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Viral infections often affect the heart. In the majority of cases, the course of the disease is benign and patients recover spontaneously. However, viral infection may persist and lead to acute cardiac failure or progress to dilated... more
Viral infections often affect the heart. In the majority of cases, the course of the disease is benign and patients recover spontaneously. However, viral infection may persist and lead to acute cardiac failure or progress to dilated cardiomyopathy. Viral infections are considered to be the most common causes of myocarditis. There is evidence that intramyocardial viral persistence is associated with progressive ventricular dysfunction, even when the infiltrate is sparse or missing. The diagnosis of viral myocarditis necessitates the detection of viral genome by molecular biology techniques and the evaluation of myocardial inflammation by the immunohistochemistry on endomyocardial biopsy samples. Autoreactive myocarditis can also only be diagnosed by endomyocardial biopsy. Infiltration of leukocytes and a negative polymerase chain reaction on microbial agents are their hallmarks. Apart from symptomatic or supportive therapy, etiologic treatment strategies have to address the underlyin...
A 36 year-old man suffered from fever, fatigue, pleurodynia and precordial discomfort. His family physician suspected febrile tracheobronchitis and treated it with ampicillin for 5 days. Because symptoms persisted an ECG was done which... more
A 36 year-old man suffered from fever, fatigue, pleurodynia and precordial discomfort. His family physician suspected febrile tracheobronchitis and treated it with ampicillin for 5 days. Because symptoms persisted an ECG was done which suggested acute myocardial infarction. The patient underwent an emergency coronary angiography which excluded coronary artery disease and aortic dissection. Pericarditis was suspected and the patient put on aspirin, 500 mg/d. Because of persisting cardiac symptoms an echocardiography was performed which revealed systolic separation between epi- and pericardium, characteristic of a small pericardial effusion after acute pericarditis. The symptoms improved after one week of treatment with diclofenac and the ECG had become normal. Two months later the patient was seen at our cardiac outpatient clinic. He had night sweats, sporadic precordial pain and severe dyspnoe. Further investigations revealed tachycardia (120/min), hypotension (95/70 mm Hg), pulsus ...
Since the establishment of cardiac resynchronization therapy in left bundle branch block and mechanical asynchrony, the adverse effects of right ventricular apical pacing have gained increasing scientific interest. The sequelae of... more
Since the establishment of cardiac resynchronization therapy in left bundle branch block and mechanical asynchrony, the adverse effects of right ventricular apical pacing have gained increasing scientific interest. The sequelae of "iatrogenic desynchronization" on cardiac structure and function as well as on patients' prognosis could be well documented. "Minimally desynchronizing" stimulation strategies could be an alternative for patients needing ventricular pacing. The search for hemodynamically more advantageous alternative right ventricular pacing sites has failed so far to deliver well validated results, and due to the somewhat higher lead dislodgment rates pure left ventricular pacing cannot be recommended, at least not in pacemaker-dependent patients. Hence there is the question for primary biventricular stimulation in patients with AV block. The results of several biventricular studies with limited numbers of patients have been promising with respect to structural and functional surrogate endpoints. Two major controlled prospective and prognostically orientated studies, the BIOPACE study and the BLOCK-HF study, are currently underway and will report results in the next few years. According to the actual guidelines of the European Society of Cardiology (ESC) the implantation of a biventricular system is recommended in patients with AV block even without left bundle branch block (Class IIa, evidence level C) if they fulfill the remaining criteria that justify the implantation of a biventricular system. According to the guidelines for pacemaker therapy of the German Cardiac Society (GCS) biventricular pacing can be considered in these patients. Both societies do expressly permit the implantation of biventricular systems with ICD backup if indicated.
A 30-year-old patient suffered from a dry cough and increasing dyspnea since two years; he further complained about non radiating chest pain and weight loss of 15 kg in the past 8 weeks. Physical examination revealed pulsus paradoxus and... more
A 30-year-old patient suffered from a dry cough and increasing dyspnea since two years; he further complained about non radiating chest pain and weight loss of 15 kg in the past 8 weeks. Physical examination revealed pulsus paradoxus and distended neck veins. On chest x-ray, signs of cardiomegaly without infiltrations were found. Echocardiographic studies demonstrated a large pericardial effusion with signs of pericardial tamponade. Pericardiocentesis and pericardioscopy was performed and pericardial as well as epimyocardial biopsy samples were taken. Serum studies revealed increased markers of myocardial infarction and hypereosinophilia without clinical evidence of parasitic, myeloproliferative, or neoplastic diseases. Diagnosis of acute eosinophilic myocarditis was established in the epimyocardial biopsy samples. Based on the clinicopathologic findings, we diagnosed Churg Strauss syndrome with cardiac involvement. We instilled 500 mg triamcinolone intrapericardially and initiated ...
Over 50 % of cases of inflammatory cardiomyopathy are caused by bacterial or viral infection, the latter frequently Parvovirus B19, enterovirus (Coxsackie B virus) or adenovirus. Regarding the pathogenesis of the disease, its early phase... more
Over 50 % of cases of inflammatory cardiomyopathy are caused by bacterial or viral infection, the latter frequently Parvovirus B19, enterovirus (Coxsackie B virus) or adenovirus. Regarding the pathogenesis of the disease, its early phase is dominated by the infectious pathogen, which directly damages the myocardium, while in the second phase an important role is played by activation of the immune system and the antiviral immune response with immunological processes. A 24-year-old woman (height 175 cm, weight 88 kg) was admitted because of recurrent exertional dyspnea. She also reported increased feeling of weakness, fainting and vertigo for the preceding six months. She reported an influenza-like infection just before the onset of these symptoms. No abnormalities were found on physical examination. But echocardiography revealed markedly reduced ventricular contractility with an ejection fraction (EF) of 30 %. A cardiac catheterization was performed, as part of which a myocardial bio...
