Late Bleeding Events in Patients Undergoing Percutaneous Coronary Intervention in the Workup Pre-TAVR.

BACKGROUND: In patients undergoing percutaneous coronary intervention (PCI) in the work-up pre-transcatheter aortic valve replacement (TAVR), the incidence and clinical impact of late bleeding events (LBEs) remain largely unknown. OBJECTIVES: This study sought to determine the incidence, clinical characteristics, associated factors, and outcomes of LBEs in patients undergoing PCI in the work-up pre-TAVR. METHODS: This was a multicenter study including 1,457 consecutive patients (mean age 81 ± 7 years; 41.5% women) who underwent TAVR and survived beyond 30 days. LBEs (>30 days post-TAVR) were defined according to the Valve Academic Research Consortium-2 criteria. RESULTS: LBEs occurred in 116 (7.9%) patients after a median follow-up of 23 (IQR: 12-40) months. Late bleeding was minor, major, and life-threatening or disabling in 21 (18.1%), 63 (54.3%), and 32 (27.6%) patients, respectively. Periprocedural (<30 days post-TAVR) major bleeding and the combination of antiplatelet and anticoagulation therapy at discharge were independent factors associated with LBEs (P ≤ 0.02 for all). LBEs conveyed an increased mortality risk at 4-year follow-up compared with no bleeding (43.9% vs 36.0; P = 0.034). Also, LBE was identified as an independent predictor of all-cause mortality after TAVR (HR: 1.39; 95% CI: 1.05-1.83; P = 0.020). CONCLUSIONS: In TAVR candidates with concomitant significant coronary artery disease requiring percutaneous treatment, LBEs after TAVR were frequent and associated with increased mortality. Combining antiplatelet and anticoagulation regimens and the occurrence of periprocedural bleeding determined an increased risk of LBEs. Preventive strategies should be pursued for preventing late bleeding after TAVR, and further studies are needed to provide more solid evidence on the most safe and effective antithrombotic regimen post-TAVR in this challenging group of patients.

Transcatheter Versus Surgical Aortic Valve Replacement in Patients With Complex Coronary Artery Disease.

OBJECTIVES: The aim of this study was to compare, in a cohort of patients with complex coronary artery disease (CAD) and severe aortic stenosis (AS), the clinical outcomes associated with transfemoral transcatheter aortic valve replacement (TAVR) (plus percutaneous coronary intervention [PCI]) versus surgical aortic valve replacement (SAVR) (plus coronary artery bypass grafting [CABG]). BACKGROUND: Patients with complex CAD were excluded from the main randomized trials comparing TAVR with SAVR, and no data exist comparing TAVR + PCI vs SAVR + CABG in such patients. METHODS: A multicenter study was conducted including consecutive patients with severe AS and complex CAD (SYNTAX [Synergy Between PCI with Taxus and Cardiac Surgery] score >22 or unprotected left main disease). A 1:1 propensity-matched analysis was performed to account for unbalanced covariates. The rates of major adverse cardiac and cerebrovascular events (MACCE), including all-cause mortality, nonprocedural myocardial infarction, need for new coronary revascularization, and stroke, were evaluated. RESULTS: A total of 800 patients (598 undergoing SAVR + CABG and 202 undergoing transfemoral TAVR + PCI) were included, and after propensity matching, a total of 156 pairs of patients were generated. After a median follow-up period of 3 years (interquartile range: 1-6 years), there were no significant differences between groups for MACCE (HR for transfemoral TAVR vs SAVR: 1.33; 95% CI: 0.89-1.98), all-cause mortality (HR: 1.25; 95% CI: 0.81-1.94), myocardial infarction (HR: 1.16; 95% CI: 0.41-3.27), and stroke (HR: 0.42; 95% CI: 0.13-1.32), but there was a higher rate of new coronary revascularization in the TAVR + PCI group (HR: 5.38; 95% CI: 1.73-16.7). CONCLUSIONS: In patients with severe AS and complex CAD, TAVR + PCI and SAVR + CABG were associated with similar rates of MACCE after a median follow-up period of 3 years, but TAVR + PCI recipients exhibited a higher risk for repeat coronary revascularization. Future trials are warranted.

Incidence, Predictor, and Clinical Outcomes of Multiple Resheathing With Self-Expanding Valves During Transcatheter Aortic Valve Replacement.

