Asunto(s)
Cateterismo Cardíaco , Trasplante de Corazón , Implantación de Prótesis de Válvulas Cardíacas , Prótesis Valvulares Cardíacas , Insuficiencia de la Válvula Tricúspide , Válvula Tricúspide , Humanos , Persona de Mediana Edad , Cateterismo Cardíaco/instrumentación , Implantación de Prótesis de Válvulas Cardíacas/instrumentación , Implantación de Prótesis de Válvulas Cardíacas/efectos adversos , Diseño de Prótesis , Resultado del Tratamiento , Válvula Tricúspide/cirugía , Válvula Tricúspide/diagnóstico por imagen , Válvula Tricúspide/fisiopatología , Insuficiencia de la Válvula Tricúspide/cirugía , Insuficiencia de la Válvula Tricúspide/diagnóstico por imagen , Insuficiencia de la Válvula Tricúspide/fisiopatología , Insuficiencia de la Válvula Tricúspide/etiologíaRESUMEN
BACKGROUND: Current treatment recommendations for patients with heart failure and secondary mitral regurgitation include transcatheter edge-to-edge repair and mitral-valve surgery. Data from randomized trials comparing these therapies are lacking in this patient population. METHODS: In this noninferiority trial conducted in Germany, patients with heart failure and secondary mitral regurgitation who continued to have symptoms despite guideline-directed medical therapy were randomly assigned, in a 1:1 ratio, to undergo either transcatheter edge-to-edge repair (intervention group) or surgical mitral-valve repair or replacement (surgery group). The primary efficacy end point was a composite of death, hospitalization for heart failure, mitral-valve reintervention, implantation of an assist device, or stroke within 1 year after the procedure. The primary safety end point was a composite of major adverse events within 30 days after the procedure. RESULTS: A total of 210 patients underwent randomization. The mean (±SD) age of the patients was 70.5±7.9 years, 39.9% were women, and the mean left ventricular ejection fraction was 43.0±11.7%. Within 1 year, at least one of the components of the primary efficacy end point occurred in 16 of the 96 patients with available data (16.7%) in the intervention group and in 20 of the 89 with available data (22.5%) in the surgery group (estimated mean difference, -6 percentage points; 95% confidence interval [CI], -17 to 6; P<0.001 for noninferiority). A primary safety end-point event occurred in 15 of the 101 patients with available data (14.9%) in the intervention group and in 51 of the 93 patients with available data (54.8%) in the surgery group (estimated mean difference, -40 percentage points; 95% CI, -51 to -27; P<0.001). CONCLUSIONS: Among patients with heart failure and secondary mitral regurgitation, transcatheter edge-to-edge repair was noninferior to mitral-valve surgery with respect to a composite of death, rehospitalization for heart failure, stroke, reintervention, or implantation of an assist device in the left ventricle at 1 year. (Funded by Abbott Vascular; MATTERHORN ClinicalTrials.gov number, NCT02371512.).
RESUMEN
BACKGROUND: Two subtypes of atrial functional mitral regurgitation (AFMR) have been described, one is characterized by Carpentier type I and the other by Carpentier type IIIb leaflet motion. OBJECTIVES: The authors sought to analyze echocardiographic characteristics and outcomes of AFMR subtypes undergoing mitral valve transcatheter edge-to-edge repair (M-TEER). METHODS: Of 1,047 consecutive patients who underwent M-TEER, the authors identified those with isolated mitral annulus dilation (Carpentier I), termed AFMR-IAD, and those with atriogenic hamstringing characterized by restricted posterior mitral leaflet motion (Carpentier IIIb), termed AFMR-AH. Echocardiographic baseline characteristics and outcomes up to 1-year were analyzed. RESULTS: A total of 128 patients (12.2%) met AFMR criteria; 75 (58.6%) were identified as AFMR-IAD and 53 (41.4%) as AFMR-AH. AFMR-AH displayed greater left atrial and left ventricular volumes, greater mitral annulus, shorter and steeper posterior mitral leaflet, and more pronounced MR (all P < 0.05). Technical success was achieved in 98.7% (AFMR-IAD) and 86.8% (AFMR-AH) of patients (P = 0.009). At discharge, device detachments were exclusively observed in AFMR-AH (10.0%). MR ≤II was achieved in 95.6% and 78.6% at 30 days (P = 0.009) and in 93.0% and 74.1% at 1 year (P = 0.038) in patients with AFMR-IAD and AFMR-AH, respectively. AFMR-AH was associated with procedural failure (OR: 1.17 [95% CI: 1.00-1.38]; P = 0.045) at 30 days (43.4% vs 24.0%; P = 0.023) and all-cause mortality (HR: 2.54 [95% CI: 1.09-5.91]; P = 0.031) at 1 year (77% vs 92%, Kaplan-Meier estimated 1-year survival; P = 0.017). CONCLUSIONS: AFMR-AH shows worse procedural and clinical outcomes following M-TEER than AFMR-IAD. Thus, vigilance regarding this pathology is warranted and alternative mitral valve therapies might need to be considered.