Evidence for manifest right ventricular dysfunction is considered a critical threshold in the development of a fatal event after acute pulmonary embolism. While the acute event impressively reflects the clinical significance of right... more
Evidence for manifest right ventricular dysfunction is considered a critical threshold in the development of a fatal event after acute pulmonary embolism. While the acute event impressively reflects the clinical significance of right ventricular function, various disorders such as idiopathic pulmonary arterial hypertension, secondary pulmonary hypertension in lung diseases, carcinoid heart disease, and portopulmonary hypertension can lead to chronic right ventricular failure. Adapted treatment makes it possible to alleviate the patients' distress and presumably also improve the prognosis. The clinical picture of right ventricular insufficiency can also be imitated in constrictive or adhesive pericarditis and pericardial tamponade. Pericardiocentesis of the tamponade provides initial hemodynamic improvement. Causal treatment is based on cytological findings and/or results of epicardial or pericardial biopsy to classify malignant and nonmalignant effusions. Cardiac surgery with pe...
Since the introduction of ACE-inhibitors into clinical practice, the diuretic treatment with the classical aldosterone antagonist spironolactone has disappeared. It was generally believed that chronic treatment with ACE-inhibitors... more
Since the introduction of ACE-inhibitors into clinical practice, the diuretic treatment with the classical aldosterone antagonist spironolactone has disappeared. It was generally believed that chronic treatment with ACE-inhibitors significantly reduces aldosterone secretion via reduction of angiotensin II-dependent aldosterone formation. However, aldosterone "escape" occurs: Even during chronic treatment with ACE-inhibitors, plasma levels of aldosterone rise again, which is associated with increased cardiovascular risk. Furthermore, extrarenal actions of aldosterone have been demonstrated, which detrimentally affect coagulation, autonomic activity, inflammatory signalling, hemodynamics, and fibrosis, subsequently leading to cardiovascular damage. Recently published studies (RALES, EPHESUS) convincingly support the concept of detrimental cardiovascular aldosterone actions even during chronic ACE-inhibition. In addition to those cardiovascular effects, aldosterone antagonism...
Indications and diagnostic value of the most important noninvasive procedures for the diagnosis of peripheral arterial disease and diseases of the supraaortic arteries are reviewed in this article with particular emphasis on cardiologic... more
Indications and diagnostic value of the most important noninvasive procedures for the diagnosis of peripheral arterial disease and diseases of the supraaortic arteries are reviewed in this article with particular emphasis on cardiologic questions. As compared to coronary artery disease, peripheral arterial disease has long been addressed as being negligible in number and importance, a view that had to be reassessed in recent years. The prevalence of claudication and critical leg ischemia has increased. Earlier diagnosis and specific therapeutic regimens will be able to prevent or at least slow progression of the disease and, thereby, major amputation. The patient's history and physical examination in addition to measurement of the ankle-brachial index (ABI; determined by dividing the systolic pressure measured by Doppler ultrasonography of the A. dorsalis pedis or A. tibialis posterior by that of the A. brachialis) usually allows for the diagnosis of peripheral arterial disease ...
Atrial fibrillation is the most frequent arrhythmia. It can impair quality of life considerably. Due to thromboembolic complications it contributes to the patients' morbidity and mortality and to the costs for their medical treatment.... more
Atrial fibrillation is the most frequent arrhythmia. It can impair quality of life considerably. Due to thromboembolic complications it contributes to the patients' morbidity and mortality and to the costs for their medical treatment. In chronic atrial fibrillation there is a need for adequate anticoagulation and heart rate control. In paroxysmal and intermittent atrial fibrillation it should be sought to prevent its progression to chronic atrial fibrillation. Since atrial fibrillation initiates negative processes of remodeling within the atrial myocardium, it has the tendency to perpetuate itself. From a theoretical point of view, it can be expected that all means which prevent episodes of atrial fibrillation or which terminate it immediately after its onset, are able to prevent or at least to delay the progression to chronic atrial fibrillation. Pharmacologic treatment is usually used to prevent recurrences of atrial fibrillation. Based on the actual data it can also be expect...
A 57-year-old white man had been travelling in Kenya for vacation until 14 days before admission. Due to apprehension about side effects, the patient had refused any malaria prophylaxis. Ten days before admission he developed low grade... more
A 57-year-old white man had been travelling in Kenya for vacation until 14 days before admission. Due to apprehension about side effects, the patient had refused any malaria prophylaxis. Ten days before admission he developed low grade temperatures and suffered from pain in the limbs, from nausea and vomiting. A new episode of tachyarrhythmia was diagnosed two days before admission and was treated by his general practitioner. Finally he was admitted to our hospital because of high temperatures, chills and progressive clinical deterioration. Autopsy revealed prominent congestion of liver, spleen and cerebral vessels as well as subdural and subarachnoidal hemorrhage. In both thin and thick peripheral blood smears Plasmodium parasites were demonstrated in approximately 30% of the eryhthrocytes and the diagnosis of Plasmodium falciparum was immediately confirmed by an immunological test. Due to the fulminant clinical and neurological deterioration with progressive hypoxaemia, the patien...
