RESUMO
AIMS: Atrial tachyarrhythmias (ATs) detected by implanted devices are often atrial fibrillation or flutter (AF) associated with stroke. We hypothesized that introduction and termination of anticoagulation based upon AT monitoring would reduce both stroke and bleeding. METHODS AND RESULTS: We randomized 2718 patients with dual-chamber and biventricular defibrillators to start and stop anticoagulation based on remote rhythm monitoring vs. usual office-based follow-up with anticoagulation determined by standard clinical criteria. The primary analysis compared the composite endpoint of stroke, systemic embolism, and major bleeding with the two strategies. The trial was stopped after 2 years median follow-up based on futility of finding a difference in primary endpoints between groups. A total of 945 patients (34.8%) developed AT, 264 meeting study anticoagulation criteria. Adjudicated atrial electrograms confirmed AF in 91%; median time to initiate anticoagulation was 3 vs. 54 days in the intervention and control groups, respectively (P < 0.001). Primary events (2.4 vs. 2.3 per 100 patient-years) did not differ between groups (HR 1.06; 95% CI 0.75-1.51; P = 0.732). Major bleeding occurred at 1.6 vs. 1.2 per 100 patient-years (HR 1.39; 95% CI 0.89-2.17; P = 0.145). In patients with AT, thromboembolism rates were 1.0 vs. 1.6 per 100 patient-years (relative risk -35.3%; 95% CI -70.8 to 35.3%; P = 0.251). Although AT burden was associated with thromboembolism, there was no temporal relationship between AT and stroke. CONCLUSION: In patients with implanted defibrillators, the strategy of early initiation and interruption of anticoagulation based on remotely detected AT did not prevent thromboembolism and bleeding. CLINICAL TRIAL REGISTRATION: IMPACT ClinicalTrials.gov identifier: NCT00559988 ( http://clinicaltrials.gov/ct2/show/NCT00559988?term=NCT00559988&rank=1 ).
Assuntos
Anticoagulantes/uso terapêutico , Fibrilação Atrial/terapia , Dispositivos de Terapia de Ressincronização Cardíaca , Desfibriladores Implantáveis , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Monitorização Ambulatorial/métodos , Método Simples-Cego , Acidente Vascular Cerebral/prevenção & controle , Telemedicina/métodos , Tromboembolia/prevenção & controle , Resultado do Tratamento , Tecnologia sem FioRESUMO
BACKGROUND: We conducted a prospective multicenter study to assess the prognostic value of combined baseline preimplant plasma levels of the biomarkers cardiac troponin T (TnT) and B-type natriuretic peptide (BNP) among cardiac resynchronization therapy (CRT) with or without defibrillator capability (CRT-D) recipients. METHODS: At CRT-D implant, patients were stratified based on detectable TnT (≥0.01 ng/mL) and elevated BNP (predefined as >440 pg/mL) levels. Patients were classified into three groups: high (both detectable TnT and high BNP), intermediate (either detectable TnT or high BNP), or low (nondetectable TnT and low BNP). Patients were followed for 12 months. Survival curves free from mortality or heart failure hospitalizations (HFH) were assessed. To assess the predictive value of biomarker category, we constructed a multivariate Cox regression model, including the covariates of age, New York Heart Association class, left ventricular ejection fraction (LVEF), and QRS duration. RESULTS: A total of 267 patients (age 66 ± 12 years, males 80%, LVEF 25% ± 8%, ischemic cardiomyopathy 52%, QRSd 155 ± 26 ms) were studied. After 1 year, there were 13 deaths and 25 HFH events. A significant difference in event-free survival among the three groups was observed, with high and intermediate categories having worse survival than low (log-rank test, P < 0.001). In the multivariate model, risk category was a significant predictor of outcome: hazard ratios were 7.34 (95% confidence interval [CI]: 2.48-21.69) and 2.50 (95% confidence interval [CI]: 1.04-6.04) for high-risk and intermediate-risk groups, respectively (P < 0.0001). CONCLUSION: Among CRT-D recipients, baseline TnT and BNP values alone or in combination provide significant prognostic value for the outcome of mortality or HFH.
