Gerhard Pölzl

Cardiac hepatopathy before and after heart transplantation

Chronic cardiac hepatopathy is a common entity in patients evaluated for heart transplantation (HTX). Hepatic injury is caused by severe heart failure resulting from prolonged recurrent congestion and/or impaired arterial perfusion. No data are available on the reversibility of cardiac hepatopathy in patients undergoing HTX. Data of 56 consecutive adult patients undergoing HTX during 2000–02 at the University Hospital of Innsbruck were analysed retrospectively. The following parameters were evaluated at the time of listing and 3, 6 and 12 months after HTX. Plasma levels of gamma‐glutamyl transferase (γ‐GT), alkaline phosphatase (AP), bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and total plasma protein. When listed for HTX, only 12% of all patients analysed had physiological values throughout the seven laboratory parameters assessed. Elevated levels of γ‐GT, AP, bilirubin, AST, ALT, LDH and total plasma protein were detected in 66.6%, 29%, 50%, 16.7%, 10%, 40% and 18% of all patients respectively. Accordingly, median plasma levels of γ‐GT, bilirubin and LDH were elevated, whereas the mean plasma level of AP was at the upper normal range. In contrast, median plasma level of AST and mean plasma levels of ALT and total plasma protein were within the normal range: γ‐GT (median, 109.0; range, 634.0 U/l; n = 36), AP (mean, 120.2 ± 78.9 U/l; n = 29), bilirubin (median, 1.3; range, 16.1 mg/dl; n = 32), LDH (median, 226.0; range, 2355.0 U/l; n = 33), AST (median, 29.0; range, 145.0 U/l; n = 36), ALT (mean, 28.3 ± 20.8 U/l; n = 36) and total plasma protein (mean, 7.2 ± 1.1 g/dl; n = 25). Within 3 months after HTX, elevated parameters except LDH significantly ameliorated: γ‐GT (median, 59.0; range, 1160.0 U/l; P = 0.011), AP (92.2 ± 75.2 U/l; P = 0.016), bilirubin (median, 0.9; range, 8.1 mg/dl; P = 0.004), LDH slightly increased (median, 281.0; range, 543.0 U/l; P = 0.039), but there was a delayed improvement of this parameter after 6 and 12 months post‐HTX. End‐stage heart failure is characterized by a cholestatic liver enzyme profile with elevated plasma levels of γ‐GT and bilirubin. These parameters significantly improve within 3 months after HTX. Therefore, chronic cardiac hepatopathy seems to be a benign, potentially reversible disease.

Repetitive use of levosimendan for treatment of chronic advanced heart failure: Clinical evidence, practical considerations, and perspectives: An expert panel consensus

BACKGROUND The intravenous inodilator levosimendan was developed for the treatment of patients with acutely decompensated heart failure. In the last decade scientific and clinical interest has arisen for its repetitive or intermittent use in patients with advanced chronic, but not necessarily acutely decompensated, heart failure. Recent studies have suggested long-lasting favourable effects of levosimendan when administered repetitively, in terms of haemodynamic parameters, neurohormonal and inflammatory markers, and clinical outcomes. The existing data, however, requires further exploration to allow for definitive conclusions on the safety and clinical efficacy of repetitive use of levosimendan. METHODS AND RESULTS A panel of 30 experts from 15 countries convened to review and discuss the existing data, and agreed on the patient groups that can be considered to potentially benefit from intermittent treatment with levosimendan. The panel gave recommendations regarding patient dosing and monitoring, derived from the available evidence and from clinical experience. CONCLUSIONS The current data suggest that in selected patients and support out-of-hospital care, intermittent/repetitive levosimendan can be used in advanced heart failure to maintain patient stability. Further studies are needed to focus on morbidity and mortality outcomes, dosing intervals, and patient monitoring. Recommendations for the design of further clinical studies are made.

[Myocarditis and sudden cardiac death in athletes. Diagnosis, treatment, and prevention].