The relation between microvolt level T wave alternans (TWA) and other noninvasive arrhythmia risk predictors was analyzed in 221 consecutive patients with idiopathic dilated cardiomyopathy (IDC) and sinus rhythm enrolled in the Marburg... more
The relation between microvolt level T wave alternans (TWA) and other noninvasive arrhythmia risk predictors was analyzed in 221 consecutive patients with idiopathic dilated cardiomyopathy (IDC) and sinus rhythm enrolled in the Marburg Cardiomyopathy Study between March 1996 and May 2000. TWA analysis was also performed in 110 healthy controls of similar age and sex. TWA during symptom-limited exercise was positive, negative and indeterminate in, respectively, 108 (49%), 65 (29%) and 48 (22%) patients with IDC versus, respectively, 5 (5%), 98 (89%) and 7 (6%) healthy controls (P < 0.05). Patients with IDC and positive TWA had a lower left ventricular (LV) ejection fraction (29 +/- 9% vs 34 +/- 10%, P < 0.05) and greater LV end-diastolic diameter (69 +/- 8 mm versus 64 +/- 6 mm, P < 0.05) than patients with negative TWA. Other variables, including age, gender, New York Heart Association functional class, presence of bundle branch block, arrhythmias on 24-hour ambulatory elec...
To determine the circadian variations and the onset mechanisms of ventricular tachyarrhythmias (VT) in patients with implantable cardioverter defibrillators, stored electrograms of 364 VT episodes occurring in 40 patients with coronary... more
To determine the circadian variations and the onset mechanisms of ventricular tachyarrhythmias (VT) in patients with implantable cardioverter defibrillators, stored electrograms of 364 VT episodes occurring in 40 patients with coronary artery disease (CAD) and in 29 patients with idiopathic dilated cardiomyopathy (DCM) were analyzed. A similar circadian distribution of VT episodes was observed in both groups, with a morning peak and less pronounced evening peak. After exclusion of patients with atrial fibrillation, VT onset was classified as (1) sudden if preceded by > or = 8 regular cycles without ventricular premature beats, (2) onset with a short-long-short interval, and (3) a more complex onset with variable patterns of ventricular premature beats before initiation of VT. Sudden onset was found in 26% and 21% of VTs in CAD and DCM respectively. A short-long-short interval preceded 29% of VTs in CAD compared to 14% of VTs in DCM (P < 0.05). A more complex onset was observed...
The cardiovascular interstitial space is largely composed of type I and III fibrillar collagens. Tissue structure, form and function are determined not only by the collagen content but also by the ratio of different collagens to each... more
The cardiovascular interstitial space is largely composed of type I and III fibrillar collagens. Tissue structure, form and function are determined not only by the collagen content but also by the ratio of different collagens to each other. Matrix metalloproteinases are members of a family of secreted and membrane-bound enzymes that are capable of degrading highly proteolytic resistant fibrillar type I and III collagens. Collagen tissue content is determined by balanced collagen synthesis and degradation. MMP activity and adverse tissue remodeling have been identified in coronary plaques in unstable angina. It has also been linked with the progression of aortic aneurysms and with left ventricular dilatation in congestive heart failure in patients with ischemic and non-ischemic cardiomyopathy. The role of MMPs in these cardiovascular diseases and possible therapeutic options are the focus of this review.
To examine the relation between cardiac autonomic tone, assessed by baroreflex sensitivity and heart rate variability, and left ventricular function, arrhythmias on Holter monitoring, and clinical variables in patients with idiopathic... more
To examine the relation between cardiac autonomic tone, assessed by baroreflex sensitivity and heart rate variability, and left ventricular function, arrhythmias on Holter monitoring, and clinical variables in patients with idiopathic dilated cardiomyopathy. A prospective observational study. 160 patients with idiopathic dilated cardiomyopathy and preserved sinus rhythm in the absence of antiarrhythmic drug treatment. Measures of heart rate variability obtained by digital 24 hour Holter recordings included the mean of all coupling intervals between normal beats (RRm), the standard deviation of the mean of normal RR intervals (SDNN), and the square root of the mean of the squared differences between adjacent normal RR intervals (rMSSD). Baroreflex sensitivity testing was performed using the phenylephrine method. Mean SDNN (SEM) was 112 (46) ms, and baroreflex sensitivity was 7.5 (5.0) ms/mm Hg. SDNN showed a weak correlation with baroreflex sensitivity (r = 0.19, p < 0.05) and wit...
The aim of the present study was to assess the effects of carvedilol therapy in addition to conventional heart failure therapy on heart rate variability (HRV) and on left ventricular function in 14 patients with mild to moderate heart... more
The aim of the present study was to assess the effects of carvedilol therapy in addition to conventional heart failure therapy on heart rate variability (HRV) and on left ventricular function in 14 patients with mild to moderate heart failure due to idiopathic dilated cardiomyopathy (IDC). After a 3- to 4-week titration period, carvedilol was titrated up to 50mg daily, or the highest dose tolerated (at least 25mg daily). Maintenance treatment was then continued for 8 weeks. Digital 24-hour Holter recordings were obtained at baseline and after 8 weeks of carvedilol therapy. HRV for the entire 24-hour period was computed in the time domain using the Oxford Medilog Excel 2 analysis system. Measures of HRV included the mean of all coupling intervals between normal beats (RRm), the standard deviation of all normal RR intervals (SDNN), the square root of the mean of the squared differences between adjacent normal RR intervals (rMSSD), and the proportion of adjacent normal RR intervals dif...
