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BACKGROUND: The underlying mechanisms responsible for the clinical benefits following coronary sinus narrowing and pressure elevation remain unclear. The present study aims to investigate whether coronary sinus narrowing improves the indexes of coronary microcirculatory function. METHODS: Patients with refractory angina who had a clinical indication for reducer implantation underwent invasive physiological assessments before and 4 months after the procedure. The primary outcome was the change in the values of the index of microcirculatory resistance. Secondary end points included changes in coronary flow reserve and the resistive resistance ratio values. Angina status was assessed with the Canadian Cardiology Society class and the Seattle Angina Questionnaire. RESULTS: Twenty-four patients with a history of obstructive coronary artery disease and prior coronary revascularization (surgical and percutaneous) treated with reducer implantation were enrolled, and 21 of them (87%) underwent repeated invasive coronary physiological assessment after 4 months. The index of microcirculatory resistance values decreased from 33.35±19.88 at baseline to 15.42±11.36 at 4-month follow-up (P<0.001; mean difference, −17.90 [95% CI, −26.16 to −9.64]). A significant (≥20% from baseline) reduction of the index of microcirculatory resistance was observed in 15 (71.4% [95% CI, 47.8%–88.7%]) patients. The number of patients with abnormal index of microcirculatory resistance (≥25) decreased from 12 (57%) to 4 (19%; P=0.016). Coronary flow reserve increased from 2.46±1.52 to 4.20±2.52 (mean difference, 1.73 [95% CI, 0.51–2.96]). Similar findings were observed for resistive resistance ratio values. Overall, 16 patients (76.1%) had an improvement of 1 Canadian Cardiology Society class. Seattle Angina Questionnaire summary score increase of around 3 points (3.01 [95% CI, 1.39–4.61]). CONCLUSIONS: Coronary sinus reduction implantation is associated with a significant improvement in the parameters of coronary microcirculatory function. These findings provide insights into the improvement of angina symptoms and may have implications for the treatment of coronary microvascular dysfunction. [ABSTRACT FROM AUTHOR]

Background: Transcatheter mitral valve replacement (TMVR) may mature to become a therapeutic option for high-risk patients with severe mitral regurgitation (MR), particularly in patients at high or prohibitive surgical risk. MR patients with preexisting aortic valve prosthesis have been excluded from most TMVR trials because of the potential risks of left ventricular outflow tract obstruction or interaction between the TMVR anchoring mechanism and the aortic prosthesis. We describe the procedural and short-term outcomes of transapical TMVR with the Tiara valve in patients experiencing severe symptomatic MR with previous aortic valve replacement (AVR)., Methods and Results: Twelve consecutive high surgical risk patients (11 men; mean age, 75±6 years) with aortic valve prosthesis and severe MR underwent TMVR with Tiara valve. Aortic valves were mechanical in 5 and biological in 7 patients, while 1 patient had previously undergone implantation of a transcatheter valve within a failed bioprosthetic surgical valve. Six patients (50%) had undergone redo surgical aortic valve replacement. Clinical characteristics of the group include prior mitral valve repair in 2, prior coronary bypass grafting surgery in 5, chronic atrial fibrillation in 7, renal failure in 9, and pacemaker/cardiac resynchronization device in 9 patients. Mean Society of Thoracic Surgery score and EuroSCORE II were 10.5±4.4 and 12.4±3.7, respectively. Mean baseline left ventricular ejection fraction was 35.5±5.3% (range, 30%-45%). The Tiara valve was implanted uneventfully in all patients. Device migration or left ventricular outflow tract obstruction was not observed. No patient required conversion to open heart surgery or periprocedural hemodynamic support. Procedural success was 100% with no death, MI, stroke, major bleeding, or access site complications at 30 days. MR was eliminated in all 12 patients immediately after implantation., Conclusions: Transapical mitral valve replacement with the Tiara valve in high-risk patients with severe MR and aortic valve prostheses is technically feasible and can be performed safely.

Background: Signal transduction through the platelet-derived growth factor (PDGF)/PDGF-receptor (PDGFR) system has been linked to vascular smooth muscle cell migration and proliferation leading to allograft vasculopathy. This study describes the effect of the tyrphostin AG-1295, a specific PDGFR tyrosine-kinase inhibitor, on neointimal formation in this disease., Methods and Results: Rat aortic allografts transplanted from dark agouti (RT1 ) donors to Wistar-Furth (RT1 ) recipients were assessed in a new treatment model for local drug delivery from polymeric carrier matrices precoated with AG-1295. Matrices were wrapped around the graft immediately after transplantation. The recipients received no background immunosuppression. At day 80 posttransplantation, intimal thickness in AG-1295-treated grafts was reduced when compared to controls (11.8+/-9.1% intimal thickness vs. 23.7+/-6.4% intimal thickness; P=0.042). This finding corresponded to inhibition of intimal PDGFR-beta expression in AG-1295-treated grafts at day 20 posttransplantation (P =0.029 vs. allogeneic controls)., Conclusions: The tyrphostin AG-1295 reduces neointimal formation in aortic allograft vasculopathy by inhibition of PDGFR-beta-triggered tyrosine phosphorylation. Local drug release of specific tyrosine-kinase inhibitors from perivascularly co-implanted polymeric carrier matrices is effective in the prophylaxis of allograft vasculopathy under selected experimental conditions.