Outcomes of transcatheter mitral valve replacement for degenerated bioprostheses, failed annuloplasty rings, and mitral annular calcification.

Aims: We sought to evaluate the outcomes of transcatheter mitral valve replacement (TMVR) for patients with degenerated bioprostheses [valve-in-valve (ViV)], failed annuloplasty rings [valve-in-ring (ViR)], and severe mitral annular calcification [valve-in-mitral annular calcification (ViMAC)]. Methods and results: From the TMVR multicentre registry, procedural and clinical outcomes of ViV, ViR, and ViMAC were compared according to Mitral Valve Academic Research Consortium (MVARC) criteria. A total of 521 patients with mean Society of Thoracic Surgeons score of 9.0 ± 7.0% underwent TMVR (322 patients with ViV, 141 with ViR, and 58 with ViMAC). Trans-septal access and the Sapien valves were used in 39.5% and 90.0%, respectively. Overall technical success was excellent at 87.1%. However, left ventricular outflow tract obstruction occurred more frequently after ViMAC compared with ViR and ViV (39.7% vs. 5.0% vs. 2.2%; P < 0.001), whereas second valve implantation was more frequent in ViR compared with ViMAC and ViV (12.1% vs. 5.2% vs. 2.5%; P < 0.001). Accordingly, technical success rate was higher after ViV compared with ViR and ViMAC (94.4% vs. 80.9% vs. 62.1%; P < 0.001). Compared with ViMAC and ViV groups, ViR group had more frequent post-procedural mitral regurgitation ≥moderate (18.4% vs. 13.8% vs. 5.6%; P < 0.001) and subsequent paravalvular leak closure (7.8% vs. 0.0% vs. 2.2%; P = 0.006). All-cause mortality was higher after ViMAC compared with ViR and ViV at 30 days (34.5% vs. 9.9% vs. 6.2%; log-rank P < 0.001) and 1 year (62.8% vs. 30.6% vs. 14.0%; log-rank P < 0.001). On multivariable analysis, patients with failed annuloplasty rings and severe MAC were at increased risk of mortality after TMVR [ViR vs. ViV, hazard ratio (HR) 1.99, 95% confidence interval (CI) 1.27-3.12; P = 0.003; ViMAC vs. ViV, HR 5.29, 95% CI 3.29-8.51; P < 0.001]. Conclusion: The TMVR provided excellent outcomes for patients with degenerated bioprostheses despite high surgical risk. However, ViR and ViMAC were associated with higher rates of adverse events and mid-term mortality compared with ViV.

Succinate receptor GPR91 provides a direct link between high glucose levels and renin release in murine and rabbit kidney.

Diabetes mellitus is the most common and rapidly growing cause of end-stage renal disease in developed countries. A classic hallmark of early diabetes mellitus includes activation of the renin-angiotensin system (RAS), which may lead to hypertension and renal tissue injury, but the mechanism of RAS activation is elusive. Here we identified a paracrine signaling pathway in the kidney in which high levels of glucose directly triggered the release of the prohypertensive hormone renin. The signaling cascade involved the local accumulation of succinate and activation of the kidney-specific G protein-coupled metabolic receptor, GPR91, in the glomerular endothelium as observed in rat, mouse, and rabbit kidney sections. Elements of signal transduction included endothelial Ca2+, the production of NO and prostaglandin (PGE2), and their paracrine actions on adjacent renin-producing cells. This GPR91 signaling cascade may serve to modulate kidney function and help remove metabolic waste products through renal hyperfiltration, and it could also link metabolic diseases, such as diabetes, or metabolic syndrome with RAS overactivation, systemic hypertension, and organ injury.

A New WATCHMAN Sizing Algorithm Utilizing Cardiac CTA.

BACKGROUND: The WATCHMAN left atrial appendage (LAA) occlusion device has emerged as an alternative for anticoagulation in patients with non-valvular atrial fibrillation who cannot tolerate oral anticoagulation therapy. Cardiac computed tomography (CTA) is increasingly being utilized to guide WATCHMAN device sizing, however no consensus algorithm exists. We present our experience with a new cardiac CTA LAA ostium area based sizing algorithm. METHODS: This is a single center, prospective study analyzing consecutive patients who underwent cardiac CTA and WATCHMAN device implantation between March 2017 and October 2019 at University Hospitals Cleveland Medical Center. Patients baseline characteristics, procedural data, and clinical outcomes were collected and analyzed. RESULTS: 115 patients were included in our study. The mean age of our population was 76.5 years ±8.3 years. 70.4% of our patients had preserved ejection fraction. The predominant indication for device implantation was gastrointestinal bleeding in 57.4% of patients. The mean CHADSVASC score was 4.68 ± 1.4. The procedure success rate was 99.1% and the mean number of device used per case of 1.15 ± 0.4 devices. Our CTA LAA ostium area based sizing algorithm accurately predicted the final deployed WATCHMAN device size in 95.6% of cases. CONCLUSION: Our study demonstrates that cardiac CTA LAA ostium area based sizing algorithm is highly accurate at predicting WATCHMAN device size and demonstrates excellent clinical outcomes with lower device utilization per case than what is reported in literature.

