[The importance of health-related quality of life at baseline in predicting event-free survival in patients with a cardiovascular risk profile]. / Die Bedeutung gesundheitsbezogener Lebensqualität für die Vorhersage des ereignisfreien Überlebens bei Patienten mit kardiovaskulärem Risikoprofil.

The importance of health-related quality of life at baseline in predicting event-free survival in patients with a cardiovascular risk profile Background: Manifest heart failure impairs all dimensions of health-related quality of life (HRQOL). However, the role of HRQOL in patients with risk factors for the development of heart failure with preserved ejection fraction (HFpEF) is only poorly understood. Objective: In this post-hoc analysis of the DIAST-CHF observational study, we tested the hypothesis whether a lower HRQOL at baseline is prognostically associated with an increase in cardiovascular events during follow-up in elderly patients with a cardiovascular risk profile. Methods: The DIAST-CHF observational study enrolled 1.937 patients aged 50 to 85 years with at least one risk factor for the development of HFpEF. HRQOL was assessed using the German version of the Short-Form-36 (SF-36) Health Survey. Results: Patients with comorbid chronic diseases, including manifest heart failure, coronary artery disease, atrial fibrillation, diabetes mellitus and depression, rated their health status (Self-rated health, SRH) significantly worse than those without comorbidities. Older age, higher body-mass index and elevated serum amino-terminal pro-brain natriuretic peptide (NTproBNP) concentration as well as lower left ventricular ejection fraction (LVEF) and impaired 6-minute walk test showed significant relationships to SRH. Kaplan-Meier analyses and Cox regression models using quartiles of either SF-36 subscales "Physical Component Summary" (PCS) or SRH groups demonstrated significant differences in event-free survival (all-cause death or cardiovascular hospitalization), whereas no difference in event-free survival was observed among the quartiles of the SF-36 subscale "Mental Component Summary" (MCS). Conclusion: In patients with risk factors for the development of HFpEF, HRQOL questionnaires are suitable instruments for risk stratification if they capture physical impairments, rather than psychological limitations of quality of life.

Reliability of peripheral arterial tonometry in patients with heart failure, diabetic nephropathy and arterial hypertension.

Endothelial dysfunction plays a major role in cardiovascular diseases and pulse amplitude tonometry (PAT) offers a non-invasive way to assess endothelial dysfunction. However, data about the reliability of PAT in cardiovascular patient populations are scarce. Thus, we evaluated the test-retest reliability of PAT using the natural logarithmic transformed reactive hyperaemia index (LnRHI). Our cohort consisted of 91 patients (mean age: 65±9.7 years, 32% female), who were divided into four groups: those with heart failure with preserved ejection fraction (HFpEF) ( n=25), heart failure with reduced ejection fraction (HFrEF) ( n=22), diabetic nephropathy ( n=21), and arterial hypertension ( n=23). All subjects underwent two separate PAT measurements at a median interval of 7 days (range 4-14 days). LnRHI derived by PAT showed good reliability in subjects with diabetic nephropathy (intra-class correlation (ICC) = 0.863) and satisfactory reliability in patients with both HFpEF (ICC = 0.557) and HFrEF (ICC = 0.576). However, in subjects with arterial hypertension, reliability was poor (ICC = 0.125). We demonstrated that PAT is a reliable technique to assess endothelial dysfunction in adults with diabetic nephropathy, HFpEF or HFrEF. However, in subjects with arterial hypertension, we did not find sufficient reliability, which can possibly be attributed to variations in heart rate and the respective time of the assessments. Clinical Trial Registration Identifier: NCT02299960.

CMR-based cardiac phenotyping in different forms of heart failure.

Heart failure (HF) is a heterogenous disease requiring precise diagnostics and knowledge of pathophysiological processes. Since structural and functional imaging data are scarce we hypothesized that cardiac magnetic resonance (CMR)-based analyses would provide accurate characterization and mechanistic insights into different HF groups comprising preserved (HFpEF), mid-range (HFmrEF) and reduced ejection fraction (HFrEF). 22 HFpEF, 17 HFmrEF and 15 HFrEF patients as well as 19 healthy volunteers were included. CMR image assessment contained left atrial (LA) and left ventricular (LV) volumetric evaluation as well as left atrioventricular coupling index (LACI). Furthermore, CMR feature-tracking included LV and LA strain in terms of reservoir (Es), conduit (Ee) and active boosterpump (Ea) function. CMR-based tissue characterization comprised T1 mapping as well as late-gadolinium enhancement (LGE) analyses. HFpEF patients showed predominant atrial impairment (Es 20.8%vs.25.4%, p = 0.02 and Ee 8.3%vs.13.5%, p = 0.001) and increased LACI compared to healthy controls (14.5%vs.23.3%, p = 0.004). Patients with HFmrEF showed LV enlargement but mostly preserved LA function with a compensatory increase in LA boosterpump (LA Ea: 15.0%, p = 0.049). In HFrEF LA and LV functional impairment was documented (Es: 14.2%, Ee: 5.4% p < 0.001 respectively; Ea: 8.8%, p = 0.02). This was paralleled by non-invasively assessed progressive fibrosis (T1 mapping and LGE; HFrEF > HFmrEF > HFpEF). CMR-imaging reveals insights into HF phenotypes with mainly atrial affection in HFpEF, ventricular affection with atrial compensation in HFmrEF and global impairment in HFrEF paralleled by progressive LV fibrosis. These data suggest a necessity for a personalized HF management based on imaging findings for future optimized patient management.

