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BACKGROUND: Whether vigorous exercise increases risk of ventricular arrhythmias for individuals diagnosed and treated for congenital long QT syndrome (LQTS) remains unknown. METHODS: The National Institutes of Health-funded LIVE-LQTS study (Lifestyle and Exercise in the Long QT Syndrome) prospectively enrolled individuals 8 to 60 years of age with phenotypic and/or genotypic LQTS from 37 sites in 5 countries from May 2015 to February 2019. Participants (or parents) answered physical activity and clinical events surveys every 6 months for 3 years with follow-up completed in February 2022. Vigorous exercise was defined as ≥6 metabolic equivalents for >60 hours per year. A blinded Clinical Events Committee adjudicated the composite end point of sudden death, sudden cardiac arrest, ventricular arrhythmia treated by an implantable cardioverter defibrillator, and likely arrhythmic syncope. A National Death Index search ascertained vital status for those with incomplete follow-up. A noninferiority hypothesis (boundary of 1.5) between vigorous exercisers and others was tested with multivariable Cox regression analysis. RESULTS: Among the 1413 participants (13% <18 years of age, 35% 18-25 years of age, 67% female, 25% with implantable cardioverter defibrillators, 90% genotype positive, 49% with LQT1, 91% were treated with beta-blockers, left cardiac sympathetic denervation, and/or implantable cardioverter defibrillator), 52% participated in vigorous exercise (55% of these competitively). Thirty-seven individuals experienced the composite end point (including one sudden cardiac arrest and one sudden death in the nonvigorous group, one sudden cardiac arrest in the vigorous group) with overall event rates at 3 years of 2.6% in the vigorous and 2.7% in the nonvigorous exercise groups. The unadjusted hazard ratio for experience of events for the vigorous group compared with the nonvigorous group was 0.97 (90% CI, 0.57-1.67), with an adjusted hazard ratio of 1.17 (90% CI, 0.67-2.04). The upper 95% one-sided confidence level extended beyond the 1.5 boundary. Neither vigorous or nonvigorous exercise was found to be superior in any group or subgroup. CONCLUSIONS: Among individuals diagnosed with phenotypic and/or genotypic LQTS who were risk assessed and treated in experienced centers, LQTS-associated cardiac event rates were low and similar between those exercising vigorously and those not exercising vigorously. Consistent with the low event rate, CIs are wide, and noninferiority was not demonstrated. These data further inform shared decision-making discussions between patient and physician about exercise and competitive sports participation. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02549664.
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Exercício Físico , Síndrome do QT Longo , Humanos , Síndrome do QT Longo/terapia , Síndrome do QT Longo/congênito , Síndrome do QT Longo/diagnóstico , Síndrome do QT Longo/fisiopatologia , Síndrome do QT Longo/mortalidade , Feminino , Masculino , Adolescente , Criança , Estudos Prospectivos , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Morte Súbita Cardíaca/prevenção & controle , Morte Súbita Cardíaca/epidemiologia , Fatores de RiscoRESUMO
BACKGROUND: Black Americans have a higher risk of nonischemic cardiomyopathy (NICM) than White Americans. We aimed to evaluate differences in the risk of tachyarrhythmias among patients with an implantable cardioverter-defibrillator (ICD). METHODS: The study population comprised 3895 ICD recipients in the United States enrolled in primary prevention ICD trials. Outcome measures included ventricular tachyarrhythmia (VTA), atrial tachyarrhythmia (ATA), ICD therapies, VTA burden (using Andersen-Gill recurrent event analysis), death, and the predicted benefit of the ICD. All events were adjudicated blindly. Outcomes were compared between self-reported Black patients versus White patients with cardiomyopathy (ischemic and NICM). RESULTS: Black patients were more likely to be female (35% versus 22%) and younger (57±12 versus 62±12 years) with a higher frequency of comorbidities. In NICM, Black patients had a higher rate of first VTA, fast VTA, ATA, and appropriate and inappropriate ICD therapy (VTA ≥170 bpm, 32% versus 20%; VTA ≥200 bpm, 22% versus 14%; ATA, 25% versus 12%; appropriate therapy, 30% versus 20%; and inappropriate therapy, 25% versus 11%; P<0.001 for all). Multivariable analysis showed that Black patients with NICM experienced a higher risk of all types of arrhythmia or ICD therapy (VTA ≥170 bpm, hazard ratio [HR] 1.71; VTA ≥200 bpm, HR 1.58; ATA, HR 1.87; appropriate therapy, HR 1.62; inappropriate therapy, HR 1.86; P≤0.01 for all), higher burden of tachyarrhythmias or therapies (VTA, HR 1.84; appropriate therapy, HR 1.84; P<0.001 for both), and a higher risk of death (HR 1.92; P=0.014). In contrast, in ischemic cardiomyopathy, the risk of all types of tachyarrhythmia, ICD therapy, or death was similar between Black patients and White patients. Both Black patients and White patients derived a significant and similar benefit from ICD implantation. CONCLUSIONS: Among patients with NICM with an ICD for primary prevention, Black patients compared with White patients had a high risk and burden of VTA, ATA, and ICD therapies with a lower survival rate. Nevertheless, the overall benefit of the ICD was maintained and was similar to that of White patients.
