Minimally Invasive Versus Transcatheter and Surgical Aortic Valve Replacement: A Propensity Matched Study.

BACKGROUND: An increasing number of options exist for the treatment of severe symptomatic aortic stenosis. The study aim was to compare short-term outcomes in patients undergoing surgical aortic valve replacement (SAVR), minimally invasive aortic valve replacement (MIAVR), and transcatheter aortic valve replacement (TAVR). METHODS: A multi-institutional retrospective review of 2,571 patients undergoing SAVR (n = 842), MIAVR via right anterior thoracotomy (n = 699) and TAVR (n = 1,030) between 2011 and 2014 was conducted. TAVR patients were further stratified as either transfemoral (TF) or transapical (TA). Propensity matching was performed between MIAVR and SAVR (384 pairs), MIAVR and TA-TAVR (115 pairs), and MIAVR and TF-TAVR (247 pairs). RESULTS: Total numbers of AVR increased between 2011 and 2014. When stratified by procedure type, MIAVR and TF-TAVR accounted for most of the growth, while TA-TAVR and SAVR each experienced a decreased volume. Propensity matched comparisons of SAVR, TF-TAVR, and TA-TAVR versus MIAVR revealed no difference in 30-day mortality. TF-TAVR versus MIAVR revealed that MIAVR had a decreased rate of stroke (0.4% versus 3.6%, p = 0.02) and increased atrial fibrillation (AF; 19.4% versus 4%, p <0.01). When compared to SAVR, MIAVR had a lower incidence of AF (19% versus 32.6%, p <0.01). MIAVR exhibited decreased ventilation time (27.2 versus 134 h, p = 0.03) and intensive care unit time (63.7 versus 92.7 h, p = 0.02) compared to TA-TAVR. CONCLUSIONS: During recent years, MIAVR and TFTAVR have experienced significant growth in volume with near-comparable short-term outcomes, while SAVR and TA-TAVR volumes have declined. These results underscore the importance of surgeons adopting MIAVR and TF-TAVR techniques in order to offer patients optimal outcomes.

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.

Risk factors for development of endocarditis and reintervention in patients undergoing right ventricle to pulmonary artery valved conduit placement.

OBJECTIVE: To determine the incidence and risk factors for endocarditis and reintervention in patients undergoing placement of right ventricle-to-pulmonary artery valve conduits. METHODS: All right ventricle-to-pulmonary artery valved conduits placed between 1995 and 2014 were included. Freedom from endocarditis, reintervention, and replacement were analyzed using the Kaplan-Meier method and parametric survival regression models. RESULTS: A total of 586 patients underwent placement of a total of 792 valved conduits, including 289 (36%) pulmonary homografts, 121 (15%) aortic homografts, 245 (31%) bovine jugular grafts, and 137 (17%) porcine heterografts. There were 474 (60%) primary placements and 318 (40%) replacements. The median duration of conduit follow-up was 7 years; 23 conduits developed endocarditis at a median of 5 years after surgery. The use of bovine jugular grafts was the sole significant risk factor associated with endocarditis (hazard ratio, 9.05; 95% confidence interval, 2.6-31.8 compared with homografts). The hazard was greater for bovine jugular grafts compared with the other conduit types and increased with time; however, bovine jugular grafts were associated with a lower risk for reintervention (P < .0001) and replacement (P = .0002). Factors associated with greater risk of both reintervention and replacement were younger age and smaller conduit size. In addition, a diagnosis of truncus arteriosus was associated with a greater risk for replacement (P = .03). CONCLUSIONS: Bovine jugular grafts are associated with a significantly greater risk of late endocarditis but with lower reintervention rates compared with other valved conduits. The risk of endocarditis and durability must be balanced during conduit selection. Antibiotic prophylaxis and a high index of suspicion for endocarditis are warranted in patients with bovine jugular grafts.

Resident Perceptions of 2-Year Versus 3-Year Cardiothoracic Training Programs.