Reduced dynamic changes in pulmonary artery compliance during isometric handgrip exercise in patients with heart failure.

Exercise intolerance is a debilitating symptom in heart failure (HF), adversely affecting both quality of life and long-term prognosis. Emerging evidence suggests that pulmonary artery (PA) compliance may be a contributing factor. This study aims to non-invasively assess PA compliance and its dynamic properties during isometric handgrip (HG) exercise in HF patients and healthy controls, using cardiovascular magnetic resonance (CMR). We prospectively enrolled 36 subjects, comprising 17 HF patients (NYHA class II and III) and 19 healthy controls. Participants performed an HG test, and we assessed changes in PA compliance and hemodynamic flow parameters using advanced CMR techniques. We also explored the relationship between CMR-derived PA compliance metrics and established clinical indicators, ensuring the validity of our findings through intra- and interobserver agreements. HF patients had significantly lower resting PA compliance compared to controls (28.9% vs. 50.1%, p < 0.01). During HG exercise, HF patients exhibited a dampened adaptability in PA compliance. Hemodynamic responses, including heart rate and blood pressure, were not significantly different between the groups. Further analyses revealed a significant correlation between changes in PA compliance and functional capacity, and an inverse relationship with NYHA class. Our study demonstrates a marked difference in PA vascular responses during HG exercise between HF patients and healthy controls. The compromised adaptability in PA compliance in HF patients is correlated with diminished functional capacity. These findings have significant clinical implications and may guide future interventional strategies in HF management.

Heart failure with preserved ejection fraction: diagnosis, risk assessment, and treatment.

The aetiology of heart failure with preserved ejection fraction (HFpEF) is heterogenous and overlaps with that of several comorbidities like atrial fibrillation, diabetes mellitus, chronic kidney disease, valvular heart disease, iron deficiency, or sarcopenia. The diagnosis of HFpEF involves evaluating cardiac dysfunction through imaging techniques and assessing increased left ventricular filling pressure, which can be measured directly or estimated through various proxies including natriuretic peptides. To better narrow down the differential diagnosis of HFpEF, European and American heart failure guidelines advocate the use of different algorithms including comorbidities that require diagnosis and rigorous treatment during the evaluation process. Therapeutic recommendations differ between guidelines. Whilst sodium glucose transporter 2 inhibitors have a solid evidence base, the recommendations differ with regard to the use of inhibitors of the renin-angiotensin-aldosterone axis. Unless indicated for specific comorbidities, the use of beta-blockers should be discouraged in HFpEF. The aim of this article is to provide an overview of the current state of the art in HFpEF diagnosis, clinical evaluation, and treatment.

A simplified approach to discriminate between healthy subjects and patients with heart failure using cardiac magnetic resonance myocardial deformation imaging.

Aims: Left ventricular global longitudinal strain (LV-GLS) shows promise as a marker to detect early heart failure (HF). This study sought to (i) establish cardiac magnetic resonance imaging (CMR)-derived LV-GLS cut-offs to differentiate healthy from HF for both acquisition-based and post-processing techniques, (ii) assess agreement, and (iii) provide a method to convert LV-GLS between both techniques. Methods and results: A secondary analysis of a prospective study enrolling healthy subjects (n = 19) and HF patients (n = 56) was conducted. LV-GLS was measured using fast strain-encoded imaging (fSENC) and feature tracking (FT). Receiver operating characteristic (ROC) analyses were performed to derive and evaluate LV-GLS cut-offs discriminating between healthy, HF with mild deformation impairment (DI), and HF with severe DI. Linear regression and Bland-Altman analyses assessed agreement. Cut-offs discriminating between healthy and HF were identified at -19.3% and -15.1% for fSENC and FT, respectively. Cut-offs of -15.8% (fSENC) and -10.8% (FT) further distinguished mild from severe DI. No significant differences in area under ROC curve were identified between fSENC and FT. Bland-Altman analysis revealed a bias of -4.01%, 95% CI -4.42, -3.50 for FT, considering fSENC as reference. Linear regression suggested a factor of 0.76 to rescale fSENC-derived LV-GLS to FT. Using this factor on fSENC-derived cut-offs yielded rescaled FT LV-GLS cut-offs of -14.7% (healthy vs. HF) and -12% (mild vs. severe DI). Conclusion: LV-GLS distinguishes healthy from HF with high accuracy. Each measurement technique requires distinct cut-offs, but rescaling factors facilitate conversion. An FT-based LV-GLS ≥ -15% simplifies HF detection in clinical routine.