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Cardiomiopatias , Desfibriladores Implantáveis , Taquicardia Ventricular , Humanos , Feminino , Estados Unidos/epidemiologia , Masculino , Brancos , Morte Súbita Cardíaca/epidemiologia , Morte Súbita Cardíaca/etiologia , Morte Súbita Cardíaca/prevenção & controle , Fatores de Risco , Arritmias Cardíacas , Taquicardia Ventricular/terapia , Taquicardia Ventricular/epidemiologia , Prevenção PrimáriaRESUMO
INTRODUCTION: Wearable cardioverter defibrillator (WCD) is utilized in patients with assumed but not yet confirmed risk for sudden cardiac death (SCD). Many of these patients also present with atrial fibrillation (AF). However, the rate of WCD-detected ventricular or atrial arrhythmia events in this specific high-risk cohort is not well understood. METHODS: In WEARIT-II, the cumulative probability of any sustained or nonsustained VT/VF (WCD-treated and nontreated), and atrial/supraventricular arrhythmias during WCD use was assessed using the Kaplan-Meier method by prior AF, with comparisons by the log-rank test. The incidence of ventricular and atrial arrhythmia events were expressed as events per 100 patient-years, and were analyzed by prior AF using negative binomial regression. RESULTS: WEARIT-II enrolled 2000 patients, 557 (28%) of whom had AF before enrollment. Cumulative probability of any sustained or nonsustained WCD-detected VT/VF during WCD use was significantly higher among patients with a history of AF than without AF (6% vs. 3%, p = .001). Similarly, the recurrent rate of any sustained or nonsustained VT/VF was significantly higher in patients with prior AF versus no prior AF (131.5 events per 100 patient-years vs. 22.7 events per 100 patient-years, p = .001). Patients with prior AF also had a significantly higher burden of any WCD-detected atrial arrhythmias/SVT/inappropriate arrhythmias therapy (183.2 events per 100 patient-years vs. 74.8 events per 100 patient-years, p < .001). CONCLUSION: Our results demonstrate that patients with a history of AF wearing the WCD for risk assessment have a higher incidence of ventricular arrhythmias that may facilitate the decision making for ICD implantation.
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Fibrilação Atrial , Desfibriladores Implantáveis , Taquicardia Ventricular , Humanos , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/terapia , Fibrilação Atrial/complicações , Cardioversão Elétrica/efeitos adversos , Morte Súbita Cardíaca/epidemiologia , Morte Súbita Cardíaca/etiologia , Morte Súbita Cardíaca/prevenção & controle , Medição de Risco , Sistema de Registros , Desfibriladores Implantáveis/efeitos adversosRESUMO
INTRODUCTION: Heart failure patients with a history of atrial fibrillation (AF) and ventricular tachycardia/ventricular fibrillation (VT/VF) are known to have worse outcomes. However, there are limited data on the temporal relationship between development of these arrhythmias and the risk of subsequent congestive heart failure (CHF) exacerbation and death. METHODS: The study cohort comprised 5511 patients implanted with an implantable cardioverter-defibrillator (ICD) in landmark clinical trials (MADIT-II, MADIT-RISK, MADIT-CRT, MADIT-RIT, and RAID) who were in sinus rhythm at enrollment. Multivariate cox analysis was performed to evaluate the time-dependent association between development of in-trial device detected AF and VT/VF with subsequent CHF exacerbation and death. RESULTS: Multivariate analysis showed that AF occurrence and VT/VF occurrence were both associated with a similar magnitude of risk for subsequent CHF exacerbation (HR = 1.73 and 1.87 respectively, p < .001 for both). In contrast, only in-trial VT/VF was associated with a significant > two-fold increase in the risk of subsequent mortality (HR = 2.13, p < .001) whereas AF occurrence was not associated with a significant mortality increase after adjustment for in-trial VT/VF (HR = 1.36, p = .096). CONCLUSION: Our findings from a large cohort of ICD recipients enrolled in landmark clinical trials show that device detected AF and VT/VF can be used to identify patients with increased risk for CHF exacerbation and mortality. These findings suggest a need for early intervention in CHF patients who develop device-detected atrial and ventricular tachyarrhythmias.
