Andrea Segreti

Regular endurance exercise is consistently associated with lower cardiovascular mortality, a favorable cardiometabolic profile, and superior cardiorespiratory fitness. However, coronary imaging studies in master endurance athletes have raised a clinically relevant paradox: despite a low burden of conventional risk factors, some athletes—particularly older men with high lifetime exercise exposure—show a greater prevalence of coronary artery calcium and subclinical coronary plaque than sedentary or less active controls. This observation has challenged the long-standing assumption that high-volume endurance exercise is uniformly protective against coronary artery disease. A binary interpretation of this literature is inadequate. Coronary flow reserve and ischemic threshold may remain adequate in some athletes, although this concept is supported by limited functional and outcome data. Based on experimental vascular biology and indirect human evidence, repetitive high-flow states during endurance exercise generate sustained laminar shear stress, cyclic wall strain, and marked increases in coronary blood flow, thereby activating endothelial mechanotransduction pathways and influencing vascular smooth muscle cell behavior, extracellular matrix remodeling, and calcification biology. These adaptations may culminate in positive arterial remodeling, luminal enlargement, and, in some individuals, a predominantly calcified plaque phenotype. Importantly, structural remodeling does not necessarily equate to functional impairment. In selected athletes, when outward remodeling and endothelial responsiveness are preserved, coronary flow reserve and ischemic threshold may remain adequate, although this concept remains supported by limited functional and outcome data. This narrative review integrates the clinical imaging literature with current concepts in vascular mechanobiology to propose that coronary remodeling in endurance athletes exists along an adaptive–maladaptive continuum shaped by cumulative exercise load, aging, sex, conventional risk factors, and biological susceptibility. This framework may help clinicians interpret CAC/CCTA findings in athletes more appropriately and avoid equating plaque burden with equivalent functional or prognostic significance.

In heart failure (HF), elevated blood lactate levels, particularly during exercise or in advanced disease stages, reflect impaired tissue perfusion and altered metabolic regulation. Beyond its traditional role as a marker of anaerobic metabolism, lactate has emerged as a dynamic indicator of metabolic reserve and ventilatory control. This narrative review summarizes current evidence on lactate dynamics at rest and during exercise, highlighting their pathophysiological and clinical relevance. In HF patients, exercise-induced lactate accumulation occurs earlier and at lower workloads, reflecting impaired oxidative capacity and reduced peripheral oxygen utilization. This phenomenon is closely associated with ventilatory inefficiency, as demonstrated by the relationship between lactate levels and the VE/VCO₂ slope during cardiopulmonary exercise testing (CPET). Emerging data suggest that lactate is not only a marker of disease severity but also a potential mediator of chemoreflex activation and abnormal ventilatory responses. Furthermore, both pharmacologic and non-pharmacologic interventions may influence lactate production and utilization, supporting its role as a potential tool for therapeutic monitoring. Overall, the integration of lactate assessment, particularly during exercise, into clinical evaluation may provide additional insight into disease mechanisms, improve risk stratification, and contribute to personalized therapeutic optimization in patients with HF.

Inherited cardiomyopathies associated with high-risk genotypes, are characterized by a disproportionate risk of malignant ventricular arrhythmias and sudden cardiac death, often independent of left ventricular systolic dysfunction or advanced structural remodeling. Traditional surveillance strategies based on intermittent electrocardiography and phenotype-driven risk assessment are insufficient to capture the dynamic and often silent progression of electrical instability in these populations. This narrative review evaluates the emerging role of artificial intelligence (AI)-enabled sensor technologies in remote arrhythmic monitoring of genetically defined cardiomyopathy cohorts. Wearable ECG devices, implantable cardiac monitors, multisensor cardiac implantable electronic device algorithms, pulmonary artery pressure sensors, and contact-free systems enable continuous acquisition of electrophysiological and hemodynamic data, generating digital biomarkers that may reflect early arrhythmic vulnerability and subclinical decompensation. AI-driven analytics enhance signal processing, automated event detection, and remote data triage, with the potential to reduce clinical workload while preserving diagnostic sensitivity. However, current evidence predominantly derives from heterogeneous heart failure or general arrhythmia populations, and prospective validation in genotype-specific cohorts remains limited. Key challenges include algorithm generalizability, signal quality in ambulatory environments, data governance, interpretability of AI models, and integration into structured remote-care pathways. The convergence of genotype-informed risk stratification and multimodal AI-enabled sensing represents a promising strategy to transition from reactive device-based protection to proactive, precision-guided arrhythmic prevention. Dedicated genotype-focused studies and standardized digital endpoints are required to support safe and effective implementation in inherited cardiomyopathies.

