A male patient aged 40 years presented following a notification from his Apple Watch indicating low cardiac fitness. The patient had been using the Apple Watch since November 2020 and received the alert in October 2021 during a trip abroad. His device revealed a progressive decline in cardiac fitness index, as shown in Figure 1. The patient had no known previous medical history, hospitalizations, or medical treatment. He was fit and engaged in high-intensity workouts several times a week. Other than occasional palpitations, he reported being asymptomatic during the months before this alert. He reported no history of smoking or use of illicit substances and no family history of cardiovascular disease, including sudden death or ischemic disease. At the time of presentation, however, he reported that his sister had been undergoing a cardiac workup at the same time due to suspected peripartum cardiomyopathy following supraventricular tachycardia (SVT) after delivery. Her echocardiography exam suggested mild globally reduced left ventricle (LV) systolic function and an ejection fraction (EF) of 45%.

Initial workup included a stress echocardiography exam demonstrating reduced global LV systolic function and an LV EF of 20% (visually estimated) without valvular malformations or regional wall abnormalities. Following these results, the patient was hospitalized and underwent a comprehensive workup, including repeated echocardiography, a 24-holter exam, and cardiac magnetic resonance imaging (MRI). Repeat echocardiography demonstrated a mildly dilated LV, severe diffuse global LV dysfunction with an EF of 23%, grade I diastolic dysfunction, a right ventricle with normal size and function, a normal left atrium, an aortic valve with minimal regurgitation, mild mitral regurgitation, and minimal tricuspid regurgitation with normal systolic pulmonary pressure. The rest of the exam was within normal limits. Cardiac MRI demonstrated a dilated LV with an LV end-diastolic diameter of 63 mm. There were no signs of late gadolinium enhancement. Normal T1 mapping was up to 1150 milliseconds and T2 mapping was up to 52 milliseconds (with normal values up to 50 milliseconds); the measured LV EF was 47%. The next step in the cardiomyopathy workup was genetic testing, which revealed a titin mutation (TTN, exon 326, c.86116C>T [p.Arg28706*]).

During hospitalization, the patient was started on a β-blocker, mineralocorticoid receptor antagonist, an angiotensin II receptor blocker, and a sodium-glucose transport protein 2 inhibitor. After hospitalization, he began a cardiac rehabilitation program with no reports of symptoms on exertion; the New York Heart Association classification was 1. Additional echocardiography in December 2021 demonstrated a LV EF of 35%. Figure 2 depicts an increase in the patient’s cardiac fitness index from November 2021 to September 2022 after treatment initiation.

The participant has provided written informed consent. All patient data has been deidentified.

In recent years, we have witnessed growth in the accessibility of oxygen consumption measurement and its potential uses in clinical cardiology. Peak VO₂ helps establish a reference for a patient’s cardiac fitness and provides insight into risk stratification for disease status, cardiac rehabilitation, and perioperative status. Oxygen consumption improvement has been shown to confer a survival benefit and minimize disease progression [19], and therefore, measurement of this parameter is useful for both one-time assessment and routine follow-up. The continuous feedback of peak VO₂ through wearable devices may allow for patient engagement in health monitoring, promote lifestyle changes, and guide clinical decision-making [20]. This case of an asymptomatic male with low peak VO₂ due to underlying cardiomyopathy demonstrates the advantages of wearable devices as a screening tool in healthy and at-risk adults, as well as the ability to monitor cardiac fitness after treatment initiation. Many other cardiac and noncardiac pathologies may be detected earlier due to their correlation to changes in peak VO₂. We discuss the various pathologies and clinical scenarios that relate to this index below.

Oxygen consumption has been shown to be decreased in various cardiac conditions, including heart failure (HF), ischemic heart disease (IHD), atrial fibrillation (AF), valvular disease, cardiomyopathy, hypertension, and other pathologies [21-23]. HF patients often experience decreased quality of life with restriction of basic activities due to dyspnea and exercise intolerance, with peak VO₂ being a well-studied estimator of functional capacity among this patient population. A study of chronic systolic HF patients showed that a 6% increase in peak VO₂ was associated with improved clinical outcomes, including all-cause mortality and hospitalizations [24]. Additional studies found that increased peak VO₂ due to systemic and skeletal muscle adaptations from high-intensity training is associated with the preservation of ejection fraction and prevention of LV remodeling [25]. From a hemodynamic standpoint, oxygen consumption has a strong linear correlation with cardiac output [26], making peak VO₂ tracking a surrogate marker for cardiac output estimation, which is essential among HF patients. Another study found that better cardiac fitness in midlife (median age 49 years) is associated with a decreased risk of developing HF and subsequent hospitalization later in life, independent of other cardiac or noncardiac risk factors (1 MET increase was associated with a 17% risk reduction) [27]. Interestingly, in a study with 63 patients with chronic AF who underwent cardioversion to sinus rhythm, peak VO₂ was monitored before the procedure and 1 month after. Peak VO₂ max after the procedure significantly increased, suggesting that low peak VO₂ accompanies AF, perhaps related to tachycardia-induced cardiomyopathy [28]. Hypertension also warrants oxygen consumption monitoring, as a prospective study reported that those in a lower VO₂ max group were almost 2 times more at risk of developing hypertension and that striving for a higher VO₂ max may be protective against hypertension [29].

