Special Issue "Acute and Chronic Heart Failure"

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Cardiology".

Deadline for manuscript submissions: closed (30 September 2019).

Special Issue Editors

Prof. Dr. Stephan Von Haehling
E-Mail Website
Guest Editor
Department of Cardiology, University Medical Center Göttingen, Göttingen, Germany
Interests: heart failure, heart failure with preserved ejection fraction, heart failure with reduced ejection fraction, iron deficiency, biomarkers, waisting, srcopenia, comorbidities
Dr. Minke H.T. Hartman
E-Mail
Guest Editor
Department of Cardiology, University Medical Center Göttingen, Göttingen, Germany
Interests: heart failure, biomarkers, coronary artery disease, myocardial infarction, cardiac imaging

Special Issue Information

Dear Colleagues,

In the last decade, treatment options for patients with heart failure have broadened with novel interventional strategies, e.g. cardiac resynchronization therapy, and pharmacologic therapies including ivabradine and sacubitril/valsartan. Nonetheless, the mortality and morbidity of patients with heart failure is still high. As a result of an increasing incidence, the clinical and economic burden of heart failure is expected to rise further in the coming decades. Heart failure is a heterogenic diagnosis and, in our opinion, the focus should lie on patient-tailored therapy. As referred to in the 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure, the current challenge is to develop targeted therapies for the specific etiologies causing heart failure (e.g. amyloidosis, peripartum cardiomyopathy). Also, innovative interventional modalities, such as percutaneous repair of mitral and tricuspid valve regurgitation, could contribute in reducing heart failure symptoms and improving outcome. Besides, comorbidities are exceptionally frequent and important in heart failure, in particular renal dysfunction, chronic obstructive pulmonary disease, anemia, iron deficiency, sleep-disordered breathing and diabetes. Early identification and optimal treatment of comorbidities in heart failure could help prevent deterioration in quality of life and eventually mortality. The aim of this special issue is to highlight new opportunities in improving diagnostics and treatments in heart failure. Potential topics are diagnostic gaps in identifying comorbidities, biomarkers to discriminate between responders and non-responders of pharmacologic therapy, and novel treatment strategies intervening in the clinical course of heart failure patients.

Prof. Dr. Stephan von Haehling
Dr. Minke H.T. Hartman
Guest Editors

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Keywords

  • Heart failure
  • Acute heart failure
  • Chronic heart failure
  • Cardiomyopathies
  • Comorbidities
  • Clinical management
  • Patient tailored therapy

Published Papers (9 papers)

