Coronary endothelial function testing may improve long-term quality of life in subjects with microvascular coronary endothelial dysfunction.

Aim: Angina pectoris in the absence of obstructive coronary artery disease (CAD) is common and is associated with poor quality of life (QOL). Coronary microvascular endothelial dysfunction is associated with myocardial ischaemia and is a common cause of angina. We hypothesise that evaluation of coronary endothelial function, its diagnosis and treatment will favourably impact QOL in patients with angina symptoms and non-obstructive CAD. Methods and results: Follow-up was done on 457 patients with chest pain and non-obstructive coronary arteries who had undergone coronary vascular reactivity evaluation by administration of intracoronary acetylcholine at the time of diagnostic study. After a mean follow-up of 8.4±4.7 years, QOL was assessed by administration of the SF-36 QOL survey. Patients diagnosed and treated for microvascular endothelial dysfunction had a higher (better) overall mental composite score (44.8 vs 40.9, p=0.036) and mental health score (44.2 vs 40.7, p=0.047), and a trend towards higher vitality scores (39.1 vs 35.9, p=0.053) and role emotional scores (43.6 vs 40.4, p=0.073), compared with patients with normal endothelial function. Conclusion: Among patients with chest pain and normal coronaries, diagnosis and treatment of coronary microvascular endothelial dysfunction in those with angina pectoris and non-obstructive CAD are associated with better QOL compared with patients with normal endothelial function.

Long-Term Sirolimus for Primary Immunosuppression in Heart Transplant Recipients.

BACKGROUND: Small studies have reported superiority of sirolimus (SRL) over calcineurin inhibitor (CNI) in mitigating cardiac allograft vasculopathy (CAV) after heart transplantation (HT). However, data on the long-term effect on CAV progression and clinical outcomes are lacking. OBJECTIVES: The aim of this study was to test the long-term safety and efficacy of conversion from CNI to SRL as maintenance therapy on CAV progression and outcomes after HT. METHODS: A cohort of 402 patients who underwent HT and were either treated with CNI alone (n = 134) or converted from CNI to SRL (n = 268) as primary immunosuppression was analyzed. CAV progression was assessed using serial coronary intravascular ultrasound during treatment with CNI (n = 99) and after conversion to SRL (n = 235) in patients who underwent at least 2 intravascular ultrasound studies. RESULTS: The progression in plaque volume (2.8 ± 2.3 mm3/mm vs. 0.46 ± 1.8 mm3/mm; p < 0.0001) and plaque index (plaque volume-to-vessel volume ratio) (12.2 ± 9.6% vs. 1.1 ± 7.9%; p < 0.0001) were significantly attenuated when treated with SRL compared with CNI. Over a mean follow-up period of 8.9 years from time of HT, all-cause mortality occurred in 25.6% of the patients and was lower during treatment with SRL compared with CNI (adjusted hazard ratio: 0.47; 95% confidence interval: 0.31 to 0.70; p = 0.0002), and CAV-related events were also less frequent during treatment with SRL (adjusted hazard ratio: 0.35; 95% confidence interval: 0.21 to 0.59; p < 0.0001). Further analyses suggested more attenuation of CAV and more favorable clinical outcomes with earlier conversion to SRL (≤2 years) compared with late conversion (>2 years) after HT. CONCLUSIONS: Early conversion to SRL is associated with attenuated CAV progression and with lower long-term mortality and fewer CAV-related events compared with continued CNI use.

Long-term endothelin receptor antagonism attenuates coronary plaque progression in patients with early atherosclerosis.

AIM: The purpose of the current study was to determine if long term treatment with an endothelin-A (ETA) receptor antagonist attenuates the progression of coronary plaques in patients with coronary endothelial dysfunction. METHODS: Thirty-five patients with non-obstructive coronary disease and coronary endothelial dysfunction were randomized in a double blind manner to treatment with placebo or ETA receptor antagonist Atrasentan (10 mg) for six months. Endothelial function was assessed by the change in coronary blood flow and coronary artery diameter in response to intracoronary acetylcholine. Normalized mean total atheroma volume (TAVMEAN), percent atheroma volume (PAV) and changes of atheroma volume were assessed by intravascular ultrasound (IVUS) at baseline and 6-month follow-up. RESULTS: In segments with coronary endothelial dysfunction, there was a significant decrease in normalized TAVMEAN and PAV at six months from baseline in the Atrasentan group compared to the placebo group median (IQR) -2.00 mm(3) (-7.28, 2.53.) vs 9.11 mm(3) (1.23, 14.05), p=0.0024 and 0.955% (-3.43, 1.70) vs 3.85% (-0.39, 14.59) p=0.010. There was no change in normalized TAV or PAV in the segments with normal endothelial function. CONCLUSION: This study demonstrates that 6-month treatment with Atrasentan attenuates progression of coronary plaque in segments with endothelial dysfunction.