Citations

Pediatric heart failure is a heterogeneous, high-risk clinical syndrome that differs fundamentally from adult heart failure in its etiologies, pathophysiology, and therapeutic responses. Although its absolute prevalence is lower, children experience disproportionate morbidity and mortality, with up to 40% of patients with symptomatic cardiomyopathy progressing to death or transplantation within 2 years of diagnosis. Congenital heart disease, cardiomyopathies, and genetic or metabolic disorders dominate the etiologic spectrum, while developmental differences in myocardial signaling, neurohormonal activation, and ventricular remodeling limit direct extrapolation of adult guideline-directed medical therapy. Evidence supporting pharmacologic treatment remains limited, and most therapies are symptom-modifying rather than outcome-modifying, particularly in single-ventricle physiology. Advances in mechanical circulatory support and heart transplantation have substantially improved survival, yet pose unique anatomic, physiological, and ethical challenges in children. This review synthesizes contemporary evidence across medical, device-based, and transplant therapies, highlights lesion- and age-specific considerations, and identifies critical research gaps needed to advance outcomes in pediatric heart failure.

Hypertension remains the leading modifiable risk factor for cardiovascular morbidity and mortality worldwide, yet blood pressure control rates remain suboptimal despite the availability of effective therapies. Contemporary guidelines increasingly recommend early use of combination therapy, recognizing that most patients require multiple agents to achieve target blood pressure. Widaplik, a recently Food and Drug Administration-approved fixed-dose, single-pill triple combination of telmisartan, amlodipine, and indapamide, represents the first triple therapy approved for initial treatment of hypertension in adults likely to need multidrug therapy. This review summarizes the pharmacologic rationale for low-dose triple therapy, highlighting complementary mechanisms targeting the renin-angiotensin-aldosterone system, vascular resistance, and sodium retention. We examine evidence from pivotal phase 3 trials demonstrating rapid, sustained blood pressure reductions, higher control rates compared with dual therapy, and favorable tolerability. We also discuss safety considerations, practical limitations, and gaps in evidence, including long-term cardiovascular outcomes. Widaplik represents a paradigm shift toward simplified, early combination therapy aimed at improving hypertension control and reducing cardiovascular risk.

Coronary microvascular dysfunction (CMD) is increasingly recognized as a central mechanism underlying myocardial ischemia, heart failure with preserved ejection fraction, and adverse cardiovascular outcomes in patients with and without obstructive coronary artery disease. The coronary microcirculation plays a critical role in regulating myocardial perfusion through tightly coordinated myogenic, metabolic, and endothelial pathways. Disruption of these mechanisms results in impaired vasodilatory capacity, abnormal coronary flow reserve, and microvascular ischemia. This review summarizes the anatomy and physiology of coronary microcirculation and examines the pathophysiologic mechanisms driving CMD, including endothelial dysfunction, structural remodeling, inflammation, and neurohormonal dysregulation. Contemporary diagnostic strategies are reviewed, with emphasis on invasive coronary function testing and advanced noninvasive imaging modalities such as positron emission tomography and cardiac magnetic resonance imaging. The clinical implications of CMD across diverse disease states, including ischemia with nonobstructive coronary arteries, heart failure, and cardiomyopathies, are discussed. Finally, current therapeutic approaches, prognostic considerations, and emerging research directions aimed at improving diagnosis and targeted treatment of CMD are highlighted.

Coronary artery spasm (CAS) is a dynamic vasomotor disorder characterized by transient, intense constriction of epicardial coronary arteries, leading to myocardial ischemia in patients with and without obstructive coronary artery disease. CAS plays a central role in vasospastic angina, ischemia with nonobstructive coronary arteries and myocardial infarction with nonobstructive coronary arteries, malignant arrhythmias, and sudden cardiac death. Its pathophysiology is multifactorial, involving endothelial dysfunction, vascular smooth muscle hyperreactivity, inflammation, oxidative stress, autonomic imbalance, and genetic susceptibility, with notable ethnic and sex-related differences. Diagnosis relies on integration of clinical features, electrocardiographic changes, and invasive coronary provocation testing using acetylcholine or ergonovine, supported by advanced imaging and functional assessment when microvascular involvement is suspected. Management is centered on calcium channel blockers and nitrates, aggressive risk factor modification, particularly smoking cessation, and individualized strategies for refractory or high-risk patients. Improved recognition and standardized diagnostic pathways are essential to optimize outcomes and reduce life-threatening complications associated with CAS.

Shock is a life-threatening state of circulatory failure characterized by inadequate tissue oxygen delivery and cellular hypoxia. Lactate has emerged as a central biomarker in the diagnosis, risk stratification, and management of shock, yet its interpretation is complex and context dependent. Although traditionally viewed as a marker of anaerobic metabolism and tissue hypoperfusion, hyperlactatemia in distributive shock, particularly sepsis, frequently reflects multifactorial mechanisms, including increased aerobic glycolysis, adrenergic stimulation, mitochondrial dysfunction, and impaired hepatic clearance. This review examines the pathophysiology and classification of shock, the biochemical basis of lactate production and clearance, and the prognostic significance of both static lactate levels and lactate kinetics. We synthesize evidence supporting lactate as a robust prognostic marker while highlighting limitations of lactate-targeted resuscitation strategies. Emerging data favor multimodal approaches integrating lactate trends with complementary perfusion markers such as capillary refill time and central venous oxygen saturation. Lactate should be interpreted as one component of a comprehensive physiological assessment rather than an isolated therapeutic target.

Sudden death in children and young adults, while uncommon, carries profound clinical and societal implications. Cardiac causes, particularly inherited arrhythmias and cardiomyopathies, account for most cases, though neurologic, toxicologic, traumatic, and infectious etiologies also contribute significantly. This review explores the epidemiology, classification, and pathophysiologic mechanisms of sudden death in this population, emphasizing early clinical warning signs and identifiable risk factors. We also outline diagnostic and preventive strategies, including electrocardiography, genetic testing, and postmortem evaluation. Despite guidelines advocating preparticipation screening, real-world implementation remains inconsistent. Advances in genomics and artificial intelligence offer new opportunities for early risk detection. Finally, we discuss public health interventions such as defibrillator access, cardiopulmonary resuscitation education, and school-based protocols as essential components of a broader prevention strategy.

Coronary artery disease (CAD) is the leading cause of death globally. Apolipoprotein A-1 (apoA-1), the primary protein component of high-density lipoprotein (HDL), facilitates reverse cholesterol transport and has emerged as a potential therapeutic target. While pharmacologic efforts to raise HDL-C levels have failed to reduce cardiovascular events, focus has shifted to HDL functionality, particularly cholesterol efflux capacity (CEC). ApoA-1 infusions have demonstrated antiatherogenic effects in preclinical models and early human trials by enhancing CEC and promoting cholesterol clearance. This review summarizes the rationale and evolving clinical trial landscape investigating apoA-1 infusions as a novel therapy for CAD prevention and treatment.