BACKGROUND: Resident perceptions of 2-year (2Y) vs 3-year (3Y) programs have never been characterized. The objective was to use the mandatory Thoracic Surgery Residents Association and Thoracic Surgery Directors Association In-Training Examination survey to compare perceptions of residents graduating from 2Y vs 3Y cardiothoracic programs. METHODS: Each year Accreditation Council for Graduate Medical Education cardiothoracic residents are required to take a 30-question survey designed by the Thoracic Surgery Residents Association and the Thoracic Surgery Directors Association accompanying the In-Training Examination with a 100% response rate. The 2013 and 2014 survey responses of residents graduating from 2Y vs 3Y training programs were compared. The Wilcoxon signed rank test was used to analyze ordinal and interval data. RESULTS: Graduating residents completed 167 surveys, including 96 from 2Y (56%) and 71 from 3Y (43%) programs. There was no difference in the perception of being prepared for the American Board of Thoracic Surgery examinations or amount of debt between 2Y and 3Y respondents. There was no difference in intended academic vs private practice. Graduating 3Y residents felt more prepared to meet case requirements and better trained, were more likely to pass their written American Board of Thoracic Surgery examinations, and were less likely to pursue additional training beyond their cardiothoracic residency. CONCLUSIONS: There was no difference in field of interest, practice type, and amount of debt between graduating 2Y vs 3Y residents. Respondents from 2Y programs expressed more difficulty in meeting case requirements, whereas residents from 3Y programs felt more prepared for independent practice and had higher American Board of Thoracic Surgery written pass rates.

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.

Glucose regulation of load-induced mTOR signaling and ER stress in mammalian heart.

BACKGROUND: Changes in energy substrate metabolism are first responders to hemodynamic stress in the heart. We have previously shown that hexose-6-phosphate levels regulate mammalian target of rapamycin (mTOR) activation in response to insulin. We now tested the hypothesis that inotropic stimulation and increased afterload also regulate mTOR activation via glucose 6-phosphate (G6P) accumulation. METHODS AND RESULTS: We subjected the working rat heart ex vivo to a high workload in the presence of different energy-providing substrates including glucose, glucose analogues, and noncarbohydrate substrates. We observed an association between G6P accumulation, mTOR activation, endoplasmic reticulum (ER) stress, and impaired contractile function, all of which were prevented by pretreating animals with rapamycin (mTOR inhibition) or metformin (AMPK activation). The histone deacetylase inhibitor 4-phenylbutyrate, which relieves ER stress, also improved contractile function. In contrast, adding the glucose analogue 2-deoxy-d-glucose, which is phosphorylated but not further metabolized, to the perfusate resulted in mTOR activation and contractile dysfunction. Next we tested our hypothesis in vivo by transverse aortic constriction in mice. Using a micro-PET system, we observed enhanced glucose tracer analog uptake and contractile dysfunction preceding dilatation of the left ventricle. In contrast, in hearts overexpressing SERCA2a, ER stress was reduced and contractile function was preserved with hypertrophy. Finally, we examined failing human hearts and found that mechanical unloading decreased G6P levels and ER stress markers. CONCLUSIONS: We propose that glucose metabolic changes precede and regulate functional (and possibly also structural) remodeling of the heart. We implicate a critical role for G6P in load-induced mTOR activation and ER stress.

Fatty acid binding protein 4 regulates VEGF-induced airway angiogenesis and inflammation in a transgenic mouse model: implications for asthma.

Neovascularization of the airways occurs in several inflammatory lung diseases, including asthma. Vascular endothelial growth factor (VEGF) plays an important role in vascular remodeling in the asthmatic airways. Fatty acid binding protein 4 (FABP4 or aP2) is an intracellular lipid chaperone that is induced by VEGF in endothelial cells. FABP4 exhibits a proangiogenic function in vitro, but whether it plays a role in modulation of angiogenesis in vivo is not known. We hypothesized that FABP4 promotes VEGF-induced airway angiogenesis and investigated this hypothesis with the use of a transgenic mouse model with inducible overexpression of VEGF165 under a CC10 promoter [VEGF-TG (transgenic) mice]. We found a significant increase in FABP4 mRNA levels and density of FABP4-expressing vascular endothelial cells in mouse airways with VEGF overexpression. FABP4(-/-) mouse airways showed a significant decrease in neovessel formation and endothelial cell proliferation in response to VEGF overexpression. These alterations in airway vasculature were accompanied by attenuated expression of proinflammatory mediators. Furthermore, VEGF-TG/FABP4(-/-) mice showed markedly decreased expression of endothelial nitric oxide synthase, a well-known mediator of VEGF-induced responses, compared with VEGF-TG mice. Finally, the density of FABP4-immunoreactive vessels in endobronchial biopsy specimens was significantly higher in patients with asthma than in control subjects. Taken together, these data unravel FABP4 as a potential target of pathologic airway remodeling in asthma.