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Fibrilação Atrial , Desfibriladores Implantáveis , Insuficiência Cardíaca , Taquicardia Ventricular , Humanos , Masculino , Feminino , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/fisiopatologia , Taquicardia Ventricular/mortalidade , Taquicardia Ventricular/terapia , Taquicardia Ventricular/etiologia , Idoso , Pessoa de Meia-Idade , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/fisiopatologia , Fibrilação Atrial/terapia , Fibrilação Atrial/mortalidade , Fatores de Risco , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/terapia , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Fibrilação Ventricular/diagnóstico , Fibrilação Ventricular/mortalidade , Fibrilação Ventricular/fisiopatologia , Fibrilação Ventricular/terapia , Fibrilação Ventricular/etiologia , Fatores de Tempo , Medição de Risco , Cardioversão Elétrica/instrumentação , Cardioversão Elétrica/efeitos adversos , Cardioversão Elétrica/mortalidade , Resultado do TratamentoRESUMO
BACKGROUND AND AIMS: De novo implanted cardiac resynchronization therapy with defibrillator (CRT-D) reduces the risk of morbidity and mortality in patients with left bundle branch block, heart failure and reduced ejection fraction (HFrEF). However, among HFrEF patients with right ventricular pacing (RVP), the efficacy of CRT-D upgrade is uncertain. METHODS: In this multicentre, randomized, controlled trial, 360 symptomatic (New York Heart Association Classes II-IVa) HFrEF patients with a pacemaker or implantable cardioverter defibrillator (ICD), high RVP burden ≥ 20%, and a wide paced QRS complex duration ≥ 150 ms were randomly assigned to receive CRT-D upgrade (n = 215) or ICD (n = 145) in a 3:2 ratio. The primary outcome was the composite of all-cause mortality, heart failure hospitalization, or <15% reduction of left ventricular end-systolic volume assessed at 12 months. Secondary outcomes included all-cause mortality or heart failure hospitalization. RESULTS: Over a median follow-up of 12.4 months, the primary outcome occurred in 58/179 (32.4%) in the CRT-D arm vs. 101/128 (78.9%) in the ICD arm (odds ratio 0.11; 95% confidence interval 0.06-0.19; P < .001). All-cause mortality or heart failure hospitalization occurred in 22/215 (10%) in the CRT-D arm vs. 46/145 (32%) in the ICD arm (hazard ratio 0.27; 95% confidence interval 0.16-0.47; P < .001). The incidence of procedure- or device-related complications was similar between the two arms [CRT-D group 25/211 (12.3%) vs. ICD group 11/142 (7.8%)]. CONCLUSIONS: In pacemaker or ICD patients with significant RVP burden and reduced ejection fraction, upgrade to CRT-D compared with ICD therapy reduced the combined risk of all-cause mortality, heart failure hospitalization, or absence of reverse remodelling.
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INTRODUCTION: Use of sodium glucose cotransporter 2 inhibitors (SGLT2i) was associated with a reduction in atrial fibrillation hospitalizations. Therefore, we aim to evaluate the effects of SGLT2i on atrial tachy-arrhythmias (ATA) in patients with cardiac implantable electronic devices (CIEDs). METHODS: All 13 888 consecutive patients implanted with a CIED in two tertiary medical centers were enrolled. Treatment with SGLT2i was assessed as a time dependent variable. The primary endpoint was the total number of ATA. Secondary endpoints included total number of ventricular tachy-arrhythmias (VTA), ATA and VTA, and death. All events were independently adjudicated blinded to the treatment. Multivariable propensity score modeling was performed. RESULTS: During a total follow-up of 24 442 patient years there were 62 725 ATA and 10 324 VTA events. Use of SGLT2i (N = 696) was independently associated with a significant 22% reduction in the risk of ATA (hazard ratio [HR] = 0.78 [95% confidence interval {CI} = 0.70-0.87]; p < .001); 22% reduction in the risk of ATA/VTA (HR = 0.78 [95% CI = 0.71-0.85]; p < .001); and with a 35% reduction in the risk of all-cause mortality (HR = 0.65 [95% CI = 0.45-0.92]; p = .015), but was not significantly associated with VTA risk (HR = 0.92 [95% CI = 0.80-1.06]; p = .26). SGLT2i were associated with a lower ATA burden in heart failure (HF) patients but not among diabetes patients (HF: HR = 0.68, 95% CI = 0.58-0.80, p < .001 vs. Diabetes: HR = 0.95, 95% CI = 0.86-1.05, p = .29; p < .001 for interaction between SGLT2i indication and ATA burden). CONCLUSION: Our real world findings suggest that in CIED HF patients, those with SGLT2i had a pronounced reduction in ATA burden and all-cause mortality when compared with those not on SGLT2i.
