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Purpose of ReviewIn this article, we review a range of digital technologies for possible application in heart failure patients, with a focus on lessons learned. We also discuss a future model of heart failure management, as digital technologies continue to become part of standard care.Recent FindingsDigital technologies are increasingly used by healthcare professionals and those living with heart failure to support more personalised and timely shared decision-making, earlier identification of problems, and an improved experience of care. The COVID-19 pandemic has accelerated the acceptability and implementation of a range of digital technologies, including remote monitoring and health tracking, mobile health (wearable technology and smartphone-based applications), and the use of machine learning to augment data interpretation and decision-making. Much has been learned over recent decades on the challenges and opportunities of technology development, including how best to evaluate the impact of digital health interventions on health and healthcare, the human factors involved in implementation and how best to integrate dataflows into the clinical pathway.SummarySupporting patients with heart failure as well as healthcare professionals (both with a broad range of health and digital literacy skills) is crucial to success. Access to digital technologies and the internet remains a challenge for some patients. The aim should be to identify the right technology for the right patient at the right time, in a process of co-design and co-implementation with patients.

Background The association of clinically meaningful changes in the Kansas City Cardiomyopathy Questionnaire Overall Summary score (KCCQ-os) with prognosis in patients with heart failure (HF) is well established. However, most studies have considered several weeks as time intervals for the serial assessments of the KCCQ-os. Therefore, we sought to investigate the changes of the KCCQ-os and their prognostic relevance between discharge and several months. Methods We assessed serial KCCQ data from the Extended Interdisciplinary Network Heart Failure (E-INH) study: between 2004 and 2007, 1022 hospitalized HF patients with a left ventricular ejection fraction (LVEF) Results Of 1022 participants, 604 patients (59%) provided complete serial KCCQ data sets at baseline and after 6, 12, and 18 months: mean (SD) age 65.6 (12.2) years, 24% women, median (quartiles) KCCQ-os at baseline 59.2 (43.2; 77.1). 345 (57%) patients died, median follow-up time 8.9 years (4.1; 10.0). There were significant median changes of KCCQ-os from baseline over time: 6-month 9.9 (−0.8; 26.8), 12-month 12.5 (−1.5; 29.4), and 18-month 13.4 (−1.1; 33.7), respectively (all p Conclusion Amongst patients with HF surviving at least 18 months after being hospitalized for decompensated HF, a change in KCCQ-os identified patients at increased risk in the years to come. This association was apparent regardless of the time point of score collection. Since Patient-Reported Outcomes as the KCCQ may be easily collected via phone or a medical application, our findings not only confirm the prognostic utility of serial health status assessments but also might be useful to triage the frequency of clinical follow-ups. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): BMBF

Background Mid-regional proadrenomedullin (MR-proADM) is a blood biomarker indicating critical illness. Its short-term prognostic relevance has been investigated in several conditions including heart failure (HF). Yet, the long-term prognostic utility is unknown. Methods We conducted a post-hoc analysis of the Extended Interdisciplinary Network for Heart Failure (E-INH) study, which investigated the long-term effects of a HF nurse-led remote patient care program (HeartNetCare-HFTM [HNC]). Patients from nine regional centers in Germany hospitalized with HF and a left ventricular ejection fraction (LVEF) Results From 919 out of the 1022 recruited patients (90%), baseline levels of MR-proADM were available: median MR-proADM 0.89 (quartiles 0.63, 1.28) nmol/l; mean age 68±12 years; 28% women; 45% in class III or IV of the New York Heart Association (NYHA) classification. Median LVEF was 31 (25, 37) %. Median levels of NT-proBNP, high sensitive C-reactive protein (hsCRP), tumor necrosis factor (TNF)-a, and interleukin-6 (IL-6) were 3045 (1087, 7759) pg/ml, 9.2 (3.3, 25.2) mg/l, 13.4 (10.4, 17.5) pg/ml, and 4.9 (2.0, 11.4) pg/ml, respectively. Higher levels of MR-proADM at baseline were associated with age, female sex, NYHA class, NT-proBNP, hsCRP, IL-6, and TNF-α, while there was an inverse association with LVEF. In the course of 10 years of follow-up, 691 (68%) patients died. Unadjusted MR-proADM strongly predicted all-cause death when used as a continuous variable (HR 1.31 per nmol/l, 95% CI 1.26–1.37; p Conclusion MR-proADM appears to be a strong and independent predictor for long-term all-cause mortality risk in HF with reduced ejection fraction (HFrEF). Therefore, assessing MR-proADM may contribute to better categorization of risk and tailored care. Its clinical utility needs to be investigated in future studies. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): BMBF