Myocarditis is the reason for sudden cardiac death in 5-22% of athletes < 35 years of age. Actually, parvovirus B19 and human herpes virus 6 are the most important pathogens. Clinical presentation of myocarditis is heterogeneous, with all courses between asymptomatic and fulminant reported. Especially in athletes it is important to take subtle discomforts seriously and initiate further evaluation. Electrocardiogram, laboratory parameters, serologic markers, and echocardiography are helpful in diagnosis of myocarditis, but are not specific. Magnetic resonance imaging (MRI) of the heart has become an important tool in the evaluation of patients with myocarditis and allows noninvasive appraisal of myocardial inflammation using late enhancement. However, MRI is not able to assess viral persistence. Therefore, endomyocardial biopsy (EMB) remains the gold standard in diagnosis of myocarditis. When considering EMB in these athletes one should not ignore spontaneous healing in 50% of patients with myocarditis. Contrariwise, specific therapy (e.g., immunosuppression, interferon, immunoglobulins) for myocarditis is only feasible after getting results of EMB. When myocarditis is verified, athletes have to withdraw from sport for at least 6 months. Before restarting physical activity, a detailed examination is necessary and most of the patients will undergo another EMB. For prevention of myocarditis and sudden cardiac death it is recommended to stop elite sport for 4 weeks after an unspecific infection. Whether moderate sport can be started earlier is unclear.ZusammenfassungMyokarditis als Ursache eines plötzlichen Herztodes wird bei Sportlern < 35 Jahre in 5–22% festgestellt. Parvovirus B19 und humanes Herpesvirus 6 sind derzeit die häufigsten Erreger einer Myokarditis in Mitteleuropa. Klinisch kann sich ein Sportler mit Myokarditis sehr unterschiedlich präsentieren, von asymptomatischen bis zu fulminanten Verläufen sind alle Facetten möglich. Speziell bei Athleten ist es wichtig, dass auch subtile Beschwerden ernst genommen werden und eine weitere Abklärung eingeleitet wird. In der Diagnostik sind Elektrokardiogramm, Laborparameter, Serologie und Echokardiogramm zwar hilfreich, aber wenig spezifisch. Die Magnetresonanztomographie hat in den letzten Jahren an Bedeutung gewonnen und erlaubt eine nichtinvasive Darstellung myokardialer Inflammation mittels Late Enhancement. Allerdings kann mit dieser Bildgebung kein Virusnachweis geführt werden. Somit bleibt die Endomyokardbiopsie (EMB) weiterhin der Goldstandard in der Myokarditisdiagnostik. Für die Indikationsstellung zur EMB ist zu berücksichtigen, dass ca. 50% der Myokarditiden spontan ausheilen. Nur anhand der Ergebnisse der EMB kann aber eine spezifische Therapie (z.B. Immunsuppression, Interferon, Immunglobuline) durchgeführt werden. Entscheidend für Sportler ist, dass im Fall einer nachgewiesenen Myokarditis zumindest für 6 Monate auf Sport verzichtet wird. Vor Wiederbeginn ist eine exakte klinische Untersuchung, in vielen Fällen inklusive einer Kontrollbiopsie, erforderlich. Zur Prävention der Myokarditis und damit eines möglichen plötzlichen Herztodes wird empfohlen, bei unspezifischen Infekten für 4 Wochen den Spitzensport zu pausieren. Ob Sport in moderater Stärke bereits früher begonnen werden kann, ist unklar.AbstractMyocarditis is the reason for sudden cardiac death in 5–22% of athletes < 35 years of age. Actually, parvovirus B19 and human herpes virus 6 are the most important pathogens. Clinical presentation of myocarditis is heterogeneous, with all courses between asymptomatic and fulminant reported. Especially in athletes it is important to take subtle discomforts seriously and initiate further evaluation. Electrocardiogram, laboratory parameters, serologic markers, and echocardiography are helpful in diagnosis of myocarditis, but are not specific. Magnetic resonance imaging (MRI) of the heart has become an important tool in the evaluation of patients with myocarditis and allows noninvasive appraisal of myocardial inflammation using late enhancement. However, MRI is not able to assess viral persistence. Therefore, endomyocardial biopsy (EMB) remains the gold standard in diagnosis of myocarditis. When considering EMB in these athletes one should not ignore spontaneous healing in 50% of patients with myocarditis. Contrariwise, specific therapy (e.g., immunosuppression, interferon, immunoglobulins) for myocarditis is only feasible after getting results of EMB. When myocarditis is verified, athletes have to withdraw from sport for at least 6 months. Before restarting physical activity, a detailed examination is necessary and most of the patients will undergo another EMB. For prevention of myocarditis and sudden cardiac death it is recommended to stop elite sport for 4 weeks after an unspecific infection. Whether moderate sport can be started earlier is unclear.

