RESUMO
BACKGROUND: The benefit:risk profile of bivalirudin versus heparin anticoagulation in patients with non-ST-segment-elevation myocardial infarction undergoing percutaneous coronary intervention (PCI) is uncertain. Study-level meta-analyses lack granularity to provide conclusive answers. We sought to compare the outcomes of bivalirudin and heparin in patients with non-ST-segment-elevation myocardial infarction undergoing PCI. METHODS: We performed an individual patient data meta-analysis of patients with non-ST-segment-elevation myocardial infarction in all 5 trials that randomized ≥1000 patients with any myocardial infarction undergoing PCI to bivalirudin versus heparin (MATRIX [Minimizing Adverse Hemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox], VALIDATE-SWEDEHEART [Bivalirudin Versus Heparin in ST-Segment and Non-ST-Segment Elevation Myocardial Infarction in Patients on Modern Antiplatelet Therapy in the Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies Registry Trial], ISAR-REACT 4 [Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment 4], ACUITY [Acute Catheterization and Urgent Intervention Triage Strategy], and BRIGHT [Bivalirudin in Acute Myocardial Infarction vs Heparin and GPI Plus Heparin Trial]). The primary effectiveness and safety end points were 30-day all-cause mortality and serious bleeding. RESULTS: A total of 12 155 patients were randomized: 6040 to bivalirudin (52.3% with a post-PCI bivalirudin infusion), and 6115 to heparin (53.2% with planned glycoprotein IIb/IIIa inhibitor use). Thirty-day mortality was not significantly different between bivalirudin and heparin (1.2% versus 1.1%; adjusted odds ratio, 1.24 [95% CI, 0.86-1.79]; P=0.25). Cardiac mortality, reinfarction, and stent thrombosis rates were also not significantly different. Bivalirudin reduced serious bleeding (both access site-related and non-access site-related) compared with heparin (3.3% versus 5.5%; adjusted odds ratio, 0.59; 95% CI, 0.48-0.72; P<0.0001). Outcomes were consistent regardless of use of a post-PCI bivalirudin infusion or routine lycoprotein IIb/IIIa inhibitor use with heparin and during 1-year follow-up. CONCLUSIONS: In patients with non-ST-segment-elevation myocardial infarction undergoing PCI, procedural anticoagulation with bivalirudin and heparin did not result in significantly different rates of mortality or ischemic events, including stent thrombosis and reinfarction. Bivalirudin reduced serious bleeding compared with heparin arising both from the access site and nonaccess sites.
Assuntos
Infarto do Miocárdio , Infarto do Miocárdio sem Supradesnível do Segmento ST , Intervenção Coronária Percutânea , Trombose , Humanos , Heparina/efeitos adversos , Infarto do Miocárdio sem Supradesnível do Segmento ST/tratamento farmacológico , Anticoagulantes/efeitos adversos , Intervenção Coronária Percutânea/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Hirudinas/efeitos adversos , Fragmentos de Peptídeos/efeitos adversos , Hemorragia/etiologia , Trombose/etiologia , Proteínas Recombinantes/efeitos adversos , Resultado do TratamentoRESUMO
BACKGROUND: Mortality after ST-segment elevation myocardial infarction (STEMI) is increased in patients with hypertension. The mechanisms underlying this association are uncertain. We sought to investigate whether patients with STEMI and prior hypertension have greater microvascular obstruction (MVO) and infarct size (IS) compared with those without hypertension. METHODS: We pooled individual patient data from 7 randomized trials of patients with STEMI undergoing primary percutaneous coronary intervention (PCI) in whom cardiac magnetic resonance imaging was performed within 1 month after reperfusion. The associations between hypertension and MVO, IS, and mortality were assessed in multivariable adjusted models. RESULTS: Among 2174 patients (61.3 ± 12.6 years, 76% male), 1196 (55.0%) had hypertension. Patients with hypertension were older, more frequently diabetic and had more extensive coronary artery disease than those without hypertension. MVO and IS measured as percent LV mass were not significantly different in patients with and without hypertension (adjusted differences 0.1, 95% CI -0.3 to 0.6, P = .61 and -0.2, 95% CI -1.5 to 1.2, P = .80, respectively). Hypertension was associated with a higher unadjusted risk of 1-year death (hazard ratio [HR] 2.28, 95% CI 1.44-3.60, P < .001), but was not independently associated with higher mortality after multivariable adjustment (adjusted HR 1.04, 95% CI 0.60-1.79, P = .90). CONCLUSION: In this large-scale individual patient data pooled analysis, hypertension was not associated with larger IS or MVO after primary PCI for STEMI.
Assuntos
Hipertensão , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Humanos , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgia , Infarto do Miocárdio com Supradesnível do Segmento ST/mortalidade , Intervenção Coronária Percutânea/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Hipertensão/complicações , Imagem Cinética por Ressonância Magnética/métodos , Idoso , Microcirculação , Imageamento por Ressonância Magnética/métodos , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND: Supersaturated oxygen (SSO2 ) has recently been approved by the U.S. Food and Drug Administration for administration after primary percutaneous coronary intervention (pPCI) in patients with anterior ST-segment elevation myocardial infarction (STEMI) based on its demonstration of infarct size reduction in the IC-HOT study. OBJECTIVES: To describe the 1-year clinical outcomes of intracoronary SSO2 treatment after pPCI in patients with anterior STEMI. METHODS: IC-HOT was a prospective, open-label, single-arm study in which 100 patients without cardiogenic shock undergoing successful pPCI of an occluded left anterior descending coronary artery were treated with a 60-min SSO2 infusion. One-year clinical outcomes were compared with a propensity-matched control group of similar patients with anterior STEMI enrolled in the INFUSE-AMI trial. RESULTS: Baseline and postprocedural characteristics were similar in the two groups except for pre-PCI thrombolysis in myocardial infarction 3 flow, which was less prevalent in patients treated with SSO2 (9.6% vs. 22.9%, p = .02). Treatment with SSO2 was associated with a lower 1-year rate of the composite endpoint of all-cause death or new-onset heart failure (HF) or hospitalization for HF (0.0% vs. 12.3%, p = .001). All-cause mortality, driven by cardiovascular mortality, and new-onset HF or HF hospitalization were each individually lower in SSO2 -treated patients. There were no significant differences between groups in the 1-year rates of reinfarction or clinically driven target vessel revascularization. CONCLUSIONS: Infusion of SSO2 following pPCI in patients with anterior STEMI was associated with improved 1-year clinical outcomes including lower rates of death and new-onset HF or HF hospitalizations.
