Publications by authors named "Christiane E Angermann"

93 Publications

A Global Perspective of Racial Differences and Outcomes in Patients Presenting with Acute Heart Failure.

Am Heart J 2021 Sep 10. Epub 2021 Sep 10.

National Heart Centre Singapore & Duke-National University of Singapore, Singapore; University Medical Centre Groningen, the Netherlands. Electronic address:

Important racial differences in characteristics, treatment, and outcomes of patient with acute heart failure (AHF) have been described. The objective of this analysis of the International REgistry to assess medical Practice with lOngitudinal obseRvation for Treatment of Heart Failure (REPORT-HF) registry was to estimate racial differences in patients with AHF according to country income level.
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http://dx.doi.org/10.1016/j.ahj.2021.09.001DOI Listing
September 2021

Dynamics of Left Ventricular Myocardial Work in Patients Hospitalized for Acute Heart Failure.

J Card Fail 2021 Jul 29. Epub 2021 Jul 29.

Comprehensive Heart Failure Center, University Hospital and University of Würzburg, Würzburg, Germany; Department of Medicine I, University Hospital Würzburg, Würzburg, Germany. Electronic address:

Background: The left ventricular ejection fraction (LVEF) is the most commonly used measure describing pumping efficiency, but it is heavily dependent on loading conditions and therefore not well-suited to study pathophysiologic changes. The novel concept of echocardiography-derived myocardial work (MyW) overcomes this disadvantage as it is based on LV pressure-strain loops. We tracked the in-hospital changes of indices of MyW in patients admitted for acute heart failure (AHF) in relation to their recompensation status and explored the prognostic utility of MyW indices METHODS AND RESULTS: We studied 126 patients admitted for AHF (mean 73 ± 12 years, 37% female, 40% with a reduced LVEF [<40%]), providing pairs of echocardiograms obtained both on hospital admission and prior to discharge. The following MyW indices were derived: global constructive and wasted work (GCW, GWW), global work index (GWI), and global work efficiency. In patients with HF with reduced ejection fraction with decreasing N-terminal prohormone B-natriuretic peptide levels during hospitalization, the GCW and GWI improved significantly, whereas the GWW remained unchanged. In patients with HF with preserved ejection fraction, the GCW and GWI were unchanged; however, in patients with no decrease or eventual increase in N-terminal prohormone B-natriuretic peptide, we observed an increase in GWW. In all patients with AHF, higher values of GWW were associated with a higher risk of death or rehospitalization within 6 months after discharge (per 10-point increment hazard ratio 1.035, 95% confidence interval 1.005-1.065).

Conclusions: Our results suggest differential myocardial responses to decompensation and recompensation, depending on the HF phenotype in patients presenting with AHF. The GWW predicted the 6-month prognosis in these patients, regardless of LVEF. Future studies in larger cohorts need to confirm our results and identify determinants of short-term and longer term changes in MyW.
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http://dx.doi.org/10.1016/j.cardfail.2021.07.004DOI Listing
July 2021

Adaptive anti-myocardial immune response following hospitalization for acute heart failure.

ESC Heart Fail 2021 Aug 2;8(4):3348-3353. Epub 2021 May 2.

Comprehensive Heart Failure Center, University and University Hospital Würzburg, Am Schwarzenberg 15, Würzburg, D-97078, Germany.

Aims: It has been hypothesized that cardiac decompensation accompanying acute heart failure (AHF) episodes generates a pro-inflammatory environment boosting an adaptive immune response against myocardial antigens, thus contributing to progression of heart failure (HF) and poor prognosis. We assessed the prevalence of anti-myocardial autoantibodies (AMyA) as biomarkers reflecting adaptive immune responses in patients admitted to the hospital for AHF, followed the change in AMyA titres for 6 months after discharge, and evaluated their prognostic utility.

Methods And Results: AMyA were determined in n = 47 patients, median age 71 (quartiles 60; 80) years, 23 (49%) female, and 24 (51%) with HF with preserved ejection fraction, from blood collected at baseline (time point of hospitalization) and at 6 month follow-up (visit F6). Patients were followed for 18 months (visit F18). The prevalence of AMyA increased from baseline (n = 21, 45%) to F6 (n = 36, 77%; P < 0.001). At F6, the prevalence of AMyA was higher in patients with HF with preserved ejection fraction (n = 21, 88%) compared with patients with reduced ejection fraction (n = 14, 61%; P = 0.036). During the subsequent 12 months after F6, that is up to F18, patients with newly developed AMyA at F6 had a higher risk for the combined endpoint of death or rehospitalization for HF (hazard ratio 4.79, 95% confidence interval 1.13-20.21; P = 0.033) compared with patients with persistent or without AMyA at F6.

Conclusions: Our results support the hypothesis that AHF may induce patterns of adaptive immune responses. More studies in larger populations and well-defined patient subgroups are needed to further clarify the role of the adaptive immune system in HF progression.
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http://dx.doi.org/10.1002/ehf2.13376DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8318503PMC
August 2021

Global Differences in Burden and Treatment of Ischemic Heart Disease in Acute Heart Failure: REPORT-HF.

JACC Heart Fail 2021 May 7;9(5):349-359. Epub 2021 Apr 7.

University of Bergen, Stavanger University Hospital, Stavanger, Norway. Electronic address:

Objectives: The primary aim of the current study was to investigate global differences in prevalence, association with outcome, and treatment of ischemic heart disease (IHD) in patients with acute heart failure (AHF) in the REPORT-HF (International Registry to Assess Medical Practice With Longitudinal Observation for Treatment of Heart Failure) registry.

Background: Data on IHD in patients with AHF are primarily from Western Europe and North America. Little is known about global differences in treatment and prognosis of patients with IHD and AHF.

Methods: A total of 18,539 patients with AHF were prospectively enrolled from 44 countries and 365 centers in the REPORT-HF registry. Patients with a history of coronary artery disease, an ischemic event causing admission for AHF, or coronary revascularization were classified as IHD. Clinical characteristics, treatment, and outcomes of patients with and without IHD were explored.

Results: Compared with 8,766 (47%) patients without IHD, 9,773 (53%) patients with IHD were older, more likely to have a left ventricular ejection fraction <40% (heart failure with reduced ejection fraction [HFrEF]), and reported more comorbidities. IHD was more common in lower income compared with high-income countries (61% vs. 48%). Patients with IHD from countries with low health care expenditure per capita or without health insurance less likely underwent coronary revascularization or used anticoagulants at discharge. IHD was independently associated with worse cardiovascular death (hazard ratio: 1.21; 95% confidence interval: 1.09 to 1.35). The association between IHD and cardiovascular death was stronger in HFrEF compared with heart failure with preserved ejection fraction (p <0.001).