Assuntos
Terapia de Ressincronização Cardíaca , Cardiomiopatias/terapia , Peptídeo Natriurético Encefálico/sangue , Troponina/sangue , Idoso , Biomarcadores/sangue , Cardiomiopatias/fisiopatologia , Feminino , Humanos , Masculino , Estudos Prospectivos , Inquéritos e Questionários , Análise de Sobrevida , Resultado do TratamentoRESUMO
Atrial fibrillation and atrial flutter are common cardiac arrhythmias associated with an increased risk of stroke in patients with additional risk factors. Anticoagulation ameliorates stroke risk, but because these arrhythmias may occur intermittently without symptoms, initiation of prophylactic therapy is often delayed until electrocardiographic documentation is obtained. The IMPACT study is a multicenter, randomized trial of remote surveillance technology in patients with implanted dual-chamber cardiac resynchronization therapy defibrillator (CRT-D) devices designed to test the hypothesis that initiation and withdrawal of oral anticoagulant therapy guided by continuous ambulatory monitoring of the atrial electrogram improve clinical outcomes by reducing the combined rate of stroke, systemic embolism, and major bleeding compared with conventional clinical management. For those in the intervention group, early detection of atrial high-rate episodes (AHRE) generates an automatic alert to initiate anticoagulation based on patient-specific stroke risk stratification. Subsequently, freedom from AHRE for predefined periods prompts withdrawal of anticoagulation to avoid bleeding. Patients in the control arm are managed conventionally, the anticoagulation decision prompted by incidental detection of atrial fibrillation or atrial flutter during routine clinical follow-up. The results will help define the clinical utility of wireless remote cardiac rhythm surveillance and help establish the critical threshold of AHRE burden warranting anticoagulant therapy in patients at risk of stroke. In this report, we describe the study design and baseline demographic and clinical features of the initial cohort (227 patients).
Assuntos
Anticoagulantes/uso terapêutico , Fibrilação Atrial/terapia , Flutter Atrial/terapia , Estimulação Cardíaca Artificial , Desfibriladores Implantáveis , Eletrocardiografia , Idoso , Anticoagulantes/efeitos adversos , Fibrilação Atrial/complicações , Fibrilação Atrial/diagnóstico , Flutter Atrial/complicações , Flutter Atrial/diagnóstico , Estudos de Coortes , Eletrocardiografia/métodos , Embolia/etiologia , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Projetos de Pesquisa , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/etiologia , TelemetriaRESUMO
BACKGROUND: Implantable cardioverter-defibrillators (ICDs) for primary prevention became standard of care after the publication of the second Multicenter Automatic Defibrillator Implantation Trial (MADIT-II) and Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT). OBJECTIVE: To determine the percentage of patients in a Veterans Affairs medical center appropriately referred for primary prophylaxis ICD and to further categorize the reasons patients are not being referred. METHODS: Echocardiograms obtained since the release of MADIT-II in 2002 were searched for a left ventricular ejection fraction (LVEF) < or = 35% and < or =30%. We randomly selected 120 patients per year from 2002 to 2006, for a total of 600 patients in each group. Data were reviewed to determine the number of ICD recipients and the reasons patients were not referred. RESULTS: In the LVEF < or = 35% group an ICD was implanted in 28% of 392 eligible patients. Nonreferral (58%) was the most common reason that eligible patients did not receive an ICD. Patients were not referred for ICD because of appropriate contraindications in 26% of cases. Overall mortality was 29% (15% with and 31% without ICD). In the LVEF < or =30% group an ICD was implanted in 33% of 388 eligible patients. Nonreferral (51%) was the most common reason that eligible patients did not receive an ICD. Patients were not referred for ICD because of appropriate contraindications in 24% of cases. Overall mortality was 28% (18% with and 32% without ICD). CONCLUSIONS: After the publication of MADIT-II and SCD-HeFT, only 42% of eligible patients with LVEF < or = 35% and 49% of patients with LVEF < or =30% were offered a potentially life-saving ICD between 2002 and 2006 in our medical center, sometimes with considerable delay.
