Outcomes of Patients Undergoing Transcatheter Aortic Valve Implantation With Incidentally Discovered Masses on Computed Tomography.

Routine preprocedural chest and abdomen computed tomography is done prior to transcatheter aortic valve implantation (TAVI), which, in turn, have led to the discovery of radiographic potentially malignant incidental masses (pMIM). It is largely unknown whether pMIM impact the outcomes of patients undergoing TAVI. In this retrospective cohort study from a single center, 1,081 patients underwent TAVI from 2012 to 2016, who had available computed tomographies, survived the index hospitalization, and also had 1 year follow-up data for review. Machine learning (backward propagation neural network)-augmented multivariable regression for mortality by pMIM was conducted. In this cohort of 1,081 patients, the mean age was 79.1 (± 9.0), 48.8% were females, 16.8% had a history of prior malignancy, and 21.1% had pMIM. One-year mortality for the entire cohort was 12.6%. The most common prior malignancies were prostate, breast, and lymphoma and the most common pMIM were present in the lung, kidneys, and thyroid. In a fully adjusted regression analysis, neither prior malignancy nor pMIM increased mortality odds. However, having both was associated with a higher 1-year mortality (odds ratio 4.02, 95% confidence interval 1.50 to 10.73, p = 0.006). In conclusion, presence of pMIM alone was not associated with an increased 1-year mortality among patients undergoing TAVI. However, the presence of pMIM and a history of prior malignancy was associated with a significant increase in 1-year mortality.

Rates, predictors, and outcomes of early readmissions after tricuspid valve surgery.

BACKGROUND: The data on readmissions following tricuspid valve repair/replacement (TVR) are scarce. We examined rates, predictors, causes, and outcomes of readmissions after TVR, using the National Readmission Database. METHODS: The International Classification of Diseases-9th version was used to identify the patients who underwent isolated TVR or concomitant aortic, mitral, and coronary bypass surgeries. Rates, causes, and outcomes were assessed using the analysis of variance and the χ2 test, and predictors of readmissions were evaluated using multivariate analysis. RESULTS: A total of 8254 patients who underwent TVR during 2013 to 2014 were included, of whom 1994 (24.16%) were isolated, and 6260 (75.84%) were performed concomitantly with other heart valve or coronary bypass surgery. A total of 1720 (20.84%) patients were readmitted within 30 days. The readmission rates were 448 (22.46%) after isolated TVR and similar after concomitant TVR (TVR + aortic valve replacement, TVR + mitral valve repair, TVR + coronary artery bypass graft, and TVR + multiple) (P = .194); whereas 1305 (20.11%) and 414 (23.45%) were after tricuspid valve repair and replacement (P = .080), respectively. The independent predictors of readmission were acute kidney injury during index visit and Charlson comorbidity index of more than 2. Mean time to readmission and median length of stay during readmission were 13.02 (±7.93) and 5 (interquartile range: 3-9) days, respectively. Total mortality during rehospitalization was 105 (6.1%), a very high (26.86%) number of patients were discharged to skilled facilities after readmission. CONCLUSIONS: One out of five patients were readmitted within 30 days after the TVR, associated with 6.1% mortality during rehospitalization, and very high need for skilled facility placement.

An Unusual Cause of Hypoxia: Ventricular Septal Defect, Pulmonary Artery Atresia, and Major Aortopulmonary Collaterals Diagnosed in the Adult Cardiac Catheterization Lab.

The association of pulmonary atresia, ventricular septal defect (VSD) and major aortopulmonary collaterals (MAPCA) is an extreme form of tetralogy of Fallot (TOF). It carries a high mortality risk if not intervened on during infancy with only 20% of unoperated patients surviving into adulthood. We present the case of a 40-year-old man who presented for evaluation prior to retinal surgery and was found to have hypoxia and a loud murmur. Cardiac catheterization was performed in the general catheterization laboratory, demonstrating a membranous VSD, pulmonary atresia, and MAPCA. We highlight the challenges and limitations that an adult interventional cardiologist may have when encountering these patients.

Preclinical Model of Hind Limb Ischemia in Diabetic Rabbits.

