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Heart failure is a systemic disease. As populations are aging worldwide, the prevalence and importance of comorbidities as major determinants of heart failure symptoms, disease progression and prognosis are increasing. Since the last version of the European Society of Cardiology guidelines for the diagnosis and treatment of heart failure was published in 2016, promising novel pharmacotherapies for chronic heart failure and its comorbidities and new device-based treatment and monitoring options have become available; however, the broad range of therapeutic options as well as the diagnostic and therapeutic implications of comorbidities render the treatment of heart failure increasingly more complex. This review aims to provide practical guidance for a rational up-to-date approach to the evidence-based management of heart failure.

Hyperkalemia increases morbidity and mortalilty risk in both in- and outpatients. Common causes are decreased renal excretion, excess intake or potassium shifting from the intra- to the extracellular space in combination with reduced renal excretion or impairment of regulation. Hyperkalemia may alter the cellular transmembrane potential and cause life-threatening arrhythmias. Heart failure patients with comorbid renal insufficiency and/or diabetes mellitus are at increased risk of developing hyperkalemia, which thus constitutes a common reason for insufficient up-titration, down-titration or discontinuation of prognostically relevant heart failure medications predisposing to hyperkalemia (e. g. angiotensin-converting-enzyme inhibitors, angiotensin-receptor blockers and mineralocorticoid receptor antagonists). New oral potassium binders may enhance treatment opportunities in this respect., Competing Interests: Bei keiner der Autorinnen besteht ein persönlicher Interessenkonflikt. Die wissenschaftliche Arbeit der Autorin Prof. Dr. Christiane Angermann wird oder wurde von folgenden Firmen/Einrichtungen finanziell unterstützt: Bundesministerium für Bildung und Forschung, Deutsche Forschungsgemeinschaft, Boehringer Ingelheim, Novartis Pharma, Vifor Deutschland. Die Autorin erhält ferner Berater- oder Vortragshonorare von den Firmen Boehriger Ingelheim, Novartis, Servier, ResMed, und Vifor Deutschland und International. Frau Dr. Louisa Gerhardt hat keine Interessenkonflikte., (© Georg Thieme Verlag KG Stuttgart · New York.)

Heart failure (HF) is an emerging epidemic associated with significant morbidity and mortality, impaired quality of life and high healthcare costs. Despite major advances in pharmacological and device-based therapies, mortality and morbidity have remained high after an index hospitalization for acute cardiac decompensation (ACD). Randomized trials evaluating various forms of noninvasive telemonitoring failed to improve rehospitalization rates in such patients, possibly due to lack of sensitivity of clinical signs and symptoms as early indicators of HF. Among different implantable monitoring devices, wireless remote monitoring of the pulmonary artery pressure (PAP) with the CardioMEMS™ sensor (Abbott, Sylmar, CA, USA) has been shown to be safe and clinically effective in the USA. The patients showed substantial reductions in hospital admissions for ACD, irrespective of left ventricular pump function, because PAP-guided HF management facilitates timely recognition of incipient ACD and appropriate modification of medical treatment before hospitalization becomes unavoidable. These encouraging results have also stimulated evaluation of this novel technology outside the USA. Studies are also underway in Europe and European HF guidelines recommend considering implantation of a CardioMEMS™ sensor in high-risk patients (class IIb-B). More technologically refined implantable hemodynamic monitoring systems allowing, for example, left atrial pressure measurements, are under development. Promising novel approaches to using information from such devices include continuous hemodynamic monitoring and patient self-management based on the pressure information. Thus, pressure-guided HF management is likely to further expand in the future and may help improve clinical outcomes also in high-risk HF populations.

Heart failure remains a frequent cause of death and is the leading reason for hospitalization in Germany although therapeutic options have significantly increased over the past years particularly in heart failure with reduced ejection fraction. Clinical symptoms are usually preceded by cardiac remodeling, which was originally defined only by left ventricular dilatation and depressed function but is also associated with typical cellular and molecular processes. Healing after acute myocardial infarction is characterized by inflammation, cellular migration and scar formation. Cardiac remodeling is accompanied by adaptive changes of the peripheral cardiovascular system. Since prevention is the primary goal, rapid diagnosis and treatment of myocardial infarction are mandatory. Early reperfusion therapy limits infarct size and enables the best possible preservation of left ventricular function. Standard pharmacotherapy includes angiotensin-converting enzyme inhibitors, angiotensin-1-receptor blockers and beta blockers. In addition, mineralocorticoid receptor antagonists have proven beneficial. Compounds specifically targeting infarct healing processes are currently under development.

