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Rainer Dietz

Publications and source records attributed to Rainer Dietz.

At least 19 recordsLinked to original sources
PubMed2007

Postoperative pulmonary arteriovenous fistula resulting in recurrent cryptogenic stroke.

We report on a 66-year-old patient with a history of two cryptogenic strokes and a patent foramen ovale (PFO) who received a transcatheter closure of his PFO in our institution, but shortly after the intervention there was still a relevant right-to-left shunt. The following work-up showed an isolated pulmonary arteriovenous fistula as the real cause for the right-to-left shunt and hence the two strokes.

Aged↗
PubMed2007

The G-231A polymorphism in the endothelin-A receptor gene is associated with lower aortic pressure in patients with dilated cardiomyopathy.

BACKGROUND: The endothelin system (ES) plays an important role in blood pressure (BP) regulation and also in the pathophysiology of idiopathic dilated cardiomyopathy (DCM). Recently, we demonstrated that a genetic polymorphism in the endothelin A (ET(A)) receptor gene was associated with survival in DCM patients. The aim of this study was to determine whether polymorphisms in the ET(A) receptor gene might be associated with the severity of DCM. METHODS: One hundred twenty-four consecutively recruited unrelated patients with DCM, who underwent a detailed phenotyping protocol, were genotyped for the ET(A) receptor G-231A polymorphism using a hybridization technique with allele-specific oligonucleotides. RESULTS: The exon 1 G-231A polymorphism of the ET(A) receptor gene, upstream of the translation start site, was significantly associated with directly measured intra-aortic pressure in that -231A allele carriers had significantly lower systolic (P = .0043), as well as mean (P = .0016) and diastolic (P = .0041) aortic pressure compared to noncarriers. The association of ET(A) G-231A with aortic pressure was independent from other factors such as prior medication, left ventricular end-diastolic diameter, age, gender, and New York Heart Association (NYHA) functional classification. However, no such association was seen for cuff BP and survival rates were not significantly different between -231A allele carriers and -231G homozygotes (log rank test, P = .66). No significant association with any other parameter investigated in the present study could be observed, even when men and women were analyzed separately. CONCLUSIONS: Our results suggest an association of genetic variation in the ET(A) receptor gene with aortic pressure in patients with DCM.

Aged↗
PubMed2006

Critical role for FoxO3a-dependent regulation of p21CIP1/WAF1 in response to statin signaling in cardiac myocytes.

Statins are widely used clinical drugs that exert beneficial growth-suppressive effects in patients with cardiac hypertrophy. We investigated the role of the cell cycle inhibitor p21(CIP1/WAF1) (p21) in statin-dependent inhibition of hypertrophic growth in postmitotic cardiomyocytes. We demonstrate that lovastatin fails to inhibit cardiac hypertrophy to angiotensin II in p21(-/-) mice and that reconstitution of p21 function by TAT.p21 protein transduction can rescue statin action in these otherwise normally developed animals. Lovastatin specifically recruits the forkhead box FoxO3a transcription factor to the p21 promoter, mediating transcriptional transactivation of the p21 gene as analyzed in isolated primary cardiomyocytes. Lovastatin also stimulates protein kinase B/Akt kinase activity, and Akt-dependent phosphorylation forces p21 in the cytoplasm, where it inhibits Rho-kinases contributing to the suppression of cardiomyocyte hypertrophy. Loss of p21 or FoxO3a by RNA interference causes a general inhibition of lovastatin signal transduction. These results suggest that p21 functions as FoxO3a downstream target to mediate an statin-derived anti-hypertrophic response. Taken together, our genetic and biochemical data delineate an essential function of p21 for statin-dependent inhibition of cardiac myocyte hypertrophy.

Animals↗
PubMed2006

Positive cardiac troponin I and T and chest pain in a patient with iatrogenic hypothyroidism and no coronary artery disease.