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Research

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Open AccessArticle
Prognostic Value of the Echocardiographic Probability of Pulmonary Hypertension in Patients with Acute Decompensated Heart Failure
J. Clin. Med. 2019, 8(10), 1684; https://doi.org/10.3390/jcm8101684 - 15 Oct 2019
Abstract
The prognostic value of pulmonary hypertension (PH) estimated by echocardiography in unselected patients with acute decompensated heart failure (ADHF) is poorly studied. Between November 2014 and September 2018, 657 patients were recruited in a prospective registry of ADHF (ClinicalTrials.gov NCT02444416). The probability of [...] Read more.
The prognostic value of pulmonary hypertension (PH) estimated by echocardiography in unselected patients with acute decompensated heart failure (ADHF) is poorly studied. Between November 2014 and September 2018, 657 patients were recruited in a prospective registry of ADHF (ClinicalTrials.gov NCT02444416). The probability of pulmonary hypertension was based on European Society of Cardiology (ESC) guidelines for echocardiographic evaluation. The median survival without all-cause mortality or readmission was 7 months. During the median follow-up period of 15 months, there were 450 events including 185 deaths. In multivariate analysis, the hazard ratio (HR) of all-cause mortality or readmission for patients with a high probability of PH was 1.67 (95% CI 1.29–2.17, p < 0.001) as compared to patients with a low or intermediate probability. The left ventricular ejection fraction (LVEF) and right ventricular function (RVF) were not associated with the primary outcome—HR 1.02 (95% CI 0.81–1.29; p = 0.84) and 0.96 (95% CI 0.76–1.23; p = 0.77) respectively. In patients admitted for ADHF, a high probability of PH as evaluated by echocardiography provided the highest independent prognostic value for mortality and readmission, whereas LVEF and RVF were not associated with prognosis. The identification of patients at high risk of PH by non-invasive measurement conveys important prognostic information and may guide management. Full article
(This article belongs to the Special Issue Acute and Chronic Heart Failure)
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Open AccessArticle
Iron Deficiency in Acute Decompensated Heart Failure
J. Clin. Med. 2019, 8(10), 1569; https://doi.org/10.3390/jcm8101569 - 01 Oct 2019
Abstract
The aim of this study was to characterize iron deficiency (ID) in acutely decompensated heart failure (ADHF) and identify whether ID is associated with dyspnea class, length of stay (LOS), biomarker levels, and echocardiographic indices of diastolic function in patients with reduced ejection [...] Read more.
The aim of this study was to characterize iron deficiency (ID) in acutely decompensated heart failure (ADHF) and identify whether ID is associated with dyspnea class, length of stay (LOS), biomarker levels, and echocardiographic indices of diastolic function in patients with reduced ejection fraction (HFrEF) and with preserved ejection fraction (HFpEF). Consecutive patients admitted with ADHF at a single tertiary center were included. Demographic information, pathology investigations, and metrics regarding hospital stay and readmission were recorded. Patients were classified as having ‘absolute’ ID if they had a ferritin level <100 ng/mL; or ‘functional’ ID if they had a ferritin 100–200 ng/mL and a transferrin saturation <20%. Of 503 patients that were recruited, 270 (55%) had HFpEF, 160 (33%) had HFREF, and 57 (12%) had heart failure with mid-range ejection fraction. ID was present in 54% of patients with HFrEF and 56% of patients with HFpEF. In the HFpEF group, ID was associated with a LOS of 11 ± 7.7 vs. 9 ± 6 days in iron replete patients, p = 0.036, and remained an independent predictor of increased LOS in a multivariate linear regression incorporating comorbidities, age, and ID status. This study corroborates a high prevalence of ID in both HFrEF and HFpEF, and further shows that in patients with HFpEF there is a prolongation of LOS not seen in HFrEF which may indicate a more prominent role for ID in HFpEF. Full article
(This article belongs to the Special Issue Acute and Chronic Heart Failure)
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Open AccessArticle
Autophagy and Inflammasome Activation in Dilated Cardiomyopathy
J. Clin. Med. 2019, 8(10), 1519; https://doi.org/10.3390/jcm8101519 - 21 Sep 2019
Abstract
Background: The clinical outcome of patients affected by dilated cardiomyopathy (DCM) is heterogeneous, since its pathophysiology is only partially understood. Interleukin 1β levels could predict the mortality and necessity of cardiac transplantation of DCM patients. Objective: To investigate mechanisms triggering sterile inflammation in [...] Read more.
