RESUMEN

Background: Transcatheter edge-to-edge repair (TEER) improved outcomes in patients with heart failure (HF) and severe secondary mitral regurgitation (SMR) compared with guideline-directed medical therapy (GDMT) alone regardless of the severity of baseline left ventricular ejection fraction (LVEF). The study aimed to evaluate the effect of early changes in LVEF after TEER and GDMT alone in patients with HF and severe SMR. Methods: Within the COAPT trial, we evaluated outcomes according to changes in LVEF from baseline to 30 days. The primary outcome was all-cause death or HF hospitalization (HFH) between 30 days and 2 years. Results: Among 432 patients with paired echocardiographic data, 182 (42.1%) had increased LVEF (LVEF change 6.0% ± 4.9%) and 250 (57.9%) had a decrease or no change in LVEF (LVEF change -6.6% ± 5.6%) from baseline to 30 days. LVEF at 30 days increased more frequently with GDMT alone compared with TEER plus GDMT (51.4% vs 33.0%; P = .0001). Between 30 days and 2 years, there were no significant differences in death or HFH in the increase LVEF and the decrease LVEF groups (58.8% vs 51.4%; multivariable-adjusted HR, 0.97; 95% CI, 0.87-1.08; P = .59). TEER plus GDMT reduced the 30-day to 2-year rate of death or HFH compared with GDMT alone consistently in patients with increase LVEF and decrease LVEF (Pint = 0.75). Conclusions: Among patients with HF and severe SMR, early improvements in LVEF were more frequent with GDMT alone compared with TEER plus GDMT but were not associated with subsequent outcomes at 2 years. TEER reduced death or HFH during 2-year follow-up irrespective of early LVEF changes.

RESUMEN

BACKGROUND: Data from a 5-year follow-up of outcomes after transcatheter edge-to-edge repair of severe mitral regurgitation, as compared with outcomes after maximal doses of guideline-directed medical therapy alone, in patients with heart failure are now available. METHODS: We randomly assigned patients with heart failure and moderate-to-severe or severe secondary mitral regurgitation who remained symptomatic despite the use of maximal doses of guideline-directed medical therapy to undergo transcatheter edge-to-edge repair plus receive medical therapy (device group) or to receive medical therapy alone (control group) at 78 sites in the United States and Canada. The primary effectiveness end point was all hospitalizations for heart failure through 2 years of follow-up. The annualized rate of all hospitalizations for heart failure, all-cause mortality, the risk of death or hospitalization for heart failure, and safety, among other outcomes, were assessed through 5 years. RESULTS: Of the 614 patients enrolled in the trial, 302 were assigned to the device group and 312 to the control group. The annualized rate of hospitalization for heart failure through 5 years was 33.1% per year in the device group and 57.2% per year in the control group (hazard ratio, 0.53; 95% confidence interval [CI], 0.41 to 0.68). All-cause mortality through 5 years was 57.3% in the device group and 67.2% in the control group (hazard ratio, 0.72; 95% CI, 0.58 to 0.89). Death or hospitalization for heart failure within 5 years occurred in 73.6% of the patients in the device group and in 91.5% of those in the control group (hazard ratio, 0.53; 95% CI, 0.44 to 0.64). Device-specific safety events within 5 years occurred in 4 of 293 treated patients (1.4%), with all the events occurring within 30 days after the procedure. CONCLUSIONS: Among patients with heart failure and moderate-to-severe or severe secondary mitral regurgitation who remained symptomatic despite guideline-directed medical therapy, transcatheter edge-to-edge repair of the mitral valve was safe and led to a lower rate of hospitalization for heart failure and lower all-cause mortality through 5 years of follow-up than medical therapy alone. (Funded by Abbott; COAPT ClinicalTrials.gov number, NCT01626079.).

Asunto(s)

Cateterismo Cardíaco , Insuficiencia Cardíaca , Implantación de Prótesis de Válvulas Cardíacas , Insuficiencia de la Válvula Mitral , Humanos , Cateterismo Cardíaco/efectos adversos , Cateterismo Cardíaco/métodos , Estudios de Seguimiento , Insuficiencia Cardíaca/terapia , Insuficiencia Cardíaca/cirugía , Implantación de Prótesis de Válvulas Cardíacas/efectos adversos , Implantación de Prótesis de Válvulas Cardíacas/métodos , Insuficiencia de la Válvula Mitral/etiología , Insuficiencia de la Válvula Mitral/cirugía , Resultado del Tratamiento

