent analysis of 364 hospitalisations for acute MI, confirmed a significant association between respiratory infections, especially influenza and MIs. It is therefore possible that administration of an influenza vaccination as both a primary or secondary preventative measure, could improve cardiovascular disease outcomes. However, a Cochrane review from 2015, concluded that among those with cardiovascular disease, influenza vaccination may reduce mortality and combined cardiovascular events but that more and higher-quality evidence is necessary to confirm these findings.
This need for more high-quality evidence was the reason for the Influenza vaccination After Myocardial Infarction (IAMI) trial undertaken by researchers from the Faculty of Health, Department of Cardiology, Orebro University, Sweden. The team hypothesised that influenza vaccination would reduce the incidence of death, further MIs and stent thrombosis, in patients with a recent MI or with high-risk coronary disease, which included those with stable coronary artery disease and 75 years of age or older with additional risk factors. Eligible patients for the trial were those with either ST-elevation myocardial infarction (STEMI) or non-STEMI. Patients were excluded if they had received an influenza vaccination during the previous 12 months. Participants were then randomised 1:1 to either influenza vaccine or placebo (saline) within 72 hours of their MI. The primary endpoint of interest was a composite of all-cause death, MI, or stent thrombosis at 12 months.
There were 2571 individuals with a mean age of 59.9 years (81% male) randomised to either arm. Overall, 54.5% of participants were admitted with STEMI and 45.2% with non-STEMI and 8 with stable coronary artery disease. Over the following 12 months, the primary outcome occurred in 5.3% of those vaccinated and 7.2% of those in the placebo group (hazard ratio, HR = 0.72, 95% CI 0.52 – 0.99, p = 0.04). The mortality rates were 2.9% (influenza vaccine) and 4.9% placebo (HR = 0.59, 95% CI 0.39 – 0.90, p = 0.014). In addition, within the influenza vaccination group, 2% experienced a subsequent MI compared to 2.4% in the placebo group (p = 0.57). None of the patients with stable coronary artery disease died.
Discussing their findings, the authors noted how the early administration of influenza vaccination led to a reduced risk of death compared to placebo. They concluded that the provision of influenza vaccination should form part of the in-hospital treatment received by patients following a myocardial infarction.
Frobert O et al. Influenza Vaccination after Myocardial Infarction:
A randomised, Double-Blind, Placebo-Controlled, multi-center Trial. Circulation 2021
23rd August 2021
Although COVID-19 is a considered to be predominately respiratory infection, a review from the end of 2020, established that infection can also result in adverse cardiovascular outcomes. For example, one study of 3,334 COVID-19 patients in the US, found a 1.6% incidence of ischaemic strokes, and an 8.9% incidence of myocardial infarction. This rate was much higher than in a Danish observational study of 5119 patients, of whom, only 0.3% experienced an acute myocardial infarction. However, many of the adverse cardiovascular outcomes have reported among those hospitalised with COVID-19 and there is a lack of data on this disease burden following infection with the virus at the population level.
This was the reason for a study led by a team from the Department of Public Health and Clinical Medicine, Umea University, Umea, Sweden. The researchers sought to quantify the relative risk of both ischaemic stroke and myocardial infarction following infection with COVID-19 using a large, nationwide register within Sweden. The team used two methods of study; the self-controlled case series (SCCS) method and a matched control cohort. In the SCCS method, an individual acts as their own control, so that only those who experience an event are included and serves as an alternative to the cohort or case-controlled study design. For comparative purposes, the researchers also used a more traditional matched cohort study. The period of study was February to September 2020 and the researchers calculated the incidence rate ratio (IRR) of both cardiovascular events following onset of COVID-19. Since an adverse cardiovascular event could have occurred on the same day as infection with COVID-19, it is possible that the event occurred independently of infection with the virus and the team therefore performed two separate analyses using either day 0 (i.e., day of exposure to COVID-19) and one excluding day 0.
Using the national registry, a total of 86,742 individuals were diagnosed with COVID-19 during the period of study with a median age of 48 years (43% male). In the SCCS study there were 186 acute myocardial infarctions, of whom 39 patients died. When day 0 was excluded, the IIR for acute myocardial infarction was 2.89 (95% CI 1.51 – 5.55) for the first week, 2.53 (95% CI 1.29 – 4.94) for the second week, although not significant for weeks 3 and 4 (IIR = 1.60, 95% CI 0.84 – 3.04). However, when day 0 was included, the IIR was significantly higher (IIR = 8.44, 95% CI 5.45 – 13.08) for the first and second weeks, but again, not significant for the third and fourth weeks. The corresponding values for ischaemic stroke were also significantly increased during the first week when day 0 was excluded (IIR = 2.97, 95% CI 1.71 – 5.15) and when day 0 was included (IIR = 6.18, 95% CI 4.06 – 9.42). In the matched cohort analysis, similar, significant increased risk were observed for both acute myocardial infarction and ischaemic stroke, irrespective of whether day 0 was included.
Based on these findings from two independent methods, the authors concluded that COVID-19 is an independent risk factor for both acute myocardial infarction and ischaemic stroke.
Katsoularis I et al. Risk of acute myocardial infarction and ischaemic stroke following COVID-19 in Sweden: a self-controlled case series and matched cohort study. Lancet 2021
11th June 2021
Acute myocarditis (aMC) has many different causes but the prevalence is unclear because the condition has similar clinical symptoms to an acute myocardial infarction (aMI). Although the diagnosis of myocarditis can be confirmed with cardiac magnetic resonance imaging, this technique is not always available. However, one approach to resolve the diagnosis involves the use of microRNAs (miRNAs), which are small, non-coding RNAs that play an important role in gene expression. Several miRNAs have been identified in the infarcted heart and this led a team from the Vascular Pathophysiology Area, Madrid, to try and identify a unique miRNA which could be used to distinguish between myocarditis and myocardial infarction. The team focused on circulating T cells, in particular T helper 17 (Th17) cells, which were confirmed as being a characteristic of myocardial injury in the acute phase of myocarditis. They performed a miRNA microarray analysis and quantitative polymerase chain reaction (qPCR) assays in Th17 cells after experimentally inducing myocarditis and myocardial infarction in mice to identify unique biomarkers.
The researchers identified the miRNA, mmu-miR-721, produced by Th17 cells in mice which was only produced in response to either autoimmune or viral myocarditis and which was absent from those with aMI. Using four patient cohorts with myocarditis, they subsequently identified a human homologue to mmu-miR-721, termed has-miR-Chr8:96. The researchers found that plasma levels of has-miR-Chr8:96 were considerably higher among myocarditis patients compared to both those with a myocardial infarction and in healthy controls. The area under the receiver-operating characteristics curve for has-miR-Chr8:96 was 0.927 (i.e., 92.7%) for distinguishing between aMC and aMI and this diagnostic value was retained even after adjusting for age, ejection fraction, and serum troponin levels.
Although the authors accepted that more work is needed to validate this biomarker in other cardiac disorders such as dilated cardiomyopathy, their preliminary findings suggest that raised plasma levels of has-miR-Chr8:96 are unique to those with myocarditis and have sufficient discriminatory power from myocardial infarction.
Blanco-Dominguez R et al. A Novel Circulating MicroRNA for the Detection of Acute Myocarditis. N Engl J Med 2021;384:2014-27