Peak VO₂ measurement is also relevant in noncardiac diseases. Studies have shown that increased oxygen consumption is associated with a lower risk of developing metabolic syndromes such as diabetes through several mechanisms. First, exercise, as reflected by improved VO₂, builds muscle that uses and removes glucose from the blood, while other reports discuss the potential role of oxidative pathway regulation in mitochondria as a potential linker between oxygen consumption and metabolic risk [30,31]. CRF has been found to have an inverse relationship with metabolic syndrome in males and females, with waist circumference being the strongest predicting factor [32]. Additional studies report that improved CRF is as effective as statin therapy in lowering the mortality risk in patients with dyslipidemia [33]. The benefit of increased peak VO₂ can also be seen among patients with chronic obstructive pulmonary disease (COPD) and is associated with reduced all-cause mortality [1]. Further investigation of the relationship between peak VO₂ and other chronic medical conditions is warranted, as low peak VO₂ is associated with ongoing disease progression in patients with rheumatoid arthritis, as estimated by inflammatory markers and subjective assessment. Cardiovascular risk factors linked to rheumatoid arthritis, such as atherosclerosis and changes in fat and muscle distribution, were decreased among patients with improved aerobic capacity [34]. Moreover, it is hypothesized that a higher peak VO₂ is protective against brain pathologies such as stroke, depression, and dementia [35-37]. To investigate the relationship between cardiorespiratory fitness and stroke risk, a study examined 16,878 asymptomatic men aged between 40 and 87 years whose fitness was followed over 10 years, reporting that a higher VO₂ was associated with a 68% lower risk of stroke death when compared to those with a low VO₂, and a moderate VO₂ was associated with a 63% decrease [35]. As discussed here, there is a widespread need for oxygen consumption evaluation among pathologies extending from cardiology, especially because many conditions may not produce symptoms until later in the disease course.

Cardiac rehabilitation is perhaps the best proof of practice for following peak VO₂ to reduce all-cause mortality and hospital admissions. For patients with acute coronary syndrome (ACS) or surgical interventions, cardiac rehabilitation is imperative for secondary prevention. Future directions for rehabilitation intend to maximize the incorporation of exercise to achieve greater aerobic capacity, which can be monitored through changes in peak VO₂ [38]. Additionally, reports comment on the advantage of objective physical activity and prognostic factor monitoring for personalized feedback, which relies less on patient recollection [39]. Peak VO₂ also allows for assessing patients’ readiness for cardiovascular and noncardiovascular surgery, with studies demonstrating its association with postoperative complications and mortality in procedures such as gastrointestinal and vascular surgeries, hepatic transplantation, lung tumor resection, and coronary artery bypass grafting [40]. Thus, this dynamic parameter may be considered in the preoperative assessment, leading to improved decision-making and outcomes. A unique role for peak VO₂ measurement is evaluating a patient’s need or readiness for heart transplantation. A study with 181 HF patients reported that the actuarial 1- and 2-year survival of the 89 patients who achieved a VO₂ equal to or <50% of predicted peak VO₂ was 74% and 43%, respectively, compared with 98% and 90% in the 92 patients who achieved >50% predicted peak VO₂ [41]. Other studies have investigated VO₂’s role in triaging for cardiac transplantation and proposed a peak VO₂ greater than 14 ml/min/kg as an appropriate cutoff value [42]. Further validation studies are needed to assess whether oxygen consumption measurement is a suitable marker for heart transplantation.

