[Guidelines on the management of stable angina pectoris: executive summary].
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Algorithms↗
Biomedical subjects
Rainer Dietz
Publications and source records attributed to Rainer Dietz.
QT prolongation and syncope with methadone, doxepin, and a beta-blocker.
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Adrenergic beta-Antagonists↗
Public awareness of heart failure in Europe: first results from SHAPE.
AIMS: Appropriate heart failure (HF) care and adequate resourcing require recognition of its clinical, social, and economic importance by the general public besides healthcare authorities and providers. The extent of public awareness in Europe is not known. METHODS AND RESULTS: A total of 7958 subjects were randomly selected from nine European countries (minimum 100/group per country). Each completed a 32-question survey on HF covering recognition, impact on health, comparative prevalence and severity, treatment, and costs. Although 86% of respondents had heard of HF, only 3% could correctly identify HF from a description of typical symptoms and signs, 31% correctly identified angina, and 51% identified transient ischaemic attack/stroke. Only 29% thought that HF signs and symptoms indicate a 'severe' condition. Most thought that HF patients should reduce all physical activity and 34% believed HF a normal consequence of ageing. Sixty-seven per cent thought that HF patients live longer than cancer patients. Only 9% believed that HF leads to greater healthcare expenditure than cancer, HIV, or diabetes. Overall, responses were comparable between countries. CONCLUSION: In Europe, community awareness of HF is low. Therefore, the general public is unlikely to demand appropriate measures by healthcare authorities and providers. A better understanding of HF could improve its prevention and management. Strategies to educate the public about HF are needed.
Adult↗
Facilitated percutaneous coronary intervention (PCI) in patients with acute ST-elevation myocardial infarction: comparison of prehospital tirofiban versus fibrinolysis before direct PCI.
AIMS: Early start of treatment including coronary revascularization has been recognized as crucial variable in the outcome of acute ST-segment elevation myocardial infarction (STEMI). The lack of availability and the realisation that an optimum reperfusion strategy will need to incorporate mechanical reperfusion as part of that strategy has led to a great deal of interest in pharmacologic reperfusion combined with mechanical reperfusion or facilitated PCI. It is not clear whether GPIIb/IIIa-blockade or fibrinolysis better facilitates PCI. METHODS: We identified 138 patients who have been primarily treated by our mobile emergency care mobile from July 2001 until February 2003 with tirofiban or fibrinolysis. Seventy-nine patients had ST-elevation myocardial infarction (STEMI) and available angiograms within 24 h. RESULTS: Forty-four patients had tirofiban (TIRO; 60.6 S.D. 11.4 years, 64% male) and 35 patients underwent fibrinolysis (FIB; 31.4% tenecteplase, 54.3% reteplase, 11.4% alteplase, 2.9% streptokinase; 58.8 S.D. 12.2 years, 80% male). Data were analyzed with respect to TIMI-flow and corrected frame count (cTFC) before and after PCI, bleeding complications at 30 days and long-term follow up for major adverse events (median 288 days; MACE: Death, hospitalized re-infarction, intracranial hemorrhage). Catheter films were re-analyzed by an investigator blinded to the prehospital therapy. Time from onset of symptoms to first medical contact was 1.98 h in TIRO compared to 0.5 h in FIB (p<0.001) and time from first prehospital medical contact to catheter was 1.46 h in the TIRO compared to 2.85 h in the FIB group (p<0.001). TIMI 3-flow before PCI was observed in 20.5% of TIRO and 62.9% in FIB (p<0.001). After PCI TIMI 3-flow was achieved in 90.5% and 90.0%, respectively (p=n.s.). Final cTFC was 24 in TIRO and 29 in FIB (p=n.s.). Visible thrombi were detected in 30.2% in TIRO and 23.5% in FIB (p=n.s.). Major bleeding occurred in one TIRO patient (fatal lung bleeding after ultima ratio abciximab on top of tirofiban), 2 patients (4.5%) received transfusions. In FIB 2 intracerebral hemorrhages, 5 transfusions (14.3%) and 3 pulmonary bleedings during mandatory ventilation were observed. After 30 days 4.5% in TIRO and 22.9% in FIB had MACE (p=0.015). During long-term follow up the primary endpoint was observed in 4.5% of TIRO and 28.6% (p=0.003) of FIB. Two patients died in TIRO and 9 patients in FIB. CONCLUSIONS: We conclude that (1) prehospital start of tirofiban for facilitated PCI is safe and effective if administered by experienced emergency physicians; (2) routine fibrinolysis should be limited to areas where catheter based therapy is not available within 90 min and (3) fibrinolysis should be given for facilitated PCI in randomized trials only at the moment.