Inherited cardiomyopathies represent a major cause of ventricular arrhythmias (VA) and sudden cardiac death (SCD), frequently occurring in the absence of advanced systolic dysfunction. Traditional strategies for the primary prevention of SCD have relied predominantly on left ventricular ejection fraction (LVEF), an approach that fails to capture the substantial biological and clinical heterogeneity of non-ischemic cardiomyopathies. Over the past decade, advances in cardiac genetics and cardiac magnetic resonance imaging have identified specific genotypes associated with a disproportionate arrhythmic risk, which often precedes overt ventricular remodeling. The 2023 European Society of Cardiology (ESC) Guidelines on cardiomyopathies formalize this paradigm shift by integrating etiology, myocardial substrate, and electrical phenotype into contemporary risk stratification. In this narrative review, we focus on cardiomyopathy-associated genotypes consistently linked to high arrhythmic risk—LMNA, truncating variants in FLNC, RBM20, PLN p.Arg14del, and desmosomal genes—and examine their molecular mechanisms, phenotypic trajectories, and arrhythmogenic profiles. We discuss how genotype-specific patterns of myocardial fibrosis, conduction disease, and VA inform implantable cardioverter-defibrillator (ICD) decision-making beyond LVEF-based thresholds. By synthesizing genetic, imaging, and clinical evidence in light of ESC 2023 recommendations, this review highlights the evolving role of genotype-informed strategies in the personalized prevention of SCD and underscores remaining gaps in evidence and risk prediction.

Heart failure (HF) is a multifaceted clinical syndrome that frequently precipitates disturbances in perfusion, ventilation, and metabolic regulation, all of which are rapidly detectable through arterial blood gas (ABG) analysis. Meanwhile, clinical markers such as lactate, arterial pH, arterial partial pressure of carbon dioxide (PaCO2), arterial partial pressure of oxygen (PaO2), bicarbonate, and electrolyte concentrations provide dynamic insight into the pathophysiologic status of patients and can serve as early indicators of decompensation. This review evaluates the clinical significance of key ABG and electrolyte parameters in both acute and chronic HF, emphasizing the prognostic value of the analyses, contribution to risk stratification, and utility in guiding therapy. In acute HF and cardiogenic shock, hyperlactatemia and acidosis are associated with increased mortality and the need for hemodynamic or ventilatory support. Furthermore, electrolyte abnormalities, particularly those involving sodium and potassium, are common and driven by neurohormonal activation, pharmacological therapies, and volume shifts. Therefore, integrating ABG and electrolyte monitoring into routine HF management can enhance diagnostic precision and support timely, targeted interventions. This narrative review synthesizes current evidence and proposes a practical framework for interpreting ABG results in the context of contemporary HF care.

Obstructive sleep apnea syndrome (OSA) is increasingly recognized as a common and clinically relevant comorbidity in coronary artery disease (CAD). Epidemiological studies demonstrate that OSA is highly prevalent among patients with CAD and independently increases the risk of myocardial infarction, accelerated atherosclerosis, and recurrent adverse events. The pathophysiological mechanisms underlying this association include intermittent hypoxia, sympathetic overactivation, oxidative stress, endothelial dysfunction, systemic inflammation, metabolic dysregulation, and pro-prothrombotic changes. These processes converge to promote coronary plaque formation, instability, and ischemia. Clinical evidence indicates that OSA contributes to silent nocturnal ischemia, higher rates of acute coronary syndromes, restenosis after percutaneous coronary intervention, and worse prognosis following myocardial infarction or surgical revascularization. Continuous positive airway pressure (CPAP) therapy improves blood pressure, endothelial function, and surrogate markers of ischemia, but large randomized trials have yielded neutral results on major cardiovascular events, largely due to suboptimal adherence. However, observational studies, however, suggest improved survival in patients who are adherent to CPAP therapy. Lifestyle interventions, particularly weight reduction, remain essential adjunctive strategies. This review synthesizes current evidence, evaluates therapeutic implications, and highlights the need for systematic OSA screening in CAD populations. Future research should focus on patient phenotyping, treatment adherence, and integrated care models to improve cardiovascular outcomes.

Obstructive Sleep Apnea (OSA) is a highly prevalent yet frequently underdiagnosed disorder strongly associated with cardiovascular morbidity and mortality. It is characterized by recurrent episodes of intermittent hypoxia, intrathoracic pressure swings, and sleep fragmentation that trigger sympathetic hyperactivation, oxidative stress, systemic inflammation, and progressive structural cardiac remodeling. These mechanisms translate into a wide range of electrocardiographic (ECG) abnormalities, including both nocturnal brady- and tachyarrhythmias, as well as daytime conduction and repolarization changes. This narrative review synthesizes current knowledge on ECG manifestations of OSA, encompassing atrial and ventricular ECG characteristics and the burden of supraventricular and ventricular arrhythmias. Emerging evidence suggests that several daytime ECG markers may represent accessible, low-cost indicators of subclinical cardiac remodeling and autonomic imbalance, with potential clinical implications. In addition, there is a rapidly evolving landscape of artificial intelligence applications and wearable-based ECG monitoring for OSA detection and risk stratification. Standardization of ECG-derived markers, validation across diverse populations, and integration into clinical workflows represent key priorities for future research. Recognizing ECG alterations associated with OSA may support earlier diagnosis, improved arrhythmic risk stratification, and more effective multidisciplinary management.

