Biomedical subjects
Publications and source records attributed to B Maisch.
This report describes a post-infarct patient with recurrent ventricular fibrillation in the absence of acute ischaemia, in whom arrhythmia recurrences could be prevented by ventricular rate stabilization of a third-generation cardioverter defibrillator. Review of the literature and clinical implications are discussed.
BACKGROUND: To date, considerable controversy exists regarding noninvasive arrhythmia risk stratification in idiopathic dilated cardiomyopathy (IDC). Methods and Results Between 1992 and 1997, 202 patients with IDC without a history of sustained ventricular tachycardia (VT) underwent echocardiography, signal-averaged electrocardiogram (ECG), and 24-hour Holter ECG in the absence of antiarrhythmic drugs. During 32 +/- 15 months of prospective follow-up, major arrhythmic events, including sustained VT, ventricular fibrillation, or sudden death, occurred in 32 (16%) of 202 patients. After adjusting for baseline medical therapy and antiarrhythmic therapy during follow-up, multivariate Cox regression analysis identified a left ventricular (LV) end-diastolic diameter >/=70 mm and nonsustained VT on Holter as the only independent arrhythmia risk predictors. The combination of an LV end-diastolic diameter >/=70 mm and nonsustained VT was associated with a 14. 3-fold risk for future arrhythmic events (95% confidence interval 2. 3-90). To further elucidate the prognostic value of LV ejection fraction, multivariate Cox analysis was repeated with ejection fraction forced to remain in the model. In the latter model, an ejection fraction </=30% combined with nonsustained VT on Holter was found to be a significant arrhythmia risk predictor with a relative risk of 14.6 (95% confidence interval 2.2-97). CONCLUSIONS: The combination of an LV end-diastolic diameter >/=70 mm and nonsustained VT on Holter, and the combination of LV ejection fraction </=30% and nonsustained VT on Holter, identify a subgroup of patients with IDC with a 14-fold risk for subsequent arrhythmic events. These findings have important implications for the design of future studies evaluating the role of prophylactic defibrillator therapy in patients with IDC.
The efficacy of RF energy versus the neodymium:yittrium aluminum-garnet laser to create linear lesions was compared in fresh ex vivo swine hearts. A total of 598 lesions were created in four locations: ostium of the pulmonary veins, trabeculated lateral left atrium, smooth posterior part of the right atrium, and the isthmus between the inferior vena cava and tricuspid valve. A 400-micron bare quartz fiber with CO2 cooling (distance to the tissue 5, 10, and 15 mm) and an RF ablation catheter (4-mm tip) were mechanically dragged over the tissue at speeds 0.5, 1.0, and 1.5 mm/s. A continuous and transmural ablation line was recorded as successful. A 100% success rate was achieved at the pulmonary veins and the isthmus at some settings of energy delivery by the laser and RF. In the thick posterior right atrium, RF resulted in transmural lesions only when associated with carbonization, while the laser produced successful ablation lines in 100% of the attempts. In the left atrium, because of the presence of prominent trabeculations, RF was unsuccessful at all settings of energy delivery. In contrast, deep photocoagulation by laser resulted in successful ablations in the left atrium in 100% of attempts. Lesion formation was faster by laser ablation and mean lesion width was at least 25% smaller with the laser than with RF. In conclusion, the formation of linear lesions at the isthmus and at the pulmonary veins was successful with the laser and RF. In the trabeculated left atrium and the thick posterior right atrium, only laser ablation was successful.
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 in the remaining 45% of VTs in CAD and 65% of VTs in DCM (P < 0.05). In conclusion, patients with DCM and CAD had similar circadian distributions of VT episodes. The majority of episodes were preceded by complex occurrence of ventricular premature beats rather than by the classic short-long-short sequence. These findings have important implications for the development of preventive pacing methods.
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 electrocardiogram, heart rate variability and baroreflex sensitivity, were not significantly different between patients with positive vs negative TWA. The prognostic significance of TWA in IDC with regard to arrhythmic events and total mortality will be determined by multivariate Cox analysis at the end of a 5-year follow-up in this ongoing study.