Conclusions: In this large global contemporary cohort of patients with AHF, IHD was more common in low-income countries and conveyed worse 1-year mortality, especially in HFrEF. Patients in regions with the greatest burden of IHD were less likely to receive coronary revascularization and treatment for IHD.
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http://dx.doi.org/10.1016/j.jchf.2020.12.015DOI Listing
May 2021

Sodium-glucose co-transporter 2 inhibition in patients hospitalized for acute decompensated heart failure: rationale for and design of the EMPULSE trial.

Eur J Heart Fail 2021 05 10;23(5):826-834. Epub 2021 Mar 10.

Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

Aims: Treatment with sodium-glucose co-transporter 2 (SGLT2) inhibitors improves outcomes in patients with chronic heart failure (HF) with reduced ejection fraction. There is limited experience with the in-hospital initiation of SGLT2 inhibitors in patients with acute HF (AHF) with or without diabetes. EMPULSE is designed to assess the clinical benefit and safety of the SGLT2 inhibitor empagliflozin compared with placebo in patients hospitalized with AHF.

Methods: EMPULSE is a randomized, double-blind, parallel-group, placebo-controlled multinational trial comparing the in-hospital initiation of empagliflozin (10 mg once daily) with placebo. Approximately 500 patients admitted for AHF with dyspnoea, signs of fluid overload, and elevated natriuretic peptides will be randomized 1:1 stratified to HF status (de-novo and decompensated chronic HF) to either empagliflozin or placebo at approximately 165 sites across North America, Europe and Asia. Patients will be enrolled regardless of ejection fraction and diabetes status and will be randomized during hospitalization and after stabilization (between 24 h and 5 days after admission), with treatment continued up to 90 days after initiation. The primary outcome is clinical benefit at 90 days, consisting of a composite of all-cause death, HF events, and ≥5 point change from baseline in Kansas City Cardiomyopathy Questionnaire total symptom score (KCCQ-TSS), assessed using a 'win-ratio' approach. Secondary outcomes include assessments of safety, change in KCCQ-TSS from baseline to 90 days and change in natriuretic peptides from baseline to 30 days.

Conclusion: The EMPULSE trial will evaluate the clinical benefit and safety of empagliflozin in patients hospitalized for AHF.
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http://dx.doi.org/10.1002/ejhf.2137DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8358952PMC
May 2021

Heart and brain interactions : Pathophysiology and management of cardio-psycho-neurological disorders.

Herz 2021 Mar 5;46(2):138-149. Epub 2021 Feb 5.

Deutsches Zentrum für Herzinsuffizienz, Universität und Universitätsklinikum Würzburg, Am Schwarzenberg 15, 97078, Würzburg, Germany.

Cardiovascular diseases (CVD) and mental health disorders (MHD; e.g. depression, anxiety and cognitive dysfunction) are highly prevalent and are associated with significant morbidity and mortality and impaired quality of life. Currently, possible interactions between pathophysiological mechanisms in MHD and CVD are rarely considered during the diagnostic work-up, prognostic assessment and treatment planning in patients with CVD, and research addressing bidirectional disease mechanisms in a systematic fashion is scarce. Besides some overarching pathogenetic principles shared by CVD and MHD, there are specific syndromes in which pre-existing neurological or psychiatric illness predisposes and contributes to CVD development (as in Takotsubo syndrome), or in which the distorted interplay between innate immune and central nervous systems and/or pre-existing CVD leads to secondary MHD and brain damage (as in peripartum cardiomyopathy or atrial fibrillation). Clinical manifestations and phenotypes of cardio-psycho-neurological diseases depend on the individual somatic, psychosocial, and genetic risk profile as well as on personal resilience, and differ in many respects between men and women. In this article, we provide arguments on why, in such conditions, multidisciplinary collaborations should be established to allow for more comprehensive understanding of the pathophysiology as well as appropriate and targeted diagnosis and treatment. In addition, we summarize current knowledge on the complex interactions between the cardiovascular and central nervous systems in Takotsubo syndrome and peripartum cardiomyopathy, and on the neurological and psychiatric complications of atrial fibrillation.
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http://dx.doi.org/10.1007/s00059-021-05022-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7966144PMC
March 2021

Trajectories of Left Ventricular Ejection Fraction After Acute Decompensation for Systolic Heart Failure: Concomitant Echocardiographic and Systemic Changes, Predictors, and Impact on Clinical Outcomes.

J Am Heart Assoc 2021 02 26;10(3):e017822. Epub 2021 Jan 26.

Comprehensive Heart Failure Centre University and University Hospital Würzburg Germany.

Background Prospective longitudinal follow-up of left ventricular ejection fraction (LVEF) trajectories after acute cardiac decompensation of heart failure is lacking. We investigated changes in LVEF and covariates at 6-months' follow-up in patients with a predischarge LVEF ≤40%, and determined predictors and prognostic implications of LVEF changes through 18-months' follow-up. Methods and Results Interdisciplinary Network Heart Failure program participants (n=633) were categorized into subgroups based on LVEF at 6-months' follow-up: normalized LVEF (>50%; heart failure with normalized ejection fraction, n=147); midrange LVEF (41%-50%; heart failure with midrange ejection fraction, n=195), or persistently reduced LVEF (≤40%; heart failure with persistently reduced LVEF , n=291). All received guideline-directed medical therapies. At 6-months' follow-up, compared with patients with heart failure with persistently reduced LVEF, heart failure with normalized LVEF or heart failure with midrange LVEF subgroups showed greater reductions in LV end-diastolic/end-systolic diameters (both <0.001), and left atrial systolic diameter (=0.002), more increased septal/posterior end-diastolic wall-thickness (both <0.001), and significantly greater improvement in diastolic function, biomarkers, symptoms, and health status. Heart failure duration <1 year, female sex, higher predischarge blood pressure, and baseline LVEF were independent predictors of LVEF improvement. Mortality and event-free survival rates were lower in patients with heart failure with normalized LVEF (=0.002). Overall, LVEF increased further at 18-months' follow-up (<0.001), while LV end-diastolic diameter decreased (=0.048). However, LVEF worsened (=0.002) and LV end-diastolic diameter increased (=0.047) in patients with heart failure with normalized LVEF hospitalized between 6-months' follow-up and 18-months' follow-up. Conclusions Six-month survivors of acute cardiac decompensation for systolic heart failure showed variable LVEF trajectories, with >50% showing improvements by ≥1 LVEF category. LVEF changes correlated with various parameters, suggesting multilevel reverse remodeling, were predictable from several baseline characteristics, and were associated with clinical outcomes at 18-months' follow-up. Repeat hospitalizations were associated with attenuation of reverse remodeling. Registration URL: https://www.controlled-trials.com; Unique identifier: ISRCTN23325295.
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http://dx.doi.org/10.1161/JAHA.120.017822DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955416PMC
February 2021

Pulmonary artery pressure-guided therapy in ambulatory patients with symptomatic heart failure: the CardioMEMS European Monitoring Study for Heart Failure (MEMS-HF).

Eur J Heart Fail 2020 10 9;22(10):1891-1901. Epub 2020 Aug 9.