Cardiogenic pulmonary edema (CPE) is a life-threatening manifestation of acute heart failure characterized by rapid accumulation of fluid in the interstitial and alveolar spaces, leading to severe dyspnea, hypoxemia, and respiratory failure. The condition arises from elevated left-sided filling pressures that increase pulmonary capillary hydrostatic pressure, disrupt alveolo-capillary barrier integrity, and impair gas exchange. Neurohormonal activation further perpetuates congestion and increases myocardial workload, creating a vicious cycle of hemodynamic overload and respiratory compromise. Respiratory support is a cornerstone of management in CPE, aimed at stabilizing oxygenation, reducing the work of breathing, and facilitating ventricular unloading while definitive therapies, such as diuretics, vasodilators, inotropes, or mechanical circulatory support (MCS), address the underlying cause. Among available modalities, non-invasive ventilation (NIV) with continuous positive airway pressure (CPAP) or bilevel positive airway pressure (BiPAP) has the strongest evidence base in moderate-to-severe CPE, consistently reducing the need for intubation and providing rapid relief of dyspnea. High-flow nasal cannula (HFNC) represents an emerging alternative in patients with moderate hypoxemia or intolerance to mask ventilation, and should be considered an adjunctive option in selected patients with less severe disease or NIV intolerance, although its efficacy in severe presentations remains uncertain. Invasive mechanical ventilation is reserved for refractory cases, while extracorporeal membrane oxygenation (ECMO) and other advanced circulatory support modalities may be necessary in cardiogenic shock. Integration of respiratory strategies with hemodynamic optimization is essential, as positive pressure ventilation favorably modulates preload and afterload, synergizing with pharmacological unloading. Future directions include personalization of ventilatory strategies using advanced monitoring, novel interfaces to improve tolerability, and earlier integration of MCS. In summary, respiratory support in CPE is both a bridge and a decisive therapeutic intervention, interrupting the cycle of hypoxemia and hemodynamic deterioration. A multidisciplinary, individualized approach remains central to improving outcomes in this high-risk population.

Inhaled medications, commonly prescribed for respiratory conditions such as asthma and exercise-induced bronchoconstriction, are increasingly scrutinized in sports medicine due to their potential performance-enhancing effects. Bronchodilators, in particular, may improve lung function, increase oxygen delivery, and influence muscle contractility, potentially enhancing athletic performance. However, supratherapeutic use raises concerns about cardiovascular risks, including tachyarrhythmias and altered autonomic balance, as well as muscle hypertrophy and sprint capacity gains. These effects blur the line between therapeutic use and doping, creating challenges for fair competition. This review explores the mechanisms by which inhaled drugs affect the cardiovascular and muscular systems, summarizes notable doping cases, and evaluates current detection methods. Despite regulatory thresholds established by the World Anti-Doping Agency, assay interpretation remains complicated by inter-individual variability, short drug half-lives, and enantiomeric differences. Addressing these gaps requires refined pharmacokinetic modeling, enantioselective assays, and metabolomic fingerprinting to safeguard both athlete health and the integrity of sport.

Myocardial work (MW), derived from non-invasive pressure–strain loop (PSL) analysis, has recently emerged as a promising echocardiographic index for assessing left ventricular performance. It integrates speckle-tracking echocardiography with estimated left ventricular pressure, providing a load-adjusted measure of myocardial performance. This technique addresses the limitations of traditional parameters such as global longitudinal strain (GLS) and ejection fraction (EF), particularly in populations exposed to dynamic loading conditions, such as athletes. Athletic training induces a spectrum of cardiac adaptations, collectively referred to as the “athlete’s heart,” which may mimic or mask pathological conditions. In this context, MW represents a valuable tool to differentiate physiological remodeling from early myocardial dysfunction or underlying cardiovascular disease (e.g., cardiomyopathies, myocarditis). The aim of this review is to explore the physiological rationale for using MW in athletes, evaluate its relationship with performance metrics (e.g., VO₂max, lactate threshold), and discuss its potential, yet still emerging and not fully validated, role in informing training adaptation and detecting subclinical cardiac conditions. Additionally, we examine MW applications across different sport disciplines (strength, mixed-sport, and endurance), highlighting its role in individualized assessment and risk stratification. By synthesizing current evidence and outlining future research directions, this work emphasizes the potential of MW to become a standard component of cardiovascular evaluation in sports cardiology.