Assuntos
Infarto do Miocárdio , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Humanos , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/terapia , Oxigênio , Intervenção Coronária Percutânea/efeitos adversos , Estudos Prospectivos , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Resultado do TratamentoRESUMO
OBJECTIVES: We examined outcomes according to lesion preparation strategy (LPS) in patients with left main coronary artery (LMCA) percutaneous coronary intervention (PCI) in the EXCEL trial. BACKGROUND: The optimal LPS for LMCA PCI is unclear. METHODS: We categorized LPS hierarchically (high to low) as: (a) rotational atherectomy (RA); (b) cutting or scoring balloon (CSB); (c) balloon angioplasty (BAL); and d) direct stenting (DIR). The primary endpoint was 3-year MACE; all-cause death, stroke, or myocardial infarction. RESULTS: Among 938 patients undergoing LMCA PCI, RA was performed in 6.0%, CSB 9.5%, BAL 71.3%, and DIR 13.2%. In patients treated with DIR, BAL, CSB, and RA, respectively, there was a progressive increase in SYNTAX score, LMCA complex bifurcation, trifurcation or calcification, number of stents, and total stent length. Any procedural complication occurred in 10.4% of cases overall, with the lowest rate in the DIR (7.4%) and highest in the RA group (16.1%) (ptrend = .22). There were no significant differences in the 3-year rates of MACE (from RA to DIR: 17.9%, 20.2%, 14.5%, 14.7%; p = .50) or ischemia-driven revascularization (from RA to DIR: 16.8%, 10.8%, 12.3%, 14.2%; p = .65). The adjusted 3-year rates of MACE did not differ according to LPS. CONCLUSIONS: The comparable 3-year outcomes suggest that appropriate lesion preparation may be able to overcome the increased risks of complex LMCA lesion morphology.
Assuntos
Doença da Artéria Coronariana , Stents Farmacológicos , Intervenção Coronária Percutânea , Ponte de Artéria Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/cirurgia , Humanos , Intervenção Coronária Percutânea/efeitos adversos , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
AIMS: The clinical impact of new-onset persistent left bundle branch block (NOP-LBBB) and permanent pacemaker implantation (PPI) on transcatheter aortic valve replacement (TAVR) recipients remains controversial. We aimed to evaluate the impact of (i) periprocedural NOP-LBBB and PPI post-TAVR on 1-year all-cause death, cardiac death, and heart failure hospitalization and (ii) NOP-LBBB on the need for PPI at 1-year follow-up. METHODS AND RESULTS: We performed a systematic search from PubMed and EMBASE databases for studies reporting raw data on 1-year clinical impact of NOP-LBBB or periprocedural PPI post-TAVR. Data from 30 studies, including 7792 patients (12 studies) and 42 927 patients (21 studies) for the evaluation of the impact of NOP-LBBB and PPI after TAVR were sourced, respectively. NOP-LBBB was associated with an increased risk of all-cause death [risk ratio (RR) 1.32, 95% confidence interval (CI) 1.17-1.49; P < 0.001], cardiac death (RR 1.46, 95% CI 1.20-1.78; P < 0.001), heart failure hospitalization (RR 1.35, 95% CI 1.05-1.72; P = 0.02), and PPI (RR 1.89, 95% CI 1.58-2.27; P < 0.001) at 1-year follow-up. Periprocedural PPI after TAVR was associated with a higher risk of all-cause death (RR 1.17, 95% CI 1.11-1.25; P < 0.001) and heart failure hospitalization (RR 1.18, 95% CI 1.03-1.36; P = 0.02). Permanent pacemaker implantation was not associated with an increased risk of cardiac death (RR 0.84, 95% CI 0.67-1.05; P = 0.13). CONCLUSION: NOP-LBBB and PPI after TAVR are associated with an increased risk of all-cause death and heart failure hospitalization at 1-year follow-up. Periprocedural NOP-LBBB also increased the risk of cardiac death and PPI within the year following the procedure. Further studies are urgently warranted to enhance preventive measures and optimize the management of conduction disturbances post-TAVR.
Assuntos
Estenose da Valva Aórtica , Marca-Passo Artificial , Substituição da Valva Aórtica Transcateter , Valva Aórtica/cirurgia , Estenose da Valva Aórtica/cirurgia , Bloqueio de Ramo/etiologia , Bloqueio de Ramo/terapia , Humanos , Fatores de Risco , Substituição da Valva Aórtica Transcateter/efeitos adversos , Resultado do TratamentoRESUMO
AIMS: Left ventricular pressure overload is associated with activation of the cardiac renin-angiotensin system, which may contribute to myocardial fibrosis and worse clinical outcomes. We sought to assess the association between treatment with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) at baseline and clinical outcomes in patients with symptomatic, severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR) in the PARTNER 2 trial and registries. METHODS AND RESULTS: A total of 3979 intermediate, high, or prohibitive risk patients who underwent TAVR in the PARTNER 2 trial and registries (excluding the valve in valve registry) were included in the study. Clinical outcomes at 2 years were compared according to baseline ACEI/ARB treatment status using Kaplan-Meier event rates and study-stratified multivariable Cox proportional hazards regression models. Sensitivity analysis was conducted using propensity score matching. Of 3979 patients who were included in the current analysis, 1736 (43.6%) were treated and 2243 (56.4%) were not treated with ACEI/ARB at baseline. Treatment with ACEI/ARB was associated with lower 2-year all-cause mortality (18.6% vs. 27.5%, P < 0.0001), cardiovascular mortality (12.3% vs. 17.9%, P < 0.0001), and non-cardiovascular mortality (7.2% vs. 11.7%, P < 0.0001). Angiotensin-converting enzyme inhibitor/ARB treatment at baseline remained independently associated with a lower hazard of 2-year all-cause and cardiovascular mortality after multivariable adjustment, and propensity score matching. CONCLUSION: In a large cohort of patients with severe symptomatic AS from the PARTNER 2 trial and registries, ACEI/ARB treatment at baseline was independently associated with a lower risk of 2-year all-cause and cardiovascular mortality.
