The Coronary ARteriogenesis with combined Heparin and EXercise therapy in chronic refractory Angina (CARHEXA) trial: A double-blind, randomized, placebo-controlled stress echocardiographic study

Abstract

Background Coronary collateral circulation exerts protective effects on myocardial ischaemia due to coronary artery disease and can be promoted by exercise with heparin co-administration. Whether this arteriogenetic effect is accompanied by functional improvement of left ventricle during stress and lessening of angina symptoms remains unknown. Aims To evaluate the anti-ischaemic efficacy of heparin plus exercise in coronary artery disease. Methods In a prospective, single-centre, randomized, double-blind study we recruited 32 ‘no-option’ patients (27 males; mean age 61 ± 8 years) with stable angina, exercise-induced ischaemia and coronary artery disease not suitable for revascularization. All underwent a two-week cycle of exercise (two exercise sessions per day, five days per week) and were randomized ( n = 16 per group) to intravenous placebo (0.9% saline) versus unfractionated heparin (5.000 IU intravenously), 10 min prior to exercise. We assessed Canadian Cardiovascular Society angina class, stress electrocardiogram and echo parameters (wall motion score index) and computed tomography angiography for collaterals. Results After two-week cycle, Canadian Cardiovascular Society class statistically decreased in both groups (heparin plus exercise group: 2.6 ± 0.7 to 1.9 ± 0.7, p < 0.001, exercise group: 2.4 ± 0.7 to 2.1 ± 0.9, p = 0.046). Only the heparin plus exercise group improved time-to-ST segment depression (before 270, 228–327 s vs. after 339, 280–360 s, p = 0.012) and wall motion score index (before 1.38 ± 0.25 vs. after 1.28 ± 0.18, p = 0.005). By multi-slice computed tomography angiography, collaterals improved in 12/15 (80%) in the heparin plus exercise group versus 2/16 (12.5%) in the exercise group ( p < 0.001). Conclusion A two-week, 10-test cycle of heparin plus exercise is better than exercise in improving angina class, myocardial ischaemia and collaterals by computed tomography angiography.

Leptomeningeal anastomoses: Mechanisms of pial collateral remodeling in ischemic stroke

“…The effects of physical exercise on collaterals can also be improved when coupled with pharmacological treatments. A recent clinical trial investigating myocardial ischemia found that patients that received heparin in addition to exercise had improved collateral flow compared to patients in the exercise alone group (Petrovic et al, 2020).…”

The Effects of Exercise on Coronary Collateral Circulation: A Review

“…Most patients in clinical settings receive heparin subcutaneously. Hence the results of both the above studies [ 15 , 28 ] may not translate into the clinical setting. These two studies had relatively small sample sizes and short durations of exercise and medication.…”

New Ultrasound Technologies for Ischemic Heart Disease Assessment and Monitoring in Cardiac Rehabilitation

“…Exercise-based cardiac rehabilitation (CR) in patients affected by CAD increases functional capacity and reduces total and cardiovascular morbidity and mortality [ 58 , 59 , 60 , 61 , 62 ]. A role in this improvement induced by exercise, may be played by reverse LV remodeling characterized by reduced LV volumes and increased LV ejection [ 63 ].…”