Exercise-based cardiac rehabilitation in stable angina pectoris: a narrative review on current evidence and underlying physiological mechanisms.

Stable angina pectoris (SAP) is a prevalent condition characterised by a high disease burden. Based on recent evidence, the need for revascularisation in addition to optimal medical treatment to reduce mortality and re-events is heavily debated. These observations may be explained by the fact that revascularisation is targeted at the local flow-limiting coronary artery lesion, while the aetiology of SAP relates to the systemic, inflammatory process of atherosclerosis, causing generalised vascular dysfunction throughout the entire vascular system. Moreover, cardiovascular events are not solely caused by obstructive plaques but are also associated with plaque burden and high-risk plaque features. Therefore, to reduce the risk of cardiovascular events and angina, and thereby improve quality of life, alternative therapeutic approaches to revascularisation should be considered, preferably targeting the cardiovascular system as a whole with a physiological approach. Exercise-based cardiac rehabilitation fits this description and is a promising strategy as a first-line treatment in addition to optimal medical treatment. In this review, we discuss the role of exercise-based cardiac rehabilitation in SAP in relation to the underlying physiological mechanisms, we summarise the existing evidence and highlight future directions.

Rapid Improvements in Physical Activity and Sedentary Behavior in Patients With Acute Myocardial Infarction Immediately Following Hospital Discharge.

Background Little is known about changes in physical activity (PA) and sedentary behavior (SB) patterns in the acute phase of a myocardial infarction (MI). We objectively assessed PA and SB during hospitalization and the first week after discharge. Methods and Results Consecutively admitted patients hospitalized with an MI were approached to participate in this prospective cohort study. SB, light-intensity PA, and moderate-vigorous intensity PA were objectively assessed for 24 h/d during hospitalization and up to 7 days after discharge in 165 patients. Changes in PA and SB from the hospital to home phase were evaluated using mixed-model analyses, and outcomes were stratified for predefined subgroups based on patient characteristics. Patients (78% men) were aged 65±10 years and diagnosed with ST-segment-elevation MI (50%) or non-ST-segment-elevation MI (50%). Sedentary time was high during hospitalization (12.6 [95% CI, 11.8-13.7] h/d) but substantially decreased following transition to the home environment (-1.8 [95% CI, -2.4 to -1.3] h/d). Furthermore, the number of prolonged sedentary bouts (≥60 minutes) decreased between hospital and home (-1.6 [95% CI, -2.0 to -1.2] bouts/day). Light-intensity PA (1.1 [95% CI, 0.8-1.6] h/d) and moderate-vigorous intensity PA (0.2 [95% CI, 0.1-0.3] h/d) were low during hospitalization but significantly increased following transition to the home environment (light-intensity PA: 1.8 [95% CI, 1.4-2.3] h/d; moderate-vigorous intensity PA: 0.4 [95% CI, 0.3-0.5] h/d; both P<0.001). Improvements in PA and SB were similar across groups, except for patients who underwent coronary artery bypass grafting and who did not improve their PA patterns after discharge. Conclusions Patients with MI demonstrate high levels of SB and low PA volumes during hospitalization, which immediately improved following discharge at the patient's home environment. Registration URL: trialsearch.who.int/; Unique identifier: NTR7646.

Impact of a comprehensive cardiac rehabilitation programme versus coronary revascularisation in patients with stable angina pectoris: study protocol for the PRO-FIT randomised controlled trial.

BACKGROUND: Currently, in the majority of patients with stable angina pectoris (SAP) treatment consists of optimal medical treatment, potentially followed by coronary angiography and subsequent coronary revascularisation if necessary". Recent work questioned the effectiveness of these invasive procedures in reducing re-events and improving prognosis. The potential of exercise-based cardiac rehabilitation on clinical outcomes in patients with coronary artery disease is well-known. However, in the modern era, no studies compared the effects of cardiac rehabilitation versus coronary revascularisation in patients with SAP. METHODS: In this multicentre randomised controlled trial, 216 patients with stable angina pectoris and residual anginal complaints under optimal medical treatment will be randomised to: 1) usual care (i.e., coronary revascularisation), or 2) a 12-month cardiac rehabilitation (CR) programme. CR consists of a multidisciplinary intervention, including education, exercise training, lifestyle coaching and a dietary intervention with a stepped decline in supervision. The primary outcome will be anginal complaints (Seattle Angina Questionnaire-7) following the 12-month intervention. Secondary outcomes include cost-effectiveness, ischemic threshold during exercise, cardiovascular events, exercise capacity, quality of life and psychosocial wellbeing. DISCUSSION: In this study, we will examine the hypothesis that multidisciplinary CR is at least equally effective in reducing anginal complaints as the contemporary invasive approach at 12-months follow-up for patients with SAP. If proven successful, this study will have significant impact on the treatment of patients with SAP as multidisciplinary CR is a less invasive and potentially less costly and better sustainable treatment than coronary revascularisations. TRIAL REGISTRATION: Netherlands Trial Register, NL9537. Registered 14 June 2021.

Association between engagement in exercise training and peak cardiac biomarker concentrations following ST-elevation myocardial infarction.