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Fibrilação Atrial , Diabetes Mellitus Tipo 2 , Insuficiência Cardíaca , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Fibrilação Atrial/complicações , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/terapia , Insuficiência Cardíaca/complicações , GlucoseRESUMO
BACKGROUND: Patients with heart failure (HF) represent a large population of patients who are at high risk for complications related to undiagnosed atrial fibrillation (AF). However, currently there are limited modalities available for early AF detection in this high-risk population. An implantable cardiac monitor (ICM) is inserted subcutaneously and can provide long-term arrhythmia information via remote monitoring. METHODS AND RESULTS: Confirm-AF is a prospective randomized, nonblinded, two arm, multicenter clinical trial to be performed in the United States, enrolling 477 patients with a history of HF hospitalization and left ventricular ejection fraction >35% from 30 medical sites. Patients will be randomized in a 2:1 fashion to undergo ICM implant with remote monitoring and symptom-triggered mobile app transmissions versus (vs.) Non-ICM management and follow-up. The primary objective of this trial is to compare the time to first detection of AF lasting > 5 min using an Abbott ICM compared to non-ICM monitoring in symptomatic HF patients. This article describes the design and analytic plan for the Confirm-AF trial. CONCLUSIONS: The Confirm-AF trial seeks to accurately define the burden of AF in high-risk HF patients with LVEF > 35% using an Abbott ICM. A finding showing significantly higher incidence of AF along with improved clinical outcomes with ICM monitoring is expected to have substantial clinical implications and may change the method of monitoring high-risk HF patients.
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Fibrilação Atrial , Insuficiência Cardíaca , Humanos , Estados Unidos , Fibrilação Atrial/complicações , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/epidemiologia , Estudos Prospectivos , Volume Sistólico , Eletrocardiografia , Eletrocardiografia Ambulatorial/métodos , Função Ventricular Esquerda , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/diagnósticoRESUMO
BACKGROUND: Percutaneous catheter ablation (CA) to achieve pulmonary vein isolation is an effective treatment for drug-refractory paroxysmal and persistent atrial fibrillation (AF). However, recurrence rates after a single AF ablation procedure remain elevated. Conventional management after CA ablation has mostly been based on clinical AF recurrence. However, continuous recordings with insertable cardiac monitors (ICMs) and patient-triggered mobile app transmissions post-CA can now be used to detect early recurrences of subclinical AF (SCAF). We hypothesize that early intervention following CA based on personalized ICM data can prevent the substrate progression that promotes the onset and maintenance of atrial arrhythmias. METHODS: This is a randomized, double-blind (to SCAF data), single-tertiary center clinical trial in which 120 patients with drug-refractory paroxysmal or persistent AF are planned to undergo CA with an ICM. Randomization will be to an intervention arm (n = 60) consisting of ICM-guided early intervention based on SCAF and patient-triggered mobile app transmissions versus a control arm (n = 60) consisting of a standard intervention protocol based on clinical AF recurrence validated by the ICM. Primary endpoint is AF burden, which will be assessed from ICMs at 15 months post-AF ablation. Secondary endpoints include healthcare utilization, functional capacity, and quality of life. CONCLUSION: We believe that ICM-guided early intervention will provide a novel, personalized approach to post-AF ablation management that will result in a significant reduction in AF burden, healthcare utilization, and improvements in functional capacity and quality of life.
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Fibrilação Atrial , Ablação por Cateter , Veias Pulmonares , Humanos , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/cirurgia , Qualidade de Vida , Eletrocardiografia , Resultado do Tratamento , Protocolos Clínicos , Ablação por Cateter/métodos , Recidiva , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND: Congenital Long QT Syndrome (LQTS) is a hereditary arrhythmic disorder. We aimed to assess the performance of current genetic variant annotation scores among LQTS patients and their predictive impact. METHODS: We evaluated 2025 patients with unique mutations for LQT1-LQT3. A patient-specific score was calculated for each of four established genetic variant annotation algorithms: CADD, SIFT, REVEL, and PolyPhen-2. The scores were tested for the identification of LQTS and their predictive performance for cardiac events (CE) and life-threatening events (LTE) and then compared with the predictive performance of LQTS categorization based on mutation location/function. Score performance was tested using Harrell's C-index. RESULTS: A total of 917 subjects were classified as LQT1, 838 as LQT2, and 270 as LQT3. The identification of a pathogenic variant occurred in 99% with CADD, 92% with SIFT, 100% with REVEL, and 86% with PolyPhen-2. However, none of the genetic scores correlated with the risk of CE (Harrell's C-index: CADD = 0.50, SIFT = 0.51, REVEL = 0.50, and PolyPhen-2 = 0.52) or LTE (Harrell's C-index: CADD = 0.50, SIFT = 0.53, REVEL = 0.54, and PolyPhen-2 = 0.52). In contrast, high-risk mutation categorization based on location/function was a powerful independent predictor of CE (HR = 1.88; p < .001) and LTE (HR = 1.89, p < .001). CONCLUSION: In congenital LQTS patients, well-established algorithms (CADD, SIFT, REVEL, and PolyPhen-2) were able to identify the majority of the causal variants as pathogenic. However, the scores did not predict clinical outcomes. These results indicate that mutation location/functional assays are essential for accurate interpretation of the risk associated with LQTS mutations.
