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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 P<0.001), and left atrial systolic diameter (P=0.002), more increased septal/posterior end‐diastolic wall‐thickness (both P<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 (P=0.002). Overall, LVEF increased further at 18‐months' follow‐up (P<0.001), while LV end‐diastolic diameter decreased (P=0.048). However, LVEF worsened (P=0.002) and LV end‐diastolic diameter increased (P=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."
We assume that a specific health constraint, e.g., a certain aspect of bodily function or quality of life that is measured by a variable X, is absent (or irrelevant) in a healthy reference population (Ref0), and it is materially present and precisely measured in a diseased reference population (Ref1). We further assume that some amount of this constraint of interest is suspected to be present in a population under study (SP). In order to quantify this issue, we propose the introduction of an intuitive measure, the population comparison index (PCI), that relates the mean value of X in population SP to the mean values of X in populations Ref0 and Ref1. This measure is defined as PCI[X] = (mean[X|SP] − mean[X|Ref0])/(mean[X|Ref1] − mean[X|Ref0]) × 100[%], where mean[X|.] is the average value of X in the respective group of individuals. For interpretation, PCI[X] ≈ 0 indicates that the values of X in the population SP are similar to those in population Ref0, and hence, the impairment measured by X is not materially present in the individuals in population SP. On the other hand, PCI[X] ≈ 100 means that the individuals in SP exhibit values of X comparable to those occurring in Ref1, i.e., the constraint of interest is equally present in populations SP and Ref1. A value of 0 < PCI[X] < 100 indicates that a certain percentage of the constraint is present in SP, and it is more than in Ref0 but less than in Ref1. A value of PCI[X] > 100 means that population SP is even more affected by the constraint than population Ref1.
Establishing a cardiac training group for patients with heart failure: the "HIP-in-Würzburg" study
(2022)
Background
Exercise training in heart failure (HF) is recommended but not routinely offered, because of logistic and safety-related reasons. In 2020, the German Society for Prevention&Rehabilitation and the German Society for Cardiology requested establishing dedicated ""HF training groups."" Here, we aimed to implement and evaluate the feasibility and safety of one of the first HF training groups in Germany.
Methods
Twelve patients (three women) with symptomatic HF (NYHA class II/III) and an ejection fraction ≤ 45% participated and were offered weekly, physician-supervised exercise training for 1 year. Patients received a wrist-worn pedometer (M430 Polar) and underwent the following assessments at baseline and after 4, 8 and 12 months: cardiopulmonary exercise test, 6-min walk test, echocardiography (blinded reading), and quality of life assessment (Kansas City Cardiomyopathy Questionnaire, KCCQ).
Results
All patients (median age [quartiles] 64 [49; 64] years) completed the study and participated in 76% of the offered 36 training sessions. The pedometer was worn ≥ 1000 min per day over 86% of the time. No cardiovascular events occurred during training. Across 12 months, NT-proBNP dropped from 986 pg/ml [455; 1937] to 483 pg/ml [247; 2322], and LVEF increased from 36% [29;41] to 41% [32;46]%, (p for trend = 0.01). We observed no changes in exercise capacity except for a subtle increase in peak VO2% predicted, from 66.5 [49; 77] to 67 [52; 78]; p for trend = 0.03. The physical function and social limitation domains of the KCCQ improved from 60 [54; 82] to 71 [58; 95, and from 63 [39; 83] to 78 [64; 92]; p for trend = 0.04 and = 0.01, respectively. Positive trends were further seen for the clinical and overall summary scores.
Conclusion
This pilot study showed that the implementation of a supervised HF-exercise program is feasible, safe, and has the potential to improve both quality of life and surrogate markers of HF severity. This first exercise experiment should facilitate the design of risk-adopted training programs for patients with HF.
Aims
There is an ongoing discussion whether the categorization of patients with heart failure according to left ventricular ejection fraction (LVEF) is scientifically justified and clinically relevant. Major efforts are directed towards the identification of appropriate cut-off values to correctly allocate heart failure-specific pharmacotherapy. Alternatively, an LVEF continuum without definite subgroups is discussed. This study aimed to evaluate the natural distribution of LVEF in patients presenting with acutely decompensated heart failure and to identify potential subgroups of LVEF in male and female patients.
Methods and results
We identified 470 patients (mean age 75 ± 11 years, n = 137 female) hospitalized for acute heart failure in whom LVEF could be quantified by Simpson's method in an in-hospital echocardiogram. Non-parametric modelling revealed a bimodal shape of the LVEF distribution. Parametric modelling identified two clusters suggesting two LVEF peaks with mean (variance) of 61% (9%) and 31% (10%), respectively. Sub-differentiation by sex revealed a sex-specific bimodal clustering of LVEF. The respective threshold differentiating between ‘high’ and ‘low’ LVEF was 45% in men and 52% in women.
