RESUMO
BACKGROUND: Tricuspid regurgitation is common in patients with severe degenerative mitral regurgitation. However, the evidence base is insufficient to inform a decision about whether to perform tricuspid-valve repair during mitral-valve surgery in patients who have moderate tricuspid regurgitation or less-than-moderate regurgitation with annular dilatation. METHODS: We randomly assigned 401 patients who were undergoing mitral-valve surgery for degenerative mitral regurgitation to receive a procedure with or without tricuspid annuloplasty (TA). The primary 2-year end point was a composite of reoperation for tricuspid regurgitation, progression of tricuspid regurgitation by two grades from baseline or the presence of severe tricuspid regurgitation, or death. RESULTS: Patients who underwent mitral-valve surgery plus TA had fewer primary-end-point events than those who underwent mitral-valve surgery alone (3.9% vs. 10.2%) (relative risk, 0.37; 95% confidence interval [CI], 0.16 to 0.86; P = 0.02). Two-year mortality was 3.2% in the surgery-plus-TA group and 4.5% in the surgery-alone group (relative risk, 0.69; 95% CI, 0.25 to 1.88). The 2-year prevalence of progression of tricuspid regurgitation was lower in the surgery-plus-TA group than in the surgery-alone group (0.6% vs. 6.1%; relative risk, 0.09; 95% CI, 0.01 to 0.69). The frequencies of major adverse cardiac and cerebrovascular events, functional status, and quality of life were similar in the two groups at 2 years, although the incidence of permanent pacemaker implantation was higher in the surgery-plus-TA group than in the surgery-alone group (14.1% vs. 2.5%; rate ratio, 5.75; 95% CI, 2.27 to 14.60). CONCLUSIONS: Among patients undergoing mitral-valve surgery, those who also received TA had a lower incidence of a primary-end-point event than those who underwent mitral-valve surgery alone at 2 years, a reduction that was driven by less frequent progression to severe tricuspid regurgitation. Tricuspid repair resulted in more frequent permanent pacemaker implantation. Whether reduced progression of tricuspid regurgitation results in long-term clinical benefit can be determined only with longer follow-up. (Funded by the National Heart, Lung, and Blood Institute and the German Center for Cardiovascular Research; ClinicalTrials.gov number, NCT02675244.).
Assuntos
Anuloplastia da Valva Cardíaca , Progressão da Doença , Insuficiência da Valva Mitral/cirurgia , Insuficiência da Valva Tricúspide/cirurgia , Valva Tricúspide/cirurgia , Idoso , Dilatação Patológica , Feminino , Seguimentos , Humanos , Análise de Intenção de Tratamento , Masculino , Valva Mitral/cirurgia , Insuficiência da Valva Mitral/complicações , Insuficiência da Valva Mitral/mortalidade , Marca-Passo Artificial , Complicações Pós-Operatórias , Qualidade de Vida , Reoperação , Análise de Sobrevida , Valva Tricúspide/patologia , Insuficiência da Valva Tricúspide/complicações , Insuficiência da Valva Tricúspide/terapiaRESUMO
BACKGROUND: Coronary artery bypass grafting (CABG) is the most common revascularization approach for the treatment of multi-vessel coronary artery disease. While the internal mammary artery is nearly universally used to bypass the left anterior descending coronary artery, autologous saphenous vein grafts (SVGs) are still the most frequently used conduits to grafts the remaining coronary artery targets. Long-term failure of these grafts, however, continues to limit the benefits of surgery. METHODS: The Cardiothoracic Surgical Trials Network trial of the safety and effectiveness of a Venous External Support (VEST) device is a randomized, multicenter, within-patient trial comparing VEST-supported versus unsupported saphenous vein grafts in patients undergoing CABG. Key inclusion criteria are the need for CABG with a planned internal mammary artery to the left anterior descending and two or more saphenous vein grafts to other coronary arteries. The primary efficacy endpoint of the trial is SVG intimal hyperplasia (plaque + media) area assessed by intravascular ultrasound at 12 months post randomization. Occluded grafts are accounted for in the analysis of the primary endpoint. Secondary confirmatory endpoints are lumen diameter uniformity and graft failure (>50% stenosis) assessed by coronary angiography at 12 months. The safety endpoints are the occurrence of major adverse cardiac and cerebrovascular events and hospitalization within 5 years from randomization. CONCLUSIONS: The results of the VEST trial will determine whether the VEST device can safely limit SVG intimal hyperplasia in patients undergoing CABG as treatment for coronary atherosclerotic disease.
Assuntos
Doença da Artéria Coronariana , Veia Safena , Angiografia Coronária , Ponte de Artéria Coronária/métodos , Doença da Artéria Coronariana/etiologia , Doença da Artéria Coronariana/cirurgia , Humanos , Veia Safena/transplante , Resultado do Tratamento , Grau de Desobstrução VascularRESUMO
BACKGROUND: Smallpox was declared eradicated in 1980, but variola virus (VARV), which causes smallpox, still exists. There is no known effective treatment for smallpox; therefore, tecovirimat is being developed as an oral smallpox therapy. Because clinical trials in a context of natural disease are not possible, an alternative developmental path to evaluate efficacy and safety was needed. METHODS: We investigated the efficacy of tecovirimat in nonhuman primate (monkeypox) and rabbit (rabbitpox) models in accordance with the Food and Drug Administration (FDA) Animal Efficacy Rule, which was interpreted for smallpox therapeutics by an expert advisory committee. We also conducted a placebo-controlled pharmacokinetic and safety trial involving 449 adult volunteers. RESULTS: The minimum dose of tecovirimat required in order to achieve more than 90% survival in the monkeypox model was 10 mg per kilogram of body weight for 14 days, and a dose of 40 mg per kilogram for 14 days was similarly efficacious in the rabbitpox model. Although the effective dose per kilogram was higher in rabbits, exposure was lower, with a mean steady-state maximum, minimum, and average (mean) concentration (Cmax, Cmin, and Cavg, respectively) of 374, 25, and 138 ng per milliliter, respectively, in rabbits and 1444, 169, and 598 ng per milliliter in nonhuman primates, as well as an area under the concentration-time curve over 24 hours (AUC0-24hr) of 3318 ng×hours per milliliter in rabbits and 14,352 ng×hours per milliliter in nonhuman primates. These findings suggested that the nonhuman primate was the more conservative model for the estimation of the required drug exposure in humans. A dose of 600 mg twice daily for 14 days was selected for testing in humans and provided exposures in excess of those in nonhuman primates (mean steady-state Cmax, Cmin, and Cavg of 2209, 690, and 1270 ng per milliliter and AUC0-24hr of 30,632 ng×hours per milliliter). No pattern of troubling adverse events was observed. CONCLUSIONS: On the basis of its efficacy in two animal models and pharmacokinetic and safety data in humans, tecovirimat is being advanced as a therapy for smallpox in accordance with the FDA Animal Rule. (Funded by the National Institutes of Health and the Biomedical Advanced Research and Development Authority; ClinicalTrials.gov number, NCT02474589 .).