Herzinsuffizienz ist mit hoher Sterblichkeit, haufigen Krankenhausaufnahmen, schlechter Lebensqualitat und steigenden Kosten assoziiert. Trotz Fortschritten bei medikamentosen und Device-basieren Therapien bleiben Mortalitat und Morbiditat nach Ersthospitalisierung wegen akuter kardialer Dekompensation (AKD) hoch. In randomisierten Studien, die den Wert verschiedener Formen des nichtinvasiven Telemonitorings pruften, wurden Hospitalisierungen wegen AKD selten vermindert, weil klinische Zeichen und Symptome keine fruhen Indikatoren der AKD darstellen, sodass bei ihrem Auftreten stationare Behandlungen oft schon unvermeidbar sind. Unter verschiedenen implantierbaren Monitoring-Devices erwies sich in den USA das drahtlose Telemonitoring des pulmonalarteriellen Drucks (PAP) mit dem CardioMEMS™-Sensor (Abbott, Sylmar, Kalifornien, USA) als sicher und klinisch effektiv. Bei so uberwachten Patienten wurden – unabhangig von der kardialen Pumpfunktion – Hospitalisierungen wegen AKD deutlich reduziert, weil die Fruherkennung hamodynamischer Dekompensationen an einem PAP-Anstieg noch vor Auftreten klinischer Symptome eine praventive Therapieanpassung ermoglichte. Derzeit wird diese Technologie auch in Europa erprobt. Die Leitlinie der Europaischen Gesellschaft fur Kardiologie empfiehlt, bei Risikopatienten die Implantation eines CardioMEMS™-Sensors zu erwagen (Klasse IIb-B). Technische Weiterentwicklungen implantierbarer Systeme erlauben z. B. die Druckmessung im linken Vorhof, die erweiterte Nutzung hamodynamischer Daten (z. B. kontinuierliche Druckmessung) oder eine Selbstuberwachung durch Patienten mit einem interaktiven Modul. Anwendungsbreite und Bedeutung druckgefuhrter Therapien werden in Zukunft absehbar weiter wachsen mit der reellen Chance einer effektiveren Vermeidung von klinischen Ereignissen auch in Risikopopulationen.

Herzinsuffizienz und Depression sind Volkskrankheiten von besonderer klinischer und okonomischer Relevanz. Verglichen mit der Normalbevolkerung findet sich bei Patienten mit Herzinsuffizienz eine komorbide Depression bis zu funfmal haufiger. Dies hat negative Auswirkungen auf die Morbiditat, Mortalitat, Lebensqualitat und Behandlungskosten. Depressive Symptome uberlappen mit denen der Herzinsuffizienz, was die Diagnose erschwert. Wenig aufwendige Screening-Instrumente, z. B. der 2 Item-Gesundheitsfragebogen fur Depression, erleichtern im klinischen Alltag die Erkennung. Bisher gibt es keine Evidenz aus randomisierten kontrollierten Studien, dass Antidepressiva bei Herzinsuffizienz Stimmung und Prognose verbessern konnen, sodass deren Einsatz eine Einzelfallentscheidung bleiben sollte. Durch korperliches Training, kognitive Verhaltenstherapie und multidisziplinare ganzheitliche Betreuungskonzepte wurden in einzelnen randomisierten Studien depressive Symptome und/oder die Prognose gebessert.