RESUMEN
Background: Fibromas are rare primary benign cardiac tumours that can become symptomatic due to expansive growth, ventricular rhythm disturbances, and sudden cardiac death. Distinguishing fibromas from other (malign) cardiac masses is essential for accurate diagnosis and treatment. While there is some experience in management of cardiac fibromas in children, management of adult patients is unknown. Case summary: We present three cases of cardiac fibroma in adult patients diagnosed by echocardiography, cardiovascular magnetic resonance (CMR), and computed tomography (CT): (1) a 55-year-old male with a left ventricular fibroma leading to reduced left ventricular ejection fraction and mitral regurgitation. He had family history of sudden cardiac death, showed premature ventricular contractions (PVCs), and was treated with a primary preventive subcutaneous implantable cardiac defibrillator (S-ICD); (2) a 39-year-old male with right ventricular fibroma as an incidental finding. He complained of episodes of PVC. Due to a low PVC burden, decision was made against ablation and the patient was planned for follow-up; and (3) an 18-year-old female with left ventricular apex fibroma detected by CMR shortly after birth and confirmed by surgical biopsy. Being asymptomatic, conservative management was pursued and follow-up by CMR planned. Discussion: Cardiac fibromas can show various clinical presentations and hence being detected late in life. Given potential complications of surgical biopsy, diagnosis of cardiac fibromas is primarily based on echocardiography, CT, and CMR. Rhythm disturbances as PVCs are common. Due to association with ventricular arrhythmias and sudden cardiac death, preventive ICD placement might be appropriate on an individual basis.
RESUMEN
AIMS: Non-ischaemic cardiomyopathy (NICMP), an incurable disease terminating in systolic heart failure (heart failure with reduced ejection fraction [HFrEF]), causes immune activation, however anti-inflammatory treatment strategies so far have failed to alter the course of this disease. Myeloperoxidase (MPO), the principal enzyme in neutrophils, has cytotoxic, pro-fibrotic and nitric oxide oxidizing effects. Whether MPO inhibition ameliorates the phenotype in NICMP remains elusive. METHODS AND RESULTS: Prognostic information from MPO was derived from proteomic data of a large human cardiovascular health cohort (n = 3289). In a murine model of NICMP, we studied the mechanisms of MPO in this disease. In a case series, the MPO inhibitor was also evaluated in NICMP patients. Individuals with increased MPO revealed higher long-term mortality and worsening of heart failure, with impaired prognosis when MPO increased during follow-up. MPO infusion attenuated left ventricular ejection fraction (LVEF) in mice with NICMP, whereas genetic ablation or inhibition of MPO decreased systemic vascular resistance (SVR, 9.4 ± 0.7 mmHg*min/ml in NICMP vs. 6.7 ± 0.8 mmHg*min/ml in NICMP/Mpo-/-mice, n = 8, p = 0.006, data expressed as mean ± standard error of the mean) and improved left ventricular function (LVEF 30.3 ± 2.2% in NICMP vs. 40.7 ± 1.1% in NICMP/Mpo-/- mice, n = 16, p < 0.0001). Four patients diagnosed with NICMP and treated with an MPO inhibitor over 12 weeks showed increase in LVEF, decline in natriuretic peptides and improved 6-min walking distance. MPO inhibitor-related changes in the proteome of NICMP patients predicted reduced mortality when related to the changes in the proteome of the above referenced cardiovascular health cohort. CONCLUSIONS: Myeloperoxidase predicts long-term outcome in HFrEF and its inhibition elicits systemic anti-inflammatory and vasodilating effects which translate into improved left ventricular function. MPO inhibition deserves further evaluation as a novel, complementary treatment strategy for HFrEF.
RESUMEN
BACKGROUND: Severe pure aortic regurgitation (AR) carries a high mortality and morbidity risk, and it is often undertreated because of the inherent surgical risk. Transcatheter heart valves (THVs) have been used off-label in this setting with overall suboptimal results. The dedicated "purpose-built" Jena Valve Trilogy (JVT, JenaValve Technology) showed an encouraging performance, although it has never been compared to other THVs. OBJECTIVES: The aim of our study was to assess the performance of the latest iteration of THVs used off-label in comparison to the purpose-built JVT in inoperable patients with severe AR. METHODS: We performed a multicenter, retrospective registry with 18 participating centers worldwide collecting data on inoperable patients with severe AR of the native valve. A bicuspid aortic valve was the main exclusion criterion. The primary endpoints were technical and device success, 1-year all-cause mortality, and the composite of 1-year mortality and the heart failure rehospitalization rate. RESULTS: Overall, 256 patients were enrolled. THVs used off-label were used in 168 cases (66%), whereas JVT was used in 88 (34%). JVT had higher technical (81% vs 98%; P < 0.001) and device success rates (73% vs 95%; P < 0.001), primarily driven by significantly lower incidences of THV embolization (15% vs 1.1%; P < 0.001), the need for a second valve (11% vs 1.1%; P = 0.004), and moderate residual AR (10% vs 1.1%; P = 0.007). The permanent pacemaker implantation rate was comparable and elevated for both groups (22% vs 24%; P = 0.70). Finally, no significant difference was observed at the 1-year follow-up in terms of mortality (HR: 0.99; P = 0.980) and the composite endpoint (HR: 1.5; P = 0.355). CONCLUSIONS: The JVT platform has a better acute performance than other THVs when used off-label for inoperable patients with severe AR. A longer follow-up is conceivably needed to detect a possible impact on prognosis.