Assuntos
Antivirais/administração & dosagem , Benzamidas/administração & dosagem , Isoindóis/administração & dosagem , Mpox/tratamento farmacológico , Infecções por Poxviridae/tratamento farmacológico , Administração Oral , Adolescente , Adulto , Idoso , Animais , Antivirais/efeitos adversos , Antivirais/farmacocinética , Benzamidas/efeitos adversos , Benzamidas/farmacocinética , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Voluntários Saudáveis , Humanos , Isoindóis/efeitos adversos , Isoindóis/farmacocinética , Macaca fascicularis , Masculino , Pessoa de Meia-Idade , Mpox/mortalidade , Monkeypox virus , Infecções por Poxviridae/mortalidade , Coelhos , Vaccinia virus , Adulto JovemRESUMO
BACKGROUND: In a randomized trial comparing mitral-valve repair with mitral-valve replacement in patients with severe ischemic mitral regurgitation, we found no significant difference in the left ventricular end-systolic volume index (LVESVI), survival, or adverse events at 1 year after surgery. However, patients in the repair group had significantly more recurrences of moderate or severe mitral regurgitation. We now report the 2-year outcomes of this trial. METHODS: We randomly assigned 251 patients to mitral-valve repair or replacement. Patients were followed for 2 years, and clinical and echocardiographic outcomes were assessed. RESULTS: Among surviving patients, the mean (±SD) 2-year LVESVI was 52.6±27.7 ml per square meter of body-surface area with mitral-valve repair and 60.6±39.0 ml per square meter with mitral-valve replacement (mean changes from baseline, -9.0 ml per square meter and -6.5 ml per square meter, respectively). Two-year mortality was 19.0% in the repair group and 23.2% in the replacement group (hazard ratio in the repair group, 0.79; 95% confidence interval, 0.46 to 1.35; P=0.39). The rank-based assessment of LVESVI at 2 years (incorporating deaths) showed no significant between-group difference (z score=-1.32, P=0.19). The rate of recurrence of moderate or severe mitral regurgitation over 2 years was higher in the repair group than in the replacement group (58.8% vs. 3.8%, P<0.001). There were no significant between-group differences in rates of serious adverse events and overall readmissions, but patients in the repair group had more serious adverse events related to heart failure (P=0.05) and cardiovascular readmissions (P=0.01). On the Minnesota Living with Heart Failure questionnaire, there was a trend toward greater improvement in the replacement group (P=0.07). CONCLUSIONS: In patients undergoing mitral-valve repair or replacement for severe ischemic mitral regurgitation, we observed no significant between-group difference in left ventricular reverse remodeling or survival at 2 years. Mitral regurgitation recurred more frequently in the repair group, resulting in more heart-failure-related adverse events and cardiovascular admissions. (Funded by the National Institutes of Health and Canadian Institutes of Health Research; ClinicalTrials.gov number, NCT00807040.).
Assuntos
Implante de Prótese de Valva Cardíaca , Insuficiência da Valva Mitral/cirurgia , Valva Mitral/cirurgia , Qualidade de Vida , Insuficiência Cardíaca/etiologia , Ventrículos do Coração/anatomia & histologia , Ventrículos do Coração/fisiopatologia , Hospitalização , Humanos , Insuficiência da Valva Mitral/complicações , Insuficiência da Valva Mitral/mortalidade , Recidiva , Reoperação/estatística & dados numéricos , Falha de Tratamento , Função Ventricular Esquerda , Remodelação VentricularRESUMO
BACKGROUND: Atrial fibrillation after cardiac surgery is associated with increased rates of death, complications, and hospitalizations. In patients with postoperative atrial fibrillation who are in stable condition, the best initial treatment strategy--heart-rate control or rhythm control--remains controversial. METHODS: Patients with new-onset postoperative atrial fibrillation were randomly assigned to undergo either rate control or rhythm control. The primary end point was the total number of days of hospitalization within 60 days after randomization, as assessed by the Wilcoxon rank-sum test. RESULTS: Postoperative atrial fibrillation occurred in 695 of the 2109 patients (33.0%) who were enrolled preoperatively; of these patients, 523 underwent randomization. The total numbers of hospital days in the rate-control group and the rhythm-control group were similar (median, 5.1 days and 5.0 days, respectively; P=0.76). There were no significant between-group differences in the rates of death (P=0.64) or overall serious adverse events (24.8 per 100 patient-months in the rate-control group and 26.4 per 100 patient-months in the rhythm-control group, P=0.61), including thromboembolic and bleeding events. About 25% of the patients in each group deviated from the assigned therapy, mainly because of drug ineffectiveness (in the rate-control group) or amiodarone side effects or adverse drug reactions (in the rhythm-control group). At 60 days, 93.8% of the patients in the rate-control group and 97.9% of those in the rhythm-control group had had a stable heart rhythm without atrial fibrillation for the previous 30 days (P=0.02), and 84.2% and 86.9%, respectively, had been free from atrial fibrillation from discharge to 60 days (P=0.41). CONCLUSIONS: Strategies for rate control and rhythm control to treat postoperative atrial fibrillation were associated with equal numbers of days of hospitalization, similar complication rates, and similarly low rates of persistent atrial fibrillation 60 days after onset. Neither treatment strategy showed a net clinical advantage over the other. (Funded by the National Institutes of Health and the Canadian Institutes of Health Research; ClinicalTrials.gov number, NCT02132767.).