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Eletrocardiografia , Síndrome do QT Longo , Humanos , Genótipo , Síndrome do QT Longo/diagnóstico , Síndrome do QT Longo/genética , Síndrome do QT Longo/complicaçõesRESUMO
BACKGROUND: The use of a Left Ventricular Assist Device (LVAD) in patients with advanced heart failure refractory to optimal medical management has progressed steadily over the past two decades. Data have demonstrated reduced LVAD efficacy, worse clinical outcome, and higher mortality for patients who experience significant ventricular tachyarrhythmia (VTA). We hypothesize that a novel prophylactic intra-operative VTA ablation protocol at the time of LVAD implantation may reduce the recurrent VTA and adverse events postimplant. METHODS: We designed a prospective, multicenter, open-label, randomized-controlled clinical trial enrolling 100 patients who are LVAD candidates with a history of VTA in the previous 5 years. Enrolled patients will be randomized in a 1:1 fashion to intra-operative VTA ablation (n = 50) versus conventional medical management (n = 50) with LVAD implant. Arrhythmia outcomes data will be captured by an implantable cardioverter defibrillator (ICD) to monitor VTA events, with a uniform ICD programming protocol. Patients will be followed prospectively over a mean of 18 months (with a minimum of 9 months) after LVAD implantation to evaluate recurrent VTA, adverse events, and procedural outcomes. Secondary endpoints include right heart function/hemodynamics, healthcare utilization, and quality of life. CONCLUSION: The primary aim of this first-ever randomized trial is to assess the efficacy of intra-operative ablation during LVAD surgery in reducing VTA recurrence and improving clinical outcomes for patients with a history of VTA.
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Desfibriladores Implantáveis , Insuficiência Cardíaca , Coração Auxiliar , Taquicardia Ventricular , Humanos , Coração Auxiliar/efeitos adversos , Estudos Prospectivos , Qualidade de Vida , Fatores de Risco , Eletrocardiografia , Arritmias Cardíacas , Taquicardia Ventricular/etiologia , Resultado do TratamentoRESUMO
BACKGROUND: There are limited data regarding racial disparities in outcomes after left ventricular assist device (LVAD) implantation. The purpose of this study was to compare clinical characteristics and the burden of readmissions by race among patients with LVAD. METHODS: The study population included 461 patients implanted with LVADs at the University of Rochester Medical Center, NY from May 2008 to March 2020. Patients were stratified by race as White patients (N = 396 [86%]) and Black patients (N = 65 [14%]). The Anderson-Gill recurrent regression analysis was used to assess the independent association between race and the total number of admissions after LVAD implant during an average follow-up of 2.45 ± 2.30 years. RESULTS: Black patients displayed significant differences in baseline clinical characteristics compared to White patients, including a younger age, a lower frequency of ischemic etiology, and a higher baseline serum creatinine. Black patients had a significantly higher burden of readmissions after LVAD implantation as compared with White patients 10 versus 7 (average number of hospitalizations per patient at 5 years of follow-up, respectively) translated into a significant 39% increased risk of recurrent readmissions after multivariate adjustment (Hazard ratio 1.39, 95% CI; 1.07-1.82, p 0.013). CONCLUSION: Black LVAD patients experience an increased burden of readmissions compared with White patients, after adjustment for baseline differences in demographics and clinical characteristics. Future studies should assess the underlying mechanisms for this increased risk including the effect of social determinants of health on the risk of readmissions in LVAD recipients.
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Insuficiência Cardíaca , Coração Auxiliar , Readmissão do Paciente , Fatores Raciais , Humanos , Brancos , Negro ou Afro-Americano , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Insuficiência Cardíaca/epidemiologia , Estudos RetrospectivosRESUMO
Sudden cardiac death (SCD) in patients with ischemic heart disease remains a leading cause of death. Prediction of who is at risk is based on the left ventricular ejection fraction (EF). However, the majority of victims of SCD have a normal EF, and the majority of patients implanted with an implantable cardioverter- defibrillator based on their EF are never treated by their device. Several parameters could allow better prediction of SCD. Several signs on the ECG and Periodic Repolarization Dynamics have been associated with increased risk. Elevated serum biomarkers such as pro-B type natriuretic peptides and serum soluble suppression of tumorigenicity 2 protein (sST2) are predictive of SCD. On the echocardiogram, global longitudinal strain, speckle tracking and relative wall thickness have been implicated. Programmed ventricular stimulation studies and cardiac magnetic resonance are promising modalities that could be further investigated. In conclusion, the EF is an imperfect tool for predicting SCD. Using the modalities reviewed, a model could be created for better prediction of patients at risk.
