Exercise across the cardiovascular continuum: expanding perspectives on its key role in contemporary clinical practice

Physical exercise has a fundamental role across the cardiovascular continuum, being a central component of different diagnostic methods while also comprising a powerful therapeutic intervention in various clinical contexts.1,2 Regarding the former, frameworks ranging from exercise testing with electrocardiographic monitoring (whether coupled with respiratory gas analyses [cardiopulmonary exercise stress testing—CPET] or without this input) to imaging modalities such as exercise stress echocardiography place substantial emphasis on its impact in the cardiovascular system.3-6 As previously discussed in different reports, these may be used for diagnostic purposes, while also being relevant for risk stratification and prognostic evaluation.3,5,7 Notably, although pharmacological agents can have an important role in modalities such as stress echocardiography, exercise has the key feature of being a physiological stressor, allowing the assessment of several components of the integrated cardiovascular response.3,4 In this background, exercise is considered a first-line option for indications such as ischemic heart disease (IHD), while also being advantageous in others such as hypertrophic cardiomyopathy (HCM).3,4,7 When appraising the role of exercise as a therapeutic intervention, a plethora of data also attests to its myriad benefits, in both primary and secondary prevention settings.1,8 Importantly, while the benefits of exercise training have been depicted in many scenarios, reports also show that this may be associated with deleterious cardiovascular effects in some individuals, leading to a major interest in tailored risk stratification.1,9 Finally, the concept that a personalized approach to exercise prescription (regarding its different facets, namely when incorporated in cardiac rehabilitation [CR] programs) is key to harnessing its full potential, akin in many respects to the strategy used for pharmacological interventions, has gained prominence.10,11 After a careful clinical assessment including a review of comorbidities and potential contraindications, exercise-based methodologies such as CPET can play a pivotal role in both risk stratification and training optimization, elegantly illustrating the dynamic bidirectional relationship between these two cornerstone applications of exercise (as both a core component of diagnostic methodologies and therapeutic interventions) (Fig. 1).1,5,10Figure 1.: Overview of some of the applications of exercise in cardiovascular medicine (details in the main text). 1) Examples include exercise stress testing with electrocardiographic monitoring, cardiopulmonary exercise stress testing, and exercise stress echocardiography.Over the years, data have reinforced the impact of exercise training in those with cardiovascular disease (CVD), namely in the setting of IHD and heart failure.1,12,13 Among these, the progressive incorporation of exercise training in comprehensive CR programs has had a major impact in patient management strategies, as highlighted by contemporary guidelines.1,13,14 Indeed, exercise-based CR is presently a class I recommendation in IHD, being associated with benefits in both morbidity and cardiovascular mortality.1,13,14 These programs are also fundamental in those with heart failure, being associated with improvements in functional capacity and quality of life, while data also report on benefits regarding hospitalizations (although some heterogeneity when considering different studies should be pondered with).1,13,15,16 Beyond these two major indications, there are also several other areas where exercise training has made substantial progress (Table 1).1,6,17-19 Among these, the fields of peripheral artery disease (PAD), HCM, and cardio-oncology have seen substantial breakthroughs, with exercise training emerging as a potentially useful intervention across different moments.1,7,17-19 Table 1 - Overview of some of the indications concerning exercise training across the cardiovascular continuum. Clinical setting* Observations Cardiovascular risk factors Examples include arterial hypertension, diabetes mellitus, dyslipidemia, or overweight/obesity Ischemic heart disease Post-acute coronary syndromesChronic coronary syndromes Heart failure Across the spectrum of heart failure Post-cardiac surgery Post-coronary or valvular surgery Peripheral artery disease Supervised exercise training in symptomatic peripheral artery disease Hypertrophic cardiomyopathy After comprehensive risk stratification frameworks Cardio-oncology Exercise as a useful intervention across the cancer patient journey Atrial fibrillation Tailored exercise programs, namely in the setting of paroxysmal or persistent atrial fibrillation *Nonexhaustive overview, including settings with exercise training as part of cardiac rehabilitation frameworks (details in the main text) and areas with potential overlap. In PAD, exercise