Asunto(s)
Insuficiencia de la Válvula Aórtica , Válvula Aórtica , Prótesis Valvulares Cardíacas , Diseño de Prótesis , Sistema de Registros , Índice de Severidad de la Enfermedad , Reemplazo de la Válvula Aórtica Transcatéter , Humanos , Insuficiencia de la Válvula Aórtica/fisiopatología , Insuficiencia de la Válvula Aórtica/mortalidad , Insuficiencia de la Válvula Aórtica/diagnóstico por imagen , Insuficiencia de la Válvula Aórtica/etiología , Femenino , Masculino , Estudios Retrospectivos , Anciano , Resultado del Tratamiento , Anciano de 80 o más Años , Factores de Riesgo , Válvula Aórtica/cirugía , Válvula Aórtica/fisiopatología , Válvula Aórtica/diagnóstico por imagen , Factores de Tiempo , Reemplazo de la Válvula Aórtica Transcatéter/efectos adversos , Reemplazo de la Válvula Aórtica Transcatéter/mortalidad , Reemplazo de la Válvula Aórtica Transcatéter/instrumentación , Readmisión del Paciente , Recuperación de la Función , Europa (Continente) , Insuficiencia Cardíaca/mortalidad , Insuficiencia Cardíaca/terapia , Insuficiencia Cardíaca/fisiopatología , Insuficiencia Cardíaca/diagnóstico , HemodinámicaRESUMEN
Background/Objectives: Previous trials reported comparable results with PASCAL and earlier MitraClip generations. Limited comparative data exist for more contemporary MitraClip generations, particularly the large MitraClip XT(R/W). We aimed to evaluate acute and 30-day outcomes in patients undergoing mitral valve transcatheter edge-to-edge repair (M-TEER) with one of the large devices, either PASCAL P10 or MitraClip XT(R/W) (3rd/4th generation). Methods: A total of 309 PASCAL-treated patients were matched by propensity score to 253 MitraClip-treated patients, resulting in 200 adequately balanced pairs. Procedural, clinical, and echocardiographic outcomes were collected for up to 30 days, including subgroup analysis for mitral regurgitation (MR) etiologies. Results: PASCAL and MitraClip patients were comparable regarding age (80 vs. 79 years), sex (female: 45.5% vs. 50.5%), and MR etiology (degenerative MR: n = 94, functional MR [FMR]: n = 96, mixed MR: n = 10 in each group). Technical success rates were comparable (96.5% vs. 96.0%; p > 0.999). At discharge, the mean gradient was higher (3.3 mmHg vs. 3.0 mmHg; p = 0.038), and the residual mitral valve orifice area was smaller in MitraClip patients (3.0 cm2 vs. 2.3 cm2; p < 0.001). At discharge, the reduction to MR ≤ 2+ was comparable (92.4% vs. 87.8%; p = 0.132). However, reduction to MR ≤ 1+ was more frequently observed in PASCAL patients (67.7% vs. 56.6%; p = 0.029), driven by the FMR subgroup (74.0% vs. 60.0%; p = 0.046). No difference was observed in 30-day mortality (p = 0.204) or reduction in NYHA-FC to ≤II (p > 0.999). Conclusions: Both M-TEER devices exhibited high and comparable rates of technical success and MR reduction to ≤2+. PASCAL may be advantageous in achieving MR reduction to ≤1+ in patients with FMR.
