Current Opinion in Cardiology最新文献

Purpose of review: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a devastating heritable channelopathy that can lead to sudden cardiac death in children and young adults. This review aims to explore genetics, the cardiac and extracardiac manifestations of mutations associated with CPVT, and the challenges involved with managing phenotypically variable variants.

Recent findings: The understanding of the genetics and mechanisms of CPVT continues to grow with recent discoveries including alternative splicing of cardiac TRDN and calmodulin gene variants. Additionally, there is an increasing recognition of the extra-cardiac manifestations such as epilepsy, neurodevelopmental delay, and glucose homeostasis abnormalities in RyR2 variant carriers. Advances in precision medicine, including the development of iPSC-derived cardiomyocytes, are valuable models for developing targeted therapeutics.

Summary: CPVT remains a complex disorder with cardiac and neurological manifestations impacting management. Early genetic testing and personalized treatment, including beta-blockers, flecainide, and ICDs, is important in improving outcomes. Ongoing research into the mechanism of each mutation will help in developing more effective, personalized therapeutics.

Purpose of review: RNA therapeutics came to global attention when mRNA-based vaccines provided an answer to the SARS-CoV-2 pandemic. The immense significance of this development notwithstanding, it is important to note that almost a decade prior to the pandemic, RNA drugs had made important inroads toward the amelioration of disease. The first class of RNA therapies to be introduced into clinical use were the antisense oligomers and siRNA drugs which generally induce a therapeutic effect by acting to brake or to modulate mRNA expression. RNA therapeutics is quickly becoming the fourth pillar of pharmacotherapy, and will have broad applications, including for the treatment of cardiovascular disease.

Recent findings: The United States (US) Food and Drug Administration (FDA) has approved several antisense oligomers (ASOs) and siRNA-based drugs to treat disorders associated with cardiovascular disease. In addition, multiple RNA-based drugs are in clinical trials to assess their safety and efficacy in patients with cardiovascular disorders, such as Zodasiran, a siRNA therapy that targets angiopoietin-like protein 3 (ANGPTL3) to reduce LDL cholesterol.

Summary: Because of limitless sequence choice; speed of design; and relative ease of synthesis, RNA drugs will be rapidly developed, will have broad applications, and will be generated at lower cost than other drug types. This review aims to highlight RNA therapies for cardiovascular diseases that are approved, and those that are under clinical evaluation.

Purpose of review: Diuretic resistance presents a harrowing obstacle in patients with decompensated heart failure and cardiac-driven cardiorenal syndrome. This conundrum not only presents clinical decision-making challenges but also portends worse outcomes for these patients. The development of device-based therapies to provide support in these cases is an attractive alternative therapeutic option. This review will describe the growing evidence supporting developments in device-based therapies for cardiorenal syndrome in patients with heart failure.

Recent findings: We describe multiple emerging technologies in this space, each classified according to its mechanism of action. 'Pushers' are devices that increase blood flow and perfusion pressure to the renal arteries. 'Pullers' reduce renal afterload by decreasing pressure in the renal veins, and 'fluid shifters' decongest the interstitium through the lymphatic system.

Summary: While early results from small clinical studies piloting these devices are promising, randomized controlled trials are needed to fully evaluate their utility in patients with heart failure. In the future, these devices may work synergistically with pharmacologic therapy to reduce average inpatient length of stay, hospitalization rates, and potentially improve mortality.

Purpose of review: Obesity is an important risk factor for heart failure with preserved ejection fraction (HFpEF). In patients who already have HFpEF, obesity contributes to high symptom burden and increased risk for heart failure (HF) hospitalization. This review examines the latest clinical trials assessing the efficacy of pharmacological interventions in the treatment of obesity-related HFpEF.

Recent findings: Recent results from randomized clinical trials (RCTs) suggest that incretin-based therapies, including glucagon-like peptide-1 receptor agonists (GLP-1 RAs) (e.g., semaglutide) and dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 RAs (e.g., tirzepatide), can improve quality of life, exercise tolerance, and markers of HF severity while promoting weight loss in patients with obesity and HFpEF. Some evidence also suggests that these therapies may reduce risk for HF hospitalizations. Additionally, exploratory analyses of the nonsteroidal mineralocorticoid receptor antagonist finerenone has been associated with reduced cardiovascular mortality and total worsening HF events across all body mass index (BMI) levels, with greater benefits observed in patients with higher BMIs.

Summary: Antiobesity medications such as semaglutide and tirzepatide may represent important treatment options for patients with obesity-related HFpEF. Additional evidence suggests that certain other HF medications may have increased efficacy in patients with obesity.