Reduced functional capacity is associated with the proportion of impaired myocardial deformation assessed in heart failure patients by CMR.

Aims: Heart failure (HF) does not only reduce the life expectancy in patients, but their life is also often limited by HF symptoms leading to a reduced quality of life (QoL) and a diminished exercise capacity. Novel parameters in cardiac imaging, including both global and regional myocardial strain imaging, promise to contribute to better patient characterization and ultimately to better patient management. However, many of these methods are not part of clinical routine yet, their associations with clinical parameters have been poorly studied. An imaging parameters that also indicate the clinical symptom burden of HF patients would make cardiac imaging more robust toward incomplete clinical information and support the clinical decision process. Methods and results: This prospective study conducted at two centers in Germany between 2017 and 2018 enrolled stable outpatient subjects with HF [n = 56, including HF with reduced ejection fraction (HFrEF), HF with mid-range ejection fraction (HFmrEF), and HF with preserved ejection fraction (HFpEF)] and a control cohort (n = 19). Parameters assessed included measures for external myocardial function, for example, cardiac index and myocardial deformation measurements by cardiovascular magnetic resonance imaging, left ventricular global longitudinal strain (GLS), the global circumferential strain (GCS), and the regional distribution of segment deformation within the LV myocardium, as well as basic phenotypical characteristics including the Minnesota Living with Heart Failure Questionnaire (MLHFQ) and the 6-minute walk test (6MWT). If less than 80% of the LV segments are preserved in their deformation capacity the functional capacity by 6MWT (6 minutes walking distance: MyoHealth ≥ 80%: 579.8 ± 177.6 m; MyoHealth 60-<80%: 401.3 ± 121.7 m; MyoHealth 40-<60%: 456.4 ± 68.9 m; MyoHealth < 40%: 397.6 ± 125.9 m, overall p-value: 0.03) as well as the symptom burden are significantly impaired (NYHA class: MyoHealth ≥ 80%: 0.6 ± 1.1 m; MyoHealth 60-<80%: 1.7 ± 1.2 m; MyoHealth 40-<60%: 1.8 ± 0.7 m; MyoHealth < 40%: 2.4 ± 0.5 m; overall p-value < 0.01). Differences were also observed in the perceived exertion assessed by on the Borg scale (MyoHealth ≥ 80%: 8.2 ± 2.3 m; MyoHealth 60-<80%: 10.4 ± 3.2 m; MyoHealth 40-<60%: 9.8 ± 2.1 m; MyoHealth < 40%: 11.0 ± 2.9 m; overall p-value: 0.20) as well as quality of life measures (MLHFQ; MyoHealth ≥ 80%: 7.5 ± 12.4 m; MyoHealth 60-<80%: 23.4 ± 23.4 m; MyoHealth 40-<60%: 20.5 ± 21.2 m; MyoHealth < 40%: 27.4 ± 24.4 m; overall p-value: 0.15)-while these differences were not significant. Conclusion: The share of LV segments with preserved myocardial contraction promises to discriminate between symptomatic and asymptomatic subjects based on the imaging findings, even when the LV ejection fraction is preserved. This finding is promising to make imaging studies more robust toward incomplete clinical information.

Half-Dose versus Single-Dose Gadobutrol for Extracellular Volume Measurements in Cardiac Magnetic Resonance.

BACKGROUND: Cardiac magnetic resonance (CMR) imaging with gadolinium-based contrast agents offers unique non-invasive insights into cardiac tissue composition. Myocardial extracellular volume (ECV) has evolved as an objective and robust parameter with broad diagnostic and prognostic implications. For the gadolinium compound gadobutrol, the recommended dose for cardiac imaging, including ECV measurements, is 0.1 mmol/kg (single dose). This dose was optimized for late enhancement imaging, a measure of focal fibrosis. Whether a lower dose is sufficient for ECV measurements is unknown. We aim to evaluate the accuracy of ECV measurements using a half dose of 0.05 mmol/kg gadobutrol compared to the standard single dose of 0.1 mmol/kg. METHODS AND RESULTS: From a contemporary trial (NCT04747366, registered 10 February 2021), a total of 25 examinations with available T1 mapping before and after 0.05 and 0.1 mmol/kg gadobutrol were analyzed. ECV values were calculated automatically from pre- and post-contrast T1 relaxation times. T1 and ECV Measurements were performed in the midventricular septum. ECV values after 0.05 and 0.1 mmol/kg gadobutrol were correlated (R2 = 0.920, p < 0.001). ECV values after 0.05 mmol/kg had a bias of +0.9% (95%-CI [0.4; 1.4], p = 0.002) compared to 0.1 mmol/kg gadobutrol, with limits of agreement from -1.5 to 3.3%. CONCLUSIONS: CMR with a half dose of 0.05 mmol/kg gadobutrol overestimated ECV by 0.9% compared with a full dose of 0.1 mmol/kg, necessitating adjustment of normal values when using half-dose ECV imaging.