Background No study has evaluated the impact of the additional manipulation demanded by multiple resheathing (MR) in patients undergoing transcatheter aortic valve replacement with repositionable self-expanding valves. Methods and Results This study included a real-world, multicenter registry involving 16 centers from Canada, Germany, Latin America, and Spain. All consecutive patients who underwent transcatheter aortic valve replacement with the Evolut R, Evolut PRO, and Portico valves were included. Patients were divided according to the number of resheathing: no resheathing, single resheathing (SR), and MR. The primary end point was device success. Secondary outcomes included procedural complications, early safety events, and 1-year mortality. In 1026 patients, the proportion who required SR and MR was 23.9% and 9.3%, respectively. MR was predicted by the use of Portico and moderate/severe aortic regurgitation at baseline (both with P<0.01). Patients undergoing MR had less device success (no resheathing=89.9%, SR=89.8%, and MR=80%; P=0.01), driven by more need for a second prosthesis and device embolization. At 30 days, there were no differences in safety events. At 1 year, more deaths occurred with MR (no resheathing=10.5%, SR=8.0%, and MR=18.8%; P=0.014). After adjusting for baseline differences and center experience by annual volume, MR associated with less device success (odds ratio, 0.42; P=0.003) and increased 1-year mortality (hazard ratio, 2.06; P=0.01). When including only the Evolut R/PRO cases (N=837), MR continued to have less device success (P<0.001) and a trend toward increased mortality (P=0.05). Conclusions Repositioning a self-expanding valve is used in a third of patients, being multiple in ≈10%. MR, but not SR, was associated with more device failure and higher 1-year mortality, regardless of the type of valve implanted.

Impact of Morbid Obesity and Obesity Phenotype on Outcomes After Transcatheter Aortic Valve Replacement.

Background There is a paucity of outcome data on patients who are morbidly obese (MO) undergoing transcatheter aortic valve replacement. We aimed to determine their periprocedural and midterm outcomes and investigate the impact of obesity phenotype. Methods and Results Consecutive patients who are MO (body mass index, ≥40 kg/m2, or ≥35 kg/m2 with obesity-related comorbidities; n=910) with severe aortic stenosis who underwent transcatheter aortic valve replacement in 18 tertiary hospitals were compared with a nonobese cohort (body mass index, 18.5-29.9 kg/m2, n=2264). Propensity-score matching resulted in 770 pairs. Pre-transcatheter aortic valve replacement computed tomography scans were centrally analyzed to assess adipose tissue distribution; epicardial, abdominal visceral and subcutaneous fat. Major vascular complications were more common (6.6% versus 4.3%; P=0.043) and device success was less frequent (84.4% versus 88.1%; P=0.038) in the MO group. Freedom from all-cause and cardiovascular mortality were similar at 2 years (79.4 versus 80.6%, P=0.731; and 88.7 versus 87.4%, P=0.699; MO and nonobese, respectively). Multivariable analysis identified baseline glomerular filtration rate and nontransfemoral access as independent predictors of 2-year mortality in the MO group. An adverse MO phenotype with an abdominal visceral adipose tissue:subcutaneous adipose tissue ratio ≥1 (VAT:SAT) was associated with increased 2-year all-cause (hazard ratio [HR], 3.06; 95% CI, 1.20-7.77; P=0.019) and cardiovascular (hazard ratio, 4.11; 95% CI, 1.06-15.90; P=0.041) mortality, and readmissions (HR, 1.81; 95% CI, 1.07-3.07; P=0.027). After multivariable analysis, a (VAT:SAT) ratio ≥1 remained a strong predictor of 2-year mortality (hazard ratio, 2.78; P=0.035). Conclusions Transcatheter aortic valve replacement in patients who are MO has similar short- and midterm outcomes to nonobese patients, despite higher major vascular complications and lower device success. An abdominal VAT:SAT ratio ≥1 identifies an obesity phenotype at higher risk of adverse clinical outcomes.

ST-Segment Elevation Myocardial Infarction Following Transcatheter Aortic Valve Replacement.

