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BACKGROUND: The role of catheter ablation in patients with symptomatic atrial fibrillation and end-stage heart failure is unknown. METHODS: We conducted a single-center, open-label trial in Germany that involved patients with symptomatic atrial fibrillation and end-stage heart failure who were referred for heart transplantation evaluation. Patients were assigned to receive catheter ablation and guideline-directed medical therapy or medical therapy alone. The primary end point was a composite of death from any cause, implantation of a left ventricular assist device, or urgent heart transplantation. RESULTS: A total of 97 patients were assigned to the ablation group and 97 to the medical-therapy group. The trial was stopped for efficacy by the data and safety monitoring board 1 year after randomization was completed. Catheter ablation was performed in 81 of 97 patients (84%) in the ablation group and in 16 of 97 patients (16%) in the medical-therapy group. After a median follow-up of 18.0 months (interquartile range, 14.6 to 22.6), a primary end-point event had occurred in 8 patients (8%) in the ablation group and in 29 patients (30%) in the medical-therapy group (hazard ratio, 0.24; 95% confidence interval [CI], 0.11 to 0.52; P<0.001). Death from any cause occurred in 6 patients (6%) in the ablation group and in 19 patients (20%) in the medical-therapy group (hazard ratio, 0.29; 95% CI, 0.12 to 0.72). Procedure-related complications occurred in 3 patients in the ablation group and in 1 patient in the medical-therapy group. CONCLUSIONS: Among patients with atrial fibrillation and end-stage heart failure, the combination of catheter ablation and guideline-directed medical therapy was associated with a lower likelihood of a composite of death from any cause, implantation of a left ventricular assist device, or urgent heart transplantation than medical therapy alone. (Funded by Else Kröner-Fresenius-Stiftung; CASTLE-HTx ClinicalTrials.gov number, NCT04649801.).
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Fibrilação Atrial , Ablação por Cateter , Insuficiência Cardíaca , Humanos , Antiarrítmicos/uso terapêutico , Fibrilação Atrial/complicações , Fibrilação Atrial/cirurgia , Ablação por Cateter/efeitos adversos , Ablação por Cateter/métodos , Alemanha , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/cirurgia , Transplante de Coração , Coração Auxiliar , Encaminhamento e Consulta , Resultado do TratamentoRESUMO
BACKGROUND AND AIMS: Risk stratification for mitral valve transcatheter edge-to-edge repair (M-TEER) is paramount in the decision-making process to appropriately select patients with severe secondary mitral regurgitation (SMR). This study sought to develop and validate an artificial intelligence-derived risk score (EuroSMR score) to predict 1-year outcomes (survival or survival + clinical improvement) in patients with SMR undergoing M-TEER. METHODS: An artificial intelligence-derived risk score was developed from the EuroSMR cohort (4172 and 428 patients treated with M-TEER in the derivation and validation cohorts, respectively). The EuroSMR score was validated and compared with established risk models. RESULTS: The EuroSMR risk score, which is based on 18 clinical, echocardiographic, laboratory, and medication parameters, allowed for an improved discrimination of surviving and non-surviving patients (hazard ratio 4.3, 95% confidence interval 3.7-5.0; P < .001), and outperformed established risk scores in the validation cohort. Prediction for 1-year mortality (area under the curve: 0.789, 95% confidence interval 0.737-0.842) ranged from <5% to >70%, including the identification of an extreme-risk population (2.6% of the entire cohort), which had a very high probability for not surviving beyond 1 year (hazard ratio 6.5, 95% confidence interval 3.0-14; P < .001). The top 5% of patients with the highest EuroSMR risk scores showed event rates of 72.7% for mortality and 83.2% for mortality or lack of clinical improvement at 1-year follow-up. CONCLUSIONS: The EuroSMR risk score may allow for improved prognostication in heart failure patients with severe SMR, who are considered for a M-TEER procedure. The score is expected to facilitate the shared decision-making process with heart team members and patients.