RESUMEN

OBJECTIVES: This study sought to assess the sex-specific outcomes in patients with heart failure (HF) with 3+ and 4+ secondary mitral regurgitation (SMR) treated with transcatheter mitral valve repair (TMVr) plus guideline-directed medical therapy (GDMT) versus GDMT alone in the COAPT trial. BACKGROUND: The impact of sex in patients with HF and severe SMR treated with TMVr with the MitraClip compared with GDMT alone is unknown. METHODS: Patients were randomized 1:1 to TMVr versus GDMT alone. Two-year outcomes were examined according to sex. RESULTS: Among 614 patients, 221 (36.0%) were women. Women were younger than men and had fewer comorbidities, but reduced quality of life and functional capacity at baseline. In a joint frailty model accounting for the competing risk of death, the 2-year cumulative incidence of the primary endpoint of all HF hospitalizations (HFH) was higher in men compared with women treated with GDMT alone. However, the relative reduction in HFHs with TMVr was greater in men (HR: 0.43; 95% CI: 0.34-0.54) than women (HR: 0.78; 95% CI: 0.57-1.05) (Pinteraction = 0.002). A significant interaction between TMVr versus GDMT alone treatment and time was present for all HFHs in women (HR: 0.57; 95% CI: 0.39-0.84, and HR: 1.39; 95% CI: 0.83-2.33 between 0-1 year and 1-2 years after randomization, respectively, Pinteraction = 0.007) but not in men (HR: 0.48; 95% CI: 0.36-0.64, and HR: 0.33; 95% CI: 0.21-0.51; Pinteraction = 0.16). Female sex was independently associated with a lower adjusted risk of death at 2 years (HR: 0.64; 95% CI: 0.46-0.90; P = 0.011). TMVr consistently reduced 2-year mortality compared with GDMT alone, irrespective of sex (Pinteraction = 0.99). CONCLUSIONS: In the COAPT trial, TMVr with the MitraClip resulted in improved clinical outcomes compared with GDMT alone, irrespective of sex. However, the impact of TMVr in reducing HFH was less pronounced in women compared with men beyond the first year after treatment. (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation [The COAPT Tria] [COAPT]; NCT01626079).

Asunto(s)

Insuficiencia Cardíaca , Implantación de Prótesis de Válvulas Cardíacas , Insuficiencia de la Válvula Mitral , Cateterismo Cardíaco , Femenino , Insuficiencia Cardíaca/cirugía , Insuficiencia Cardíaca/terapia , Humanos , Masculino , Insuficiencia de la Válvula Mitral/cirugía , Calidad de Vida , Resultado del Tratamiento

RESUMEN

OBJECTIVES: We report the 30-day outcomes from the roll-in cohort of the CLASP IID trial, representing the first procedures performed by each site. BACKGROUND: The currently enrolling CLASP IID/IIF pivotal trial is a multicenter, prospective, randomized trial assessing the safety and effectiveness of the PASCAL transcatheter valve repair system in patients with clinically significant MR. The trial allows for up to three roll-in patients per site. METHODS: Eligibility criteria were: DMR ≥3+, prohibitive surgical risk, and deemed suitable for transcatheter repair by the local heart team. Trial oversight included a central screening committee and echocardiographic core laboratory. The primary safety endpoint was a 30-day composite MAE: cardiovascular mortality, stroke, myocardial infarction (MI), new need for renal replacement therapy, severe bleeding, and non-elective mitral valve re-intervention, adjudicated by an independent clinical events committee. Thirty-day echocardiographic, functional, and quality of life outcomes were assessed. RESULTS: A total of 45 roll-in patients with mean age of 83 years and 69% in NYHA class III/IV were treated. Successful implantation was achieved in 100%. The 30-day composite MAE rate was 8.9% including one cardiovascular death (2.2%) due to severe bleeding from a hemorrhagic stroke, one MI, and no need for re-intervention. MR≤1+ was achieved in 73% and ≤2+ in 98% of patients. 89% of patients were in NYHA class I/II (p < .001) with improvements in 6MWD (30 m; p = .054) and KCCQ (17 points; p < .001). CONCLUSIONS: Early results representing sites with first experience with the PASCAL repair system showed favorable 30-day outcomes in patients with DMR≥3+ at prohibitive surgical risk.

Asunto(s)

Implantación de Prótesis de Válvulas Cardíacas , Insuficiencia de la Válvula Mitral , Anciano de 80 o más Años , Implantación de Prótesis de Válvulas Cardíacas/efectos adversos , Humanos , Insuficiencia de la Válvula Mitral/diagnóstico por imagen , Insuficiencia de la Válvula Mitral/cirugía , Estudios Prospectivos , Calidad de Vida , Resultado del Tratamiento

RESUMEN

BACKGROUND: In the COAPT trial, transcatheter mitral valve repair with the MitraClip plus maximally tolerated guideline-directed medical therapy (GDMT) improved clinical outcomes compared with GDMT alone in symptomatic patients with heart failure (HF) and 3+ or 4+ secondary mitral regurgitation (SMR) due to left ventricular (LV) dysfunction. AIMS: In this COAPT substudy, we sought to evaluate two-year outcomes in HF patients with reduced LV ejection fraction (HFrEF; LVEF ≤40%) versus preserved LVEF (HFpEF; LVEF >40%) and in those with severe (LVEF ≤30%) versus moderate (LVEF >30%) LV dysfunction. METHODS: The principal effectiveness outcome was the two-year rate of death from any cause or HF hospitalisations (HFH). Subgroup analysis with interaction testing was performed according to baseline LVEF; 472 patients (82.1%) had HFrEF (mean LVEF 28.0%±6.2%; range 12% to 40%) and 103 (17.9%) had HFpEF (mean LVEF 46.6%±4.9%; range 41% to 65%), while 292 (50.7%) had severely depressed LVEF (LVEF ≤30%; mean LVEF 23.9%±3.8%) and 283 (49.3%) had moderately depressed LVEF (LVEF >30%; mean LVEF 39.0%±6.8%). RESULTS: The two-year rate of death or HFH was 56.7% in patients with HFrEF and 53.4% with HFpEF (HR 1.16, 95% CI: 0.86-1.57, p=0.32). MitraClip reduced the two-year rate of death or HFH in patients with HFrEF (HR 0.50, 95% CI: 0.39-0.65) and HFpEF (HR 0.60, 95% CI: 0.35-1.05), pint=0.55. MitraClip was consistently effective in reducing the individual endpoints of mortality and HFH, improving MR severity, quality of life, and six-minute walk distance in patients with HFrEF, HFpEF, LVEF ≤30%, and LVEF >30%. CONCLUSIONS: In the COAPT trial, among patients with HF and 3+ or 4+ SMR who remained symptomatic despite maximally tolerated GDMT, the MitraClip was consistently effective in improving survival and health status in patients with severe and moderate LV dysfunction and those with preserved LVEF.