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OBJECTIVE: The platelet phenotype in certain patients and clinical contexts may differ from healthy conditions. We evaluated platelet activation through specific receptors in healthy men and women, comparing this to patients presenting with ST-segment-elevation myocardial infarction and non-ST-segment-elevation myocardial infarction. Approach and Results: We identified independent predictors of platelet activation through certain receptors and a murine MI model further explored these findings. Platelets from healthy women and female mice are more reactive through PARs (protease-activated receptors) compared with platelets from men and male mice. Multivariate regression analyses revealed male sex and non-ST-segment-elevation myocardial infarction as independent predictors of enhanced PAR1 activation in human platelets. Platelet PAR1 signaling decreased in women and increased in men during MI which was the opposite of what was observed during healthy conditions. Similarly, in mice, thrombin-mediated platelet activation was greater in healthy females compared with males, and lesser in females compared with males at the time of MI. CONCLUSIONS: Sex-specific signaling in platelets seems to be a cross-species phenomenon. The divergent platelet phenotype in males and females at the time of MI suggests a sex-specific antiplatelet drug regimen should be prospectively evaluated.
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Plaquetas/metabolismo , Infarto do Miocárdio sem Supradesnível do Segmento ST/sangue , Ativação Plaquetária , Receptor PAR-1/sangue , Infarto do Miocárdio com Supradesnível do Segmento ST/sangue , Idoso , Animais , Plaquetas/efeitos dos fármacos , Estudos de Casos e Controles , Modelos Animais de Doenças , Feminino , Humanos , Masculino , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Fenótipo , Ativação Plaquetária/efeitos dos fármacos , Fatores Sexuais , Transdução de Sinais , Trombina/farmacologiaRESUMO
AIMS: To evaluate the benefit of speckle tracking radial strain imaging (STRSI)-guided left ventricular (LV) lead (LVL) positioning in cardiac resynchronization therapy (CRT) in patients (pts) with ischaemic cardiomyopathy with CRT indication. METHODS AND RESULTS: We conducted a prospective randomized controlled trial. Patients were enrolled in nine centres with 2:1 randomization into two groups (guided vs. control). Patients underwent STRSI to identify the optimal LV position from six LV segments at midventricular level. Implantation via STRSI was attempted for recommended segment in the guided group only. Follow-up included echocardiography (6 months) and clinical evaluation (6 and 12 months). The primary endpoint was comparison % reduction in LV end-systolic volume at 6 months with baseline. Secondary endpoints included hospitalizations for heart failure and death, and improvement in additional echocardiographic measurements and quality of life score. A total of 172 patients (115 guided vs. 57 control) were enrolled. In the guided group, 60% of the implanted LV leads were adjudicated to be successfully located at the recommended segment, whereas in the control group 44% reached the best STRSI determined segment. There was no difference between the groups in any of the primary or secondary endpoints at 6 and 12 months. CONCLUSION: Our findings suggest that echo-guided implantation of an LV lead using STRSI does not improve the clinical or echocardiographic response compared with conventional implantation.
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Terapia de Ressincronização Cardíaca , Cardiomiopatias , Insuficiência Cardíaca , Isquemia Miocárdica , Terapia de Ressincronização Cardíaca/efeitos adversos , Terapia de Ressincronização Cardíaca/métodos , Dispositivos de Terapia de Ressincronização Cardíaca , Cardiomiopatias/diagnóstico por imagem , Cardiomiopatias/terapia , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/terapia , Ventrículos do Coração , Humanos , Isquemia Miocárdica/complicações , Isquemia Miocárdica/diagnóstico por imagem , Isquemia Miocárdica/terapia , Estudos Prospectivos , Qualidade de Vida , Resultado do TratamentoRESUMO
OBJECTIVES: The objective of this single-center, pilot, prospective, and historical control study is to evaluate safety and feasibility outcomes associated with left atrial appendage exclusion (LAAE) concomitant with left ventricular assist device (LVAD) implantation via less invasive surgery (LIS) as a stroke prevention strategy. METHODS: A predefined number of 30 eligible subjects scheduled for LIS LVAD with LAAE were enrolled in the prospective arm between January 2020 and February 2021. Eligible retrospective LIS LVAD patients without LAAE were propensity-matched in a 1:1 ratio with the prospective arm subjects. The primary study objectives were to evaluate the safety, feasibility, and efficacy of the LAAE concomitant with LIS LVAD. RESULTS: Preoperative characteristics of patients in the Non-LAAE and LAAE groups were similar. LAAE was successfully excluded in all prospective patients (100%). Primary safety endpoints of chest tube output within the first 24 postoperative hours, Reoperation for bleeding within 48 h, and index hospitalization mortality demonstrated comparable safety of LAAE versus Non-LAAE with LIS LVAD. Cox proportional hazard regression demonstrated that LAAE with LIS LVAD was associated with 37% and 49% reduction in the risk of stroke and disabling stroke, respectively (p > .05). CONCLUSION: Results from our pilot study demonstrated the safety and feasibility of LAAE concomitant with LIS LVAD as a stroke prevention strategy. This is the first prospective study describing LAAE performed concomitantly to less invasive LVAD implantation. The efficacy of LAAE in long-term stroke prevention needs to be confirmed in future prospective randomized clinical trials.