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Implante de Prótese de Valva Cardíaca , Insuficiência da Valva Mitral , Humanos , Insuficiência da Valva Mitral/cirurgia , Inteligência Artificial , Coração , Ecocardiografia , Fatores de Risco , Resultado do TratamentoRESUMO
BACKGROUND AND AIMS: Benefit of tricuspid regurgitation (TR) correction and timing of intervention are unclear. This study aimed to compare survival rates after surgical or transcatheter intervention to conservative management according to a TR clinical stage as assessed using the TRI-SCORE. METHODS: A total of 2,413 patients with severe isolated functional TR were enrolled in TRIGISTRY (1217 conservatively managed, 551 isolated tricuspid valve surgery, and 645 transcatheter valve repair). The primary endpoint was survival at 2 years. RESULTS: The TRI-SCORE was low (≤3) in 32%, intermediate (4-5) in 33%, and high (≥6) in 35%. A successful correction was achieved in 97% and 65% of patients in the surgical and transcatheter groups, respectively. Survival rates decreased with the TRI-SCORE in the three treatment groups (all P < .0001). In the low TRI-SCORE category, survival rates were higher in the surgical and transcatheter groups than in the conservative management group (93%, 87%, and 79%, respectively, P = .0002). In the intermediate category, no significant difference between groups was observed overall (80%, 71%, and 71%, respectively, P = .13) but benefit of the intervention became significant when the analysis was restricted to patients with successful correction (80%, 81%, and 71%, respectively, P = .009). In the high TRI-SCORE category, survival was not different to conservative management in the surgical and successful repair group (61% and 68% vs 58%, P = .26 and P = .18 respectively). CONCLUSIONS: Survival progressively decreased with the TRI-SCORE irrespective of treatment modality. Compared to conservative management, an early and successful surgical or transcatheter intervention improved 2-year survival in patients at low and, to a lower extent, intermediate TRI-SCORE, while no benefit was observed in the high TRI-SCORE category.
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Procedimentos Cirúrgicos Cardíacos , Implante de Prótese de Valva Cardíaca , Insuficiência da Valva Tricúspide , Humanos , Resultado do Tratamento , Cateterismo CardíacoRESUMO
Sleep-disordered breathing is common in patients with coronary artery disease undergoing coronary artery bypass grafting. Sleep-disordered breathing is associated with increased perioperative morbidity, arrhythmias (e.g. atrial fibrillation) and mortality. This study investigated the impact of sleep-disordered breathing on the postoperative course after coronary artery bypass grafting, including development of atrial fibrillation. This prospective single-centre cohort study included adults undergoing coronary artery bypass grafting. All were screened for sleep-disordered breathing (polygraphy) and atrial fibrillation (electrocardiogram) preoperatively; those with known sleep-disordered breathing or atrial fibrillation were excluded. Endpoints included new-onset atrial fibrillation, duration of mechanical ventilation, time in the intensive care unit, and postoperative infection. Regression analysis was performed to identify associations between sleep-disordered breathing and these outcomes. A total of 508 participants were included (80% male, median age 68 years). The prevalence of any (apnea-hypopnea index ≥ 5 per hr), moderate (apnea-hypopnea index = 15-30 per hr) and severe (apnea-hypopnea index > 30 per hr) sleep-disordered breathing was 52.9%, 9.3% and 10.2%, respectively. All-cause 30-day mortality was 0.98%. After adjustment for age and sex, severe sleep-disordered breathing was associated with longer respiratory ventilation support (crude odds ratio [95% confidence interval] 5.28 [2.18-12.77]; p < 0.001) and higher postoperative infection rates (crude odds ratio 3.32 [1.45-7.58]; p < 0.005), but not new-onset atrial fibrillation or mortality. New-onset atrial fibrillation was significantly associated with postoperative infection and prolonged hospital stay. The significant associations between sleep-disordered breathing and several adverse outcomes after coronary artery bypass grafting support the need for preoperative sleep-disordered breathing screening in individuals undergoing cardiac surgery.
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Cardiac decompensation is associated with worse prognosis in patients with heart failure. Reliable methods to predict cardiac decompensation events are not yet available. Sleep-disordered breathing (SDB) is a frequent comorbidity in heart failure, and it has been shown to correlate with heart failure severity. This prospective observational trial investigated SDB characteristics in patients with heart failure with the aim to identify patterns that may predict early cardiac decompensation. Patients with heart failure with diagnosed SDB and hospitalised for cardiac decompensation were prospectively enrolled and treated with adaptive servo-ventilation (ASV). SDB characteristics, daily body weight and clinical cardiac decompensation events were collected over a 1-year follow-up. Clinical events were categorised by an independent clinical event committee. A total of 43 patients were enrolled (81% male, mean [SD] age 71 [11] years, body mass index 30 kg/m2 , 95% New York Heart Association function class III or IV, mean [SD] left ventricular ejection fraction 37% [11%], median apnea-hypopnoea index [AHI] of 37 events/h). A total of 48 cardiac decompensation events were recorded during the 1-year study period. Respiratory rate was found to be significantly lower in patients with cardiac decompensation. The AHI and applied inspiratory pressure ASV-device support were significantly increased 10 days before a clinical cardiac decompensation event. Device usage was also found to be significantly decreased 2 nights before cardiac decompensation. Device-derived respiratory data in ASV therapy devices for SDB may therefore serve as a monitoring tool to predict early clinical cardiac decompensation events. Prediction and avoidance of cardiac decompensation, in turn, may attenuate serious health consequences in patients with heart failure.