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.

Herzinsuffizienz beeintrachtigt die Lebenserwartung und die Lebensqualitat. Neben belastenden korperlichen Symptomen sind dafur kognitive Dysfunktion, Depression und Angst verantwortlich. Diese psychischen Komorbiditaten sind bei Herzinsuffizienten vielfach haufiger als in der Normalbevolkerung. Angesichts der hohen Zahl Betroffener haben sie neben der klinischen auch soziookonomische Relevanz. Demografische, biologische, verhaltensbezogene und psychosoziale Faktoren spielen bei der reziproken Interaktion der somatischen und psychischen Gesundheitsstorungen eine Rolle. Wenig aufwendige Screeningverfahren erlauben, auch die psychischen Komorbiditaten zu erkennen. Multidisziplinare, auf Patientenbedurfnisse individuell abgestimmte Behandlungsansatze konnen Befinden und aktive Mitarbeit an der Krankheitsbewaltigung und damit potenziell auch die schlechte Prognose der Herzinsuffizienz verbessern.

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.

Statins reduce cardiomyocyte hypertrophy in animal models of hypertrophic cardiomyopathy, aortic banding and heart failure after myocardial infarction. We investigated the effect of the hydroxymethylglutaryl coenzyme A reductase inhibitor atorvastatin on left ventricular (LV) mass in patients with hypertrophic cardiomyopathy in a randomized placebo-controlled double-blind pilot study.Patients with hypertrophic cardiomyopathy were randomized to be treated once daily by atorvastatin 80 mg or placebo for nine months. LV mass was assessed by serial cardiac magnetic resonance imaging. LV systolic and diastolic function was determined by echocardiography. Markers of collagen metabolism and inflammation were also assessed.Out of 78 screened patients with hypertrophic cardiomyopathy 28 (2 x 14) patients were eligible for randomization. Eleven patients in each group completed the study with cardiac magnetic resonance imaging assessments meeting the evaluation standards at baseline and at follow-up. Low-density lipoprotein cholesterol levels in the atorvastatin group decreased from 3.24 +/- 1.14 mmol L(-1) (125 +/- 44 mg dL(-1)) at baseline to 1.37 +/- 0.49 mmol L(-1) (53 +/- 19 mg dL(-1)) at follow-up (P0.001), but were unchanged in the placebo group. Baseline LV mass was 228 +/- 51 g in the placebo and 232 +/- 67 g in the atorvastatin group. The primary endpoint of change in LV mass from baseline to follow-up was 2 +/- 10% in the atorvastatin group versus 0 +/- 13% in the placebo group (P = NS). Parameters of LV volumes and diameters, systolic and diastolic function, and markers of collagen metabolism were also unchanged in both groups.In patients with hypertrophic cardiomyopathy, this randomized placebo-controlled double-blind pilot study did not demonstrate an effect of 9-month treatment with atorvastatin 80 mg on LV mass reduction.

Die Stresechokardiographie hat sich als nutzliches nichtinvasives Verfahren zum Nachweis von Restenosen nach perkutaner transluminaler Koronarangioplastie bewahrt. Um die Wertigkeit der Dobutamin-Stresechokardiographie (DSE) fur die Diagnose von Restenosen nach intrakoronarer Stentimplantation zu prufen, wurden 50 Patienten (59±10 Jahre; Eingefaserkrankung, n=16, Mehrgefaserkrankung, n=34) nach Stentimplantation untersucht. 6 Monate nach Stentimplantation wurden eine DSE (5–40mcg/kg/min, 0–1mg Atropin) und eine Kontrollangiographie innerhalb von 48 h durchgefuhrt. Eine Restenose wurde mittels quantitativer Koronarangiographie als minimaler Lumendiameter (LD)

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.