Assuntos
Amiodarona/uso terapêutico , Antiarrítmicos/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Procedimentos Cirúrgicos Cardíacos , Frequência Cardíaca/efeitos dos fármacos , Complicações Pós-Operatórias/tratamento farmacológico , Antagonistas Adrenérgicos beta/uso terapêutico , Idoso , Amiodarona/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Antiarrítmicos/efeitos adversos , Fibrilação Atrial/terapia , Procedimentos Cirúrgicos Cardíacos/mortalidade , Terapia Combinada , Cardioversão Elétrica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/terapiaRESUMO
BACKGROUND: In a trial comparing coronary-artery bypass grafting (CABG) alone with CABG plus mitral-valve repair in patients with moderate ischemic mitral regurgitation, we found no significant difference in the left ventricular end-systolic volume index (LVESVI) or survival after 1 year. Concomitant mitral-valve repair was associated with a reduced prevalence of moderate or severe mitral regurgitation, but patients had more adverse events. We now report 2-year outcomes. METHODS: We randomly assigned 301 patients to undergo either CABG alone or the combined procedure. Patients were followed for 2 years for clinical and echocardiographic outcomes. RESULTS: At 2 years, the mean (±SD) LVESVI was 41.2±20.0 ml per square meter of body-surface area in the CABG-alone group and 43.2±20.6 ml per square meter in the combined-procedure group (mean improvement over baseline, -14.1 ml per square meter and -14.6 ml per square meter, respectively). The rate of death was 10.6% in the CABG-alone group and 10.0% in the combined-procedure group (hazard ratio in the combined-procedure group, 0.90; 95% confidence interval, 0.45 to 1.83; P=0.78). There was no significant between-group difference in the rank-based assessment of the LVESVI (including death) at 2 years (z score, 0.38; P=0.71). The 2-year rate of moderate or severe residual mitral regurgitation was higher in the CABG-alone group than in the combined-procedure group (32.3% vs. 11.2%, P<0.001). Overall rates of hospital readmission and serious adverse events were similar in the two groups, but neurologic events and supraventricular arrhythmias remained more frequent in the combined-procedure group. CONCLUSIONS: In patients with moderate ischemic mitral regurgitation undergoing CABG, the addition of mitral-valve repair did not lead to significant differences in left ventricular reverse remodeling at 2 years. Mitral-valve repair provided a more durable correction of mitral regurgitation but did not significantly improve survival or reduce overall adverse events or readmissions and was associated with an early hazard of increased neurologic events and supraventricular arrhythmias. (Funded by the National Institutes of Health and Canadian Institutes of Health Research; ClinicalTrials.gov number, NCT00806988.).
Assuntos
Ponte de Artéria Coronária , Insuficiência da Valva Mitral/cirurgia , Valva Mitral/cirurgia , Infarto do Miocárdio/cirurgia , Feminino , Seguimentos , Humanos , Tempo de Internação , Masculino , Insuficiência da Valva Mitral/etiologia , Insuficiência da Valva Mitral/mortalidade , Infarto do Miocárdio/complicações , Readmissão do Paciente/estatística & dados numéricos , Complicações Pós-Operatórias , Qualidade de Vida , Acidente Vascular Cerebral/etiologia , Taquicardia Supraventricular/etiologia , Remodelação VentricularRESUMO
Importance: Left ventricular assist device (LVAD) therapy improves myocardial function, but few patients recover sufficiently for explant, which has focused attention on stem cells to augment cardiac recovery. Objective: To assess efficacy and adverse effects of intramyocardial injections of mesenchymal precursor cells (MPCs) during LVAD implant. Design, Setting, and Participants: A randomized phase 2 clinical trial involving patients with advanced heart failure, undergoing LVAD implant, at 19 North American centers (July 2015-August 2017). The 1-year follow-up ended August 2018. Interventions: Intramyocardial injections of 150 million allogeneic MPCs or cryoprotective medium as a sham treatment in a 2:1 ratio (n = 106 vs n = 53). Main Outcomes and Measures: The primary efficacy end point was the proportion of successful temporary weans (of 3 planned assessments) from LVAD support within 6 months of randomization. This end point was assessed using a Bayesian analysis with a predefined threshold of a posterior probability of 80% to indicate success. The 1-year primary safety end point was the incidence of intervention-related adverse events (myocarditis, myocardial rupture, neoplasm, hypersensitivity reactions, and immune sensitization). Secondary end points included readmissions and adverse events at 6 months and 1-year survival. Results: Of 159 patients (mean age, 56 years; 11.3% women), 155 (97.5%) completed 1-year of follow-up. The posterior probability that MPCs increased the likelihood of successful weaning was 69%; below the predefined threshold for success. The mean proportion of successful temporary weaning from LVAD support over 6 months was 61% in the MPC group and 58% in the control group (rate ratio [RR], 1.08; 95% CI, 0.83-1.41; P = .55). No patient experienced a primary safety end point. Of 10 prespecified secondary end points reported, 9 did not reach statistical significance. One-year mortality was not significantly different between the MPC group and the control group (14.2% vs 15.1%; hazard ratio [HR], 0.89; 95%, CI, 0.38-2.11; P = .80). The rate of serious adverse events was not significantly different between groups (70.9 vs 78.7 per 100 patient-months; difference, -7.89; 95% CI, -39.95 to 24.17; P = .63) nor was the rate of readmissions (0.68 vs 0.75 per 100 patient-months; difference, -0.07; 95% CI, -0.41 to 0.27; P = .68). Conclusions and Relevance: Among patients with advanced heart failure, intramyocardial injections of mesenchymal precursor cells, compared with injections of a cryoprotective medium as sham treatment, did not improve successful temporary weaning from left ventricular assist device support at 6 months. The findings do not support the use of intramyocardial mesenchymal stem cells to promote cardiac recovery as measured by temporary weaning from device support. Trial Registration: clinicaltrials.gov Identifier: NCT02362646.
