Dilated cardiomyopathy

Abstract: Dilated cardiomyopathy is a severe pathology of the heart with poorly understood etiology. Disruption of the gene encoding the negative immunoregulatory receptor PD-1 in BALB/c mice, but not in BALB/c RAG-2-/- mice, caused dilated cardiomyopathy with severely impaired contraction and sudden death by congestive heart failure. Affected hearts showed diffuse deposition of immunoglobulin G (IgG) on the surface of cardiomyocytes. All of the affected PD-1-/- mice exhibited high-titer circulating IgG autoantibodies reactive to a 33-kilodalton protein expressed specifically on the surface of cardiomyocytes. These results indicate that PD-1 may be an important factor contributing to the prevention of autoimmune diseases.

Abstract: BACKGROUND Because systolic and diastolic dysfunction frequently coexist, it is hypothesized that a combined measure of left ventricular chamber performance may be more reflective of overall cardiac dysfunction than systolic or diastolic measures alone. METHODS Study patients consisted of 170 subjects: 70 normals, 47 patients with severe dilated cardiomyopathy in NYHA class III-IV awaiting cardiac transplantation and 53 patients with idiopathic dilated cardiomyopathy of intermediate severity [NYHA class II, ejection fractions (EF) 30-50%]. EF, stroke volume and cardiac indexes were measured using conventional echo-Doppler methods. Pre-ejection period/ejection time (PEP/ET), isovolumetric relaxation time (IRT), isovolumetric contraction time/ET (ICT/ET) were also measured. A new derived index of myocardial performance: (ICT+IRT)/ET, was obtained by subtracting ET from the interval between cessation and onset of the mitral inflow velocity to give the sum of ICT and IRT. RESULTS The index was easily measured, reproducible, and had a narrow range in normals. The mean value of the index was significantly different between normal, intermediate and pre-transplant subjects (0.39 +/- 0.05, 0.59 +/- 0.10 and 1.06 +/- 0.24, respectively, p < 0.001 for all comparisons). The degree of inter-group overlap was smaller for the index compared to PEP/ET, ICT/ET and other parameters. Within functional groups, the value of the index did not appear to be related to heart rate, mean arterial pressure and the degree of mitral regurgitation. CONCLUSION (ICT+IRT)/ET is a conceptually new, simple and reproducible Doppler index of combined systolic and diastolic myocardial performance in patients with primary myocardial systolic dysfunction.

Abstract: BACKGROUNDB-type or brain natriuretic peptide (BNP) is a novel natriuretic peptide secreted from the heart that forms a peptide family with A-type or atrial natriuretic peptide (ANP), and its plasma level has been shown to be increased in patients with congestive heart failure. This study was designed to examine the sources and mechanisms of the secretion of BNP in comparison with those of ANP in control subjects and in patients with heart failure.METHODS AND RESULTSWe measured the plasma levels of BNP as well as ANP in 16 patients with dilated cardiomyopathy (11 men and 5 women; mean age, 59 years) and 18 control subjects (9 men and 9 women; mean age, 54 years) by sampling blood from the femoral vein, the aortic root, the anterior interventricular vein (AIV), and the coronary sinus using the newly developed immunoradiometric assay systems. In the control subjects, there was no significant difference in the plasma ANP level between the aortic root and the AIV (24.0 +/- 5.2 pg/mL versus 32.2 +/- 17.0 pg/mL...

Abstract: Background— Heart failure treatment depends partly on the underlying cause of the disease. We evaluated cardiovascular magnetic resonance (CMR) for the problem of differentiating dilated cardiomyopathy (DCM) from left ventricular (LV) dysfunction caused by coronary artery disease (CAD). Methods and Results— Late gadolinium enhancement with CMR was performed in 90 patients with heart failure and LV systolic dysfunction (63 patients with DCM and unobstructed coronary arteries and 27 with significant CAD at angiography). We also studied 15 control subjects with no coronary risk factors and/or unobstructed coronary arteries. None (0%) of the control subjects had myocardial gadolinium enhancement; however, all patients (100%) with LV dysfunction and CAD had enhancement, which was subendocardial or transmural. In patients with DCM, there were 3 findings: no enhancement (59%); myocardial enhancement indistinguishable from the patients with CAD (13%); and patchy or longitudinal striae of midwall enhancement clearly different from the distribution in patients with CAD (28%). Conclusions— Gadolinium CMR is a powerful technique to distinguish DCM from LV dysfunction related to CAD and yields new insights in DCM. These data suggest that using the coronary angiogram as the arbiter for the presence of LV dysfunction caused by CAD could have lead to an incorrect assignment of DCM cause in 13% of patients, possibly because of coronary recanalization after infarction. The midwall myocardial enhancement in patients with DCM is similar to the fibrosis found at autopsy; it has not previously been visualized in vivo and warrants further investigation. CMR may become a useful alternative to routine coronary angiography in the diagnostic workup of DCM.

Abstract: Background—Ventricular pacing can improve hemodynamics in heart failure patients, but direct effects on left ventricular (LV) function from varying pacing site and atrioventricular (AV) delay remain unknown. We hypothesized that the magnitude and location of basal intraventricular conduction delay critically influences pacing responses and that single-site pacing in the delay-activated region yields similar or better responses to biventricular pacing. Methods and Results—Aortic and LV pressures were measured in 18 heart failure patients (mean±SD: LV ejection fraction, 19±7%; LV end-diastolic pressure, 25±8 mm Hg; QRS duration, 157±36 ms). Data under normal sinus rhythm were compared with ventricular pacing (VDD) at varying sites and AV delays (randomized order). Right ventricular (RV) apical or midseptal pacing had negligible contractile/systolic effects. However, LV free-wall pacing raised dP/dtmax by 23.7±19.0% and pulse-pressure by 18.0±18.4% (P<0.01). Biventricular pacing yielded less change (+12.8±9....