Influence of percutaneous mitral valve repair using the MitraClip® system on renal function in patients with severe mitral regurgitation.

BACKGROUND: In patients with mitral regurgitation (MR), changes in cardiac stroke volume, and thus renal preload and afterload may affect kidney function. Percutaneous mitral valve repair (PMVR) with the MitraClip® system can be a therapeutic alternative to surgical valve repair. The influence of MitraClip® therapy on renal function and clinical outcome parameters is unknown. METHODS AND RESULTS: Sixty patients with severe MR underwent PMVR using the MitraClip® system in an open-label observational study. Patients were stratified according to their renal function. All clips have been implanted successfully. Effective reduction of MR by 2-3 grades acutely improved KDOQI class. Lesser MR reduction (MR reduction of 0-1 grades) led to worsening of renal function in patients with pre-existing normal or mild (KDOQI 1-2) compared to severe (KDOQI 3-4) renal dysfunction. Reduction of MR was associated with improvement in Minnesota Living with Heart Failure Questionnaire (MLHFQ), NYHA-stadium, and 6-minute walk test. CONCLUSION: Successful PMVR was associated with an improvement in renal function. The improvement in renal function was associated with the extent of MR reduction and pre-existing kidney dysfunction. Our data emphasize the relevance of PVMR to stabilize the cardiorenal axis in patients with severe MR.

Cocoa flavanol intake improves endothelial function and Framingham Risk Score in healthy men and women: a randomised, controlled, double-masked trial: the Flaviola Health Study.

Cocoa flavanol (CF) intake improves endothelial function in patients with cardiovascular risk factors and disease. We investigated the effects of CF on surrogate markers of cardiovascular health in low risk, healthy, middle-aged individuals without history, signs or symptoms of CVD. In a 1-month, open-label, one-armed pilot study, bi-daily ingestion of 450 mg of CF led to a time-dependent increase in endothelial function (measured as flow-mediated vasodilation (FMD)) that plateaued after 2 weeks. Subsequently, in a randomised, controlled, double-masked, parallel-group dietary intervention trial (Clinicaltrials.gov: NCT01799005), 100 healthy, middle-aged (35-60 years) men and women consumed either the CF-containing drink (450 mg) or a nutrient-matched CF-free control bi-daily for 1 month. The primary end point was FMD. Secondary end points included plasma lipids and blood pressure, thus enabling the calculation of Framingham Risk Scores and pulse wave velocity. At 1 month, CF increased FMD over control by 1·2 % (95 % CI 1·0, 1·4 %). CF decreased systolic and diastolic blood pressure by 4·4 mmHg (95 % CI 7·9, 0·9 mmHg) and 3·9 mmHg (95 % CI 6·7, 0·9 mmHg), pulse wave velocity by 0·4 m/s (95 % CI 0·8, 0·04 m/s), total cholesterol by 0·20 mmol/l (95 % CI 0·39, 0·01 mmol/l) and LDL-cholesterol by 0·17 mmol/l (95 % CI 0·32, 0·02 mmol/l), whereas HDL-cholesterol increased by 0·10 mmol/l (95 % CI 0·04, 0·17 mmol/l). By applying the Framingham Risk Score, CF predicted a significant lowering of 10-year risk for CHD, myocardial infarction, CVD, death from CHD and CVD. In healthy individuals, regular CF intake improved accredited cardiovascular surrogates of cardiovascular risk, demonstrating that dietary flavanols have the potential to maintain cardiovascular health even in low-risk subjects.

Safety and efficacy of deep sedation as compared to general anaesthesia in percutaneous mitral valve repair using the MitraClip system.

OBJECTIVE: To characterize the safety and efficacy of deep sedation (DS) as compared to general anaesthesia (GA) in percutaneous mitral valve repair (PMVR) using the MitraClip system. BACKGROUND: PMVR with the MitraClip system has emerged as a therapeutic alternative to surgical valve repair in high-risk patients. The PMVR procedure is typically performed under GA. Due to their high surgical risk, avoidance of GA in many of those patients would be desirable. METHODS: In an open-label observational study 21 patients with severe mitral regurgitation were randomized to either GA or DS using propofol. Primary endpoints of this comparison were related to safety with rate of conversion from DS to GA, bleeding, aspiration, and pneumonia. Secondary endpoints were related to efficacy with procedural, in-hospital, and mid-term outcome at 1 month. RESULTS: All clips have been implanted successfully in both groups. No conversion from DS to GA was necessary. Four patients undergoing GA suffered from upper respiratory tract infections and two from peripheral vascular complications during placement of central venous catheter for GA. Short- and mid-term efficacy were comparable in both groups with a reduced hospital stay in the DS group. CONCLUSION: PVMR in high-risk patients performed under DS is as safe and effective as with GA, preventing complications related to GA and shortening hospital stay.

Oxygen dependence of endothelium-dependent vasodilation: importance in chronic obstructive pulmonary disease.