Heart failure and depression are widespread diseases and of particular clinical and economic relevance. Compared with the general population depression is up to 5‑times more common in patients with heart failure, with adverse effects on morbidity, mortality, quality of life and treatment costs. Depressive symptoms overlap with those of heart failure which renders diagnosis difficult. Simple screening tools, e. g. the two-item patient health questionnaire, help to recognize depression in the clinical routine. To date, there is no evidence that antidepressant pharmacotherapy improves mood and clinical outcomes in patients with heart failure and comorbid depression and antidepressant pharmacotherapy remains to be decided on a case by case basis; however, physical training, cognitive behavioral therapy and multidisciplinary comprehensive disease management improved symptoms and/or prognosis in a limited number of randomized studies.

Depression is common in heart failure and associated with impaired quality of life. It impacts adversely on clinical outcomes. Both diseases are widespread in the general population with increasing prevalence and treatment costs. They are therefore also of socio-economic relevance. Various interrelated biological and behavioral factors (e.g. lower treatment adherence in depressed patients with heart failure) seem to play a pathophysiological role, and there is growing evidence that both diseases may also share genetic susceptibilities. Simple screening tools ease depression diagnosis in clinical practice, although the clinical profile of both disorders overlaps. To date, there is no evidence that antidepressant pharmacotherapy improves depressive symptoms, mortality and morbidity in patients with heart failure and comorbid depression, but physical training, cognitive behavioral therapy and comprehensive disease management improved symptoms and/or prognosis in individual randomized studies., (© Georg Thieme Verlag KG Stuttgart · New York.)

Acute heart failure (AHF) is frequent, often life threatening and followed by emergency hospitalization. Leading symptoms are dyspnea, edema and fatigue. A broad spectrum of risk factors, cardiac diseases and comorbidities predisposes to AHF. Typical triggers (e. g. arrhythmias) modulate the individual clinical picture. Their misinterpretation may delay the diagnosis, which always needs to be ascertained by cardiac imaging (echocardiography). Rescue therapy aims at amelioration of symptoms and stabilization of vital parameters. In contrast to chronic heart failure evidence of the efficacy of available treatments is limited and in the past innovations have been sparse in this area. The clinical course is characterized by high short- and long-term mortality and repeat cardiac decompensations, but seamless multidisciplinary care and better knowledge and self-supervision on the patients' side might improve prognosis. Today, too little attention is paid to the palliative needs of patients with AHF., (© Georg Thieme Verlag KG Stuttgart · New York.)

The rising prevalence and increasing disease-related costs render chronic heart failure a rapidly growing socioeconomic challenge. The concerted action of guideline-adjusted therapy and holistic patient care is essential to achieve improvements in mortality, morbidity, functional status and quality of life of patients with symptomatic heart failure. Holistic care strategies comprise consideration of comorbidities and individual needs, lifestyle recommendations and multidisciplinary management programs for high-risk symptomatic patients in addition to basic medication and surgical therapies. For optimal patient care and coaching, seamless interaction is required between in-hospital treatment and outpatient facilities. Moreover, the palliative needs of heart failure patients need to be considered, a topic that is currently not receiving enough attention.

Rising prevalence and disease-related costs render chronic heart failure a rapidly growing socioeconomic challenge. Guideline-adjusted diagnosis and appropriate therapy are successful in improving mortality, morbidity, functional status and quality of life of patients with chronic left ventricular failure. Corresponding state-of-art recommendations were recently published in the updated European and American treatment guidelines. They determine a stepwise escalation of pharmacological and surgical treatment measures according to increasing disease severity. Still, the complexity of the heart failure syndrome demands to tailor diagnostic procedures and therapy to the patients' individual needs and circumstances.

Cardiac amyloidosis represents a prognostically relevant comorbidity in multiple myeloma. We report the case of a patient in whom severe heart failure symptoms as a consequence of cardiac AL-amyloidosis resolved after tandem high-dose melphalan therapy followed by autologous blood-stem cell transplantation. Partial regression of cardiac amyloid deposits and improvement of cardiac function were objectified.

A major depressive episode is diagnosed based on several well-defined criteria as the presence of depressed mood and loss of interest. According to a large meta-analysis the prevalence of major depression in patients with chronic heart failure is more than 20%. Etiological factors include individual (genetic) disposition and social environment as well as psychosocial stress and biological risk factors related to the chronic cardiac illness. As in coronary artery disease, mortality rates are increased in patients suffering from heart failure and comorbid depression. Possible mechanisms mediating this relationship include both biological (e.g. severity of chronic heart failure, autonomic and immunological dysregulation, multiple comorbidities) and behavioral factors (health behavior, compliance with pharmacological and non-pharmacological therapy). Shared pathophysiological mechanisms as well as a common genetic disposition are also discussed. Simple screening instruments and effective treatment options (psychotherapy, selective serotonin re-uptake inhibitors) are available. However, at present evidence is lacking that beyond improvement of depression these strategies impact favorably on morbidity and mortality.