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Insuficiência Cardíaca , Síndromes da Apneia do Sono , Humanos , Masculino , Idoso , Feminino , Volume Sistólico , Função Ventricular Esquerda , Resultado do Tratamento , Síndromes da Apneia do Sono/complicações , Síndromes da Apneia do Sono/diagnóstico , Síndromes da Apneia do Sono/terapia , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/terapiaRESUMO
AIMS: Current troponin cut-offs suggested for the post-operative workup of patients following coronary artery bypass graft (CABG) surgery are based on studies using non-high-sensitive troponin assays or are arbitrarily chosen. We aimed to identify an optimal cut-off and timing for a proprietary high-sensitivity cardiac troponin I (hs-cTnI) assay to facilitate post-operative clinical decision-making. METHODS AND RESULTS: We performed a retrospective analysis of all patients undergoing elective isolated CABG at our centre between January 2013 and May 2019. Of 4684 consecutive patients, 161 patients (3.48%) underwent invasive coronary angiography after surgery, of whom 86 patients (53.4%) underwent repeat revascularization. We found an optimal cut-off value for peak hs-cTnI of >13 000â ng/L [>500× the upper reference limit (URL)] to be significantly associated with repeat revascularization within 48â h after surgery, which was internally validated through random repeated sampling with 1000 iterations. The same cut-off also predicted 30-day major adverse cardiovascular events and all-cause mortality after a median follow-up of 3.1 years, which was validated in an external cohort. A decision tree analysis of serial hs-cTnI measurements showed no added benefit of hs-cTnI measurements in patients with electrocardiographic or echocardiographic abnormalities or haemodynamic instability. Likewise, early post-operative hs-cTnI elevations had a low yield for clinical decision-making and only later elevations (at 12-16â h post-operatively) using a threshold of 8000â ng/L (307× URL) were significantly associated with repeat revascularization with an area under the curve of 0.92 (95% confidence interval 0.88-0.95). CONCLUSION: Our data suggest that for hs-cTnI, higher cut-offs than currently recommended should be used in the post-operative management of patients following CABG.
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Ponte de Artéria Coronária , Infarto do Miocárdio , Troponina I , Biomarcadores/sangue , Tomada de Decisão Clínica , Humanos , Cuidados Pós-Operatórios , Estudos Retrospectivos , Troponina I/sangueRESUMO
Molecular processes underlying right ventricular (RV) dysfunction (RVD) and right heart failure (RHF) need to be understood to develop tailored therapies for the abatement of mortality of a growing patient population. Today, the armament to combat RHF is poor, despite the advancing identification of pathomechanistic processes. Mitochondrial dysfunction implying diminished energy yield, the enhanced release of reactive oxygen species, and inefficient substrate metabolism emerges as a potentially significant cardiomyocyte subcellular protagonist in RHF development. Dependent on the course of the disease, mitochondrial biogenesis, substrate utilization, redox balance, and oxidative phosphorylation are affected. The objective of this review is to comprehensively analyze the current knowledge on mitochondrial dysregulation in preclinical and clinical RVD and RHF and to decipher the relationship between mitochondrial processes and the functional aspects of the right ventricle (RV).
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Insuficiência Cardíaca , Mitocôndrias , Humanos , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/fisiopatologia , Mitocôndrias/metabolismo , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Oxirredução , Disfunção Ventricular Direita/tratamento farmacológico , Disfunção Ventricular Direita/fisiopatologia , Espécies Reativas de Oxigênio/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Antioxidantes/farmacologia , Antioxidantes/uso terapêuticoRESUMO
The causes of mitral regurgitation (MR) can be broadly divided into primary and secondary causes. Although primary MR is caused by degenerative alterations of the mitral valve and the mitral valve apparatus, secondary (functional) MR is multifactorial and related to dilation of the left ventricle and/or mitral annulus commonly resulting in concomitant restriction of the leaflets. Therefore, the treatment of secondary MR (SMR) is complex and includes guideline directed heart failure therapy along with surgical and transcatheter approaches that have shown effectiveness in certain subgroups. This review aims to provide insight into current advances in diagnosis and management of SMR.