We addressed the hypothesis that hypercaloric diets induce hyperkinetic hypertension irrespective of day-night cycle and locomotor activity that is associated with altered cardiac myosin isozymes. Normotensive rats with implanted... more
We addressed the hypothesis that hypercaloric diets induce hyperkinetic hypertension irrespective of day-night cycle and locomotor activity that is associated with altered cardiac myosin isozymes. Normotensive rats with implanted radiotelemetry pressure transducers were fed increasing amounts of coconut fat (8, 16, and 24%, each for 2 wk) corresponding to 20-47% of total calories from fat. Thereafter, increasing amounts of sucrose (16, 32, and 50%) and fructose (50%) were added to the 24% fat diet corresponding to 13-40% of total calories from sugar. In contrast to the fat diets, the 32% and 50% sucrose diets as well as the 50% fructose diets increased (P < 0.05) blood pressure (systolic maximum +13 mmHg, diastolic maximum +4 mmHg, mean maximum +7 mmHg) and heart rate (maximum +50 beats/min) irrespective of the day-night cycle and the unaltered locomotor activity. Furthermore, body weight increased (P < 0.05) during the 32% and 50% sucrose feedings. The increased blood pressur...
Chest pain can arise from cardiovascular or noncardiovascular causes. Among the latter are the skin, the chest wall, intrathoracic structures, or subdiaphragmatic organs. The problem to attribute the chest discomfort to either the heart... more
Chest pain can arise from cardiovascular or noncardiovascular causes. Among the latter are the skin, the chest wall, intrathoracic structures, or subdiaphragmatic organs. The problem to attribute the chest discomfort to either the heart or extracardiac organs arises because the heart, pleura, aorta, and esophagus are all supplied by sensory fibers from the same spinal segments. In contrast to the diseases mentioned above, angina pectoris in sensu strictu is defined as chest pain or discomfort of cardiac origin that arises because of temporary imbalance between myocardial oxygen supply and demand. The metabolic oxygen requirements of the myocardium are essentially dictated by myocardial contraction since only a fraction of the consumed oxygen is needed by the quiescent heart. Therefore, the factors that primarily influence myocardial oxygen consumption include heart rate, the force of cardiac contraction, and myocardial wall tension, as determined by pressure (afterload), volume (pre...
The vascular endothelium is the inner lining of all blood vessels and serves as an important autocrine and paracrine organ, that regulates vascular wall functions. Because of its strategic location between the circulating blood and the... more
The vascular endothelium is the inner lining of all blood vessels and serves as an important autocrine and paracrine organ, that regulates vascular wall functions. Because of its strategic location between the circulating blood and the vascular wall, the endothelium interacts with cellular and neurohumoral mediators, thus controlling vascular contractile state and cellular composition. The vascular endothelium maintains vascular homeostasis by modulating blood vessel tone, by regulating local cellular growth and extracellular matrix deposition and by controlling hemostatic as well as inflammatory responses. One of the best characterized and most important substances released from the endothelium is nitric oxide (NO). NO is a soluble gas which is continuously synthesized from the amino acid L-arginine in endothelial cells by the constitutively expressed nitric oxide synthase. The most important stimuli represent physical factors such as shear stress and pulsatile stretching of the ve...
A considerable number of large scale clinical trials provide clear evidence that cholesterol lowering is one of the most important risk-reduction strategies for secondary and primary prevention of coronary artery disease. Unlike the older... more
A considerable number of large scale clinical trials provide clear evidence that cholesterol lowering is one of the most important risk-reduction strategies for secondary and primary prevention of coronary artery disease. Unlike the older studies with fibrates, the most recent trials of cholesterol-lowering therapies with the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors have clearly shown that their use can reduce coronary artery disease and total mortality as well as the need for expensive hospitalization and revascularization procedures. Studies such as the Scandinavian Simvastatin Survival Study (4S), the West of Scotland Coronary Prevention Study (WOS), the Cholesterol and Recurrent Events (CARE) trial and most recently the Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) as well as numerous other investigations, have established that decreasing elevated levels of low-density lipoprotein (LDL) cholesterol will result in a reduction in ...
Such new technologies are associated with potential problems for patients with pacemakers which have not yet been adequately investigated. External sources of interference may inhibit or, in the case of dual chamber devices, trigger, the... more
Such new technologies are associated with potential problems for patients with pacemakers which have not yet been adequately investigated. External sources of interference may inhibit or, in the case of dual chamber devices, trigger, the pacemaker, change its program or cause thermal damage to electrode tips leading to elevation of the stimulation threshold, or may destroy both hardware and software components. To prevent such problems, protective measures such as screening, sensitivity filters, asynchronous stimulation, and the bipolar electrodes have been developed. Detection by the pacemaker of a constant source of interference automatically activates an anti-interference circuit providing a fixed stimulating frequency. In contrast, interference by a pulsed or strongly amplitude-modulated signal can inhibit pacemaker function for a lengthy period and thus cause symptoms and possibly syncope.
An increasing number of clinical and experimental studies point to a contribution of various infectious organisms like chlamydia pneumoniae or herpesviruses to atherosclerosis in man. Cytomegalovirus induces atherosclerotic lesions in... more
An increasing number of clinical and experimental studies point to a contribution of various infectious organisms like chlamydia pneumoniae or herpesviruses to atherosclerosis in man. Cytomegalovirus induces atherosclerotic lesions in animals. In vitro studies reveal functional changes of endothelial cells after infection with cytomegalovirus. Infection with this virus renders endothelial cells immunogenic for cellular and humoral immune reactions. In man a significant association of infections with herpesviruses and atherosclerosis could be established in several studies. Cytomegalovirus infection has been incriminated as an independent risk factor in restenosis after coronary angioplasty.