training is a cornerstone of optimized management, as illustrated in contemporary guidelines.17,20,21 In those with PAD, supervised exercise training can improve walking distance (namely without pain) and quality of life, while positively contributing to overall cardiovascular risk optimization.17,20-23 Interestingly, also in those submitted to revascularization, exercise training can provide substantial benefits, supporting its role as a combined strategy.17,20 Finally, determining the ankle-brachial index after exercise may also be useful in the diagnostic process of PAD.17,20,21 Albeit exercise has at times been viewed as possibly deleterious in those with HCM, the paradigm concerning its role has markedly expanded over the past decades.1,7 Although the recognition of HCM as a cause of sudden cardiac death, coupled with several mechanisms that could influence this risk during exercise (particularly vigorous exercise), has previously resulted in a considerably restrictive view, current data support a more individualized approach.1,7,24,25 While a detailed discussion is beyond the scope of this article, an integrated approach encompassing, among others, clinical, imaging, and functional data is presently paramount during overall assessment and shared decision-making processes.1,7,25-27 Although there are still several caveats that should be acknowledged (namely regarding exercise dosing or optimal risk stratification, as well as characteristics pertaining to study designs), data from different studies have also supported this concept.28-30 In this regard, studies encompassing both those with obstructive and nonobstructive phenotypes have shown that moderate-intensity exercise was associated with functional benefits, with a balanced safety signal.28-30 In HCM, exercise can also form a central part of patient assessment strategies.7,25 Beyond providing guidance for exercise prescription in this patient population (incorporating a detailed focus on red flags such as decreased systolic arterial blood pressure or arrhythmias), CPET is also valuable by contributing prognostic information, with variables such as the peak oxygen uptake or ventilatory efficiency being among those particularly informative.25 In addition, exercise stress echocardiography can also be useful (being a class I, level B recommendation in both European and American guidelines on this topic) in symptomatic patients with resting left ventricular outflow tract gradients below 50 mmHg, to assess dynamic changes.7,25 Moreover, exercise stress echocardiography can allow the assessment of mitral regurgitation, further emphasizing its versatility and the value of exercise as a physiological stressor (namely when compared with others such as dobutamine, as underscored in current guidelines).7 Cardio-oncology is another area that has been at the forefront, with insights from different studies showing various potential benefits of exercise training, ranging from those in functional capacity and quality of life to risk factor improvements.1,18,19,31 In this field, exercise has been applied across different time points of the cancer patient journey.1,18,32 This is echoed in guidelines from the European Society of Cardiology on sports cardiology and exercise in patients with CVD, which provide a class I (level A) recommendation for regular exercise in those with cancer, while the latest cardio-oncology guidelines provide a class IIa recommendation for the participation of cancer survivors at high cardiovascular risk in cardio-oncology rehabilitation programs.1,31 While the latter encompass (similar to classical CR programs) several facets beyond exercise, it should be recalled that exercise training is a core component of these interventions.33,34 Of note, while data have underscored the role of exercise training as a pivotal ancillary strategy, there has also been substantial interest in its broader impact, including regarding the immune response and metabolic pathways.35-37 Although there are still several hindrances in this area, further studies are set to continue expanding knowledge in terms of these effects and their possible implications.35,36,38,39 As discussed above, in contemporary settings, exercise shows substantial relevance as both a core component of diagnostic methodologies and as a robust therapeutic intervention.1,2,16,18,22 Importantly, a personalized approach is critical to achieve its full potential benefits, while mitigating potential adverse effects.1,9,10,39-42 While data reinforce the benefits of exercise across various moments of the cardiovascular continuum, challenges related to optimal implementation strategies and framework designs should be the focus of continued research.1,16,18,21,33,36,43 As we approach the end of the first quarter of the 21st century, reflecting on the challenges posed by and the impact of CVD, appraising the current applications and future horizons of exercise remains center stage to continuously improve overall individualized care strategies.