Co-infection with two Chlamydophila species in a case of fulminant myocarditis.

Objective:The aim of this study is to describe a case of fulminant myocarditis caused by co-infection with Chlamydophila pneumoniae and Chlamydophila psittaci in order to facilitate diagnosis and clinical management of patients suffering from this rare but life-threatening condition. Design:Case report. Setting:Intensive care unit of Innsbruck Medical University. Patient:A 24-yr-old patient admitted with septicemia and cardiac failure. Interventions:Cardiopulmonary resuscitation, extracorporal membrane oxygenation, implantation of an extracorporal cardiac assist device, and antibiotic treatment with erythromycin. Measurements and Main Results:Cp. pneumoniae and Cp. psittaci were identified by means of polymerase chain reaction and electron microscopy in the patient’s myocytes. Successful weaning off the ventricular assist device was performed within 2 wks after commencement of antibiotic therapy. Conclusions:This case report demonstrates co-infection with Cp. pneumoniae and Cp. psittaci to be a hitherto unknown cause of fulminant myocarditis. There is a particular risk of misdiagnosis of viral myocarditis, which must be avoided. Patients should be transferred to a center where extracorporal membrane oxygenation therapy and molecular diagnosis of all members of the family Chlamydiaceae are available.

Myokarditis als Ursache des plötzlichen Herztodes bei Sportlern

Myocarditis is the reason for sudden cardiac death in 5-22% of athletes < 35 years of age. Actually, parvovirus B19 and human herpes virus 6 are the most important pathogens. Clinical presentation of myocarditis is heterogeneous, with all courses between asymptomatic and fulminant reported. Especially in athletes it is important to take subtle discomforts seriously and initiate further evaluation. Electrocardiogram, laboratory parameters, serologic markers, and echocardiography are helpful in diagnosis of myocarditis, but are not specific. Magnetic resonance imaging (MRI) of the heart has become an important tool in the evaluation of patients with myocarditis and allows noninvasive appraisal of myocardial inflammation using late enhancement. However, MRI is not able to assess viral persistence. Therefore, endomyocardial biopsy (EMB) remains the gold standard in diagnosis of myocarditis. When considering EMB in these athletes one should not ignore spontaneous healing in 50% of patients with myocarditis. Contrariwise, specific therapy (e.g., immunosuppression, interferon, immunoglobulins) for myocarditis is only feasible after getting results of EMB. When myocarditis is verified, athletes have to withdraw from sport for at least 6 months. Before restarting physical activity, a detailed examination is necessary and most of the patients will undergo another EMB. For prevention of myocarditis and sudden cardiac death it is recommended to stop elite sport for 4 weeks after an unspecific infection. Whether moderate sport can be started earlier is unclear.ZusammenfassungMyokarditis als Ursache eines plötzlichen Herztodes wird bei Sportlern < 35 Jahre in 5–22% festgestellt. Parvovirus B19 und humanes Herpesvirus 6 sind derzeit die häufigsten Erreger einer Myokarditis