Behçet's disease is a chronic relapsing systemic vasculitis of unknown etiology, affecting predominantly oral and genital mucocutaneous tissues and also the eyes. The disease is spread worldwide with a higher prevalence rate in countries along the ancient Silk Route, but it is rare (1-10/100,000) in Central and Northern Europe. Genetic, environmental, immunologic, inflammatory and rheologic factors are involved in the pathogenesis and the course of the disease. Any vascularized organ may be affected. Eye involvement is frequent, and may eventually result in loss of vision. Further important complications are cerebral manifestations, thrombotic syndromes, and arterial aneurysms with a high risk of rupture. Diagnosis and therapy of Behçet's disease are best managed by an interdisciplinary team. Skin lesions may be controlled by systemic treatment with colchicine, alternatively with dapsone, and in severe cases with thalidomide. Active systemic disease should be treated more aggressively using immunosuppressants. Despite advances in treatment relapses are still frequent, and systemic disease remains associated with an adverse prognosis.

Amyloidoses are a heterogeneous group of multisystem disorders, which are characterized by an extracellular deposition of amyloid fibrils. Typically affected are the heart, liver, kidneys, and nervous system. More than half of the patients die due to cardiac involvement. Clinical signs of cardiac amyloidosis are edema of the lower limbs, hepatomegaly, ascites and elevated jugular vein pressure, frequently in combination with dyspnea. There can also be chest pain, probably due to microvessel disease. Dysfunction of the autonomous nervous system or arrhythmias may cause low blood pressure, dizziness, or recurrent syncope. The AL amyloidosis caused by the deposition of immunoglobulin light chains is the most common form. It can be performed by monoclonal gammopathy. The desirable treatment therapy consists of high-dose melphalan therapy twice followed by autologous stem cell transplantation. Due to the high peritransplantation mortality, selection of appropriate patients is mandatory. The ATTR amyloidosis is an autosomal dominant disorder caused by the amyloidogenic form of transthyretin, a plasmaprotein that is synthesized in the liver. Therefore, liver transplantation is the only curative therapy. The symptomatic treatment of cardiac amyloidosis is based on the current guidelines for chronic heart failure according to the patient's New York Heart Association (NYHA) state. Further types of amyloidosis with possible cardiac involvement comprise the senile systemic amyloidosis caused by the wild-type transthyretin, secondary amyloidosis after chronic systemic inflammation, and the beta(2)-microglobulin amyloidosis after long-term dialysis treatment.

Diagnostic criteria of heart failure (HF) are the presence of typical signs, symptoms, and objective evidence of cardiac dysfunction. Exertional dyspnea is a key symptom but highly unspecific, calling for standardised focused diagnostic algorithms. These include 12-lead ECG, chest X-ray, routine laboratory values, measurement of natriuretic peptides, and the quantification of systolic and diastolic dysfunction by echocardiographic methods. Further options in the diagnostic armamentarium comprise laevocardiography, coronary angiography, scintigraphic techniques, cardiac computer tomography, cardiac magnetic resonance imaging, and endomyocardial biopsy. As a primary diagnostic aim, the underlying cause of heart failure should be determined in all subjects because the therapeutic strategy may depend on this information.

Chronic heart failure is an increasingly frequent clinical syndrome, characterized by reduced physical performance, dyspnea and an adverse prognosis. It is associated with age, indicating that it will become more common. Diagnosis requires the characterization of cardiac dysfunction and a precise definition of the underlying cardiac disease. Treatment guidelines of the cardiac societies, which were updated 2005, recommend therapy with ACE-inhibitors, AT1 receptor antagonists, beta-blockers, aldosterone antagonists and digitalis. It is essential, however, to consider the individual circumstances such as underlying disease, age as well as the frequent complications and comorbidities.