Aged↗
Letter regarding article by Sharkey et al, "Acute and reversible cardiomyopathy provoked by stress in women from the United States".
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Acute Disease↗
Diagnostic performance of cardiovascular magnetic resonance in patients with suspected acute myocarditis: comparison of different approaches.
OBJECTIVES: The aim of this research was to identify the diagnostic performance of gadolinium-enhanced and T2-weighted cardiovascular magnetic resonance (CMR) in suspected acute myocarditis. BACKGROUND: Acute myocarditis is difficult to diagnose; CMR provides various means to visualize myocardial inflammatory changes. A CMR approach with clear-cut diagnostic criteria would be desirable. METHODS: We investigated 25 patients with suspected acute myocarditis (18 males, 44 +/- 17 years) and 23 healthy controls (13 males, 29 +/- 10 years). Cardiovascular magnetic resonance studies included the following sequences: 1) T2-weighted triple inversion recovery; 2) T1-weighted spin echo before and over 4 min after gadolinium injection; and 3) inversion recovery-gradient echo 10 min after gadolinium injection. Qualitative and quantitative image analysis was performed for: 1) focal and global T2 signal intensity (SI); 2) myocardial global relative enhancement (gRE); and 3) areas of late gadolinium enhancement (LGE). RESULTS: Both global T2 SI and gRE were higher in patients than in controls (T2: 2.3 +/- 0.4 vs. 1.7 +/- 0.4; p < 0.0001, gRE: 6.8 +/- 4.0 vs. 3.7 +/- 2.3; p < 0.001). The sensitivity, specificity, and diagnostic accuracy for T2 (cutoff value of 1.9) were 84%, 74%, and 79%, respectively; gRE: (cutoff value of 4.0) 80%, 68%, and 74.5% respectively; LGE: 44%, 100%, and 71%, respectively. The best diagnostic performance was obtained when "any-two" of the three sequences were positive in the same patient yielding a 76% sensitivity, 95.5% specificity, and 85% diagnostic accuracy. CONCLUSIONS: A combined CMR approach using T2-weighted imaging, early and late gadolinium enhancement, provides a high diagnostic accuracy and is a useful tool in the diagnosis and assessment of patients with suspected acute myocarditis.
Acute Disease↗
Blood pressure-independent ETA and AT1 receptor blocker effects on the coronaries of rats harboring human renin and angiotensinogen genes.
BACKGROUND: Blood pressure-independent (BP) effects of angiotensin (Ang) II and endothelin (ET) on coronaries (remodeling) in high renin hypertension are incompletely understood. METHODS: We studied the effects of subdepressor doses of Ang II receptor (AT1) blockade with losartan (10 mg/kg/day gavage) and endothelin A receptor (ETA) blockade with LU135252 (30 mg/kg/day) on the coronaries of rats harboring human renin and angiotensinogen genes (dTGR). Nontransgenic Sprague-Dawley rats were controls. The rats were treated between the ages of 6 and 10 weeks. Coronary cross-sectional area [CSA; 0.79 x (external diameter2 - internal diameter2)], cell proliferation, and infiltration of monocytes/macrophages were determined. RESULTS: Monotherapy did not lower BP while combination treatment did (p < 0.05). All treatments reduced mortality (p < 0.01). CSA was decreased by all treatments compared to vehicle, independent of blood pressure (p < 0.05). Extensive proliferation by PCNA staining and infiltration of ED-1-positive cells was diminished by both treatment and the combination. CONCLUSIONS: The data show that Ang II promotes coronary inflammation and remodeling, in part independent of blood pressure but dependent upon ET signaling. Combination treatment directed at both pathways may improve outcome, independent of blood pressure reduction.
Angiotensin II Type 1 Receptor Blockers↗
Blood oxygen level-dependent MRI of tissue oxygenation: relation to endothelium-dependent and endothelium-independent blood flow changes.