in Mitteleuropa. Klinisch kann sich ein Sportler mit Myokarditis sehr unterschiedlich präsentieren, von asymptomatischen bis zu fulminanten Verläufen sind alle Facetten möglich. Speziell bei Athleten ist es wichtig, dass auch subtile Beschwerden ernst genommen werden und eine weitere Abklärung eingeleitet wird. In der Diagnostik sind Elektrokardiogramm, Laborparameter, Serologie und Echokardiogramm zwar hilfreich, aber wenig spezifisch. Die Magnetresonanztomographie hat in den letzten Jahren an Bedeutung gewonnen und erlaubt eine nichtinvasive Darstellung myokardialer Inflammation mittels Late Enhancement. Allerdings kann mit dieser Bildgebung kein Virusnachweis geführt werden. Somit bleibt die Endomyokardbiopsie (EMB) weiterhin der Goldstandard in der Myokarditisdiagnostik. Für die Indikationsstellung zur EMB ist zu berücksichtigen, dass ca. 50% der Myokarditiden spontan ausheilen. Nur anhand der Ergebnisse der EMB kann aber eine spezifische Therapie (z.B. Immunsuppression, Interferon, Immunglobuline) durchgeführt werden. Entscheidend für Sportler ist, dass im Fall einer nachgewiesenen Myokarditis zumindest für 6 Monate auf Sport verzichtet wird. Vor Wiederbeginn ist eine exakte klinische Untersuchung, in vielen Fällen inklusive einer Kontrollbiopsie, erforderlich. Zur Prävention der Myokarditis und damit eines möglichen plötzlichen Herztodes wird empfohlen, bei unspezifischen Infekten für 4 Wochen den Spitzensport zu pausieren. Ob Sport in moderater Stärke bereits früher begonnen werden kann, ist unklar.AbstractMyocarditis is the reason for sudden cardiac death in 5–22% of athletes < 35 years of age. Actually, parvovirus B19 and human herpes virus 6 are the most important pathogens. Clinical presentation of myocarditis is heterogeneous, with all courses between asymptomatic and fulminant reported. Especially in athletes it is important to take subtle discomforts seriously and initiate further evaluation. Electrocardiogram, laboratory parameters, serologic markers, and echocardiography are helpful in diagnosis of myocarditis, but are not specific. Magnetic resonance imaging (MRI) of the heart has become an important tool in the evaluation of patients with myocarditis and allows noninvasive appraisal of myocardial inflammation using late enhancement. However, MRI is not able to assess viral persistence. Therefore, endomyocardial biopsy (EMB) remains the gold standard in diagnosis of myocarditis. When considering EMB in these athletes one should not ignore spontaneous healing in 50% of patients with myocarditis. Contrariwise, specific therapy (e.g., immunosuppression, interferon, immunoglobulins) for myocarditis is only feasible after getting results of EMB. When myocarditis is verified, athletes have to withdraw from sport for at least 6 months. Before restarting physical activity, a detailed examination is necessary and most of the patients will undergo another EMB. For prevention of myocarditis and sudden cardiac death it is recommended to stop elite sport for 4 weeks after an unspecific infection. Whether moderate sport can be started earlier is unclear.

Können CMV-Infekte nach Herztransplantation durch dreimonatige antivirale Prophylaxe reduziert werden? 7 Jahre Erfahrung mit Ganciclovir