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Insuficiência Cardíaca , Implante de Prótese de Valva Cardíaca , Insuficiência da Valva Mitral , Humanos , Insuficiência da Valva Mitral/diagnóstico , Insuficiência da Valva Mitral/etiologia , Insuficiência da Valva Mitral/cirurgia , Valva Mitral/diagnóstico por imagem , Valva Mitral/cirurgia , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/terapia , Cateterismo Cardíaco/métodos , Resultado do TratamentoRESUMO
OBJECTIVES: This study evaluates the impact of transcatheter tricuspid valve interventions (TTVI) on cognitive function (CF), quality of life (QOL), and exercise capacity in late-stage heart failure with preserved ejection fraction (HFpEF) and relevant tricuspid regurgitation (TR). BACKGROUND: Reduced cardiac output (CO) critically affects CF. Severe TR aggravates CO reduction in HFpEF, while TTVI has been demonstrated to re-establish CO to a significant extent. The effect of TTVI on CF of HFpEF patients has so far not been investigated. METHODS: Assessment of CF was performed using the standardized Montreal Cognitive Assessment test in 34 symptomatic HFpEF patients with at least severe TR before and 3 months after TTVI alongside echocardiographic examinations and assessment of exercise capacity and QOL. RESULTS: Median age of the patients was 81.0 [78.8; 83.0] years and 50.0% were female. CF was impaired in 67.6% of the patients. TR ≤ moderate was achieved in 94.1% of the cases. Overall CF improved significantly (from 20.6 ± 3.9 to 23.0 ± 4.4; p = 0.001). Particularly, significant improvements were identified in the executive function (p < 0.001) and memory (p = 0.008). In addition, linear regression analysis demonstrated a significant collinearity of improvement between executive function as well as memory and increased CO (ρ = 0.695; p < 0.001 and ρ = 0.628; p < 0.001, respectively). The walked distance and QOL also improved significantly 3 months after TTVI. CONCLUSION: Cognitive impairment is highly prevalent in HFpEF patients with severe TR. TTVI results in an improved CF, especially with regard to executive function and memory. These improvements also correlate with more efficient hemodynamics reflected by increased CO.
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Insuficiência Cardíaca , Implante de Prótese de Valva Cardíaca , Insuficiência da Valva Tricúspide , Humanos , Feminino , Masculino , Valva Tricúspide , Qualidade de Vida , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/terapia , Implante de Prótese de Valva Cardíaca/efeitos adversos , Implante de Prótese de Valva Cardíaca/métodos , Volume Sistólico , Cateterismo Cardíaco/efeitos adversos , Cateterismo Cardíaco/métodos , Resultado do Tratamento , Fatores de Tempo , Cognição , Índice de Gravidade de DoençaRESUMO
BACKGROUND: During viral-induced myocarditis, immune cells migrate towards the site of infection and secrete proteases, which in turn can act as sheddases by cleaving extracellular domains of transmembrane proteins. We were interested in the shedding of the Coxsackie- and adenovirus receptor (CAR) that acts as an entry receptor for both eponymous viruses, which cause myocarditis. CAR shedding by secreted immune proteases could result in a favourable outcome of myocarditis as CAR's extracellular domain would be removed from the cardiomyocytes' surface leading to decreased susceptibility to ongoing viral infections. METHODS AND RESULTS: In this work, matrix metalloproteinases and serine proteinases were screened for their proteolytic activity towards human CAR. Whereas matrix metalloproteinases, proteinase 3, and cathepsin G did not cleave human recombinant CAR or only within long incubation times, neutrophil elastase showed a distinct cleavage pattern of CAR's extracellular domain that was time- and dose-dependent. Neutrophil elastase cleaves CAR at its membrane-proximal immunoglobulin domain as we determined by nanoLC-MS/MS. Furthermore, neutrophil elastase treatment of cells reduced CAR surface levels as seen by flow cytometry and immunofluorescence microscopy. CONCLUSIONS: With this study, we show that CAR might be a target for shedding by neutrophil elastase.
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Elastase de Leucócito , Espectrometria de Massas em Tandem , Proteína de Membrana Semelhante a Receptor de Coxsackie e Adenovirus , Humanos , Receptores ViraisRESUMO
Cardiac amyloidosis (CAM), the most common cardiac storage disease is associated with significant changes in left-ventricular (LV) morphology and function. To gain particular insights into LV systolic longitudinal myocardial mechanics we investigated seven parameters derived by speckle-tracking-echocardiography (STE) in patients with confirmed CAM (n = 59). The results were compared with those of individuals with healthy heart (n = 150) and another primary myocardial disease with also thickened myocardium and severe diastolic and systolic LV-dysfunction (symptomatic LV-non-compaction-cardiomyopathy, LV-NC, n = 30). In addition to standard echocardiographical measures, the STE-derived data were evaluated and documented utilizing polar-diagrams to obtain overviews of longitudinal myocardial mechanics of the entire LV. Compared with healthy individuals, patients with CAM and LV-NC showed significantly reduced LV-ejection-fraction (EF), global longitudinal systolic peak-strain, strain-rate, and displacement. Pre-systolic stretch-index, post-systolic index, and the EF/global peak-longitudinal-strain-ratio (EF/S) were increased. In contrast to healthy-hearts and the LV-NC group only patients with CAM demonstrated significantly reduced time-to-peak systolic longitudinal strain and time-to-peak strain-rate. Although the level of the segmental values in longitudinal mechanics was significantly different between the groups, comparable intraventricular baso-apical parameter-gradients were found for systolic longitudinal peak-strain and strain-rate, pre-systolic-stretch-index, post-systolic-index, and peak systolic displacement. Compared to ATTR-amyloidosis (ATTR-CAM), patients with AL-amyloidosis (AL-CAM) demonstrated significantly lower end-diastolic and end-systolic LV-volumes, LV-mass-indices, relative apical strain, time-to-peak systolic longitudinal strain, and time-to-peak longitudinal strain-rate. CAM and LV-NC demonstrated altered myocardial mechanics with significantly different STE-derived echocardiographical parameters. ATTR-amyloidosis and AL-amyloidosis had at least significantly different time-to-peak strain, time-to-peak strain-rate and relative apical sparing values.