Moving toward gender equity in the cardiology and cardiovascular research workforce in Germany: a report from the German Cardiac Society.

Aims: Although the share of women in cardiology in Germany is growing steadily, this does not translate into leadership positions. Medical societies play a crucial role in shaping the national and international medical and scientific environment. The German Cardiac Society (DGK) aims to serve the public discourse on gender-equity by systematic analysis of data on gender representation within the society and in Germany. Methods and results: We present gender disaggregated data collection of members, official organs, working groups, scientific meetings, as well as awards of the DGK based on anonymized exports from the DGK office as well as on data gathered from the DGK web page. From 2000 to 2020, the overall number of DGK members as well as the share of women increased (12.5% to 25.3%). In 2021, the share of women ranged from 40% to 50% in earlier career stages but was substantially lower at senior levels (23.9% of consulting/attending physicians, 7.1% of physicians-in-chief, 3.4% of directors). The share of women serving in DGK working groups had gained overall proportionality, but nuclei and speaker positions were largely held by men. Boards and project groups were predominantly represented by men as well. At the DGK-led scientific meetings, women contributed more often in junior relative to (invited) senior roles. Conclusion: Increasing numbers of women in cardiology and in the DGK over the past 20 years did not translate into the respective increase in representation of women in leadership positions. There is an urgent need to identify and, more importantly, to overcome barriers towards gender equity. Transparent presentation of society-related data is the first step for future targeted actions in this regard.

Quantification of myocardial extracellular volume without blood sampling.

Aims: Cardiac magnetic resonance (CMR) T1 relaxation time mapping is an established technique primarily used to identify diffuse interstitial fibrosis and oedema. The myocardial extracellular volume (ECV) can be calculated from pre- and post-contrast T1 relaxation times and is a reproducible parametric index of the proportion of volume occupied by non-cardiomyocyte components in myocardial tissue. The conventional calculation of the ECV requires blood sampling to measure the haematocrit (HCT). Given the high variability of the HCT, the blood collection is recommended within 24 h of the CMR scan, limiting its applicability and posing a barrier to the clinical routine use of ECV measurements. In recent years, several research groups have proposed a method to determine the ECV by CMR without blood sampling. This is based on the inverse relationship between the T1 relaxation rate (R1) of blood and the HCT. Consequently, a 'synthetic' HCT could be estimated from the native blood R1, avoiding blood sampling. Methods and results: We performed a review and meta-analysis of published studies on synthetic ECV, as well as a secondary analysis of previously published data to examine the effect of the chosen regression modell on bias. While, overall, a good correlation and little bias between synthetic and conventional ECV were found in these studies, questions regarding its accuracy remain. Conclusion: Synthetic HCT and ECV can provide a 'non-invasive' quantitative measurement of the myocardium's extracellular space when timely HCT measurements are not available and large alterations in ECV are expected, such as in cardiac amyloidosis. Due to the dependency of T1 relaxation times on the local setup, calculation of local formulas using linear regression is recommended, which can be easily performed using available data.

Noninvasive evaluation of pulmonary artery stiffness in heart failure patients via cardiovascular magnetic resonance.