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Apêndice Atrial , Insuficiência Cardíaca , Coração Auxiliar , Acidente Vascular Cerebral , Humanos , Estudos Retrospectivos , Estudos Prospectivos , Apêndice Atrial/cirurgia , Projetos Piloto , Resultado do Tratamento , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Insuficiência Cardíaca/cirurgiaRESUMO
BACKGROUND: Right ventricular failure (RVF) remains one of the major causes of morbidity and mortality after left ventricular assist device (LVAD) implantation. We sought to compare immediate postoperative invasive hemodynamics and the risk of RVF following two different surgical approaches: less invasive surgery (LIS) versus full sternotomy (FS). METHODS: The study population comprised all 231 patients who underwent implantation of a HeartMate 3 (Abbott) LVAD at our institution from 2015 to 2020, utilizing an LIS (n = 161; 70%) versus FS (n = 70; 30%) surgical approach. Outcomes included postoperative invasive hemodynamic parameters, vasoactive-inotropic score (VIS), RVF during index hospitalization, and 6-month mortality. RESULTS: Baseline clinical characteristics of the two groups were similar. Multivariate analysis showed that LIS, compared with FS, was associated with the improved cardiac index (CI) at the sixth postoperative hour (p = .036) and similar CI at 24 h, maintained by lower VIS at both timepoints (p = .002). The LIS versus FS approach was also associated with a three-fold lower incidence of in-hospital severe RVF (8.7% vs. 28.6%, p < .001) and need for RVAD support (5.0% vs. 17.1%, p = .003), and with 68% reduction in the risk of 6-month mortality after LVAD implantation (Hazard ratio, 0.32; CI, 0.13-0.78; p = .012). CONCLUSION: Our findings suggest that LIS, compared with FS, is associated with a more favorable hemodynamic profile, as indicated by similar hemodynamic parameters maintained by lower vasoactive-inotropic support during the acute postoperative period. These findings were followed by a reduction in the risk of severe RVF and 6-month mortality in the LIS group.
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Insuficiência Cardíaca , Coração Auxiliar , Disfunção Ventricular Direita , Coração Auxiliar/efeitos adversos , Hemodinâmica , Humanos , Período Pós-Operatório , Estudos Retrospectivos , Disfunção Ventricular Direita/etiologiaRESUMO
AIMS: The benefit of prophylactic implantable cardioverter-defibrillator (ICD) is not uniform due to differences in the risk of life-threatening ventricular tachycardia (VT)/ventricular fibrillation (VF) and non-arrhythmic mortality. We aimed to develop an ICD benefit prediction score that integrates the competing risks. METHODS AND RESULTS: The study population comprised all 4531 patients enrolled in the MADIT trials. Best-subsets Fine and Gray regression analysis was used to develop prognostic models for VT (≥200 b.p.m.)/VF vs. non-arrhythmic mortality (defined as death without prior sustained VT/VF). Eight predictors of VT/VF (male, age < 75 years, prior non-sustained VT, heart rate > 75 b.p.m., systolic blood pressure < 140 mmHg, ejection fraction ≤ 25%, myocardial infarction, and atrialarrhythmia) and 7 predictors of non-arrhythmic mortality (age ≥ 75 years, diabetes mellitus, body mass index < 23 kg/m2, ejection fraction ≤ 25%, New York Heart Association ≥II, ICD vs. cardiac resynchronization therapy with defibrillator, and atrial arrhythmia) were identified. The two scores were combined to create three MADIT-ICD benefit groups. In the highest benefit group, the 3-year predicted risk of VT/VF was three-fold higher than the risk of non-arrhythmic mortality (20% vs. 7%, P < 0.001). In the intermediate benefit group, the difference in the corresponding predicted risks was attenuated (15% vs. 9%, P < 0.01). In the lowest benefit group, the 3-year predicted risk of VT/VF was similar to the risk of non-arrhythmic mortality (11% vs. 12%, P = 0.41). A personalized ICD benefit score was developed based on the distribution of the two competing risks scores in the study population (https://is.gd/madit). Internal and external validation confirmed model stability. CONCLUSIONS: We propose the novel MADIT-ICD benefit score that predicts the likelihood of prophylactic ICD benefit through personalized assessment of the risk of VT/VF weighed against the risk of non-arrhythmic mortality.