Assuntos
Desfibriladores Implantáveis/estatística & dados numéricos , Cardioversão Elétrica/mortalidade , Hospitais de Veteranos/estatística & dados numéricos , Seleção de Pacientes , Encaminhamento e Consulta/estatística & dados numéricos , Disfunção Ventricular Esquerda/mortalidade , Disfunção Ventricular Esquerda/prevenção & controle , Idoso , California/epidemiologia , Cardioversão Elétrica/estatística & dados numéricos , Feminino , Humanos , Masculino , Prevalência , Estudos Retrospectivos , Análise de Sobrevida , Taxa de SobrevidaRESUMO
BACKGROUND: Prostacyclins improve symptoms and survival in pulmonary arterial hypertension (PAH). In response to risks associated with external delivery systems, an implantable IV infusion system was developed. A multicenter, prospective, single-arm, clinical trial (DelIVery for PAH) was conducted to evaluate this system for treprostinil in PAH. This analysis describes the findings related to the implant procedure. METHODS: Patients (N = 64) with PAH (World Health Organization group 1) receiving stable IV treprostinil were enrolled. Patients were transitioned to a temporary peripheral IV infusion catheter prior to the procedure. System implantation was performed at 10 centers under general anesthesia or deep IV sedation by clinicians from various specialties. Central venous access was via the cephalic, subclavian, jugular, or axillary vein. Using an introducer and fluoroscopic guidance, the distal tip of the infusion catheter was placed at the superior caval-atrial junction. The catheter was tunneled from the venous access site to an abdominal subcutaneous pocket, where the pump was placed. RESULTS: Of the 64 patients enrolled, four exited prior to implantation. All 60 implant procedures were successful. At baseline, all patients were receiving treprostinil via an external pump at a mean dose of 71.4 ± 27.8 ng/kg/min (range: 22-142 ng/kg/min). The implant averaged 102 ± 32 min (range: 47-184 min). Clinically significant implant procedure-related complications included one pneumothorax, two infections, and one episode of atrial fibrillation. There were three postimplantation catheter dislocations in two patients. Common implant-related events that were not complications included implant site pain (83%) and bruising (17%). CONCLUSIONS: The procedure for inserting a fully implantable system for treprostinil was successfully performed, with few complications. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01321073; URL: www.clinicaltrials.gov.
Assuntos
Cateterismo Venoso Central/métodos , Epoprostenol/análogos & derivados , Hipertensão Pulmonar/tratamento farmacológico , Bombas de Infusão Implantáveis , Anti-Hipertensivos/administração & dosagem , Relação Dose-Resposta a Droga , Epoprostenol/administração & dosagem , Feminino , Seguimentos , Humanos , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/fisiopatologia , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Pressão Propulsora Pulmonar/efeitos dos fármacos , Resultado do TratamentoRESUMO
Implanted cardiac arrhythmia devices can detect atrial tachyarrhythmias (atrial high-rate episodes [AHREs]) that are considered to correlate with atrial fibrillation and risk of stroke. In the IMPACT trial, oral anticoagulation was initiated when AHREs were detected by implanted cardioverter-defibrillators and withdrawn when they abated, according to a protocol accounting both for AHRE duration as detected by remote device monitoring and stroke risk assessment. In this analysis, we ascertained determinants of time in therapeutic range (TTR) among protocol-determined vitamin K antagonist-treated patients during the trial. We enrolled 2,718 patients with at least 1 additional stroke risk factor (CHADS2 score ≥1) at 104 arrhythmia centers. The sex, age <60, medical history, treatments interacting with VKA, tobacco use (2 points) and race (2 points for non-Caucasian) (SAMe-TT2R2) score is a simple clinical-derived score designed to aid decision-making on whether a patient is likely to achieve good anticoagulation control on vitamin K antagonist (e.g., warfarin), which was calculated and related to TTR achieved using the Rosendaal method. We analyzed 229 patients (mean age 66.7 years; mean CHADS2 score 2.85 [SD 1.1]) with mean TTR of 0.536 (SD 0.23) overall. Univariate analysis identified 5 variables associated with differences in mean TTR. Mean TTR was lower in those who were women (p = 0.031), of black race (p = 0.005) and in New York Heart Association class IV (p = 0.014), whereas hemoglobin >13.5 g/dl (p = 0.010) and New York Heart Association class I (p = 0.037) were associated with higher mean TTR. There was a significant difference in mean TTR value between US and non-US sites (Canada and Germany) (mean TTR for US: 0.513 vs non-US: 0.686; p <0.0001). Mean TTR was significantly lower (Δ = 0.1382, 95% CI 0.0382 to 0.2382) for patients with SAMe-TT2R2 scores of 4 (p = 0.007) and higher (Δ = 0.0612, 95% CI 0.0005 to 0.1219) for patients with SAMe-TT2R2 scores of 1 (p = 0.048). Linear regression confirmed a significant association between lower SAMe-TT2R2 score and improved anticoagulation control (p = 0.0021) with a 1-unit decrease in SAMe-TT2R2 score associated with an increase in TTR of 0.0404 (95% CI 0.0149 to 0.0659). In conclusion, clinical, geographical, and demographic factors were associated with the quality of anticoagulation control as reflected by TTR. Although overall TTR in this population was poor, lower SAMe-TT2R2 scores were associated with better TTR.