Angiography-based quantitative flow ratio versus fractional flow reserve in patients with coronary artery disease and severe aortic stenosis.

AIMS: The aim of this study was to investigate the diagnostic performance of quantitative flow ratio (QFR) in assessing the physiological relevance of coronary lesions in the presence of severe aortic valve stenosis (SAS). METHODS AND RESULTS: A total of 115 SAS patients (138 coronary arteries) were included. Functional assessment of coronary stenoses was performed with fractional flow reserve (FFR) before transcatheter aortic valve implantation (TAVI). Subsequently, QFR was calculated at a central core laboratory, blinded to FFR results. The diagnostic yield of QFR was assessed using FFR as reference. Coronary stenoses were intermediate (diameter stenosis 48±10%, FFR 0.84 [0.77-0.89], QFR 0.82 [0.73-0.89]). Per-vessel sensitivity, specificity, area under the ROC curve and accuracy of QFR were 84% (95% CI: 71-92%), 80% (95% CI: 69-88%), 0.88 (95% CI: 0.82-0.93) and 81%, respectively. Diagnostic accuracy of QFR decreased significantly in patients with aortic valve area (AVA) <0.60 cm2. Diagnostic performance of QFR was superior to angiography in assessing the FFR-based functional significance (AUC 0.88 [95% CI: 0.82-0.93] vs 0.74 [95% CI: 0.66-0.81], respectively; p=0.0002). CONCLUSIONS: Compared with FFR, QFR has a good diagnostic yield and is superior to angiography in assessing the functional relevance of coronary lesions in SAS patients awaiting TAVI, particularly when AVA is ≥0.6 cm2.

Risk Prediction Model for Cardiac Implantable Electronic Device Implantation After Transcatheter Aortic Valve Replacement.

OBJECTIVES: The aim of this study was to develop and validate a risk prediction model for high-grade atrioventricular block requiring cardiac implantable electronic device (CIED) implantation after transcatheter aortic valve replacement (TAVR). BACKGROUND: High-grade atrioventricular block requiring CIED remains a significant sequelae following TAVR. Although several pre-operative characteristics have been associated with the risk of post-operative CIED implantation, an accurate and validated risk prediction model is not established yet. METHODS: This was a single center, retrospective study of consecutive patients who underwent TAVR from March 10, 2011, to October 8, 2018. This cohort sample was randomly divided into a derivation cohort (group A) and a validation cohort (group B). A scoring system for risk prediction of post-TAVR CIED implantation was devised using logistic regression estimates in group A and the calibration and validation were done in group B. RESULTS: A total of 1,071 patients underwent TAVR during the study period. After excluding pre-existing CIED, a total of 888 cases were analyzed (group A: 507 and group B: 381). Independent predictive variables were as follows: self-expanding valve (1 point), hypertension (1 point), pre-existing first-degree atrioventricular block (1 point), and right bundle branch block (2 points). The resulting score was calculated from the total points. The internal validation in group B showed an ideal linear relationship in calibration plot (R2 = 0.933) and a good predictive accuracy (area under the curve: 0.693; 95% confidence interval: 0.627 to 0.759). CONCLUSIONS: This prediction model accurately predicts post-operative risk of CIED implantation with simple pre-operative parameters.

Predicted Coronary Occlusion and Impella Salvage During Valve-in-Valve Transcatheter Aortic Valve Replacement.

We describe an interesting case of a 71 years old fragile female, with progressive shortness of breath on exertion and ankle swelling, cardiac failure NYHA class III. She also had chest irradiation due to Hodgkin's disease many years before, previous surgical aortic valve replacement using bioprosthetic stent-less Freestyle #25 mm valve (Medtronic, Inc) in 2000 for severe aortic stenosis, history of cardiac arrest in 2012 and angioplasty to ostial RCA, PCI to ostial RCA in 2014, CABG (RA graft to RCA) in 2014 (RCA intra-stent restenosis with refractory ischemia), anemia requiring regular transfusions, bronchiectasis and chronic kidney disease. Because of the great comorbidities, STS 4.9% and worsening of the symptoms due to severe aortic valve regurgitation, heart team decided to perform "valve-in-valve" Transcatheter Aortic Valve Replacement (VIV-TAVR), but we already predicted coronary occlusion while performing this procedure because of the low left main coronary ostium and short aortic valve sinus. So regarding the probable left main coronary occlusion during the valve implantation, we decided to perform the placement of a not deployed stent inside the left main prior to the valve procedure, and to deploy it in case the predicted left main occlusion occurred. So just after the VIV-TAVR procedure, we observed left main coronary occlusion and the patient got ischemic cardiogenic shock and cardiac arrest, so we performed immediate PCI and deployed the bailout stent. After some minutes of chest compressions, an Impella mechanical circulatory support system (Abiomed, Danvers, MA) had to be installed. Patient recovered spontaneous circulation, and after hemodynamic stabilization, she was sent to the Intensive Coronary Unit, without further complications. She was discharged successfully without neurological or cardiac sequelae after 1 week.