Background: In Germany, primary healthcare for patients with chronic diseases needs to be improved. Taking the example of depression, congestive heart failure, diabetes and diseases of the musculoskeletal system we analyzed to which extent the 'Chronic Care Model' allows for improvements., Methods: Diagnosis-specific health assessment; adaptation of the 'Chronic Care Model' to the German healthcare system; peer reviewed discussions of the potentials for improving primary care of the chronically ill. RESULTS/DISCUSSION OF THE HEALTHCARE SITUATION: 1) Diagnosis and therapy of chronic diseases comply insufficiently with the evidence. 2) Patients are too passive and/or receive only little effective support. 3) Treatments are often uncoordinated and fragmented. 4) The follow-up of treatment results is often neglected. 5) Approaches to indicated diseases are promising., Conclusions: The'Chronic Care Model' could improve chronic care in Germany. Disease Management Programs (DMP) should amend multimorbidity and individual healthcare and/or facilitate implementation in general practice.

The importance of sex- and gender-related features of various diseases regarding the impact of different risk factors on the natural course of disease, the response to therapy and outcome have only more recently been appreciated. Studies investigating sex- and gender-related aspects in rheumatoid arthritis (RA) are scarce. Unambiguous classification of factors of potential pathogenetic relevance or with the capacity to influence clinical course and disease management into sex- or gender- related aspects is difficult (Figure 1). The majority of RA patients is female. As illustrated by Figure 2, available evidence indicates a progressive decline in the incidence of this disease over the past 40 years in both men and women. There appears to be a cyclical pattern in the annual incidence rates with peaks and troughs occurring for both sexes, but at different times, which suggests the changing exposure to environmental factors which may promote or decrease RA. Current knowledge suggests that RA is characterized by chronic local and systemic inflammation which may trigger accelerated atherogenesis. Sex hormones may also play a pathogenetic role. Androgens and estrogens may stimulate the production of inflammatory cytokines in the synovial fluid. These cytokines then may influence sex hormone metabolism thus modifying sex hormone levels (Figure 3). Compared to the general population (Figures 4 and 5), the risk of cardiovascular morbidity and mortality is significantly increased in patients with rheumatic diseases and in particular in RA. This is evidenced by a higher incidence of congestive heart failure (Figure 6), coronary artery disease and (frequently silent) myocardial infarction, as well as sudden cardiac death. Several studies have demonstrated a significantly increased standardized mortality ratio in RA and identified cardiovascular events as the most frequent cause. Compared with expected mortality rates in the normal population, women with RA have a significantly more compromised life expectancy than men (Table 1). Amongst factors with uneven distribution between sexes are traditional cardiovascular risk factors (Table 2), but also more recently recognized potential risk indicators or risk modifiers such as inflammatory markers and sex hormones. Drugs directed against RA may influence the natural course of cardiovascular disease, as, e. g., indicated by the increased rates of cardiac events and stroke associated with cyclooxygenase-(COX-)2 inhibitor treatment. In contrast, the effect of pharmacotherapy for cardiovascular diseases on the course of RA is unexplored. Prospective cohort studies aiming at early detection of cardiovascular morbidity and precise and detailed characterization of disease manifestations will be required in order to more thoroughly understand the interplay of factors and conditions determining an individuals' risk for developing cardiovascular comorbidity in autoimmune diseases. This article summarizes the available evidence for sex- and gender-related differences in the disease manifestation of rheumatic disorders as well as in cardiovascular risk factors with an emphasis on the cardiovascular comorbidity observed in RA.

Irrespective of improved medical and interventional therapeutic options, mortality among patients with acute heart failure and cardiogenic shock has remained disappointingly high. Early diagnosis and rapid initiation of basic treatment measures to improve hemodynamics and metabolism are of vital importance until causal therapy, e. g. revascularization, is initiated. Due to the principal difficulty to set up larger clinical trials, in patients with cardiogenic shock empirical rather than firm evidence supports the various treatment and management strategies currently in use. Continuous hemodynamic monitoring to tailor fluid therapy, new drugs, and prognostic markers have been developed for the treatment and monitoring of cardiogenic shock, all of which await testing in larger-scale studies. Ongoing challenges remain the right ventricular pump failure or hemodynamically compromising arrhythmia which may be either cause or consequence of cardiogenic shock.

Patients' health-related quality of life is increasingly being included as an additional endpoint when evaluating the treatment of chronic heart failure. Although generic self-report instruments measuring health-related quality of life are available, there is a lack of disease-specific instruments covering various dimensions of quality of life with high reliability, validity and sensitivity to chance. Thus, the aim of the present study was to evaluate the German version of a new heart failure-specific quality of life measure, the Kansas City Cardiomyopathy Questionnaire (KCCQ). The sample consisted of 233 consecutively recruited outpatients of a university department in Germany. Test-retest-reliability was high (intraclass correlation coefficient 0.93 for both the Functional State and the Clinical Summary total scores). Construct validity was demonstrated with strong correlations to respective subscales of the SF-36. Known groups validity was shown by both statistically and clinically significant differences between NYHA classes. The examination of sensitivity to change yielded promising results. The questionnaire was well accepted by the participating patients. The KCCQ proved to be a reliable and valid self-report instrument for measuring disease-specific quality of life in chronic heart failure.