INTRODUCTION: Epidemiological studies have shown increased morbidity and mortality in patients with coronary artery disease (CAD) and chronic obstructive pulmonary disease (COPD). We aimed to characterize the oxygen dependence of endothelial function in patients with CAD and coexisting COPD. MATERIAL AND METHODS: In CAD patients with and without COPD (n = 33), we non-invasively measured flow-mediated dilation (FMD) and intima-media thickness (IMT) of the brachial artery (BA), forearm blood flow (FBF), and perfusion of the cutaneous microcirculation with laser Doppler perfusion imaging (LDPI). In an experimental setup, vascular function was assessed in healthy volunteers (n = 5) breathing 12% oxygen or 100% oxygen in comparison to room air. RESULTS: COPD was associated with impaired FMD (3.4 ±0.5 vs. 4.2 ±0.6%; p < 0.001) and increased IMT (0.49 ±0.04 vs. 0.44 ±0.04 mm; p <0.01), indicating functional and structural alterations of the BA in COPD. Forearm blood flow and LDPI were comparable between the groups. Flow-mediated dilation correlated with capillary oxygen pressure (pO2, r = 0.608). Subgroup analysis in COPD patients with pO2 > 65 mm Hg and pO2 ≤ 65 mm Hg revealed even lower FMD in patients with lower pO2 (3.0 ±0.5 vs. 3.7 ±0.4%; p < 0.01). Multivariate analysis showed that pO2 was a predictor of FMD independent of the forced expiratory volume and pack years. Exposure to hypoxic air led to an acute decrease in FMD, whereby exposure to 100% oxygen did not change vascular function. CONCLUSIONS: Our data suggest that in CAD patients with COPD, decreased systemic oxygen levels lead to endothelial dysfunction, underlining the relevance of cardiopulmonary interaction and the potential importance of pulmonary treatment in secondary prevention of vascular disease.

Safety of percutaneous coronary intervention in patients with acute ischemic stroke/transient ischemic attack and acute coronary syndrome.

BACKGROUND: Cardiac events in patients with acute stroke are frequent. Urgent PCI in myocardial infarction is crucial to improve outcome. However, the situation is complex as intracranial hemorrhage is a frequent complication of stroke but antithrombotic medication is indispensable during and after PCI. Therefore in this study, we aimed to investigate the safety of percutaneous coronary intervention (PCI) in patients hospitalized with acute ischemic stroke and concomitant acute coronary syndrome (ACS). METHODS AND RESULTS: In a single-center, case-series study we investigated 80 patients hospitalized with acute stroke/transient ischemic attack (TIA) and concomitant ACS undergoing coronary angiography. Patients with subsequent PCI were compared to patients with medical treatment alone. The primary end point was the composite of death, recurrent MI, coronary re-intervention, recurrent stroke or bleeding during 1-year follow-up. The secondary end point consisted of the components of the primary end point. Age, gender and cardiovascular risk factors did not differ between groups. However, severity of initial stroke and coronary artery disease was higher in the PCI group. Accordingly, antiplatelet medication with aspirin and clopidogrel was prescribed more frequently in the PCI group. Nevertheless, during 1-year follow-up, the primary end point did not differ between groups [38 vs. 50 %, odds ratio (OR) 1.7, CI 0.69-4.07, P = 0.23]. Intracranial hemorrhage was even numerically lower in patients undergoing PCI (5 vs. 3 %, OR 0.4, CI 0.04-5.6, P = 0.46). CONCLUSIONS: The primary and secondary end points were not enhanced in patients undergoing PCI. Therefore PCI is safe in patients with stroke/TIA and concomitant ACS.

Troponin T in Prediction of Culprit Lesion Coronary Artery Disease and 1-Year Major Adverse Cerebral and Cardiovascular Events in Patients with Acute Stroke.

Troponin T (TnT) elevation above the 99th percentile upper reference limit (URL) is considered diagnostic of acute myocardial infarction (MI). Non-specific increases of TnT are frequent in acute stroke patients. However, in these patients, correct diagnosis of MI is crucial because the antithrombotic medications used to treat acute MI might be harmful and produce intracranial bleeding. In this study, we aimed to associate enhanced TnT levels defined by different cutoff values with occurrence of culprit lesion coronary artery disease (CAD) as well as 1-year major adverse cerebral and cardiovascular events (MACCEs). In this cohort study, we investigated 84 consecutive patients with acute ischemic stroke and concomitant MI. TnT levels were measured using a fourth-generation TnT assay. The incidence of culprit lesion CAD was determined by coronary angiography. MACCEs were recorded during 1-year follow-up. Culprit lesion CAD occurred in 55 % of patients, and 1-year MACCE in 37 %. TnT levels above the manufacturers' provided 99th URL (TnT > 0.01) were not associated with culprit lesion CAD (relative risk [RR], 1.3; 95 % confidence interval [CI] 0.96-1.8; P = 0.09). Slightly increased cutoff level (TnT > 0.03) increased specificity and was associated with culprit lesion CAD without decreasing sensitivity (RR, 1.5; 95 % CI 1.1-2.2; P = 0.021) and 1-year MACCE (RR, 1.7; 95 % CI 1.3-2.3; P < 0.001). Slightly increasement of the TnT cutoff level predicted MACCEs and is superior in prediction of culprit lesion CAD in stroke patients without being less sensitive. This finding has to be confirmed in large-scale clinical trials.