Internal Medicine III Cardiology, Angiology, Intensive Care, Saarland University Medical Centre, Homburg, Germany.

Aims: Heart failure (HF) leads to repeat hospitalisations and reduces the duration and quality of life. Pulmonary artery pressure (PAP)-guided HF management using the CardioMEMS™ HF system was shown to be safe and reduce HF hospitalisation (HFH) rates in New York Heart Association (NYHA) class III patients. However, these findings have not been replicated in health systems outside the United States. Therefore, the CardioMEMS European Monitoring Study for Heart Failure (MEMS-HF) evaluated the safety, feasibility, and performance of this device in Germany, The Netherlands, and Ireland.

Methods And Results: A total of 234 NYHA class III patients (68 ± 11 years, 22% female, ≥1 HFH in the preceding year) from 31 centres were implanted with a CardioMEMS sensor and underwent PAP-guided HF management. One-year rates of freedom from device- or system-related complications and from sensor failure (co-primary outcomes) were 98.3% [95% confidence interval (CI) 95.8-100.0] and 99.6% (95% CI 97.6-100.0), respectively. Survival rate was 86.2%. For the 12 months post- vs. pre-implant, HFHs decreased by 62% (0.60 vs. 1.55 events/patient-year; hazard ratio 0.38, 95% CI 0.31-0.48; P < 0.0001). After 12 months, mean PAP decreased by 5.1 ± 7.4 mmHg, Kansas City Cardiomyopathy Questionnaire (KCCQ) overall/clinical summary scores increased from 47.0 ± 24.0/51.2 ± 24.8 to 60.5 ± 24.3/62.4 ± 24.1 (P < 0.0001), and the 9-item Patient Health Questionnaire sum score improved from 8.7 ± 5.9 to 6.3 ± 5.1 (P < 0.0001).

Conclusion: Haemodynamic-guided HF management proved feasible and safe in the health systems of Germany, The Netherlands, and Ireland. Physician-directed treatment modifications based on remotely obtained PAP values were associated with fewer HFH, sustainable PAP decreases, marked KCCQ improvements, and remission of depressive symptoms.
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http://dx.doi.org/10.1002/ejhf.1943DOI Listing
October 2020

Post-discharge prognosis of patients admitted to hospital for heart failure by world region, and national level of income and income disparity (REPORT-HF): a cohort study.

Lancet Glob Health 2020 03;8(3):e411-e422

Vanderbilt University Medical Center, Department of Emergency Medicine, Nashville, TN, USA. Electronic address:

Background: Heart failure is a global public health problem, affecting a large number of individuals from low-income and middle-income countries. REPORT-HF is, to our knowledge, the first prospective global registry collecting information on patient characteristics, management, and prognosis of acute heart failure using a single protocol. The aim of this study was to investigate differences in 1-year post-discharge mortality according to region, country income, and income inequality.

Methods: Patients were enrolled during hospitalisation for acute heart failure from 358 centres in 44 countries on six continents. We stratified countries according to a modified WHO regional classification (Latin America, North America, western Europe, eastern Europe, eastern Mediterranean and Africa, southeast Asia, and western Pacific), country income (low, middle, high) and income inequality (according to tertiles of Gini index). Risk factors were identified on the basis of expert opinion and knowledge of the literature.

Findings: Of 18 102 patients discharged, 3461 (20%) died within 1 year. Important predictors of 1-year mortality were old age, anaemia, chronic kidney disease, presence of valvular heart disease, left ventricular ejection fraction phenotype (heart failure with reduced ejection fraction [HFrEF] vs preserved ejection fraction [HFpEF]), and being on guideline-directed medical treatment (GDMT) at discharge (p<0·0001 for all). Patients from eastern Europe had the lowest 1-year mortality (16%) and patients from eastern Mediterranean and Africa (22%) and Latin America (22%) the highest. Patients from lower-income countries (ie, ≤US$3955 per capita; hazard ratio 1·58, 95% CI 1·41-1·78), or with greater income inequality (ie, from the highest Gini tertile; 1·25, 1·13-1·38) had a higher 1-year mortality compared with patients from regions with higher income (ie, >$12 235 per capita) or lower income inequality (ie, from the lowest Gini tertile). Compared with patients with HFrEF, patients with HFpEF had a lower 1-year mortality with little variation by income level (p for HFrEF vs HFpEF <0·0001).

Interpretation: Acute heart failure is associated with a high post-discharge mortality, particularly in patients with HFrEF from low-income regions with high income inequality. Regional differences exist in the proportion of eligible patients discharged on GDMT, which was strongly associated with mortality and might reflect lack of access to post-discharge care and prescribing of GDMT.

Funding: Novartis Pharma.
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http://dx.doi.org/10.1016/S2214-109X(20)30004-8DOI Listing
March 2020

[Diagnostics and treatment of chronic heart failure : Update 2020].

Herz 2020 Feb 3. Epub 2020 Feb 3.

Deutsches Zentrum für Herzinsuffizienz, Universität und Universitätsklinikum Würzburg, Haus A 15, Am Schwarzenberg 15, 97078, Würzburg, Deutschland.

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.
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http://dx.doi.org/10.1007/s00059-019-04877-zDOI Listing
February 2020

Syncopes and clinical outcome in heart failure: results from prospective clinical study data in Germany.

ESC Heart Fail 2020 06 30;7(3):942-952. Epub 2020 Jan 30.

Department of Internal Medicine and Cardiology, Charité - Universitätsmedizin Berlin, Campus Virchow Klinikum, Medizinische Klinik m. S. Kardiologie, Augustenburger Platz 1, 13353, Berlin, Germany.

Aims: Whereas syncopal episodes are a frequent complication of cardiovascular disorders, including heart failure (HF), little is known whether syncopes impact the prognosis of patients with HF. We aimed to assess the impact of a history of syncope (HoS) on overall and hospitalization-free survival of these patients.

Methods And Results: We pooled the data of prospective, nationwide, multicentre studies conducted within the framework of the German Competence Network for Heart Failure including 11 335 subjects. Excluding studies with follow-up periods <10 years, we assessed 5318 subjects. We excluded a study focusing on cardiac changes in patients with an HIV infection because of possible confounding factors and 849 patients due to either missing key parameters or missing follow-up data, resulting in 3594 eligible subjects, including 2130 patients with HF [1564 patients with heart failure with reduced ejection fraction (HFrEF), 314 patients with heart failure with mid-range ejection fraction, and 252 patients with heart failure with preserved ejection fraction (HFpEF)] and 1464 subjects without HF considered as controls. HoS was more frequent in the overall cohort of patients with HF compared with controls (P < 0.001)-mainly driven by the HFpEF subgroup (HFpEF vs. controls: 25.0% vs. 12.8%, P < 0.001). Of all the subjects, 14.6% reported a HoS. Patients with HFrEF in our pooled cohort showed more often syncopes than subjects without HF (15.0% vs. 12.8%, P = 0.082). Subjects with HoS showed worse overall survival [42.4% vs. 37.9%, hazard ratio (HR) = 1.21, 99% confidence interval (0.99, 1.46), P = 0.04] and less days alive out of hospital [HR = 1.39, 99% confidence interval (1.18, 1.64), P < 0.001] compared with all subjects without HoS. Patients with HFrEF with HoS died earlier [30.3% vs. 41.6%, HR = 1.40, 99% confidence interval (1.12, 1.74), P < 0.001] and lived fewer days out of hospital than those without HoS. We could not find these changes in mortality and hospital-free survival in the heart failure with mid-range ejection fraction and HFpEF cohorts. HoS represented a clinically high-risk profile within the HFrEF group-combining different risk factors. Further analyses showed that among patients with HFrEF with HoS, known cardiovascular risk factors (e.g. age, male sex, diabetes mellitus, and anaemia) were more prevalent. These constellations of the risk factors explained the effect of HoS in a multivariable Cox regression models.