RESUMEN
BACKGROUND: We assessed the efficacy and safety of tadalafil, a phosphodiesterase type 5 inhibitor, in patients with heart failure with preserved ejection fraction and combined postcapillary and precapillary pulmonary hypertension. METHODS: In the double-blind PASSION study (Phosphodiesterase-5 Inhibition in Patients With Heart Failure With Preserved Ejection Fraction and Combined Post- and Pre-Capillary Pulmonary Hypertension), patients with heart failure with preserved ejection fraction and combined postcapillary and precapillary pulmonary hypertension were randomized 1:1 to receive tadalafil at a target dose of 40 mg or placebo. The primary end point was the time to the first composite event of adjudicated heart failure hospitalization or all-cause death. Secondary end points included all-cause mortality and improvements in New York Heart Association functional class or ≥10% improvement in 6-minute walking distance from baseline. RESULTS: Initially targeting 372 patients, the study was terminated early because of disruption in study medication supply. At that point, 125 patients had been randomized (placebo: 63; tadalafil: 62,). Combined primary end-point events occurred in 20 patients (32%) assigned to placebo and 17 patients (27%) assigned to tadalafil (hazard ratio, 1.02 [95% CI, 0.52-2.01]; P=0.95). There was a possible signal of higher all-cause mortality in the tadalafil group (hazard ratio, 5.10 [95% CI, 1.10-23.69]; P=0.04). No significant between-group differences were observed in other secondary end points. Serious adverse events occurred in 29 participants (48%) in the tadalafil group and 35 (56%) in the placebo group. CONCLUSIONS: The PASSION trial, terminated prematurely due to study medication supply disruption, does not support tadalafil use in patients with heart failure with preserved ejection fraction and combined postcapillary and precapillary pulmonary hypertension, with potential safety concerns and no observed benefits in primary and secondary end points. REGISTRATION: URL: https://www.clinicaltrialsregister.eu/; Unique identifier: 2017-003688-37. URL: https://drks.de; Unique identifier: DRKS -DRKS00014595.
Asunto(s)
Insuficiencia Cardíaca , Hipertensión Pulmonar , Inhibidores de Fosfodiesterasa 5 , Volumen Sistólico , Tadalafilo , Humanos , Tadalafilo/uso terapéutico , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/mortalidad , Insuficiencia Cardíaca/fisiopatología , Masculino , Femenino , Volumen Sistólico/efectos de los fármacos , Hipertensión Pulmonar/tratamiento farmacológico , Hipertensión Pulmonar/mortalidad , Hipertensión Pulmonar/fisiopatología , Anciano , Persona de Mediana Edad , Método Doble Ciego , Inhibidores de Fosfodiesterasa 5/uso terapéutico , Inhibidores de Fosfodiesterasa 5/efectos adversos , Resultado del TratamientoRESUMEN
BACKGROUND: A novel echocardiography-based definition of atrial functional tricuspid regurgitation (A-FTR) has shown superior outcomes in patients undergoing conservative treatment or tricuspid valve transcatheter edge-to-edge repair. Its prognostic significance for transcatheter tricuspid valve annuloplasty (TTVA) outcomes is unknown. OBJECTIVES: This study sought to investigate prognostic, clinical, and technical implications of A-FTR phenotype in patients undergoing TTVA. METHODS: This multicenter study investigated clinical and echocardiographic outcomes up to 1 year in 165 consecutive patients who underwent TTVA for A-FTR (characterized by the absence of tricuspid valve tenting, midventricular right ventricular [RV] dilatation, and impaired left ventricular ejection fraction) and nonatrial functional tricuspid regurgitation (NA-FTR). RESULTS: A total of 62 A-FTR and 103 NA-FTR patients were identified, with the latter exhibiting more pronounced RV remodeling. Compared to baseline, the tricuspid regurgitation (TR) grade at discharge was significantly reduced (P < 0.001 for both subtypes), and TR ≤II was achieved more frequently in A-FTR (85.2% vs 60.8%; P = 0.001). Baseline TR grade and A-FTR phenotype were independently associated with TR ≤II at discharge and 30 days. In multivariate analyses, A-FTR phenotype was a strong predictor (OR: 5.8; 95% CI: 2.1-16.1; P < 0.001) of TR ≤II at 30 days. At 1 year, functional class had significantly improved compared to baseline (both P < 0.001). One-year mortality was lower in A-FTR (6.5% vs 23.8%; P = 0.011) without significant differences in heart failure hospitalizations (13.3% vs 22.7%; P = 0.188). CONCLUSIONS: Direct TTVA effectively reduces TR in both A-FTR, which is a strong and independent predictor of achieving TR ≤II, and NA-FTR. Even though NA-FTR showed more RV remodeling at baseline, both phenotypes experienced similar symptomatic improvement, emphasizing the benefit of TTVA even in advanced disease stages. Additionally, phenotyping was of prognostic relevance in patients undergoing TTVA.