Incidence and prevalence of chronic heart failure are continuously increasing. Today, heart failure of different etiologies represents the most frequent cause of death in industrialized countries. Improvements in heart failure diagnosis and treatment have decreased lethality. In this context, a valid diagnosis, causative therapy of treatable heart failure etiologies, and efficient pharmacological as well as non-pharmacological management strategies are of equal importance. The principal goals of therapy are prevention, maintenance or even improvement of quality of life and the decrease of heart-failure-related morbidity and mortality.

In patients with heart failure, increased wall stretch due to volume and pressure overload leads to an increase in circulating natriuretic peptides (ANP and BNP and their N-terminal fragments NT-proANP and NT-proBNP). Plasma BNP levels commonly considered normal (< 20 pg/ml) are influenced by age, sex, and also by genetic factors. ANP and BNP are synthesized and released by atrial and ventricular myocytes (Figure 1). In subjects with acute dyspnea, a BNP plasma concentration of 100 pg/ml has been established as a cutoff value for the diagnosis of heart failure yielding a very high negative predictive value coupled with an acceptable positive predictive value (Figure 3). However, recent evidence suggests that much more subtle elevations of plasma BNP may also indicate an increased long-term risk of cardiovascular events and death (Figure 2). In acute heart failure, natriuretic peptides correlate with ventricular pressure and volume overload, as well as with NYHA functional class. They can, however, not reliably discriminate between heart failure due to reduced ejection fraction and heart failure with preserved systolic function (Figure 4). Thus, elevated BNP or NT-proBNP levels always demand further clarification of heart failure etiology using echocardiography as the method of choice. As indicated by the algorithm for a BNP-based differential diagnosis of acute heart failure symptoms (Figure 5), a variety of noncardiac causes may also lead to moderate elevations of the markers (BNP plasma concentrations of 100-400 pg/ml). In addition, normal marker levels may be observed in > 20% of patients with long-term stable heart failure. Thus, increased plasma concentrations of natriuretic peptides are not strictly specific for heart diseases and also lack sensitivity in the chronic compensated state. Diuretics, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor antagonists, and spironolactone have been shown to decrease BNP and NT-proBNP in parallel with clinical and hemodynamic improvement. In patients hospitalized for decompensated heart failure, predischarge plasma BNP levels reflect the risk of future death and rehospitalization (Figure 6). Although adjusting heart failure treatment to reduce plasma NT-proBNP levels may improve outcome, a general recommendation for monitoring drug therapy using this marker should not be derived from this observation. General practitioners may, in the future, use BNP or NT-proBNP as a rule-out test for heart failure and preselect patients for further diagnostic work-up on the basis of an elevated plasma level. Within the framework of the German network for heart failure the multicentric "Handheld-BNP Study" will clarify, whether echocardiography using low-price simple handcarried devices could be used as an alternative or, more likely, as a complementary diagnostic tool to further improve heart failure diagnosis in primary care.

The incidence and prevalence of cardiac insufficiency increases dramatically in the elderly. The reason for this is the more frequent cardiac disease in this age group, the functional effects of which compound the sequence of the physiological aging and exogenous noxae. The clinical presentation of heart failure in the elderly may be atypical, echocardiography should always be performed to confirm the diagnosis and obtain a better evaluation of the underlying condition, before therapeutic measures are initiated. For, in the elderly in particular, treatment must be planned on an individual basis. Primarily, reversible cardiac or extracardiac disorders, potential triggers of cardiac insufficiency, must be identified and treated. All the data currently available indicate that in the elderly, too, all the established options for specific treatment should be utilized. While the reservations often applied to the use of drugs to treat chronic cardiac insufficiency--in particular the treatment of acute myocardiac infarction by thrombolysis or acute intervention--and based on a fear of iatrogenic complications, are understandable, but to date do not justify such a stance. Although contraindications in the elderly are more common and complications not always avoidable, old patients can also benefit from these therapeutic measures.