Conclusions: In a large cohort of patients with HF, HoS was found to be a clinically and easily accessible predictor of both overall and hospitalization-free survival in patients with HFrEF and should thus routinely be assessed.
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http://dx.doi.org/10.1002/ehf2.12605DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7261586PMC
June 2020

Global Differences in Characteristics, Precipitants, and Initial Management of Patients Presenting With Acute Heart Failure.

JAMA Cardiol 2020 04;5(4):401-410

Department of Emergency Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.

Importance: Acute heart failure (AHF) precipitates millions of hospital admissions worldwide, but previous registries have been country or region specific.

Objective: To conduct a prospective contemporaneous comparison of AHF presentations, etiologic factors and precipitants, treatments, and in-hospital outcomes among global regions through the International Registry to Assess Medical Practice with Longitudinal Observation for Treatment of Heart Failure (REPORT-HF).

Design, Setting, And Participants: A total of 18 553 adults were enrolled during a hospitalization for AHF. Patients were recruited from the acute setting in Western Europe (WE), Eastern Europe (EE), Eastern Mediterranean and Africa (EMA), Southeast Asia (SEA), Western Pacific (WP), North America (NA), and Central and South America (CSA). Patients with AHF were approached for consent and excluded only if there was recent participation in a clinical trial. Patients were enrolled from July 23, 2014, to March 24, 2017. Statistical analysis was conducted from April 18 to June 29, 2018; revised analyses occurred between August 6 and 29, 2019.

Main Outcomes And Measures: Heart failure etiologic factors and precipitants, treatments, and in-hospital outcomes among global regions.

Results: A total of 18 553 patients were enrolled at 358 sites in 44 countries. The median age was 67.0 years (interquartile range [IQR], 57-77), 11 372 were men (61.3%), 9656 were white (52.0%), 5738 were Asian (30.9%), and 867 were black (4.7%). A history of HF was present in more than 50% of the patients and 40% were known to have a prior left-ventricular ejection fraction lower than 40%. Ischemia was a common AHF precipitant in SEA (596 of 2329 [25.6%]), WP (572 of 3354 [17.1%]), and EMA (364 of 2241 [16.2%]), whereas nonadherence to diet and medications was most common in NA (306 of 1592 [19.2%]). Median time to the first intravenous therapy was 3.0 (IQR, 1.4-5.6) hours in NA; no other region had a median time above 1.2 hours (P < .001). This treatment delay remained after adjusting for severity of illness (P < .001). Intravenous loop diuretics were the most common medication administered in the first 6 hours of AHF management across all regions (65.4%-89.9%). Despite similar initial blood pressure across all regions, inotropic agents were used approximately 3 times more often in SEA, WP, and EE (11.3%-13.5%) compared with NA and WE (3.1%-4.3%) (P < .001). Older age (odds ratio [OR], 1.0; 95% CI, 1.00-1.02), HF etiology (ischemia: OR, 1.65; 95% CI, 1.11-2.44; valvular: OR, 2.10; 95% CI, 1.36-3.25), creatinine level greater than 2.75 mg/dL (OR, 1.85; 95% CI, 0.71-2.40), and chest radiograph signs of congestion (OR, 2.03; 95% CI, 1.39-2.97) were all associated with increased in-hospital mortality. Similarly, younger age (OR, -0.04; 95% CI, -0.05 to -0.02), HF etiology (ischemia: OR, 0.77; 95% CI, 0.26-1.29; valvular: OR, 2.01; 95% CI, 1.38-2.65), creatinine level greater than 2.75 mg/dL (OR, 1.16; 95% CI, 0.31-2.00), and chest radiograph signs of congestion (OR, 1.02; 95% CI, 0.57-1.47) were all associated with increased in-hospital LOS.

Conclusions And Relevance: Data from REPORT-HF suggest that patients are similar across regions in many respects, but important differences in timing and type of treatment exist, identifying region-specific gaps in medical management that may be associated with patient outcomes.
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http://dx.doi.org/10.1001/jamacardio.2019.5108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6990673PMC
April 2020

The trialist's perspective: what do you need to prove for remote monitoring devices to be approved?

Eur Heart J Suppl 2019 Dec 31;21(Suppl M):M57-M60. Epub 2019 Dec 31.

Department of Medicine I- and Comprehensive Heart Failure Center, University Hospital and University of Würzburg, Am Schwarzenberg 15, 97078 Würzburg, Germany.

Due to contrasting results from clinical trials, remote monitoring devices have so far rarely been approved for heart failure (HF) management in European countries. Implementation of telemedicine into clinical practice of heart failure outpatient care is still limited. As part of an expert meeting on physiological monitoring in the complex mutimorbid HF patient, the needs to establish evidence supporting the use of devices in heart failure outpatient care was discussed according to a trialist's perspective. This document reflects the key points debated by a multidisciplinary panel of leading international experts on this topic.
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http://dx.doi.org/10.1093/eurheartj/suz214DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6937513PMC
December 2019

[Hyperkalemia - Pathophysiology, prognostic significance and treatment options].

Dtsch Med Wochenschr 2019 11 28;144(22):1576-1584. Epub 2019 Oct 28.

Medizinische Klinik I und Deutsches Zentrum für Herzinsuffizienz, Universität und Universitätsklinikum Würzburg, Würzburg, Deutschland.

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.
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http://dx.doi.org/10.1055/a-0762-8244DOI Listing
November 2019

Vitamin D deficiency in patients with diastolic dysfunction or heart failure with preserved ejection fraction.

ESC Heart Fail 2019 Apr 19;6(2):262-270. Epub 2019 Feb 19.

Department of Cardiology, University of Göttingen, Göttingen, Germany.

Aims: Vitamin D deficiency is prevalent in heart failure (HF), but its relevance in early stages of heart failure with preserved ejection fraction (HFpEF) is unknown. We tested the association of 25-hydroxyvitamin D [25(OH)D] serum levels with mortality, hospitalizations, cardiovascular risk factors, and echocardiographic parameters in patients with asymptomatic diastolic dysfunction (DD) or newly diagnosed HFpEF.