Ein Hauptproblem im Langzeitverlauf nach Herztransplantationen stellt die Entwicklung einer Transplantatvaskulopathie dar. In dieser prospektiven Studie wurde die Wertigkeit der quantitativen Dobutamin-Stresechokardiographie zur Diagnostik der Transplantatvaskulopathie (TVP) mit der Koronarangriographie und dem intravaskularen Ultraschall verglichen. Insgesamt wurden bei 80 Patienten in der Spatphase nach Herztransplantation (≥ 12 Monate postoperativ) 144 Dobutamin-Stresechokardiogramme durchgefuhrt. Neben der ublichen regionalen Wandbewebungsanalyse im 2D-Echokardiogramm wurde auch die systolische Wanddickenzunahme von Septum und linksventrikularer Hinterwand im M-Mode-Echokardiogramm ausgewertet. Bei Patienten mit invasiv bestatigter TVP war die Wanddickenzunahme von Septum und Hinterwand in Ruhe wie auch unter maximalem Stres signifikant niedriger als bei Patienten ohne TVP. Bei einer Untergruppe von Patienten ohne TVP und ohne sonstige kardiale Auffalligkeiten (n = 23) wurden Normwerte fur die M-Mode-Parameter erstellt und folgende Untergrenzen ermittelt: systolische Wanddickenzunahme des Septums in Ruhe < 17,2 %, unter maximaler Dobutaminzufuhr < 45,9 %; systolische Dickenzunahme der Hinterwand in Ruhe < 41,6 %, unter maximalem Stres < 67,6 %. Im Vergleich zu den invasiven Verfahren zeigte die 2D-Analyse eine Sensitivitat von 76 % (Spezifitat 82 %) zur Erkennung der TVP. Die alleinige M-Mode-Auswertung der Wanddickenzunahme hatte eine Sensitivitat von 63 % (Spezifitat 76%), die Kombination beider echokardiographischer Verfahren ergab eine Sensitivitat von 85 % (Spezifitat 71 %). Zusammenfassend stellt die Dobutamin-Stresechokardiographie eine zuverlassige nichtinvasive Methode zur Diagnostik der TVP dar; die M-Mode-Analyse verbessert die Sensititvitat der 2D-Auswertung. Die beschriebenen Normwerte der M-Mode-Stresechokardiographie konnen als Referenz bei anderen Untersuchungen herzplantierter Patienten dienen.

Peripartum cardiomyopathy (PPCM) is a rare disease of the heart muscle that affects women with previously unknown heart diseases during pregnancy or in the first months after delivery. Cardinal symptoms are dyspnoea and fluid retention. However, tachycardia, cardiogenic thromboembolism and other clinical signs of cardiac dysfunction may also herald this uncommon cause of heart failure. The estimated incidence of PPCM shows large regional variations: in Europe and the United States it is between 1:2000 and 1:4000. The markedly higher incidence rates observed in Haitian or South African women (up to 1:300) suggest that genetic or environmental factors may play a pathogenetic role. However, the underlying aetiology of PPCM still is unclear. Besides genetic susceptibility an abnormal autoimmune response against cardiac tissue components, viral infections or an irregular activity of cathepsin D generating a potentially cardio-toxic splice variant of prolactin have been discussed. New therapeutic strategies as immune modulation or prolactin inhibition were therefore suggested, but are not yet established. Treatment strategies focus on the standard therapies for heart failure and its complications. During pregnancy heart failure therapy is limited to substances without fetotoxic effects. But even with optimal heart failure therapy the course of the disease exhibits large variations ranging from full recovery to deterioration of heart function and even early cardiac death. This review cumulates the current knowledge on PPCM and aims to raise awareness for this rare and potentially life-threatening disorder amongst all medical professionals involved in the care for pregnant women.