OBJECTIVES: The contribution of endothelial function to tissue oxygenation is not well understood. Muscle blood oxygen level-dependent MRI (BOLD MRI) provides data largely dependent on hemoglobin (Hb) oxygenation. We used BOLD MRI to assess endothelium-dependent signal intensity (SI) changes. METHODS AND RESULTS: We investigated mean BOLD SI changes in the forearm musculature using a gradient-echo technique at 1.5 T in 9 healthy subjects who underwent a protocol of repeated acetylcholine infusions at 2 different doses (16 and 64 microg/min) and N(G)-monomethyl-L-arginine (L-NMMA; 5 mg/min) into the brachial artery. Sodium nitroprusside was used as a control substance. For additional correlation with standard methods, the same protocol was repeated, and forearm blood flow was measured by strain gauge plethysmography. We obtained a significant increase in BOLD SI during acetylcholine infusion (64 microg/min) and a significant decrease for L-NMMA infusion (P<0.005 for both). BOLD SI showed a different kinetic signal than did blood flow, particularly after intermittent ischemia and at high flow rates. CONCLUSIONS: In standard endothelial function tests, BOLD MRI detects a dissociation of tissue Hb oxygenation from blood flow. BOLD MRI may be a useful adjunct in assessing endothelial function.
Acetylcholine↗
Requirement of nuclear factor-kappaB in angiotensin II- and isoproterenol-induced cardiac hypertrophy in vivo.
BACKGROUND: In vitro experiments have proposed a role of nuclear factor-kappaB (NF-kappaB), a transcription factor, in cardiomyocyte hypertrophy and protection against apoptosis. Currently, the net effect on cardiac remodeling in vivo under common stress stimuli is unclear. METHODS AND RESULTS: We have generated mice with cardiomyocyte-restricted expression of the NF-kappaB super-repressor IkappaBalphaDeltaN (DeltaN(MHC)) using the Cre/lox technique. DeltaN(MHC) mice displayed an attenuated hypertrophic response compared with control mice on infusion of angiotensin II (Ang II) or isoproterenol by micro-osmotic pumps, as determined by echocardiography (left ventricular wall dimensions: control plus Ang II, x1.5+/-0.1 versus sham; DeltaN(MHC) plus Ang II, x1.1+/-0.1 versus sham; P<0.05; n> or =9), heart weight, and histological analysis. Real-time reverse-transcriptase polymerase chain reaction showed significantly reduced expression of hypertrophy markers beta-myosin heavy chain and atrial natriuretic peptide in Ang II-treated DeltaN(MHC) mice (P<0.05 versus control plus Ang II; n=4). Neither cardiomyocyte apoptosis nor left ventricular dilatation was observed. In cultured adult rat cardiomyocytes, NF-kappaB DNA binding activity was increased by both Ang II- and interleukin-6-related cytokines. The latter are known to be released by cardiac fibroblasts on Ang II stimulation and thus could locally increase the NF-kappaB response of cardiomyocytes. Finally, results from in vitro and in vivo experiments suggest a role for NF-kappaB in the regulation of prohypertrophic interleukin-6 receptor gp130 on mRNA levels. CONCLUSIONS: These results indicate that targeted inhibition of NF-kappaB in cardiomyocytes in vivo is sufficient to impair Ang II- and isoproterenol-induced hypertrophy without increasing the susceptibility to apoptosis.
Angiotensin II↗
Prevalence of cardiac beta-myosin heavy chain gene mutations in patients with hypertrophic cardiomyopathy.
Hypertrophic cardiomyopathy (HCM) is a frequent, autosomal-dominant cardiac disease and manifests predominantly as left ventricular hypertrophy. Mutations in the cardiac beta-myosin heavy chain gene (MYH7) are responsible for the disease in about 30% of cases where mutations were identified. We clinically evaluated a large group of 147 consecutive HCM patients from three cardiology centers in Germany, Poland, and Kyrgyzstan according to the same protocol. The DNA of the patients was systematically analyzed in the whole coding region of the MYH7 gene using PCR, single-strand conformation polymorphism analysis, and automated sequencing. Eleven different missense mutations (including seven novel ones) in 11 unrelated patients were identified, showing a mutation frequency of 7.5% in the study population. We further examined the families of five patients (three of German, one of Polish, and one of Kyrgyz origin) with 32 individuals in total. We observed a clear, age-dependent penetrance with onset of disease symptoms in the fourth decade of life. Genotype-phenotype correlations were different for each mutation, whereas the majority was associated with an intermediate/malign phenotype. In conclusion, we report a systematic molecular screening of the complete MYH7 gene in a large group of consecutive HCM patients, leading to a genetic diagnosis in 38 individuals. Information about the genotype in an individual from one family could be very useful for the clinician, especially when dealing with healthy relatives in doubt of their risk about developing HCM. The increasing application of genetic screening and the increasing knowledge about genotype-phenotype correlations will hopefully lead to an improved clinical management of HCM patients.