Local association between endothelial dysfunction and intimal hyperplasia: relevance in peripheral artery disease.

BACKGROUND: Endothelial dysfunction is a key factor in the development of atherosclerosis. Commonly, endothelial function is determined in the brachial artery, whereas patients with peripheral artery disease (PAD) present with lower limb atherosclerosis. We hypothesized that in PAD, a segmental or local association exists between endothelial dysfunction and atherosclerotic structural changes. METHODS AND RESULTS: We used ultrasound to study endothelial function as flow-mediated vasodilation, intima media thickness, and local stiffness of the superficial femoral artery (SFA) and brachial artery (BA). PAD patients with symptomatic SFA or below-the-knee disease were compared with age-matched patients without PAD and young healthy controls. PAD patients with SFA or below-the-knee disease exhibited endothelial dysfunction of the proximal SFA (flow-mediated vasodilation: 3.9±0.6%, 3.7±0.6%) compared with healthy controls (7.4±1.0%) and patients without PAD (5.4±0.6%). Brachial artery flow-mediated vasodilation values were not different in PAD patients with SFA or below-the-knee disease compared with patients without PAD, but they were significantly lower than those of healthy controls. Endothelial dysfunction correlated with increased intima media thickness or plaque thickness at the site of flow-mediated vasodilation measurement across vascular sites. In PAD patients with SFA disease, SFA flow-mediated vasodilation was further impaired within and distal to stenosis (prestenosis 3.9±0.6%, intrastenosis 2.3±0.7%, poststenosis 2.5±0.6%) and recovered within 24 hours after SFA balloon angioplasty to prestenotic values but not to the brachial artery or SFA values in patients without PAD or controls. CONCLUSION: A close association exists between local endothelial function and atherosclerotic structural remodeling, suggesting that in PAD, local and segmental factors-in addition to systemic factors-influence local endothelial function. Our data point toward a pathophysiological role for lower extremity endothelial dysfunction in PAD.

Percutaneous mitral valve repair using the MitraClip system in patients with anemia.

BACKGROUND: Patients with anemia show a negative outcome in percutaneous coronary intervention, transcatheter aortic valve replacement and cardiac surgery. The impact of anemia on periprocedural major adverse cardiac and cerebrovascular events (MACCE) and mortality in patients undergoing treatment of severe mitral regurgitation (MR) with percutaneous mitral valve repair using the MitraClip system is not known. OBJECTIVE: To assess whether percutaneous mitral valve repair with the MitraClip system is safe and effective in patients with anemia. METHODS AND RESULTS: 80 patients with severe and moderate-to-severe MR were included in this open-label observational single-center study. Anemia was prevalent in 51.3% of patients (n=41). MitraClip devices were successfully implanted in 97.6% (n=40) of patients with anemia and in 97.4% (n=38) of patients without anemia (p=0.971). Periprocedural MACCE occurred in 4.9% (n=2) of patients with anemia and 5.1% (n=2) of patients without anemia (p=0.959). Thirty-day mortality was 2.4% (n=1) in patients with anemia and 5.1% (n=2) in patients without anemia (p=0.611). Follow up of up to 12 months showed a significant improvement of NYHA class and quality of life evaluated by the Minnesota Living with Heart Failure Questionnaire in both groups. One-year survival was 80.5% in patients with anemia and 84.6% in patients without anemia (p=0.634). CONCLUSION: Mitral valve repair with the MitraClip system can be performed safely and efficiently in patients with anemia. Anemia does not affect clinical outcome and quality of life in patients undergoing mitral valve repair.

Safety and efficacy of percutaneous mitral valve repair using the MitraClip® system in patients with diabetes mellitus.

BACKGROUND: Patients with diabetes mellitus show a negative outcome in percutaneous coronary intervention, aortic valve replacement and cardiac surgery. The impact of diabetes on patients undergoing treatment of severe mitral regurgitation (MR) using the MitraClip system is not known. We therefore sought to assess whether percutaneous mitral valve repair with the MitraClip system is safe and effective in patients with diabetes mellitus. METHODS AND RESULTS: We included 58 patients with severe and moderate-to-severe MR in an open-label observational single-center study. Ninteen patients were under oral medication or insulin therapy for type II diabetes mellitus. MitraClip devices were successfully implanted in all patients with diabetes and in 97.4% (n = 38) of patients without diabetes (p = 0.672). Periprocedural major cardiac adverse and cerebrovascular events (MACCE) occurred in 5.1% (n = 2) of patients without diabetes whereas patients with diabetes did not show any MACCE (p = 0.448). 30-day mortality was 1.7% (n = 1) with no case of death in the diabetes group. Short-term follow up of three months showed a significant improvement of NYHA class and quality of life evaluated by the Minnesota Living with Heart Failure Questionnaire in both groups, with no changes in the 6-minute walk test. CONCLUSIONS: Mitral valve repair with the MitraClip system is safe and effective in patients with type II diabetes mellitus. TRIAL REGISTRATION: MitraClip Registry NCT02033811.