Peripheral vascular disease is a widespread clinical problem that affects millions of patients worldwide. A major consequence of peripheral vascular disease is the development of ischemia. In severe cases, patients can develop critical limb ischemia in which they experience constant pain and an increased risk of limb amputation. Current therapies for peripheral ischemia include bypass surgery or percutaneous interventions such as angioplasty with stenting or atherectomy to restore blood flow. However, these treatments often fail to the continued progression of vascular disease or restenosis or are contraindicated due to the overall poor health of the patient. A promising potential approach to treat peripheral ischemia involves the induction of therapeutic neovascularization to allow the patient to develop collateral vasculature. This newly formed network alleviates peripheral ischemia by restoring perfusion to the affected area. The most frequently employed preclinical model for peripheral ischemia utilizes the creation of hind limb ischemia in healthy rabbits through femoral artery ligation. In the past, however, there has been a strong disconnect between the success of preclinical studies and the failure of clinical trials regarding treatments for peripheral ischemia. Healthy animals typically have robust vascular regeneration in response to surgically induced ischemia, in contrast to the reduced vascularity and regeneration in patients with chronic peripheral ischemia. Here, we describe an optimized animal model for peripheral ischemia in rabbits that includes hyperlipidemia and diabetes. This model has reduced collateral formation and blood pressure recovery in comparison to a model with a higher cholesterol diet. Thus, the model may provide better correlation with human patients with compromised angiogenesis from the common co-morbidities that accompany peripheral vascular disease.

Preload Sensitivity with TORVAD Counterpulse Support Prevents Suction and Overpumping.

PURPOSE: This study compares preload sensitivity of continuous flow (CF) VAD support to counterpulsation using the Windmill toroidal VAD (TORVAD). The TORVAD is a two-piston rotary pump that ejects 30 mL in early diastole, which increases cardiac output while preserving aortic valve flow. METHODS: Preload sensitivity was compared for CF vs. TORVAD counterpulse support using two lumped parameter models of the cardiovascular system: (1) an open-loop model of the systemic circulation was used to obtain ventricular function curves by isolating the systemic circulation and prescribing preload and afterload boundary conditions, and (2) a closed-loop model was used to test the physiological response to changes in pulmonary vascular resistance, systemic vascular resistance, heart rate, inotropic state, and blood volume. In the open-loop model, ventricular function curves (cardiac output vs left ventricular preload) are used to assess preload sensitivity. In the closed-loop model, left ventricular end systolic volume is used to assess the risk of left ventricular suction. RESULTS: At low preloads of 5 mmHg, CF support overpumps the circulation compared to TORVAD counterpulse support (cardiac output of 3.3 L/min for the healthy heart, 4.7 with CF support, and 3.5 with TORVAD counterpulse support) and has much less sensitivity than counterpulse support (0.342 L/min/mmHg for the healthy heart, 0.092 with CF support, and 0.306 with TORVAD counterpulse support). In the closed-loop model, when PVR is increased beyond 0.035 mmHg s/mL, CF support overpumps the circulation and causes ventricular suction events, but TORVAD counterpulse support maintains sufficient ventricular volume and does not cause suction. CONCLUSIONS: Counterpulse support with the TORVAD preserves aortic valve flow and provides physiological sensitivity across all preload conditions. This should prevent overpumping and minimize the risk of suction.

Predictors of Left Ventricular Outflow Tract Obstruction After Transcatheter Mitral Valve Replacement.

OBJECTIVES: The aim of this study was to evaluate the predictors of left ventricular outflow tract (LVOT) obstruction after transcatheter mitral valve replacement (TMVR). BACKGROUND: LVOT obstruction is a major concern with TMVR, but limited data exist regarding its predictors and impact on outcomes. METHODS: Patients with pre-procedural multidetector row computed tomography (MDCT) undergoing TMVR for failed mitral bioprosthetic valves (valve-in-valve), annuloplasty rings (valve-in-ring), and mitral annular calcification (valve-in-MAC) were included in this study. Echocardiographic and procedural characteristics were recorded, and comprehensive assessment with MDCT was performed to identify the predictors of LVOT obstruction (defined as an increment of mean LVOT gradient ≥10 mm Hg from baseline). The new LVOT (neo-LVOT) area left after TMVR was estimated by embedding a virtual valve into the mitral annulus on MDCT, simulating the procedure. RESULTS: Among 194 patients with pre-procedural MDCT undergoing TMVR (valve-in-valve, 107 patients; valve-in-ring, 50 patients; valve-in-MAC, 37 patients), LVOT obstruction was observed in 26 patients (13.4%), with a higher rate after valve-in-MAC than valve-in-ring and valve-in-valve (54.1% vs. 8.0% vs. 1.9%; p < 0.001). Patients with LVOT obstruction had significantly higher procedural mortality compared with those without LVOT obstruction (34.6% vs. 2.4%; p < 0.001). Receiver-operating characteristic curve analysis showed that an estimated neo-LVOT area ≤1.7 cm2 predicted LVOT obstruction with sensitivity of 96.2% and specificity of 92.3%. CONCLUSIONS: LVOT obstruction after TMVR was associated with higher procedural mortality. A small estimated neo-LVOT area was significantly associated with LVOT obstruction after TMVR and may help identify patients at high risk for LVOT obstruction.