Background: The clinical outcome of patients affected by dilated cardiomyopathy (DCM) is heterogeneous, since its pathophysiology is only partially understood. Interleukin 1β levels could predict the mortality and necessity of cardiac transplantation of DCM patients. Objective: To investigate mechanisms triggering sterile inflammation in dilated cardiomyopathy (DCM). Methods: Hearts explanted from 62 DCM patients were compared with 30 controls, employing immunohistochemistry, cellular and molecular biology, as well as metabolomics studies. Results: Although misfolded protein accumulation and aggresome formation characterize DCM hearts, aggresomes failed to trigger the autophagy lysosomal pathway (ALP), with consequent accumulation of both p62SQSTM1 and dysfunctional mitochondria. In line, DCM hearts are characterized by accumulation of lipoperoxidation products and activation of both redox responsive pathways and inflammasome. Consistently with the fact that mTOR signaling may impair ALP, we observed, an increase in DCM activation, together with a reduction in the nuclear localization of Transcription Factor EB -TFEB- (a master regulator of lysosomal biogenesis). These alterations were coupled with metabolomic alterations, including accumulation of branched chain amino acids (BCAAs), known mTOR activators. Consistently, reduced levels of PP2Cm, a phosphatase that regulates the key catabolic step of BCAAs, coupled with increased levels of miR-22, a regulator of PP2Cm levels that triggers senescence, characterize DCM hearts. The same molecular defects were present in clinically relevant cells isolated from DCM hearts, but they could be reverted by downregulating miR-22. Conclusion: We identified, in human DCM, a complex series of events whose key players are miR-22, PP2Cm, BCAA, mTOR, and ALP, linking loss of proteostasis with inflammasome activation. These potential therapeutic targets deserve to be further investigated. Full article
(This article belongs to the Special Issue Acute and Chronic Heart Failure)
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Open AccessArticle
Patients with Heart Failure and Preserved Ejection Fraction Are at Risk of Gastrointestinal Bleeding
J. Clin. Med. 2019, 8(8), 1240; https://doi.org/10.3390/jcm8081240 - 17 Aug 2019
Abstract
Aims. Two thirds of patients with heart failure and preserved ejection fraction (HFpEF) have an indication for oral anticoagulation (OAC) to prevent thromboembolic events. However, evidence regarding the safety of OAC in HFpEF is limited. Therefore, our aim was to describe bleeding events [...] Read more.
Aims. Two thirds of patients with heart failure and preserved ejection fraction (HFpEF) have an indication for oral anticoagulation (OAC) to prevent thromboembolic events. However, evidence regarding the safety of OAC in HFpEF is limited. Therefore, our aim was to describe bleeding events and to find predictors of bleeding in a large HFpEF cohort. Methods and Results. We recorded bleeding events in a prospective HFpEF cohort. Out of 328 patients (median age 71 years (interquartile range (IQR) 67–77)), 64.6% (n = 212) were treated with OAC. Of those, 65.1% (n = 138) received vitamin-K-antagonists (VKA) and 34.9% (n = 72) non-vitamin K oral anticoagulants (NOACs). During a median follow-up time of 42 (IQR 17–63) months, a total of 54 bleeding events occurred. Patients on OAC experienced more bleeding events (n = 49 (23.1%) versus n = 5 (4.3%), p < 0.001). Major drivers of events were gastrointestinal (GI) bleeding (n = 18 (36.7%)]. HAS-BLED (Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Concomitantly) score (hazard ratios (HR) of 2.15 (95% confidence interval (CI) 1.65–2.79, p < 0.001)) was the strongest independent predictor for overall bleeding. In the subgroup of GI bleeding, mean right atrial pressure (mRAP: HR of 1.13 (95% CI 1.03–1.25, p = 0.013)) and HAS-BLED score (HR of 1.74 (95% CI 1.15–2.64, p = 0.009)] remained significantly associatiated with bleeding events after adjustment. mRAP provided additional prognostic value beyond the HAS-BLED score with an improvement from 0.63 to 0.71 (95% CI 0.58–0.84, p for comparison 0.032), by C-statistic. This additional prognostic value was confirmed by significant improvements in net reclassification index (61.3%, p = 0.019) and integrated discrimination improvement (3.4%, p = 0.015). Conclusion. OAC-treated HFpEF patients are at high risk of GI bleeding. High mRAP as an indicator of advanced stage of disease was predictive for GI bleeding events and provided additional risk stratification information beyond that obtained by HAS-BLED score. Full article
(This article belongs to the Special Issue Acute and Chronic Heart Failure)
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Open AccessArticle
Antiarrhythmic Effect of Sacubitril-Valsartan: Cause or Consequence of Clinical Improvement?
J. Clin. Med. 2019, 8(6), 869; https://doi.org/10.3390/jcm8060869 - 18 Jun 2019
Abstract
Sacubitril/Valsartan (LCZ696) reduced sudden cardiac death in the PARADIGM-HF trial. However, the mechanism by which LCZ696 reduces ventricular arrhythmias remains unclear. The aim of this study was to compare electrocardiographic (ECG) parameters and mechanical dispersion index, assessed by left ventricular (LV) global longitudinal [...] Read more.
Sacubitril/Valsartan (LCZ696) reduced sudden cardiac death in the PARADIGM-HF trial. However, the mechanism by which LCZ696 reduces ventricular arrhythmias remains unclear. The aim of this study was to compare electrocardiographic (ECG) parameters and mechanical dispersion index, assessed by left ventricular (LV) global longitudinal strain (GLS), before and after LCZ696 therapy. We prospectively evaluated chronic Heart Failure (HF) patients with LV ejection fraction ≤40%, despite optimal medical and device therapy, in which LCZ696 therapy was started, while no additional HF treatment was expected to change. ECG and transthoracic echocardiographic data were gathered in the week before starting LCZ696 and at six months of therapy. A semiautomated analysis of LV GLS was performed and mechanical dispersion index was defined as the standard deviation from 16 time intervals corresponding to each LV segment. Of the 42 patients, 35 completed the six month follow-up, since two patients died and five discontinued treatment for adverse events. QTc interval (451.9 vs. 426.0 ms, p < 0.001), QRS duration (125.1 vs. 120.8 ms, p = 0.033) and mechanical dispersion index (88.4 vs. 78.1 ms, p = 0.036) were significantly reduced at six months. LCZ696 therapy is associated with a reduction in QTc interval, QRS duration and mechanical dispersion index as assessed by LV GLS. Full article