Asunto(s)

Insuficiencia Cardíaca , Insuficiencia de la Válvula Mitral , Disfunción Ventricular Izquierda , Humanos , Válvula Mitral/diagnóstico por imagen , Válvula Mitral/cirugía , Insuficiencia de la Válvula Mitral/diagnóstico por imagen , Insuficiencia de la Válvula Mitral/cirugía , Calidad de Vida , Volumen Sistólico , Resultado del Tratamiento , Función Ventricular Izquierda

RESUMEN

BACKGROUND: In the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation) trial, transcatheter mitral valve repair (TMVr) resulted in fewer heart failure hospitalizations (HFHs) and lower mortality at 24 months in patients with heart failure (HF) with mitral regurgitation (MR) secondary to left ventricular dysfunction compared with guideline-directed medical therapy (GDMT) alone. OBJECTIVES: This study determined if these benefits persisted to 36 months and if control subjects who were allowed to cross over at 24 months derived similar benefit. METHODS: This study randomized 614 patients with HF with moderate-to-severe or severe secondary MR, who remained symptomatic despite maximally tolerated GDMT, to TMVr plus GDMT versus GDMT alone. The primary effectiveness endpoint was all HFHs through 24-month follow-up. Patients have now been followed for 36 months. RESULTS: The annualized rates of HFHs per patient-year were 35.5% with TMVr and 68.8% with GDMT alone (hazard ratio [HR]: 0.49; 95% confidence interval [CI]: 0.37 to 0.63; p < 0.001; number needed to treat (NNT) = 3.0; 95% CI: 2.4 to 4.0). Mortality occurred in 42.8% of the device group versus 55.5% of control group (HR: 0.67; 95% CI: 0.52 to 0.85; p = 0.001; NNT = 7.9; 95% CI: 4.6 to 26.1). Patients who underwent TMVr also had sustained 3-year improvements in MR severity, quality-of-life measures, and functional capacity. Among 58 patients assigned to GDMT alone who crossed over and were treated with TMVr, the subsequent composite rate of mortality or HFH was reduced compared with those who continued on GDMT alone (adjusted HR: 0.43; 95% CI: 0.24 to 0.78; p = 0.006). CONCLUSIONS: Among patients with HF and moderate-to-severe or severe secondary MR who remained symptomatic despite GDMT, TMVr was safe, provided a durable reduction in MR, reduced the rate of HFH, and improved survival, quality of life, and functional capacity compared with GDMT alone through 36 months. Surviving patients who crossed over to device treatment had a prognosis comparable to those originally assigned to transcatheter therapy. (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation [COAPT]; NCT01626079).

Asunto(s)

Insuficiencia Cardíaca/mortalidad , Insuficiencia Cardíaca/terapia , Insuficiencia de la Válvula Mitral/cirugía , Válvula Mitral/cirugía , Anciano , Cardiotónicos/uso terapéutico , Femenino , Hospitalización/estadística & datos numéricos , Humanos , Masculino , Insuficiencia de la Válvula Mitral/mortalidad , Calidad de Vida , Índice de Severidad de la Enfermedad

RESUMEN

BACKGROUND: The aim of this study was to examine the relationship between baseline left ventricular (LV) geometry and outcomes after transcatheter aortic valve replacement (TAVR). METHODS: Patients undergoing TAVR (n = 206) had baseline LV geometry classified as (1) concentric hypertrophy, (2) eccentric hypertrophy, (3) concentric remodeling, or (4) normal. Descriptive statistics, Kaplan-Meier time-to-event analysis, and Cox regression were performed. RESULTS: Distribution of baseline LV geometry differed between male and female patients (χ2 = 16.83, P = .001) but not at 1 month (χ2 = 2.56, P = .47) or 1 year (χ2 = 5.68, P = .13). After TAVR, a majority of patients with concentric hypertrophy evolved to concentric remodeling. Survival differed across LV geometry groups at 1 year (χ2[3] = 8.108, P = .044, log-rank test) and at 6.5 years (χ2[3] = 9.023, P = .029, log-rank test). Compared with patients with concentric hypertrophy, patients with normal geometry (hazard ratio, 2.25; 95% CI, 1.12-4.54; P = .023) and concentric remodeling (hazard ratio, 1.89; 95% CI, 1.12-3.17; P = .016) had higher rates of all-cause mortality. CONCLUSIONS: Baseline concentric hypertrophy confers a survival advantage after TAVR. Although baseline patterns of LV geometry appear gender specific (with women demonstrating more concentric hypertrophy), this difference resolves after TAVR.