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Amiloidose , Amiloidose de Cadeia Leve de Imunoglobulina , Disfunção Ventricular Esquerda , Amiloidose/diagnóstico por imagem , Ventrículos do Coração , Humanos , Amiloidose de Cadeia Leve de Imunoglobulina/diagnóstico por imagem , Miocárdio , Sístole , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/etiologia , Função Ventricular EsquerdaRESUMO
Coronary artery bypass grafting (CABG) is the recommended type of revascularization procedure in patients with left main or three-vessel disease and is considered an alternative when percutaneous coronary intervention is not feasible. We evaluated registry data to obtain long-term outcome data.All patients ≤45 years in whom CABG was performed between 2009 and 2019 were selected from the Heart and Diabetes Center NRW, Germany. Cox regression analysis was applied to estimate the incidence risk of events after surgery.A total of 209 patients (81.8% male) were included. Mean (standard deviation) follow-up duration was 5.8 (3.1) years. The combined outcome of death, stroke, myocardial infarction, or repeated revascularization occurred in 31 patients (14.8%). Estimated mean time to event was 8.5 (standard error: 0.22) years. By the end of the follow-up period, 8 patients (3.8%) had died, among whom 2 (1.0%) died within 1 month after surgery, 1 (0.5%) within 1 year, 1 (0.5%) within 2 years, and 4 (1.9%) after 2 years.Risk factors independently associated with postsurgery events were angina pectoris CCS (Canadian Cardiovascular Society) class IV (adjusted hazard ratio [HR]: 4.954; 95% confidence interval [CI]: 1.322-18.563; p = 0.018) and STS (Society of Thoracic Surgeons) score (adjusted HR: 1.152 per scoring point; 95% CI: 1.040-1.276; p = 0.007).After performing CABG in patients ≤45 years, event-free long-term outcomes were observed in the majority of patients. Presence of angina pectoris CCS class IV and higher STS scores were independently associated with adverse postsurgery events.
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Doença da Artéria Coronariana , Stents Farmacológicos , Intervenção Coronária Percutânea , Angina Pectoris/etiologia , Canadá , Ponte de Artéria Coronária/efeitos adversos , Ponte de Artéria Coronária/métodos , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/cirurgia , Stents Farmacológicos/efeitos adversos , Feminino , Humanos , Masculino , Intervenção Coronária Percutânea/efeitos adversos , Prognóstico , Resultado do TratamentoRESUMO
Secondary (or functional) mitral regurgitation (SMR) occurs frequently in chronic heart failure (HF) with reduced left ventricular (LV) ejection fraction, resulting from LV remodelling that prevents coaptation of the valve leaflets. Secondary mitral regurgitation contributes to progression of the symptoms and signs of HF and confers worse prognosis. The management of HF patients with SMR is complex and requires timely referral to a multidisciplinary Heart Team. Optimization of pharmacological and device therapy according to guideline recommendations is crucial. Further management requires careful clinical and imaging assessment, addressing the anatomical and functional features of the mitral valve and left ventricle, overall HF status, and relevant comorbidities. Evidence concerning surgical correction of SMR is sparse and it is doubtful whether this approach improves prognosis. Transcatheter repair has emerged as a promising alternative, but the conflicting results of current randomized trials require careful interpretation. This collaborative position statement, developed by four key associations of the European Society of Cardiology-the Heart Failure Association (HFA), European Association of Percutaneous Cardiovascular Interventions (EAPCI), European Association of Cardiovascular Imaging (EACVI), and European Heart Rhythm Association (EHRA)-presents an updated practical approach to the evaluation and management of patients with HF and SMR based upon a Heart Team approach.