BACKGROUND In the early phase after heart transplantation (HTX) patients are at high risk for infection because of intensified immunosuppression. This retrospective study evaluates the efficacy of a three-month antiviral cytomegalovirus (CMV) prophylaxis. PATIENTS AND METHODS 133 patients received a three-month combined intravenous and oral CMV prophylaxis with Ganciclovir (Cymevene after HTX between 1997 and April 2003 (group II). They were compared to a historical group consisting of 40 patients, who had undergone HTX between 1995 and 1996 (group I; CMV-prophylaxis: hyperimmune globuline (Cytotect) for the first post-operative month in combination with orally administered aciclovir (Zovirax) for 6 months). Demographic data of organ recipients and donors in both groups were comparable, except for underlying cardiac diseases (p = 0.016). All patients had identical postoperative immunosuppressive regimes. RESULTS Group II had a significantly lower mortality rate (GI: 37.5%, GII: 9.8%; p < 0.001); one year survival (p = 0.001) and overall survival (p = 0.001) were significantly better than in group I. Patients of group II had fewer rejection episodes > or = grade II ISHLT requiring treatment (p < 0.001). Group II presented significantly fewer positive CMV blood samples (p = 0.005) and CMV infections (26% versus 47,5% in GI; p = 0.008), and a later onset of infections after HTX than group I (group I with a mean interval of 5.8 weeks after HTX, group II: 24.8 weeks after HTX; p < 0.001). CONCLUSION Incidence of CMV infection was significantly lowered under ganciclovir prophylaxis, infections occurred at a later time point after HTX, when patients were immunologically more competent. The proportion of higher grade rejection episodes was markedly reduced and survival was improved.SummaryBackgroundIn the early phase after heart transplantation (HTX) patients are at high risk for infection because of intensified immunosuppression. This retrospective study evaluates the efficacy of a three-month antiviral cytomegalovirus (CMV) prophylaxis.Patients and methods133 patients received a three-month combined intravenous and oral CMV prophylaxis with Ganciclovir (Cymevene®) after HTX between 1997 and April 2003 (group II). They were compared to a historical group consisting of 40 patients, who had undergone HTX between 1995 and 1996 (group I; CMV-prophylaxis: hyperimmune globuline (Cytotect®) for the first post-operative month in combination with orally administered aciclovir (Zovirax®) for 6 months).Demographic data of organ recipients and donors in both groups were comparable, except for underlying cardiac diseases (p=0.016). All patients had identical postoperative immunosuppressive regimes.ResultsGroup II had a significantly lower mortality rate (GI: 37.5%, GII: 9.8%; p<0.001); one year survival (p=0.001) and overall survival (p=0.001) were significantly better than in group I. Patients of group II had fewer rejection episodes ≥ grade II ISHLT requiring treatment (p<0.001).Group II presented significantly fewer positive CMV blood samples (p=0.005) and CMV infections (26% versus 47,5% in GI; p=0.008), and a later onset of infections after HTX than group I (group I with a mean interval of 5.8 weeks after HTX, group II: 24.8 weeks after HTX; p<0.001).ConclusionIncidence of CMV infection was significantly lowered under ganciclovir prophylaxis, infections occurred at a later time point after HTX, when patients were immunologically more competent. The proportion of higher grade rejection episodes was markedly reduced and survival was improved.ZusammenfassungHintergrund und FragestellungIn der frühen Phase nach Herztransplantation (HTX), der Zeit intensivster Immunsuppression, haben Patienten ein hohes Infektionsrisiko. Diese retrospektive Kohortenstudie evaluiert die Wirksamkeit einer dreimonatigen antiviralen Cytomegalievirus (CMV)-Prophylaxe.Patienten und Methodik133 Patienten (Gruppe II: HTX 1997 — April 2003) erhielten eine dreimonatige kombiniert intravenös-orale CMV-Prophylaxe (Ganciclovir-Cymevene®) und wurden mit einer historischen Gruppe I (40 Patienten, HTX 1995-1996; CMV-Prophylaxe: CMV-Hyperimmunglobulin [Cytotect®] im 1. postoperativen Monat; Aciclovir [Zovirax®] oral über 6 Monate) verglichen.Demographische Daten der Spender und Ernpfänqer beider Gruppen zeigten keine relevanten Unterschiede (ausgenommen cardiale Grunderkrankungen; p=0,016). In beiden Gruppen wurde ein identes immunsuppressives Regime verwendet.ErgebnisseIn Gruppe II war die Mortalität hochsignifikant geringer (GI: 37,5%, GIl: 9,8%, p<0,001), das Einjahresüberleben (p=0,001) und das Gesamtüberleben (p 0,001) hochsignifikant besser als in Gruppe I. Patienten der Gruppe II hatten hochsignifikant weniger höhergradige, therapiewürdige Abstoßungen (≥ Grad II nach ISHLT) (p<0,001).In Gruppe II fanden sich signifikant weniger positive CMV-Bluttests (p=0,005) und CMV-Infektionen (25,6% vs. 47,5% in GI; p=0,008), diese traten hochsignifikant später nach der HTX auf als in Gruppe I (GI: im Mittel 5,8 Wochen nach HTX, GII: 23,6 Wochen, p<0,001).FolgerungenUnter Ganciclovirprophylaxe war die Inzidenz der CMV-Infekte nicht nur signifikant reduziert, sie wurden zudem in eine spätere Phase nach HTX, in der Patienten immunologisch wiederum kompetenter sind, verschoben. Höhergradige Abstoßungen waren in der Ganciclovirgruppe hochsignifikant seltener, die zudem ein verbessertes Einjahres- und Langzeitüberleben aufweist.

