Characteristics of a large sample of candidates for permanent ventricular pacing included in the Biventricular Pacing for Atrio-ventricular Block to Prevent Cardiac Desynchronization Study (BioPace).

AIMS: The general clinical profile of European pacemaker recipients who require predominant ventricular pacing (VP) is scarcely known. We examined the demographic and clinical characteristics of the 1808 participants (out of 1833 randomized patients) of the ongoing Biventricular Pacing for Atrio-ventricular Block to Prevent Cardiac Desynchronization (BioPace) study. METHODS AND RESULTS: BioPace recruited patients between May 2003 and September 2007 predominantly in European medical centres. We analysed demographic data and described clinical characteristics and electrophysiological parameters prior to device implantation in 1808 enrolled patients. The mean age ± standard deviation (SD) of the 1808 patients was 73.5 ± 9.2 years, 1235 (68%) were men, 654 (36%) presented without structural heart disease, 547 (30%) had ischemic, 355 (20%) hypertensive, 146 (8%) valvular, and 102 (6%) non-ischemic dilated cardiomyopathy. Mean left ventricular ejection fraction was 55.4 ± 12.3%. The main pacing indications were (a) permanent and intermittent atrioventricular (AV) block in 973 (54%), (b) atrial fibrillation with slow ventricular rate in 313 (17%), and (c) miscellaneous bradyarrhythmias in 522 (29%) patients. Mean QRS duration was 118.5 ± 30.5 ms, left bundle branch block was present in 316 (17%), and atrial tachyarrhythmias in 426 (24%) patients. CONCLUSION: To the best of our knowledge, this sample is a representative source of description of the general profile of European pacemaker recipients who require predominant VP. Patients' characteristics included advanced age, predominantly male gender, preserved left ventricular systolic function, high-grade AV block, narrow QRS complex, and atrial tachyarrhythmias, the latter being present in nearly one-fourth of the cohort.

The MINERVA study design and rationale: a controlled randomized trial to assess the clinical benefit of minimizing ventricular pacing in pacemaker patients with atrial tachyarrhythmias.

BACKGROUND: Dual-chamber (DDD) pacing has generally been regarded as "physiologic pacing" and therefore expected to be superior to ventricular pacing. Major randomized trials have so far failed to demonstrate significant reductions in the incidences of mortality, stroke, and heart failure. It has been shown that unnecessary ventricular pacing in patients with sinus node dysfunction or only intermittent atrioventricular block is associated with ventricular desynchronization and increased risk of atrial tachyarrhythmias (ATA). METHODS: The MINimizE Right Ventricular pacing to prevent Atrial fibrillation and heart failure (MINERVA) study is a prospective, multi-center, randomized, international, single-blind, controlled trial designed to determine whether physiologic pacing through the managed ventricular pacing (MVP) algorithm combined with preventive atrial pacing (PAP) and atrial antitachycardia pacing (ATP) is superior to standard DDD pacing in terms of 2-year reduction in death, permanent ATA, and cardiovascular hospitalizations. Patients with standard class I or II indications for permanent DDD pacing and history of ATA will receive a Medtronic EnRhythm implantable pacemaker (Medtronic, Minneapolis, MN). After a 1-month run-in period, patients will be randomized in a 1:1:1 manner to the DDD (control group, all OFF), the DDDRP (MVP + PAP + ATP ON), and the MVP group (only MVP ON). Up to 1,300 patients will be included in approximately 70 centers in Europe, the Middle East, and Asia. CONCLUSIONS: The MINERVA study will make an important contribution to the management of patients with paroxysmal ATA and accepted indications for dual-chamber pacemaker implantation by determining whether physiologic pacing combined with PAP and ATP is superior to standard DDD pacing in terms of reduction of mortality, incidence of permanent ATA, and cardiovascular hospitalizations.

Gene expression profiling from endomyocardial biopsy tissue allows distinction between subentities of dilated cardiomyopathy.

OBJECTIVE: Expression profile analysis using endomyocardial biopsy specimens from patients with cardiomyopathies promises to improve the differential diagnosis of heart failure. METHODS: In this study, left ventricular endomyocardial biopsy specimens were obtained from 50 patients and histopathologically classified according to the World Heart Federation Task Force criteria as having dilated cardiomyopathy (n = 17), inflammatory cardiomyopathy (n = 11), myocarditis (n = 15), or pericarditis (n = 7). Microarrays were performed by hybridization of synthesized complementary DNA against a Lab-Arraytor60-combi microarray (SIRS-Lab, Jena, Switzerland). Differentially expressed genes were clustered hierarchically according to their variation in hybridization signals. RESULTS: In samples from patients with dilated cardiomyopathy, two different types of gene expression profiles were distinguishable. One pattern was unique for dilated cardiomyopathy and inflammatory cardiomyopathy, respectively, and the other more closely resembled that seen in samples from inflammatory heart disease. Additionally, we confirmed the microarray data by showing that dilated cardiomyopathy is associated with a reduced myocardial toll-like receptor 9 expression that resulted from progressive loss of functional cardiomyocytes. Taken together, our data demonstrate the utility and validity of microarrays from endomyocardial biopsy specimens in detecting subentities of dilated cardiomyopathy that do not differ histopathologically, but transcriptionally, from each other. The gene expression profile observed in one subgroup of patients with dilated cardiomyopathy is indicative of ongoing immune activation, albeit infiltrating immunocompetent cells were not detected histopathologically. CONCLUSION: Thus, our transcriptional data indicate that dilated cardiomyopathy constitutes a heterogeneous disease with an broad overlap to inflammatory heart disease.