Assuntos
Estenose da Valva Aórtica , Substituição da Valva Aórtica Transcateter , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Valva Aórtica/cirurgia , Estenose da Valva Aórtica/cirurgia , Humanos , Sistema de Registros , Sistema Renina-Angiotensina , Substituição da Valva Aórtica Transcateter/efeitos adversos , Resultado do TratamentoRESUMO
AIMS: B-type natriuretic peptide (BNP) is a cardiac neurohormone that is secreted in response to ventricular volume expansion and pressure overload. There are conflicting data regarding the association between BNP levels and outcomes after transcatheter aortic valve replacement (TAVR). We therefore sought to assess the association between baseline BNP and adverse outcomes in patients with symptomatic, severe aortic stenosis (AS), and left ventricular ejection fraction (LVEF) ≥50%, undergoing TAVR in the PARTNER 2 Trial and Registry. METHODS AND RESULTS: A total of 1782 patients were included in the analysis, and BNP was evaluated both as a continuous log-transformed value and by a priori categories: low (<50 pg/mL), normal (≥50 and <100 pg/mL), moderately elevated (≥100 and <400 pg/mL), or markedly elevated (≥400 pg/mL). Clinical outcomes from discharge to 2 years were compared between patients according to their baseline BNP level, using Kaplan-Meier event rates and multivariable Cox proportional hazards regression models. After adjustment, spline curves revealed a non-linear association between log-transformed BNP and all-cause and cardiovascular mortality in which both the lowest and highest values were associated with increased mortality. Two-year all-cause mortality rates for those with low (n = 86), normal (n = 202), moderately elevated (n = 885), and markedly elevated (n = 609) baseline BNP were 20.0%, 9.8%, 17.7%, and 26.1%, respectively. In adjusted models, compared to a normal baseline BNP, low [adjusted hazard ratio (HR) 2.6, 95% confidence interval (CI) 1.3-5.0, P-value 0.005], moderately elevated (adjusted HR 1.6, 95% CI 1.0-2.6, P-value 0.06), and markedly elevated (adjusted HR 2.1, 95% CI 1.3-3.5, P-value 0.003) BNP were associated with increased all-cause mortality, driven by cardiovascular mortality. CONCLUSIONS: In a large cohort of patients with severe symptomatic AS and preserved LVEF undergoing TAVR, all-cause and cardiovascular mortality rates at 2 years were higher in patients with low and markedly elevated BNP levels. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/ unique identifier #NCT01314313, #NCT02184442, #NCT03222128, and #NCT03222141.
Assuntos
Estenose da Valva Aórtica , Substituição da Valva Aórtica Transcateter , Valva Aórtica/cirurgia , Estenose da Valva Aórtica/cirurgia , Humanos , Peptídeo Natriurético Encefálico , Sistema de Registros , Fatores de Risco , Volume Sistólico , Resultado do Tratamento , Função Ventricular EsquerdaRESUMO
OBJECTIVES: This multicenter retrospective study of the initial U.S. experience evaluated the safety and efficacy of temporary cardiac pacing with the Tempo® Temporary Pacing Lead. BACKGROUND: Despite increasing use of temporary cardiac pacing with the rapid growth of structural heart procedures, temporary pacing leads have not significantly improved. The Tempo lead is a new temporary pacing lead with a soft tip intended to minimize the risk of perforation and a novel active fixation mechanism designed to enhance lead stability. METHODS: Data from 269 consecutive structural heart procedures were collected. Outcomes included device safety (absence of clinically significant cardiac perforation, new pericardial effusion, or sustained ventricular arrhythmia) and efficacy (clinically acceptable pacing thresholds with successful pace capture throughout the index procedure). Postprocedure practices and sustained lead performance were also analyzed. RESULTS: The Tempo lead was successfully positioned in the right ventricle and achieved pacing in 264 of 269 patients (98.1%). Two patients (0.8%) experienced loss of pace capture. Procedural mean pace capture threshold (PCT) was 0.7 ± 0.8 mA. There were no clinically significant perforations, pericardial effusions, or sustained device-related arrhythmias. The Tempo lead was left in place postprocedure in 189 patients (71.6%) for mean duration of 43.3 ± 0.7 hr (range 2.5-221.3 hr) with final PCT of 0.84 ± 1.04 mA (n = 80). Of these patients, 84.1% mobilized out of bed with no lead dislodgment. CONCLUSION: The Tempo lead is safe and effective for temporary cardiac pacing for structural heart procedures, provides stable peri and postprocedural pacing and allows mobilization of patients who require temporary pacing leads.
