Regular physical activity has a beneficial impact on the cardiovascular system. However, the intense and prolonged exertion typical of professional athletes and amateur marathon runners can lead to adaptive changes in the heart. These changes encompass both structural and functional modifications, which may have positive or negative effects on cardiac function and contribute to the development of so-called "athlete's heart." Prolonged exercise induces adaptations at the molecular and cellular levels, including altered gene expression and remodeling of myocardial proteins. It may also cause transient elevations in biomarkers such as N-terminal pro-brain natriuretic peptide (NT-proBNP) and high-sensitivity troponin. Some athletes experience cardiac arrhythmias, including atrial fibrillation. Morphological changes, such as myocardial hypertrophy or chamber dilation, can be assessed using echocardiography. Studies have reported potentially benign valvular abnormalities, as well as cases of myocardial fibrosis and arrhythmias. Early diagnosis of cardiac conditions in marathon runners is essential for effective prevention and health monitoring. This article reviews the current data on cardiac changes in endurance athletes, based on the literature from the past decade. The ESC guidelines also emphasize the importance of interpreting diagnostic findings within the context of physiological adaptations to training—referred to as “athlete’s heart”—which may mimic pathological changes, but are typically reversible and not associated with an increased risk of sudden cardiac death [ 6 ]. Intense exercise can cause a transient increase in biomarkers commonly used in clinical practice to assess cardiac function, such as N-terminal pro-brain natriuretic peptide (NT-proBNP) and high-sensitivity troponin [ 7 , 8 ]. These changes are more likely to reflect the body’s adaptation to significant and prolonged physical exertion rather than permanent cardiac damage. In the later part of the race, increased SV allows for a reduction in HR, thus adjusting cardiac output (CO) accordingly [ 29 ]. Changes in HR and SV together contribute to the overall increase in CO during exercise. Cardiac workload remains submaximal and relatively stable for most of the run duration [ 27 , 30 , 31 , 32 ]. This hemodynamic pattern is illustrated in Figure 1 . The reduced resting heart rate commonly observed in endurance athletes is most likely due to long-term, intense endurance training, which leads to enhanced vagal tone and reduced sympathetic activity in marathon runners [ 33 ]. Figure 1 Hemodynamic changes in the right heart during exercise: a schematic diagram. The IL-33/ST2 axis is activated in the heart in response to mechanical overload or injury, leading to the inhibition of myocardial fibrosis and hypertrophy. Marathon running causes a significant increase in sST2 concentration, with higher levels observed in runners with better performance. It has been shown that male sex, exercise intensity, and greater body weight loss during the marathon are directly associated with sST2 levels [ 74 , 75 ]. Beyond biomarker changes, recent studies have elucidated key molecular signaling pathways that mediate exercise-induced cardiac remodeling. Own elaboration. 2.2. Cardiac Pathological and Physiological Alterations 2.2.1. Cardiac Fibrosis Long-term stress and chronic volume overload resulting from intensive training can lead to progressive remodeling of myocardial fibers in the subendocardial and subepicardial layers of the heart muscle. In athletes, post-exercise myocardial fibrosis has been observed—ranging from minor changes in the RV, which may represent a benign effect of chronic activity, to extensive areas of intramyocardial and diffuse fibrosis [ 46 , 47 , 48 , 49 , 50 ]. Ang II and ET-1 stimulate the development of pathological hypertrophy through activation of the mitogen-activated protein kinase (MAPK) and calcineurin pathways. These processes promote cardiomyocyte apoptosis and necrosis, replaced by excessive collagen deposition in the extracellular matrix. This leads to increased stiffness of the heart walls, systolic and diastolic dysfunction, and fibrosis of the conduction system, which may cause arrhythmias, including AF [ 34 , 49 , 102 ]. Persistently elevated CO in the early post-race period leads to increased wall tension and dilation of the right atrium and ventricle, resulting in the release of cytoplasmic markers—this effect is not necessarily related to cardiomyocyte necrosis [ 15 , 23 , 112 ]. Some data suggest that long-term, high-intensity exercise may lead to atherosclerotic changes in the coronary arteries—despite the generally favorable lipid profile of athletes. Endurance athletes often show increased LV internal diameter and mild eccentric hypertrophy, enabling sufficient cardiac output during exercise [ 29 ]. The duration of diastole depends on heart rate, while LV filling is influenced by hydration status and blood flow redistribution; blood pressure affects afterload [ 127 ]. Prolonged volume overload and excessive sympathetic activation may lead to the development of heart failure with preserved ejection fraction (HFpEF), and less commonly, heart failure with reduced ejection fraction (HFrEF). Conclusions Regular cardiologic examinations, including echocardiography, resting and exercise ECG, and monitoring of cardiac biomarkers, are essential for detecting pathological changes. Advanced imaging methods such as CMR can aid in identifying myocardial fibrosis, which in some athletes may increase the risk of arrhythmias and heart failure. The long-term consequences of intensive training may include an increased risk of cardiac arrhythmias, and in rare cases, the development of cardiomyopathy. Although physical activity has well-documented health benefits, caution is warranted, especially in athletes with a family history of cardiovascular disease or prior cardiac issues.