MELAS Syndrome and Kidney Disease Without Fanconi Syndrome or Proteinuria: A Case Report

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS syndrome) represents one of the most frequent mitochondrial disorders. The majority of MELAS cases are caused by m.3243A>G mutation in the mitochondrial MT-TL1 gene, which encodes the mitochondrial tRNALeu(UUR). Kidney involvement usually manifests as Fanconi syndrome or focal segmental glomerulosclerosis. We describe a patient with MELAS mutation, cardiomyopathy, and chronic kidney disease without Fanconi syndrome, proteinuria, or hematuria. While the patient was waitlisted for heart transplantation, her kidney function deteriorated from an estimated glomerular filtration rate of 33 to 20mL/min/1.73m2 within several months. Kidney biopsy was performed to distinguish decreased kidney perfusion from intrinsic kidney pathology. Histologic examination of the biopsy specimen showed only a moderate degree of tubular atrophy and interstitial fibrosis, but quantitative analysis of the m.3243A>G mitochondrial DNA mutation revealed high heteroplasmy levels of 89% in the kidney. Functional assessment showed reduced activity of mitochondrial enzymes in kidney tissue, which was confirmed by immunohistology. In conclusion, we describe an unusual case of MELAS syndrome with chronic kidney disease without apparent proteinuria or tubular disorders associated with Fanconi syndrome, but widespread interstitial fibrosis and a high degree of heteroplasmy of the MELAS specific mutation and low mitochondrial activity in the kidney.

Cardiac sarcoidosis mimicking arrhythmogenic right ventricular dysplasia

Isolated manifestation of sarcoidosis in the heart is very rare. The present work describes the case of a 41-year-old woman with ventricular tachycardia and severe symptoms of heart failure in June 2006. Clinical, MRI and echocardiographic findings revealed the diagnosis of an arrhythmogenic right ventricular dysplasia. Due to the severe progression of the disease, cardiac transplantation was performed in August 2007. Histopathological examination of the explanted heart, however, revealed numerous non-necrotising granulomas with giant cells, lymphocytic infiltration and interstitial fibrosis, finally confirming the diagnosis of a myocardial sarcoidosis.

Repetitive use of levosimendan in advanced heart failure: need for stronger evidence in a field in dire need of a useful therapy

Patients in the latest stages of heart failure are severely compromised, with poor quality of life and frequent hospitalizations. Heart transplantation and left ventricular assist device implantation are viable options only for a minority, and intermittent or continuous infusions of positive inotropes may be needed as a bridge therapy or as a symptomatic approach. In these settings, levosimendan has potential advantages over conventional inotropes (catecholamines and phosphodiesterase inhibitors), such as sustained effects after initial infusion, synergy with beta-blockers, and no increase in oxygen consumption. Levosimendan has been suggested as a treatment that reduces re-hospitalization and improves quality of life. However, previous clinical studies of intermittent infusions of levosimendan were not powered to show statistical significance on key outcome parameters. A panel of 45 expert clinicians from 12 European countries met in Rome on November 24-25, 2016 to review the literature and envision an appropriately designed clinical trial addressing these needs. In the earlier FIGHT trial (daily subcutaneous injection of liraglutide in heart failure patients with reduced ejection fraction) a composite Global Rank Score was used as primary end-point where death, re-hospitalization, and change in N-terminal-prohormone-brain natriuretic peptide level were considered in a hierarchical order. In the present study, we tested the same end-point post hoc in the PERSIST and LEVOREP trials on oral and repeated i.v. levosimendan, respectively, and demonstrated superiority of levosimendan treatment vs placebo. The use of the same composite end-point in a properly powered study on repetitive levosimendan in advanced heart failure is strongly advocated.