Assuntos
Insuficiência Cardíaca/terapia , Coração Auxiliar , Transplante de Células-Tronco Mesenquimais , Teorema de Bayes , Remoção de Dispositivo , Epistaxe/etiologia , Feminino , Seguimentos , Hemorragia Gastrointestinal/etiologia , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Coração Auxiliar/efeitos adversos , Humanos , Injeções , Masculino , Transplante de Células-Tronco Mesenquimais/efeitos adversos , Pessoa de Meia-Idade , Miocárdio , Falha de Prótese , Volume Sistólico , Falha de Tratamento , Disfunção Ventricular EsquerdaRESUMO
BACKGROUND: Among patients undergoing mitral-valve surgery, 30 to 50% present with atrial fibrillation, which is associated with reduced survival and increased risk of stroke. Surgical ablation of atrial fibrillation has been widely adopted, but evidence regarding its safety and effectiveness is limited. METHODS: We randomly assigned 260 patients with persistent or long-standing persistent atrial fibrillation who required mitral-valve surgery to undergo either surgical ablation (ablation group) or no ablation (control group) during the mitral-valve operation. Patients in the ablation group underwent further randomization to pulmonary-vein isolation or a biatrial maze procedure. All patients underwent closure of the left atrial appendage. The primary end point was freedom from atrial fibrillation at both 6 months and 12 months (as assessed by means of 3-day Holter monitoring). RESULTS: More patients in the ablation group than in the control group were free from atrial fibrillation at both 6 and 12 months (63.2% vs. 29.4%, P<0.001). There was no significant difference in the rate of freedom from atrial fibrillation between patients who underwent pulmonary-vein isolation and those who underwent the biatrial maze procedure (61.0% and 66.0%, respectively; P=0.60). One-year mortality was 6.8% in the ablation group and 8.7% in the control group (hazard ratio with ablation, 0.76; 95% confidence interval, 0.32 to 1.84; P=0.55). Ablation was associated with more implantations of a permanent pacemaker than was no ablation (21.5 vs. 8.1 per 100 patient-years, P=0.01). There were no significant between-group differences in major cardiac or cerebrovascular adverse events, overall serious adverse events, or hospital readmissions. CONCLUSIONS: The addition of atrial fibrillation ablation to mitral-valve surgery significantly increased the rate of freedom from atrial fibrillation at 1 year among patients with persistent or long-standing persistent atrial fibrillation, but the risk of implantation of a permanent pacemaker was also increased. (Funded by the National Institutes of Health and the Canadian Institutes of Health Research; ClinicalTrials.gov number, NCT00903370.).
Assuntos
Fibrilação Atrial/cirurgia , Ablação por Cateter/métodos , Doenças das Valvas Cardíacas/cirurgia , Valva Mitral/cirurgia , Idoso , Fibrilação Atrial/complicações , Fibrilação Atrial/prevenção & controle , Doenças Cardiovasculares/mortalidade , Ablação por Cateter/efeitos adversos , Eletrocardiografia Ambulatorial , Feminino , Doenças das Valvas Cardíacas/complicações , Implante de Prótese de Valva Cardíaca , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Qualidade de Vida , Prevenção SecundáriaRESUMO
BACKGROUND: Ischemic mitral regurgitation is associated with increased mortality and morbidity. For surgical patients with moderate regurgitation, the benefits of adding mitral-valve repair to coronary-artery bypass grafting (CABG) are uncertain. METHODS: We randomly assigned 301 patients with moderate ischemic mitral regurgitation to CABG alone or CABG plus mitral-valve repair (combined procedure). The primary end point was the left ventricular end-systolic volume index (LVESVI), a measure of left ventricular remodeling, at 1 year. This end point was assessed with the use of a Wilcoxon rank-sum test in which deaths were categorized as the lowest LVESVI rank. RESULTS: At 1 year, the mean LVESVI among surviving patients was 46.1±22.4 ml per square meter of body-surface area in the CABG-alone group and 49.6±31.5 ml per square meter in the combined-procedure group (mean change from baseline, -9.4 and -9.3 ml per square meter, respectively). The rate of death was 6.7% in the combined-procedure group and 7.3% in the CABG-alone group (hazard ratio with mitral-valve repair, 0.90; 95% confidence interval, 0.38 to 2.12; P=0.81). The rank-based assessment of LVESVI at 1 year (incorporating deaths) showed no significant between-group difference (z score, 0.50; P=0.61). The addition of mitral-valve repair was associated with a longer bypass time (P<0.001), a longer hospital stay after surgery (P=0.002), and more neurologic events (P=0.03). Moderate or severe mitral regurgitation was less common in the combined-procedure group than in the CABG-alone group (11.2% vs. 31.0%, P<0.001). There were no significant between-group differences in major adverse cardiac or cerebrovascular events, deaths, readmissions, functional status, or quality of life at 1 year. CONCLUSIONS: In patients with moderate ischemic mitral regurgitation, the addition of mitral-valve repair to CABG did not result in a higher degree of left ventricular reverse remodeling. Mitral-valve repair was associated with a reduced prevalence of moderate or severe mitral regurgitation but an increased number of untoward events. Thus, at 1 year, this trial did not show a clinically meaningful advantage of adding mitral-valve repair to CABG. Longer-term follow-up may determine whether the lower prevalence of mitral regurgitation translates into a net clinical benefit. (Funded by the National Institutes of Health and the Canadian Institutes of Health Research; ClinicalTrials.gov number, NCT00806988.).