OBJECTIVE: 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. DESIGN: A prospective observational study. PATIENTS: 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. RESULTS: 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 with left ventricular ejection fraction (r = 0.29, p < 0.05). SDNN showed no significant correlation with age (r = -0.07), the presence of non-sustained ventricular tachycardia (r = -0.13), or left ventricular end diastolic diameter (r = -0.07). In addition, baroreflex sensitivity showed no significant correlation with age (r = -0.13), non-sustained ventricular tachycardia (r = -0.08), left ventricular end diastolic diameter (r = 0.09), or ejection fraction (r = 0.14). CONCLUSIONS: The weak correlation between baroreflex sensitivity and heart rate variability suggests that these two indices explore different aspects of cardiac autonomic control in patients with idiopathic dilated cardiomyopathy. The weak or absent correlation between baroreflex sensitivity, heart rate variability, and other potential non-invasive risk predictors, including left ventricular ejection fraction, left ventricular end diastolic diameter, and non-sustained ventricular tachycardia on Holter monitoring, indicate that these variables may have independent prognostic value in idiopathic dilated cardiomyopathy.
Familial defective apolipoprotein (apo) B-100 (FDB) is a frequent cause of hypercholesterolemia. Hypercholesterolemia in homozygous FDB is less severe than in homozygotes for familial hypercholesterolemia. Recently, we showed decreased low density lipoprotein (LDL) apoB-100 fractional catabolism and decreased production of LDL due to an enhanced removal of apoE-containing precursors in a patient with homozygous FDB. The effects of defective apoB-100 on high density lipoprotein (HDL) metabolism are unknown. We studied HDL apoA-I metabolism in this FDB patient and in 6 control subjects by using (2)H(3)-L-leucine as a tracer. ApoA-I levels were normal in all study subjects. However, the fractional catabolic rate and the production rate of apoA-I were increased, by 79% and 70%, respectively, in FDB; the fractional catabolic rate of apoA-I in FDB was 0.34 day(-1) compared with 0.19+/-0.03 day(-1) in normal controls. The production rate of apoA-I in FDB was 18.4 mg. kg(-1). d(-1) compared with 10.8+/-2.3 mg. kg(-1). d(-1) in controls. Thus, we have shown for the first time that defective apoB-100 may influence HDL kinetics. The increase in total HDL turnover might enhance reverse cholesterol transport and could contribute to the seemingly benign clinical course of FDB compared with that of familial hypercholesterolemia.
The authors studied 134 patients with unstable angina pectoris symptoms and 32 subjects without coronary artery disease (CAD) for the presence of classical risk factors such as hypercholesterolemia, smoking, and family history of CAD. In addition they analyzed plasma insulin levels, lipoprotein (a) (Lp [a]) levels, and antibody titers against Chlamydia pneumoniae. All patients had a heart catheterization. Patients with diabetes mellitus were excluded from the study. Fasting insulin, low-density lipoprotein (LDL) cholesterol and Chlamydia pneumoniae immunoglobulin G (IgG) and IgA antibody titers did not show any difference in CAD from healthy control subjects, whereas Lp(a) was increased and high-density lipoprotein (HDL) decreased in CAD patients. These data indicate that lipoprotein (a), low HDL cholesterol, and smoking, but neither hyperinsulinemia nor elevated Chlamydia pneumoniae titers, are risk factors or predictors for CAD.
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Pressure overload of the heart is associated with a perturbed gene expression of the cardiomyocyte leading to an impaired pump function. The ensuing neuro-endocrine activation results in disordered influences of angiotensin II and catecholamines on gene expression. To assess whether angiotensin II type 1 receptor inhibition can also counteract a raised sympathetic nervous system activity, spontaneously hypertensive rats fed a hypercaloric diet were treated with eprosartan (daily 90 mg/kg body wt) and cardiovascular parameters were monitored with implanted radiotelemetry pressure transducers. Both, blood pressure and heart rate were increased (p < 0.05) by the hypercaloric diet. Although eprosartan reduced (p < 0.05) the raised systolic and diastolic blood pressure, the diet-induced rise in heart rate was blunted only partially. In addition to drugs interfering with the enhanced catecholamine influence, compounds should be considered that selectively affect cardiomyocyte gene expression via 'metabolic' signals.