Conclusions
In patients presenting with acute heart failure, LVEF clustered in two subgroups and exhibited profound sex-specific distributional differences. These findings might enrich the scientific process to identify distinct subgroups of heart failure patients, which might each benefit from respectively tailored (pharmaco)therapies.
Objectives
The aim of this study was to explore the left ventricular (LV) deformation changes and the potential impact of deformation on outcome in patients with proven light-chain (AL) amyloidosis and LV hypertrophy.
Background
Cardiac involvement in AL amyloidosis patients is associated with poor outcome. Detecting regional cardiac function by advanced non-invasive techniques might be favorable for predicting outcome.
Methods
LV longitudinal, circumferential and radial peak systolic strains (Ssys) were assessed by speckle tracking imaging (STI) in 44 biopsy-proven systemic AL amyloidosis patients with LV hypertrophy (CA) and in 30 normal controls. Patients were divided into compensated (n = 18) and decompensated (n = 26) group based on clinical assessment and followed-up for a median period of 345 days.
Results
Ejection fraction (EF) was preserved while longitudinal Ssys (LSsys) was significantly reduced in both compensated and decompensated groups. Survival was significantly reduced in decompensated group (35% vs. compensated 78%, P = 0.001). LSsys were similar in apical segments and significantly reduced in basal segments between two patient groups. LSsys at mid-segments were significantly reduced in all LV walls of decompensated group. Patients were further divided into 4 subgroups according to the presence or absence of reduced LSsys in no (normal), only basal (mild), basal and mid (intermediate) and all segments of the septum (severe). This staging revealed continuously worse prognosis in proportion to increasing number of segments with reduced LSsys (mortality: normal 14%, mild 27%, intermediate 67%, and severe 64%). Mid-septum LSsys<11% suggested a 4.8-fold mortality risk than mid-septum LSsys≥11%. Multivariate regression analysis showed NYHA class and mid-septum LSsys were independent predictors for survival.
Conclusions
Reduced deformation at mid-septum is associated with worse prognosis in systemic amyloidosis patients with LV hypertrophy.
Background
Troponin elevation is common in ischemic stroke (IS) patients. The pathomechanisms involved are incompletely understood and comprise coronary and non-coronary causes, e.g. autonomic dysfunction. We investigated determinants of troponin elevation in acute IS patients including markers of autonomic dysfunction, assessed by heart rate variability (HRV) time domain variables.
Methods
Data were collected within the Stroke Induced Cardiac FAILure (SICFAIL) cohort study. IS patients admitted to the Department of Neurology, Würzburg University Hospital, underwent baseline investigation including cardiac history, physical examination, echocardiography, and blood sampling. Four HRV time domain variables were calculated in patients undergoing electrocardiographic Holter monitoring. Multivariable logistic regression with corresponding odds ratios (OR) and 95% confidence intervals (CI) was used to investigate the determinants of high-sensitive troponin T (hs-TnT) levels ≥14 ng/L.
Results
We report results from 543 IS patients recruited between 01/2014–02/2017. Of those, 203 (37%) had hs-TnT ≥14 ng/L, which was independently associated with older age (OR per year 1.05; 95% CI 1.02–1.08), male sex (OR 2.65; 95% CI 1.54–4.58), decreasing estimated glomerular filtration rate (OR per 10 mL/min/1.73 m2 0.71; 95% CI 0.61–0.84), systolic dysfunction (OR 2.79; 95% CI 1.22–6.37), diastolic dysfunction (OR 2.29; 95% CI 1.29–4.02), atrial fibrillation (OR 2.30; 95% CI 1.25–4.23), and increasing levels of C-reactive protein (OR 1.48 per log unit; 95% CI 1.22–1.79). We did not identify an independent association of troponin elevation with the investigated HRV variables.
Conclusion
Cardiac dysfunction and elevated C-reactive protein, but not a reduced HRV as surrogate of autonomic dysfunction, were associated with increased hs-TnT levels in IS patients independent of established cardiovascular risk factors.
Background:
Mitral regurgitation in ischemic heart disease (IMR) is a strong predictor of outcome but until now, pathophysiology is not sufficiently understood and treatment is not satisfying. We aimed to systematically evaluate structural and functional mitral valve leaflet and annular characteristics in patients with IMR to determine the differences in geometric and dynamic changes of the MV between significant and mild IMR.