Assuntos
Ponte de Artéria Coronária , Insuficiência da Valva Mitral/cirurgia , Isquemia Miocárdica/cirurgia , Idoso , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência da Valva Mitral/etiologia , Isquemia Miocárdica/complicações , Complicações Pós-Operatórias/epidemiologia , Qualidade de Vida , Remodelação VentricularRESUMO
Importance: Stroke is a major complication of surgical aortic valve replacement (SAVR). Objective: To determine the efficacy and adverse effects of cerebral embolic protection devices in reducing ischemic central nervous system (CNS) injury during SAVR. Design, Setting, and Participants: A randomized clinical trial of patients with calcific aortic stenosis undergoing SAVR at 18 North American centers between March 2015 and July 2016. The end of follow-up was December 2016. Interventions: Use of 1 of 2 cerebral embolic protection devices (n = 118 for suction-based extraction and n = 133 for intra-aortic filtration device) vs a standard aortic cannula (control; n = 132) at the time of SAVR. Main Outcomes and Measures: The primary end point was freedom from clinical or radiographic CNS infarction at 7 days (± 3 days) after the procedure. Secondary end points included a composite of mortality, clinical ischemic stroke, and acute kidney injury within 30 days after surgery; delirium; mortality; serious adverse events; and neurocognition. Results: Among 383 randomized patients (mean age, 73.9 years; 38.4% women; 368 [96.1%] completed the trial), the rate of freedom from CNS infarction at 7 days was 32.0% with suction-based extraction vs 33.3% with control (between-group difference, -1.3%; 95% CI, -13.8% to 11.2%) and 25.6% with intra-aortic filtration vs 32.4% with control (between-group difference, -6.9%; 95% CI, -17.9% to 4.2%). The 30-day composite end point was not significantly different between suction-based extraction and control (21.4% vs 24.2%, respectively; between-group difference, -2.8% [95% CI, -13.5% to 7.9%]) nor between intra-aortic filtration and control (33.3% vs 23.7%; between-group difference, 9.7% [95% CI, -1.2% to 20.5%]). There were no significant differences in mortality (3.4% for suction-based extraction vs 1.7% for control; and 2.3% for intra-aortic filtration vs 1.5% for control) or clinical stroke (5.1% for suction-based extraction vs 5.8% for control; and 8.3% for intra-aortic filtration vs 6.1% for control). Delirium at postoperative day 7 was 6.3% for suction-based extraction vs 15.3% for control (between-group difference, -9.1%; 95% CI, -17.1% to -1.0%) and 8.1% for intra-aortic filtration vs 15.6% for control (between-group difference, -7.4%; 95% CI, -15.5% to 0.6%). Mortality and overall serious adverse events at 90 days were not significantly different across groups. Patients in the intra-aortic filtration group vs patients in the control group experienced significantly more acute kidney injury events (14 vs 4, respectively; P = .02) and cardiac arrhythmias (57 vs 30; P = .004). Conclusions and Relevance: Among patients undergoing SAVR, cerebral embolic protection devices compared with a standard aortic cannula did not significantly reduce the risk of CNS infarction at 7 days. Potential benefits for reduction in delirium, cognition, and symptomatic stroke merit larger trials with longer follow-up. Trial Registration: clinicaltrials.gov Identifier: NCT02389894.
Assuntos
Valva Aórtica/cirurgia , Infarto Encefálico/prevenção & controle , Dispositivos de Proteção Embólica , Implante de Prótese de Valva Cardíaca/efeitos adversos , Próteses Valvulares Cardíacas , Injúria Renal Aguda/etiologia , Idoso , Estenose da Valva Aórtica/cirurgia , Arritmias Cardíacas/etiologia , Infarto Encefálico/etiologia , Delírio/etiologia , Dispositivos de Proteção Embólica/efeitos adversos , Feminino , Humanos , Incidência , Masculino , Complicações Pós-Operatórias/prevenção & controle , Fatores de Risco , Resultado do TratamentoRESUMO
BACKGROUND: Allogeneic mesenchymal precursor cells (MPCs) injected during left ventricular assist device (LVAD) implantation may contribute to myocardial recovery. This trial explores the safety and efficacy of this strategy. METHODS AND RESULTS: In this multicenter, double-blind, sham-procedure controlled trial, 30 patients were randomized (2:1) to intramyocardial injection of 25 million MPCs or medium during LVAD implantation. The primary safety end point was incidence of infectious myocarditis, myocardial rupture, neoplasm, hypersensitivity reaction, and immune sensitization (90 days after randomization). Key efficacy end points were functional status and ventricular function while temporarily weaned from LVAD support (90 days after randomization). Patients were followed up until transplant or 12 months after randomization, whichever came first. Mean age was 57.4 (±13.6) years, mean left ventricular ejection fraction was 18.1%, and 66.7% were destination therapy LVADs. No safety events were observed. Successful temporary LVAD weaning was achieved in 50% of MPC and 20% of control patients at 90 days (P=0.24); the posterior probability that MPCs increased the likelihood of successful weaning was 93%. At 90 days, 3 deaths (30%) occurred in control patients, and none occurred in MPC patients. Mean left ventricular ejection fraction after successful wean was 24.0% (MPC=10) and 22.5% (control=2; P=0.56). At 12 months, 30% of MPC patients and 40% of control patients were successfully temporarily weaned from LVAD support (P=0.69), and 6 deaths (30%) occurred in MPC patients. Donor-specific HLA sensitization developed in 2 MPC and 3 control patients and resolved by 12 months. CONCLUSIONS: In this preliminary trial, administration of MPCs appeared to be safe, and there was a potential signal of efficacy. Future studies will evaluate the potential for higher or additional doses to enhance the ability to wean LVAD recipients off support. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01442129.