Adolescent↗
Returning hypertrophy after surgery in a patient with hypertrophic cardiomyopathy caused by a myosin-binding protein C mutation.
We report a 13-year follow-up of a patient who underwent both myectomy and septal ablation due to hypertrophic cardiomyopathy caused by a cardiac myosin-binding protein C gene mutation. After myectomy the patient again developed significant septal hypertrophy at the operated septal area with a need for a second interventional therapy. This exceptional case underscores the remarkable ability of the heart muscle to show a continuous hypertrophic process over many years.
Adult↗
Regulation of vascular smooth muscle cell proliferation: role of NF-kappaB revisited.
The transcription factor NF-kappaB regulates cell cycle progression and proliferation in a number of cell types. An important unresolved issue is the potential role of NF-kappaB in the proliferation of vascular smooth muscle cells (VSMCs) as a basis for the development of vascular disease. To investigate the contribution of NF-kappaB to mitogen-induced proliferation of VSMCs, a knock-in mouse model expressing the NF-kappaB superrepressor IkappaBalphaDeltaN (c(IkappaBalphaDeltaN)) was used. Comparing wild-type and IkappaBalphaDeltaN-expressing VSMCs, we found that proliferation rates did not differ after mitogenic stimulation by platelet-derived growth-factor-BB (PDGF-BB) or serum. In line with this, NF-kappaB activation was not observed in VSMCs derived from transgenic mice expressing an NF-kappaB-dependent lacZ reporter (c((Igk)3conalacZ)). We further show, that classical mitogenic signaling pathways (namely mitogen-activated protein kinase [MAPK] and the phosphatidyl-inositol-3-OH-kinase [PI3K] pathways) control VSMC proliferation, but independently of NF-kappaB activation. In contrast to VSMCs, mouse embryonic fibroblasts (MEFs) derived from IkappaBalphaDeltaN-expressing mice showed significantly impaired proliferation rates after mitogenic stimulation. This was reflected by strongly impaired cyclin D1 expression in serum-stimulated MEFs derived from (c(IkappaBalphaDeltaN)) mice. These results implicate that essential pathogenetic functions of NF-kappaB in the development of atherosclerosis involve apoptotic and inflammatory signaling of VSMCs rather than proliferation. They further provide genetic evidence for a cell-type restricted requirement of NF-kappaB in the control of cellular proliferation.
Animals↗
Platelet degranulation is associated with progression of intima-media thickness of the common carotid artery in patients with diabetes mellitus type 2.
BACKGROUND: Platelets play a key role in atherogenesis and thromboembolic complications in patients with type 2 diabetes. METHODS AND RESULTS: We prospectively examined the relationship between systemic platelet activation and progression of carotid wall thickness within 1 year in 105 patients with type 2 diabetes. The intima-media thickness (IMT) of the common carotid artery was measured bilaterally at study entry and after 1 year. Platelet activation was assessed with the use of immunologic markers of platelet activation (CD62P, CD63, and CD40L) and flow cytometry. The prevalence for progression of atherosclerotic carotid disease in this population was 55.2%. We found that platelet degranulation (CD63 and CD40L) correlated with progression of IMT within 1 year (CD63: r=0.231, P=0.022; CD40L: r=0.230, P=0.029). Diabetic patients with progression of IMT had a significantly increased expression of CD63 compared with patients with stable carotid disease (mean intensity of immunofluorescence; median, interquartile range: 17.1 [12.4, 25.8] versus 11.9 [7.7, 19.8]; P=0.004). Multivariate logistic regression analysis revealed that degranulation of platelet CD63 is a predictor for progression of IMT independently of classical cardiovascular risk factors and hemoglobin A1c in diabetic patients (P=0.017). CONCLUSIONS: Enhanced systemic platelet degranulation is associated with progression of carotid artery disease in type 2 diabetes.
Aged↗
Effect of noradrenaline and isoproterenol on lipopolysaccharide-induced tumor necrosis factor-alpha production in whole blood from patients with chronic heart failure and the role of beta-adrenergic receptors.
Increased levels of tumor necrosis factor-alpha (TNF-alpha) correlate with poor prognoses in chronic heart failure (CHF). This study demonstrated that noradrenaline and isoproterenol inhibit TNF-alpha production in patients with CHF in ex vivo whole blood in a dose-dependent fashion. The beta-blocker bisoprolol abolishes this effect.