Asunto(s)
Cateterismo Cardíaco , Anuloplastia de la Válvula Cardíaca , Implantación de Prótesis de Válvulas Cardíacas , Insuficiencia de la Válvula Tricúspide , Válvula Tricúspide , Humanos , Insuficiencia de la Válvula Tricúspide/fisiopatología , Insuficiencia de la Válvula Tricúspide/cirugía , Insuficiencia de la Válvula Tricúspide/diagnóstico por imagen , Insuficiencia de la Válvula Tricúspide/mortalidad , Femenino , Masculino , Anciano , Válvula Tricúspide/fisiopatología , Válvula Tricúspide/diagnóstico por imagen , Válvula Tricúspide/cirugía , Cateterismo Cardíaco/instrumentación , Cateterismo Cardíaco/efectos adversos , Resultado del Tratamiento , Factores de Tiempo , Implantación de Prótesis de Válvulas Cardíacas/efectos adversos , Implantación de Prótesis de Válvulas Cardíacas/instrumentación , Implantación de Prótesis de Válvulas Cardíacas/mortalidad , Anuloplastia de la Válvula Cardíaca/efectos adversos , Anuloplastia de la Válvula Cardíaca/mortalidad , Anuloplastia de la Válvula Cardíaca/instrumentación , Factores de Riesgo , Anciano de 80 o más Años , Recuperación de la Función , Remodelación Ventricular , Función Ventricular Izquierda , Fenotipo , Función Ventricular Derecha , Estudios Retrospectivos , Persona de Mediana Edad , Volumen Sistólico , Valor Predictivo de las PruebasRESUMEN
BACKGROUND AND OBJECTIVES: In light of limited intensive care capacities and a lack of accurate prognostic tools to advise caregivers and family members responsibly, this study aims to determine whether automated cerebral CT (CCT) analysis allows prognostication after out-of-hospital cardiac arrest. METHODS: In this monocentric, retrospective cohort study, a supervised machine learning classifier based on an elastic net regularized logistic regression model for gray matter alterations on nonenhanced CCT obtained after cardiac arrest was trained using 10-fold cross-validation and tested on a hold-out sample (random split 75%/25%) for outcome prediction. Following the literature, a favorable outcome was defined as a cerebral performance category of 1-2 and a poor outcome of 3-5. The diagnostic accuracy was compared with established and guideline-recommended prognostic measures within the sample, that is, gray matter-white matter ratio (GWR), neuron-specific enolase (NSE), and neurofilament light chain (NfL) in serum. RESULTS: Of 279 adult patients, 132 who underwent CCT within 14 days of cardiac arrest with good imaging quality were identified. Our approach discriminated between favorable and poor outcomes with an area under the curve (AUC) of 0.73 (95% CI 0.59-0.82). Thus, the prognostic power outperformed the GWR (AUC 0.66, 95% CI 0.56-0.76). The biomarkers NfL, measured at days 1 and 2, and NSE, measured at day 2, exceeded the reliability of the imaging markers derived from CT (AUC NfL day 1: 0.87, 95% CI 0.75-0.99; AUC NfL day 2: 0.90, 95% CI 0.79-1.00; AUC NSE day: 2 0.78, 95% CI 0.62-0.94). DISCUSSION: Our data show that machine learning-assisted gray matter analysis of CCT images offers prognostic information after out-of-hospital cardiac arrest. Thus, CCT gray matter analysis could become a reliable and time-independent addition to the standard workup with serum biomarkers sampled at predefined time points. Prospective studies are warranted to replicate these findings.
Asunto(s)
Paro Cardíaco Extrahospitalario , Aprendizaje Automático Supervisado , Tomografía Computarizada por Rayos X , Humanos , Paro Cardíaco Extrahospitalario/diagnóstico por imagen , Masculino , Femenino , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Pronóstico , Sustancia Gris/diagnóstico por imagen , Sustancia Gris/patología , Encéfalo/diagnóstico por imagen , Estudios de CohortesRESUMEN
AIMS: Paradoxical low-flow, low-gradient aortic stenosis (pLFLG AS) may represent a diagnostic challenge, and its pathophysiology is complex. While left ventricular (LV) systolic function is preserved, right ventricular dysfunction (RVD) and consecutive LV underfilling may contribute to low-flow and reduced stroke volume index, and to adverse outcomes following transcatheter aortic valve implantation (TAVI). The aim of this study was to evaluate the potential role of RVD in pLFLG AS, and to assess the impact of pre-procedural RVD on clinical outcomes after TAVI in patients with pLFLG AS. METHODS AND RESULTS: Out of 2739 native AS patients, who received TAVI at the University of Cologne Heart Center between March 2013 and June 2021, 114 patients displayed pLFLG AS and were included in this study. Right ventricular (RV) function was assessed by transthoracic echocardiography, and a fractional area change (FAC) ≤35% and/or a tricuspid annular plane systolic excursion (TAPSE) <18 mm determined RVD. In addition, the TAPSE/systolic pulmonary artery pressure ratio (TAPSE/sPAP) was monitored as a measure of RV-pulmonary arterial (PA) coupling. An impaired FAC and TAPSE was present in 21.9% and 45.6% of patients, respectively, identifying RVD in 50.0%. RVD (p = 0.016), reduced FAC (p = 0.049), reduced TAPSE (p = 0.035) and impaired RV-PA coupling (TAPSE/sPAP ratio <0.31 mm/mmHg; p = 0.009) were associated with significantly higher all-cause mortality compared to patients with normal RV function. After adjustment for sex, age, body mass index, EuroSCORE II, previous myocardial infarction and mitral regurgitation, independent predictors for all-cause mortality were FAC, sPAP, TAPSE/sPAP ratio, right atrial area, RV diameter and tricuspid regurgitation. CONCLUSIONS: Adverse RV remodelling, RVD and impaired RV-PA coupling provide an explanation for low-flow and reduced stroke volume index in a subset of patients with pLFLG AS, and are associated with excess mortality after TAVI.