We report about a 41-year old male patient who presented to the emergency room with acute chest pain, exertion dyspnoea, muscle stiffness, myalgia and adynamia. There was no history of coronary artery disease but known arterial hypertension and insulin dependent diabetes mellitus. Four weeks before submission the patient had been thyroidectomized after he had been diagnosed with papillary thyroid carcinoma and was now awaiting further radioiodine therapy. The thyroid-stimulating hormone level was markedly elevated to 67 mU/l (normal range 0.27-4.20 mU/l) and fT4 significantly reduced to 0.19 ng/ml (normal range 0.9-1.9 ng/ml). CK was elevated to 328 U/l, cardiac Troponin I (Stratus CS) above the threshold with 0.13 microg/l and Elecsys third generation troponin T above the threshold with 0.04 microg/l. The electrocardiogram showed a normal sinus rhythm and did not reveal any signs of ST-elevation or -depression. During follow-up a cardiac MRI was performed, showing normal dimensions and function but a very small area of diffuse myocardial damage, atypical of ischemic injury. In coronary angiography normal coronary arteries were found. We conclude that cardiac troponins I and T may be elevated in severe hypothyroidism without coronary artery disease due to diffuse myocardial injury which can be imaged by MRI.

Adult↗
PubMed2006

Contrast-enhanced cardiovascular magnetic resonance imaging of right ventricular infarction.

OBJECTIVES: We assessed the role of late enhancement cardiovascular magnetic resonance imaging (LE-CMR) for the diagnosis of right ventricular infarction (RVI). BACKGROUND: Right ventricular infarction occurs in about one-half of patients with inferior myocardial infarction (MI). It is associated with an unfavorable prognosis, but established methods often lack the diagnostic accuracy to detect it. Late enhancement cardiovascular magnetic resonance imaging accurately detects left ventricular MI. METHODS: Thirty-seven patients with acute inferior MI were included. To test for RVI, they prospectively underwent a physical examination, an electrocardiogram (ECG) for ST-segment elevation in the V4r right precordial lead, and an echocardiogram. After coronary reperfusion, LE-CMR was performed for assessing presence and extent of late enhancement in the right ventricular (RV) wall. The LE-CMR data were compared with the other results; interobserver variability was assessed. The LE-CMR was repeated after 13 months. RESULTS: Late enhancement cardiovascular magnetic resonance imaging detected RVI in 21 of 37 (57%) patients with acute inferior MI. Interobserver variability was very good (kappa 0.83); physical exam was positive for RVI in 7 of 37 (19%) patients, V4r ECG in 13 of 37 (35%) patients, and echocardiogram in 6 of 37 (16%) patients. The LE-CMR findings for RVI showed only mild agreement with findings for RVI on physical exam (kappa 0.30), V(4)r ECG (kappa 0.38), and echocardiography (kappa 0.32). Irreversible injury of the RV persisted at 13 months (kappa 0.85). CONCLUSIONS: In patients with acute inferior MI, RVI is more frequently detected by LE-CMR than by current standard diagnostic techniques. Further CMR studies might allow for analyzing its clinical and prognostic relevance.

Aged↗
PubMed2006

Mutations in the EGF-CFC gene cryptic are an infrequent cause of congenital heart disease.

Cryptic (CFC1), a member of the epidermal growth factor-Cripto/FRL-1/Cryptic (EGF-CFC) gene family, is involved in the evolutionarily conserved establishment of left-right lateral asymmetry. Inactivation of Cfc1 in mice results in laterality defects and complex cardiac malformations. Similarly, mutations in the human CFC1 gene have been identified in patients with heterotaxy syndrome. The cardiac defects in humans resemble those in mice lacking Cfc1. We postulated that some patients with isolated cardiac malformations could also have mutations in the CFC1 gene. Our analysis of the CFC1 gene in 167 patients with congenital heart disease revealed a novel A145T missense variant in 3 patients with type II atrial septal defect. Furthermore, we found the previously characterized R78W polymorphism in another patient with type II atrial septal defect. However, the A145T sequence alteration was also identified in 3 controls, suggesting that this variant is a polymorphism. We conclude that CFC1 variants could be a rare cause of congenital heart disease in patients without laterality defects.

