His-bundle pacing versus biventricular pacing in cardiac resynchronization therapy patients: A crossover design comparison.

BACKGROUND: Cardiac resynchronization therapy (CRT) typically is attempted with biventricular pacing (BiVP). One-third of patients are nonresponders. His-bundle pacing (HBP) has been evaluated as an alternative means of effecting CRT because it generates truly physiologic ventricular activation, as evidenced in part by the morphologic identity between normally conducted and paced QRS complexes. OBJECTIVE: The purpose of this study was to assess the feasibility of, and clinical response to, permanent HBP as an alternative to BiVP in CRT-indicated patients. METHODS: Patients were implanted with a right atrial pacing lead, defibrillation lead, left ventricular (LV) lead via the coronary sinus, and HBP lead. His and LV leads were plugged into the LV port via a Y-adapter. After successful implant, patients were randomized in single patient-blinded fashion to either HBP or BiVP. After 6 months, patients were crossed over to the other pacing modality and followed for another 6 months. Quality-of-life assessments, echocardiographic measurements, New York Heart Association classification, and 6-minute hall walk test were obtained at baseline and at each 6-month follow-up. RESULTS: Twenty-nine patients were enrolled; 21 (72%) demonstrated electrical resynchronization (QRS narrowing) at implant. Twelve patients completed the crossover analysis at 1 year. Clinical outcomes (quality of life, New York Heart Association functional class, 6-minute hall walk test, LV ejection fraction) were significantly improved for both pacing modes compared with baseline measures. CONCLUSION: In this crossover comparison between HBP and BiVP, HBP was found to effect an equivalent CRT response. QRS narrowing was observed in 21 of 29 patients, suggesting this approach may be feasible in more patients with left bundle branch block than previously assumed.

Electrical resynchronization induced by direct His-bundle pacing.

BACKGROUND: Biventricular pacing (BiV) to effect cardiac resynchronization therapy can be technically difficult and fails to elicit a clinical response in 30% to 40% of patients. Direct His-bundle pacing (DHBP) theoretically could obviate some of these problems. Although DHBP is capable of narrowing the QRS in some patients, the consistency with which this can be achieved has not been characterized. OBJECTIVE: The purpose of this study was to restore His-Purkinje functionality in consecutive patients undergoing de novo clinically mandated cardiac resynchronization therapy. METHODS: DHBP was temporarily implemented at the time of implantation of a permanent BiV system in patients referred for cardiac resynchronization therapy. Native conduction, DHBP, and BiV QRS duration were compared. All patients presenting for BiV cardiac resynchronization therapy were eligible for the study. Ten patients were studied. RESULTS: DHBP was successfully implemented in all 10 patients. In 7 of 10 patients, DHBP narrowed the QRS significantly compared with native conduction and BiV (mean QRS duration: native 171 +/- 13 ms, DHBP 148 +/- 11 ms, BiV 158 +/- 21, P <.0001). QRS narrowing with DHBP was specifically attributable to capture of latent His-Purkinje tissue. DHBP lead implantation time (16 minutes) was shorter than standard left ventricular lead implantation time (42 minutes). CONCLUSION: DHBP was readily implemented in patients with standard indications for BiV cardiac resynchronization therapy. In most patients studied, DHBP resulted in a significantly narrower QRS compared with native conduction. DHBP may offer a physiologic alternative to BiV for cardiac resynchronization therapy.

Six-month follow-up of patients with in-hospital thrombocytopenia during heparin-based anticoagulation (from the Complications After Thrombocytopenia Caused by Heparin [CATCH] registry).

Thrombocytopenia is a predictor of adverse outcomes in patients with acute coronary syndromes and in critically ill patients. The Complications After Thrombocytopenia Caused by Heparin (CATCH) registry was designed to explore the incidence, management, and clinical consequences of in-hospital thrombocytopenia occurring during heparin-based anticoagulation in diverse clinical settings. We conducted a prospective observational study of 37 United States hospitals participating in the CATCH registry to assess the relation of in-hospital thrombocytopenia to long-term outcomes. A total of 2,104 patients at increased risk of developing in-hospital thrombocytopenia or thrombosis were identified, and the 6-month mortality and rehospitalization rates were determined. Thrombocytopenia was not a significant predictor of 6-month mortality. In an adjusted model for in-hospital death in this cohort, thrombocytopenia had an odds ratio of 3.59 (95% confidence interval 2.24 to 5.77). The postdischarge mortality rate at 6 months was 9.7%. No significant difference was observed in the long-term mortality between patients who developed thrombocytopenia and those who did not. Thrombocytopenia was a weak, but statistically significant, predictor of a composite of mortality and rehospitalization at 6 months (hazards ratio 0.80, 95% confidence interval 0.65 to 0.98, p = 0.03). In conclusion, the 6-month mortality rate among heparin-treated patients with thrombocytopenia is high, although the risk independently related to thrombocytopenia appears to be restricted to the acute hospital phase.

Contribution of bleeding and thromboembolic events to in-hospital mortality among patients with thrombocytopenia treated with heparin.