RESUMEN
Background/Objectives: Chronic total occlusion (CTO) is a prevalent finding in patients with coronary artery disease and is associated with increased mortality. Prior reports on the efficacy of percutaneous coronary intervention (PCI) compared to optimal medical therapy (OMT) were controversial. Following the emergence of recently published new evidence, a meta-analysis is warranted. The current meta-analysis assessed the effects of PCI compared to OMT in the treatment of CTO. Methods: A structured literature search was performed. Randomized controlled trials (RCTs) and non-randomized controlled studies of interventions were eligible. The primary outcome was an accumulated composite of cardiac mortality, myocardial infarction and target vessel/lesion revascularization events. Results: Thirty-two studies reporting on 11260 patients were included. Of these, 5712 (50.7%) were assigned to the PCI and 5548 (49.3%) were allocated to the OMT group. The primary outcome occurred in 14.6% of the PCI and 20.1% of the OMT group (12 trials, OR 0.66, 95% CI 0.50 to 0.88, p = 0.005, I2 = 67%). Subgrouping demonstrated a consistent reduction in the primary outcome for the PCI group in RCTs (six trials, OR 0.58, 95% CI 0.33 to 0.99, p = 0.05). The primary outcome reduction was irrespective of the study design, and it was replicable in sensitivity and subgroup analyses. Advantages in other outcomes were rather related to statistical pooling effects and dominated by observational data. Conclusions: CTO-PCI was associated with improved patient-oriented primary outcome compared to OMT in a study-level meta-analysis. This composite outcome effect was mainly driven by target vessel treatment, but a significant reduction in mortality and myocardial infarction was observed, irrespectively. These findings have hypothesis-generating implications. Future RCTs with adequate statistical power are eagerly awaited.
RESUMEN
Introduction: Myocardial infarction (MI) is a significant contributor to morbidity and mortality worldwide. Many individuals who survive the acute event continue to experience heart failure (HF), with inflammatory and healing processes post-MI playing a pivotal role. Polymorphonuclear neutrophils (PMN) and monocytes infiltrate the infarcted area, where PMN release high amounts of the heme enzyme myeloperoxidase (MPO). MPO has numerous inflammatory properties and MPO plasma levels are correlated with prognosis and severity of MI. While studies have focused on MPO inhibition and controlling PMN infiltration into the infarcted tissue, less is known on MPO's role in monocyte function. Methods and results: Here, we combined human data with mouse and cell studies to examine the role of MPO on monocyte activation and migration. We revealed a correlation between plasma MPO levels and monocyte activation in a patient study. Using a mouse model of MI, we demonstrated that MPO deficiency led to an increase in splenic monocytes and a decrease in cardiac monocytes compared to wildtype mice (WT). In vitro studies further showed that MPO induces monocyte migration, with upregulation of the chemokine receptor CCR2 and upregulation of inflammatory pathways identified as underlying mechanisms. Conclusion: Taken together, we identify MPO as a pro-inflammatory mediator of splenic monocyte recruitment and activation post-MI and provide mechanistic insight for novel therapeutic strategies after ischemic injury.
Asunto(s)
Monocitos , Infarto del Miocardio , Peroxidasa , Animales , Infarto del Miocardio/inmunología , Infarto del Miocardio/patología , Infarto del Miocardio/metabolismo , Peroxidasa/metabolismo , Monocitos/inmunología , Monocitos/metabolismo , Humanos , Ratones , Masculino , Movimiento Celular , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL , Femenino , Neutrófilos/inmunología , Neutrófilos/metabolismo , Ratones Noqueados , Receptores CCR2/metabolismo , Persona de Mediana EdadRESUMEN
Transcatheter aortic valve replacement (TAVR) has become an established alternative to surgical aortic valve replacement (AVR) for patients with moderate-to-high perioperative risk. Periprocedural TAVR complications decrease with growing expertise of implanters. Nevertheless, TAVR can still be accompanied by life-threatening adverse events such as intraprocedural cardiopulmonary resuscitation (CPR). This study analyzed the role of a reduced left-ventricular ejection fraction (LVEF) in intraprocedural complications during TAVR. Perioperative and postoperative outcomes from patients undergoing TAVR in a high-volume center (600 cases per year) were analyzed retrospectively with regard to their left-ventricular ejection fraction. Patients with a reduced left-ventricular ejection fraction (EF ≤ 40%) faced a significantly higher risk of perioperative adverse events. Within this cohort, patients were significantly more often in need of mechanical ventilation (35% vs. 19%). These patients also underwent CPR (17% vs. 5.8%), defibrillation due to ventricular fibrillation (13% vs. 5.4%), and heart-lung circulatory support (6.1% vs. 2.5%) more often. However, these intraprocedural adverse events showed no significant impact on postoperative outcomes regarding in-hospital mortality, stroke, or in-hospital stay. A reduced preprocedural LVEF is a risk factor for intraprocedural adverse events. With respect to this finding, the identified patient cohort should be treated with more caution to prevent intraprocedural incidents.