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OBJECTIVES AND BACKGROUND: Percutaneous edge-to-edge mitral valve (MV) repair (PMVR) is broadly applied in high-risk patients with relevant mitral regurgitation (MR). We investigated the incidence of cleft-like indentations (CLI) and their impact on PMVR. METHODS AND RESULTS: In a retrospective single center analysis including 263 patients undergoing PMVR with the MitraClip®-system between 11/2012 and 7/2016, MV anatomy was assessed by 3-dimensional transesophageal echocardiography. CLI were present in 37/263 patients (14.1%). Of these, 62.2% had 1 CLI, 27% had 2 CLI, and 10.8% had 3 CLI, mostly concerning segment P2 or P2/3 of the MV. Baseline characteristics were similarly distributed. Interestingly, most patients with CLI suffered from secondary MR (n = 29, 78%). The number of deployed MitraClips was higher in patients with CLI (2 [1.25-2] vs. 2 [1, 2], p = .035), whereas procedural as well as clinical success was similar: MR grade (1.2 vs. 1.5, p = .061), vena contracta width (4.2 vs. 4.5 mm, p = .293), dPmean (4.2 vs. 4.0 mmHg, p = .618) at discharge and NYHA class at 30 days did not differ between groups. Periprocedural complications were rare and equally distributed between groups. At 30 days, MR reduction persisted in patients with CLI (95.8% of these selected patients had a MR grade ≤ 2). CONCLUSIONS: CLI of the MV are common in patients undergoing PMVR, also when presenting mainly with secondary MR. While the number of clips needed to address MR is slightly higher in patients with CLI, procedural success rates appear not to be affected. PMVR seems to be a safe treatment option for patients with CLI.
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Implante de Prótese de Valva Cardíaca , Insuficiência da Valva Mitral , Ecocardiografia Transesofagiana , Implante de Prótese de Valva Cardíaca/efeitos adversos , Humanos , Valva Mitral/diagnóstico por imagem , Valva Mitral/cirurgia , Insuficiência da Valva Mitral/diagnóstico por imagem , Insuficiência da Valva Mitral/cirurgia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Left ventricular (LV) non-compaction cardiomyopathy (LV-NC) is rare, and data of segmental myocardial mechanics are largely lacking. We investigated myocardial longitudinal mechanics in adults with symptomatic LV-NC (n = 30) versus individuals with healthy hearts (n = 150). The contribution of compacted and non-compacted myocardial layer to systolic LV function has to be determined. METHODS: Seven parameters derived from speckle tracking echocardiography were evaluated and documented utilizing polar-diagrams to obtain overviews of myocardial mechanics of the entire LV. RESULTS: According to embryonal myocardial development, non-compacted myocardium was mostly located in mid-ventricular and apical segments of the free LV wall. LV ejection fraction was reduced in LV-NC (34 ± 15%, healthy 63 ± 5%, P < .0001). The compact wall layer in LV-NC demonstrated increasing systolic radial thickness (diastolic 5.6 ± 1.4, systolic 6.5 ± 1.4mm, P = .016), whereas the non-compacted layer remained unchanged or tended to decrease in thickness (diastolic 17.6 ± 5.3, systolic 16.0 ± 4.6mm, P = .22). Compared with heart-healthy individuals in LV-NC peak systolic longitudinal strain (healthy -21.1% vs. LV-NC -8.8, P < .0001), peak systolic longitudinal strain-rate (-1.23%/s vs. -0.64, P < .0001), and peak longitudinal displacement (12.1 vs. 5.6 mm, P < .0001) were reduced, while pre-systolic stretch index (1.31% vs. 3.2%, P < .0001) and post-systolic index (2.5% vs. 15.9%, P < .0001) increased. Time-to-peak longitudinal strain (371 vs. 389 ms, P = .065) and time-to-peak longitudinal strain rate (181 vs. 200 ms, P = .0677) did not differ significantly. In LV-NC, there were no significant differences between analyses using an interpolated endocardial border along the edges of the recesses and the endocardial edge of the compact wall layer. Hence, LV function appeared to depend only on the thin compact wall layer. CONCLUSION: In LV-NC, myocardial efficiency is severely diminished compared with healthy controls and LV function seemed to depend mainly on the compact myocardial wall layer.