(This article belongs to the Special Issue Acute and Chronic Heart Failure)
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Open AccessArticle
Heterogeneous Metabolic Response to Exercise Training in Heart Failure with Preserved Ejection Fraction
J. Clin. Med. 2019, 8(5), 591; https://doi.org/10.3390/jcm8050591 - 29 Apr 2019
Abstract
The prevalence of heart failure with preserved ejection fraction (HFpEF) is constantly increasing and no evidence-based pharmacological treatment option is available. While exercise training (ET) improves diastolic function, its metabolic mechanisms in HFpEF are unclear. We assessed the metabolic response to 12 weeks [...] Read more.
The prevalence of heart failure with preserved ejection fraction (HFpEF) is constantly increasing and no evidence-based pharmacological treatment option is available. While exercise training (ET) improves diastolic function, its metabolic mechanisms in HFpEF are unclear. We assessed the metabolic response to 12 weeks of ET in patients with HFpEF by performing a post hoc analysis of the EX-DHF-P trial (ISRCTN86879094). Plasma concentrations of 188 endogenous metabolites were measured in 44 ET and 20 usual care (UC) patients at baseline and 3-months follow-up. Metabolic differences between ET and UC from baseline to follow-up were compared and differential responses to ET were examined by random forest feature selection. ET prevented the increase of acetylornithine and carnitine as well as the decrease of three glycerophospholipids. After ET, two opposite metabolic response clusters were identified. Cluster belonging was associated with perceived well-being at baseline and changes in low-density lipoprotein but not with cardiorespiratory, ventilatory or echocardiographic parameters. These two ET-induced metabolic response patterns illustrate the heterogeneity of the HFpEF patient population. Our results suggest that other biological parameters might be helpful besides clinical variables to improve HFpEF patient stratification. Whether this approach improves response prediction regarding ET and other treatments should be explored. Full article
(This article belongs to the Special Issue Acute and Chronic Heart Failure)
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Open AccessArticle
The Predictivity of N-Terminal Pro b-Type Natriuretic Peptide for All-Cause Mortality in Various Follow-Up Periods among Heart Failure Patients
J. Clin. Med. 2019, 8(3), 357; https://doi.org/10.3390/jcm8030357 - 13 Mar 2019
Abstract
Plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) is an excellent prognostic–predictive tool in heart failure (HF) patients, but its plasma level changes following therapy. The comparison of prognosis–predictivity of a single measurement of plasma NT-pro BNP in different follow-up periods in acute HF patients [...] Read more.
Plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) is an excellent prognostic–predictive tool in heart failure (HF) patients, but its plasma level changes following therapy. The comparison of prognosis–predictivity of a single measurement of plasma NT-pro BNP in different follow-up periods in acute HF patients has been less studied. This study aimed to evaluate whether the association between initial plasma NT-proBNP levels and all-cause mortality would decrease along with an increased follow-up period in patients with acute HF. The retrospective study was carried out, enrolling adult patients with hospitalization-requiring acute HF who fulfilled the predefined criteria from January 1, 2011, to December 31, 2013. We evaluated the independent predictors of 12-month mortality, and subsequently compared the predictivity of NT-proBNP level at initial presentation for 1-, 3-, 6-, 9- and 12-month mortality. In total, 269 patients (mean age, 74.45 ± 13.59 years; female, 53.9%) were enrolled. The independent predictors of 12-month mortality included higher “Charlson Comorbidity Index” (adjusted hazard ratio (aHR) = 1.22; 95% confidence interval (CI), 1.10–1.34), increased “age” (aHR = 1.07; 95% CI, 1.04–1.10), “administration of vasopressor” (aHR = 3.43; 95% CI, 1.76–6.71), “underwent cardiopulmonary resuscitation” (aHR = 4.59; 95% CI, 1.76–6.71), and without “angiotensin-converting enzyme inhibitors/angiotensin receptor blocker” (aHR = 0.41; 95% CI, 1.86–11.31) (all p <0.001). “Plasma NT-pro BNP level ≧11,755 ng/L” was demonstrated as an independent predictor in 1-month (aHR = 2.37; 95% CI, 1.10–5.11; p = 0.028) and 3-month mortality (aHR = 1.98; 95% CI, 1.02–3.86; p = 0.045) but not in more extended follow-up. The outcome predictivity of plasma NT-proBNP levels diminished in a longer follow-up period in hospitalized acute HF patients. In conclusion, these findings remind physicians to act with caution when using a single plasma level of NT-proBNP to predict patient outcomes with a longer follow-up period. Full article
(This article belongs to the Special Issue Acute and Chronic Heart Failure)
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Review

