Role of nitric oxide in the vasodilator effect of recombinant human growth hormone in patients with dilated cardiomyopathy.

OBJECTIVE: Dilated cardiomyopathy is characterized by elevated arterial vascular resistance and impaired nitric oxide (NO)-dependent vasodilation. Insulin-like growth factor-I (IGF-I) has been shown to stimulate endothelial NO-synthase resulting in endothelium-dependent vasodilation. Growth hormone (GH) substitution therapy leads in GH-deficient patients to significant increases of IGF-I which may alter systemic vascular resistance by stimulating NO production. This study was designed to evaluate the effects of treatment with recombinant human growth hormone (GH) on NO production and NO-dependent vascular effects in patients with dilated cardiomyopathy. METHODS: 50 patients with dilated cardiomyopathy were randomly assigned to double-blind treatment with 2 I.U. of GH or placebo for 3 months. Central hemodynamics were determined by Swan-Ganz catheter and cardiac output was obtained by the thermodilution method. Serum GH and IGF-I levels were measured and systemic NO production was determined from urinary nitrate and cyclic GMP excretion rates in 42 patients. RESULTS: GH treatment caused in comparison to the placebo group a significant increase of IGF-I by 91 ng/ml (P = 0.0001). Urinary excretion rates of nitrate and cyclic GMP increased also significantly by 38 mumol/mmol creatinine (P = 0.027) and 65 nmol/mmol creatinine (P = 0.003), respectively. The parallel increase of both marker molecules indicates increased systemic NO production during GH treatment. CONCLUSION: GH treatment induces a significant, but moderate increase of systemic NO production in patients with dilated cardiomyopathy. This effect may be mediated by IGF-I stimulating endothelial NO synthase.

[Influence of image quality on the diagnostic accuracy of dobutamine stress magnetic resonance imaging in comparison with dobutamine stress echocardiography for the noninvasive detection of myocardial ischemia]. / Einfluss der Bildqualität auf die Genauigkeit der nichtinvasiven Ischämiediagnostik mit der Dobutamin-Stressmagnetresonanztomographie im Vergleich zur Dobutamin-Stressechokardiographie.

The analysis of wall motion abnormalities with dobutamine stress echocardiography is an established method for the detection of myocardial ischemia. With ultrafast magnetic resonance tomography, the application of identical stress protocols as used for echocardiography is possible. In 208 consecutive patients (147 M, 61 F) with suspected coronary artery disease, dobutamine stress echocardiography partially using harmonic imaging and dobutamine stress magnetic resonance tomography (DSMR) were performed prior to cardiac catheterization. DSMR images were acquired during short breath holds in 3 short axis-, a 4-, and a 2-chamber view using a turbo gradient echo technique. Patients were examined at rest and during a standard dobutamine-atropine scheme until submaximal heart rate was reached. Regional wall motion was assessed in a 16 segment model. Significant coronary heart disease was defined as angiographic >/=50% diameter stenosis. With DSMR, significantly more patients yielded very good (69%) or good (13%) image quality in comparison with dobutamine stress echocardiography (20% and 31%, p<0. 05). Moderate image quality occurred in 16% with MR and 41% with dobutamine stress echocardiography (p<0.05), 2% and 8% were non-diagnostic. With each technique 18 patients could not be examined (DSE: emphysema: 10, adipositas: 8, DSMR: claustrophobia: 11, adipositas: 6, contraindication: 1). Four patients did not reach target heart rate. In 107 patients, significant coronary artery disease was found. With DSMR sensitivity was 88.7% (dobutamine stress echocardiography: 74.3%; p<0.05) and specificity 85.7% (dobutamine stress echocardiography: 69.8%; p <0.05). This difference was most pronounced in the group with moderate echocardiographic image quality. High dose DSMR is superior to dobutamine stress echocardiography and can replace this technique especially in patients with moderate echocardiographic image quality.

Investigation of a family with autosomal dominant dilated cardiomyopathy defines a novel locus on chromosome 2q14-q22.