An update on the management and outcomes of cancer patients with severe aortic stenosis.

OBJECTIVES: We compared the outcomes of aortic valve replacement (AVR) by transcatheter (TAVR) and surgical (SAVR) routes with those of optimal medical management in patients with cancer and severe aortic stenosis (AS). BACKGROUND: Cancer therapy requires optimal cardiac output; however, the treatment of AS in cancer patients is not established. METHODS: Cancer patients with severe AS during January 2009 through February 2018 at a large cancer center were identified. Demographic and clinical characteristics including previous or active cancer diagnosis, history of chest radiotherapy, AS treatment, and survival were collected. Univariate Cox proportional hazards regression, the Kaplan-Meier analysis, and log-rank tests were used to compare overall survival (OS) between AS treatment groups. RESULTS: Sixty-five cancer patients with severe AS were identified; 28 received optimal medical treatment alone, 30 received TAVR, and seven received SAVR. The patients were predominantly male (n = 44, 68%) with a mean age of 71.17 years. The median OS was 9.87 months, and the most common cause of death was cancer (n = 29, 94% of deaths). AVR was associated with a lower risk of death than no AVR (hazard ratio [HR] 0.38, P = 0.007), and patients who underwent TAVR (HR 0.36, P = 0.01) had better survival than those with no AVR. Malignancy type, stage, and treatment were not associated with OS. CONCLUSIONS: Patients with cancer and severe AS who underwent AVR, predominantly TAVR, experienced better survival than those who had no AVR regardless of cancer type or cancer treatment. TAVR may be considered in patients with cancer and AS.

National 10-year trends and outcomes of isolated and concomitant tricuspid valve surgery.

BACKGROUND: The data on the trends and comparative outcomes after isolated and concomitant tricuspid valve repair/replacement (TVR) is scarce. METHODS: The International Classification of Diseases - 9th version was used to identify the patients who underwent TVR, using the National Inpatient Sample. Outcomes were evaluated using the analysis of variance and Chi-square test, and trends across the years were tested via Cochran-Armitage Test. RESULTS: Of 6868 patients who underwent TVR between 2005-14, 1601 (23%) were isolated. Over the 10-years period, the number of total and isolated TVR has steadily increased (P<0.001). The proportion of patients undergoing repair has increased compared to replacement. Overall in-hospital mortality was 8.5% and 7.7% (p=0.28), permanent pacemaker requirement was 11.24% and 10.69% (P=0.53), blood transfusion rates were 32.6% and 37.9% (P<0.001), and the post-procedure length of stay (LOS) was 14.1±0.44 and 12.5±0.17 days (P<0.001) after isolated and concomitant TVR respectively. High (26.25%) number of patients were discharged to skilled facility. The operative mortality associated with TV repair was lower than with replacement (6.8% versus 11.15%, P<0.001), but the mortality trend over the 10-years has stayed relatively stable. Independent predictors of mortality were age >50 years, heart failure, cerebrovascular accident, end-stage renal disease, peripheral vascular disease, liver disease, and TV replacement. CONCLUSIONS: Both isolated and concomitant TVR has increased over the last 10 years, however is associated with high mortality, complications, need for skilled facility placement, and longer LOS. The mortality after TV replacement was significantly higher than that after repair.

Five-year outcomes of transcatheter reduction of significant mitral regurgitation in high-surgical-risk patients.