Heart failure (HF) presents manifestations in both cardiac and vascular abnormalities. Pulmonary hypertension (PH) is prevalent in up 50% of HF patients. While pulmonary arterial hypertension (PAH) is closely associated with pulmonary artery (PA) stiffness, the association of HF caused, post-capillary PH and PA stiffness is unknown. We aimed to assess and compare PA stiffness and blood flow hemodynamics noninvasively across HF entities and control subjects without HF using CMR. We analyzed data of a prospectively conducted study with 74 adults, including 55 patients with HF across the spectrum (20 HF with preserved ejection fraction [HFpEF], 18 HF with mildly-reduced ejection fraction [HFmrEF] and 17 HF with reduced ejection fraction [HFrEF]) as well as 19 control subjects without HF. PA stiffness was defined as reduced vascular compliance, indicated primarily by the relative area change (RAC), altered flow hemodynamics were detected by increased flow velocities, mainly by pulse wave velocity (PWV). Correlations between the variables were explored using correlation and linear regression analysis. PA stiffness was significantly increased in HF patients compared to controls (RAC 30.92 ± 8.47 vs. 50.08 ± 9.08%, p < 0.001). PA blood flow parameters were significantly altered in HF patients (PWV 3.03 ± 0.53 vs. 2.11 ± 0.48, p < 0.001). These results were consistent in all three HF groups (HFrEF, HFmrEF and HFpEF) compared to the control group. Furthermore, PA stiffness was associated with higher NT-proBNP levels and a reduced functional status. PA stiffness can be assessed non-invasively by CMR. PA stiffness is increased in HFrEF, HFmrEF and HFpEF patients when compared to control subjects.Trial registration The study was registered at the German Clinical Trials Register (DRKS, registration number: DRKS00015615).

Virtual cardiovascular magnetic resonance training proves feasible and effective: survey data from international participants of the CMR Academy Berlin, Germany.

Aims: This study aims to evaluate the success of the cardiovascular magnetic resonance (CMR) imaging Academy Berlin's transition from in-person to online CMR imaging training during the global pandemic 2020 and to gather recommendations for future courses. Methods and results: We conducted an online survey targeting CMR course participants from both the pre-pandemic, in-person era and the pandemic, online era of the CMR Academy Berlin. The survey primarily used Likert-type questions to assess participants' experiences and preferences.A total of 61 out of 158 invited participants (38.61%) completed the survey, with 31 (50.82%) being in-person alumni and 30 (49.18%) being online alumni. Both in-person [83.87% (26/31)] and online [83.33% (25/30)] participants rated the course as either 'very good' or 'excellent', and both groups found the course either 'extremely helpful' or 'very helpful'. However, a higher percentage of in-person participants [96.77% (30/31)] felt comfortable asking questions compared to online participants [83.33% (25/30); P = 0.025]. The majority in both groups preferred a written exam [total: 75.41% (46/61); in-person alumni: 77.42% (24/31); online alumni 73.33% (22/30)]. In terms of course format preferences, in-person courses were preferred by both in-person alumni [38.71% (12/31)] and online alumni [60% (18/30)], almost as much as a hybrid format combining in-person and online elements [in-person alumni: 41.94% (13/31), online alumni: 30% (9/30)]. Conclusion: The transition from in-person to online CMR training at the CMR Academy Berlin was successful in maintaining overall satisfaction. However, there is room for improvement in terms of increased interaction, particularly for online participants. Future CMR- and potentially also cardiac computer tomography-courses should consider adopting a hybrid format to accommodate participants' preferences and enhance their learning experience, especially to gain level II competency, whereas level I virtual only might be sufficient.

The COVID-19 pandemic has greatly changed the landscape of medical education, necessitating the shift from traditional in-person learning to online platforms. This study evaluated how well an online training programme for cardiovascular magnetic resonance imaging (CMR) was received by doctors who attended the CMR Academy in Berlin, Germany. We asked both in-person and online course participants about their experiences and preferences for future courses. A total of 61 out of 158 participants (38.61%) responded to our survey. Both in-person and online attendees rated the course as either 'very good' or 'excellent'. However, more in-person attendees felt comfortable asking questions during the course compared to online attendees. In terms of future courses, most of the participants preferred a blend of in-person and online learning, known as a hybrid format. They felt that online learning had some benefits, such as increased access, especially during a pandemic. However, they missed the interaction and engagement that in-person learning provides. They also preferred written exams to be conducted online. This study emphasizes the need for future CMR training to be more flexible and include both online and in-person elements. This would not only accommodate the participants' preferences but also enhance their learning experience. It also stresses the importance of interaction during the learning process, which needs to be improved in online platforms. The findings can potentially inform the development of educational frameworks in other areas of medical imaging, like cardiac computer tomography (CT).

CMR detects decreased myocardial deformation in asymptomatic patients at risk for heart failure.