Asunto(s)

Estenosis de la Válvula Aórtica , Reemplazo de la Válvula Aórtica Transcatéter , Válvula Aórtica/cirugía , Estenosis de la Válvula Aórtica/diagnóstico , Estenosis de la Válvula Aórtica/cirugía , Femenino , Humanos , Hipertrofia Ventricular Izquierda/diagnóstico por imagen , Masculino , Factores de Riesgo , Factores Sexuales , Función Ventricular Izquierda , Remodelación Ventricular

Asunto(s)

Infecciones por Coronavirus , Cardiopatías , Pandemias , Neumonía Viral , Reemplazo de la Válvula Aórtica Transcatéter , Betacoronavirus , COVID-19 , Consenso , Humanos , SARS-CoV-2 , Resultado del Tratamiento , Triaje

Asunto(s)

Cateterismo Cardíaco/instrumentación , Catéteres Cardíacos , Enfermedad de la Arteria Coronaria/diagnóstico , Reserva del Flujo Fraccional Miocárdico , Transductores de Presión , Enfermedad de la Arteria Coronaria/fisiopatología , Diseño de Equipo , Humanos , Miniaturización , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados

RESUMEN

BACKGROUND: The thin-strut SYNERGY stent has an abluminal everolimus-eluting bioabsorbable polymer coating designed to facilitate vascular healing and reduce risk of stent thrombosis. In the multicenter, randomized EVOLVE II trial (The EVOLVE II Clinical Trial to Assess the SYNERGY Stent System for the Treatment of Atherosclerotic Lesion[s]), SYNERGY was noninferior to the durable polymer PROMUS Element Plus everolimus-eluting stent for the primary end point of 1-year target lesion failure. Longer-term clinical follow-up will support the relative efficacy and safety of SYNERGY. METHODS: Patients with ≤3 native coronary lesions (reference vessel diameter ≥2.25-≤4.00 mm; length ≤34 mm) in ≤2 major epicardial vessels were randomized 1:1 to SYNERGY (N=838) or PROMUS Element Plus (N=846). EVOLVE II included a Diabetes substudy which pooled patients with diabetes mellitus from the randomized controlled trial (n=263) and from a sequential, single-arm substudy (N=203). RESULTS: The 5-year target lesion failure rate was 14.3% for SYNERGY and 14.2% for PROMUS Element Plus (P=0.91). Landmark analysis demonstrated similar rates of target lesion failure from discharge to 1-year (P=0.90) and from 1 to 5 years (P=0.94). Definite/probable stent thrombosis was infrequent in both arms (SYNERGY 0.7% versus PROMUS Element Plus 0.9%; P=0.75). There were no significant differences in the rates of cardiac death, myocardial infarction, or revascularization. Among patients with diabetes mellitus, the target lesion failure rate to 1-year was noninferior to a prespecified performance goal and to 5 years was 17.0%. CONCLUSIONS: SYNERGY demonstrated comparable outcomes to PROMUS Element Plus, with low rates of stent thrombosis and adverse events through 5 years of follow-up. Five-year clinical outcomes were favorable in patients with diabetes mellitus. These data support the long-term safety and effectiveness of SYNERGY in a broad range of patients. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01665053.

Asunto(s)

Implantes Absorbibles , Fármacos Cardiovasculares/administración & dosificación , Enfermedad de la Arteria Coronaria/terapia , Diabetes Mellitus/terapia , Stents Liberadores de Fármacos , Everolimus/administración & dosificación , Intervención Coronaria Percutánea/instrumentación , Polímeros , Anciano , Fármacos Cardiovasculares/efectos adversos , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/mortalidad , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/mortalidad , Everolimus/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/mortalidad , Diseño de Prótesis , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento

RESUMEN

BACKGROUND: Left ventricular filling pressure (LVFP) has been demonstrated to be a major predictor of poor cardiovascular outcomes. However, estimation of LVFP in patients with aortic stenosis is limited by the high prevalence of significant mitral annular calcification. The aim of this study was to investigate the effect of transcatheter aortic valve replacement on LVFP and the relationship of LVFP to mortality and hospitalization. METHODS: This was a single-center, retrospective study of 140 consecutive patients in sinus rhythm with significant mitral annular calcification who underwent transcatheter aortic valve replacement for severe aortic stenosis from May 2011 to June 2015. Mean follow-up duration was 3.06 ± 1.48 years (minimum, 2.4 years; maximum, 6.5 years). Diastolic function was assessed using recently proposed criteria for those with significant mitral annular calcification. High LVFP was defined as a mitral E/A ratio > 1.8 or a ratio of 0.8 to 1.8 and isovolumic relaxation time < 80 msec. RESULTS: At baseline, the proportion of patients with high LVFP was 40.7%, similar to 1 month (39.7%) (P = .86). However, the proportion of patients with high LVFP was significantly decreased at 1 year compared with those at baseline (26.9% vs 40.7%, P = .02). Multivariate analysis showed that high LVFP at baseline significantly increased risk for all-cause mortality compared with patients with normal LVFP (hazard ratio, 2.84; 95% confidence interval, 1.33-6.05; P = .007). CONCLUSIONS: High baseline LVFP was associated with a significantly increased all-cause mortality, and LVFP does not improve in the short term but only at 1 year after transcatheter aortic valve replacement.

