Pharmacotherapy for Coronary Artery Disease and Acute Coronary Syndrome in the Aging Population.

PURPOSE OF REVIEW: To provide a comprehensive summary of relevant studies and evidence concerning the utilization of different pharmacotherapeutic and revascularization strategies in managing coronary artery disease and acute coronary syndrome specifically in the older adult population. RECENT FINDINGS: Approximately 30% to 40% of hospitalized patients with acute coronary syndrome are older adults, among whom the majority of cardiovascular-related deaths occur. When compared to younger patients, these individuals generally experience inferior clinical outcomes. Most clinical trials assessing the efficacy and safety of various therapeutics have primarily enrolled patients under the age of 75, in addition to excluding those with geriatric complexities. In this review, we emphasize the need for a personalized and comprehensive approach to pharmacotherapy for coronary heart disease and acute coronary syndrome in older adults, considering concomitant geriatric syndromes and age-related factors to optimize treatment outcomes while minimizing potential risks and complications. In the realm of clinical practice, cardiovascular and geriatric risks are closely intertwined, with both being significant factors in determining treatments aimed at reducing negative outcomes and attaining health conditions most valued by older adults.

Role of Colchicine in Cardiovascular Disorders.

Inflammation has played a pivotal role in atherosclerosis and other cardiovascular disorders, prompting the exploration of anti-inflammatory therapies to improve cardiovascular outcomes. Colchicine, a well-established agent in conditions such as gout and familial Mediterranean fever, has emerged as a promising novel anti-inflammatory agent in the realm of cardiovascular diseases. Its ability to target both traditional risk factors and residual inflammatory risk marks a significant advancement in cardiovascular prevention strategies, indicating a new era in cardiovascular care. Landmark trials have supported the efficacy and safety of low-dose colchicine in reducing major adverse cardiovascular events when combined with standard therapies. In addition, its endorsement by major cardiovascular societies underscores its significance as the first targeted anti-inflammatory therapy for cardiovascular disease. However, careful monitoring for drug interactions and adverse effects, particularly on kidney and liver function, is essential for safe use. In this review, we aim to comprehensively summarize the mechanisms of action of colchicine, its molecular and biochemical targets in various cardiovascular conditions, and its pharmacokinetics, and delve deeply into the existing evidence on its safety and efficacy in the treatment of cardiovascular disorders, including coronary artery disease, pericarditis, atrial fibrillation, and heart failure.

Pharmacotherapy and revascularization strategies of peripheral artery disease.

The global epidemiological transition of atherosclerotic vascular diseases is witnessing a rapid redistribution of its burden, shifting from high-income to low- and middle-income countries. With a wide clinical spectrum, spanning from intermittent claudication to more complex critical limb threatening ischemia, nonhealing ulcers, gangrene as well as acute limb ischemia, peripheral artery disease is often faced with the challenges of under-diagnosis and under-treatment despite its high prevalence. The management of peripheral arterial disease in patients with multiple comorbidities presents a formidable challenge and remains a pressing global health concern. In this review, we aim to provide an in-depth overview of the pathophysiology of peripheral artery disease and explore evidence-based management strategies encompassing pharmacological, lifestyle, interventional, and surgical approaches. By addressing these challenges, the review contributes to a better understanding of the evolving landscape of peripheral artery disease, offering insights into effective and holistic management strategies.

Clinical outcomes of intravenous iron therapy in patients with heart failure and iron deficiency: Meta-analysis and trial sequential analysis of randomized clinical trials.

BACKGROUND: Iron deficiency in patients with heart failure (HF) is underdiagnosed and undertreated. The role of intravenous (IV) iron is well-established to improve quality of life measures. Emerging evidence also supports its role in preventing cardiovascular events in patients with HF. METHODOLOGY: We conducted a literature search of multiple electronic databases. Randomized controlled trials that compared IV iron to usual care among patients with HF and reported cardiovascular (CV) outcomes were included. Primary outcome was the composite of first heart failure hospitalization (HFH) or CV death. Secondary outcomes included HFH (first or recurrent), CV death, all-cause mortality, hospitalization for any cause, gastrointestinal (GI) side effects, or any infection. We performed trial sequential and cumulative meta-analyses to evaluate the effect of IV iron on the primary endpoint, and on HFH. RESULTS: Nine trials enrolling 3337 patients were included. Adding IV iron to usual care significantly reduced the risk of first HFH or CV death [risk ratio (RR) 0.84; 95 % confidence interval (CI) 0.75-0.93; I2 = 0 %; number needed to treat (NNT) 18], which was primarily driven by a reduction in the risk of HFH of 25 %. IV iron also reduced the risk of the composite of hospitalization for any cause or death (RR 0.92; 95 % CI 0.85-0.99; I2 = 0 %; NNT 19). There was no significant difference in the risk of CV death, all-cause mortality, adverse GI events, or any infection among patients receiving IV iron compared to usual care. The observed benefits of IV iron were directionally consistent across trials and crossed both the statistical and trial sequential boundaries of benefit. CONCLUSION: In patients with HF and iron deficiency, the addition of IV iron to usual care reduces the risk of HFH without affecting the risk of CV or all-cause mortality.