RESUMEN
BACKGROUND: Mitral transcatheter edge-to-edge repair (M-TEER) is a guideline-recommended treatment option for patients with severe symptomatic mitral regurgitation (MR). Outcomes with the PASCAL system in a post-market setting have not been established. OBJECTIVES: The authors report 30-day and 1-year outcomes from the MiCLASP (Transcatheter Repair of Mitral Regurgitation with Edwards PASCAL Transcatheter Valve Repair System) European post-market clinical follow-up study. METHODS: Patients with symptomatic, clinically significant MR were prospectively enrolled. The primary safety endpoint was clinical events committee-adjudicated 30-day composite major adverse event rate and the primary effectiveness endpoint was echocardiographic core laboratory-assessed MR severity at discharge compared with baseline. Clinical, echocardiographic, functional, and quality-of-life outcomes were assessed at 1 year. RESULTS: A total of 544 patients were enrolled (59% functional MR, 30% degenerative MR). The 30-day composite major adverse event rate was 6.8%. MR reduction was significant from baseline to discharge and sustained at 1 year with 98% of patients achieving MR ≤2+ and 82.6% MR ≤1+ (all P < 0.001 vs baseline). One-year Kaplan-Meier estimate for survival was 87.3%, and freedom from heart failure hospitalization was 84.3%. Significant functional and quality-of-life improvements were observed at 1 year, including 71.6% in NYHA functional class I/II, 14.4-point increase in Kansas City Cardiomyopathy Questionnaire score, and 24.2-m improvement in 6-minute walk distance (all P < 0.001 vs baseline). CONCLUSIONS: One-year outcomes of this large cohort from the MiCLASP study demonstrate continued safety and effectiveness of M-TEER with the PASCAL system in a post-market setting. Results demonstrate high survival and freedom from heart failure hospitalization, significant and sustained MR reduction, and improvements in symptoms, functional capacity, and quality of life.
Asunto(s)
Insuficiencia Cardíaca , Implantación de Prótesis de Válvulas Cardíacas , Insuficiencia de la Válvula Mitral , Humanos , Estudios de Seguimiento , 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 , Resultado del Tratamiento , Implantación de Prótesis de Válvulas Cardíacas/efectos adversos , Cateterismo Cardíaco/efectos adversosRESUMEN
Novel dedicated devices allow transcatheter treatment of pure aortic regurgitation (AR). The JenaValve Trilogy Heart Valve System was introduced as the first dedicated and on-label AR transcatheter aortic valve replacement system, implementing a locator-based and calcium-independent anchoring mechanism. Here, we present the first-in-human transcatheter aortic valve replacement for pure AR via a transcaval access in a patient with prohibitive alternative arterial accesses.
RESUMEN
AIMS: While invasively determined congestion holds mechanistic and prognostic significance in acute heart failure (HF), its role in patients with tricuspid regurgitation (TR)-related right- heart failure (HF) undergoing transcatheter tricuspid valve intervention (TTVI) is less well established. A comprehensive understanding of congestion patterns might aid in procedural planning, risk stratification, and the identification of patients who may benefit from adjunctive therapies before undergoing TTVI. The aim of this study was to investigate the role of congestion patterns in patients with severe TR and its implications for TTVI. METHODS AND RESULTS: Within a multicentre, international TTVI registry, 813 patients underwent right heart catheterization (RHC) prior to TTVI and were followed up to 24 months. The median age was 80 (interquartile range 76-83) years and 54% were women. Both mean right atrial pressure (RAP) and pulmonary capillary wedge pressure (PCWP) were associated with 2-year mortality on Cox regression analyses with Youden index-derived cut-offs of 17 mmHg and 19 mmHg, respectively (p < 0.01 for all). However, RAP emerged as an independent predictor of outcomes following multivariable adjustments. Pre-interventionally, 42% of patients were classified as euvolaemic (RAP <17 mmHg, PCWP <19 mmHg), 23% as having left-sided congestion (RAP <17 mmHg, PCWP ≥19 mmHg), 8% as right-sided congestion (RAP ≥17 mmHg, PCWP <19 mmHg), and 27% as bilateral congestion (RAP ≥17 mmHg, PCWP ≥19 mmHg). Patients with right-sided or bilateral congestion had the lowest procedural success rates and shortest survival times. Congestion patterns allowed for discerning specific patient's physiology and specifying prognostic implications of right ventricular to pulmonary artery coupling surrogates. CONCLUSION: In this large cohort of invasively characterized patients undergoing TTVI, congestion patterns involving right-sided congestion were associated with low procedural success and higher mortality rates after TTVI. Whether pre-interventional reduction of right-sided congestion can improve outcomes after TTVI should be established in dedicated studies.