Assuntos
Estimulação Cardíaca Artificial , Procedimentos Cirúrgicos Cardíacos , Marca-Passo Artificial , Assistência Perioperatória/instrumentação , Idoso , Idoso de 80 Anos ou mais , Estimulação Cardíaca Artificial/efeitos adversos , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Desenho de Equipamento , Feminino , Frequência Cardíaca , Humanos , Masculino , Segurança do Paciente , Assistência Perioperatória/efeitos adversos , Sistema de Registros , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Estados Unidos , Função Ventricular DireitaRESUMO
OBJECTIVES: We sought to compare clinical outcomes after percutaneous coronary intervention (PCI) in patients on versus not on hemodialysis (HD) and examine whether high on-treatment platelet reactivity (HPR) further impacts outcomes among patients on HD. BACKGROUND: Both chronic kidney disease (CKD) and HPR are predictors of major adverse cardiac events (MACE) after PCI. METHODS: Two-year outcomes of patients from the prospective, multicenter ADAPT-DES study (N = 8,582) were analyzed according to HD status at enrollment. All patients underwent platelet function testing with the VerifyNow assay; HPR on clopidogrel was defined as P2Y12 reaction units (PRU) >208. RESULTS: Compared with non-HD patients, patients on HD (n = 85) had significantly higher baseline PRU (median 254 vs. 188, p = .001) and more frequently had HPR (61.7% vs. 42.5%, p < .001). HD was associated with increased 2-year rates of MACE (death, myocardial infarction (MI) or definite stent thrombosis (ST); 23.4% vs. 10.7%, p < .001). HD was also strongly associated with 2-year overall mortality, cardiac death, MI, target vessel revascularization, major bleeding, stroke and ST. Following adjustment for HPR and other covariates, HD was independently associated with overall mortality, MI, ST, and major bleeding at 2 years. The relationship between HD status and 2-year MACE was consistent in patients with and without HPR (Pinteraction = .78). CONCLUSIONS: Nearly two-thirds of patients on HD exhibited HPR on clopidogrel, and both HD and HPR were independently associated with 2-year adverse outcomes after DES implantation. However, the deleterious impact of HD on clinical outcomes was present in both patients with and without HPR.
Assuntos
Aspirina/uso terapêutico , Clopidogrel/uso terapêutico , Doença da Artéria Coronariana/terapia , Terapia Antiplaquetária Dupla , Intervenção Coronária Percutânea , Inibidores da Agregação Plaquetária/uso terapêutico , Diálise Renal , Insuficiência Renal Crônica/terapia , Idoso , Aspirina/efeitos adversos , Clopidogrel/efeitos adversos , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/mortalidade , Trombose Coronária/mortalidade , Trombose Coronária/prevenção & controle , Stents Farmacológicos , Terapia Antiplaquetária Dupla/efeitos adversos , Terapia Antiplaquetária Dupla/mortalidade , Feminino , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/instrumentação , Intervenção Coronária Percutânea/mortalidade , Inibidores da Agregação Plaquetária/efeitos adversos , Testes de Função Plaquetária , Estudos Prospectivos , Sistema de Registros , Diálise Renal/efeitos adversos , Diálise Renal/mortalidade , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/mortalidade , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Transcatheter aortic valve replacement (TAVR) is increasingly used to treat patients with severe aortic stenosis (AS). Cardiovascular magnetic resonance imaging (CMR) provides reliable and reproducible estimates for assessment of cardiac structure and function after TAVR. The goal of this study was to conduct a systematic review and meta-analysis of the literature to assess left ventricular (LV) volumes, mass and function by CMR after TAVR. METHODS: Using Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines, we searched PubMed and Embase for studies reporting CMR findings before and at least 1 month after TAVR. Main factors of interest were LV end-diastolic volume index (LVEDVi), LV end-systolic volume index (LVESVi), LV mass index (LVMi), and left ventricular ejection fraction (LVEF). Standardized mean differences (SMD) were pooled by random effects meta-analytic techniques. RESULTS: Of 453 screened publications, 10 studies (published between 2012 and 2018) were included. A total of 305 patients completed pre- and post-TAVR follow-up CMR (mean age range 78.6-85.0 years, follow-up range 6-15 months). Random effects analysis showed TAVR resulted in reduced LVEDVi (SMD: -0.25, 95% CI: - 0.43 to - 0.07, P = 0.006), LVESVi (SMD: -0.24, 95% CI: - 0.44 to - 0.05, P = 0.01), LVMi (SMD: -0.82, 95% CI: - 1.0 to - 0.63, P < 0.001) and increased LVEF (SMD: 22, 95% CI: 6 to 38%, P = 0.006). Heterogeneity across studies was low (I2: 0%, Pheterogeneity > 0.05 for all). The median reduction was 4 ml/m2 (IQR: 3.1 to 8.2) for LVEDVi, 5 ml/m2 (IQR: 3.0 to 6.0) for LVESVi, and 15.1 g/m2 (IQR: 11.8 to 18.3) for LVMi. The median increase for LVEF was 3.4% (IQR 1.0 to 4.6%). CONCLUSIONS: CMR demonstrates reverse LV remodeling occurrs within 6-15 months after TAVR, with reductions in LVEDVi, LVESVi and LVMi, and increased LVEF.