Epidermal Growth Factor↗
PubMed2006

Optimization of cardiac resynchronization guided by Doppler echocardiography: haemodynamic improvement and intraindividual variability with different pacing configurations and atrioventricular delays.

AIMS: Cardiac resynchronization therapy (CRT) improves symptoms in heart failure patients with intraventricular conduction delay (IVCD). Different pacing modalities produce variable activation patterns and are likely to result in different haemodynamic changes. The objective of this study was to demonstrate acute haemodynamic changes with different CRT configurations. METHODS AND RESULTS: In 26 patients (left ventricular ejection fraction 22.7+/-6.1%, QRS 176+/-29 ms, New York Heart Association III/IV 18/8), a CRT device was implanted. An optimization procedure was performed including left (LVPEI) and right ventricular pre-ejection intervals, interventricular mechanical delay (IVD), left ventricular filling fraction (FTc), and myocardial performance index (MPI) during left and biventricular pacing with three different atrioventricular (AV) delays. An optimal mode and AV delay were defined. LVPEI changed from 166+/-27 to 139+/-25 ms, IVD from 49+/-19 to 6+/-18 ms, MPI from 0.98+/-0.25 to 0.62+/-0.22, and FTc from 0.42+/-0.08 to 0.51+/-0.08 (P<0.001 for all comparisons). The variability was 39+/-20 ms for LVPEI, 55+/-24 ms for IVD, 0.11+/-0.07 for FTc, and 0.35+/-0.18 for MPI. CONCLUSION: Optimized resynchronization in heart failure patients with IVCD produces marked acute improvement of the altered cardiac cycle timing. The variability of Doppler parameters with different CRT modalities underlines the necessity of individualized settings and suggests that the patients' benefit may be jeopardized without optimization.

Cardiac Pacing, Artificial↗
PubMed2006

Cardiac hypertrophy in transgenic rats expressing a dominant-negative mutant of the natriuretic peptide receptor B.

Natriuretic peptides (NP) mediate their effects by activating membrane-bound guanylyl cyclase-coupled receptors A (NPR-A) or B (NPR-B). Whereas the pathophysiological role of NPR-A has been widely studied, only limited knowledge on the cardiovascular function of NPR-B is available. In vitro studies suggest antiproliferative and antihypertrophic actions of the NPR-B ligand C-type NP (CNP). Because of the lack of a specific pharmacological inhibitor, these effects could not clearly be attributed to impaired NPR-B signaling. Recently, gene deletion revealed a predominant role of NPR-B in endochondral ossification and development of female reproductive organs. However, morphological abnormalities and premature death of NPR-B-deficient mice preclude detailed cardiovascular phenotyping. In the present study, a dominant-negative mutant (NPR-BDeltaKC) was used to characterize CNP-dependent NPR-B signaling in vitro and in transgenic rats. Here we demonstrate that reduced CNP- but not atrial NP-dependent cGMP response attenuates antihypertrophic potency of CNP in vitro. In transgenic rats, NPR-BDeltaKC expression selectively reduced NPR-B but not NPR-A signaling. NPR-BDeltaKC transgenic rats display progressive, blood pressure-independent cardiac hypertrophy and elevated heart rate. The hypertrophic phenotype is further enhanced in chronic volume overload-induced congestive heart failure. Thus, this study provides evidence linking NPR-B signaling to the control of cardiac growth.

Animals↗
PubMed2006

Percutaneous coronary intervention in patients with end-stage renal disease.

Patients with end-stage renal disease (ESRD) represent a growing number of patients in the cardiac catheterization laboratories worldwide. This is a consequence of the growing absolute number of ESRD patients in developed countries, better noninvasive diagnostic tools, better catheterization facilities and last-but-not-least better education of referring physicians about the incidence and prognosis of coronary artery disease (CAD) for patients with ESRD. There is growing evidence of the positive impact of coronary revascularization on long-term outcome of these patients. ESRD patients have a high comorbidity and are therefore better candidates for the less invasive approach using percutaneous coronary intervention (PCI) rather than coronary artery bypass surgery (CABG). From the view of the interventional cardiologist, ESRD patients represent one of the most challenging patient cohort concerning technical challenges and potential risk of complication for the patient. Percutaneous coronary intervention (PCI) including debulking techniques and stent implantation is the current standard therapy for patients with symptomatic single-vessel disease (SVD) and the preferred therapy for most patients with focal, polyfocal or even diffuse multi-vessel disease (MVD). Coronary bypass surgery is reserved for a decreasing number of patients with mechanically untreatable coronary lesions and unprotected left main stem stenosis. The problem of restenosis and subsequent target lesion revascularization has been decreased to a minimum by the use of drug-eluting stents (DES), even though prospective randomized trials including ESRD patients are lacking. In case of acute coronary syndromes, the need for immediate coronary angiography and subsequent revascularization by means of PCI should be pointed out.