Methods:
Thirty-seven patients with IMR (18 mild (m)MR, 19 significant (moderate+severe) (s)MR) and 33 controls underwent TEE. 3D volumes were analyzed using 3D feature-tracking software.
Results:
All IMR patients showed a loss of mitral annular motility and non-planarity, whereas mitral annulus dilation and leaflet enlargement occurred in sMR only. Active-posterior-leaflet-area decreased in early systole in all three groups accompanied by an increase in active-anterior-leaflet-area in early systole in controls and mMR but only in late systole in sMR.
Conclusions:
In addition to a significant enlargement and loss in motility of the MV annulus, patients with significant IMR showed a spatio-temporal alteration of the mitral valve coaptation line due to a delayed increase in active-anterior-leaflet-area. This abnormality is likely to contribute to IMR severity and is worth the evaluation of becoming a parameter for clinical decision-making. Further, addressing the leaflets aiming to increase the active leaflet-area is a promising therapeutic approach for significant IMR. Additional studies with a larger sample size and post-operative assessment are warranted to further validate our findings and help understand the dynamics of the mitral valve.
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.
Background:
Adherence to pharmacotherapeutic treatment guidelines in patients with heart failure (HF) is of major prognostic importance, but thorough implementation of guidelines in routine care remains insufficient. Our aim was to investigate prevalence and characteristics of HF in patients with coronary heart disease (CHD), and to assess the adherence to current HF guidelines in patients with HF stage C, thus identifying potential targets for the optimization of guideline implementation.
Methods:
Patients from the German sample of the European Action on Secondary and Primary Prevention by Intervention to Reduce Events (EuroAspire) IV survey with a hospitalization for CHD within the previous six to 36 months providing valid data on echocardiography as well as on signs and symptoms of HF were categorized into stages of HF: A, prevalence of risk factors for developing HF; B, asymptomatic but with structural heart disease; C, symptomatic HF. A Guideline Adherence Indicator (GAI-3) was calculated for patients with reduced (≤40%) left ventricular ejection fraction (HFrEF) as number of drugs taken per number of drugs indicated; beta-blockers, angiotensin converting enzyme inhibitors/angiotensin receptor blockers, and mineralocorticoid receptor antagonists (MRA) were considered.
Results:
509/536 patients entered analysis. HF stage A was prevalent in n = 20 (3.9%), stage B in n = 264 (51.9%), and stage C in n = 225 (44.2%) patients; 94/225 patients were diagnosed with HFrEF (42%). Stage C patients were older, had a longer duration of CHD, and a higher prevalence of arterial hypertension. Awareness of pre-diagnosed HF was low (19%). Overall GAI-3 of HFrEF patients was 96.4% with a trend towards lower GAI-3 in patients with lower LVEF due to less thorough MRA prescription.
Conclusions:
In our sample of CHD patients, prevalence of HF stage C was high and a sizable subgroup suffered from HFrEF. Overall, pharmacotherapy was fairly well implemented in HFrEF patients, although somewhat worse in patients with more reduced ejection fraction. Two major targets were identified possibly suited to further improve the implementation of HF guidelines: 1) increase patients´ awareness of diagnosis and importance of HF; and 2) disseminate knowledge about the importance of appropriately implementing the use of mineralocorticoid receptor antagonists.
Trial registration:
This is a cross-sectional analysis of a non-interventional study. Therefore, it was not registered as an interventional trial.
Background
The guideline recommendation to not measure carotid intima-media thickness (CIMT) for cardiovascular risk prediction is based on the assessment of just one single carotid segment. We evaluated whether there is a segment-specific association between different measurement locations of CIMT and cardiovascular risk factors.
Methods
Subjects from the population-based STAAB cohort study comprising subjects aged 30 to 79 years of the general population from Würzburg, Germany, were investigated. CIMT was measured on the far wall of both sides in three different predefined locations: common carotid artery (CCA), bulb, and internal carotid artery (ICA). Diabetes, dyslipidemia, hypertension, smoking, and obesity were considered as risk factors. In multivariable logistic regression analysis, odds ratios of risk factors per location were estimated for the endpoint of individual age- and sex-adjusted 75th percentile of CIMT.
Results
2492 subjects were included in the analysis. Segment-specific CIMT was highest in the bulb, followed by CCA, and lowest in the ICA. Dyslipidemia, hypertension, and smoking were associated with CIMT, but not diabetes and obesity. We observed no relevant segment-specific association between the three different locations and risk factors, except for a possible interaction between smoking and ICA.
Conclusions
As no segment-specific association between cardiovascular risk factors and CIMT became evident, one simple measurement of one location may suffice to assess the cardiovascular risk of an individual.