Detection of acute cardiac allograft rejection (AR) remains an important clinical challenge. The role of Doppler echocardiography for the non-invasive diagnosis of AR is controversial, in particular with regard to milder forms of rejection. This study was designed to evaluate the potential of Doppler echocardiography for the non-invasive diagnosis of mild AR. Serial measurements of left and right ventricular filling parameters were performed in 31 heart transplant recipients and compared with simultaneously obtained endomyocardial biopsies. To account for biological and technical variability, consecutive rejection-free studies were used to calculate 95% confidence limits for mitral and tricuspid maximum early flow velocity and pressure half time. Measurements obtained during mild AR were then compared to these data. The study demonstrated that all parameters varied considerably between consecutive rejection-free examinations. Changes in left and right ventricular filling parameters during mild A R rarely exceeded the calculated 95% confidence limits. Thus Doppler echocardiography appears of little value for the non-invasive diagnosis of mild acute cardiac rejection.

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.

BACKGROUND This prospective study was designed to examine whether left ventricular (LV) hypertrophy of the denervated transplanted heart may be reversed by medical therapy and, if so, to investigate the time course of this process and its effect on exercise capacity, myocardial function, and cardiac hemodynamics. METHODS AND RESULTS Ten hypertensive heart transplant recipients with LV hypertrophy were evaluated before therapy with enalapril plus furosemide alone or combined with verapamil, at initial blood pressure (BP) control and after 3, 6, 9, and 12 months, using 24-hour noninvasive ambulatory BP monitoring, M-mode and two-dimensional echocardiography, and supine bicycle ergometry. Average 24-hour systolic and diastolic BP declined from 158 +/- 10 and 104 +/- 7 mm Hg to 129 +/- 9 and 84 +/- 10 mm Hg at initial BP control (p less than 0.005 and p less than 0.025, respectively) and total peripheral resistance from 1,687 +/- 177 to 1,376 +/- 122 dyne.sec.cm-5 (p less than 0.025), remaining normal thereafter. Exercise capacity remained unchanged during the study. LV mass, mass-to-volume ratio, and end-diastolic septal plus posterior wall thickness decreased progressively from 211 +/- 30 g, 2.49 +/- 0.62 g/ml, and 25.7 +/- 2.6 mm to 184 +/- 26 g, 2.22 +/- 0.46 g/ml, and 22.5 +/- 1.9 mm after 3 months (all p less than 0.025) and to 174 +/- 25 g, 2.07 +/- 0.38 g/ml, and 21.5 +/- 1.5 mm after 6 months (all p less than 0.005), remaining unaltered at 9 and 12 months. A correlation was found between the decrease in average 24-hour mean BP and LV mass after 3 months of antihypertensive therapy (r = 0.71, p less than 0.05). Systolic meridional wall stress, LV end-diastolic and stroke volume, ejection fraction, and cardiac output remained unchanged throughout the observation period. CONCLUSIONS The results indicate that regression of LV hypertrophy is induced by effective antihypertensive therapy in the denervated transplanted heart. The extent of decrease in average 24-hour BP appears to be the main determinant for the extent of reduction in LV mass. LV afterload as characterized by systolic meridional wall stress, LV size and pump function, and physical exercise capacity of the transplant patients are not influenced by the therapeutic regimen chosen in this study.

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.

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.