Assuntos
Estenose da Valva Aórtica/cirurgia , Valva Aórtica/cirurgia , Ventrículos do Coração/diagnóstico por imagem , Imageamento por Ressonância Magnética , Substituição da Valva Aórtica Transcateter , Função Ventricular Esquerda , Remodelação Ventricular , Idoso , Idoso de 80 Anos ou mais , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/fisiopatologia , Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/fisiopatologia , Feminino , Ventrículos do Coração/fisiopatologia , Humanos , Masculino , Valor Preditivo dos Testes , Recuperação de Função Fisiológica , Fatores de Tempo , Substituição da Valva Aórtica Transcateter/efeitos adversos , Resultado do TratamentoRESUMO
AIMS: Transcatheter aortic valve replacement (TAVR) is now an established therapy for intermediate-risk surgical candidates with symptomatic, severe aortic stenosis. The clinical impact of new-onset left bundle branch block (LBBB) after TAVR remains controversial and has not been studied in intermediate-risk patients. We therefore sought to analyse outcomes associated with new LBBB in a large cohort of intermediate-risk patients treated with TAVR. METHODS AND RESULTS: A total of 2043 patients underwent TAVR in the PARTNER II trial and S3 intermediate-risk registry and survived to hospital discharge. Patients were excluded from the current analysis due to baseline conduction disturbances, pre-existing permanent pacemaker (PPM), and new PPM during the index hospitalization. Clinical outcomes at 2 years were compared between patients with and without persistent, new-onset LBBB at hospital discharge, and multivariable analysis was performed to identify predictors of mortality. Among 1179 intermediate-risk patients, new-onset LBBB at discharge occurred in 179 patients (15.2%). Patients with new LBBB were similar to those without except for more frequent diabetes and more frequent treatment with SAPIEN 3 vs. SAPIEN XT. At 2 years, new LBBB was associated with increased rates of all-cause mortality (19.3% vs. 10.8%, P = 0.002), cardiovascular mortality (16.2% vs. 6.5%, P < 0.001), rehospitalization, and new PPM implantation. By multivariable analysis, new LBBB remained an independent predictor of 2-year all-cause [hazard ratio (HR) 1.98, 95% confidence interval (95% CI) 1.33, 2.96; P < 0.001] and cardiovascular (HR 2.66 95% CI 1.67, 4.24; P < 0.001) mortality. New LBBB was also associated with worse left ventricular systolic function at 1 and 2-year follow-up. CONCLUSIONS: In a large cohort of intermediate-risk patients from the PARTNER II trial and registry, persistent, new-onset LBBB occurred in 15.2% of patients without baseline conduction disturbances or pacemaker. New LBBB was associated with adverse clinical outcomes at 2 years, including all-cause and cardiovascular mortality, rehospitalization, new pacemaker implantation, and worsened left ventricular systolic function. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov #NCT01314313 and NCT03222128.
Assuntos
Estenose da Valva Aórtica/cirurgia , Bloqueio de Ramo/etiologia , Complicações Pós-Operatórias/etiologia , Substituição da Valva Aórtica Transcateter/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Masculino , Medição de Risco , Resultado do TratamentoRESUMO
AIMS: The prognostic implications of periprocedural myocardial infarction (PMI) after percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) remain controversial. We examined the 3-year rates of mortality among patients with and without PMI undergoing left main coronary artery intervention randomized to PCI with everolimus-eluting stents vs. CABG in the large-scale, multicentre, prospective, randomized EXCEL trial. METHODS AND RESULTS: By protocol, PMI was defined using an identical threshold for PCI and CABG [creatinine kinase-MB (CK-MB) elevation >10× the upper reference limit (URL) within 72 h post-procedure, or >5× URL with new Q-waves, angiographic vessel occlusion, or loss of myocardium on imaging]. Cox proportional hazards modelling was performed controlling for age, sex, hypertension, diabetes mellitus, left ventricular ejection fraction, SYNTAX score, and chronic obstructive pulmonary disease (COPD). A total of 1858 patients were treated as assigned by randomization. Periprocedural MI occurred in 34/935 (3.6%) of patients in the PCI group and 56/923 (6.1%) of patients in the CABG group [odds ratio 0.61, 95% confidence interval (CI) 0.40-0.93; P = 0.02]. Periprocedural MI was associated with SYNTAX score, COPD, cross-clamp duration and total procedure duration, and not using antegrade cardioplegia. By multivariable analysis, PMI was associated with cardiovascular death and all-cause death at 3 years [adjusted hazard ratio (HR) 2.63, 95% CI 1.19-5.81; P = 0.02 and adjusted HR 2.28, 95% CI 1.22-4.29; P = 0.01, respectively]. The effect of PMI was consistent for PCI and CABG for cardiovascular death (Pinteraction = 0.56) and all-cause death (Pinteraction = 0.59). Peak post-procedure CK-MB ≥10× URL strongly predicted mortality, whereas lesser degrees of myonecrosis were not associated with prognosis. CONCLUSION: In the EXCEL trial, PMI was more common after CABG than PCI, and was strongly associated with increased 3-year mortality after controlling for potential confounders. Only extensive myonecrosis (CK-MB ≥10× URL) was prognostically important.