Aims: The main management strategy of heart failure with preserved ejection fraction (HFpEF) is prevention since HFpEF is associated with many cardiovascular (CV) risk factors, especially since HFpEF is linked to a high risk for both mortality and recurrent heart failure (HF) hospitalizations. Therefore, there is a need for new tools to identify patients with a high risk profile early. Regional strain assessment by CMR seems to be superior in describing deformation impairment in HF. The MyoHealth score is a promising tool to identify cardiac changes early. Methods and results: Heart failure patients irrespective of LVEF and asymptomatic controls were recruited, and CMR based measures were obtained. For this analysis the asymptomatic control group (n = 19) was divided into asymptomatic subjects without CV co-morbidities or evidence of cardiac abnormalities and (n = 12) and asymptomatic subjects with CV co-morbidities or evidence of cardiac abnormalities (n = 7) as well as patients with HFpEF (n = 19). We performed CMR scans at rest and during a stress test using isometric handgrip exercise (HG). Assessing the MyoHealth score at rest revealed preserved regional strain in 85 ± 9% of LV segments in controls, 73 ± 11% in at Risk subjects and 73 ± 8% in HFpEF patients. During stress the MyoHealth score was 84 ± 7% in controls, 83 ± 7 in at risk subjects and 74 ± 11 in HFpEF patients. Conclusion: In summary, we show for the first time that asymptomatic subjects with increased CV risk present with HFpEF like impaired myocardial deformation at rest, while they show results like controls under HG stress. The potential of preventive treatment in this group of patients merits further investigation in future. Clinical trial registration: [https://drks.de/search/de/trial/DRKS00015615], identifier [DRKS00015615].

Evaluation of the HFA-PEFF Score: results from the prospective DIAST-CHF cohort.

AIMS: Although the number of patients suffering from heart failure with preserved ejection fraction (HFpEF) increases, the routine diagnosis remains a challenge. In the absence of a pathognomonic sign for HFpEF or specific treatment strategies, a prognosis-based characterization of suspected patients remains promising for both the risk stratification of the patients and a disease definition. The Heart Failure Association (HFA) of the European Society of Cardiology has introduced an algorithm with different levels of likelihood regarding the diagnosis of HFpEF, the HFA-PEFF score. We aimed to evaluate the predictive value of this algorithm in a large cohort regarding mortality, symptom burden, and the functional status. METHODS AND RESULTS: DIAST-CHF is a multicentre, population-based, prospective, observational study in subjects with at least one risk factor for HFpEF between the age of 50 and 85. We calculated the HFA-PEFF score (n = 1668) and analysed the risk groups for overall mortality, cardiovascular hospitalization, and submaximal functional capacity (6-min walk distance) at baseline and after a follow-up period of 10 years. Patients with high HFA-PEFF score values 5&6 showed a higher mortality than those with an intermediate score (score values 2-4) and low score values (high 21.3% vs. intermediate 10.1% vs. low 4.3%, P < 0.001). Also, the burden of MACE (death, cardiovascular hospitalization, new myocardial infarction, first diagnosis of HF) was increased in the high score values group (high 40.7% vs. intermediate 25.9% vs. low 13.9%, P < 0.001). Similarly, patients with higher scores had higher cumulative incidences of cardiovascular hospitalizations (P = 0.011). Subjects with higher scores also had lower 6-min walk distance both at baseline and during follow-up. CONCLUSIONS: The HFA-PEFF score provides a reliable instrument to stratify suspected HFpEF patients by their risk for mortality, symptom burden, and functional status in cohort at risk with a follow-up period of 10 years. As high HFA-PEFF scores are associated with worse outcome, the HFA-PEFF algorithm describes a defining approach towards HFpEF.

Influence of baseline parameters on one-year physical, mental, and health-related quality of life in patients with heart failure and preserved ejection fraction.

AIMS: To identify baseline parameters longitudinally influencing overall health-related quality of life (HRQoL), physical function and mental health 1 year later in patients with chronic heart failure and preserved ejection fraction (HFpEF). METHODS AND RESULTS: We performed post hoc analyses of the randomized aldosterone in diastolic heart failure (Aldo-DHF) trial, including 422 patients with HFpEF and NYHA class II or III. Overall HRQoL, measured by the Minnesota Living with Heart Failure Questionnaire (MLHFQ), physical functioning and mental health, both measured by the Short Form 36 Health Survey (SF-36), after 12 months were predicted in correlation analyses and multivariate regression analyses with continuous values and worst versus three better HRQoL quartiles as dependent variables. The mean age of the study population was 66.8 ± 7.6 years, 52.4% were female, and 86.0% had NYHA class II. All HRQoL variables at 1 year were predicted by their respective baseline values (all P < 0.001), which were also the best variables to predict lowest versus higher HRQoL quartiles (all P < 0.001). For overall HRQoL, six-minute-walking-distance (P = 0.009), Borg-score (P = 0.001), coronary heart disease (P = 0.036) and SF-36 role-emotional (P = 0.005) independently predicted one-year-outcome, while depression diagnosis (P = 0.044), self-reported health status (P = 0.023) and PHQ depression (P = 0.001) were only significant predictors when excluding MLHFQ total score at baseline. In logistic regression analyses, only SF-36 role-emotional (P = 0.016) independently predicted overall HRQoL group status at follow up. For physical functioning, Borg-score (P ≤ 0.001), 6 min walking distance (P = 0.005), coronary heart disease (P = 0.009), and SF-36 vitality (P = 0.001) were significant independent predictors, also when excluding baseline physical functioning. Low SF-36 vitality (P = 0.021) and presence of coronary heart disease (P = 0.027) independently predicted a patient's membership in the lowest quartile 1 year later. For mental health, SF-36 physical functioning (P = 0.025) and HADS anxiety (P = 0.046) were independent predictors, while self-rated fatigue and poor performance (P = 0.033) and SF-36 vitality (P = 0.008) only served as significant predictors when excluding mental health at baseline. HADS anxiety (P = 0.009) also served as independent predictor of a patient's group status after 1 year. CONCLUSION: Overall HRQoL, physical functioning, and mental health of HFpEF patients 1 year later are mainly influenced by their respective baseline values. Other self-rated baseline parameters also showed independent effects while objective severity measures had limited predictive value.

