While current guidelines recommend amiodarone and dronedarone for rhythm control in patients with atrial fibrillation (AF) and coronary artery disease (CAD), there was no comparative study of ...antiarrhythmic drugs (AADs) on the cardiovascular outcomes in general practice.
This study included patients with AF and CAD who received their first prescription of amiodarone, class Ic AADs (flecainide, propafenone), dronedarone or sotalol between January 2016 and December 2020. The primary outcome was a composite of hospitalization for heart failure (HHF), stroke, acute myocardial infarction (AMI), and cardiovascular death. We used Cox proportional regression models, including with inverse probability of treatment weighting (IPTW), to estimate the relationship between AADs and cardiovascular outcomes.
Among the AF cohort consisting of 8752 patients, 1996 individuals had CAD, including 477 who took dronedarone and 1519 who took other AADs. After a median follow-up of 38 months, 46.3% of patients who took dronedarone and 54.4% of patients who took other AADs experienced cardiovascular events. Compared to dronedarone, the use of other AADs was associated with increased cardiovascular events after adjusting for covariates (hazard ratio HR 1.531, 95% confidence interval CI 1.112–2.141, p = 0.023) and IPTW (HR 1.491, 95% CI 1.174–1.992, p = 0.012). The secondary analysis showed that amiodarone and class Ic drugs were associated with an increased risk of HHF. The low number of subjects in the sotalol group limits data interpretation.
For patients with AF and CAD, dronedarone was associated with better cardiovascular outcomes than other AADs. Amiodarone and class Ic AADs were associated with a higher risk of cardiovascular events, particularly HHF.
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•In this study cohort in Taiwan, 53.5% of patients with AF and CAD took amiodarone as first-line AAD, 23.9% took dronedarone, 19.7% took class Ic drugs and 2.9% took sotalol.•For patients with AF and CAD, dronedarone was associated with better cardiovascular outcomes than other AADs.•Amiodarone and class Ic AADs were associated with a higher risk of cardiovascular events, particularly hospitalization for heart failure (HHF).•Our study suggested that dronedarone is the preferred first-line choice for rhythm control in patients with AF and CAD.
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•Potentially, sulfonylureas (SU) may attenuate the cardiovascular benefits of glucagon-like peptide-1 receptor agonists (GLP-1 RAs).•Possible interactions were examined by post-hoc ...analyses of the EXSCEL trial.•Sulfonylureas did not modulate the effect of GLP-1 RAs on cardiovascular outcomes.•SU treatment need not be altered to optimize the cardiovascular effects of GLP-1 RAs.
To examine whether the cardiovascular effects of glucagon-like peptide-1 (GLP-1) receptor agonists are attenuated by concurrent sulfonylurea (SU) therapy in a post-hoc analysis of the Exenatide Study of Cardiovascular Event Lowering (EXSCEL).
We investigated whether SUs, as a class or by specific type, modulated the effects of once-weekly exenatide (EQW) on EXSCEL cardiovascular outcomes in intent-to-treat analyses of all trial participants, categorized as SU users or nonusers. Marginal structural models were used to evaluate whether there were differential EQW effects by SU category on major adverse cardiovascular events (MACE), depending on duration of SU use (6, 12, and 18 months). EQW-by-SU type interaction p-values and hazard ratios (95 % CIs) for EQW versus placebo for each baseline SU type (glibenclamide, gliclazide, glimepiride, other SUs) were calculated.
Neither SU use nor baseline SU type modified the effect of EQW on time to MACE (pinteraction = 0.88 and 0.78, respectively), nor did individual SU types, including glibenclamide (a systemically wide-acting SU).
SUs did not modulate the effect of EQW on cardiovascular outcomes, suggesting that SU treatment choices need not be altered to optimize the cardiovascular effects of GLP-1 receptor agonists in people with type 2 diabetes.
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In this video, Javed Butler, MD, introduces the series on the use of SGLT2 inhibitors in heart failure. He discusses the epidemiology of heart failure and the effects of SGLT2 ...inhibitors on heart failure outcomes. Jonathan Rich, MD, joins to summarize the effects of SGLT2 inhibitors from dedicated trials in patients with heart failure.