As with this patient’s case, most individuals with cardiomyopathy accompanied by decreased left ventricular systolic dysfunction are asymptomatic until the development of advanced disease [43]. It is difficult to estimate the number needed to screen to prevent cardiac events as the data concerning the validity of wearable peak VO₂ is preliminary and the true scope of the asymptomatic cardiac patients’ burden is uncertain. However, serial peak VO₂ measurements have been shown to be advantageous in certain populations, such as those with congenital heart diseases. In a study with 1375 adult cyanotic and noncyanotic heart disease patients followed for 10 years while undergoing serial CPETs, the combination of peak VO₂ and heart rate reserve provided strong prognostic insight for mortality [44]. Another study in adults with a Fontan circulation who completed at least two maximal CPETs found that a decrease in peak VO₂ is a predictor of death or transplant, regardless of initial peak VO₂ [45]. These studies suggest that peak VO₂ measurements may be a useful prognostic marker for heart disease burden due to congenital heart defects, and perhaps in individuals similar to our patient after further studies are performed. We suggest there may be a place for using peak VO₂ data among both apparently healthy adults and those in high-risk populations as a first warning sign, triggering further workup. With most screening tools, there is a concern that false-positive data will cause unnecessary, costly, and, at times, hazardous workups. We believe that a more precise role for this tool will be only determined after a careful assessment is performed with robust scientific methodology and sufficient statistical power.

As reviewed here, a large body of evidence suggests the potential role of integrating peak VO₂ into various clinical scenarios. The option to access data routinely and continuously using a wearable device necessitates reconsidering peak VO₂’s ideal place in clinical settings. Wearable devices can at least partially replace a patient’s need to seek a CPET, which remains a logistically complex exam mostly limited to medical institutions, resulting in inconvenience for patients and poor accessibility. Reports recognize the potential of wearables for primary and secondary prevention but also identify barriers and limitations such as cost, data security, and false-positive results leading to unnecessary intervention and subsequent burden on the health care system [46]. The heterogeneity of methods used to collect data, along with the continuous device updates, similarly presents challenges for standardization [39]. Other reports have introduced a guide for integrating wearable devices into cardiovascular care with considerations for incorporating data into electronic medical records, staff education, index cutoffs, and frequency of review [47]. Further limitations of wearable devices include the inability to measure peak carbon dioxide production (VCO₂) and anaerobic threshold values, which serve as additional prognostic factors measured during CPETs. Peak VCO₂ is the amount of carbon dioxide exhaled from the body over time and reflects exercise capacity, whereas the anaerobic threshold is the point of substantially increased minute ventilation relative to VO₂ and represents a rise in lactic acid production. The anaerobic threshold suggests the functional capacity of HF patients, with a lower measurement indicating decreased capacity. It can also distinguish between cardiac and noncardiac conditions, with fatigue before the threshold point being less indicative of a cardiac condition [48].

We demonstrated that wearable devices could streamline the process from the onset of disease manifestation to therapeutic intervention. Indeed, a potential new trend that medical providers will need to address is the presentation of peak VO₂ or parallel indices by the patient through wearables at an early phase or as the trigger for a diagnostic workflow before other modalities, especially among HF patients. Moreover, routine peak VO₂ measurement in HF patients allows for another objective variable to assess, in addition to standard parameters such as weight, blood pressure, and heart rate, which addresses the issue of sparse, unbiased indices by broadening the opportunity for concrete data collection. Measuring this index continuously and remotely, which is not relevant for CPETs and other conventional methods that calculate peak VO₂, allows patients to present earlier in the usual diagnostic workflow. After diagnosis and treatment initiation, peak VO₂ can be monitored using the wearable device, as demonstrated in this patient’s case. Health care providers and patients can be more informed about cardiac fitness during a treatment or rehabilitation regimen and accordingly adjust interventions while preventing clinical exacerbations. There is potential to improve clinical outcomes through enhanced monitoring of functional capacity parameters and cardiac fitness; however, devices should be used cautiously and only for adult populations in the appropriate clinical setting to prevent adverse use. Additional prospective studies are needed to enable this change while being supported with scientific evidence and an official classification as a medical-grade device. With the exponentially growing distribution of wearable devices, it may be less of a challenge to conduct these studies and obtain policy-changing evidence in a short period of time.

This report demonstrates the potential utility of routine peak VO₂ measurement for screening cardiac and noncardiac diseases to elucidate therapeutic options for patients in an accelerated timeframe and leverage widespread technology to initiate early interventions. Peak VO₂ provides a glimpse into risk stratification, rehabilitation, and perioperative care. Greater awareness of cardiorespiratory fitness among apparently healthy adults and those with high cardiovascular risk is needed and may result in impactful interventions.