Cardiac Surgical Procedures↗
PubMed2006

Stabilization of hypoxia inducible factor rather than modulation of collagen metabolism improves cardiac function after acute myocardial infarction in rats.

UNLABELLED: Prolyl hydroxylase domain-containing enzymes (PHD) hydroxylate a proline residue that controls the degradation of hypoxia inducible factor (HIF). Hypoxia inhibits this hydroxylation thus increasing HIF levels. HIF is upregulated in ischemic tissues, growing tumors and in nonischemic, mechanically stressed myocardium. Pharmacological inhibition of prolyl 4-hydroxylase (P4-H) stabilizes HIF-protein in vitro and may modulate collagen turnover. The aims of this study were to investigate whether inhibition of P4-H protects myocardium against ischemia, and whether the observed effects are related to modulation of collagen metabolism or due to the stabilization of HIF. METHODS: Rats were treated with a specific P4-H inhibitor (P4-HI) or vehicle starting 2 days before induction of myocardial infarction (MI). Rats were investigated 7 or 30 days after MI. Induction of HIF-1alpha and -2alpha was visualized by immunohistochemistry. Expression of growth factors (connective tissue growth factor, Osteopontin) and mRNA expression and protein levels of Collagen I and III as well as HIF-2alpha were measured. RESULTS: P4-HI augments HIF in the myocardium as early as 24 h after treatment. P4-HI did not alter the MI-induced enhanced expression of growth factors and collagen. Treatment with P4-HI significantly reduced heart and lung weight, improved left ventricular contractility, prevented left ventricular enlargement and improved left ventricular ejection fraction without affecting infarct size after 30 days. CONCLUSIONS: Specific inhibition of the P4-H improved cardiac function without affecting the infarct size after experimental myocardial infarction in rats. Stabilization of HIF rather than inhibition of collagen maturation by P4-HI may prevent cardiac remodeling after MI.

Animals↗
PubMed2006

Apoptosis repressor with caspase recruitment domain is required for cardioprotection in response to biomechanical and ischemic stress.

BACKGROUND: Ischemic heart disease and heart failure are associated with an increased loss of cardiomyocytes due to apoptosis. Whether cardiomyocyte apoptosis plays a causal role in the pathogenesis of heart failure remains enigmatic. The apoptosis repressor with caspase recruitment domain (ARC) is a recently discovered antiapoptotic factor with a highly specific expression pattern in striated muscle and neurons. ARC is a master regulator of cardiac death signaling because it is the only known factor that specifically inhibits both the intrinsic and extrinsic apoptotic death pathway. In this study we attempted to elucidate the physiological role of ARC and to understand pathophysiological consequences resulting from its deletion. METHODS AND RESULTS: We generated ARC-deficient mice, which developed normally to adulthood and had no abnormality in cardiac morphology and function under resting conditions. On biomechanical stress induced by aortic banding, ARC-deficient mice developed accelerated cardiomyopathy compared with littermate controls, which was characterized by reduced contractile function, cardiac enlargement, and myocardial fibrosis. Likewise, ischemia/reperfusion injury of ARC-deficient mice resulted in markedly increased myocardial infarct sizes. Although in both instances a significant increase in apoptotic cardiomyocytes could be observed in ARC-deficient mice, neither in vitro nor in vivo studies revealed any effect of ARC on classic hypertrophic cardiomyocyte growth responses. The pathophysiological relevance of downregulated ARC levels was underscored by specimens from failing human hearts showing markedly reduced ARC protein levels. CONCLUSIONS: Our study identifies a tissue-specific antiapoptotic factor that is downregulated in human failing myocardium and that is required for cardioprotection in pressure overload and ischemia.