BACKGROUNDSupranormal ejection fraction by echocardiography in clinically referred patient populations has been associated with an increased risk of cardiovascular disease (CVD). The prognostic ...implication of supranormal left ventricular ejection fraction (LVEF)-assessed by cardiac magnetic resonance (CMR)-in healthy, community-dwelling individuals is unknown. OBJECTIVESThe purpose of this study is to investigate the prognostic implication of supranormal LVEF as assessed by CMR and its inter-relationship with stroke volume among community-dwelling adults without CVD. METHODSParticipants from the MESA (Multi-Ethnic Study of Atherosclerosis) and DHS (Dallas Heart Study) cohorts free of CVD who underwent CMR with LVEF above the normal CMR cutoff (≥57%) were included. The association between cohort-specific LVEF categories and risk of clinically adjudicated major adverse cardiovascular events (MACE) was assessed using adjusted Cox models. Subgroup analysis was also performed to evaluate the association of LVEF and risk of MACE among individuals stratified by left ventricular stroke volume index. RESULTSThe study included 4,703 participants from MESA and 2,287 from DHS with 727 and 151 MACE events, respectively. In adjusted Cox models, the risk of MACE was highest among individuals in LVEF Q4 (vs Q1) in both cohorts after accounting for potential confounders (MESA: HR = 1.27 95% CI: 1.01-1.60, P = 0.04; DHS: HR = 1.72 95% CI: 1.05-2.79, P = 0.03). A significant interaction was found between the continuous measures of LVEF and left ventricular stroke volume index (P interaction = 0.02) such that higher LVEF was significantly associated with an increased risk of MACE among individuals with low but not high stroke volume. CONCLUSIONSAmong community-dwelling adults without CVD, LVEF in the supranormal range is associated with a higher risk of adverse cardiovascular outcomes, particularly in those with lower stroke volume.
Long COVID has a multifactorial nature with multiple pathophysiological factors at play.Viral factors, host factors (including systemic inflammation, and metabolic, endocrine, and endothelial ...dysfunction) and downstream impacts (tissue damage from the initial infection, hypoxia, dysbiosis, and autonomic nervous system dysfunction) are key elements underpinning the condition.Various factors culminate in the long-term persistence of the disorder (i.e., a thrombotic endothelialitis characterized by endothelial inflammation, hyperactivated platelets, and fibrinaloid microclots).We suggest a multipronged treatment agenda for Long COVID treatment trials, incorporating drugs targeting all potential mechanisms, including viral persistence, autoimmunity, immune dysregulation, and gut dysbiosis; with endothelialitis and coagulation abnormalities as two priorities.
Acute COVID-19 infection is followed by prolonged symptoms in approximately one in ten cases: known as Long COVID. The disease affects ~65 million individuals worldwide. Many pathophysiological processes appear to underlie Long COVID, including viral factors (persistence, reactivation, and bacteriophagic action of SARS CoV-2); host factors (chronic inflammation, metabolic and endocrine dysregulation, immune dysregulation, and autoimmunity); and downstream impacts (tissue damage from the initial infection, tissue hypoxia, host dysbiosis, and autonomic nervous system dysfunction). These mechanisms culminate in the long-term persistence of the disorder characterized by a thrombotic endothelialitis, endothelial inflammation, hyperactivated platelets, and fibrinaloid microclots. These abnormalities of blood vessels and coagulation affect every organ system and represent a unifying pathway for the various symptoms of Long COVID.
In GALACTIC-HF (Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure) (n = 8,256), the cardiac myosin activator, omecamtiv mecarbil, significantly ...reduced the primary composite endpoint (PCE) of time-to-first heart failure event or cardiovascular death in patients with heart failure and reduced ejection fraction (EF) (≤35%).
The purpose of this study was to evaluate the influence of baseline EF on the therapeutic effect of omecamtiv mecarbil.
Outcomes in patients treated with omecamtiv mecarbil were compared with placebo according to EF.
The risk of the PCE in the placebo group was nearly 1.8-fold greater in the lowest EF (≤22%) compared with the highest EF (≥33%) quartile. Amongst the pre-specified subgroups, EF was the strongest modifier of the treatment effect of omecamtiv mecarbil on the PCE (interaction as continuous variable, p = 0.004). Patients receiving omecamtiv mecarbil had a progressively greater relative and absolute treatment effect as baseline EF decreased, with a 17% relative risk reduction for the PCE in patients with baseline EF ≤22% (n = 2,246; hazard ratio: 0.83; 95% confidence interval: 0.73 to 0.95) compared with patients with EF ≥33% (n = 1,750; hazard ratio: 0.99; 95% confidence interval: 0.84 to 1.16; interaction as EF by quartiles, p = 0.013). The absolute reduction in the PCE increased with decreasing EF (EF ≤22%; absolute risk reduction, 7.4 events per 100 patient-years; number needed to treat for 3 years = 11.8), compared with no reduction in the highest EF quartile.