Assuntos
Anticoagulantes/administração & dosagem , Fibrilação Atrial/complicações , Desfibriladores Implantáveis , Medição de Risco , Acidente Vascular Cerebral/prevenção & controle , Administração Oral , Idoso , Fibrilação Atrial/terapia , Coagulação Sanguínea/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Acidente Vascular Cerebral/etiologia , Resultado do TratamentoRESUMO
Expression of different cytokines and growth factors after myocardial injury has been associated with fibroplasia and dilatation versus reverse remodeling and myocardial repair. Specifically, the proinflammatory/fibrotic mediators: interleukin (IL)-6, epidermal growth factor, and fibroblast growth factor (FGF)-2 cause fibroplasia, whereas reparative cytokines including: IL-1α, IL-1ß, IL-4, and IL-13 can limit fibrosis. In appropriate patients, cardiac resynchronization therapy (CRT) reverses cardiomyopathy and improves outcome. However, a significant proportion will not respond to this therapy. We conducted this study to assess the association of proinflammatory/fibrotic and/or reparative immune response mediators at baseline with outcome after CRT. In the multicenter RISK study, plasma samples were collected prospectively before CRT implantation. Plasma IL-6, epidermal growth factor, FGF-2, IL-1α, IL-1ß, IL-4, and IL-13 were evaluated by Luminex technology. The primary outcome was predefined as freedom from heart failure hospitalization or death and a decrease in echocardiographic end-systolic volume of >15% at 12 months. To determine associations with the outcome, multivariate logistic regression models including baseline clinical characteristics and the specific cytokines and growth factors were constructed. On multivariate analysis of 257 patients, detectable reparative cytokine IL-13 was significantly associated with the primary outcome (odds ratio 3.79; 95% CI 2.10 to 6.82, p <0.0001). In contrast, detectable proinflammatory/fibrotic growth factor FGF-2 was negatively associated (odds ratio 0.31; 95% CI, 0.14 to 0.68; p = 0.004). In conclusion, in CRT recipients, baseline levels of inflammatory mediators affecting cardiac fibrosis versus repair were associated with subsequent clinical outcome.
Assuntos
Terapia de Ressincronização Cardíaca/métodos , Citocinas/sangue , Insuficiência Cardíaca/sangue , Inflamação/sangue , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Volume Sistólico/fisiologia , Remodelação Ventricular/fisiologia , Idoso , Biomarcadores/sangue , Ecocardiografia , Feminino , Seguimentos , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/terapia , Humanos , Masculino , Prognóstico , Estudos Retrospectivos , Fatores de Tempo , Resultado do TratamentoRESUMO
Malignant ventricular arrhythmias can result from isolated right ventricular infarction, and reports of this phenomenon in the literature are rare. We present a case of a 46-year-old man with acute onset of chest pain angiographically confirmed to be a result of isolated occlusion of a right ventricular branch artery. He developed ventricular fibrillation within 5 hours of symptom onset. This case highlights the point that despite its benign clinical appearance and preserved left ventricular function, necrosis of right ventricular tissue can have life-threatening consequences.