BACKGROUND: Among patients with acute coronary syndrome following transcatheter aortic valve replacement (TAVR), those presenting with ST-segment elevation myocardial infarction (STEMI) are at highest risk. OBJECTIVES: The goal of this study was to determine the clinical characteristics, management, and outcomes of STEMI after TAVR. METHODS: This was a multicenter study including 118 patients presenting with STEMI at a median of 255 days (interquartile range: 9 to 680 days) after TAVR. Procedural features of STEMI after TAVR managed with primary percutaneous coronary intervention (PCI) were compared with all-comer STEMI: 439 non-TAVR patients who had primary PCI within the 2 weeks before and after each post-TAVR STEMI case in 5 participating centers from different countries. RESULTS: Median door-to-balloon time was higher in TAVR patients (40 min [interquartile range: 25 to 57 min] vs. 30 min [interquartile range: 25 to 35 min]; p = 0.003). Procedural time, fluoroscopy time, dose-area product, and contrast volume were also higher in TAVR patients (p < 0.01 for all). PCI failure occurred more frequently in patients with previous TAVR (16.5% vs. 3.9%; p < 0.001), including 5 patients in whom the culprit lesion was not revascularized owing to coronary ostia cannulation failure. In-hospital and late (median of 7 months [interquartile range: 1 to 21 months]) mortality rates were 25.4% and 42.4%, respectively (20.6% and 38.2% in primary PCI patients), and estimated glomerular filtration rate <60 ml/min (hazard ratio [HR]: 3.02; 95% confidence interval [CI]: 1.42 to 6.43; p = 0.004), Killip class ≥2 (HR: 2.74; 95% CI: 1.37 to 5.49; p = 0.004), and PCI failure (HR: 3.23; 95% CI: 1.42 to 7.31; p = 0.005) determined an increased risk. CONCLUSIONS: STEMI after TAVR was associated with very high in-hospital and mid-term mortality. Longer door-to-balloon times and a higher PCI failure rate were observed in TAVR patients, partially due to coronary access issues specific to the TAVR population, and this was associated with poorer outcomes.

Procedural Characteristics and Late Outcomes of Percutaneous Coronary Intervention in the Workup Pre-TAVR.

OBJECTIVES: This study sought to determine, in patients undergoing percutaneous coronary intervention (PCI) during the work-up pre-transcatheter aortic valve replacement (TAVR): 1) the clinical and peri-procedural PCI characteristics; 2) the long-term outcomes; and 3) the clinical events in those patients with complex coronary features. BACKGROUND: A PCI is performed in about 25% of TAVR candidates, but procedural features and late outcomes of pre-TAVR PCI remain largely unknown. METHODS: Multicenter study including 1197 consecutive patients who had PCI in the work-up pre-TAVR. A total of 1,705 lesions (1.5 ± 0.7 lesions per patient) were included. Death, stroke, myocardial infarction, and major adverse cardiovascular and cerebrovascular events (MACCE) were recorded, as well as target lesion failure (TLF) and target vessel failure (TVF). RESULTS: One-half of patients exhibited a multivessel disease and the mean SYNTAX (SYNergy between PCI with TAXUS and Cardiac Surgery) score was 12.1 ± 9.1. The lesions were of B2/C type, calcified, bifurcation, and ostial in 49.9%, 45.8%, 21.4%, and 19.3% of cases, respectively. After a median follow-up of 2 (interquartile range: 1 to 3) years, a total of 444 (37.1%) patients presented an MACCE. Forty patients exhibited TVF (3.3%), with TLF identified in 32 (2.7%) patients. By multivariable analysis, previous peripheral artery disease (p < 0.001), chronic obstructive pulmonary disease (p = 0.002), atrial fibrillation (p = 0.003), diabetes mellitus (p = 0.012), and incomplete revascularization (p = 0.014) determined an increased risk of MACCE. In patients with unprotected left main or SYNTAX score >32 (n = 128), TLF, TVF, and MACCE rates were 3.9%, 6.3%, and 35.9%, respectively (p = 0.378; p = 0.065, and p = 0.847, respectively, vs. the rest of the population). CONCLUSIONS: Patients undergoing PCI in the work-up pre-TAVR frequently exhibited complex coronary lesions and multivessel disease. PCI was successful in most cases, and TLF and TVF rates at 2-year follow-up were low, also among patients with high-risk coronary features. However, overall MACCE occurred in about one-third of patients, with incomplete revascularization determining an increased risk. These results should inform future studies to better determine the optimal revascularization strategy pre-TAVR.