HISTORY AND CLINICAL FINDINGS: A 40-year-old man with histologically proven sarcoidosis, known for 15 years, which had involved the myocardium was hospitalized because of intractable heart failure (NYHA class IV). An implantation of an intracardiac defibrillator for ventricular arrhythmias (Lown type IVa) had preceded. On physical examination severe dyspnea at rest cough and fever were noted. INVESTIGATIONS: The erythrocyte sedimentation rate (88/104 mm), C-reactive protein (250 mg/l) and white cell count (20/nl) were markedly increased. Serum sodium (113 mmol/l), potassium (3.0 mmol/l) and chloride (64 mmol/l) were markedly reduced, while creatinine (2.5 mg/dl) and urea (82 mg/dl) were elevated due to renal failure. The chest radiogram demonstrated central venous congestion, cardiomegaly and right pericardial infiltration. There were no obvious changes due to sarcoidosis and computed tomography did not indicate pulmonary involvement by sarcoidosis. The echocardiogram revealed severe impairment of left ventricular function with an ejection fraction of ca. 14%. DIAGNOSIS, TREATMENT AND COURSE: Heart failure (NYHA class IV), caused by a dilated cardiomyopathy of sarcoidosis, was accompanied by pneumonia which responded to antibiotics. But the chronic heart failure failed to improve on drug treatment and cardiac transplantation was undertaken. The explanted myocardium was examined histologically, immunologically and virologically. Antibodies were demonstrated against vascular endothelium, sarcolemma and endocardium (IgG and IgA), but not by PCR against cytomegalovirus, enterovirus and adenovirus. The transplantation was without complication and, under azathioprine and methylprednisolone, one rejection had occurred until now. The patient has been working full-time since 2 years in his previous occupation of lorry driver. There has been no evidence of renewed sarcoidosis activity. CONCLUSION: Sarcoidosis may involve the myocardium in up to 25% of cases. Clinically relevant symptoms are even more rare. Sarcoidosis should be included in the differential diagnosis of unexplained serious arrhythmias or cardiomyopathy, particularly in young persons. Cardiac transplantation may have to be contemplated if drug or pacemaker treatment fails to control heart failure.
Time domain heart rate variability measurements and echocardiographic studies were performed in 35 patients with carcinoid syndrome. Carcinoid heart disease was present in 18 patients (51%). Heart rate variability parameters (standard deviation of all normal RR intervals, percentage of the number of pairs of adjacent normal RR intervals differing by >50 ms) were significantly reduced in patients with than in those without carcinoid heart disease.
From a registry of 136 patients undergoing pericardiocentesis, 14 patients with autoimmune and 15 patients with neoplastic effusions were selected. All underwent pericardioscopy, epicardial and pericardial biopsy with histologic, immunohistologic, and polymerase chain reaction/or in situ hybridization analysis for microbial DNAs and RNA. Pericardioscopy identified neoplastic effusions by the high occurrence of protrusions. Fibrin threads and layers and neovascularization were found in both groups. For identification of the inflammatory and neoplastic process, the combined analysis of the cytology of the effusion and epicardial biopsy evaluation proved to be most important. Epicardial biopsy demonstrated a slightly higher sensitivity for identifying neoplastic disorders in the pericardium than cytology alone. Pericardial biopsy was inconclusive. Intrapericardial administration of 1 g of crystalloid triamcinolone in autoreactive pericarditis prevented recurrence in 13 of the 14 cases after 3 months and in 12 of the 14 cases after 1 year. In neoplastic effusion, intrapericardial administration of 50 mg cis-platin for 24 h prevented recurrence of a hemodynamically relevant effusion after 3 months in all, and after 6-12 months in 14 of 15 patients. Mortality in neoplastic effusion due to noncardiac tumor progression was 47 and 80%, respectively, after 3 and 6 months, as can be expected in endstage neoplastic disease. This pilot study demonstrates that local drug application is feasible, life-saving, and well tolerated by the patients. It opens perspectives for local drug application in other cardiac disorders as well.
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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 risk of coronary artery disease. In addition, HMG-CoA reductase inhibition reduces the risk for cerebral ischemia. Recent data indicate that less than half of patients with coronary artery disease receive cholesterol-lowering therapy, and few meet the LDL-cholesterol goal. Therefore clinicians treating coronary artery disease need to emphasize secondary prevention and recognize the key role of cholesterol-lowering therapy. The challenge for clinicians is to apply the important lessons learned from these clinical trials to an "evidence-based" patient care.
