Recover with INOCA: A randomized, prospective study of a cardiac rehabilitation program in patients with ischemia with nonobstructive coronary artery disease (INOCA)

Abstract Introduction Cardiac rehabilitation programs (CRP) are a crucial intervention in the management of ischemic heart disease. However, most of the evidence comes from studies on obstructive coronary artery disease, being INOCA (Ischemia with Nonobstructive Coronary Artery Disease) patients underrepresented. Main objective: to evaluate the effect of CRP on maximal functional capacity (V02peak) in INOCA patients, compared to standard recommendations. Methods INOCA patients were 1:1 randomly assigned to home-based CRP program for 3 months (treatment group) or standard recommendations (control group) as shown in Figure 1. The primary endpoint was the difference in VO2peak between baseline and 3 months in both groups. Secondary endpoints were CRP impact on quality of life, adherence to mediterranean diet, emotional state, functional independence, angina episodes and sleep quality. A sample of 24 patients was powered to demonstrate a 4.5 ml/kg/min difference in VO2peak (80% statistical power and 15% loss rate). We selected pure VSA (vasospasm) and pure MCA (microvascular) endotypes for the inclusion. Results 68% of the study population were women and mean age was 59.9 years old. 55% of patients were MCA and 45% were VSA. There were no differences between groups in terms of age, gender and cardiovascular risk at baseline clinical characteristics. CRP was associated with a significant improvement in VO2peak of 4.3 ml/kg/min (p=0.04), as well as increase in submaximal functional capacity (VO2 at VT1), whereas the control group experienced a decrease in VO2peak and no change in submaximal capacity (Figure 2A). Indeed, difference between groups in VO2peak (primary endpoint) was 4.9 ml/kg/min (p=0.0004). Additionally, the CRP led to significant increase in chronotropic response, muscle mass percentage and peripheral muscle efficiency, with no changes observed in the control group. The CRP also enhanced quality of life, functional independence and reduced monthly angina episodes compared to control group (Figure 2B). Besides, CRP group showed (although non statistically significant) improvements in emotional state, Mediterranean diet adherence and sleep quality; these parameters remained unchanged in the control group. There were no complications during the CRP. Conclusions A home-based CRP was safe and effective in improving functional capacity (main outcome), as well as muscle mass, strength, exercise volume, quality of life, functional independence and monthly angina episodes in INOCA patients. No differences were found between groups in terms of emotional state, Mediterranean diet adherence, and sleep quality, which may need a powered sample. Larger trials with extended follow-up are needed to confirm long-term benefits and broader applicability of this intervention.Fig 1:Flowchart of our study Fig 2:Results of our study