OBJECTIVES: This study evaluates the 5-year clinical outcomes of transcatheter mitral valve (MV) repair with the MitraClip device in patients at high risk for MV surgery treated in the Endovascular Valve Edge-to-Edge Repair (EVEREST) II High Risk Study (HRS). METHODS: Patients with mitral regurgitation (MR) 3+ or 4+ and predicted surgical mortality risk ≥12% or surgeon assessment based on prespecified high-risk factors were enrolled. Patients prospectively consented to 5 years of follow-up. RESULTS: At 5 years, clinical follow-up was achieved in 90% of 78 enrolled patients. The rate of postprocedural adverse events declined from 30 days to 1 year follow-up and was stable thereafter through 5 years. Two patients (2.6%) developed mitral stenosis (MS). Two patients underwent MV surgery, including one due to MS. A total of 42 deaths were reported through 5 years. Effectiveness measures at 5 years showed reductions in MR severity to ≤2+ in 75% of patients (p=0.0107), left ventricular (LV) end-diastolic volume (-38.2 mL; 95% CI -55.0 to -21.4; p<0.0001) and LV end-systolic volume (-14.6 mL; 95% CI -27.7 to -1.5; p=0.0303) compared with baseline. The New York Heart Association (NYHA) functional class improved from baseline to 5 years (p<0.005), and septal-lateral annular dimensions remained stable with no indication of mitral annular dilation through 5 years. CONCLUSIONS: The EVEREST II HRS demonstrated long-term safety and efficacy of MitraClip in high-surgical-risk patients through 5 years. The observed mortality was most likely a consequence of the advanced age and comorbidity profile of the enrolled patients, while improvements in NYHA class in surviving patients were durable through long-term follow-up. TRIAL REGISTRATION NUMBER: NCT01940120.

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.

Cost-effectiveness of percutaneous patent foramen ovale closure as secondary stroke prevention.

OBJECTIVE: Compared to medical therapy alone, percutaneous closure of patent foramen ovale (PFO) further reduces risk of recurrent ischemic strokes in carefully selected young to middle-aged patients with a recent cryptogenic ischemic stroke. The objective of this study was to evaluate the cost-effectiveness of this therapy in the context of the United Kingdom (UK) healthcare system. METHODS: A Markov cohort model consisting of four health states (Stable after index stroke, Post-Minor Recurrent Stroke, Post-Moderate Recurrent Stroke, and Death) was developed to simulate the economic outcomes of device-based PFO closure compared to medical therapy. Recurrent stroke event rates were extracted from a randomized clinical trial (RESPECT) with a median of 5.9-year follow-up. Health utilities and costs were obtained from published sources. One-way and probabilistic sensitivity analyses (PSA) were performed to assess robustness. The model was discounted at 3.5% and reported in 2016 Pounds Sterling. RESULTS: Compared with medical therapy alone and using a willingness-to-pay (WTP) threshold of £20,000, PFO closure reached cost-effectiveness at 4.2 years. Cost-effectiveness ratios (ICERs) at 4, 10, and 20 years were £20,951, £6,887, and £2,158, respectively. PFO closure was cost-effective for 89% of PSA iterations at year 10. Sensitivity analyses showed that the model was robust. CONCLUSIONS: Considering the UK healthcare system perspective, percutaneous PFO closure in cryptogenic ischemic stroke patients is a cost-effective stroke prevention strategy compared to medical therapy alone. Its cost-effectiveness was driven by substantial reduction in recurrent strokes and patients' improved health-related quality-of-life.

Outcomes and readmissions after transcatheter and surgical aortic valve replacement in patients with cirrhosis: A propensity matched analysis.

BACKGROUND: The data on the comparative outcomes and readmissions after transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR) in patients with cirrhosis are limited. We compared mortality, complications, discharge disposition, 30-day readmission rates, length of stay, and cost of hospitalization in cirrhotic patients undergoing TAVR and SAVR. METHODS: The National Inpatient Sample (NIS) and the National Readmission Database (NRD) were used for the study. The International Classification of Diseases-9th version was used to define cohorts of patients undergoing TAVR and SAVR. Patients undergoing concomitant other valve or coronary bypass surgery were excluded. Propensity-score matching was used to compare the outcomes between the groups. RESULTS: From 2012 to 2014, a total of 126 and 157 patients with cirrhosis underwent TAVR and SAVR, respectively. Of the 283 patients, 16 (5.7%) died during the same hospitalization. We found 345 patients with cirrhosis who had undergone an aortic valve replacement (156 with TAVR, and 189 with SAVR) in the 2013 and 2014 NRD. On propensity matching, there were no significant differences between the in-hospital mortality, readmissions, hospitalization costs, and discharges to home within the TAVR and SAVR groups. However, post-procedure length of stay (6.3 vs. 10.2 days; P < 0.001) and blood transfusion rates (22% vs. 58%; P < 0.001) were significantly lower in TAVR patients. CONCLUSIONS: Cirrhotic patients undergoing TAVR has high, but similar mortality and 30-day readmission rates when compared to SAVR; however, has shorter length of stay and lower blood transfusion rates.