In recent years a large number of coronary artery disease risk factors were discovered. The knowledge of these factors improves the estimate of the coronary artery disease (CAD) risk--however it still remains to be only an "estimate". A perfect prediction of an upcoming CAD event is not possible, despite all high score laboratory technology. Therefore the use of specialized laboratory procedures should be applied carefully. Knowing the blood levels of cholesterol, triglycerides, HDL- and LDL-cholesterol and Lp(a) can be sufficient for many therapeutical decisions. Severe dyslipidemia, familial CAD and CAD without any obvious reasons demand a more specialized work-up, however, risk stratification factors such as family history, clinical history (CAD, hypertension, diabetes mellitus, smoker) and genetics are crucial, apart from the above mentioned laboratory values. Purely on the basis of the lipidologic baseline concentrations we can't give well based recommendations for the treatment of individual patients. Currently there are expert systems available which allow a risk estimate once important laboratory values (LDL cholesterol, HDL cholesterol, Triglycerides) as well as clinical data (blood pressure, family history, clinical history) are available. This system can be accessed by internet under "http:/(/)www.chd-taskforce.com".
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 vessel wall as well as circulating and locally released vasoactive substances. The endothelium can be seen as a biosensor, reacting to a large variety of stimuli and therefore maintaining adequate NO release. A large number of risk factors for atherosclerosis including hypercholesterolemia, systemic hypertension, smoking and diabetes have been associated with impaired endothelial NO-mediated vasodilation. "Endothelial dysfunction" is an early marker of atherosclerosis and may be closely related to the disease process. In acute coronary syndromes dysfunctional endothelium may trigger the devastating event of plaque rupture by promoting adhesion of leukocytes, vasoconstriction, activation of platelets and thrombos formation. Atherosclerotic blood vessels are further characterized by activation through zytokines and expression of cellular adhesion molecules such as vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and endothelial-leukocyte adhesion molecule-1 (E-Selectin). After adhesion to the endothelium mononuclear cells migrate to the subendothelial space to take up oxidized LDL, thus transforming into foam cells, a hall mark of early atherosclerotic lesions. A number of conditions including infection with Chlamydia pneumoniae may cause continuous activation of the endothelium and inflammation of the vessel wall. Continuous endothelial dysfunction and activation, caused by risk factors and infection, represent the basis for atherogenesis and acute coronary syndromes.
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 (preload), and wall thickness. Extracoronary diseases, e.g. hypertensive heart disease, aortic stenosis or cardiomyopathies, can influence these factors and induce angina pectoris (Figure 1). On the other hand, different diseases influencing the oxygen supply, e.g. anemia, can cause angina pectoris, too. In addition, the modulation of the coronary tone by mediators and cytokines can cause angina, coronary spasm being one example. The neurophysiological substrate of angina pectoris are ganglia which are present within the heart, particularly in epicardial fat. The sympathetic nervous system is the main conveyer of afferent pain fibers from the heart and pericardium, but many fibers may travel by the vagus and the phrenic nerves. Therefore, multiple thoracic structures may cause similar pain syndromes in the distressed patient. The blood supply of intrinsic cardiac ganglia arises primarily from branches of the proximal coronary arteries. Adenosine, among a number of substances, can modulate the activity generated by cardiac afferent nerve endings and intrinsic cardiac neurones. During myocardial ischemia adenosine is released in large quantities into the interstitial space. Given as an intravenous bolus to healthy volunteers or to patients with ischemic heart disease and angina pectoris, adenosine provokes angina pectoris-like pain, which is similar to habitual angina pectoris with regard to quality and location. But other mediators (e.g. bradykinin, histamine, prostaglandins, potassium, lactate) can be involved in the development of angina pectoris, too. As most emphasis should be given to the most serious causes first, the cardiologist has to consider ischemic cardiac disease in the differential diagnosis of nearly every case of acute chest pain. The differential diagnosis contains several causes of nonischemic cardiac chest pain. Dissecting aortic aneurysm may cause severe anterior chest pain that can be mistaken for myocardial infarction. Patients frequently will note the sudden onset of the pain rather than the relatively slower onset of ischemic pain. Furthermore, they feel as a tear and describe it as the most severe pain they have ever had. Pericarditis can be characterized as a sharp precordial knife-like pain that is often increased by lying down, breathing, swallowing, or any other thoracic motion. Radiation of pericardial pain is often relieved by sitting up or leaning forward. It may involve the shoulders, upper back, and neck because of the irritation of the diaphragmatic pleura. Acute pulmonary embolism is associated with severe chest pain. It may mimic acute myocardial infarction. Pulmonary embolism should be suspected when dyspnea or tachypnea seems to be disproportionate to the severity of the chest pain. Diffuse esophageal spasm is the extracardiac condition that is confused most often with ischemic cardiac chest pain. This pain presents as a deep thoracic pain that may be present over most of the thorax. It may extend down the anterome