Prehospital initiation of tirofiban in patients with ST-elevation myocardial infarction undergoing primary angioplasty (On-TIME 2): a multicentre, double-blind, randomised controlled trial.

BACKGROUND: The most effective magnitude and timing of antiplatelet therapy is important in patients with acute ST-elevation myocardial infarction (STEMI). We investigated whether the results of primary coronary angioplasty (PCI) can be improved by the early administration of the glycoprotein IIb/IIIa blocker tirofiban at first medical contact in the ambulance or referral centre. METHODS: We undertook a double-blind, randomised, placebo-controlled trial in 24 centres in the Netherlands, Germany, and Belgium. Between June 29, 2006, and Nov 13, 2007, 984 patients with STEMI who were candidates to undergo PCI were randomly assigned to either high-bolus dose tirofiban (n=491) or placebo (N=493) in addition to aspirin (500 mg), heparin (5000 IU), and clopidogrel (600 mg). Randomisation was by blinded sealed kits with study drug, in blocks of four. The primary endpoint was the extent of residual ST-segment deviation 1 h after PCI. Analysis was by intention to treat. The trial is registered, number ISRCTN06195297. FINDINGS: 936 (95%) patients were randomly assigned to treatment after a prehospital diagnosis of myocardial infarction in the ambulance. Median time from onset of symptoms to diagnosis was 76 min (IQR 35-150). Mean residual ST deviation before PCI (10.9 mm [SD 9.2] vs 12.1 mm [9.4], p=0.028) and 1 h after PCI (3.6 mm [4.6] vs 4.8 mm [6.3], p=0.003) was significantly lower in patients pretreated with high-bolus dose tirofiban than in those assigned to placebo. The rate of major bleeding did not differ significantly between the two groups (19 [4%] vs 14 [3%]; p=0.36). INTERPRETATION: Our finding that routine prehospital initiation of high-bolus dose tirofiban improved ST-segment resolution and clinical outcome after PCI, emphasises that further platelet aggregation inhibition besides high-dose clopidogrel is mandated in patients with STEMI undergoing PCI.

Biventricular stimulation to prevent cardiac desynchronization: rationale, design, and endpoints of the 'Biventricular Pacing for Atrioventricular Block to Prevent Cardiac Desynchronization (BioPace)' study.

Despite the deleterious effects of cardiac dyssynchrony and the positive effects of cardiac resynchronization therapy, patients with high-degree atrioventricular block continue to receive desynchronizing right ventricular (RV) pacing systems. Although it is unclear whether the negative effects of RV pacing and left bundle branch block (LBBB) are comparable, and whether they depend on the presence and the degree of structural heart disease, one may hypothesize that RV pacing may have similar effects to LBBB. In the BioPace trial, the long-term effects of RV pacing vs. biventricular pacing will be prospectively compared in 1200 pacemaker patients with high likelihood of mostly paced ventricular events, regardless of whether in sinus rhythm or in atrial fibrillation (AF). After echocardiographic examination of left ventricular (LV) function, patients will be randomly assigned to the implantation of an RV vs. a biventricular pacing system and followed for up to 5 years. Primary study endpoints are survival, quality of life (QoL), and the distance covered in a 6-min hall walk (6-MHW) at 24 months after implantation. Secondary endpoints are QoL and the 6-MHW result at 12 months after implantation, hospitalization rate, LV dimensions, LV ejection fraction, and the development of chronic AF and other adverse events.

Marked improvement in left ventricular function and significant reverse left ventricular remodeling within 3 months of cardiac resynchronization therapy in patients with dilated cardiomyopathy.

We monitored reverse left ventricular (LV) remodeling and LV function during the first 6 months of cardiac resynchronization therapy (CRT) in 34 patients (mean age = 55.3 +/- 13.6 years, 28 men) with dilated cardiomyopathy (DCM), left bundle branch block, in stable New York Heart Association class III, and on fixed drug regimen who underwent implantation of CRT systems with or without cardioverter defibrillator back-up. QRS-complex duration was reduced from 169.69 +/- 19.6 ms (SD) to 144.1 +/- 23.4 ms during CRT. Parasternal M-mode and apical 2D-echocardiography was performed before and 3 and 6 months after device implantation. LV enddiastolic (EDD) and endsystolic (ESD) diameters were measured, and biplane LV enddiastolic (EDV), and endsystolic (ESV) volumes and ejection fractions (EF) were calculated using a modified Simpson formula. Significant decreases in LVEDD (P = 0.0064 at 3 months and P = 0.021 at 6 months), LVESD (P = 0.023 at 3 months, and P = 0.003 at 6 months), and LVESV (P = 0.006 resp. P = 0.007), and increases in LVEF (P = 0.003 at 3 months and P < 0.001 at 6 months) were observed. Mean LVEF increased from 23% at baseline to 39% at 6 months. CRT induced prominent reverse LV remodeling and significantly increased LVEF within a few months in patients with DCM.