Ruhepuls und funktionelle Einschränkungen als prognostische Parameter bei herzinsuffizienten Patienten im tatsächlichen Leben. Daten aus dem Herzinsuffizienz-Register der ÖKG

PURPOSE Elevated heart rate (70 beats per minute-bpm or more) is a predictor of impaired prognosis in patients with ischemic heart failure. The Austrian Working Group on Heart Failure has established a registry in May 2006 for all patients referred to dedicated heart failure clinics with a planned follow-up after 12 ± 3 months. Here we report an analysis of the prognostic impact of elevated heart rate at referral in a well-defined cohort of heart failure patients. METHODS Between May 2006 and October 2009 1904 patients have been documented in the Austrian Heart Failure Registry. One thousand threehundred and sixty three patients (72%) had sinus rhythm at referral. Kaplan-Meier and Cox proportional hazards regression analyses were used to compare overall and cardiovascular mortality between high (70 bpm or more) and low heart-rate groups. Patients who were lost-to-follow-up (n = 166) were censored at the time of last contact. RESULTS At baseline in 793 patients (58%) heart rate has been elevated (70 bpm or more) while in 562 patients it has been below 70 bpm, in 8 patients no baseline heart rate has been recorded. Groups were equally balanced regarding age, gender and cardiovascular risk factors with the exception of smokers (more active smokers in the high heart-rate group: 23 vs 14%; p = 0.001) and valvular cause of heart failure (more frequent in the high heart-rate group: 3% vs 1%; p = 0.012). Patients in the high heart-rate group had significantly higher median NT-pro-BNP (1470 pg/ml, IQR 499-4188 pg/ml) compared to patients in the low heart-rate group (784 pg/ml, IQR 314-2162 pg/ml; p < 0.001). NYHA functional classes III and IV have been more frequent in the high heart-rate group than in the low heart-rate group (32% and 22%, respectively; p < 0.001) while reduced left ventricular ejection fraction (39% or less) has been more frequent in the high heart-rate group than in the low heart-rate group (71% and 61%, respectively; p < 0.001). In the high heart-rate group treatment with beta-blockers has been less frequent than in the low heart rate group (76% and 86%, respectively; p < 0.01) while dosage of beta-blocker therapy has been comparable in both groups. Of the 75 patients who died within 3.5 years 38 deaths had a cardiovascular cause. Cox proportional hazards analysis revealed that high NYHA functional class (III and IV) and elevated heart rate (70 bpm or more) were the best predictors of overall mortality while cardiovascular mortality could best be predicted by NYHA functional classes III and IV. CONCLUSION Higher NYHA-functional classes and elevated heart rate are predictors of adverse outcome in chronic heart failure patients.SummaryPURPOSE: Elevated heart rate (70 beats per minute-bpm or more) is a predictor of impaired prognosis in patients with ischemic heart failure. The Austrian Working Group on Heart Failure has established a registry in May 2006 for all patients referred to dedicated heart failure clinics with a planned follow-up after 12 ± 3 months. Here we report an analysis of the prognostic impact of elevated heart rate at referral in a well-defined cohort of heart failure patients. METHODS: Between May 2006 and October 2009 1904 patients have been documented in the Austrian Heart Failure Registry. One thousand threehundred and sixty three patients (72%) had sinus rhythm at referral. Kaplan-Meier and Cox proportional hazards regression analyses were used to compare overall and cardiovascular mortality between high (70 bpm or more) and low heart-rate groups. Patients who were lost-to-follow-up (n = 166) were censored at the time of last contact. RESULTS: At baseline in 793 patients (58%) heart rate has been elevated (70 bpm or more) while in 562 patients it has been below 70 bpm, in 8 patients no baseline heart rate has been recorded. Groups