Left Ventricular Unloading With Impella Versus IABP in Patients With VA-ECMO: A Systematic Review and Meta-Analysis.

Venoarterial extracorporeal membrane oxygenation (VA-ECMO) use for circulatory support in cardiogenic shock results in increased left ventricular (LV) afterload. The use of concomitant Impella or intra-aortic balloon pump (IABP) have been proposed as adjunct devices for LV unloading. The authors sought to compare head-to-head efficacy and safety outcomes between the 2 LV unloading strategies. We conducted a search of Medline, EMBASE, and Cochrane databases to identify studies comparing the use of Impella to IABP in patients on VA-ECMO. The primary outcome of interest was in-hospital mortality. The secondary outcomes included transition to durable LV assist devices/cardiac transplantation, stroke, limb ischemia, need for continuous renal replacement therapy, major bleeding, and hemolysis. Pooled risk ratios (RRs) with 95% confidence interval and heterogeneity statistic I2 were calculated using a random-effects model. A total of 7 observational studies with 698 patients were included. Patients on VA-ECMO unloaded with Impella vs IABP had similar risk of short-term all-cause mortality, defined as either 30-day or in-hospital mortality- 60.8% vs 64.9% (RR 0.93 [0.71 to 1.21], I2 = 71%). No significant difference was observed in transition to durable LV assist devices/cardiac transplantation, continuous renal replacement therapy initiation, stroke, or limb ischemia between the 2 strategies. However, the use of VA-ECMO with Impella was associated with increased risk of major bleeding (57.2% vs 39.7%) (RR 1.66 [1.12 to 2.44], I2 = 82%) and hemolysis (31% vs 7%) (RR 4.61 [1.24 to 17.17], I2 = 66%) compared with VA-ECMO, along with IABP. In conclusion, in patients requiring VA-ECMO for circulatory support, the concomitant use of Impella or IABP had comparable short-term mortality. However, Impella use was associated with increased risk of major bleeding and hemolysis.

Direct Oral Anticoagulants: An Overview of Indications, Pharmacokinetics, Comorbidities, and Perioperative Management.

Direct oral anticoagulants (DOACs) have catalyzed a significant paradigm shift in the landscape of anticoagulant therapy, emerging as pivotal agents for the prevention of stroke in atrial fibrillation and venous thromboembolism. Although the absolute advantages of DOACs over vitamin K antagonists (VKAs) may appear modest, clinical guidelines advocate for their preference across various indications, attributing this endorsement to their ease of administration and heightened safety. DOACs find application in preventing and treating diverse cardiovascular conditions. With the progressive expansion of DOAC utility, clinicians encounter intricate decisions concerning the selection of appropriate agents, determination of optimal treatment duration, and utilization within specialized patient subgroups. Extensive evidence has substantiated the noninferiority or superiority of DOACs compared with VKAs in both prophylaxis and treatment of thromboembolic events. Notably, routine monitoring to evaluate treatment efficacy is not mandated for DOACs; however, they exhibit interactions with co-administered drugs and exert influence on functional coagulation assessments. This review aims to synthesize existing literature, encompassing the delineation of appropriate clinical indications, tailored employment in patients with specific concurrent conditions, needs in monitoring parameters, seamless transitions during shifts between anticoagulant regimens, and a glimpse into forthcoming perspectives in this evolving field.

Experimental drugs for supraventricular tachycardia: an analysis of early phase clinical trials.

INTRODUCTION: Supraventricular tachycardias (SVT) are a diverse group of commonly encountered arrhythmias arising at or above the atrioventricular (AV) node. Conventional anti-arrhythmic medications are restricted by extensive side-effect profiles and limited efficacy. Catheter ablation has emerged as a first-line therapy for many arrhythmias but is not a suitable option for all patients. This has prompted the exploration of novel pharmacological approaches targeting specific molecular mechanisms of SVT. AREAS COVERED: This review article aims to summarize recent advancements in pharmacological therapeutics for SVT and their clinical implications. The understanding of molecular mechanisms underlying these arrhythmias, particularly atrial fibrillation, has opened up new possibilities for targeted interventions. Beyond the manipulation of ion channels and membrane potentials, pharmacotherapy now focuses on upstream targets such as inflammation, oxidative stress, and structural remodeling. This review strives to provide a comprehensive overview of recent advancements in pharmacological therapeutics directed at the management of SVT. We begin by providing a brief summary of the mechanisms and management of commonly encountered SVT before delving into individual agents, which in turn are stratified based on their molecular treatment targets. EXPERT OPINION: The evolving landscape of pharmacologic therapy offers hope for more personalized and tailored interventions in the management of SVT.