Assuntos
Insuficiência Cardíaca/terapia , Coração Auxiliar , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais , Disfunção Ventricular Esquerda/terapia , Adulto , Idoso , Terapia Baseada em Transplante de Células e Tecidos/efeitos adversos , Terapia Baseada em Transplante de Células e Tecidos/métodos , Método Duplo-Cego , Feminino , Neoplasias Cardíacas/epidemiologia , Humanos , Incidência , Masculino , Transplante de Células-Tronco Mesenquimais/efeitos adversos , Pessoa de Meia-Idade , Miocardite/epidemiologia , Resultado do TratamentoRESUMO
BACKGROUND: Ventricular assist devices (VADs) improve survival and quality of life in patients with advanced heart failure, but their use is frequently complicated by infection. There are limited data on the microbiology and epidemiology of these infections. METHODS AND RESULTS: One hundred fifty patients scheduled for VAD implantation were enrolled (2006-2008) at 11 US cardiac centers and followed prospectively until transplantation, explantation for recovery, death, or for 1 year. Eighty-six patients (57%) received HeartMate II devices. Data were collected on potential preoperative, intraoperative, and postoperative risk factors for infection. Clinical, laboratory, and microbiological data were collected for suspected infections and evaluated by an infectious diseases specialist. Thirty-three patients (22%) developed 34 VAD-related infections with an incidence rate of 0.10 per 100 person-days (95% confidence interval, 0.073-0.142). The median time to infection was 68 days. The driveline was the most commonly infected site (n=28); 18 (64%) were associated with invasive disease. Staphylococci were the most common pathogen (47%), but pseudomonas or other Gram-negative bacteria caused 32% of infections. A history of depression and elevated baseline serum creatinine were independent predictors of VAD infection (adjusted hazard ratio=2.8 [P=0.007] and 1.7 [P=0.023], respectively). The HeartMate II was not associated with a decreased risk of infection. VAD infection increased 1-year mortality (adjusted hazard ratio=5.6; P<0.0001). CONCLUSIONS: This prospective, multicenter study demonstrates that infection frequently complicates VAD placement and is a continuing problem despite the use of newer, smaller devices. Depression and renal dysfunction may increase the risk of VAD infection. VAD infection is a serious consequence because it adversely affects patient survival. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01471795.
Assuntos
Infecções por Bactérias Gram-Negativas/epidemiologia , Coração Auxiliar/microbiologia , Infecções Relacionadas à Prótese/epidemiologia , Infecções Relacionadas à Prótese/microbiologia , Infecções por Pseudomonas/epidemiologia , Infecções Estafilocócicas/epidemiologia , Adulto , Idoso , Infecções Cardiovasculares/epidemiologia , Infecções Cardiovasculares/microbiologia , Creatinina/sangue , Depressão/epidemiologia , Feminino , Infecções por Bactérias Gram-Negativas/microbiologia , Insuficiência Cardíaca/terapia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
Importance: Intimal hyperplasia and subsequent saphenous vein graft failure may have significant adverse clinical effects in patients undergoing coronary artery bypass surgery. External support of saphenous vein grafts has the potential to prevent vein graft dilation and hence slow the rate of intimal hyperplasia and increase long-term vein patency. Objective: To determine efficacy, as measured by intimal hyperplasia, and safety of an external saphenous vein graft support device in patients undergoing a coronary bypass graft procedure. Design, Setting, and Participants: This within-patient randomized, open-label, multicenter study was conducted at 17 Cardiothoracic Surgical Trials Network centers in North America. Between January 2018 and February 2019, 224 patients with multivessel coronary artery disease undergoing isolated bypass surgery were enrolled. For each patient, 1 of 2 vein grafts was randomized to receive external support or no support. Interventions: External vein graft support or no support. Main Outcomes and Measures: The primary efficacy end point was intimal hyperplasia area assessed by intravascular ultrasound at 12 months postrandomization for each study graft. Secondary confirmatory end points were lumen diameter uniformity assessed by angiography and graft failure (≥50% stenosis) by quantitative coronary angiography. Major cardiac and cerebrovascular events were collected through month 12. Results: Among 224 patients (mean [SD] age, 65.8 [8.3] years; 178 [79.5%] male), 203 (90.6%) were eligible for intravascular ultrasound, of which 85 (41.9%) had at least 1 study graft occluded or severely diseased at 12 months (55 supported, 56 unsupported). After imputation of data missing because of graft occlusion or severe disease, the estimated mean (SE) intimal hyperplasia area was 5.11 (0.16) mm2 in supported grafts and 5.79 (0.20) mm2 in unsupported grafts (P = .07). In a sensitivity analysis of 113 patients with both grafts imaged, the mean intimal hyperplasia area was 4.58 (0.18) mm2 and 5.12 (0.23) mm2 in supported and unsupported grafts, respectively (P = .04). By 12 months, 5 patients (2.2%) died and 16 patients (7.1%) experienced a major cardiac or cerebrovascular event. Conclusions and Relevance: The 12-month difference in intimal hyperplasia area between supported and unsupported grafts did not achieve statistical significance. Cumulative mortality and major cardiac or cerebrovascular events rates were similar to those in other randomized coronary artery bypass trials. Further investigation to assess the effect of external graft support devices on long-term graft patency and clinical outcomes is warranted. Trial Registration: ClinicalTrials.gov Identifier: NCT03209609.
Assuntos
Oclusão de Enxerto Vascular , Veia Safena , Idoso , Ponte de Artéria Coronária/métodos , Feminino , Oclusão de Enxerto Vascular/etiologia , Oclusão de Enxerto Vascular/patologia , Oclusão de Enxerto Vascular/prevenção & controle , Humanos , Hiperplasia/etiologia , Hiperplasia/patologia , Masculino , Veia Safena/transplante , Grau de Desobstrução VascularRESUMO
OBJECTIVE: To determine the relationship between body mass index (BMI) at the time of transplant and posttransplant survival and morbidity. SUMMARY BACKGROUND DATA: The recent International Society for Heart and Lung Transplantation listing criteria for heart transplantation stated that candidates should achieve a BMI <30 kg/m-or percent ideal body weight <140%-before listing for cardiac transplantation. However, data to support these recommendations are limited and often conflicting. METHODS: United Network of Organ Sharing provided de-identified patient-level data. Analysis included 19,593 orthotopic heart transplant recipients aged >or=18 years and transplanted January 1 1995-December 31 2005. Follow-up data were provided through February 8, 2008. Recipients were stratified by BMI at the time of transplantation: BMI <18.5 (underweight), 18.5 to 24.99 (normal weight), 25 to 29.99 (overweight), 30 to 34.99 (obesity class I), and >or=35 (obesity class II/III). The primary outcome measure was post-transplant survival. RESULTS: Risk-adjusted median survival in the underweight, normal weight, overweight, obesity I, and obesity II/III groups was 8.31, 10.20, 10.03, 9.51, and 9.05 years, respectively. In multivariate Cox proportional hazards regression, BMI in the overweight (HR = 1.08, 0.99-1.17; P = 0.055) and obesity I (HR = 1.05, 0.99-1.12; P = 0.091) ranges were not associated with significantly diminished survival. However, BMI in the underweight (HR = 1.26, 1.11-1.43; P < 0.001) and obesity II/III (HR = 1.18, 1.01-1.38; P = 0.030) ranges were associated with diminished posttransplant survival. CONCLUSION: Findings from this analysis do not suggest that obesity I (BMI of 30-34.99) is associated with significantly higher morbidity and mortality. However, underweight and obesity II/III recipients have significantly higher morbidity and mortality compared with other groups.