Asunto(s)

Estenosis de la Válvula Aórtica/cirugía , Ventrículos Cardíacos/fisiopatología , Estenosis de la Válvula Mitral/etiología , Válvula Mitral/diagnóstico por imagen , Reemplazo de la Válvula Aórtica Transcatéter/métodos , Función Ventricular Izquierda/fisiología , Presión Ventricular/fisiología , Anciano de 80 o más Años , Estenosis de la Válvula Aórtica/complicaciones , Estenosis de la Válvula Aórtica/mortalidad , Calcinosis/complicaciones , Calcinosis/diagnóstico , Calcinosis/fisiopatología , Causas de Muerte/tendencias , Diástole , Ecocardiografía Doppler , Femenino , Estudios de Seguimiento , Ventrículos Cardíacos/diagnóstico por imagen , Humanos , Masculino , Estenosis de la Válvula Mitral/diagnóstico , Estenosis de la Válvula Mitral/mortalidad , Estenosis de la Válvula Mitral/fisiopatología , Estudios Retrospectivos , Tasa de Supervivencia/tendencias , Factores de Tiempo , Resultado del Tratamiento , Estados Unidos/epidemiología

RESUMEN

BACKGROUND: Among patients with heart failure who have mitral regurgitation due to left ventricular dysfunction, the prognosis is poor. Transcatheter mitral-valve repair may improve their clinical outcomes. METHODS: At 78 sites in the United States and Canada, we enrolled patients with heart failure and moderate-to-severe or severe secondary mitral regurgitation who remained symptomatic despite the use of maximal doses of guideline-directed medical therapy. Patients were randomly assigned to transcatheter mitral-valve repair plus medical therapy (device group) or medical therapy alone (control group). The primary effectiveness end point was all hospitalizations for heart failure within 24 months of follow-up. The primary safety end point was freedom from device-related complications at 12 months; the rate for this end point was compared with a prespecified objective performance goal of 88.0%. RESULTS: Of the 614 patients who were enrolled in the trial, 302 were assigned to the device group and 312 to the control group. The annualized rate of all hospitalizations for heart failure within 24 months was 35.8% per patient-year in the device group as compared with 67.9% per patient-year in the control group (hazard ratio, 0.53; 95% confidence interval [CI], 0.40 to 0.70; P<0.001). The rate of freedom from device-related complications at 12 months was 96.6% (lower 95% confidence limit, 94.8%; P<0.001 for comparison with the performance goal). Death from any cause within 24 months occurred in 29.1% of the patients in the device group as compared with 46.1% in the control group (hazard ratio, 0.62; 95% CI, 0.46 to 0.82; P<0.001). CONCLUSIONS: Among patients with heart failure and moderate-to-severe or severe secondary mitral regurgitation who remained symptomatic despite the use of maximal doses of guideline-directed medical therapy, transcatheter mitral-valve repair resulted in a lower rate of hospitalization for heart failure and lower all-cause mortality within 24 months of follow-up than medical therapy alone. The rate of freedom from device-related complications exceeded a prespecified safety threshold. (Funded by Abbott; COAPT ClinicalTrials.gov number, NCT01626079 .).

Asunto(s)

Implantación de Prótesis de Válvulas Cardíacas , Insuficiencia de la Válvula Mitral/cirugía , Anciano , Anciano de 80 o más Años , Terapia Combinada , Femenino , Insuficiencia Cardíaca/etiología , Insuficiencia Cardíaca/mortalidad , Insuficiencia Cardíaca/cirugía , Prótesis Valvulares Cardíacas/efectos adversos , Implantación de Prótesis de Válvulas Cardíacas/efectos adversos , Hospitalización/estadística & datos numéricos , Humanos , Análisis de Intención de Tratar , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Válvula Mitral/cirugía , Insuficiencia de la Válvula Mitral/tratamiento farmacológico , Insuficiencia de la Válvula Mitral/mortalidad , Intervención Coronaria Percutánea , Falla de Prótesis , Volumen Sistólico , Resultado del Tratamiento , Disfunción Ventricular Izquierda/etiología