Genetic and Molecular Mechanisms in Brugada Syndrome.

Brugada syndrome is a rare hereditary arrhythmia disorder characterized by a distinctive electrocardiogram pattern and an elevated risk of ventricular arrhythmias and sudden cardiac death in young adults. Despite recent advances, it remains a complex condition, encompassing mechanisms, genetics, diagnosis, arrhythmia risk stratification, and management. The underlying electrophysiological mechanism of Brugada syndrome requires further investigation, with current theories focusing on abnormalities in repolarization, depolarization, and current-load match. The genetic basis of the syndrome is strong, with mutations found in genes encoding subunits of cardiac sodium, potassium, and calcium channels, as well as genes involved in channel trafficking and regulation. While the initial discovery of mutations in the SCN5A gene provided valuable insights, Brugada syndrome is now recognized as a multifactorial disease influenced by several loci and environmental factors, challenging the traditional autosomal dominant inheritance model. This comprehensive review aims to provide a current understanding of Brugada syndrome, focusing on its pathophysiology, genetic mechanisms, and novel models of risk stratification. Advancements in these areas hold the potential to facilitate earlier diagnosis, improve risk assessments, and enable more targeted therapeutic interventions.

Drug Reaction With Eosinophilia and Systemic Symptoms-Associated Perimyocarditis After Initiation of Anti-tuberculosis Therapy: A Case Report.

A 34-year-old female who was recently placed on anti-tuberculosis medication with rifampin, isoniazid, pyrazinamide, and levofloxacin therapy for suspected tuberculosis reinfection presented with subjective fevers, rash, and generalized fatigue. Labs showed signs of end-organ damage with eosinophilia and leukocytosis. One day later, the patient became hypotensive with a worsening fever, and an electrocardiogram showed new diffuse ST segment elevations with an elevated troponin. An echocardiogram revealed a reduction in ejection fraction with diffuse hypokinesis, and cardiac magnetic resonance imaging (MRI) showed circumferential myocardial edema with subepicardial and pericardial inflammation. Prompt diagnosis of drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome using the European Registry of Severe Cutaneous Adverse Reaction (RegiSCAR) criteria and discontinuation of therapy was initiated. Due to the hemodynamic instability of the patient, the patient was started on systemic corticosteroids and cyclosporine, with the improvement of her symptoms and rash. A skin biopsy was performed, which revealed perivascular lymphocytic dermatitis, consistent with DRESS syndrome. As the patient's ejection fraction improved spontaneously with corticosteroids, the patient was discharged with oral corticosteroids, and a repeat echocardiogram showed full recovery of ejection fraction. Perimyocarditis is a rare complication of DRESS syndrome that is associated with degranulation and the release of cytotoxic agents into myocardial cells. Early discontinuation of offending agents and initiation of corticosteroids are essential to rapid recovery of ejection fraction and improved clinical outcomes. Multimodality imaging, including MRI, should be used to confirm perimyocardial involvement and guide the necessity for mechanical support or transplant. Further research should be on the mortality of DRESS syndrome with and without myocardial involvement, with an increased emphasis on cardiac evaluation in DRESS syndrome.

Prognostic significance of incorporating exercise tissue doppler mitral annular early diastolic velocity in exercise diastolic dysfunction assessment.

BACKGROUND: The existing algorithm for defining exercise-induced diastolic dysfunction incorporates resting e' velocity as a surrogate of myocardial relaxation. The additive prognostic value of incorporating post-exercise e' velocity in definition of exercise-induced diastolic dysfunction is poorly studied. AIM: To define the additive prognostic value of post-exercise e' septal velocity in the assessment of exercise-induced diastolic dysfunction compared to the traditional approach. METHODS: This retrospective study included 1409 patients undergoing exercise treadmill echocardiography with available full set of diastolic variables. Doppler measures of diastolic function included resting septal e' velocity, post-exercise septal e' velocity, post-exercise E/e' ratio, and post-exercise tricuspid regurgitant jet velocity. Approaches incorporating resting septal e' velocity and post-exercise septal e' velocity were compared in defining exercise-induced diastolic dysfunction, and for association with adverse cardiovascular outcomes. RESULTS: The mean age of study subjects was 56.3 ± 16.5 years and 791 (56%) patients were women. A total of 524 patients had disagreement between resting and post exercise septal e' velocities, and these values showed only weak agreement (kappa statistics: .28, P = .02). All categories of the traditional exercise-induced DD approach incorporating resting septal e' velocity witnessed reclassification when exercise septal e' velocity was used. When both approaches were compared, increased event rates were only evident when both approaches agreed on exercise-induced diastolic dysfunction (HR: 1.92, P < .001, 95% CI: 1.37-2.69). This association persisted after multivariable adjustment and propensity score matching for covariates. CONCLUSION: Incorporation of post-exercise e' velocity into the set of variables defining exercise-induced diastolic dysfunction can improve the prognostic utility of diastolic function assessment.