Assuntos
Doença das Coronárias/complicações , Infarto do Miocárdio/etiologia , Disfunção Ventricular Direita/etiologia , Fibrilação Ventricular/etiologia , Doença Aguda , Adulto , Eletrocardiografia , Parada Cardíaca/etiologia , Parada Cardíaca/fisiopatologia , Ventrículos do Coração/patologia , Ventrículos do Coração/fisiopatologia , Humanos , Masculino , Infarto do Miocárdio/tratamento farmacológico , Disfunção Ventricular Direita/fisiopatologia , Fibrilação Ventricular/tratamento farmacológico , Fibrilação Ventricular/fisiopatologiaRESUMO
BACKGROUND: Heart rate (HR) and systolic BP (SBP) are significant multivariate predictors of survival in patients with pulmonary arterial hypertension (PAH) as part of a 19-element formula. To what extent HR and BP alone predict survival and future hospitalization in patients with PAH is unknown. METHODS: We analyzed data from the Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL Registry), a prospective, observational study of patients with PAH. Patients were analyzed by quintile (Q) according to values of HR, SBP, and SBP/HR. Kaplan-Meier curves were calculated by Q for survival and freedom from hospitalization. RESULTS: For patients in the worst Q, 1-year survival after enrollment was 85% ± 2% for SBP, 86% ± 2% for HR, and 84% ± 2% for SBP/HR vs 91% ± 1% for the middle three Qs (P < .001). Hospitalization occurred more frequently than mortality but with a similar pattern among Qs. One-year survival after first follow-up of patients in the worst Q for change (Δ) in SBP since enrollment was 85% ± 2% (P = .004), 86% ± 2% for ΔHR (P = .12), and 84% ± 2% for ΔSBP/HR (P = .024) vs the middle three Qs (ΔSBP: 91% ± 1%; ΔHR: 90% ± 1%; ΔSBP/HR: 90% ± 1%). CONCLUSIONS: Changes in vital signs from enrollment to first follow-up were less predictive of mortality than the values of vital-sign parameters at either enrollment or first follow-up. HR, SBP, and SBP/HR at enrollment identified high-risk groups with survival differences of 5% to 7% and freedom from hospitalization differences of 9% to 11% vs lower-risk groups. SBP/HR defines the highest-risk group, including most of the high-risk patients defined by HR and SBP separately. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00370214; URL: www.clinicaltrials.gov.
Assuntos
Pressão Sanguínea/fisiologia , Gerenciamento Clínico , Frequência Cardíaca/fisiologia , Hipertensão Pulmonar/fisiopatologia , Hipertensão Pulmonar Primária Familiar , Feminino , Seguimentos , Hospitalização/estatística & dados numéricos , Humanos , Hipertensão Pulmonar/mortalidade , Hipertensão Pulmonar/terapia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Taxa de Sobrevida/tendências , Estados Unidos/epidemiologiaAssuntos
Anticorpos Monoclonais Humanizados/efeitos adversos , Arritmias Cardíacas/induzido quimicamente , Arritmias Cardíacas/diagnóstico , Ligante RANK/antagonistas & inibidores , Arritmias Cardíacas/sangue , Desfibriladores Implantáveis , Denosumab , Eletrocardiografia , Eletrólitos/sangue , Sistema de Condução Cardíaco/efeitos dos fármacos , Sistema de Condução Cardíaco/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Taquicardia Ventricular/complicaçõesAssuntos
Pressão Sanguínea/fisiologia , Coração/fisiologia , Isquemia Miocárdica/prevenção & controle , Trocador de Sódio e Cálcio/genética , Animais , Feminino , Homozigoto , Masculino , Camundongos , Camundongos Transgênicos , Modelos Animais , Células Musculares/fisiologia , Isquemia Miocárdica/genética , Valores de ReferênciaRESUMO
We successfully implanted 11 pacemakers, 6 defibrillators, and 1 biventricular pacemaker in 18 pediatric patients (15 female; 4 to 15 years, average age: 9) using the retropectoral transvenous approach with a hidden axillary incision. The average follow-up period was 24 months (range 49 months). Eight patients had congenital structural heart conditions (d-transposition of great arteries S/P Mustard operation, d-transposition of great arteries S/P arterial switch operation, truncus arteriosus, right ventricular diverticula, ventricular septal defect, hypertrophic cardiomyopathy). Four patients had acquired heart conditions (dilated cardiomyopathy, myocarditis). Excellent sensing and pacing thresholds were achieved in all attempted implantations. There was no pneumothorax. There was one lead dislodgement. One lead fracture distant from the subclavian vein occurred 4 months after implantation. Implantation of pacemakers and defibrillators via axillary incisions can be safe and effective in pediatric patients. This approach avoids skin erosion when implanting large devices such as defibrillators or biventricular devices in small patients with limited muscle mass while achieving superior aesthetic results. The axillary or extrathoracic venous entry site avoids subclavian crush syndrome.