Assuntos
Ponte de Artéria Coronária/efeitos adversos , Doença da Artéria Coronariana/terapia , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/mortalidade , Intervenção Coronária Percutânea/efeitos adversos , Idoso , Estudos de Casos e Controles , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/diagnóstico por imagem , Creatina Quinase Forma MB/análise , Stents Farmacológicos/efeitos adversos , Everolimo/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mortalidade/tendências , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/metabolismo , Período Perioperatório/estatística & dados numéricos , Prognóstico , Estudos Prospectivos , Doença Pulmonar Obstrutiva Crônica/complicações , Volume Sistólico/fisiologia , Função Ventricular Esquerda/fisiologiaRESUMO
BACKGROUND: Elevated B-type natriuretic peptide (BNP) is reflective of impaired cardiac function and is associated with worse prognosis among patients with coronary artery disease (CAD). We sought to assess the association between baseline BNP, adverse outcomes, and the relative efficacy of percutaneous coronary intervention (PCI) versus coronary artery bypass grafting (CABG) in patients with left main CAD. METHODS: The EXCEL trial (Evaluation of XIENCE Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization) randomized patients with left main CAD and low or intermediate SYNTAX scores (Synergy Between PCI With TAXUS and Cardiac Surgery) to PCI with everolimus-eluting stents versus CABG. The primary end point was the composite of all-cause death, myocardial infarction, or stroke. We used multivariable Cox proportional hazards regression to assess the associations between normal versus elevated BNP (≥100 pg/mL), randomized treatment, and the 3-year risk of adverse events. RESULTS: BNP at baseline was elevated in 410 of 1037 (39.5%) patients enrolled in EXCEL. Patients with elevated BNP levels were older and more frequently had additional cardiovascular risk factors and lower left ventricular ejection fraction than those with normal BNP, but had similar SYNTAX scores. Patients with elevated BNP had significantly higher 3-year rates of the primary end point (18.6% versus 11.7%; adjusted hazard ratio [HR], 1.62; 95% confidence interval [CI], 1.16-2.28; P=0.005) and higher mortality (11.5% versus 3.9%; adjusted HR, 2.49; 95% CI, 1.48-4.19; P=0.0006), both from cardiovascular and noncardiovascular causes. In contrast, there were no significant differences in the risks of myocardial infarction, stroke, ischemia-driven revascularization, stent thrombosis, graft occlusion, or major bleeding. A significant interaction ( Pinteraction=0.03) was present between elevated versus normal BNP and treatment with PCI versus CABG for the adjusted risk of the primary composite end point at 3 years among patients with elevated BNP (adjusted HR for PCI versus CABG, 1.54; 95% CI, 0.96-2.47) versus normal BNP (adjusted HR, 0.74; 95% CI, 0.46-1.20). This interaction was stronger when log(BNP) was modeled as a continuous variable ( Pinteraction=0.002). CONCLUSIONS: In the EXCEL trial, elevated baseline BNP levels in patients with left main CAD undergoing revascularization were independently associated with long-term mortality but not nonfatal adverse ischemic or bleeding events. The relative long-term outcomes after PCI versus CABG for revascularization of left main CAD may be conditioned by the baseline BNP level. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01205776.
Assuntos
Ponte de Artéria Coronária , Doença da Artéria Coronariana/terapia , Estenose Coronária/terapia , Peptídeo Natriurético Encefálico/sangue , Intervenção Coronária Percutânea , Idoso , Biomarcadores/sangue , Ponte de Artéria Coronária/efeitos adversos , Ponte de Artéria Coronária/mortalidade , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/mortalidade , Estenose Coronária/sangue , Estenose Coronária/diagnóstico por imagem , Estenose Coronária/mortalidade , Stents Farmacológicos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/instrumentação , Intervenção Coronária Percutânea/mortalidade , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento , Regulação para CimaRESUMO
BACKGROUND: The prognostic impact of high-sensitivity C-reactive protein (CRP) levels in patients with left main coronary artery disease (LMCAD) treated with percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) is unknown. We sought to determine the effect of elevated baseline CRP levels on the 3-year outcomes after LMCAD revascularization and to examine whether CRP influenced the relative outcomes of PCI versus CABG. METHODS: In the EXCEL trial, patients with LMCAD and Synergy between PCI with Taxus and Cardiac Surgery (SYNTAX) scores ≤32 were randomized to PCI versus CABG. The primary composite outcome of death, myocardial infarction (MI), or stroke was analyzed according to baseline CRP levels. RESULTS: Among 999 patients with available CRP levels, median CRP was 3.10 mg/L (interquartile range 1.12-6.40 mg/L). The rate of the primary composite end point of death, MI, or stroke at 3 years steadily increased with greater baseline CRP levels. The adjusted relationship between the 3-year composite rate of death, MI, or stroke and baseline CRP modeled as a continuous log-transformed variable demonstrated steadily increasing event rates with greater CRP levels (adjusted hazard ratio, 1.26, 95% CI 1.10-1.44, P = .0008). Similarly, patients with CRP ≥10 mg/L had a 3-fold higher risk of the 3-year primary end point compared to patients with lower CRP levels (adjusted hazard ratio 2.92, 95% CI 1.88-4.54, P < .0001). The association between an elevated CRP level and the adjusted 3-year risk of the primary composite end point did not differ according to revascularization strategy (Pinteraction = .75). CONCLUSIONS: In patients with LMCAD undergoing revascularization, elevated baseline CRP levels were strongly associated with subsequent death, MI, and stroke at 3 years, irrespective of the mode of revascularization. Further studies are warranted to determine whether anti-inflammatory therapies may improve the prognosis of high-risk patients with LMCAD following revascularization.
Assuntos
Proteína C-Reativa/análise , Ponte de Artéria Coronária , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/cirurgia , Intervenção Coronária Percutânea , Idoso , Biomarcadores/sangue , Causas de Morte , Comorbidade , Doença da Artéria Coronariana/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/etiologia , Prognóstico , Acidente Vascular Cerebral/etiologia , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Chronic kidney disease (CKD) is associated with an increased risk of adverse cardiovascular outcomes, in patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI). However, most studies used bare-metal stents or first-generation drug-eluting stents, and less guideline-directed therapy to reduce cardiovascular risk was reported in CKD patients. This study investigates the impact of moderate-CKD on patients undergoing PCI in the current era. METHODS: Patient level data were pooled from 2 multicenter randomized trials (BIONICS and NIREUS trials) with a near "all-comers" design, comparing PCI with ridaforolimus-eluting stents vs. zotarolimus-eluting stents in patients with CAD. Patients were classified according to the presence or absence of moderate-CKD, defined as creatinine clearance (CrCl) <60 mL/min. We compared baseline characteristics, angiographic findings, and clinical outcomes 1-year post-PCI. RESULTS: 236/2,201 (10.7%) patients had CKD, mean CrCl of 50.3 + 7.8 mL/min. These patients were generally older and more often with hypertension than non-CKD patients, but the use of guideline-directed therapy was similar between the groups. CKD was associated with an increased risk of cardiovascular death (hazard ratio [HR] 6.08; 95% CI 2.11-17.51; p < 0.001), but with a reduced occurrence of repeated revascularization, including ischemia-driven revascularization (HR 0.47; 95% CI 0.24-0.92; p < 0.05). The rate of repeated angiography per severe cardiovascular adverse event was significantly lower in the CKD than the non-CKD group (23/38 [61%] vs. 253/334 [76%], p < 0.05). CONCLUSIONS: Moderate-CKD in patients with CAD was associated with higher rates of all-cause and cardiovascular mortality, yet with a lower risk of revascularization 1-year following PCI. Lack of guideline-directed medical therapy does not explain the adverse outcome of CKD patients.