Methods And Results: We measured 25(OH)D serum levels in outpatients with risk factors for DD or history of HF derived from the DIAST-CHF study. Participants were comprehensively phenotyped including physical examination, echocardiography, and 6 min walk test and were followed up to 5 years. Quality of life was evaluated by the Short Form 36 (SF-36) questionnaire. We included 787 patients with available 25(OH)D levels. Median 25(OH)D levels were 13.1 ng/mL, mean E/e' medial was 13.2, and mean left ventricular ejection fraction was 59.1%. Only 9% (n = 73) showed a left ventricular ejection fraction <50%. Fifteen per cent (n = 119) of the recruited participants had symptomatic HFpEF. At baseline, participants with 25(OH)D levels in the lowest tertile (≤10.9 ng/L; n = 263) were older, more often symptomatic (oedema and fatigue, all P ≤ 0.002) and had worse cardiac [higher N-terminal pro-brain natriuretic peptide (NT-proBNP) and left atrial volume index, both P ≤ 0.023], renal (lower glomerular filtration rate, P = 0.012), metabolic (higher uric acid levels, P < 0.001), and functional (reduced exercise capacity, 6 min walk distance, and SF-36 physical functioning score, all P < 0.001) parameters. Increased NT-proBNP, uric acid, and left atrial volume index and decreased SF-36 physical functioning scores were independently associated with lower 25(OH)D levels. There was a higher risk for lower 25(OH)D levels in association with HF, DD, and atrial fibrillation (all P ≤ 0.004), which remained significant after adjusting for age. Lower 25(OH)D levels (per 10 ng/mL decrease) tended to be associated with higher 5 year mortality, P = 0.05, hazard ratio (HR) 1.55 [1.00; 2.42]. Furthermore, lower 25(OH)D levels (per 10 ng/mL decrease) were related to an increased rate of cardiovascular hospitalizations, P = 0.023, HR = 1.74 [1.08; 2.80], and remained significant after adjusting for age, P = 0.046, HR = 1.63 [1.01; 2.64], baseline NT-proBNP, P = 0.048, HR = 1.62 [1.01; 2.61], and other selected baseline characteristics and co-morbidities, P = 0.043, HR = 3.60 [1.04; 12.43].

Conclusions: Lower 25(OH)D levels were associated with reduced functional capacity in patients with DD or HFpEF and were significantly predictive for an increased rate of cardiovascular hospitalizations, also after adjusting for age, NT-proBNP, and selected baseline characteristics and co-morbidities.
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http://dx.doi.org/10.1002/ehf2.12413DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6437442PMC
April 2019

The omega-3 index in patients with heart failure: A prospective cohort study.

Prostaglandins Leukot Essent Fatty Acids 2019 01 28;140:34-41. Epub 2018 Nov 28.

Comprehensive Heart Failure Center, University and University Hospital Würzburg, Germany; Dept. of Internal Medicine I - Cardiology, University Hospital Würzburg, Germany. Electronic address:

Background: Epidemiologic studies on the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in heart failure are scarce, while one large intervention trial demonstrated a modest benefit.

Methods: This is a secondary analysis from the Interdisciplinary Network Heart Failure (INH) program. Patients hospitalized for systolic heart failure were enrolled and followed for 36 months. At baseline, whole blood samples from 899 patients were analyzed for fatty acid composition using a standardized analytical procedure (HS-Omega-3 Index®, O3-I). Associations of the O3-I with markers of heart failure severity, clinical characteristics, biomarkers, and mortality were analyzed.

Results: The mean O3-I was 3.7 ± 1.0%. Patient mean age was 68 ± 12 years (72% male, 43% in New York Heart Association (NYHA) class III or IV, mean LVEF 30 ± 8%). During follow-up 258 patients (28.7%) died. After adjustment for potential confounders, the O3-I showed weak associations with uncured malignancy, end-systolic diameter of the left atrium, left ventricular end-diastolic and end-systolic diameters, and blood lipids and other laboratory parameters (all p < 0.05), but not with NYHA class, left ventricular ejection fraction, and the underlying cause of heart failure. The O3-I did not predict the 3-year mortality risk.

Conclusions: Our results show a marked depletion of omega-3 fatty acids in patients hospitalized for decompensated heart failure (suggested target range 8-11%). Although the O3-I was associated with a panel of established risk indicators in heart failure, it did not predict mortality risk.

Clinical Trial Registration: www.controlled-trials.com; ISRCTN23325295.
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http://dx.doi.org/10.1016/j.plefa.2018.11.012DOI Listing
January 2019

Depression, Anxiety, and Cognitive Impairment : Comorbid Mental Health Disorders in Heart Failure.

Curr Heart Fail Rep 2018 12;15(6):398-410

Department of Internal Medicine I and Comprehensive Heart Failure Center, University and University Hospital of Würzburg, Am Schwarzenberg 15, 97078, Würzburg, Germany.

Purpose Of Review: Depression, anxiety, and cognitive impairment constitute established risk markers for incident cardiovascular disease (CVD) and are associated with impaired life expectancy and quality of life and high hospitalization rates and healthcare expenditure. This review summarizes current knowledge about mental health disorders in patients with CVD and heart failure (HF).

Recent Findings: Emerging evidence suggests various shared pathophysiological mechanisms between psychological comorbidities and CVD (e.g., systemic inflammation and autonomic dysfunction). Bi-directional interactions involving the central nervous and cardiovascular systems may help explain the rising prevalence of comorbid mood disorders with increasing CVD severity and support the concept of alternative pathophysiological mechanisms in the presence of severe somatic illness, making symptoms less responsive or unresponsive to psychotropic pharmacotherapy. Considering high prevalence and negative impact of psychological comorbidities in CVD and HF, routine care should integrate screening for these conditions. Multidisciplinary treatment approaches with active patient participation in disease management were shown to improve outcomes. However, better understanding of factors mediating the adverse prognostic effects of mood disorders is needed. This might enable more targeted treatment and possibly also facilitate better understanding of the pathophysiological mechanisms driving CVD.
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http://dx.doi.org/10.1007/s11897-018-0414-8DOI Listing
December 2018

Symptom patterns and clinical outcomes in women versus men with systolic heart failure and depression.

Clin Res Cardiol 2019 Mar 10;108(3):244-253. Epub 2018 Aug 10.

Department of Medicine I, Comprehensive Heart Failure Center, University Hospital and University of Würzburg, Am Schwarzenberg 15, 97078, Würzburg, Germany.

Background: Depression is more common in females than in males and is 3-5 times more prevalent in patients with heart failure (HF) than in the general population. The 9-item Patient Health Questionnaire (PHQ-9) is a validated depression screening instrument; higher sum-scores predict adverse clinical outcomes. Sex- and gender differences in PHQ-9 symptom profile, diagnostic and prognostic properties, and impact on health-related quality of life (HRQOL) have not been comprehensively studied in HF patients.