Diagnosis of inflammatory dilated cardiomyopathy relies on the histological and immunohistological examination of endomyocardial biopsies. Only with the demonstration of the etiological agents in the myocardium specific therapy can be... more
Diagnosis of inflammatory dilated cardiomyopathy relies on the histological and immunohistological examination of endomyocardial biopsies. Only with the demonstration of the etiological agents in the myocardium specific therapy can be attempted. Whereas the spontaneous course of endemic myocarditis with little hemodynamic impairment is fair, the prognosis of symptomatic myocarditis and dilated cardiomyopathy is poor, with complete restitution in 35% and a 10-year survival rate of 30%. Restriction of physical activity is a validated form of therapy with normalization of the heart size in 40 to 60%. Symptomatic medical therapy consists of digitalis, diuretics, ACE-inhibitors and vasodilators and betablocker therapy, where a reduction of mortality was demonstrated in clinical (sub)studies up to 60%. Specific forms of therapy in inflammatory cardiomyopathy rely on the demonstration or lack of viral persistence or signs of autoreactivity in the myocardial tissue. Immunosuppressive therap...
The most recent WHO/ISFC classification of cardiomyopathies (1995) describes as cardiomyopathies all heart muscle diseases, which demonstrate a disturbance of cardiac function. It distinguishes primarily according to hemodynamic criteria... more
The most recent WHO/ISFC classification of cardiomyopathies (1995) describes as cardiomyopathies all heart muscle diseases, which demonstrate a disturbance of cardiac function. It distinguishes primarily according to hemodynamic criteria the following 5 forms: 1. dilated (DCM), 2. hypertrophic (HCM), 3. restrictive (RCM) from 4. arrhythmogenic right ventricular (ARVCM) and assembles in 5. non-classified cardiomyopathies (NKCM) the non-classifiable forms. When compared to the 18-year-old former classification several points have been altered: 1. ARVCM has been introduced as a new entity. 2. The new term ischemic cardiomyopathy has been reserved for the remodeling process of the non-infarcted myocardium and does not mean hemodynamic alterations of an infarcted area (aneurysm), of stunned or hibernating myocardium. Hypertensive cardiomyopathy corresponds to left ventricular hypertrophy in hypertensive patients, valvular cardiomyopathy identifies cardiomegaly, which cannot sufficiently ...
Endstage coronary artery disease still remains a therapeutic challenge. An increasing number of patients is no longer amenable for direct revascularization by PTCA or coronary bypass surgery and does also no longer respond to maximum... more
Endstage coronary artery disease still remains a therapeutic challenge. An increasing number of patients is no longer amenable for direct revascularization by PTCA or coronary bypass surgery and does also no longer respond to maximum medical therapy. This fact has directed the interest again towards surgical techniques of indirect revascularization, which had been introduced by Beck and other surgeons more than 60 years ago. Among these attempts we can also find transmyocardial needle punctures, firstly performed by Sen in Bombay. In the early eighties it was Mirhoseini, who used a laser for creating these transmural channels, primarily in combination with coronary bypass surgery at the arrested heart and later on together with Crew as a sole therapy at the beating heart. The idea behind this transmyocardial laser revascularization (TMLR) was a "reptilization" of the human heart, which meant a direct blood supply from the ventricle into the ischemic myocardium. Whereas thi...
To establish a psychological stress model, we characterized in rats the effects of chronic (5-6 wk) scheduled food pellet feeding (35 mg/80 s for 8 h/day). Because the scheduled intake of pellets required that rats have access to 80% of... more
To establish a psychological stress model, we characterized in rats the effects of chronic (5-6 wk) scheduled food pellet feeding (35 mg/80 s for 8 h/day). Because the scheduled intake of pellets required that rats have access to 80% of ad libitum intake, the effect of food restriction was also examined by withholding food intermittently for 24 or 48 h each, followed by 24 h free access to food. Cardiac norepinephrine concentration was significantly increased (1,076 +/- 169 vs. 693 +/- 107 ng/g, P < 0.05) in rats subjected to pellet feeding compared with pair-fed rats (same amount of pellets in one portion) or 24- or 48-h intermittently fasted rats; similarly, the epinephrine content of adrenal glands was increased (P < 0.05). Left ventricular rate of sarcoplasmic reticulum Ca2+ uptake was decreased (P < 0.05) compared with pair-fed rats, reaching values observed for 24-h fasted rats, whereas the proportion of alpha-myosin heavy chains was only slightly reduced. Thus the sc...
In 240 tachycardias with wide QRS-complex (> or = 120 ms), the value of the "old" ECG criteria published in 1978 by Wellens and coworkers was compared to the "new" ECG criteria published in 1991 by Brugada and... more
In 240 tachycardias with wide QRS-complex (> or = 120 ms), the value of the "old" ECG criteria published in 1978 by Wellens and coworkers was compared to the "new" ECG criteria published in 1991 by Brugada and coworkers for the differential diagnosis of tachycardias with wide QRS-complex. As main result of the study, it could be demonstrated that with the old as well as with the new ECG criteria a sensitivity of more than 90% for the correct diagnosis ventricular tachycardia can be reached. The specificity of the old and new ECG criteria for the diagnosis ventricular tachycardia is 70% and 72% for tachycardias with right bundle branch block configuration and 87% each for tachycardias with left bundle branch block configuration. The combined use of the old and the new ECG criteria in this study could not increase sensitivity and specificity for the diagnosis of ventricular tachycardia. Therefore, it does not appear to be important for the differential diagnosis...