Assuntos
Doença da Artéria Coronariana/cirurgia , Intervenção Coronária Percutânea/estatística & dados numéricos , Insuficiência Renal Crônica/epidemiologia , Reoperação/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Angiografia/estatística & dados numéricos , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/mortalidade , Stents Farmacológicos , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Intervenção Coronária Percutânea/instrumentação , Período Pós-Operatório , Ensaios Clínicos Controlados Aleatórios como Assunto , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/diagnóstico , Fatores de Risco , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
OBJECTIVES: We sought to identify clinical, electrocardiographic (ECG), and angiographic characteristics that are predictive of 3-year mortality after primary percutaneous coronary intervention (PCI) in patients with non-anterior ST-elevation myocardial infarction (NA-STEMI) from the Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) trial. BACKGROUND: Which patients with NA-STEMI undergoing PCI have a poor prognosis is uncertain. METHODS: NA-STEMI was defined as ST-segment elevation in lateral (V5, V6, I, aVL), inferior (II, III, aVF), or inferolateral (I, II, III, aVF, and V5-V6) ECG leads or posterior myocardial infarction with ST-segment depression of ≥1 mm in ≥2 contiguous anterior leads. Cox regression was used to identify independent predictors of 3-year mortality. Missing data were imputed using multiple imputation. RESULTS: In HORIZONS-AMI, 2,578/3,602 patients had no prior coronary artery bypass grafting, underwent single-vessel PCI, and had baseline ECG data assessed in an independent core laboratory. Among them, 1,495 (58.0%) had NA-STEMI. Patients with NA-STEMI had lower 3-year mortality risk than those with anterior STEMI (4.5% versus 7.1%, P = 0.004). The independent predictors of increased 3-year mortality in NA-STEMI were older age (median > 59.0 years), diabetes, reduced LVEF (≤50%), Killip class ≥2, post-procedure TIMI flow 0-2 versus 3, renal insufficiency, and ST-resolution <30% at 60 min post-PCI. Patients with 0, 1, 2, 3, and ≥4 of these risk factors had 3-year mortality rates of 1.8%, 2.3%, 3.1%, 6.1%, and 36.3%, respectively (P < 0.0001). CONCLUSIONS: Although NA-STEMI carries a better prognosis than anterior STEMI, high-risk patient cohorts with NA-STEMI may be identified who have substantial 3-year mortality.
Assuntos
Intervenção Coronária Percutânea/mortalidade , Infarto do Miocárdio com Supradesnível do Segmento ST/mortalidade , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Idoso , Angiografia Coronária , Eletrocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/instrumentação , Valor Preditivo dos Testes , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem , Stents , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Acute myocarditis carries a variable prognosis. We evaluated the morbidity and mortality rates in patients with acute myocarditis and admission electrocardiographic predictors of outcome. METHODS AND RESULTS: Patients admitted to a tertiary hospital with a clinical diagnosis of acute myocarditis were evaluated; 193 patients were included. Median follow-up was 5.7 years, 82% were male, and overal median age was 30 years (range 21-39). The most common clinical presentations were chest pain (77%) and fever (53%). The 30-day survival rate was 98.9%. Overall survival during follow-up was 94.3%. The most common abnormalities observed on electrocardiography were T-wave changes (36%) and ST-segment changes (32%). Less frequent changes included abnormal T-wave axis (>105° or < -15°; 16%), abnormal QRS axis (12%), QTc >460 ms (11%), and QRS interval ≥120 ms (5%). Wide QRS-T angle (≥100°) was demonstrated in 13% of the patients and was associated with an increased mortality rate compared with patients with a narrow QRS-T angle (20% vs 4%; P = .007). The rate of heart failure among patients with a wide QRS-T angle was significantly higher (36% vs 10%; P = .001). Cox regression analysis demonstrated that a wide QRS-T angle (≥100°) was a significant independent predictor of heart failure (hazard ratio [HR] 3.20, 95% confidence interval [CI] 1.35-7.59; P < .01) and of the combined end point of death or heart failure (HR 2.56, 95% CI 1.14-5.75; P < .05). CONCLUSIONS: QRS-T angle is a predictor of increased morbidity and mortality in acute myocarditis.
Assuntos
Eletrocardiografia/mortalidade , Miocardite/mortalidade , Miocardite/fisiopatologia , Doença Aguda , Adulto , Eletrocardiografia/tendências , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Morbidade/tendências , Mortalidade/tendências , Miocardite/diagnóstico , Valor Preditivo dos Testes , Estudos Retrospectivos , Adulto JovemRESUMO
INTRODUCTION: Aortic stenosis is the most common significant valvular disease in the western world. These patients are treated operatively unless they are at high operative risk or inoperable. During the last decade an alternative approach has evolved - transcatheter aortic valve implantation (TAVI). This method was shown to be at least as effective and safe as the operative one. However, very little data exists on long term follow-up (5 years and above), especially regarding valve durability and patient survival. OBJECTIVES: To present a long term follow-up on patients who underwent transcutaneous self-expandable aortic valve implantation in our department between the years 2008-2011. METHODS: In September 2008 the first CoreValve implantation was performed in Israel at Hadassah Medical Center. All records of patients who were transplanted between 9.2008 and 10.2011 were reviewed. The function of the valve early after the procedure was compared to its function at the end of the follow-up period. RESULTS: A total of 38 patients (out of 71) survived at least 54 months, of them, 19 have an echocardiography examination at the end of the follow-up period. In all patients the implanted valve was found to function well at the end of the follow-up period, without significant stenosis or paravalvular leak. In fact, in approximately half of these patients, the degree of paravalvular leak decreased during the follow-up period. DISCUSSION: On long term (5 years) follow-up of patients who were implanted with the self-expandable aortic valve (CoreValve), no deterioration of the valve was observed. In fact, in approximately half of the patients, a decrease in the severity of the paravalvular leak was demonstrated.