Animals↗
PubMed2006

Genetic and phenotypic analysis of dilated cardiomyopathy with conduction system disease: demand for strategies in the management of presymptomatic lamin A/C mutant carriers.

BACKGROUND: One-third of cases of dilated cardiomyopathy (DCM) is of familial aetiology. Several genes have been reported to cause the autosomal dominant form of DCM. AIMS: To analyze the lamin A/C gene (LMNA) in 31 unrelated patients with DCM and conduction system disease (CSD). METHODS: Patients and family members underwent physical examination, ECG/Holter-ECG, echocardiography, and selective coronary angiography. Genetic analysis of all coding exons of LMNA was performed using PCR and sequencing. RESULTS: Three different LMNA mutations (Arg377His, c.1397delA, c.424_425ins21nt) were identified in three families with autosomal dominant disease comprised of 39 individuals. 21 individuals were mutation carriers, of whom 12 were symptomatic. We observed a progressive and age-dependent form of DCM with CSD and arrhythmias. First, the patients developed a moderate left ventricular dilatation without symptoms. Later, systolic function declined progressively and the patients became symptomatic resulting in a high mortality due to sudden death and heart failure. CONCLUSIONS: Genetic screening leads to the identification of symptomatic and asymptomatic mutant carriers. The latter at a young age should be regarded as "presymptomatic" because of the age-dependent disease manifestation. New guidelines are required for the management of these individuals.

Adolescent↗
PubMed2006

Elective percutaneous coronary intervention immediately impairs resting microvascular perfusion assessed by cardiac magnetic resonance imaging.

BACKGROUND: Percutaneous coronary intervention (PCI) is known to induce atherosclerotic plaque rupture, which may affect resting distal microvascular perfusion either through distal microvascular spasm or through embolization. We evaluated the effect of PCI on resting microvascular flow. METHODS: We performed cardiovascular magnetic resonance imaging to assess left ventricular systolic function and microvascular perfusion in 15 patients with stable coronary artery disease before and within 24 hours after PCI and in 10 control subjects without obstructive coronary artery disease on a clinical 1.5-T CMR scanner. Microvascular perfusion was evaluated at rest after injecting a bolus of gadolinium-diethylenetriamine pentaacetic acid (0.1 mmol/kg) by calculating the time to 50% maximum myocardial enhancement (T50% max), as well as the relative upslope, of the myocardial signal intensity curve. Regional perfusion and systolic thickening were evaluated using a 16-segment left ventricular model with the slice locations matched anatomically pre-PCI and post-PCI. The relative contrast delay in the region of myocardium subtended by the PCI artery was calculated by subtracting the T50% max of a remote region from the PCI region. RESULTS: In subjects with coronary artery disease, PCI resulted in a regional contrast delay (mean delay 0.6 +/- 0.2 seconds post-PCI vs 0.0 +/- 0.2 seconds pre-PCI, P < .05) and a reduction in the relative upslope (8.6 +/- 0.5 post-PCI vs 10.1 +/- 0.7 pre-PCI, P = .02), consistent with reduced microvascular perfusion. This was unaccompanied by any change in regional systolic thickening (54% +/- 7% pre-PCI vs 53% +/- 5% post-PCI, P = NS). CONCLUSIONS: The data show PCI-induced impairment of resting microvascular perfusion in the area of myocardium subtended by the treated artery after PCI, a likely consequence of iatrogenic atherosclerotic plaque rupture.

Aged↗
PubMed2006

A systematic meta-analysis of the efficacy and heterogeneity of disease management programs in congestive heart failure.