Assuntos
Índice de Massa Corporal , Transplante de Coração/mortalidade , Peso Corporal , Feminino , Transplante de Coração/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Guias de Prática Clínica como Assunto , Taxa de Sobrevida , Listas de EsperaRESUMO
BACKGROUND: Several studies have compared outcomes for coronary-artery bypass grafting (CABG) and percutaneous coronary intervention (PCI), but most were done before the availability of stenting, which has revolutionized the latter approach. METHODS: We used New York's cardiac registries to identify 37,212 patients with multivessel disease who underwent CABG and 22,102 patients with multivessel disease who underwent PCI from January 1, 1997, to December 31, 2000. We determined the rates of death and subsequent revascularization within three years after the procedure in various groups of patients according to the number of diseased vessels and the presence or absence of involvement of the left anterior descending coronary artery. The rates of adverse outcomes were adjusted by means of proportional-hazards methods to account for differences in patients' severity of illness before revascularization. RESULTS: Risk-adjusted survival rates were significantly higher among patients who underwent CABG than among those who received a stent in all of the anatomical subgroups studied. For example, the adjusted hazard ratio for the long-term risk of death after CABG relative to stent implantation was 0.64 (95 percent confidence interval, 0.56 to 0.74) for patients with three-vessel disease with involvement of the proximal left anterior descending coronary artery and 0.76 (95 percent confidence interval, 0.60 to 0.96) for patients with two-vessel disease with involvement of the nonproximal left anterior descending coronary artery. Also, the three-year rates of revascularization were considerably higher in the stenting group than in the CABG group (7.8 percent vs. 0.3 percent for subsequent CABG and 27.3 percent vs. 4.6 percent for subsequent PCI). CONCLUSIONS: For patients with two or more diseased coronary arteries, CABG is associated with higher adjusted rates of long-term survival than stenting.
Assuntos
Angioplastia Coronária com Balão , Ponte de Artéria Coronária , Doença das Coronárias/mortalidade , Doença das Coronárias/terapia , Stents , Idoso , Idoso de 80 Anos ou mais , Doença das Coronárias/cirurgia , Reestenose Coronária/epidemiologia , Reestenose Coronária/prevenção & controle , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , New York/epidemiologia , Modelos de Riscos Proporcionais , Sistema de Registros , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida , Resultado do TratamentoRESUMO
OBJECTIVE: To examine patterns of resource use and the cost of care for patients with advanced heart failure treated with medical management (MM) during the final 2 years of life. METHODS AND RESULTS: The study population (n=47, mean age 70.4 years+/-7.06) included patients randomized to the MM arm of the Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure trial. Inpatient and outpatient use data were obtained from the clinical dataset and Centers for Medicare and Medicaid Services (beginning January 1, 1998). Cost and resource use were tracked from the date of death (t(d)) backward in 3-month intervals (eg, t(d-1), t(d-2)). In the primary analysis, costs were summed across intervals. The mean cost of MM in the final 2 years of life was $156,169, with 50.5% ($78,880.39) expended in the final 6 months. The mean quarterly cost increased (P < .01) 4.9-fold from t(d-8) ($8,816 +/- $14,270) to t(d-1) ($42,836 +/- $41,407). The number of inpatient days increased (P < .01) 6.6-fold from 3.8+/-4.7 days to 22.2+/-23.5 days during the same time intervals. CONCLUSION: This current economic analysis extends on previous findings by demonstrating that medical therapy in advanced and end-stage heart failure is associated with significant costs and resource consumption; these costs and resource consumption increase significantly as death approaches.
Assuntos
Recursos em Saúde/economia , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/economia , Doença Aguda , Fatores Etários , Idoso , Análise Custo-Benefício , Progressão da Doença , Feminino , Recursos em Saúde/estatística & dados numéricos , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Medicare/economia , Modelos Econômicos , Fatores de Tempo , Resultado do Tratamento , Estados UnidosRESUMO
BACKGROUND: Mediastinal infections are a potentially devastating complication of cardiac operations. This study analyzed the frequency, risk factors, and perioperative outcomes of mediastinal infections after cardiac operations. METHODS: In 2010, 5,158 patients enrolled in a prospective study evaluating infections after cardiac operations and their effect on readmissions and mortality for up to 65 days after the procedure. Clinical and demographic characteristics, operative variables, management practices, and outcomes were compared for patients with and without mediastinal infections, defined as deep sternal wound infection, myocarditis, pericarditis, or mediastinitis. RESULTS: There were 43 mediastinal infections in 41 patients (cumulative incidence, 0.79%; 95% confidence interval [CI] 0.60% to 1.06%). Median time to infection was 20.0 days, with 65% of infections occurring after the index hospitalization discharge. Higher body mass index (hazard ratio [HR] 1.06; 95% CI, 1.01 to 1.10), higher creatinine (HR, 1.25; 95% CI, 1.13 to 1.38), peripheral vascular disease (HR, 2.47; 95% CI, 1.21 to 5.05), preoperative corticosteroid use (HR, 3.33; 95% CI, 1.27 to 8.76), and ventricular assist device or transplant surgery (HR, 5.81; 95% CI, 2.36 to 14.33) were associated with increased risk of mediastinal infection. Postoperative hyperglycemia (HR, 3.15; 95% CI, 1.32 to 7.51) was associated with increased risk of infection in nondiabetic patients. Additional length of stay attributable to mediastinal infection was 11.5 days (bootstrap 95% CI, 1.88 to 21.11). Readmission rates and mortality were five times higher in patients with mediastinal infection than in patients without mediastinal infection. CONCLUSIONS: Mediastinal infection after a cardiac operation is associated with substantial increases in length of stay, readmissions, and death. Reducing these infections remains a high priority, and improving post-operative glycemic management may reduce their risk in patients without diabetes.