Unlabelled: Stress echocardiography has been shown to be a valuable noninvasive method for the diagnosis of restenosis after coronary angioplasty. To determine the usefulness of dobutamine stress echocardiography (DSE) for assessment of restenosis after intracoronary stent implantation, we studied 50 patients (59+/-10 years; 1-vessel disease, n=16; multivessel disease, n=34) after stent implantation. After 6 month, both DSE (5-40 mcg/kg/min, 0-1mg atropine) and angiography were performed within 48 hours and evaluated in a blinded fashion. Restenosis was defined by quantitative coronary angiography as minimal lumen diameter (LD) <50% of average reference LD. Diagnostic criteria of DSE were new or worsening wall motion abnormalities in corresponding perfusion territories during stress. Angiography revealed restenosis in 8 patients; one patient had a denovostenosis distal to the stented segment (8 x left anterior descending artery, 1 ACVB to the right coronary artery). In 6 of these 9 patients, DSE was positive (mean reduction of LD 88+/-7%; sensitivity 67%), in 3 patients negative (mean reduction of LD 62+/-7%, 1 x termination of DSE because of wall motion abnormalities in an area not supplied by the stented vessel). In 38 of 41 patients without restenosis, DSE showed no stress-induced wall motion abnormalities in the LV area supplied by the stented vessel (specificity 93%)., Conclusions: DSE is a useful noninvasive method for detecting restenosis after intracoronary stent implantation. With negative DSE at follow-up, a functionally relevant stent restenosis is highly unlikely.

This prospective study was designed to compare quality of life, life satisfaction, and subjective ratings of health before and at variable time intervals after heart transplantation (HTx). 175 patients were included between February 1994 and December 1997. Every six months before and 1 1/2, 3, 6, and 12 months after HTx, they received the following standardized and validated questionnaires: German SF 36, heart failure and specific transplant symptom list, global quality of life assessment, Munich life quality dimension list, expected/experienced life changes after HTx. Inclusion criteria were the acceptance of the patient on the waiting list for HTx, good command of the German language, and a minimum age of 18 years. During data evaluation, median (Me), mean (M), and standard deviation (SD) were created from individual parameters. Quality of life was rated as very poor by 84% of patients with congestive heart failure. Only 6 weeks after HTx, 74% rated their quality of life as significantly better. Before HTx 80% were very unsatisfied about their health status and 87% about physical performance. Six weeks after HTx, this parameter improved significantly and 76% were very satisfied about their health status and 50% about physical performance. While somatic changes expected before HTx corresponded well with experienced ones, psychological improvements were smaller than expected, but one year after HTx they were significant (before: M = 3.66; SD = 0.9; Range (R) = 3.78 vs 12 months postop: M = 4.61; SD = 0.6; R = 2.67; p < 0.05). Quality of life correlated before HTx best with subjectively rated health (r = 0.61, p < 0.01) and 6 months after with satisfaction about health status (r = 0.76, p < 0.01). Only in 25% were expected improvements fulfilled regarding sexual activity/satisfaction, professional situation, and recreational activities. 90% of post-transplant patients reported physical complaints, most by effects of immunsuppression, but were coping well. The study shows that already 6 weeks after successful HTx all quality of life parameters improved significantly. Despite some unfulfilled expectations and complaints, the postoperative life situation of HTx patients appeared significantly improved.

Problem and Objective: Cardiac allograft vasculopathy influences long-term survival of patients after heart transplantation. Donor-transmitted coronary artery disease may contribute to the further development of cardiac allograft vasculopathy. The aim of this study was to characterize by intracoronary ultrasound the extent and frequency of transmitted coronary artery disease., Patients and Methods: Intravascular ultrasound studies were performed at routine angiography in 33 patients (26 men, 7 women, mean age 51 [23-69] years) early after heart transplantation. Plaque morphology was analysed in 153 coronary segments of 52 epicardial coronary arteries., Results: Relevant atherosclerosis (defined as maximal plaque thickness > or = 0.5 mm in at least one coronary segment) was found in 17 patients (52%), while angiography showed irregularities in only 7 patients (21%). Maximal plaque thickness in patients with relevant atherosclerosis was 1.13 +/- 0.32 mm, mean plaque index was 19.2 +/- 10.2%. Plaque formation was eccentric, and plaques were predominantly located in proximal segments. Morphologic changes affecting more than one segment were found in 52% of the patients. Comparing clinical factors, only donor age predicted the degree of atherosclerosis., Conclusions: In more than one half of the patients studied early after heart transplantation, Intravascular ultrasound revealed epicardial atherosclerotic lesions which were incompletely identified by coronary angiography. The degree of atherosclerosis was closely related to donor age. The potential influence of donor transmitted coronary artery disease on the progression of transplant coronary artery disease requires further longitudinal studies.