CARDIAC allograft vasculopathy (CAV) remains a main factor limiting long-term survival after heart transplantation (HTX). Manifestations of CAV include focal stenoses as well as diffuse longitudinal involvement of vessels and small vessel disease. The clinical diagnosis is difficult, as the heart is denervated and usually remains without functionally relevant reinnervation. Routine coronary angiography is therefore the mainstay of diagnosis of CAV; this technique, however, shows a pure luminogram and is not able to detect early changes of CAV, ie, changes in the thickness of the vessel wall. Intravascular ultrasound (IVUS) has emerged as most sensitive invasive method for diagnosis of CAV. IVUS, however, can only be used to analyze the major epicardial vessels and is not able to investigate the entire coronary artery tree. In addition, both angiography and IVUS are invasive, costly and not free of risk. Several tests employed for noninvasive detection of CAV have proven unsatisfactory. In some studies, this may be related to the mode of provocation of ischemia: physical exercise may be not adequate after HTX, as the chronotropic response to exercise is blunted due to denervation. Stress tests using vasodilators as dipyridamole, which induces relative differences of perfusion, may be less reliable in diffuse CAV, but appear to be superior to exercise tests. Pharmacologic stress testing using dobutamine can overcome the problems associated with other stress modalities. Indeed, dobutamine stress echocardiography (DSE) has emerged as the most promising noninvasive method for diagnosis of CAV. This article reviews our experience and published data on assessment of CAV by DSE.

Mitogen-activated protein kinases (MAPK) are centrally involved in several mechanisms important for heart failure such as apoptosis, activation of inflammatory responses and cell proliferation. We therefore evaluated the effect of the selective p38 MAPK inhibitor SB 239063 on progression of left ventricular remodelling after myocardial infarction (MI) in rats.Rats were treated for 9 weeks with placebo or SB 239063 by gavage (15 mg kg(-1)) twice daily starting 7 days after ligation of the left anterior descending artery. Serial transthoracic echocardiography was performed at days 7, 36 and 70.Over the 9 weeks, mortality was not different between the groups. On echocardiography, animals after myocardial infarction exhibited significant left ventricular dilatation as expected (week 10, end-systolic diameter, placebo sham 5.21+/- 0.34 vs. placebo MI 8.44+/- 0.57 mm). However, there was no difference between placebo and SB 239063-treated rats (week 10, end-systolic diameter, SB MI 7.76+/- 0.74 mm, not significantly different from placebo MI). Haemodynamics changed accordingly. Moreover, SB 239063 had no effect on left ventricular hypertrophy. Treatment with SB 239063 significantly reduced cytokine expression of tumour necrosis factor and interleukin-1beta after myocardial infarction. However, collagen content was not influenced by the treatment.Despite a reduction of inflammation, treatment with the p38 inhibitor SB 239063 does not affect cardiac remodelling and cardiac function when treatment is started 7 days after myocardial infarction.

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.

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.

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.

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.

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%).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.

Accelerated bone loss is a well-recognized complication after cardiac transplantation (HTx) due to immunosuppressive therapy. The purpose of this prospective, longitudinal, randomized, placebo-controlled, double-blind study was to investigate the effect of calcitriol (1,25-dihydroxyvitamin D3) in the prevention of bone loss and fracture rate after HTx.Basic therapy included 1000 mg of calcium daily and sex hormone replacement in hypogonadal patients. A total of 132 patients (111 male, 21 female; mean age: 51+/-10 years; 35+/-25 months after HTx) were randomized to 0.25 microg of calcitriol or placebo. Bone mineral density (BMD, g/cm2; T score, %) of the lumbar spine and x-rays for the assessment of vertebral fractures were performed at baseline and after 12, 24, and 36 months. Biochemical indexes of mineral metabolism were measured every 3 months.Overall BMD was significantly decreased after HTx (T score 87+/-13%). BMD increased continuously within the study period in the calcitriol group (1 year: 2.2+/-4.8%; 2 years: 3.9+/-5.4%; 3 years: 5.7+/-4.4%) as well as in the placebo group (1 year: 1.8+/-4.9%; 2 years: 3.7+/-6.5%; 3 years: 6.1+/-7.8%) without statistical difference between the groups. Fracture incidence was low during the study interval (1 year: 2.0%; 2 years: 3.4%; 3 years: 0%). Hypogonadism (20%) was associated with a lower BMD (78+/-12% vs. 88+/-12%; P0.01) and a higher increase (35%) after hormone replacement in comparison to normogonadal patients. Increased intact parathyroid hormone and bone resorption markers decreased significantly during therapy.Calcium supplementation and sex hormone replacement in hypogonadism proved a sufficient long-term prevention therapy to improve decreased BMD and to prevent fractures after HTx. Besides immunosuppression, both concomitant hypogonadism and secondary hyperparathyroidism play a major role in the long-term bone loss and should therefore be monitored and treated adequately. Low-dose calcitriol demonstrated no significant extra benefit regarding BMD and fracture rate in the long-term period after HTx.