Despite intense research efforts, the etiology of primary hypertension remains ill-defined. During our work on molecular influences of lifestyle factors on hypertension, the question arose to what extent cellular and molecular events... more
Despite intense research efforts, the etiology of primary hypertension remains ill-defined. During our work on molecular influences of lifestyle factors on hypertension, the question arose to what extent cellular and molecular events could be involved in alcohol-induced hypertension. There is increasing evidence that alcohol initiates central as well as peripheral reactions which in a synergistic manner have a hypertensive action. Thus, alcohol diminishes the baro (presso) reflex by interacting with receptors in the brain stem, i.e. nucleus tractus solitarii and rostral ventrolateral medulla. In addition, alcohol induces an increased sympathetic outflow, most probably linked to secretion of corticotropin-releasing hormone. The increased sympathetic outflow is expected not only to induce adrenoceptor-mediated reactions (vasoconstriction, heart rate increase) but to stimulate oxidation reactions. Deleterious peripheral actions result from acetaldehyde which binds to macromolecules if ...
The direct toxic effect of alcohol and its metabolite acetaldehyde has been demonstrated both in laboratory animals and in humans. Alterations in the mitochondrial ultrastructure and the dilatation of the sarcoplasmatic reticulum have... more
The direct toxic effect of alcohol and its metabolite acetaldehyde has been demonstrated both in laboratory animals and in humans. Alterations in the mitochondrial ultrastructure and the dilatation of the sarcoplasmatic reticulum have been shown after an acute infusion of alcohol in the heart. These changes correlate with decreased mitochondrial function, defects in protein synthesis and the occurrence of arrhythmias. The risk of developing alcoholic cardiomyopathy is related to both the mean daily alcohol intake and the duration of drinking, but there is much individual susceptibility to the toxic effect of alcohol. Most patients, in whom alcoholic cardiomyopathy develops, have been drinking over 80 g/d for more than 5 years. The clinical diagnosis of alcoholic cardiomyopathy reflects the coexistence of global myocardial dysfunction in a heavy drinker in whom no other cause for myocardial disease was found. In studies focussing on alcoholic cardiomyopathy the surprising histologic ...
The association between alcohol use and rhythm disturbances, particularly supraventricular tachyarrhythmias in apparently healthy people is called "holiday heart syndrome". The syndrome was first described in persons with heavy... more
The association between alcohol use and rhythm disturbances, particularly supraventricular tachyarrhythmias in apparently healthy people is called "holiday heart syndrome". The syndrome was first described in persons with heavy alcohol consumption, who typically presented at weekends or after holidays, but it may also occur in patients who usually drink little or no alcohol. The most common rhythm disorder is atrial fibrillation, which usually converts to normal sinus rhythm within 24 hours. The incidence of the holiday heart syndrome depends on the drinking habits of the studied population. The holiday heart syndrome should be considered particularly as a diagnosis in patients without overt heart disease presenting with new onset atrial fibrillation. Though recurrences occur, the clinical course is benign and specific antiarrhythmic therapy is usually not warranted.
This review examines the immunologic rationale for immunosuppressive and immunomodulating therapy in man and experimental animal. The controversy if immunosuppressive treatment is beneficial in myocarditis will continue even after the... more
This review examines the immunologic rationale for immunosuppressive and immunomodulating therapy in man and experimental animal. The controversy if immunosuppressive treatment is beneficial in myocarditis will continue even after the American myocarditis trial. It is obvious that in viral heart disease immunosuppressive drugs should be avoided, in autoreactive forms of myocarditis with proven humoral and cellular effector mechanisms they may be used in controlled randomized trials to validate or negate their benefit. Immunomodulating factors e.g. immunostimulatory or antiviral substances like ribaverin, the interleukins and interferons have demonstrate some effect in experimental animal myocarditis but proof for the efficiency in man is still lacking. Hyperimmunoglobulin therapy appears to be of particular interest because of the little side effects and positive results in CMV associated myopericarditis in man.
Hypertrophic cardiomyopathy is characterized by an unexplained hypertrophy of the left ventricle, particularly the interventricular septum. Although point mutations in the beta-myosin chain gene have been found in several US families in... more
Hypertrophic cardiomyopathy is characterized by an unexplained hypertrophy of the left ventricle, particularly the interventricular septum. Although point mutations in the beta-myosin chain gene have been found in several US families in familiar hypertrophic cardiomyopathy, the pathogenetic pathways leading to myocyte hypertrophy, the most important feature, are still not clear. To examine whether activation (expression) of nuclear proto-oncogenes may play a role in hypertrophic cardiomyopathy, endomyocardial biopsies from 13 patients with hypertrophic cardiomyopathy were examined using monoclonal antibodies against c-myc, c-fos and c-jun. The nuclear proto-oncogenes c-fos, c-jun and c-myc were expressed in 53, 60, and 50%, respectively, of patients with hypertrophic cardiomyopathy. In control biopsies, c-myc was detectable in only 10% of the patients, while c-fos and c-jun were always undetectable. These results show that nuclear proto-oncogenes are induced in patients with hypertr...
Cytomegaloviruses(CMV) belong to a group of cardiotropic DNA-viruses with well-documented but sporadic cardiac involvement. By in situ hybridization with a biotinylated cDNA probe CMV-DNA was analysed in 2 different series of... more
Cytomegaloviruses(CMV) belong to a group of cardiotropic DNA-viruses with well-documented but sporadic cardiac involvement. By in situ hybridization with a biotinylated cDNA probe CMV-DNA was analysed in 2 different series of patients(1982-1988; 1989-1991) in the endomyocardial biopsy specimens of 35 patients with active myocarditis as defined by the Dallas criteria, and of 35 patients with acute perimyocarditis (pericardial effusion and cardiomegaly or segmental wall motion abnormality and/or an endomyocardial biopsy positive for active myocarditis) were analysed. 51% of patients with active myocarditis, 65% positive findings were observed in patients with perimyocarditis when all positive signals in the myocardium were taken into account. Since in interstitial cells and the vascular endothelium HCMV-DNA was also detected in controls we conclude that only HCMV-DNA in the nuclei are specific for HCMV-associated myocarditis. The incidence of positive signals in the myocytes was lower...