In heart failure patients with reduced EF, omecamtiv mecarbil produced greater therapeutic benefit as baseline EF decreased. These findings are consistent with the drug’s mechanism of selectively improving systolic function and presents an important opportunity to improve the outcomes in a group of patients at greatest risk. (Registrational Study With Omecamtiv Mecarbil/AMG 423 to Treat Chronic Heart Failure With Reduced Ejection Fraction GALACTIC-HF; NCT02929329)
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The long-term cardiovascular outcomes in COVID-19 survivors remain largely unclear. The aim of this study was to investigate the long-term cardiovascular outcomes in COVID-19 survivors.
This study ...used the data from the US Collaborative Network in TriNetX. From a cohort of more than 42 million records between 1 January 2019 and 31 March 2022, a total of 4,131,717 participants who underwent SARS-CoV-2 testing were recruited. Study population then divided into two groups based on COVID-19 test results. To avoid reverse causality, the follow-up initiated 30 days after the test, and continued until 12 months. Hazard ratios (HRs) and 95% Confidence intervals (CIs) of the incidental cardiovascular outcomes were calculated between propensity score–matched patients with versus without SARS-CoV-2 infection. Subgroup analyses on sex, and age group were also conducted. Sensitivity analyses were performed using different network, or stratified by hospitalization to explore the difference of geography and severity of COVID-19 infection.
The COVID-19 survivors were associated with increased risks of cerebrovascular diseases, such as stroke (HR 95% CI = 1.618 1.545-1.694), arrhythmia related disorders, such as atrial fibrillation (HR 95% CI = 2.407 2.296-2.523), inflammatory heart disease, such as myocarditis (HR 95% CI =4.406 2.890-6.716), ischemic heart disease(IHD), like ischemic cardiomyopathy (HR 95% CI = 2.811 2.477-3.190), other cardiac disorders, such as heart failure (HR 95% CI =2.296 2.200-2.396) and thromboembolic disorders (e.g. pulmonary embolism: HR 95% CI =2.648 2.443-2.870). The risks of two composite endpoints, major adverse cardiovascular event (HR 95% CI = 1.871 1.816–1.927) and any cardiovascular outcome (HR 95% CI = 1.552 1.526–1.578), were also higher in the COVID-19 survivors than in the controls. Moreover, the survival probability of the COVID-19 survivors dramatically decreased in all the cardiovascular outcomes. The risks of cardiovascular outcomes were evident in both male and female COVID-19 survivors. Furthermore, the risk of mortality was higher in the elderly COVID-19 survivors (age ≥ 65 years) than in the young ones. Sensitivity analyses presented roughly similar results globally. Furthermore, the impact of COVID-19 on cardio-related outcomes appeared to be more pronounced in inpatients than in outpatients.
The 12-month risk of incidental cardiovascular diseases is substantially higher in the COVID-19 survivors than the non-COVID-19 controls. Clinicians and patients with a history of COVID-19 should pay attention to their cardiovascular health in long term.
The Fundamental Research Funds for the Central public welfare research institutes and Young Elite Scientists Sponsorship Program by CACM.
Iron deficiency and heart failure frequently co-occur, sparking clinical research into the role of iron repletion in this condition over the last 20 years. Although early nonrandomized studies and ...subsequent moderate-sized randomized controlled trials showed an improvement in symptoms and functional metrics with the use of intravenous iron, 3 recent larger trials powered to detect a difference in hard cardiovascular outcomes failed to meet their primary endpoints. Additionally, there are potential concerns related to side effects from intravenous iron, both in the short and long term. This review discusses the basics of iron biology and regulation, the diagnostic criteria for iron deficiency and the clinical evidence for intravenous iron in heart failure, safety concerns, and alternative therapies. We also make practical suggestions for the management of patients with iron deficiency and heart failure and outline key areas in need of future research.
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•Iron deficiency and heart failure frequently occur concurrently and are associated with adverse cardiovascular outcomes.•Early trials of intravenous iron repletion in patients with heart failure found improvements in symptoms and functional capacity, but subsequent large trials failed to confirm objective consistent benefit.•Side effects of and alternatives to intravenous iron repletion warrant careful consideration.
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