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Cardiomiopatias , Disfunção Ventricular Esquerda , Adulto , Cardiomiopatias/diagnóstico por imagem , Humanos , Miocárdio , Volume Sistólico , Sístole , Disfunção Ventricular Esquerda/diagnóstico por imagem , Função Ventricular EsquerdaRESUMO
Nitro-oleic acid (NO2-OA), a nitric oxide (NO)- and nitrite (NO2-)-derived electrophilic fatty acid metabolite, displays anti-inflammatory and anti-fibrotic signaling actions and therapeutic benefit in murine models of ischemia-reperfusion, atrial fibrillation, and pulmonary hypertension. Muscle LIM protein-deficient mice (Mlp-/-) develop dilated cardiomyopathy (DCM), characterized by impaired left ventricular function and increased ventricular fibrosis at the age of 8 weeks. This study investigated the effects of NO2-OA on cardiac function in Mlp-/- mice both in vivo and in vitro. Mlp-/- mice were treated with NO2-OA or vehicle for 4 weeks via subcutaneous osmotic minipumps. Wildtype (WT) littermates treated with vehicle served as controls. Mlp-/- mice exhibited enhanced TGFß signalling, fibrosis and severely reduced left ventricular systolic function. NO2-OA treatment attenuated interstitial myocardial fibrosis and substantially improved left ventricular systolic function in Mlp-/- mice. In vitro studies of TGFß-stimulated primary cardiac fibroblasts further revealed that the anti-fibrotic effects of NO2-OA rely on its capability to attenuate fibroblast to myofibroblast transdifferentiation by inhibiting phosphorylation of TGFß downstream targets. In conclusion, we demonstrate a substantial therapeutic benefit of NO2-OA in a murine model of DCM, mediated by interfering with endogenously activated TGFß signaling.
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Anti-Inflamatórios/uso terapêutico , Cardiomiopatia Dilatada/tratamento farmacológico , Nitrocompostos/uso terapêutico , Ácidos Oleicos/uso terapêutico , Função Ventricular Esquerda/efeitos dos fármacos , Animais , Anti-Inflamatórios/farmacologia , Cardiomiopatia Dilatada/genética , Cardiomiopatia Dilatada/patologia , Avaliação Pré-Clínica de Medicamentos , Fibroblastos/metabolismo , Fibrose , Coração/efeitos dos fármacos , Proteínas com Domínio LIM/genética , Camundongos , Proteínas Musculares/genética , Miocárdio/metabolismo , Nitrocompostos/farmacologia , Ácidos Oleicos/farmacologia , Fator de Crescimento Transformador beta/metabolismoRESUMO
The Coxsackie- and adenovirus receptor (CAR) mediates homophilic cell-cell contacts and susceptibility to both human pathogenic viruses through its membrane-distal immunoglobulin domain. In the present study, we screened five missense variants of the human CAR gene for their influence on adenovector or Coxsackievirus entry into Chinese hamster ovary cells. The CAR variants facilitated virus internalisation to a similar extent as wild type CAR. This underlines CAR's presumed invariance and essential physiological role in embryogenesis.
Assuntos
Proteína de Membrana Semelhante a Receptor de Coxsackie e Adenovirus/genética , Infecções por Coxsackievirus/genética , Enterovirus/fisiologia , Mutação de Sentido Incorreto , Internalização do Vírus , Animais , Células CHO , Proteína de Membrana Semelhante a Receptor de Coxsackie e Adenovirus/química , Proteína de Membrana Semelhante a Receptor de Coxsackie e Adenovirus/metabolismo , Infecções por Coxsackievirus/metabolismo , Cricetulus , Interações Hospedeiro-Patógeno , Humanos , Domínios ProteicosRESUMO
PURPOSE: Central sleep apnea (CSA) is a highly common comorbidity in heart failure (HF) patients and is known to deteriorate quality of life and prognosis. Effective treatment options are scarce. Transvenous phrenic nerve stimulation (PNS) has been shown to be effective and safe in CSA treatment in HF. However, lead implantation may be difficult or fail due to anatomical or technical challenges. We report novel and innovative approaches applying different interventional techniques to enhance PNS implantation success, allowing otherwise missing CSA treatment. METHODS: Twenty-seven consecutive HF patients (86% male, mean age: 69 ± 11 years; reduced left ventricular ejection fraction in 16 patients (57%)) were included in this study who were unable to tolerate or had contraindications for mask-based therapy. We evaluated PNS total implantation success, procedural characteristics, and feasibility and success rates of intravascular interventions to facilitate PNS lead implantation in otherwise ineffective procedures. RESULTS: Seven lead implantation attempts (24%) required additional intravascular interventional action to facilitate successful implantation, mainly consisting of balloon angioplasties to allow optimal PNS lead placement. Two procedures remained unsuccessful and two patients underwent a second procedure due to stimulation side effects and lead fracture respectively. All over, no complications resulted from application of interventional techniques to achieve a 93% implantation success rate. CONCLUSION: Transvenous PNS lead placement for CSA treatment can be difficult and challenging. However, interventional intravascular techniques markedly increase implantation success and thereby allow application of this therapy for effective CSA treatment in most patients without additional complications.