Echocardiography has contributed considerably to the evolution in the management of patients with infective endocarditis. There is a clear hierarchy with respect to sensitivity of the different methods is superior when compared to 2-D and... more
Echocardiography has contributed considerably to the evolution in the management of patients with infective endocarditis. There is a clear hierarchy with respect to sensitivity of the different methods is superior when compared to 2-D and M-mode echocardiography in identifying both vegetations and perivalvular complications e.g. abscess formation, aneurysms, mural endocardial lesions. For patients with suspected endocarditis, in whom vegetations can not be clearly identified or in whom abscess formation is suspected with transthoracic echocardiography (TTE), transesophageal echocardiography (TEE) with mono- or multiplane scans has become the standard diagnostic procedure. For the examination of prosthetic valves it is the method of choice. It has even been suggested that it is employed as routine measure in all patients with suspected infective endocarditis. TEE is a safe semi-invasive technique with an extremely low complication rate and high sensitivity. Its specificity depends la...
Familial hypertrophic cardiomyopathy (FHC) is an autosomal dominant disease which has a benign clinical course in most patients but carries also the risk of sudden cardiac death. Initial genetic studies have revealed the beta-myosin heavy... more
Familial hypertrophic cardiomyopathy (FHC) is an autosomal dominant disease which has a benign clinical course in most patients but carries also the risk of sudden cardiac death. Initial genetic studies have revealed the beta-myosin heavy chain (beta-MHC) gene on chromosome 14q11-q12 as morbid gene. Several mutations have been identified, almost all of them are missense mutations of the area in the gene coding for the globular head region of the myosin. The codon 403 has been found to be a hot-spot for mutations. Both, mutant myosin messenger RNA and proteins have been found in cardiac and in skeletal muscle, indicating the presence of a normal protein synthesis of the mutant allele. Histological studies show that gross alterations in protein assembly do not occur (e.g. by introducing the 403Arg-->Gln mutation in cell expression systems) and in-vitro motility of distinct mutations may be reduced in comparison to wild type myosin. The exact mechanism, however, how myosin mutations...
We report the case of a 51-year-old patient with a Paget von Schrötter-Syndrome of the right arm who underwent a successful lysis therapy with 9 x 10(6) IU streptokinase (Streptase) i.v. over 3 days. 36 h after ending the lysis therapy he... more
We report the case of a 51-year-old patient with a Paget von Schrötter-Syndrome of the right arm who underwent a successful lysis therapy with 9 x 10(6) IU streptokinase (Streptase) i.v. over 3 days. 36 h after ending the lysis therapy he developed a generalized eczema, which was interpreted as a drug-induced allergic reaction of the arthus type (Coombs III). He received methylprednisolone p.o. with an initial dose of 40 mg, tapered to 0 over 5 days. One day after the efflorent rash the patient developed fever for 12 h (with 38.8 degrees C maximum) and a gonarthritis of the left knee, and 24 h later of both knees. An echocardiogram showed a small pericardial effusion without hemodynamic influence. On the following 2 days a minimal proteinuria of 0.28 and 0.22 g/l was found. Subsequently and after a follow-up of 2 years, the patient was totally free of pathologic clinical and laboratory findings. We interpret this unusual case as a delayed hypersensitivity reaction to streptokinase w...
We describe a 63-year old female patient presenting with increasing dyspnea on exertion. The chest X-ray was suggestive but not compelling for Ebstein's anomaly. Although Ebstein's anomaly is most often discovered first in... more
We describe a 63-year old female patient presenting with increasing dyspnea on exertion. The chest X-ray was suggestive but not compelling for Ebstein's anomaly. Although Ebstein's anomaly is most often discovered first in childhood, rare cases, such as ours, are described in late adulthood, however. Obesity may be one reason why it was not possible in our patient to detect the characteristic features in transthoracic echocardiography. The diagnosis of Ebstein's anomaly could be established only by transesophageal echocardiography: There the right atrium was grossly enlarged due to the distal insertion of the septal tricuspid valve leaflet. Colour flow echocardiography clearly demonstrated severe tricuspid valve incompetence. No additional congenital or acquired cardiac disorder could be detected. Cardiac catheterization confirmed the echocardiographical findings, whereas magnetic resonance tomography did not show the abnormal insertion of the tricuspid valve leaflet. If...
Primary tumors of the heart, in contrast to secondary metastatic tumors show a very rare occurrence. About 25% of all primary cardiac tumors are malignant with angiosarcomas being the most frequent type of tumor. The clinical presentation... more
Primary tumors of the heart, in contrast to secondary metastatic tumors show a very rare occurrence. About 25% of all primary cardiac tumors are malignant with angiosarcomas being the most frequent type of tumor. The clinical presentation include pericardial tamponade by hemorrhagic pericardial effusion, right heart failure, lung embolism and thoracal pain. Diagnostic procedures include echocardiography, magnetic resonance imaging, CT scan, angiography, pericardioscopy and finally surgical exploration. We report on a 27-year old pregnant woman (23rd week) with a malignant primary angiosarcoma of the right atrium. The patient was admitted to the hospital with progressive shortening of breath due to pericardial tamponade from pericardial effusion. A tumor of the right atrium was detected by echocardiography. Diagnostic procedures had to consider the pregnancy of the patient. Transesophageal echocardiography, magnetic resonance imaging and finally angiography of the right heart with tu...