Methods And Results: This post hoc analysis from the Interdisciplinary Network Heart Failure program enrolled 852/1022 participants (67 ± 13 years, 28% female) who completed the PHQ-9 at hospital discharge after cardiac decompensation. All had a left ventricular ejection fraction ≤ 40%. Women had a higher mean PHQ-9 sum-score than men (8.4 ± 5.6 vs. 7.4 ± 5.5; p = 0.027), and higher proportions rated the following items ≥ 2 (i.e., present on ≥ 50% of days): 'feeling down, hopeless' (25.8 vs. 18.0%; p = 0.011); 'fatigue' (51.9 vs. 37.2%; p < 0.001); and 'trouble concentrating' (21.6 vs. 15.4%; p = 0.032). A PHQ-9 sum-score ≥ 10 predicted increased mortality in women [hazard ratio 1.91 (95% confidence interval 1.06-3.43); p = 0.030] and men [2.10 (1.43-3.09); p < 0.001] and was associated with worse HRQOL (p < 0.001 for all comparisons). Sum-scores ≥ 10 predicted higher re-hospitalization rates in men only [1.35 (1.08-1.69); p = 0.008].

Conclusions: Differences in several PHQ-9 items indicated sex- or gender-specific depression symptomatology in HF. For both sexes, HRQOL and survival were worse when PHQ-9 sum-score was ≥ 10, but higher sum-scores predicted higher re-hospitalization rates in men only. Considering these specific aspects might help optimize care strategies in HF.
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http://dx.doi.org/10.1007/s00392-018-1348-6DOI Listing
March 2019

The Comprehensive Heart Failure Centre in Würzburg, Germany.

Eur Heart J 2018 May;39(20):1757-1760

Professor of Medicine and Cardiology, Comprehensive Heart Failure Centre, Building A15, University & University Hospital Würzburg, Am Schwarzenberg 15, 97078 Würzburg, Tel: ++49-931-201-46502, Fax: ++49-931-201-646502, © SebastianZiegaus.

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http://dx.doi.org/10.1093/eurheartj/ehy202DOI Listing
May 2018

Safety and feasibility of pulmonary artery pressure-guided heart failure therapy: rationale and design of the prospective CardioMEMS Monitoring Study for Heart Failure (MEMS-HF).

Clin Res Cardiol 2018 Nov 19;107(11):991-1002. Epub 2018 May 19.

Saarland University Medical Center, Homburg, Germany.

Background: Wireless monitoring of pulmonary artery (PA) pressures with the CardioMEMS HF™ system is indicated in patients with New York Heart Association (NYHA) class III heart failure (HF). Randomized and observational trials have shown a reduction in HF-related hospitalizations and improved quality of life in patients using this device in the United States.

Objective: MEMS-HF is a prospective, non-randomized, open-label, multicenter study to characterize safety and feasibility of using remote PA pressure monitoring in a real-world setting in Germany, The Netherlands and Ireland.

Methods And Results: After informed consent, adult patients with NYHA class III HF and a recent HF-related hospitalization are evaluated for suitability for permanent implantation of a CardioMEMS™ sensor. Participation in MEMS-HF is open to qualifying subjects regardless of left ventricular ejection fraction (LVEF). Patients with reduced ejection fraction must be on stable guideline-directed pharmacotherapy as tolerated. The study will enroll 230 patients in approximately 35 centers. Expected duration is 36 months (24-month enrolment plus ≥ 12-month follow-up). Primary endpoints are freedom from device/system-related complications and freedom from pressure sensor failure at 12-month post-implant. Secondary endpoints include the annualized rate of HF-related hospitalization at 12 months versus the rate over the 12 months preceding implant, and health-related quality of life. Endpoints will be evaluated using data obtained after each subject's 12-month visit.

Conclusions: The MEMS-HF study will provide robust evidence on the clinical safety and feasibility of implementing haemodynamic monitoring as a novel disease management tool in routine out-patient care in selected European healthcare systems.

Trial Registration: ClinicalTrials.gov; NCT02693691.
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http://dx.doi.org/10.1007/s00392-018-1281-8DOI Listing
November 2018

Point-of-care B-type natriuretic peptide and portable echocardiography for assessment of patients with suspected heart failure in primary care: rationale and design of the three-part Handheld-BNP program and results of the training study.

Clin Res Cardiol 2018 Feb 15;107(2):95-107. Epub 2017 Nov 15.

Comprehensive Heart Failure Center, University and Department of Medicine I, Cardiology, University Hospital Würzburg, Am Schwarzenberg 15, 97078, Würzburg, Germany.

Background: Patients with suspected heart failure (HF) often present first to general practitioners (GPs). Timely and accurate HF diagnosis and reliable prognostic information have remained unmet goals in primary care, where patient evaluation often relies on clinical assessment only. The Handheld-BNP program investigates whether additional use of portable echocardiography (ECHO) and point-of-care determination of B-type natriuretic peptide (BNP) improves the accuracy of HF diagnosis and aids risk prediction in primary care.

Methods And Results: A research network was established between 2 academic centers, 2 × 6 cardiologists, and 2 × 24 GPs inexperienced with ECHO and BNP. The Training Study investigates the feasibility of implementing GP use and interpretation of ECHO and BNP. After training, competence is assessed using multiple-choice testing (pass mark: > 80% correct diagnoses). In the cluster-randomized four-arm Screening Study, each GP passes in random order through four study arms: clinical assessment (CA), CA + BNP, CA + ECHO, and CA + ECHO + BNP. Cardiologists' diagnoses serve as reference. Primary endpoint is the rate of correct GP diagnoses per study arm. In the Prognostic Follow-Up Study, patients are followed up centrally for 72 months. Forty-four GPs were successfully trained. With 225 ± 34 (75 ± 3) and 233 ± 28 (81 ± 7) min, respectively, total ECHO (BNP) training times were similar between centers I and II. Furthermore, training results did not differ between centers.

Conclusions: Standardized training of limited duration enabled GPs to use ECHO and BNP for HF diagnosis. The Handheld-BNP program will provide robust evaluation of the diagnostic effectiveness and prognostic value of these tools in primary care.

Trial Registration: http://www.controlled-trials.com (ISRCTN23325295).
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http://dx.doi.org/10.1007/s00392-017-1181-3DOI Listing
February 2018

Bromocriptine for the treatment of peripartum cardiomyopathy: a multicentre randomized study.

Eur Heart J 2017 Sep;38(35):2671-2679

Department of Cardiology and Angiology, Hannover Medical School, Carl-Neuberg-Str. 1. D-30625 Hannover, Germany.

Aims: An anti-angiogenic cleaved prolactin fragment is considered causal for peripartum cardiomyopathy (PPCM). Experimental and first clinical observations suggested beneficial effects of the prolactin release inhibitor bromocriptine in PPCM.