Dilated cardiomyopathy (DCM) is a leading cause of heart failure and the most frequent indication for heart transplantation in young patients. Probably >25% of DCM cases are of familial etiology. We report here genetic localization in a three-generation German family with 12 affected individuals with autosomal dominant familial DCM characterized by ventricular dilatation, impaired systolic function, and conduction disease. After exclusion of known DCM loci, we performed a whole-genome screen and detected linkage of DCM to chromosome 2q14-q22. Investigation of only affected individuals defines a 24-cM interval between markers D2S2224 and D2S2324; when unaffected individuals are also included, the critical region decreases to 11 cM between markers D2S2224 and D2S112, with a peak LOD score of 3.73 at recombination fraction 0 at D2S2339. The identification of an additional locus for familial autosomal dominant DCM underlines the genetic heterogeneity and may assist in the elucidation of the causes of this disease.

[Long-term outcome of therapy of recurrent myocardial ischemia after surgical revascularization]. / Langzeitergebnis der Therapie wiederauftretender myokardialer Ischämie nach operativer Revaskularisation.

UNLABELLED: Although there are randomized data for CABG vs. medical therapy and CABG vs. PTCA in primary therapy of CAD, there is few evidence on the appropriate therapy of recurrent angina after prior CABG. We analyzed data from 1265 consecutive patients (pts.) presenting for recurrent angina after previous CABG who required either re-CABG (n = 67), PTCA (n = 768) or medical therapy alone (medRx) (n = 430) at our institution during 1986 through 1996. Outcome after index therapy is monitored during 45 +/- 34 months. The 3 therapeutic groups were similar with respect to gender (84% male), age at therapy (60 years), prevalence of diabetes (22%), and time to first ischemic event after primary CABG (37 months). Actuarial survival was significantly higher in the PTCA-group at 1, 5 and 10 years after therapy of recurrent angina, despite the freedom from subsequent re-intervention was significantly lower (1-year-survival 95% [37%] vs. 95% [3%] medRx vs. 79% [4%] re-CABG, 5-year-survival 87% [57%] vs. 78% [17%] medRx vs. 50% [4%] re-CABG and 10-year-survival 72% [65%] vs. 63% [31%] medRx vs. 50% [15%] re-CABG resp., p < 0.0001, [numbers in brackets represent corresponding values for incidence of re-intervention, p < 0.0001]). These findings were similar after adjustment for different baseline characteristics. Following this adjustment multivariate Cox-analysis identified age beyond 70 years, diabetes mellitus and therapy: redo-CABG as independent correlates for mortality for the entire group. THERAPY: angioplasty was identified as an independent correlate for survival. In contrast, therapy: angioplasty was an independent correlate for re-intervention after therapy. CONCLUSIONS: In this nonrandomized series of patients with recurrent angina after previous CABG, an initial strategy of angioplasty resulted in a significant higher overall survival, although this regimen is associated with a greater need for subsequent revascularization procedures.

Noninvasive diagnosis of ischemia-induced wall motion abnormalities with the use of high-dose dobutamine stress MRI: comparison with dobutamine stress echocardiography.

BACKGROUND: The analysis of wall motion abnormalities with dobutamine stress echocardiography (DSE) is an established method for the detection of myocardial ischemia. With ultrafast magnetic resonance tomography, identical stress protocols as used for echocardiography can be applied. METHODS AND RESULTS: In 208 consecutive patients (147 men, 61 women) with suspected coronary artery disease, DSE with harmonic imaging and dobutamine stress magnetic resonance (DSMR) (1.5 T) were performed before cardiac catheterization. DSMR images were acquired during short breath-holds in 3 short-axis views and a 4- and a 2-chamber view (gradient echo technique). Patients were examined at rest and during a standard dobutamine-atropine scheme until submaximal heart rate was reached. Regional wall motion was assessed in a 16-segment model. Significant coronary heart disease was defined as >/=50% diameter stenosis. Eighteen patients could not be examined by DSMR (claustrophobia 11 and adipositas 6) and 18 patients by DSE (poor image quality). Four patients did not reach target heart rate. In 107 patients, coronary artery disease was found. With DSMR, sensitivity was increased from 74.3% to 86.2% and specificity from 69.8% to 85.7% (both P<0.05) compared with DSE. Analysis for women yielded similar results. CONCLUSIONS: High-dose dobutamine magnetic resonance tomography can be performed with a standard dobutamine/atropine stress protocol. Detection of wall motion abnormalities by DSMR yields a significantly higher diagnostic accuracy in comparison to DSE.