Purpose of review: This review presents contemporary data on epidemiology, common presentations, investigations and diagnostic algorithms, treatment and prognosis. It particularly focuses on topics of most relevance to heart failure specialists, including what left ventricle (LV) function changes can be expected after treatment and outcomes to all standard and advanced heart failure therapies.

Recent findings: Around 5% of sarcoidosis patients have clinically manifest cardiac sarcoidosis (CS), presenting with significant arrhythmias (such as conduction disturbances and ventricular arrhythmias) or newly developed unexplained heart failure. These cardiac symptoms (including sudden cardiac death) may be the initial manifestations of CS. While cardiac magnetic resonance imaging (CMR) is the preferred method for identifying fibrosis in the myocardium, FDG-positron emission tomography (FDG-PET) helps in identifying active inflammation within the myocardium and aids in managing immunosuppressive treatment. The concept of isolated CS is much debated. However very importantly, recent data have shown that some patients diagnosed with 'clinically and imaging isolated CS' are subsequently found to have genetic cardiomyopathy. The management of CS involves a comprehensive approach including medications for immunosuppression, all standard heart failure medication and, in high-risk patient's implantable cardioverter defibrillators (ICDs). In CS patients with terminal heart failure who do not respond to medical and surgical interventions, heart transplantation and ventricular assist devices should be considered. Long-term results after transplantation are generally favorable and comparable to non-CS patients. The degree of left ventricular dysfunction remains a crucial prognostic factor in CS cases. Outcomes for CS have very significantly improved, over the last two decades due to earlier diagnosis, advanced heart failure treatments, and the strategic use of ICD therapy.

Summary: Outcomes for CS have significantly improved, over the last two decades due to earlier diagnosis, advanced heart failure treatments, and the strategic use of ICD therapy.

Purpose of review: Review advancements in therapies for transthyretin (ATTR-CM) and immunoglobulin light chain (AL-CM) cardiac amyloidosis.

Recent findings: In ATTR-CM, tafamidis remains the cornerstone therapy, with Food and Drug Administration (FDA) approval for over 5 years. Acoramidis, another transthyretin stabilizer, has very recently been FDA-approved following positive results in the ATTRibute-CM trial. Vutrisiran, a transthyretin gene silencer, demonstrated efficacy in the HELIOS-B trial and awaits FDA review. Eplontersen's CARDIO-TTRansform trial, the largest ATTR-CM study to date, is expected to report by late 2025. Innovative approaches such as NTLA-2001 (a CRISPR-Cas9 therapy) and fibril depleters like ALXN2220 and coramitug are advancing in clinical trials. In AL-CM, daratumumab, cyclophosphamide, bortezomib, and dexamethasone (Dara-CyBorD) has established itself as the standard of care. Novel antiplasma cell therapies include CAR-T cells and bispecific antibodies (teclistimab) and fibril depleters. Birtamimab improved survival in advanced AL-CM during the VITAL trial and is under investigation in AFFIRM-AL. Anselamimab is in phase III CARES trials, whereas AT-02 undergoes early-phase testing for ATTR-CM and AL-CM.

Summary: The therapeutic landscape for ATTR-CM and AL-CM is rapidly evolving, driven by novel therapies targeting diverse mechanisms. Ongoing clinical trials promise to further refine the standard of care and improve outcomes for patients with cardiac amyloidosis.

Purpose of review: Infective endocarditis (IE) is a complex disease with increasing global incidence. This review explores recent trends in IE infection patterns, including healthcare-associated IE (HAIE), drug-use-associated IE (DUA-IE), multidrug-resistant organisms (MDROs), and challenges in managing prosthetic valve and device-related infections.

Recent findings: Staphylococcus aureus has emerged as the leading cause of IE, especially in HAIE and DUA-IE cases. Increasingly prevalent MDROs, such as methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci, pose further clinical challenges. Advances in molecular diagnostics have improved the detection of culture-negative endocarditis. The introduction of the AngioVAC percutaneous aspiration device promises to change the management of right and possibly some left sided IE. Multidisciplinary team management and early surgery have demonstrated improved outcomes including partnerships with psychiatry and addictions services for those with intravenous DUA-IE.

Summary: IE presents significant diagnostic and therapeutic challenges due to evolving infection patterns, MDROs, and HAIE. Early diagnosis using advanced imaging, appropriate early antimicrobial therapy, and multidisciplinary care, including timely surgery, are critical for optimizing patient outcomes.