Valve-in-Valve Transcatheter Aortic Valve Implantation: A Novel Approach to Treat Paravalvular Leak.

Enlarging or "cracking" a surgical stented bioprosthetic valve during valve-in-valve transcatheter aortic valve implantation (TAVI) increases orifice area, reducing transvalvular energy losses. We demonstrate that TAVI with valve cracking can be used to treat paravalvular leak (PVL) while providing optimal aortic valve physiology. A 61-year-old woman with a history of aortic valve replacement with a stented bioprosthesis presented with heart failure. Transthoracic echocardiography revealed severe prosthetic aortic valve stenosis with PVL and severe regurgitation. The patient underwent valve-in-valve TAVI with valve cracking. This successfully treated both the stenosis and the PVL with regurgitation.

Clinical trends in surgical, minimally invasive and transcatheter aortic valve replacement†.

OBJECTIVES: Transcatheter aortic valve replacement (TAVR) and minimally invasive aortic valve replacement (MIAVR) have emerged as alternatives to surgical aortic valve replacement (SAVR) via traditional sternotomy. However, their effect on clinical practice remains unclear. The study's objective is to describe clinical trends between TAVR, MIAVR and SAVR in patients with severe aortic stenosis (AS). METHODS: This retrospective observational study analyzed trends in isolated severe aortic valve replacement (AVR) among three high volume TAVR, MIAVR and SAVR centres in the United States. The cohort included 2571 patients from 2011 through 2014 undergoing SAVR ( n = 842), MIAVR ( n = 699) and TAVR ( n = 1030) further stratified into transapical (TA-TAVR) and trans-femoral (TF-TAVR). RESULTS: Total AVR volume increased +107% with increases in TF-TAVR (+595%) and MIAVR (+57%). However, SAVR (-15%) and TA-TAVR (-49%) decreased from 2013 to 2014. In the final year, risk stratification by age ≥ 80, redo AVR, patients receiving dialysis and STS score >8% revealed increases in TF-TAVR and MIAVR, while SAVR decreased for all groups. CONCLUSIONS: TF-TAVR and MIAVR increased while SAVR and TA-TAVR trended down in the latter periods, which underscore a paradigm shift in the treatment of severe AS and the importance of surgeon adoption of TF-TAVR and MIAVR techniques. As the demand for minimally invasive modalities increases, further studies comparing MIAVR versus TF-TAVR in low and intermediate risk patients are warranted.

Traditional Sternotomy Versus Minimally Invasive Aortic Valve Replacement in Patients Stratified by Ejection Fraction.

OBJECTIVE: Low ejection fraction (EF < 40%) portends adverse outcomes in patients undergoing valvular heart surgery. The role of traditional median sternotomy aortic valve replacement (SAVR) compared with minimally invasive aortic valve replacement (MIAVR) in this cohort remains incompletely understood. METHODS: A multi-institutional retrospective review of 1503 patients who underwent SAVR (n = 815) and MIAVR via right anterior thoracotomy (n = 688) from 2011 to 2014 was performed. Patients were stratified into two groups: EF of less than 40% and EF of 40% or more. In each EF group, SAVR and MIAVR patients were propensity matched by age, sex, body mass index, race, diabetes, hypertension, dyslipidemia, dialysis, cerebrovascular disease, cardiovascular disease, cerebrovascular accident, peripheral vascular disease, last creatinine level, EF, previous MI and cardiogenic shock, and the Society for Thoracic Surgeons (STS) score. RESULTS: Among patients with an EF of 40% or more (377 pairs), patients who underwent MIAVR compared with SAVR had decreased intensive care unit hours (56.8% vs 84.6%, P < 0.001), postoperative length of stay (7.1 vs 7.9 days, P = 0.04), incidence of atrial fibrillation (18.8% vs 38.7%, P < 0.001), bleeding (0.8% vs 3.2%, P = 0.04), and a trend toward decreased 30-day mortality (0.3% vs 1.3%, P = 0.22). The STS scores were largely equivalent in patients undergoing MIAVR compared with SAVR (2.4% vs 2.6%, P = 0.09). In patients with an EF of less than 40% (35 pairs), there was no difference in intensive care unit hours (69% vs 72.6%, P = 0.80), postoperative length of stay (10.3 vs 7.2 days, P = 0.13), 30-day mortality (3.8% vs 0.8%, P = 0.50), or the STS score (3.3% vs 3.2%, P = 0.68). CONCLUSIONS: Minimally invasive aortic valve replacement in patients with preserved EF was associated with improved short-term outcomes compared with SAVR. In patients with left ventricular dysfunction, short-term outcomes between MIAVR and SAVR are largely equivalent.