Assuntos
Terapia de Ressincronização Cardíaca , Desfibriladores Implantáveis , Taquicardia Ventricular , Idoso , Arritmias Cardíacas/terapia , Humanos , Masculino , Fatores de Risco , Taquicardia Ventricular/terapia , Fibrilação Ventricular/terapiaRESUMO
BACKGROUND: The new high-sensitivity cardiac troponin T (hs-cTnT) is now widely used in the United States. OBJECTIVES: We aimed to examine outcomes associated with the introduction of the new 5th generation hs-cTnT assay among patients presenting to the emergency department (ED) with cardiovascular (CV) disorders. METHODS: The study comprised 5377 patients presenting to the ED with CV disorders between January and September 2018. Outcomes included rates of direct ED discharge, cardiac testing/procedures, and mortality. CV indications for troponin testing were categorized as rule-out acute coronary syndrome (RO-ACS) and other-CV (O-CV). RESULTS: Mean age was 62 ± 17 years, and 47% were female. Demographics and medical history did not differ significantly between the troponin groups. The use of hs-cTnT was associated with increased rates of direct discharge from the ED in the RO-ACS (48% vs. 37%; p < 0.01), but not in the O-CV (25% vs. 25%) cohort. Cardiac tests/procedures were more often performed after hs-cTnT vs. cTnT testing in both cohorts (45% vs. 41% for RO-ACS, and 33% vs. 28% for O-CV; p < 0.05 for both). Multivariate analysis demonstrated that hs-cTnT was not associated with a significant increase in postdischarge mortality in both cohorts (RO-ACS: hazard ratio = 1.47 [p = 0.13], O-CV: hazard ratio = 0.97 [p = 0.87]). CONCLUSIONS: Among patients with RO-ACS, hs-cTnT implementation resulted in increased rates of direct home discharge from the ED, without a significant increase in postdischarge mortality. Among patients presenting with O-CV indication, hs-cTnT implementation resulted in increased rates of cardiac testing procedures without an effect of ED discharge rates or long-term mortality.
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Síndrome Coronariana Aguda , Doenças Cardiovasculares , Síndrome Coronariana Aguda/diagnóstico , Assistência ao Convalescente , Idoso , Biomarcadores , Doenças Cardiovasculares/diagnóstico , Serviço Hospitalar de Emergência , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Alta do Paciente , Troponina , Troponina TRESUMO
INTRODUCTION: In patients with atrial fibrillation (AF) at risk for stroke, dabigatran 150 mg twice a day (DE150) is superior to warfarin for stroke prevention. However, there is paucity of data with respect to bleeding risk at this dose in elderly patients (≥75 years). We aimed to evaluate the safety of DE150 in comparison to warfarin in a real-world population with AF and low bleeding risk (HAS-BLED score ≤2). METHODS: In this prospective observational study, 754 consecutive patients with AF and HAS-BLED score ≤2 were included. We compared outcome of elderly patients (age ≥75 tears) to younger patients (age <75 years). The primary end point was the combined incidence of all-cause mortality, stroke, systemic emboli, and major bleeding event during a mean follow-up of 1 year. RESULTS: There were 230 (30%) elderly patients, 151 patients were treated with warfarin, and 79 were treated with DE150. Fifty-two patients experienced the primary endpoint during the 1-year follow-up. Among the elderly, at 1-year of follow-up, the cumulative event rate of the combined endpoint in the DE150 and warfarin was 8.9 and 15.9% respectively (p = 0.14). After adjustment for age and gender, patients who were treated with DE150 had a nonsignificant difference in the risk for the combined end point as patients treated with warfarin both among the elderly and among the younger population (HR 0.58, 95% C.I = 0.25-1.39 and HR = 1.12, 95% C.I 0.62-2.00, respectively [p for age-group-by-treatment interaction = 0.83). CONCLUSIONS: Our results suggest that Dabigatran 150 mg twice a day can be safely used among elderly AF patients with low bleeding risk.
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Dabigatrana , Hemorragia , Idoso , Dabigatrana/efeitos adversos , Hemorragia/induzido quimicamente , Hemorragia/epidemiologia , HumanosRESUMO
INTRODUCTION: Cardiac resynchronization therapy (CRT) may be pro-arrhythmic in patients with non-left bundle branch block (non-LBBB). We hypothesized that combined assessment of risk factors (RF) for ventricular tachyarrhythmias (VTAs) can be used to stratify non-LBBB patients for CRT implantation. METHODS: The study comprised 412 non-LBBB patients from MADIT-CRT randomized to CRT-D (n = 215) versus ICD only (n = 197). Best-subset regression analysis was performed to identify RF associated with increased VTA risk in CRT-D patients without LBBB. The primary end point was first occurrence of sustained VTA during follow-up. Secondary end points included VTA/death and appropriate shock. RESULTS: Four RFs were associated with increased VTA risk: blood urea nitrogen >25mg/dl, ejection fraction <20%, prior nonsustained VT, and female gender. Among CRT-D patients, 114 (53%) had no RF, while 101 (47%) had ≥1 RF. The 4-year cumulative probability of VTA was higher among those with ≥1 RF compared with those without RF (40% vs. 14%, p < .001). Multivariate analysis showed that in patients without RF, treatment with CRT-D was associated with a 61% reduction in VTA compared with ICD-only therapy (p = .002), whereas among patients with ≥1 RF, treatment with CRT-D was associated with a corresponding 73% (p = .025) risk increase. Consistent results were observed when the secondary end points of VTA/death and appropriate ICD shocks were assessed. CONCLUSION: Combined assessment of factors associated with increased risk for VTA can be used for improved selection of non-LBBB patients for CRT-D.