Plasma Biomarker Profiling in Heart Failure Patients with Preserved Ejection Fraction before and after Spironolactone Treatment: Results from the Aldo-DHF Trial.

The pathophysiology of heart failure with preserved ejection fraction (HFpEF) is poorly understood and therapeutic strategies are lacking. This study aimed to identify plasma proteins with pathophysiological relevance in HFpEF and with respect to spironolactone-induced effects. We assessed 92 biomarkers in plasma samples from 386 HFpEF patients-belonging to the Aldo-DHF trial-before (baseline, BL) and after one-year treatment (follow up, FU) with spironolactone (verum) or a placebo. At BL, various biomarkers showed significant associations with the two Aldo-DHF primary end point parameters: 33 with E/e' and 20 with peak VO2. Ten proteins including adrenomedullin, FGF23 and inflammatory peptides (e.g., TNFRSF11A, TRAILR2) were significantly associated with both parameters, suggesting a role in the clinical HFpEF presentation. For 13 proteins, expression changes from BL to FU were significantly different between verum and placebo. Among them were renin, growth hormone, adrenomedullin and inflammatory proteins (e.g., TNFRSF11A, IL18 and IL4RA), indicating distinct spironolactone-mediated effects. BL levels of five proteins, e.g., inflammatory markers such as CCL17, IL4RA and IL1ra, showed significantly different effects on the instantaneous risk for hospitalization between verum and placebo. This study identified plasma proteins with different implications in HFpEF and following spironolactone treatment. Future studies need to define their precise mechanistic involvement.

Myocardial deformation assessed among heart failure entities by cardiovascular magnetic resonance imaging.

AIMS: Although heart failure (HF) is a leading cause for hospitalization and mortality, normalized and comparable non-invasive assessment of haemodynamics and myocardial action remains limited. Moreover, myocardial deformation has not been compared between the guideline-defined HF entities. The distribution of affected and impaired segments within the contracting left ventricular (LV) myocardium have also not been compared. Therefore, we assessed myocardial function impairment by strain in patients with HF and control subjects by magnetic resonance imaging after clinically phenotyping these patients. METHODS AND RESULTS: This prospective study conducted at two centres in Germany between 2017 and 2018 enrolled stable outpatient subjects with HF [n = 56, including HF with reduced ejection fraction (HFrEF), HF with mid-range ejection fraction (HFmrEF), and HF with preserved ejection fraction (HFpEF)] and a control cohort (n = 12). Parameters assessed included measures for external myocardial function, for example, cardiac index and myocardial deformation measurements by cardiovascular magnetic resonance imaging, left ventricular global longitudinal strain (GLS), the global circumferential strain (GCS) and the regional distribution of segment deformation within the LV myocardium, as well as basic phenotypical characteristics. Comparison of the cardiac indices at rest showed no differences neither between the HF groups nor between the control group and HF patients (one-way ANOVA P = 0.70). The analysis of the strain data revealed differences between all groups in both LV GLS (One-way ANOVA: P < 0.01. Controls vs. HFpEF: -20.48 ± 1.62 vs. -19.27 ± 1.25. HFpEF vs. HFmrEF: -19.27 ± 1.25 vs. -15.72 ± 2.76. HFmrEF vs. HFrEF: -15.72 ± 2.76 vs. -11.51 ± 3.97.) and LV GCS (One-way ANOVA: P < 0.01. Controls vs. HFpEF: -19.74 ± 2.18 vs. -17.47 ± 2.10. HFpEF vs. HFmrEF: -17.47 ± 2.10 vs. -12.78 ± 3.47. HFrEF: -11.41 ± 3.27). Comparing the segment deformation distribution patterns highlighted the discriminating effect between the groups was much more prominent between the groups (one-way ANOVA P < 0.01) when compared by a score combining regional effects and a global view on the LV. Further analyses of the patterns among the segments affected showed that while the LVEF is preserved in HFpEF, the segments impaired in their contractility are located in the ventricular septum. The worse the LVEF is, the more segments are affected, but the septum remains an outstanding location with the most severe contractility impairment throughout the HF entities. CONCLUSIONS: While cardiac index at rest did not differ significantly between controls and stable HF patients suffering from HFrEF, HFmrEF, or HFpEF, the groups did differ significantly in LV GLS and LV GCS values. Regional strain analysis revealed that the LV septum is the location affected most, with reduced values already visible in HFpEF and further reductions in HFmrEF and HFrEF.