Saúde, espiritualidade e religiosidade na visão dos estudantes de medicina / Health, spirituality, and religiosity: medical students' views

JUSTIFICATIVA E OBJETIVOS: Diversos estudos demonstram relações entre espiritualidade/religiosidade e saúde,porém esses conceitos não são consensuais. Objetiva-se compreender quais são os conceitos de espiritualidade trazidos pelos estudantes de medicina e sua relação com a religiosidade. MÉTODO: Aplicou-se um questionário aos discentes de uma escola médica brasileira contendo: conceito de espiritualidade;relação entre "saúde e espiritualidade" e a religiosidade de cada estudante. Comparou-se então o grau de religiosidade dos estudantes frente aos conceitos trazidos por meio dos testes de Qui-quadrado e Mann-Whitney. RESULTADOS: Dos 210 estudantes avaliados, a espiritualidade foi conceituada principalmente como "crença em algo transcendente à matéria", "crença e relação com Deus / religiosidade" e "busca de sentido e significado para a vida humana". O assunto foi correlacionado com "humanização da medicina" e "interferência positiva/negativa da religiosidade na saúde". As dimensões de religiosidade dos alunos moldaram o modo de entender esses conceitos de forma significativa. CONCLUSÃO: O presente estudo traz uma reflexão da falta de homogeneidade obtida por estudantes de medicina frente a conceitos e relações entre espiritualidade e medicina. Essa falta de homogeneidade é um passo importante no intuito de ampliar a discussão do assunto no âmbito da graduação médica, para que o estudante possa ter contato com esses valores e criar uma visão própria sobre o tema, visando uma abordagem mais integrativa do paciente.

BACKGROUND AND OBJECTIVES: Several studies have shown a relation between spirituality/religiosity and health; however, there is no consensus on these definitions. This study aims to understand medical students' concepts regarding spirituality,and if their religiosity can influence these concepts. METHOD: A questionnaire was given out to students from a Brazilian medical school including: definition of spirituality, connection between "spirituality and health" and each student's religiosity. For a comparison between students' religiosity and theconcepts, Chi-square and Mann-Whitney tests were used. RESULTS: From 210 students evaluated, spirituality was predominantly defined as "transcendent belief", "belief andrelation with God/religiosity" and "search for meaning to humanlife". Spirituality and health were associated with "humanization of medicine" and "positive or negative influence of religiosity on health". In addition, students' dimensions for religiosity significantly influenced the way they understand these concepts. CONCLUSION: This study brings a reflection over the lack of a uniform concept among medical students regarding spirituality and health. This lack of homogeneity is an important step to expand the discussion of this subject in the medical education, so that the students have contact with these values and create their own view about it, aiming at a more integrative approach of the patient.

Chlorpromazine quantification in human plasma by UPLC-electrospray ionization tandem mass spectrometry. Application to a comparative pharmacokinetic study.

In the present study a method to quantify chlorpromazine in human plasma using cyclobenzaprine as the internal standard (IS) is described. The analyte and the IS were extracted from human plasma by a liquid-liquid extraction with diethyl ether/dichloromethane (70/30, v/v) and analyzed by an ultra performance liquid chromatography (UPLC) coupled to an electrospray tandem triple quadrupole mass spectrometer in positive mode (UPLC-ES(+)-MS/MS). Chromatography was performed isocratically on an Aquity UPLC BEH C18 1.7 µm (50 mm × 2.1 mm i.d.) operating at 40°C. The mobile phase was a mixture of 65% water+1% formic acid and 35% of acetonitrile at a flow-rate of 0.5 mL/min. The lowest concentration quantified was 0.5 ng/mL and a linear calibration curve over the range 0.5-200 ng/mL was obtained, showing intra-assay precisions from 2.4 to 5.8%, and inter-assay precisions from 3.6 to 9.9%. The intra-assay accuracies ranged from 96.9 to 102.5%, while the inter-assay accuracies ranged from 94.1 to 100.3%. This analytical method was applied in a relative bioavailability study in order to compare a test chlorpromazine 100 mg simple dose formulation versus a reference in 57 volunteers of both sexes. The study was conducted in an open randomized two-period crossover design and with a fourteen days washout period. Plasma samples were obtained over a 144-h interval. Since the 90% CI for both C(max), AUC(last) and AUC(0-inf) were within the 80-125% interval proposed by the Food and Drug Administration and ANVISA, it was concluded that chlorpromazine 100 mg/dose was bioequivalent to the reference formulation, according to both the rate and extent of absorption.