Adrenergic beta-Antagonists↗
The impact of anaemia and kidney function in congestive heart failure and preserved systolic function.
BACKGROUND: The importance of anaemia in chronic heart failure was highlighted recently by different cohort studies. The aim of this study was to assess the prevalence of anaemia and its relationship to renal function, left ventricular function and symptoms of heart failure. METHODS: We surveyed cases of patients admitted to the Department of Cardiology during 22 consecutive months. Laboratory measurements, blood pressure and echocardiographic parameters were obtained with standardized methods. RESULTS: Out of a total number of 2941 patients, 238 patients (8.1%) had haemoglobin values <11 g/dl. There was a positive association of anaemia with the symptoms of heart failure with a lowering of the median haemoglobin from 14.2 g/dl [New York Heart Association (NYHA) I] to 12.9 g/dl (NYHA IV, P<0.001). Interestingly, anaemia was not associated with left ventricular function or any left ventricular parameters. Symptoms of heart failure, however, were associated with kidney function. The estimated glomerular filtration rate (GFR) was 82 ml/min at NYHA I and 59 ml/min at NYHA IV, P<0.05. There was an association between impaired renal function and haemoglobin values. Haemoglobin was 14.2 g/dl in the group with normal renal function and 11.1 g/dl in the group with a GFR <25 ml/min (P<0.001). Even in patients with normal renal function (878 patients, GFR >85 ml/min), we still found an association of anaemia with the symptoms of heart failure. Haemoglobin was 14.5 g/dl at NYHA I and 13.4 g/dl at NYHA IV, P<0.0001. CONCLUSION: Anaemia is found in 8.1% of patients admitted to cardiology service. Anaemia was clearly associated with symptoms of congestive heart failure even in patients with normal renal function. Anaemia was not associated with left ventricular function.
Aged↗
[Arrhythmogenic right ventricular cardiomyopathy].
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a primary myocardial disorder that is characterized by localized or diffuse atrophy of predominantly right ventricular myocardium with subsequent replacement by fatty and fibrous tissue. Arrhythmias of right ventricular origin are the main clinical manifestation. Affected patients present with ventricular premature beats and nonsustained or sustained ventricular tachycardia demonstrating a left bundle branch block pattern. However, since ventricular tachycardia may also degenerate into ventricular fibrillation, sudden death may be the first manifestation of ARVC.In recent years, ARVC has been more and more recognized as an important and frequent cause of ventricular tachyarrhythmias and sudden cardiac death, particularly in young patients and athletes, with apparently normal hearts. Evidence of the disease is found in 30-50% of family members. ARVC is a genetically heterogeneous disease. The diagnosis is based on electrocardiographic abnormalities and the identification of regional or global right ventricular dysfunction and fibrolipomatosis. Although several potentially causative genes have been identified, currently, genetic testing is not part of the routine diagnostic work-up.An implantable cardioverter-defibrillator is indicated in selected high-risk patients with ARVC (i. e., patients with life-threatening ventricular tachycardia or survivors of sudden cardiac death). The clinical course of the disease is often characterized by progression. In individual patients heart transplantation may become necessary.
Arrhythmogenic Right Ventricular Dysplasia↗
[Cardiomyopathy and immune competence in heart insufficiency].
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Cardiac Output, Low↗
Practical recommendations for the use of ACE inhibitors, beta-blockers, aldosterone antagonists and angiotensin receptor blockers in heart failure: putting guidelines into practice.
Surveys of prescribing patterns in both hospitals and primary care have usually shown delays in translating the evidence from clinical trials of pharmacological agents into clinical practice, thereby denying patients with heart failure (HF) the benefits of drug treatments proven to improve well-being and prolong life. This may be due to unfamiliarity with the evidence-base for these therapies, the clinical guidelines recommending the use of these treatments or both, as well as concerns regarding adverse events. ACE inhibitors have long been the cornerstone of therapy for systolic HF irrespective of aetiology. Recent trials have now shown that treatment with beta-blockers, aldosterone antagonists and angiotensin receptor blockers also leads to substantial improvements in outcome. In order to accelerate the safe uptake of these treatments and to ensure that all eligible patients receive the most appropriate medications, a clear and concise set of clinical recommendations has been prepared by a group of clinicians with practical expertise in the management of HF. The objective of these recommendations is to provide practical guidance for non-specialists, in order to increase the use of evidenced based therapy for HF. These practical recommendations are meant to serve as a supplement to, rather than replacement of, existing HF guidelines.
Adrenergic beta-Antagonists↗