Atrial fibrillation (AF) is the most common cardiac arrhythmia, characterized by irregular atrial activity. AF is related to increased risk of thromboembolic events, heart failure, and premature mortality. Recent advances in our understanding of its pathophysiology include a potentially central role for inflammation and presence of cardiovascular risk factors. The role of physical activity and exercise in the development and progression of AF, however, are not yet fully understood. Physical activity is protective for modifiable cardiovascular risk factors, including those associated with AF. Indeed, emerging research has demonstrated beneficial effects of exercise on AF-specific outcomes, including AF recurrence postablation. Counterintuitively, the prevalence of AF in veteran endurance athletes seems higher compared with the general population. In this review, we discuss the novel evidence and underlying mechanisms underpinning the role of exercise as medicine in the development and management of AF but also the counterintuitive detrimental role of excessive endurance exercise. Finally, we advocate regular (but not long-term high-intensity endurance) exercise training as a safe and effective strategy to reduce the risk of incident AF and to minimize the associated risk of secondary cardiovascular events.

Regular exercise confers multifaceted and well-established health benefits. Yet, transient and asymptomatic increases in markers of cardio-renal injury are commonly observed in ultra-endurance athletes during and after competition. This has raised concerns that chronic recurring insults could cause long-term cardiac and/or renal damage. Indeed, extreme endurance exercise (EEE) over decades has sometimes been linked with untoward cardiac effects, but a causal relation with acute injury markers has not yet been established. Here, we summarize the current knowledge on markers of cardiac and/or renal injury in EEE athletes, outline the possible interplay between cardiac and kidney damage, and explore the roles of various factors in the development of potential exercise-related cardiac damage, including underlying diseases, medication, sex, training, competition, regeneration, mitochondrial dysfunction, oxidative stress, and inflammation. In conclusion, despite the undisputed health benefits of regular exercise, we speculate, based on the intimate link between heart and kidney diseases, that in rare cases excessive endurance sport may induce adverse cardio-renal interactions that under specific, hitherto undefined conditions could result in persistent cardiac damage. We highlight future research priorities and provide decision support for athletes and clinical consultants who are seeking safe strategies for participation in EEE training and competition. Download PDF Abstract Regular exercise confers multifaceted and well-established health benefits. Yet, transient and asymptomatic increases in markers of cardio-renal injury are commonly observed in ultra-endurance athletes during and after competition. This has raised concerns that chronic recurring insults could cause long-term cardiac and/or renal damage. Indeed, extreme endurance exercise (EEE) over decades has sometimes been linked with untoward cardiac effects, but a causal relation with acute injury markers has not yet been established. Cardiac hypertrophy Cardiovascular Diseases Cardiology Chronic kidney disease Kidney Diseases Sports Medicine Cardiovascular Responses to Endurance Exercise FormalPara Key Points Clear evidence for long-term cardiac and/or renal damage resulting from chronic recurring insults from extreme endurance exercising is still missing. A better understanding of this association is important to enable endurance athletes to reap all the health benefits from exercising without risk of cardiac/renal adversities. However, long-term consequences of repeated acute events and the role of potential cardio-renal feedback loops remain unknown, primarily due to the inherent complexity of appropriate study designs. Even so, both the predictive importance of creatinine levels for troponin elevations after marathon running [ 11 ] and the well-known association between heart and kidney damage (cardio-renal syndrome) [ 12 ] suggest the existence of such a relationship [ 13 ]. The investigation of possible causal associations between clinical observations and long-term high-intensity and/or high-volume endurance exercise is an important future endeavor to allow athletes to safely practice health-promoting exercise. This review provides a summary of common exercise-induced increases in markers of cardio-renal injury, and evaluates the hitherto poorly understood link between permanent heart damage and kidney injury, in an attempt to lay the groundwork for future studies as well as to provide guidance for athletes and clinical consultants on which parameters to consider when advising individuals who are engaging in EEE. Systemic hypertension is a well-established risk factor for the development of heart diseases, including the onset and progression of AF [ 49 ], and it may also cause renal damage [ 50 ], initiating the vicious cycle of cardio-renal syndrome [ 12 ]. Damage to one of these organs is often associated with dysfunction or damage of the other, due to the cardio-renal crosstalk [ 12 ]. An increase of a multitude of biomarkers in response to (extreme) endurance exercise (Fig. 3 ), which potentially could lead to adverse cardio-renal consequences in the long-term, has been reported. Fig. 3.5.2 Mitochondrial Dysfunction, Renin–Angiotensin–Aldosterone System (RAAS), Oxidative Stress, and Inflammation Several mechanisms may link EEE, increased kidney and cardiac injury markers, and long-term cardiac damage. For example, mitochondrial dysfunction, including mitochondrial fragmentation, is recognized as a key factor in AKI [ 107 ] and in cardio-renal syndromes [ 62 ]. On the other hand, mitochondria strongly benefit from endurance exercise. Insufficient regeneration time between repeated endurance competitions and training is a plausible explanation for incomplete repair and long-term effects of exercise-induced kidney damage and myocardial injury. Finally, reparative processes of heart and kidney may be temporally different. This depends on the genetic background and individual experiences, including exposures to repeated episodes of severe stress, in particular if they differentially affect either the myocardium or kidneys. Such individual factors may explain how repetitive challenges, for example by EEE, could evoke either kidney damage alone, heart damage alone, or both together. Long-term prospective studies investigating the potential of accumulating transient damage of heart and kidneys as causative factors for rare permanent cardiac damage in long distance runners are important to better understand the role of the cardio-renal interplay in pathogenesis. Based on the intimate link between heart and kidney diseases [ 12 ], it is reasonable to speculate that excessive endurance sport may induce adverse cardio-renal interactions that under specific, hitherto undefined conditions could result in persistent cardiac damage [ 13 ]. The increase of cardiac and/or renal injury markers following marathon and ultramarathon