Assuntos
Terapia por Estimulação Elétrica/métodos , Insuficiência Cardíaca/complicações , Nervo Frênico/fisiopatologia , Apneia do Sono Tipo Central/terapia , Idoso , Nível de Alerta/fisiologia , Feminino , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Polissonografia , Estudos Prospectivos , Apneia do Sono Tipo Central/complicações , Volume Sistólico , Resultado do TratamentoRESUMO
RATIONALE: Ventricular arrhythmias remain the leading cause of death in patients suffering myocardial ischemia. Myeloperoxidase, a heme enzyme released by polymorphonuclear neutrophils, accumulates within ischemic myocardium and has been linked to adverse left ventricular remodeling. OBJECTIVE: To reveal the role of myeloperoxidase for the development of ventricular arrhythmias. METHODS AND RESULTS: In different murine models of myocardial ischemia, myeloperoxidase deficiency profoundly decreased vulnerability for ventricular tachycardia on programmed right ventricular and burst stimulation and spontaneously as assessed by ECG telemetry after isoproterenol injection. Experiments using CD11b/CD18 integrin-deficient (CD11b-/-) mice and intravenous myeloperoxidase infusion revealed that neutrophil infiltration is a prerequisite for myocardial myeloperoxidase accumulation. Ventricles from myeloperoxidase-deficient (Mpo-/-) mice showed less pronounced slowing and decreased heterogeneity of electric conduction in the peri-infarct zone than wild-type mice. Expression of the redox-sensitive gap junctional protein Cx43 (Connexin 43) was reduced in the peri-infarct area of wild-type compared with Mpo-/- mice. In isolated wild-type cardiomyocytes, Cx43 protein content decreased on myeloperoxidase/H2O2 incubation. Mapping of induced pluripotent stem cell-derived cardiomyocyte networks and in vivo investigations linked Cx43 breakdown to myeloperoxidase-dependent activation of matrix metalloproteinase 7. Moreover, Mpo-/- mice showed decreased ventricular postischemic fibrosis reflecting reduced accumulation of myofibroblasts. Ex vivo, myeloperoxidase was demonstrated to induce fibroblast-to-myofibroblast transdifferentiation by activation of p38 mitogen-activated protein kinases resulting in upregulated collagen generation. In support of our experimental findings, baseline myeloperoxidase plasma levels were independently associated with a history of ventricular arrhythmias, sudden cardiac death, or implantable cardioverter-defibrillator implantation in a cohort of 2622 stable patients with an ejection fraction >35% undergoing elective diagnostic cardiac evaluation. CONCLUSIONS: Myeloperoxidase emerges as a crucial mediator of postischemic myocardial remodeling and may evolve as a novel pharmacological target for secondary disease prevention after myocardial ischemia.
Assuntos
Arritmias Cardíacas/metabolismo , Isquemia Miocárdica/metabolismo , Miócitos Cardíacos/metabolismo , Peroxidase/deficiência , Remodelação Ventricular/fisiologia , Animais , Arritmias Cardíacas/patologia , Células Cultivadas , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Isquemia Miocárdica/patologia , Miócitos Cardíacos/patologia , Técnicas de Cultura de ÓrgãosRESUMO
Objective- The leukocyte heme-enzyme MPO (myeloperoxidase) exerts proinflammatory effects on the vascular system primarily linked to its catalytic properties. Recent studies have shown that MPO, depending on its cationic charge, mediates neutrophil recruitment and activation. Here, we further investigated MPO's extracatalytic properties and its effect on endothelial glycocalyx (EG) integrity. Approach and Results- In vivo staining of murine cremaster muscle vessels with Alcian Blue 8GX provided evidence of an MPO-dependent decrease in anionic charge of the EG. MPO binding to the glycocalyx was further characterized using Chinese hamster ovary cells and its glycosaminoglycan mutants-pgsA-745 (mutant Chinese hamster ovary cells lacking heparan sulfate and chondroitin sulfate glycosaminoglycan) and pgsD-677 (mutant Chinese hamster ovary cells lacking heparan sulfate glycosaminoglycan), which revealed heparan sulfate as the main mediator of MPO binding. Further, EG integrity was assessed in terms of thickness using intravital microscopy of murine cremaster muscle. A significant reduction in EG thickness was observed on infusion of catalytically active MPO, as well as mutant inactive MPO and cationic polymer polylysine. Similar effects were also observed in wild-type mice after a local inflammatory stimulus but not in MPO-knockout mice. The reduction in EG thickness was reversed after removal of vessel-bound MPO, suggesting a possible physical collapse of the EG. Last, experiments with in vivo neutrophil depletion revealed that MPO also induced neutrophil-mediated shedding of the EG core protein, Sdc1 (syndecan-1). Conclusions- These findings provide evidence that MPO, via ionic interaction with heparan sulfate side chains, can cause neutrophil-dependent Sdc1 shedding and collapse of the EG structure.