Asunto(s)
Cateterismo Cardíaco , Sistema de Registros , Insuficiencia de la Válvula Tricúspide , Humanos , Femenino , Masculino , Insuficiencia de la Válvula Tricúspide/fisiopatología , Insuficiencia de la Válvula Tricúspide/complicaciones , Insuficiencia de la Válvula Tricúspide/diagnóstico , Anciano , Cateterismo Cardíaco/métodos , Anciano de 80 o más Años , Presión Esfenoidal Pulmonar/fisiología , Insuficiencia Cardíaca/terapia , Insuficiencia Cardíaca/fisiopatología , Índice de Severidad de la Enfermedad , Pronóstico , Implantación de Prótesis de Válvulas Cardíacas/métodos , Válvula Tricúspide/fisiopatología , Resultado del TratamientoRESUMEN
Purpose: The introduction of HER2-targeting antibody drug conjugates (ADCs) offers new treatment options for female breast cancer patients (FBC) expressing low levels of HER2 (HER2 low). No evidence was found that HER2 low describes a new FBC subtype. There is a lack of studies determining the impact of HER2 low in male breast cancer (MBC). In this study, we evaluate the prevalence of HER2 low in primary MBC and correlate the results with patient characteristics. Patients and Methods: In this study, histological specimens were obtained from 120 male patients diagnosed and treated for primary invasive breast cancer from 1995 to 2022 at Breast Cancer Units in Bergisch Gladbach, Chemnitz, and Zwickau, Germany. HER2 immunostaining and in situ hybridization were performed by central pathology and evaluated based on the ASCO/CAP guidelines. The correlation of expression of HER2 low with tumor biological characteristics and patient outcomes was investigated. Results: Out of all cases, four patients (3.3%) showed HER2 positivity (3+), 39 (32.5%) patients were classified as HER2 low, 7 (5.8%) were HER2 2+ (no amplification), 32 (26.7%) were HER2 1+, and 77 (64.2%) were classified as HER2 zero. Out of 77 HER2 zero cases, 47 tumors (61.0%) showed incomplete staining, with <10% of tumor cells classified as HER2 ultralow. No statistical correlation between HER2 low and tumor biological characteristics and patients' survival was found. Conclusion: Our findings show a notable, albeit lower, prevalence of HER2 low expression in primary MBC. However, tumors expressing HER2 low do not show specific tumor biological features to define a new breast cancer subtype in MBC. Our results suggest that a significant number of MBC patients could benefit from ADCs, as shown in FBC. Further studies are required to better understand HER2 low breast cancer, both generally and in MBC.
RESUMEN
BACKGROUND: Surgery remains the only recommended intervention for patients with native aortic regurgitation. A transcatheter therapy to treat patients at high risk for mortality and complications with surgical aortic valve replacement represents an unmet need. Commercial transcatheter heart valves in pure aortic regurgitation are hampered by unacceptable rates of embolisation and paravalvular regurgitation. The Trilogy transcatheter heart valve (JenaValve Technology, Irvine, CA, USA) provides a treatment option for these patients. We report outcomes with transfemoral transcatheter aortic valve implantation (TAVI) in patients with pure aortic regurgitation using this dedicated transcatheter heart valve. METHODS: The ALIGN-AR trial is a prospective, multicentre, single-arm study. We recruited symptomatic patients (aged ≥18 years) with moderate-to-severe or severe aortic regurgitation at high risk for mortality and complications after surgical aortic valve replacement at 20 US sites for treatment with the Trilogy transcatheter heart valve. The 30-day composite primary safety endpoint was compared for non-inferiority with a prespecified performance goal of 40·5%. The primary efficacy endpoint was 1-year all-cause mortality compared for non-inferiority with a performance goal of 25%. This trial is registered with ClinicalTrials.gov, NCT04415047, and is ongoing. FINDINGS: Between June 8, 2018, and Aug 29, 2022, we screened 346 patients. We excluded 166 (48%) patients and enrolled 180 (52%) patients with symptomatic aortic regurgitation deemed high risk by the heart team and independent screening committee assessments. The mean age of the study population was 75·5 years (SD 10·8), and 85 (47%) were female, 95 (53%) were male, and 131 (73%) were White. Technical success was achieved in 171 (95%) patients. At 30 days, four (2%) deaths, two (1%) disabling strokes, and two (1%) non-disabling strokes occurred. Using standard Valve Academic Research Consortium-2 definitions, the primary safety endpoint was achieved, with events occurring in 48 (27% [97·5% CI 19·2-34·0]) patients (pnon-inferiority<0·0001), with new pacemaker implantation in 36 (24%) patients. The primary efficacy endpoint was achieved, with mortality in 14 (7·8% [3·3-12·3]) patients at 1 year (pnon-inferiority<0·0001). INTERPRETATION: This study shows the safety and effectiveness of treating native aortic regurgitation using a dedicated transcatheter heart valve to treat patients with symptomatic moderate-to-severe or severe aortic regurgitation who are at high risk for mortality or complications after surgical aortic valve replacement. The observed short-term clinical and haemodynamic outcomes are promising as are signs of left ventricular remodelling, but long-term follow-up is necessary. FUNDING: JenaValve Technology.