Randomized Comparison of Percutaneous Repair and Surgery for Mitral Regurgitation: 5-Year Results of EVEREST II.

BACKGROUND: In EVEREST II (Endovascular Valve Edge-to-Edge Repair Study), treatment of mitral regurgitation (MR) with a novel percutaneous device showed superior safety compared with surgery, but less effective reduction in MR at 1 year. OBJECTIVES: This study sought to evaluate the final 5-year clinical outcomes and durability of percutaneous mitral valve (MV) repair with the MitraClip device compared with conventional MV surgery. METHODS: Patients with grade 3+ or 4+ MR were randomly assigned to percutaneous repair with the device or conventional MV surgery in a 2:1 ratio (178:80). Patients prospectively consented to 5 years of follow-up. RESULTS: At 5 years, the rate of the composite endpoint of freedom from death, surgery, or 3+ or 4+ MR in the as-treated population was 44.2% versus 64.3% in the percutaneous repair and surgical groups, respectively (p = 0.01). The difference was driven by increased rates of 3+ to 4+ MR (12.3% vs. 1.8%; p = 0.02) and surgery (27.9% vs. 8.9%; p = 0.003) with percutaneous repair. After percutaneous repair, 78% of surgeries occurred within the first 6 months. Beyond 6 months, rates of surgery and moderate-to-severe MR were comparable between groups. Five-year mortality rates were 20.8% and 26.8% (p = 0.4) for percutaneous repair and surgery, respectively. In multivariable analysis, treatment strategy was not associated with survival. CONCLUSIONS: Patients treated with percutaneous repair more commonly required surgery for residual MR during the first year after treatment, but between 1- and 5-year follow-up, comparably low rates of surgery for MV dysfunction with either percutaneous or surgical therapy endorse the durability of MR reduction with both repair techniques. (EVEREST II Pivotal Study High Risk Registry; NCT00209274).

Endothelin-1 release during the early phase of reperfusion is a mediator of myocardial reperfusion injury.

PURPOSE: In acute myocardial infarction, left ventricular (LV) unloading reduces endothelin-1 (ET-1) release. We tested that endogenous ET-1 released during acute myocardial infarction might mediate ischemia/reperfusion (I/R) injury by stimulating increased intracellular calcium concentration, [Ca(2+)]i, and apoptosis. METHODS: Rabbits were subjected to 1 h of coronary artery occlusion followed by 3 h of reperfusion. Unloading was initiated 15 min prior to reperfusion and was maintained during reperfusion. The control group was subjected to reperfusion. Animals were treated with ET-1 receptor antagonist BQ123. In parallel, isolated rabbit cardiomyocytes subjected to simulated I/R with or without ET-1 or BQ123, intracellular Ca(2+) and cell death were assessed with flow cytometry. RESULTS: LV unloading prior to reperfusion reduced myocardial ET-1 release at 2 h of reperfusion. Infarct size was reduced in unloaded and BQ123 groups versus controls. LV unloading and BQ123 treatment reduced the percentage of apoptotic cells associated with increases in Bcl-2 protein levels in ischemic regions. BQ123 reduced both ET-1-induced [Ca(2+)]i increase and cell death for myocytes subjected to stimulated I/R. CONCLUSION: We propose that components of reperfusion injury involve ET-1 release which stimulates calcium overload and apoptosis. Intravenous ET-1 receptor blockade prior to reperfusion may be a protective adjunct to reperfusion therapy in acute myocardial infarction patients.