The diagnostic and prognostic value of galectin-3 in patients at risk for heart failure with preserved ejection fraction: results from the DIAST-CHF study.

AIMS: Galectin-3 (Gal-3) predicts long-term outcome among patients with heart failure (HF) with preserved ejection fraction (HFpEF). The ability of Gal-3 to diagnose and predict incident HFpEF in a cohort at risk for HFpEF is of particular interest. We aimed to determine the association between Gal-3 and clinical manifestations of HFpEF, the relationship between Gal-3 and all-cause mortality, or the composite of cardiovascular hospitalization and death. METHODS AND RESULTS: The observational Diast-CHF study included patients aged 50 to 85 years with ≥1 risk factor for HF (e.g. hypertension, diabetes mellitus, and atherosclerotic disease) or previously suspected HF. Patients were followed for 10 years. The association between Gal-3, evidence of diastolic dysfunction, and Framingham criteria for HF was examined. All deaths and hospitalizations were adjudicated as cardiovascular or non-cardiovascular. The analysis population was composed of 1386 subjects (67 years old, 50.9% female). The area under the receiver operating characteristic curve to diagnose HFpEF was 0.71. At a cut-off value of 13.57 ng/mL, sensitivity was 0.61 and specificity was 0.73 for Gal-3, and the diagnostic power to detect HFpEF was superior to N-terminal pro-brain natriuretic peptide (area under the receiver operating characteristic curve 0.59, P > 0.001). Baseline Gal-3 was associated with risk factors for HF (P < 0.001). Higher levels of Gal-3 predicted incident HFpEF (P < 0.05), adjusted all-cause mortality (P < 0.001), and the adjusted composite of cardiovascular hospitalization and death (P < 0.001), both independent from N-terminal pro-brain natriuretic peptide. CONCLUSIONS: Gal-3 differentiated patients with HFpEF from an overall cohort of well-characterized patients with risk factors for HFpEF. Independent of other factors, baseline Gal-3 levels were associated with a higher risk for incident HFpEF, mortality, or the composite of cardiovascular hospitalization and death over 10 year follow-up. In conjunction with clinical parameters, Gal-3 adds a statistically significant value for the diagnosis of HFpEF within this study, yet the clinical relevance remains debatable.

Economic impact of heart failure with preserved ejection fraction: insights from the ALDO-DHF trial.

AIMS: Although heart failure (HF) with preserved ejection fraction (HFpEF) is a leading cause for hospitalization, its overall costs remain unclear. Therefore, we assessed the health care-related costs of ambulatory HFpEF patients and the effect of spironolactone. METHODS AND RESULTS: The aldosterone receptor blockade in diastolic HF trial is a multicentre, prospective, randomized, double-blind, placebo-controlled trial conducted between March 2007 and April 2011 at 10 sites in Germany and Austria that included 422 ambulatory patients [mean age: 67 years (standard deviation: 8); 52% women]. All subjects suffered from chronic New York Heart Association (NYHA) class II or III HF and preserved left ventricular ejection fraction of 50% or greater. They also showed evidence of diastolic dysfunction. Patients were randomly assigned to receive 25 mg of spironolactone once daily (n = 213) or matching placebo (n = 209) with 12 months of follow-up. We used a single-patient approach to explore the resulting general cost structure and included medication, number of general practitioner and cardiologist visits, and hospitalization in both acute and rehabilitative care facilities. The average annual costs per patient in this cohort came up to €1, 118 (±2,475), and the median costs were €332. We confirmed that the main cost factor was hospitalization and spironolactone did not affect the overall costs. We identified higher HF functional class (NYHA), male patients with low haemoglobin level, with high oxygen uptake (VO2 max) and coronary artery disease, hyperlipidaemia, and atrial fibrillation as independent predictors for higher costs. CONCLUSIONS: In this relatively young, oligosymptomatic, and with regard to the protocol without major comorbidities patient cohort, the overall costs are lower than expected compared with the HFrEF population. Further investigation is needed to investigate the impact of, for example, comorbidities and their effect over a longer period of time. Simultaneously, this analysis suggests that prevention of comorbidities are necessary to reduce costs in the health care system.

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