RESUMEN

BACKGROUND: Measurement of fractional flow reserve (FFR) to guide coronary revascularization lags despite robust supportive data, partly because of the handling characteristics of traditional coronary pressure wires. An optical pressure-monitoring microcatheter, which can be advanced over a traditional coronary guidewire, facilitates FFR assessment but may underestimate pressure wire-derived FFR. METHODS AND RESULTS: In this prospective, multicenter trial, 169 patients underwent FFR assessment with a pressure wire alone and with a pressure microcatheter over the pressure wire. An independent core laboratory performed quantitative coronary angiography and evaluated all pressure tracings. The primary end point was the bias or difference between the microcatheter FFR and the pressure wire FFR, as assessed by Bland-Altman analysis. The mean difference between the microcatheter and the pressure wire-derived FFR values was -0.022 (95% confidence interval, -0.029 to -0.015). On multivariable analysis, reference vessel diameter (P=0.027) and lesion length (P=0.044) were independent predictors of bias between the 2 FFR measurements. When the microcatheter FFR was added to this model, it was the only independent predictor of bias (P<0.001). The mean FFR value from the microcatheter was significantly lower than from the pressure wire (0.81 versus 0.83; P<0.001). In 3% of cases (95% confidence interval, 1.3%-6.7%), there was clinically meaningful diagnostic discordance, with the FFR from the pressure wire >0.80 and that from the microcatheter <0.75. These findings were similar when including all 210 patients with site-reported paired FFR data. CONCLUSIONS: An optical, pressure-monitoring microcatheter measures lower FFR compared with a pressure wire, but the diagnostic impact appears to be minimal in most cases. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02577484.

Asunto(s)

Cateterismo Cardíaco/instrumentación , Catéteres Cardíacos , Enfermedad de la Arteria Coronaria/diagnóstico , Estenosis Coronaria/diagnóstico , Vasos Coronarios/fisiopatología , Reserva del Flujo Fraccional Miocárdico , Transductores de Presión , Anciano , Distribución de Chi-Cuadrado , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/fisiopatología , Estenosis Coronaria/fisiopatología , Vasos Coronarios/diagnóstico por imagen , Diseño de Equipo , Femenino , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Análisis Multivariante , Valor Predictivo de las Pruebas , Estudios Prospectivos , Reproducibilidad de los Resultados , Índice de Severidad de la Enfermedad , Procesamiento de Señales Asistido por Computador , Estados Unidos

RESUMEN

BACKGROUND: Drug eluting stents with durable polymers may be associated with hypersensitivity, delayed healing, and incomplete endothelialization, which may contribute to late/very late stent thrombosis and the need for prolonged dual antiplatelet therapy. Bioabsorbable polymers may facilitate stent healing, thus enhancing clinical safety. The SYNERGY stent is a thin-strut, platinum chromium metal alloy platform with an ultrathin bioabsorbable Poly(D,L-lactide-co-glycolide) abluminal everolimus-eluting polymer. We performed a multicenter, randomized controlled trial for regulatory approval to determine noninferiority of the SYNERGY stent to the durable polymer PROMUS Element Plus everolimus-eluting stent. METHODS AND RESULTS: Patients (n=1684) scheduled to undergo percutaneous coronary intervention for non-ST-segment-elevation acute coronary syndrome or stable coronary artery disease were randomized to receive either the SYNERGY stent or the PROMUS Element Plus stent. The primary end point of 12-month target lesion failure was observed in 6.7% of SYNERGY and 6.5% PROMUS Element Plus treated subjects by intention-to-treat (P=0.83 for difference; P=0.0005 for noninferiority), and 6.4% in both the groups by per-protocol analysis (P=0.0003 for noninferiority). Clinically indicated revascularization of the target lesion or definite/probable stent thrombosis were observed in 2.6% versus 1.7% (P=0.21) and 0.4% versus 0.6% (P=0.50) of SYNERGY versus PROMUS Element Plus-treated subjects, respectively. CONCLUSIONS: In this randomized trial, the SYNERGY bioabsorbable polymer everolimus-eluting stent was noninferior to the PROMUS Element Plus everolimus-eluting stent with respect to 1-year target lesion failure. These data support the relative safety and efficacy of SYNERGY in a broad range of patients undergoing percutaneous coronary intervention. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01665053.

Asunto(s)

Implantes Absorbibles/estadística & datos numéricos , Síndrome Coronario Agudo/cirugía , Materiales Biocompatibles/administración & dosificación , Implantación de Prótesis Vascular , Enfermedad de la Arteria Coronaria/cirugía , Everolimus/administración & dosificación , Intervención Coronaria Percutánea , Implantes Absorbibles/efectos adversos , Anciano , Materiales Biocompatibles/efectos adversos , Materiales Biocompatibles/química , Dioxanos , Stents Liberadores de Fármacos/estadística & datos numéricos , Everolimus/efectos adversos , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Compuestos de Platino , Polímeros/administración & dosificación , Polímeros/efectos adversos , Resultado del Tratamiento