were equally balanced regarding age, gender and cardiovascular risk factors with the exception of smokers (more active smokers in the high heart-rate group: 23 vs 14%; p = 0.001) and valvular cause of heart failure (more frequent in the high heart-rate group: 3% vs 1%; p = 0.012). Patients in the high heart-rate group had significantly higher median NT-pro-BNP (1470 pg/ml, IQR 499–4188 pg/ml) compared to patients in the low heart-rate group (784 pg/ml, IQR 314–2162 pg/ml; p < 0.001). NYHA functional classes III and IV have been more frequent in the high heart-rate group than in the low heart-rate group (32% and 22%, respectively; p < 0.001) while reduced left ventricular ejection fraction (39% or less) has been more frequent in the high heart-rate group than in the low heart-rate group (71% and 61%, respectively; p < 0.001). In the high heart-rate group treatment with beta-blockers has been less frequent than in the low heart rate group (76% and 86%, respectively; p < 0.01) while dosage of beta-blocker therapy has been comparable in both groups. Of the 75 patients who died within 3.5 years 38 deaths had a cardiovascular cause. Cox proportional hazards analysis revealed that high NYHA functional class (III and IV) and elevated heart rate (70 bpm or more) were the best predictors of overall mortality while cardiovascular mortality could best be predicted by NYHA functional classes III and IV. CONCLUSION: Higher NYHA-functional classes and elevated heart rate are predictors of adverse outcome in chronic heart failure patients.ZusammenfassungHINTERGRUND: Ein hoher Ruhepuls (70/min oder mehr) ist bei ischämischer Herzinsuffizienz ein Prädiktor für eine eingeschränkte Prognose. Die Arbeitsgruppe Herzinsuffizienz der Österreichischen Kardiologischen Gesellschaft betreibt seit Mai 2006 ein Register für erstmalig zugewiesene Patienten, für die auch ein Follow-up nach 12 ± 3 Monaten vorgesehen ist. Hier berichten wir erstmals die Daten einer Auswertung im Hinblick auf den prognostischen Wert eines erhöhten Ruhepulses in diesem Kollektiv. METHODIK: Zwischen Mai 2006 und Oktober 2009 wurden insgesamt 1904 Patienten in das Register eingeschlossen. 1363 Patienten (72 %) waren im Sinusrhythmus. Kaplan–Meier Analyse und Cox-Regressionsanalyse wurden zur Bestimmung der Gesamt- sowie cardiovaskulären Mortalität in der Hochpuls- (70 Schläge/min oder mehr) und Niedrigpulsgruppe verwendet. Patienten ohne dokumentiertes Follow-up (n = 166) wurden bei Letztkontakt zensiert. ERGEBNISSE: Bei Erstvorstellung hatten 793 Patienten (58 %) einen Ruhepuls von 70 oder mehr, 562 Patienten hatten einen Ruhepuls unter 70/min, bei 8 Patienten war keine Herzfrequenz dokumentiert. Die Gruppen waren hinsichtlich Alter, Geschlecht und cardiovaskulärer Risikofaktoren vergleichbar, in der Hochpulsgruppe waren signifikant mehr aktive Raucher (23 vs 14 %; p = 0,001) und mehr valvuläre Ursachen einer Herzinsuffizienz (3 vs 1 %; p = 0,012). Patienten in der Hochpulsgruppe hatten signifikant höhere mediane NT-pro-BNP-Werte (1470 pg/ml, IQR 499–4188 pg/ml) als Patienten in der Niedrigpulsgruppe (784 pg/ml, IQR 314–2162 pg/ml; p < 0,001). Die NYHA-Klassen III und IV waren in der Hochpulsgruppe häufiger anzutreffen als in der Niedrigpulsgruppe (32 vs 22 %; p < 0,001), eine stark reduzierte linksventrikuläre Funktion (LV-EF ≤ 39 %) fand sich ebenfalls in der Hochpulsgruppe häufiger (71 vs 61 %; p < 0,001). In der Hochpulsgruppe wurden Betablocker seltener verabreicht (76 vs 86 %; p < 0,01), die Dosierungen waren aber vergleichbar mit der Niedrigpulsgruppe. 75 Patienten sind innerhalb von 3,5 Jahren verstorben, 38 davon an cardiovaskulären Ursachen. NYHA III und IV sowie ein Ruhepuls von 70/min oder mehr waren die besten Prädiktoren der Gesamtmortalität, die besten Prädiktoren für die cardiovaskuläre Mortalität waren NYHA III und IV. SCHLUSSFOLGERUNG: Eine hohe NYHA-Klasse sowie ein hoher Ruhepuls sind die besten Prädiktoren für eine schlechte Prognose bei chronischer Herzinsuffizienz.