We report the case of a 59-year old patient with the rare combination of silicosis and rheumatoid arthritis, which is called Caplan's syndrome. The patient presented with right heart failure caused by a pericardial tumor compressing... more
We report the case of a 59-year old patient with the rare combination of silicosis and rheumatoid arthritis, which is called Caplan's syndrome. The patient presented with right heart failure caused by a pericardial tumor compressing the right and the left ventricle. By means of several imaging techniques it was possible to elucidate the topographic relations of the tumor. Definite signs of malignant growth were not found. Despite his elevated perioperative risk we decided to operate on the patient. During the operation macroscopic and histologic evidence revealed that the tumor was not a neoplastic process but consisted of an organized hemopericardium. This demonstrates that pericarditis in rheumatoid arthritis can be hemorrhagic and can mimick a malignant pericardial tumor. The decision to operate was first supported by the findings of the applied imaging techniques, the normal endomyocardial biopsy, and the clinical course and were later confirmed in situ.
In a 63-year old patient with a history of aortic valve replacement in 1986, a reduced hemoglobin of 91 g/l was found by a family physician. Since serum LDH was also increased, the patient was diagnosed to suffer from mechanically... more
In a 63-year old patient with a history of aortic valve replacement in 1986, a reduced hemoglobin of 91 g/l was found by a family physician. Since serum LDH was also increased, the patient was diagnosed to suffer from mechanically induced, hemolytic anemia and presented at our hospital for further diagnosis and evaluation of the aortic valve prosthesis.
The case of a 76-year-old diabetic patient with known aortic valve sclerosis is reported. One week after implantation of a permanent pacemaker system (indication: 2nd degree AV-block type Mobitz) he developed fever. Large endocarditic... more
The case of a 76-year-old diabetic patient with known aortic valve sclerosis is reported. One week after implantation of a permanent pacemaker system (indication: 2nd degree AV-block type Mobitz) he developed fever. Large endocarditic vegetations were found on the aortic and mitral valve (blood cultures: were positive for Staphylococcus aureus). Also from the pacemaker bed Staphylococcus aureus was isolated and an antibiotic treatment including vancomycin was started. Nevertheless the patient developed insufficiencies of both the aortic and mitral valves and became hemodynamically unstable. Due to cerebral embolisms and further deterioration of the patient's overall clinical state the already planned operative replacement of the aortic and mitral valve could not be performed. The patient died because of left ventricular failure after pacemaker infection which was complicated by endocarditis.
The clinical and immunological 8-year follow-up of a 45-year old female with hypereosinophilic syndrome and cardiac involvement of Löffler's fibroplastic endocarditis which was complicated by infective endocarditis during... more
The clinical and immunological 8-year follow-up of a 45-year old female with hypereosinophilic syndrome and cardiac involvement of Löffler's fibroplastic endocarditis which was complicated by infective endocarditis during immunosuppressive treatment is presented. All 3 stages of the disease were documented by clinical and histologic data: stage 1 by biopsy proven eosinophilic myocarditis and arteritis, stage 2 with Berlin blue positive parietal thrombosis, and the fibrotic features of stage 3 both by fibrosis in the latest biopsies and by echocardiography. It was remarkable, however, that this classic clinical case of Löffler's endocarditis lacked a few serological markers postulated to be found regularly, e.g., a positive staining for the cationic protein and major ribonucleases. Instead, the patient demonstrated all the immunological features of autoreactive myocarditis with cytolytic, complement fixing antimyolemmal antibodies. After an initial loading dose of 120 mg pred...
Cytomegalovirus (CMV) genes were detected by in situ hybridization in 25 Chinese patients with viral myocarditis (VMC). The positive hybridization signals were found in cardiomyocytes (6 cases, 24%), capillary endothelial cells (4 cases,... more
Cytomegalovirus (CMV) genes were detected by in situ hybridization in 25 Chinese patients with viral myocarditis (VMC). The positive hybridization signals were found in cardiomyocytes (6 cases, 24%), capillary endothelial cells (4 cases, 16%) and interstitial cells (7 cases, 28%). The difference between VMC and control group (16 cases died of brain trauma and 10 cases of congenital heart diseases was statistically significant. There was no definite pathomorphological relationship between the detection of CMV genes and myocardial lesions. The results suggest that CMV infection may be one of the causes of myocarditis and chronic stimulation of the immune system induced by CMV may be a possible pathogenesis of this disease.
The term accelerated idioventricular rhythm describes an ectopic ventricular rhythm with 3 or more consecutive ventricular premature beats with a rate faster than the normal ventricular intrinsic escape rate of 30 to 40 beats per minute,... more
The term accelerated idioventricular rhythm describes an ectopic ventricular rhythm with 3 or more consecutive ventricular premature beats with a rate faster than the normal ventricular intrinsic escape rate of 30 to 40 beats per minute, but slower than ventricular tachycardia. Accelerated idioventricular rhythm differs from ventricular tachycardia by additional features such as the onset with a long coupling interval, the end by a gradual decrease of the ventricular rate or increase of the sinus rate and, last but not least, by a good prognosis. Clinically, accelerated idioventricular rhythm can occur in any form of structural heart disease and occasionally in adults or children without structural heart disease. Accelerated idioventricular rhythm most often can be seen in patients with coronary artery disease. Its occurrence after thrombolysis during acute myocardial infarction is a marker of successful reperfusion. Since accelerated idioventricular rhythm is usually hemodynamicall...

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