Cardiac allograft vasculopathy (CAV) remains a major problem after heart transplantation. This prospective study was performed to analyze the value of quantitative dobutamine stress echocardiography for the diagnosis of CAV compared with coronary angiography and intravascular ultrasound (IVUS). In 80 patients late (> or = 12 months) after cardiac transplantation, a total of 144 studies were evaluated. In addition to the usually performed regional wall motion analysis of 2D-echocardiograms, systolic thickening of septum and left ventricular posterior wall was quantified by M-mode echocardiography. In patients with CAV by invasive angiography and/or IVUS, systolic thickening of the septum and posterior wall was significantly lower at rest and at maximum dobutamine infusion than in patients without CAV. From a subgroup of 23 studies in transplant recipients without TVP or other cardiac complications, normal values for the M-mode parameters were calculated. The lower limits were: systolic thickening of septum at rest, > 17.2%, at maximum stress, > 45.9%; systolic thickening of left ventricular posterior wall at rest, > 41.6%, at maximum stress, > 67.6%. Regional wall motion analysis of 2D-echocardiograms had a sensitivity of 76% (specificity 82%) for diagnosis of CAV defined by invasive methods, evaluation of wall thickening by M-mode alone had a sensitivity of 63% (specificity 76%). The combined 2D- and M-mode-echocardiographic analysis yielded a sensitivity of 85% (specificity 71%). In summary, dobutamine stress echocardiography is a useful method for the noninvasive diagnosis of CAV. The quantitative M-mode analysis improves the sensitivity of the 2D-analysis. The calculated normal values for the M-mode parameters in heart transplant recipients may serve as reference for other studies.

Experimental studies from our laboratory demonstrated that acute cardiac rejections (AR) are associated with an increase in myocardial echo amplitudes which correlate with the histologic severity of AR. The aim of the present study was to test whether AR-induced myocardial structural changes would also alter the spatial distribution of the myocardial echo amplitudes, assessed by echocardiographic texture analysis, and whether this method would improve the sensitivity of AR diagnosis. Echocardiographic LV long axis views were daily recorded in 12 dogs after cervical heterotopic heart transplantation (mean survival time: 16.1 days; immunosuppression: cyclosporine, azathioprine and prednisolone; AR treatment: pulsed steroids) under strictly standardized conditions and digitized into a 256 x 256 x 8 pixel matrix. Texture analysis using Co-occurrence- and Run Length Matrix was performed in 45 x 12 pixel-sized regions of interest (ROI) within the septum (VS) and posterior wall (PW) in end-diastole. Results obtained without AR were then compared with those during biopsy-proven mild, moderate and severe AR. Severe AR are associated with a significant increase in Co-occurrence Matrix parameters within the septum and posterior wall (Contrast: VS: 3.1 +/- 0.7 vs. 3.9 +/- 1.1, p < 0.05. PW: 1.8 +/- 0.5 vs. 2.3 +/- 1.0, p < 0.05. Variance: VS: 19 +/- 15 vs. 36 +/- 18, p < 0.05. PW: 11 +/- 6 vs. 21 +/- 8, p < 0.01). During mild and moderate AR no significant changes in texture measurements were found. Testing the influence of ROI placement on myocardial echo amplitude, texture measurements showed a high variability in comparison to mean gray level (up to 30% vs. < 5%).(ABSTRACT TRUNCATED AT 250 WORDS)

Infection remains a major problem in the early phase after heart transplantation. Immunosuppressive therapy is the most important predisposing factor. It may also reactivate preexisting latent endogenous infections. Unspecific symptoms and a chronic clinical course, as described in this report, may suggest infective endocarditis of the cardiac allograft. From this case, we do not suggest a general antibiotic prophylaxis for heart transplant recipients; however, special precaution should be considered in heart transplant patients with a history of endocarditis.

Introduction of ciclosporin A into immunosuppressive therapy is considered a major progress in improving results of organ transplantation. Clinical use of ciclosporin, however, is limited by a low therapeutic index and toxic side effects. Therefore, interactions of ciclosporin with other drugs are clinically important. In our study, we used enalapril, furosemide and verapamil for treatment of arterial hypertension in cardiac transplant recipients and investigated the influence of these drugs on ciclosporin whole blood trough levels. The antihypertensive regimen used in this study normalized blood pressure in each of the 25 patients. Enalapril and furosemide did not influence ciclosporin levels. Adding verapamil, however, resulted in a significant increase of ciclosporin levels, whereas cessation of the drug in one patient treated with verapamil only lowered ciclosporin levels. Thus, when verapamil is introduced or discontinued in patients on ciclosporin, close monitoring of ciclosporin levels and dosage adjustment are necessary. Besides its specific effects verapamil allows reduction of ciclosporin dosage necessary to maintain unaltered levels, which is important regarding cost of therapy. In general, use of any drug with unknown influence on ciclosporin levels requires careful monitoring, even if information exists on other substances of the same group of drugs in this respect. This is especially indicated in drugs known to influence the hepatic cytochrome P450 enzyme system.