Methods And Results: In this multicentre trial, 63 PPCM patients with left ventricular ejection fraction (LVEF) ≤35% were randomly assigned to short-term (1W: bromocriptine, 2.5 mg, 7 days) or long-term bromocriptine treatment (8W: 5 mg for 2 weeks followed by 2.5 mg for 6 weeks) in addition to standard heart failure therapy. Primary end point was LVEF change (delta) from baseline to 6 months assessed by magnetic resonance imaging. Bromocriptine was well tolerated. Left ventricular ejection fraction increased from 28 ± 10% to 49 ± 12% with a delta-LVEF of + 21 ± 11% in the 1W-group, and from 27 ± 10% to 51 ± 10% with a delta-LVEF of + 24 ± 11% in the 8W-group (delta-LVEF: P = 0.381). Full-recovery (LVEF ≥ 50%) was present in 52% of the 1W- and in 68% of the 8W-group with no differences in secondary end points between both groups (hospitalizations for heart failure: 1W: 9.7% vs. 8W: 6.5%, P = 0.651). The risk within the 8W-group to fail full-recovery after 6 months tended to be lower. No patient in the study needed heart transplantation, LV assist device or died.

Conclusion: Bromocriptine treatment was associated with high rate of full LV-recovery and low morbidity and mortality in PPCM patients compared with other PPCM cohorts not treated with bromocriptine. No significant differences were observed between 1W and 8W treatment suggesting that 1-week addition of bromocriptine to standard heart failure treatment is already beneficial with a trend for better full-recovery in the 8W group.

Clinical Trial Registration: ClinicalTrials.gov, study number: NCT00998556.
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http://dx.doi.org/10.1093/eurheartj/ehx355DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5837241PMC
September 2017

Prognostic potential of midregional pro-adrenomedullin following decompensation for systolic heart failure: comparison with cardiac natriuretic peptides.

Eur J Heart Fail 2017 09 17;19(9):1166-1175. Epub 2017 May 17.

Comprehensive Heart Failure Center, University and University Hospital Würzburg, Würzburg, Germany.

Aims: Whereas guidelines recommend the routine use of natriuretic peptides (NPs) in heart failure (HF) care, the clinical relevance and prognostic potential of midregional pro-adrenomedullin (MR-proADM) is less well established. We aimed to compare the prognostic potential of MR-proADM after acute decompensation for systolic HF with that of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and midregional pro-atrial NP (MR-proANP), to investigate the significance of high/rising MR-proADM, and to evaluate the incremental prognostic yield of repeat measurements.

Methods And Results: The Interdisciplinary Network Heart Failure (INH) programme enrolled patients hospitalized for acute systolic HF and followed them for 18 months (100% complete). Of 1022 INH participants, 917 (68 ± 12 years, 28% female) who had biomaterials available were enrolled. High MR-proADM was associated with more impaired left ventricular function, higher comorbidity burden, lower doses of HF medications, and lower likelihood of left ventricular reverse remodelling. Compared with NPs, MR-proADM had superior prognostic significance (concordance index 0.72 for all-cause mortality), improved Cox regression models including NPs (P < 0.001), and was the only biomarker also predicting non-cardiac death (hazard ratio 1.8 vs. 1.0). In the setting of low NPs, patients with high MR-proADM experienced non-cardiac death more often. Six month MR-proADM enhanced models including baseline MR-proADM (P < 0.001) for prediction of all-cause death (net reclassification index: 0.48, 95% confidence interval 0.19-0.78).

Conclusion: MR-proADM was found to correlate with the global disease burden in HF and proved a potent prognostic indicator, capturing the risk for both cardiac and non-cardiac death. Serial MR-proADM measurements further enhanced risk assessment, thus facilitating substantial reclassification.
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http://dx.doi.org/10.1002/ejhf.859DOI Listing
September 2017

Prevalence and clinical impact of iron deficiency and anaemia among outpatients with chronic heart failure: The PrEP Registry.

Clin Res Cardiol 2017 Jun 22;106(6):436-443. Epub 2017 Feb 22.

Department of Medicine I, Comprehensive Heart Failure Center, University Hospital Würzburg, University of Würzburg, Würzburg, Germany.

Background: Iron deficiency (ID) and anaemia are common in heart failure (HF). The prospective, observational PReP registry (Prävalenz des Eisenmangels bei Patienten mit Herzinsuffizienz) studied prevalence and clinical impact of ID and anaemia in HF outpatients attending cardiology practices in Germany.

Methods And Results: A total of 42 practices enrolled consecutive patients with chronic HF [left ventricular ejection fraction (LVEF) ≤45%]. ID was defined as serum ferritin <100 µg/l, or serum ferritin ≥100 µg/l/<300 µg/l plus transferrin saturation <20%, and anaemia as haemoglobin <13 g/dl (12 g/dl) in men (women). Exercise capacity was assessed using spiroergometry (69.4%) or 6-min walk test (30.4%). Amongst 1198 PReP-participants [69.0  ± 10.6 years, 25.3% female, New York Heart Association (NYHA) class 2.4  ± 0.5, LVEF 35.3 ± 7.2%], ID was found in 42.5% (previously unknown in all), and anaemia in 18.9% (previously known in 4.8%). ID was associated with female gender, lower body weight and haemoglobin, higher NYHA class and natriuretic peptide (NP) levels (all p < 0.05). ID was also more common in anaemic than non-anaemic patients (p < 0.0001), and 9.8% of PrEP-participants had both, ID and anaemia. On spiroergometry, ID independently predicted maximum exercise capacity even after multivariable adjustment, including anaemia (p = 0.0004). In all PrEP-participants, ID predicted reduced physical performance (adjusted for age, gender, anaemia, serum creatinine, C-reactive protein, LVEF, and NP level).

Conclusions: Despite high prevalence, ID was previously unknown in all PrEP-participants, and anaemia was often unappreciated. Given the clinical relevance, treatability, and independent association with reduced physical performance, ID should be considered more in real-world ambulatory healthcare settings and ID-screening be advocated to cardiologists in such populations.
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http://dx.doi.org/10.1007/s00392-016-1073-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5442200PMC
June 2017

Prognostic significance of serial high-sensitivity troponin I measurements following acute cardiac decompensation-correlation with longer-term clinical outcomes and reverse remodelling.

Int J Cardiol 2017 Apr 5;232:199-207. Epub 2017 Jan 5.

Department of Internal Medicine I, University Hospital Würzburg, Germany and; Comprehensive Heart Failure Center, University Hospital Würzburg, Germany. Electronic address:

Background: This study investigated the correlation of levels of and changes in serial high-sensitivity cardiac troponin I (hsTnI) with subsequent clinical event rates and changes in cardiac morphology and function in patients hospitalized for acutely decompensated heart failure (ADHF).