RESUMEN

AIMS: We sought to determine the feasibility of conducting percutaneous coronary intervention (PCI) in high-risk acute coronary syndrome (ACS) patients utilising the REG1 system consisting of pegnivacogin, an aptameric factor IXa inhibitor, and its controlling agent anivamersen. METHODS AND RESULTS: In RADAR, ACS patients were randomised to pegnivacogin 1 mg/kg with 25%, 50%, 75%, or 100% anivamersen reversal or unfractionated heparin. Of the 640 patients randomised, 388 (61%) underwent PCI. Major modified ACUITY 30-day bleeding rates were 18% (25% reversal), 12% (50% reversal), 9% (75% reversal), and 7% (100% reversal), compared with 11% with heparin. The corresponding total bleeding rates were 68%, 39%, 35%, 34%, and 38% (heparin). Ischaemic events were less frequent in those receiving pegnivacogin versus heparin (4.4% vs. 7.3%, p=0.3). Thirty-day urgent TVR (1.1% vs. 0.9%, p=1.0), myocardial infarction (4.0% vs. 6.4%, p=0.3), and angiographic complication (11.2% and 10.8%, p=0.9) rates were similar with pegnivacogin and heparin. There were no incidences of clot formation on guidewires or catheters. CONCLUSIONS: High-level factor IXa inhibition in ACS patients undergoing PCI, with at least 50% reversal, has a favourable bleeding profile and appears effective at suppressing ischaemic events and thrombotic complications. Larger phase trials in PCI are warranted. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov NCT00932100.

Asunto(s)

Síndrome Coronario Agudo/tratamiento farmacológico , Anticoagulantes/uso terapéutico , Aptámeros de Nucleótidos/uso terapéutico , Hemorragia/inducido químicamente , Infarto del Miocardio/tratamiento farmacológico , Intervención Coronaria Percutánea , Anciano , Aptámeros de Nucleótidos/administración & dosificación , Femenino , Heparina/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Intervención Coronaria Percutánea/métodos , Resultado del Tratamiento

RESUMEN

In acute coronary syndromes, risk stratification is essential, particularly in patients without ST elevation, and is based upon clinical, electrocardiogram (ECG), and biological markers. Among them, recent and repeated attacks of angina, ST-segment deviation from baseline on the admission ECG as well as elevated markers of myonecrosis (particularly increased troponin levels), myocardial dysfunction (B-type natriuretic peptide [BNP]; N-terminal prohormone of BNP[NT-proBNP]), and inflammation (high-sensitivity C-reactive protein) are predictors of an adverse outcome. These variables can be incorporated into broader risk predictive scores, among which the TIMI (Thrombolysis in Myocardial Infarction) and GRACE (Global Registry of Acute Coronary Events) scores are the most widely used. Two general therapeutic strategies (routine invasive vs conservative or selective invasive) are employed in the treatment of non-ST-segment elevation acute coronary syndrome (NSTEACS). Evidence-based analysis and the current American College of Cardiology/American Heart Association/Society for Cardiac Angiography and Interventions clinical practice guidelines recommend an early invasive treatment strategy (8-24 h) for intermediate or high clinical risk patients with NSTEACS.

Asunto(s)

Síndrome Coronario Agudo/terapia , Revascularización Miocárdica/métodos , Síndrome Coronario Agudo/diagnóstico , Biomarcadores/sangre , Humanos , Selección de Paciente , Pronóstico , Medición de Riesgo/métodos , Factores de Tiempo

RESUMEN

OBJECTIVE: Prediabetic states are associated with accelerated atherosclerosis, but the availability of mouse models to study connections between these diseases has been limited. The aim of this study was to test the selective role of impaired insulin receptor/insulin receptor substrate-1 signaling on atherogenesis. METHODS AND RESULTS: To address the effects of impaired insulin signaling associated with hyperinsulinemia on atherosclerosis in the absence of obesity and hyperglycemia, we generated insulin receptor (Insr)/insulin receptor substrate-1 (Insr1) double heterozygous apolipoprotein (Apoe)-knockout mice (Insr(+/-)Irs1(+/-)Apoe(-/-)) mice. Insr(+/-)Irs1(+/-)Apoe(-/-) mice fed a Western diet for 15 weeks showed elevated levels of fasting insulin compared to Insr(+/+)Irs1(+/+)Apoe(-/-) mice. There were no significant differences in glucose, triglyceride, HDL, VLDL, cholesterol levels or free fatty acid in the plasma of Insr(+/-)Irs1(+/-)Apoe(-/-) and Insr(+/+)Irs1(+/+)Apoe(-/-) mice. Atherosclerotic lesions were increased in male (brachiocephalic artery) and female (aortic tree) Insr(+/-)Irs1(+/-)Apoe(-/-) compared to Insr(+/+)Irs1(+/+)Apoe(-/-) mice. Bone marrow transfer experiments demonstrated that nonhematopoietic cells have to be Insr(+/-)Irs1(+/-) to accelerate atherosclerosis. Impaired insulin signaling resulted in decreased levels of vascular phospho-eNOS, attenuated endothelium-dependent vasorelaxation and elevated VCAM-1 expression in aortas of Insr(+/-)Irs1(+/-)Apoe(-/-) mice. In addition, phospho-ERK and vascular smooth muscle cell proliferation were significantly elevated in aortas of Insr(+/-)Irs1(+/-)Apoe(-/-) mice. CONCLUSIONS: These results demonstrate that defective insulin signaling is involved in accelerated atherosclerosis in Insr(+/-)Irs1(+/-)Apoe(-/-) mice by promoting vascular dysfunction and inflammation.