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; p0.05). Quality of life correlated before HTx best with subjectively rated health (r = 0.61, p0.01) and 6 months after with satisfaction about health status (r = 0.76, p0.01). 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.

The aim of this study was to investigate whether adult human cardiomyocytes may reexpress vimentin and whether this is linked to cellular activation.Myocardial samples of 81 heart transplant recipients (n=183) and patients with dilated cardiomyopathy (n=10) were investigated by immunohistochemistry with the use of the marker molecule vimentin, the muscle-specific protein desmin, and Ki67, a marker for cell activation.Vimentin protein expression in cardiomyocytes was found in 28 samples of transplant recipients and 5 myocardial samples of patients with dilated cardiomyopathy. Coexpression of vimentin and Ki67 was found in 52 of 340 vimentin-positive cardiomyocytes.We suggest that the vimentin/Ki67 coexpression indicates cell activation processes as the result of different growth stimuli.

HE MACROLIDE lactone tacrolimus (FK506) is a new immunosuppressive drug that has demonstrated to be 10 to 100 times more potent than cyclosporine A. After forming a complex with the immunophilin FK506binding protein, the complex acts in a similar fashion to the cyclosporine-immunophilin complex, resulting in an inhibition of calcineurin, a calcium-dependent serine/threonine protein phosphatase. This inhibition prevents the assembly of the functional transcription of interleukin 2. Although tacrolimus has reputedly less severe side effects, recent experimental studies have demonstrated an increase of bone formation and bone resorption, accompanied by a significant reduction in percent trabecular area. 1 The present study was undertaken to assess the effects of tacrolimus-based immunosuppression on bone mineral metabolism after orthotopic heart transplantation.

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.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.Relevant atherosclerosis (defined as maximal plaque thicknessor = 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.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.

Previous Doppler studies of transmitral flow profiles in heart transplant recipients suggested left ventricular (LV) diastolic dysfunction. The influence of left atrial filling and emptying on mitral Doppler profiles in heart transplant recipients has not been studied systematically. In the present study, pulmonary venous flow profiles, mitral flow profiles, left atrial area change and mitral annulus motion were analyzed in 20 orthotopic heart transplant recipient and 20 control subjects by transthoracic and transesophageal echocardiography and Doppler. Mitral flow profiles revealed a "restrictive" pattern with a high early-to-late diastolic flow velocity ratio in transplant patients (2.16 +/- 0.52 vs. 1.30 +/- 0.25, p0.0001), which was mainly due to a reduced late diastolic maximum mitral flow velocity (32.6 +/- 8.3 vs. 51.6 +/- 12.4 cm/s, p0.0001). Left atrial area change (35.9 +/- 13.9 vs. 58.1 +/- 17.0%, p0.0006) and mitral annulus motion (9.2 +/- 3.3 vs. 12.2 +/- 2.0%, p0.05) were reduced in transplant recipients, compared to controls. Pulmonary venous flow parameters in transplant recipients were markedly altered during systole, when pulmonary venous flow parameters are influenced primarily by atrial function rather than by diastolic LV properties: peak systolic flow velocity (45.5 +/- 8.2 vs. 62.3 +/- 14.0 cm/s, p0.001), maximum flow velocity ratio (0.87 +/- 0.19 vs. 1.45 +/- 0.33), time velocity integral of pulmonary venous flow during systole (9.3 +/- 2.3 vs. 17.1 +/- 4.0 cm, p0.001) and the systolic fraction of the time velocity integral (52.6 +/- 10.8 vs. 68.5 +/- 6.8%, p0.001) were lower in heart transplant recipients than in controls. These findings are compatible with atrial dysfunction and reduced mitral annulus motion. The results of this study indicate that LV diastolic dysfunction is not the only possible cause of altered transmitral Doppler profiles in heart transplant recipients. Atrial abnormalities represent a major contributing factor to altered mitral and pulmonary venous flow patterns. Analysis of transmitral Doppler profiles alone are therefore not adequate for analysis of diastolic LV function in heart transplant recipients.