Assuntos
Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Mediastinite/epidemiologia , Infecção da Ferida Cirúrgica/epidemiologia , Feminino , Seguimentos , Cardiopatias/cirurgia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Alta do Paciente/tendências , Readmissão do Paciente/tendências , Estudos Prospectivos , Fatores de Risco , Taxa de Sobrevida/tendências , Fatores de Tempo , Resultado do Tratamento , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: The CTSN (Cardiothoracic Surgical Trials Network) recently reported no difference in left ventricular end-systolic volume index or in survival at 2 years between patients with severe ischemic mitral regurgitation (MR) randomized to mitral valve repair or replacement. However, replacement provided more durable correction of MR and fewer cardiovascular readmissions. Yet, costeffectiveness outcomes have not been addressed. METHODS AND RESULTS: We conducted a cost-effectiveness analysis of the surgical treatment of ischemic MR based on the CTSN trial (n=126 for repair; n=125 for replacement). Patient-level data on readmissions, survival, qualityof- life, and US hospital costs were used to estimate costs and quality-adjusted life years per patient over the trial duration and a 10-year time horizon. We performed microsimulation for extrapolation of outcomes beyond the 2 years of trial data. Bootstrap and deterministic sensitivity analyses were done to address parameter uncertainty. In-hospital cost estimates were $78 216 for replacement versus $72 761 for repair (difference: $5455; 95% uncertainty interval [UI]: −778421 193) while 2-year costs were $97 427 versus $96 261 (difference: $1166; 95% UI: −16 25317 172), respectively. Quality-adjusted life years at 2 years were 1.18 for replacement versus 1.23 for repair (difference: −0.05; 95% UI: −0.17 to 0.07). Over 5 and 10 years, the benefits of reduction in cardiovascular readmission rates with replacement increased, and survival minimally improved compared with repair. At 5 years, cumulative costs and quality-adjusted life years showed no difference on average, but by 10 years, there was a small, uncertain benefit for replacement: $118 023 versus $119 837 (difference: −$1814; 95% UI: −27 144 to 22 602) and qualityadjusted life years: 4.06 versus 3.97 (difference: 0.09; 95% UI: −0.87 to 1.08). After 10 years, the incremental cost-effectiveness of replacement continued to improve. CONCLUSIONS: Our cost-effectiveness analysis predicts potential savings in cost and gains in quality-adjusted survival at 10 years when mitral valve replacement is compared with repair for severe ischemic MR. These projected benefits, however, were small and subject to variability. Efforts to further delineate predictors of long-term outcomes in patients with severe ischemic MR are needed to optimize surgical decisions for individual patients, which should yield more cost-effective care. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00807040.
Assuntos
Implante de Prótese de Valva Cardíaca/economia , Custos Hospitalares , Anuloplastia da Valva Mitral/economia , Insuficiência da Valva Mitral/economia , Insuficiência da Valva Mitral/cirurgia , Valva Mitral/cirurgia , Isquemia Miocárdica/complicações , Idoso , Simulação por Computador , Análise Custo-Benefício , Feminino , Implante de Prótese de Valva Cardíaca/efeitos adversos , Implante de Prótese de Valva Cardíaca/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Anuloplastia da Valva Mitral/efeitos adversos , Anuloplastia da Valva Mitral/mortalidade , Insuficiência da Valva Mitral/diagnóstico , Insuficiência da Valva Mitral/mortalidade , Modelos Econômicos , Isquemia Miocárdica/mortalidade , Readmissão do Paciente/economia , Qualidade de Vida , Anos de Vida Ajustados por Qualidade de Vida , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento , Estados UnidosRESUMO
New surgical procedures, imaging modalities, and medical devices have improved therapy for many patients and made treatment possible for others who have had few options in the past. In February 2004, the National Heart, Lung, and Blood Institute's (NHLBI) Advisory Council proposed that the institute evaluate the status and future directions in cardiac surgery. In response to this recommendation, the NHLBI convened a working group of cardiac surgeons on May 7 and 8, 2004, to assess the state of cardiac surgery research, identify critical gaps in current knowledge, determine areas of opportunity, and obtain specific recommendations for future research activities. The working group discussed surgical revascularization, novel surgical approaches, valvular research directions, biotechnology and cell-based therapy, heart failure, imaging modalities, and barriers to clinical research and presents its recommendations here.
Assuntos
Procedimentos Cirúrgicos Cardíacos/normas , Procedimentos Cirúrgicos Cardíacos/métodos , Procedimentos Cirúrgicos Cardíacos/tendências , Transplante de Células , Diagnóstico por Imagem/métodos , Previsões , Cardiopatias/patologia , Cardiopatias/terapia , Humanos , Complicações Pós-Operatórias/prevenção & controle , PesquisaRESUMO
BACKGROUND: Studies that are the basis of recommended volume thresholds for CABG surgery are outdated and not reflective of recent advances in the field. This study examines both hospital and surgeon volume-mortality relations for CABG surgery through the use of a population-based clinical data set. METHODS AND RESULTS: Data from New York's clinical CABG surgery registry from 1997 to 1999 (total number of procedures, 57 150) were used to examine the individual and combined impact of annual hospital volume and annual surgeon volume on in-hospital mortality rates after adjusting for differences in severity of illness. Significantly lower risk-adjusted mortality rates occurred above all annual hospital volume thresholds between 200 and 800 and above all surgeon volume thresholds between 50 and 200. The number needed to treat (NNT) at higher-volume providers to avoid a death was minimized for a hospital threshold volume of 100 (NNT=50) and a surgeon threshold volume of 50 (NNT=118). The risk-adjusted mortality rate (RAMR) for patients undergoing surgery performed by surgeons with volumes of > or =125 in hospitals with volumes of > or =600 was 1.89%. The RAMR was significantly higher (2.67%) for patients undergoing surgery performed by surgeons with volumes of <125 in hospitals with volumes of <600. CONCLUSIONS: Higher-volume surgeons and hospitals continue to have lower risk-adjusted mortality rates, and patients undergoing surgery performed by higher-volume surgeons in higher-volume hospitals have the lowest mortality rates.