Background: Regular exercise training is an important factor in prevention of myocardial infarction (MI). However, little is known whether exercise engagement prior to MI is related to the magnitude of post-MI cardiac biomarker concentrations and clinical outcomes. Objectives: We tested the hypothesis that exercise engagement in the week prior MI is related to lower cardiac biomarker concentrations following ST-elevated MI (STEMI). Methods: We recruited hospitalised STEMI patients and assessed the amount of exercise engagement in the 7 days preceding MI onset using a validated questionnaire. Patients were classified as 'exercise' if they performed any vigorous exercise in the week prior MI, or as 'control' if they did not. Post-MI peak concentrations of high-sensitive cardiac troponin T (peak-hs-cTnT) and creatine kinase (peak-CK) were examined. We also explored whether exercise engagement prior MI is related to the clinical course (duration of hospitalisation and incidence of in-hospital, 30-day and 6-month major adverse cardiac events (reinfarction, target vessel revascularisation, cardiogenic shock or death)). Results: In total, 98 STEMI patients were included, of which 16% (n=16) was classified as 'exercise', and 84% (n=82) as 'control'. Post-MI peak-hs-cTnT and peak-CK concentrations were lower in the exercise group (941 (645-2925) ng/mL; 477 (346-1402) U/L, respectively) compared with controls (3136 (1553-4969) ng/mL, p=0.010; 1055 (596-2019) U/L, p=0.016, respectively). During follow-up, no significant differences were found between both groups. Conclusion: Engagement in exercise is associated with lower cardiac biomarker peak concentrations following STEMI. These data could provide further support for the cardiovascular health benefits of exercise training.

Exercise-based cardiac rehabilitation vs. percutaneous coronary intervention for chronic coronary syndrome: impact on morbidity and mortality.

AIMS: Accumulating evidence questions the clinical value of percutaneous coronary intervention (PCI) for patients with chronic coronary syndrome (CCS). We therefore compare the impact of exercise-based cardiac rehabilitation (CR) vs. PCI in patients with CCS on 18-month mortality and morbidity, and evaluate the effects of combining PCI with exercise-based CR. METHODS AND RESULTS: A retrospective cohort study was conducted in March 2021. An online, real-world dataset of CCS patients was acquired, utilizing TriNetX, a global federated health research network. Patients with CCS who received PCI were first compared with patients who were prescribed exercise-based CR. Second, we compared patients who received both CR + PCI vs. CR alone. For both comparisons, patients were propensity-score matched by age, sex, race, comorbidities, medications, and procedures. We ascertained 18-month incidence of all-cause mortality, rehospitalization, and cardiovascular comorbidity [stroke, acute myocardial infarction (AMI), and new-onset heart failure]. The initial cohort consisted of 18 383 CCS patients. Following propensity score matching, exercise-based CR was associated with significantly lower odds of all-cause mortality [0.37 (95% confidence interval (CI): 0.29-0.47)], rehospitalization [0.29 (95% CI: 0.27-0.32)], and cardiovascular morbidities, compared to PCI. Subsequently, patients that received both CR + PCI did not have significantly different odds for all-cause mortality [1.00 (95% CI: 0.63-1.60)], rehospitalization [1.00 (95% CI: 0.82-1.23)], AMI [1.11 (95% CI: 0.68-1.81)], and stroke [0.71 (95% CI: 0.39-1.31)], compared to CR only. CONCLUSIONS: Compared to PCI, exercise-based CR associated with significantly lower odds of 18-month all-cause mortality, rehospitalization, and cardiovascular morbidity in patients with CCS, whilst combining PCI and exercise-based CR associated with lower incident heart failure only.

Exploring the Influence of Alcohol Industry Funding in Observational Studies on Moderate Alcohol Consumption and Health.

Funding of research by industry in general can lead to sponsorship bias. The aim of the current study was to conduct an initial exploration of the impact of sponsorship bias in observational alcohol research by focusing on a broad spectrum of health outcomes. The purpose was to determine whether the outcome depended on funding source. We focused on moderate alcohol consumption and used meta-analyses that are the basis of several international alcohol guidelines. These meta-analyses included observational studies that investigated the association of alcohol consumption with 14 different health outcomes, including all-cause mortality, several cardiovascular diseases and cancers, dementia, and type 2 diabetes. Subgroup analyses and metaregressions were conducted to investigate the association between moderate alcohol consumption and the risk of different health outcomes, comparing findings of studies funded by the alcohol industry, ones not funded by the alcohol industry, and studies with an unknown funding source. A total of 386 observational studies were included. Twenty-one studies (5.4%) were funded by the alcohol industry, 309 studies (80.1%) were not funded by the alcohol industry, and for the remaining 56 studies (14.5%) the funding source was unknown. Subgroup analyses and metaregressions did not show an effect of funding source on the association between moderate alcohol intake and different health outcomes. In conclusion, only a small proportion of observational studies in meta-analyses, referred to by several international alcohol guidelines, are funded by the alcohol industry. Based on this selection of observational studies the association between moderate alcohol consumption and different health outcomes does not seem to be related to funding source.

Cyclophilin D ablation is associated with increased end-ischemic mitochondrial hexokinase activity.

Both the absence of cyclophilin D (CypD) and the presence of mitochondrial bound hexokinase II (mtHKII) protect the heart against ischemia/reperfusion (I/R) injury. It is unknown whether CypD determines the amount of mtHKII in the heart. We examined whether CypD affects mtHK in normoxic, ischemic and preconditioned isolated mouse hearts. Wild type (WT) and CypD-/- mouse hearts were perfused with glucose only and subjected to 25 min ischemia and reperfusion. At baseline, cytosolic and mtHK was similar between hearts. CypD ablation protected against I/R injury and increased ischemic preconditioning (IPC) effects, without affecting end-ischemic mtHK. When hearts were perfused with glucose, glutamine, pyruvate and lactate, the preparation was more stable and CypD ablation-resulted in more protection that was associated with increased mtHK activity, leaving little room for additional protection by IPC. In conclusion, in glucose only-perfused hearts, deletion of CypD is not associated with end-ischemic mitochondrial-HK binding. In contrast, in the physiologically more relevant multiple-substrate perfusion model, deletion of CypD is associated with an increased mtHK activity, possibly explaining the increased protection against I/R injury.