Asunto(s)

Apolipoproteínas E/deficiencia , Aterosclerosis/genética , Aterosclerosis/fisiopatología , Heterocigoto , Proteínas Sustrato del Receptor de Insulina/genética , Receptor de Insulina/genética , Transducción de Señal/fisiología , Animales , Apolipoproteínas E/genética , Aterosclerosis/patología , Proliferación Celular , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Femenino , Proteínas Sustrato del Receptor de Insulina/fisiología , Sistema de Señalización de MAP Quinasas/fisiología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Músculo Liso Vascular/patología , Óxido Nítrico Sintasa de Tipo III/metabolismo , Receptor de Insulina/fisiología

Asunto(s)

Angioplastia de Balón/efectos adversos , Antiinflamatorios/administración & dosificación , Aterosclerosis/terapia , Músculo Liso Vascular/efectos de los fármacos , Nanopartículas , Prednisolona/administración & dosificación , Stents , Angioplastia de Balón/instrumentación , Animales , Antiinflamatorios/química , Antiinflamatorios/farmacología , Aterosclerosis/tratamiento farmacológico , Aterosclerosis/metabolismo , Aterosclerosis/patología , Benzamidinas/química , Proliferación Celular/efectos de los fármacos , Constricción Patológica , Modelos Animales de Enfermedad , Ácidos Grasos/química , Humanos , Arteria Ilíaca/efectos de los fármacos , Arteria Ilíaca/lesiones , Inyecciones Intravenosas , Liposomas , Metales , Músculo Liso Vascular/lesiones , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patología , Prednisolona/química , Prednisolona/farmacocinética , Diseño de Prótesis , Prevención Secundaria

RESUMEN

High levels of circulating soluble CD40 ligand (sCD40L) are frequently found in patients with hypercholesterolemia, diabetes, ischemic stroke, or acute coronary syndromes, predicting an increased rate of atherosclerotic plaque rupture and restenosis after coronary/carotid interventions. Clinical restenosis is characterized in part by exaggerated neointima formation, but the underlying mechanism remains incompletely understood. This study investigated the role of elevated sCD40L in neointima formation in response to vascular injury in an atherogenic animal model and explored the molecular mechanisms involved. apoE(-/-) mice fed a Western diet developed severe hypercholesterolemia, significant hyperglycemia, and high levels of plasma sCD40L. Neointima formation after carotid denudation injury was exaggerated in the apoE(-/-) mice. In vivo, blocking CD40L with anti-CD40L monoclonal antibody attenuated the early accumulation of Ly-6G(+) neutrophils and Gr-1(+) monocytes (at 3 days) and the late accumulation of Mac-2(+) macrophages (at 28 days) in the denudated arteries; it also reduced the exaggerated neointima formation at 28 days. In vitro, recombinant CD40L stimulated platelet P-selectin and neutrophil Mac-1 expression and platelet-neutrophil co-aggregation and adhesive interaction. These effects were abrogated by anti-CD40L or anti-Mac-1 monoclonal antibody. Moreover, recombinant CD40L stimulated neutrophil oxidative burst and release of matrix metalloproteinase-9 in vitro. We conclude that elevated sCD40L promotes platelet-leukocyte activation and recruitment and neointima formation after arterial injury, potentially through enhancement of platelet P-selectin and leukocyte Mac-1 expression and oxidative activity.

Asunto(s)

Ligando de CD40/metabolismo , Movimiento Celular , Leucocitos/patología , Antígeno de Macrófago-1/metabolismo , Enfermedades Vasculares/patología , Animales , Apolipoproteínas E/deficiencia , Arterias/metabolismo , Arterias/patología , Plaquetas/metabolismo , Antígenos CD40/metabolismo , Ligando de CD40/sangre , Ligando de CD40/genética , Adhesión Celular , Dieta , Humanos , Hiperplasia , Masculino , Metaloproteinasa 9 de la Matriz/metabolismo , Ratones , Ratones Endogámicos C57BL , Neutrófilos/enzimología , Neutrófilos/patología , Activación Plaquetaria , Estallido Respiratorio , Solubilidad , Propiedades de Superficie

RESUMEN

Percutaneous coronary intervention (PCI) has played an integral role in the therapeutic management strategies for patients who present with either acute coronary syndromes or stable angina pectoris. The COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) trial enrolled patients with chronic stable angina and at least 1 significant (> or =70%) angiographic coronary stenosis who were randomly assigned to an initial treatment of either PCI in conjunction with optimal medical therapy or optimal medical therapy alone. Although the initial management strategy of PCI did not reduce the risk of death, myocardial infarction, or other major cardiovascular events, improvement in angina-free status and a reduction in the requirement for subsequent revascularization was observed. An in-depth analysis of the COURAGE trial design and execution is provided.

Asunto(s)

Angina Inestable/terapia , Angioplastia Coronaria con Balón , Estenosis Coronaria/terapia , Ensayos Clínicos Controlados Aleatorios como Asunto , Antagonistas Adrenérgicos beta/uso terapéutico , Aspirina/uso terapéutico , Angiografía Coronaria , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Isquemia Miocárdica/terapia , Cooperación del Paciente , Inhibidores de Agregación Plaquetaria/uso terapéutico , Retratamiento , Resultado del Tratamiento