In a population of patients experiencing thrombocytopenia while treated with heparin, bleeding and thromboses are well-appreciated complications, but their relative contributions to mortality have been less well described. In this population, the aims of this study were (1) to identify the independent predictors of bleeding and (2) to compare the incidence and the strength of association of bleeding and of new thromboses to in-hospital mortality. The independent predictors of bleeding and in-hospital mortality were identified using multivariate logistic regression models on the 1,478 patients who developed thrombocytopenia after their enrollment in the Complications After Thrombocytopenia Caused by Heparin (CATCH) study. The independent predictors of bleeding were chronic hematologic disorders, intra-aortic balloon pump, congestive heart failure, and platelet count nadir <120 x 10(9)/L. Although bleeding (n = 141 [10%]) and thromboembolic complications (n = 135 [9%]) were equally prevalent, the former was less strongly associated than the latter with in-hospital mortality (odds ratio 1.75, 95% confidence interval 1.01 to 3.03, and odds ratio 2.77, 95% confidence interval 1.67 to 4.61, respectively). In conclusion, medical management should be directed mainly at the prevention of thromboembolic complications, while additionally considering the risk for bleeding.

Evaluation and management of thrombocytopenia and suspected heparin-induced thrombocytopenia in hospitalized patients: The Complications After Thrombocytopenia Caused by Heparin (CATCH) registry.

BACKGROUND: Thrombocytopenia and heparin-induced thrombocytopenia (HIT) are potentially devastating paradoxical side effects of heparin therapy. We explored the evaluation, management, and clinical consequences of thrombocytopenia occurring during heparin therapy in diverse clinical settings. METHODS: CATCH was a prospective observational study that enrolled 3,536 patients in 48 US hospitals. Data were collected on 3 strata: patients receiving any form of heparin for > or =96 hours (n = 2,420); cardiac care unit (CCU) patients treated with heparin who developed thrombocytopenia (n = 1,090); patients who had an HIT assay performed (n = 449). RESULTS: Thrombocytopenia occurred in 36.4% of patients in the prolonged heparin stratum and was associated with an increased risk of death or thromboembolic complication (OR 1.5, 95% CI 1.2-1.9). Among a subset of patients whose clinical presentation suggested they were at high risk for HIT, suspicion for HIT was uncommon (prolonged heparin stratum 19.8%, CCU stratum 37.6%) and often did not arise until > or =1 day after patients developed thrombocytopenia. Often patients were not evaluated for HIT until after they had had a thromboembolic complication (prolonged heparin stratum 43.8%, CCU stratum 61%). Even after HIT was suspected, patients often continued to receive heparin. Direct thrombin inhibitor use was infrequent (prolonged heparin stratum 29.4%, CCU stratum 35.6%). Among the few patients who underwent evaluation, HIT was confirmed in 46.7% of the prolonged heparin stratum and 31.4% of the CCU stratum. CONCLUSIONS: Thrombocytopenia is common among patients receiving heparin, and it is associated with substantial risk for catastrophic complications. Despite the high risk for HIT in this population, recognition, evaluation, and appropriate treatment are infrequent and delayed.

Incidence and prognostic significance of thrombocytopenia in patients treated with prolonged heparin therapy.

BACKGROUND: Despite widespread heparin use in clinical practice, the associated development of thrombocytopenia is an underrecognized and undertreated complication. METHODS: We analyzed data from consecutive hospitalized patients treated with heparin (unfractionated or low molecular weight) for 4 days or longer to determine the incidence, predictors, prognostic significance, and management of "thrombocytopenia," defined as a platelet count less than 150 x 10(9)/L, reduction in platelet count of 50% or more from the admission level, or both. RESULTS: We enrolled 2420 patients (median age, 65.2 years; 43.8% women) in 48 US hospitals. Thrombocytopenia occurred in 881 patients (36.4%; 95% confidence interval [CI], 34.5%-38.3%). Of those who developed thrombocytopenia, 5.1% died, compared with 1.6% of those without thrombocytopenia (odds ratio [OR], 3.4; 95% CI, 2.1-5.6; P< .001). Thrombocytopenia was also associated with greater risk of myocardial infarction (OR, 2.1; 95% CI, 1.5-2.8; P< .001) and congestive heart failure (OR, 1.3; 95% CI, 1.1-1.6; P= .01). After adjustment for important covariates, thrombocytopenia remained an independent predictor of thrombotic and hemorrhagic events. A relative reduction in platelet count of more than 70% was the strongest independent predictor of death (OR, 13.4; 95% CI, 6.5-27.6; P< .001), followed by a relative reduction in platelet count of 50% to 70%, worse Killip class, occurrence of thromboembolic complications, older age, and longer duration of heparin therapy. CONCLUSIONS: Thrombocytopenia occurs frequently after prolonged heparin therapy and is strongly associated with worse short-term clinical outcome. The relative reduction in platelet count is a powerful independent predictor of all-cause mortality in hospitalized patients.

The use of implantable cardioverter defibrillators for the prevention of sudden cardiac death: a review of the evidence and implications.

Sudden cardiac death (SCD) claims approximately 460,000 lives per year in the United States, and half of these deaths occur in people with a history of coronary artery disease. Patients with left ventricular dysfunction and a history of myocardial infarction are at especially high risk. There is now strong evidence from multiple well-designed randomized controlled trials that implantable cardioverter defibrillators (ICDs) save lives when used for both primary and secondary prevention. As indications for ICD implantation have broadened, considerable debate has taken place because of the substantial cost involved in widespread ICD utilization. This article summarizes the epidemiology of SCD, reviews the evidence supporting the use of ICDs in patients with ischemic cardiomyopathy, and explores some of the controversy surrounding ICD utilization that has arisen in the wake of recent trials that have utilized ICDs for the primary prevention of SCD.