BACKGROUND: We sought to systematically combine the evidence on efficacy of disease management programs (DMPs) in the treatment of congestive heart failure (CHF), to identify and explain heterogeneity of results from prior studies of DMPs, and to assess potential publication bias from these studies. METHODS AND RESULTS: We conducted a systematic literature search on randomized clinical trials investigating the effect of DMPs on CHF outcomes and performed meta-analyses and meta-regressions comparing DMPs and standard care for mortality and rehospitalization. We included 36 studies from 13 different countries (with data from 8341 patients). Our meta-analysis yielded a pooled risk difference of 3% (95% confidence interval [CI] 1-6%, P < .01) for mortality and of 8% (95% CI 5-11%, P < .0001) for rehospitalization, both favoring DMP. Factors explaining heterogeneity between studies included severity of disease, proportion of beta-blocker at baseline, country, duration of follow-up, and mode of postdischarge contact. No statistically significant publication bias was detected. CONCLUSION: DMPs have the potential to reduce morbidity and mortality for patients with CHF. The benefit of the intervention depends on age, severity of disease, guideline-based treatment at baseline, and DMP modalities. Future studies should directly compare the effect of different aspects of disease management programs for different populations.

Age Factors↗
PubMed2006

Left ventricular outflow tract planimetry by cardiovascular magnetic resonance differentiates obstructive from non-obstructive hypertrophic cardiomyopathy.

The relation to the pressure gradient as assessed by echocardiography and the CMR-derived planimetry of the LVOT is not known, no values for the differentiation of obstruction exist. We studied 37 patients with hypertrophic cardiomyopathy and 14 healthy controls using standard sequences with 3D coverage of the left ventricular outflow tract. A cutoff value of 2.7 cm2 identified obstruction as defined by echocardiography with 100% accuracy. CMR planimetry at rest is a promising tool to evaluate patients with hypertrophic cardiomyopathy.

Adult↗
PubMed2006

Resource utilization and costs in the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) programme.

AIMS: More treatments are needed to improve clinical outcomes in chronic heart failure (HF). It is, however, important that treatments for a condition as common as HF are affordable. We have carried out a prospective economic analysis of the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) programme. METHODS AND RESULTS: Patients with NYHA class II-IV HF and LVEF < or =0.40 were randomized to CHARM-Alternative if intolerant of an ACE-inhibitor or to CHARM-Added if taking an ACE-inhibitor. Patients with a LVEF >0.40 were randomized in CHARM-Preserved. Each trial compared the effect of candesartan to placebo on the primary outcome of cardiovascular death or HF hospitalization. Detailed information was prospectively collected on hospital admissions, procedures/operations and drugs. A cost-consequence analysis was performed for France, Germany and the UK for CHARM-Overall and a cost-effectiveness analysis for the low LVEF trials. The cost of candesartan was substantially offset by a reduction in hospital admissions, especially for HF. In the cost-consequence analysis, candesartan was cost-saving in most scenarios for CHARM-Alternative and Added but the marginal annual net cost per patient was upto 372 euros per year in CHARM-Preserved, in which candesartan did not reduce the primary outcome significantly. In the cost-effectiveness analysis of patients with a LVEF < or = 0.40, candesartan was cost-saving in some scenarios and in the others the maximum cost per life year gained was 3881 euros. CONCLUSION: Candesartan improves functional class, reduces the risk of hospital admission, and increases survival in patients with a HF and a LVEF < or =0.40 at an acceptable cost.

Angiotensin II Type 1 Receptor Blockers↗
PubMed2006

Cardiac magnetic resonance and cardiac magnetic field mapping in a patient with stress-induced cardiomyopathy (tako-tsubo).

We encountered a 65-year-old woman with typical electrocardiogram (ECG) changes and new-onset left ventricular dysfunction with apical ballooning that exhibited typical changes of tako-tsubo-like cardiomyopathy. We used cardiac magnetic resonance (CMR) and cardiac magnetic field mapping (CMFM) to detect changes in structural, mechanical, and electrophysiological myocardial properties during follow-up. CMR displayed an acute myocardial injury, but neither fibrosis nor necrosis. CMFM exhibited severely disturbed repolarization with an inhomogeneous magnetic field. These pathological findings persisted much longer than the abnormalities detected by CMR and the ECG.

Aged↗