Importance of hospital entry: walk-in STEMI and primary percutaneous coronary intervention.

INTRODUCTION: Patients with ST elevation myocardial infarction (STEMI) require rapid identification and triage to initiate reperfusion therapy. Walk-in STEMI patients have longer treatment times compared to emergency medical service (EMS) transported patients. While effective triage of large numbers of critically ill patients in the emergency department is often cited as the reason for treatment delays, additional factors have not been explored. The purpose of this study was to evaluate baseline demographic and clinical differences between walk-in and EMS-transported STEMI patients and identify factors associated with prolonged door to balloon (D2B) time in walk-in STEMI patients. METHODS: We performed a retrospective review of 136 STEMI patients presenting to an urban academic teaching center from January 2009 through December 2010. Baseline demographics, mode of hospital entry (walk-in versus EMS transport), treatment times, angiographic findings, procedures performed and in-hospital clinical events were collected. We compared walk-in and EMS-transported STEMI patients and identified independent factors of prolonged D2B time for walk-in patients using stepwise logistic regression analysis. RESULTS: Walk-in patients (n=51) were more likely to be Latino and presented with a higher heart rate, higher systolic blood pressure, prior history of diabetes mellitus and were more likely to have an elevated initial troponin value, compared to EMS-transported patients. EMS-transported patients (n=64) were more likely to be white and had a higher prevalence of left main coronary artery disease, compared to walk-in patients. Door to electrocardiogram (ECG), ECG to catheterization laboratory (CL) activation and D2B times were significantly longer for walk-in patients. Walk-in patients were more likely to have D2B time >90 minutes, compared to EMS- transported patients; odds ratio 3.53 (95% CI 1.03, 12.07), p=0.04. Stepwise logistic regression identified hospital entry mode as the only independent predictor for prolonged D2B time. CONCLUSION: Baseline differences exist between walk-in and EMS-transported STEMI patients undergoing primary percutaneous coronary intervention (PCI). Hospital entry mode was the most important predictor for prolonged treatment times for primary PCI, independent of age, Latino ethnicity, heart rate, systolic blood pressure and initial troponin value. Prolonged door to ECG and ECG to CL activation times are modifiable factors associated with prolonged treatment times in walk-in STEMI patients. In addition to promoting the use of EMS transport, efforts are needed to rapidly identify and expedite the triage of walk-in STEMI patients.

Connexin 40 and ATP-dependent intercellular calcium wave in renal glomerular endothelial cells.

Endothelial intracellular calcium ([Ca(2+)](i)) plays an important role in the function of the juxtaglomerular vasculature. The present studies aimed to identify the existence and molecular elements of an endothelial calcium wave in cultured glomerular endothelial cells (GENC). GENCs on glass coverslips were loaded with Fluo-4/Fura red, and ratiometric [Ca(2+)](i) imaging was performed using fluorescence confocal microscopy. Mechanical stimulation of a single GENC caused a nine-fold increase in [Ca(2+)](i), which propagated from cell to cell throughout the monolayer (7.9 +/- 0.3 microm/s) in a regenerative manner (without decrement of amplitude, kinetics, and speed) over distances >400 microm. Inhibition of voltage-dependent calcium channels with nifedipine had no effect on the above parameters, but the removal of extracellular calcium reduced Delta[Ca(2+)](i) by 50%. Importantly, the gap junction uncoupler alpha-glycyrrhetinic acid or knockdown of connexin 40 (Cx40) by transfecting GENCs with Cx40 short interfering RNA (siRNA) almost completely eliminated Delta[Ca(2+)](i) and the calcium wave. Breakdown of extracellular ATP using a scavenger cocktail (apyrase and hexokinase) or nonselective inhibition of purinergic P2 receptors with suramin, had similar blocking effects. Scraping cells off along a line eliminated physical contact between cells but did not effect calcium wave propagation. Using an ATP biosensor technique, we detected a significant elevation in extracellular ATP (Delta = 76 +/- 2 microM) during calcium wave propagation, which was abolished by Cx40 siRNA treatment (Delta = 6 +/- 1 microM). These studies suggest that connexin 40 hemichannels and extracellular ATP are key molecular elements of the glomerular endothelial calcium wave, which may serve important juxtaglomerular functions.