Though endomyocardial biopsy has remained the gold standard for diagnosing acute cardiac rejection (AR), this invasive method does not provide adequate means for close monitoring of the rejection process. In order to assess the usefulness of M-Mode- and two-dimensional (2D) echocardiography for the noninvasive diagnosis of AR in heart transplant recipients on cyclosporin, 45 patients (mean age 40.6 +/- 8.8 years, 19.9 +/- 14.4 months postoperatively) were evaluated prospectively. Mean observation time was 9.1 +/- 4.8 months. Echocardiographic examination techniques were strictly standardized; besides measurements of left (LV) and right ventricular (RV) diastolic wall thickness and of the isovolumic relaxation time, computerized frame-by-frame-analysis was applied to LV short axis cross sections for the determination of diastolic cavity cross-sectional area and extent and mean velocity of systolic and diastolic area change. To account for technical and biological variability, 95%-confidence limits were calculated for each parameter from two rejection-free examinations, allowing identification of significant changes during AR. In this study, 36 biopsy-proven AR occurred in 19 patients. Compared to control values, mean heart rate increased from 86.2 +/- 10.2 to 94.6 +/- 15.1 b/min (p less than 0.05), diastolic septal + posterior wall thickness from 21.2 +/- 4.1 to 24.9 +/- 6.2 mm (p less than 0.001) and RV free wall thickness from 6.3 +/- 1.1 to 8.9 +/- 1.8 mm (p less than 0.001). Isovolumic relaxation time decreased from 73.2 +/- 14.4 to 54.8 +/- 16.6 ms (p less than 0.001), diastolic cross-sectional area from 12.8 +/- 2.0 to 11.1 +/- 2.2 cm2 (p less than 0.05), relative area change from 65.8 +/- 9.8 to 49.1 +/- 14.4% (p less than 0.001) and systolic and diastolic area change velocities from 28.1 +/- 7.8 and 41.8 +/- 8.5 cm2/s to 18.9 +/- 5.6 and 28.6 +/- 9.2 cm2/s, respectively (p less than 0.001). Though significant changes occurred during AR, most measurements remained within the normal range. Thus, in individual patients, AR could only be suspected in comparison to the control measurements. None of the examined parameters allowed to establish the diagnosis of AR in all instances. However, when the measurements of all parameters were considered together, 35 of the 36 AR diagnosed by biopsy could also be identified by echocardiography, including all requiring intensified immunosuppressive therapy. Mild AR was not always detected, and the differential diagnosis between LV hypertrophy and AR required an endomyocardial biopsy in some instances.(ABSTRACT TRUNCATED AT 400 WORDS)

The de novo hypertension, which develops in most cardiac transplant recipients within the first postoperative months, is multicausal, though toxic side-effects of cyclosporin A seem to play a key role. In order to analyze the circadian behavior of arterial blood pressure and heart rate after cardiac transplantation (HTX) and to evaluate the effect of an antihypertensive regimen on these parameters, 24-h noninvasive ambulatory blood pressure and heart rate monitoring was performed in 10 hypertensive cardiac transplant recipients on cyclosporin A (mean age 42.3 +/- 11.2 years, 14.3 +/- 8.3 months after HTX) before antihypertensive therapy and after introduction of an antihypertensive regimen with the ACE-inhibitor enalapril plus furosemide alone or combined with verapamil. The study demonstrated a complete loss of the usual nocturnal decline in blood pressure in cardiac transplant recipients (mean systolic and diastolic blood pressure 149 +/- 8 and 102 +/- 7 mm Hg during daytime and 152 +/- 8 and 104 +/- 9 mmHg at night). Antihypertensive therapy lowered the blood pressure level effectively, but did not influence the circadian pattern (mean systolic and diastolic blood pressure 121 +/- 8 and 81 +/- 4 mmHg during daytime and 121 +/- 9 and 83 +/- 3 mmHg at night, all p less than or equal to 0.001). Heart rate, in contrast, showed a significant, though in comparison to normal, a blunted decrease at night (mean heart rate 94 +/- 6 beats per min during daytime and 84 +/- 8 beats per min at night, p less than or equal to 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)