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, p0.05. PW: 1.8 +/- 0.5 vs. 2.3 +/- 1.0, p0.05. Variance: VS: 19 +/- 15 vs. 36 +/- 18, p0.05. PW: 11 +/- 6 vs. 21 +/- 8, p0.01). 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)

Conventional active stress tests for the evaluation of coronary artery disease are not feasible for patients in whom a significant blood pressure increase during a stress procedure should be avoided, for example, those with a coexisting aortic aneurysm. Transesophageal echocardiography (TEE) with simultaneous atrial pacing is a new, highly specific, and sensitive stress technique for the detection of coronary artery disease. Furthermore, TEE can be performed safely with only mild blood pressure increases. Therefore in the present case report of a 70-year-old male, application of combined TEE and atrial pacing was used successfully to exclude the hemodynamic significance of a circumflex artery stenosis and avoided a significant blood pressure increase before surgical correction of an abdominal aortic aneurysm.

Transthorakale M-Mode, 2D- und Doppler-Echokardiographie sind etablierte Verfahren bei Diagnostik und Therapie von Patienten mit Vorhofflimmern (51). Neben Ventrikelfunktion, Wanddicken, Grose der Ventrikel und insbesondere auch der Vorhofe konnen die Klappenmorphologie und -funktion beurteilt werden. Zudem konnen Hinweise auf die Atiologie des Vorhofflimmerns gewonnen werden (Klappenvitien, Kardiomyopathie, koronare Herzerkrankung, hypertensive Herzerkrankung, Perikarditis). Auch als Folgen des Vorhofflimmerns entstandene Thromben konnen in Einzelfallen diagnostiziert werden (54).

Clinical application of echocardiographic tissue characterization necessitates measurements through the chest wall. Different distances between transducer and myocardial region of interest result in variable attenuation effects. Therefore, meaningful comparisons of myocardial echo intensity measurements are difficult with current equipment. The present study aims at the quantification and compensation of depth-dependent attenuation effects. Ten normals, 14 patients with mild (n = 7) or moderate (n = 7) hypertensive left ventricular hypertrophy and 10 transplant candidates were examined. Gain-independent logarithmically amplified, demodulated radiofrequency signals of parasternal long axis cross-sections were digitized. Mean myocardial echo intensities were determined in septal and posterior wall regions of interest. The slope of attenuation was determined from these clinically obtained data by plotting the distances between transducer and regions of interest against myocardial echo intensities. An attenuation coefficient derived from this slope was used for compensation of the depth-dependent losses of myocardial echo intensity. Compared with normals, compensated mean myocardial echo intensities were significantly lower in mild or moderate hypertensive left ventricular hypertrophy, but showed no significant difference in transplant candidates. Despite several limitations, the method employed in this study appears to be a possible approach to in vivo quantification and compensation of attenuation.

OKT3 monoclonal antibody has proved to be a potent immunosuppressive agent in treating refractory heart allograft rejections. Recently, however, an increased incidence of lymphoproliferative disorders after OKT3 therapy has been found. This short report describes the rapid growth of a cutaneous neuroendocrine (Merkel Cell) carcinoma, a rare tumor of the dermis promoted by OKT3 administration. Because OKT3 therapy seems to be associated with an increased incidence of neoplasms, frequent patient follow-up is essential.