Assuntos
Estenose da Valva Aórtica/cirurgia , Substituição da Valva Aórtica Transcateter/métodos , Valva Aórtica , Seguimentos , Humanos , Israel , Desenho de Prótese , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) tubes are commonly utilized as a method of enteral feeding in patients unable to obtain adequate oral nutrition. Although some studies have shown improved mortality in select populations, the safety and effectiveness of PEG insertion in patients with dementia compared with those with other neurological diseases or head and neck malignancy remains less well defined. OBJECTIVE: To evaluate the nutritional effectiveness, rate of rehospitalization, and risk of mortality among patients with dementia compared with patients with other neurological diseases or head and neck cancers who undergo PEG placement. MATERIALS AND METHODS: We conducted a retrospective analysis from a prospective database of patients who underwent PEG placement at an academic tertiary center between 2008 and 2013. The following data were collected: indication for PEG, patient demographics, biochemical markers of nutritional status rehospitalization, and survival rates. RESULTS: During the study period, 392 patients underwent PEG tube placement. Indications for PEG were dementia (N=165, group A), cerebrovascular accident (N=124, group B), and other indications such as oropharyngeal cancers and motor neuron disease (N=103, group C). The mean follow-up time after PEG was 18 months (range, 3 to 36 mo). No differences in baseline demographics were noted. PEG insertion in the dementia (group A) neither reduced the rehospitalization rate 6 months' postprocedure compared with groups B and C (2.45 vs. 1.86 and 1.65, respectively; P=0.05), nor reduced the mortality rate within the first year post-PEG placement (75% vs. 58% and 38% for groups A, B, and C, respectively, P=0.001), as well, it did not improve survival at 1 month after the procedure (15% vs. 3.26% and 7.76%, for groups A, B, C, respectively, P<0.01). The presence of dementia was also associated with shorter mean time to death (7.2 vs. 8.85 and 8 mo for groups A, B, C, respectively, P<0.05). The rate of improvement of the nutritional biomarker albumin was lower in the dementia group [3.1. to 2.9 vs. 3.2 to 3.3 and 3 to 3.3 g/dL for groups A, B, and C, respectively (P<0.02)]. Multivariate regression analysis showed that the presence of dementia was an independent predictor for mortality rate within the first year and 1-month mortality rate in patients undergoing PEG insertion with odds ratio 3.22 (95% confidence interval, 1.52-4.32) and odds ratio 2.52 (95% confidence interval, 1.22-3.67). CONCLUSIONS: PEG insertion in patients with dementia neither improve both short-term and long-term mortality nor rehospitalization rate as compared with patients who underwent PEG placement for alternate indications such as other neurological diseases or head and neck malignancy and even was associated with shorter time to death. Furthermore, PEG insertion in patients with dementia did not improve albumin. Therefore, careful selection of patients with dementia is warranted before PEG placement weighing the risks and benefits on a personalized basis.
Assuntos
Demência/fisiopatologia , Nutrição Enteral/instrumentação , Gastroscopia/instrumentação , Gastrostomia/instrumentação , Desnutrição/terapia , Estado Nutricional , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Tomada de Decisão Clínica , Bases de Dados Factuais , Demência/mortalidade , Demência/psicologia , Nutrição Enteral/efeitos adversos , Nutrição Enteral/mortalidade , Feminino , Gastroscopia/efeitos adversos , Gastroscopia/mortalidade , Gastrostomia/efeitos adversos , Gastrostomia/mortalidade , Avaliação Geriátrica/métodos , Humanos , Masculino , Desnutrição/mortalidade , Desnutrição/fisiopatologia , Desnutrição/psicologia , Pessoa de Meia-Idade , Avaliação Nutricional , Readmissão do Paciente , Seleção de Pacientes , Recuperação de Função Fisiológica , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Albumina Sérica Humana/metabolismo , Fatores de Tempo , Resultado do TratamentoRESUMO
Small-conductance Ca(2+)-activated K(+) (SK or K(Ca)2) channels are widely expressed in the CNS. In several types of neurons, these channels were shown to become activated during repetitive firing, causing early spike frequency adaptation. In CA1 pyramidal cells, SK channels in dendritic spines were shown to regulate synaptic transmission. However, the presence of functional SK channels in the somata and their role in controlling the intrinsic firing of these neurons has been controversial. Using whole-cell voltage-clamp and current-clamp recordings in acute hippocampal slices and focal applications of irreversible and reversible SK channel blockers, we provide evidence that functional SK channels are expressed in the somata and proximal dendrites of adult rat CA1 pyramidal cells. Although these channels can generate a medium duration afterhyperpolarizing current, they play only an auxiliary role in controlling the intrinsic excitability of these neurons, secondary to the low voltage-activating, noninactivating K(V)7/M channels. As long as K(V)7/M channels are operative, activation of SK channels during repetitive firing does not notably affect the spike output of CA1 pyramidal cells. However, when K(V)7/M channel activity is compromised, SK channel activation significantly and uniquely reduces spike output of these neurons. Therefore, proximal SK channels provide a "second line of defense" against intrinsic hyperexcitability, which may play a role in multiple conditions in which K(V)7/M channels activity is compromised, such as hyposmolarity.