Methods And Results: HsTnI levels were determined in 875 ADHF patients before discharge from hospital (baseline cohort) and clinical outcomes assessed after 180days. HsTnI was re-measured at 180days in 456/875 patients (follow-up cohort). Follow-up hsTnI values were grouped according to baseline hsTnI tertiles; echocardiographic changes from 0-180days and event rates from 180-540days were assessed in these subgroups. At baseline and 180-day follow-up, hsTnI levels were elevated (>0.06ng/mL) in 322/875 (37%) and 68/456 (15%) patients, respectively. At 180days, 85/875 patients (9.7%) had died (cardiovascular causes: 56/875 [6.4%]). Hazard ratios (HR) and 95% confidence intervals (CI) for all-cause and cardiovascular mortality (per two-fold hsTnI increase) were 1.2 (1.0-1.3; p=0.004) and 1.2 (1.1-1.4; p=0.001), respectively. In the follow-up cohort, 35/456 patients (7.7%) died between days 180 and 540 (cardiovascular death: 20/456, 4.4%). HsTnI was a significant predictor of cardiovascular re-hospitalization within 180-540days (HR 1.2, 95% CI 1.0-1.4; p=0.028). Patients with hsTnI in the lowest tertile at follow-up had more frequent and more pronounced reverse cardiac remodelling on echocardiography.

Conclusions: Elevated baseline hsTnI was common and associated with adverse clinical outcomes. Changes in hsTnI from baseline to 180-day follow-up predicted longer-term risk. Low or decreasing hsTnI was associated with better reverse cardiac remodelling and more favourable long-term outcomes. CLINICAL TRIAL REGISTRATION URL: http://www.controlled-trials.com. Unique identifier: ISRCTN23325295.
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http://dx.doi.org/10.1016/j.ijcard.2017.01.021DOI Listing
April 2017

A functional variant of the neuropeptide S receptor-1 gene modulates clinical outcomes and healthcare utilization in patients with systolic heart failure: results from the Interdisciplinary Network Heart Failure (INH) Study.

Eur J Heart Fail 2017 03 18;19(3):314-323. Epub 2016 Dec 18.

Comprehensive Heart Failure Center, University Hospital and University of Würzburg, Würzburg, Germany.

Aims: Psychopathologies may occur in heart failure (HF) and can be associated with adverse outcomes. Amongst neuropeptide S receptor gene functional sequence variants, the T-allele [asparagine(107)isoleucine, NPSR1 rs324981] has been identified as a risk factor for increased anxiety/overinterpretation of bodily symptoms. We investigated all-cause death and re-hospitalization (composite primary endpoint, CPEP) and healthcare utilization in patients hospitalized for decompensated systolic HF with the TT vs. the AT/AA genotype.

Methods And Results: Participants in the Interdisciplinary Network Heart Failure programme were eligible if consenting to genetic testing (n = 924) and randomization to usual care (UC, n = 464) or nurse-co-ordinated disease management (DM, n = 460). Follow-up was 180 days (100% complete). Compared with AT/AA carriers (n = 726), TT genotype carriers (n = 198) had more CPEP events [47% vs. 39%, hazard ratio (HR) 1.27, 95% confidence interval (CI) 1.01-1.61, P = 0.044] and were more frequently re-hospitalized (43% vs. 35%, HR 1.31, 95% CI 1.02-1.67, P = 0.033); mortality rate was similar in both groups (HR 1.11, 95% CI 0.68-1.81, P = 0.664). In subjects undergoing DM, CPEP and re-hospitalization occurred more often in TT (51% and 47%) than in AT/AA carriers (36% and 33%; HR 2.14, 95% CI 1.44-3.19, and HR 2.29, 95% CI 1.52-3.44, genotype/treatment interaction both P = 0.007). Furthermore, TT genotype carriers undergoing DM visited cardiologists and other specialists more often than AT/AA carriers (P = 0.009 and P = 0.005). With UC, event rates did not differ between genotype subgroups.

Conclusion: We identified a psychogenetic determinant of clinical outcomes and healthcare utilization after acute HF, which was modulated by the type of care. Future investigations need to clarify whether NPSR1 genotyping might further enhance the concept of 'personalized' medicine in HF.

Trial Registration: ISRCTN23325295.
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http://dx.doi.org/10.1002/ejhf.706DOI Listing
March 2017

Frequency and prognostic impact of mid-expiratory flow reduction in stable patients six months after hospitalisation for heart failure with reduced ejection fraction.

Int J Cardiol 2017 Jan 28;227:727-733. Epub 2016 Oct 28.

University Hospital Würzburg and University of Würzburg, Comprehensive Heart Failure Center, Würzburg, Germany; University Hospital Würzburg, Department of Internal Medicine I, Würzburg, Germany; Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.

Aim: This study investigates the prevalence and prognostic impact of central and small airways obstruction (CAO and SAO) in patients with stable heart failure (HF).

Methods & Results: Spirometry was performed in 585 outpatients (mean age 65±12years, 75% male) six months after hospitalisation for acute decompensation secondary to HF with ejection fraction <40%. We assessed forced expiratory volume in the first second (FEV1), forced vital capacity (FVC) and mid-expiratory flow (MEF) at 50% of FVC. CAO was defined by FEV1/FVC <0.7. SAO was defined by FEV1/FVC ≥0.7 plus MEF <60% of predicted value. CAO and SAO were excluded in 359 patients (61% of all). MEF <60% predicted was found in 226 patients (39% of all), among those 88 with CAO (15% of all) and 138 (24% of all) with SAO. During a twelve month follow-up, 42 patients (7.2%) died. Mortality rates of patients with CAO and SAO were comparable (12.5% and 10.9%, respectively, p=0.74), and both higher than in patients without airways obstruction (4.5%, both p<0.01). In univariable Cox regression analysis, both CAO and SAO were associated with 2-fold increased all-cause mortality risk (hazard ratios [95% confidence intervals]: 2.78 [1.33-6.19], p=0.007 and 2.51 [1.24-5.08], p=0.010, respectively). Adjustment for determinants of CAO and SAO, prognostic markers of heart failure and comorbidities attenuated the association of mortality with CAO but not with SAO.

Conclusions: SAO is more common than CAO and indicates an increased mortality risk in HF. Thus, reduced MEF may be a feature of patients at risk and merits special attention in HF management.
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http://dx.doi.org/10.1016/j.ijcard.2016.10.071DOI Listing
January 2017

Escitalopram and Outcomes Among Patients With Depression and Heart Failure-Reply.

JAMA 2016 Oct;316(14):1494-1495

Department of Medicine I (Cardiology), University Hospital Würzburg, Würzburg, Germany.

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http://dx.doi.org/10.1001/jama.2016.13888DOI Listing
October 2016

[Depression and heart failure - a dangerous combination].

Dtsch Med Wochenschr 2016 Aug 24;141(17):1222-7. Epub 2016 Aug 24.

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.
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http://dx.doi.org/10.1055/s-0042-108681DOI Listing
August 2016
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