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Open AccessReview
Sex and Heart Failure with Preserved Ejection Fraction: From Pathophysiology to Clinical Studies
J. Clin. Med. 2019, 8(6), 792; https://doi.org/10.3390/jcm8060792 - 04 Jun 2019
Cited by 1
Abstract
Heart failure with preserved ejection fraction (HFpEF) represents the most frequent form of heart failure in women, with almost two-fold higher prevalence than in men. Studies have revealed sex-specific HFpEF pathophysiology, and suggested the possibility of a sex-specific therapeutic approach in these patients. [...] Read more.
Heart failure with preserved ejection fraction (HFpEF) represents the most frequent form of heart failure in women, with almost two-fold higher prevalence than in men. Studies have revealed sex-specific HFpEF pathophysiology, and suggested the possibility of a sex-specific therapeutic approach in these patients. Some cardiovascular risk factors, such as arterial hypertension, obesity, diabetes mellitus, coronary artery disease, atrial fibrillation, and race, show specific features that might be responsible for the development of HFpEF in women. These risk factors are related to specific cardiovascular changes—left ventricular diastolic dysfunction and hypertrophy, ventricular–vascular coupling, and impaired functional capacity—that are related to specific cardiac phenotype and HFpEF development. However, there is no agreement regarding outcomes in women with HFpEF. For HFpEF, most studies have found higher hospitalization rates for women than for men. Mortality rates are usually not different. Pharmacological treatment in HFpEF is challenging, along with many unresolved issues and questions raised. Available data on medical therapy in patients with HFpEF show no difference in outcomes between the sexes. Further investigations are necessary to better understand the pathophysiology and mechanisms of HFpEF, as well as to improve and eventually develop sex-specific therapy for HFpEF. Full article
(This article belongs to the Special Issue Acute and Chronic Heart Failure)
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Open AccessReview
Biomarkers in the Diagnosis, Management, and Prognostication of Perioperative Right Ventricular Failure in Cardiac Surgery—Are We There Yet?
J. Clin. Med. 2019, 8(4), 559; https://doi.org/10.3390/jcm8040559 - 25 Apr 2019
Cited by 2
Abstract
Right ventricular failure (RVF) is a major risk factor for end organ morbidity and mortality following cardiac surgery. Perioperative RVF is difficult to predict and detect, and to date, no convenient, accurate, or reproducible measure of right ventricular (RV) function is available. Few [...] Read more.
Right ventricular failure (RVF) is a major risk factor for end organ morbidity and mortality following cardiac surgery. Perioperative RVF is difficult to predict and detect, and to date, no convenient, accurate, or reproducible measure of right ventricular (RV) function is available. Few studies have examined the use of biomarkers in RVF, and even fewer have examined their utility in the perioperative setting of patients undergoing cardiac surgery. Of the available classes of biomarkers, this review focuses on biomarkers of (1) inflammation and (2) myocyte injury/stress, due to their superior potential in perioperative RV assessment, including Galectin 3, ST2/sST2, CRP, cTN/hs-cTn, and BNP/NT-proBNP. This review was performed to help highlight the importance of perioperative RV function in patients undergoing cardiac surgery, to review the current modalities of RV assessment, and to provide a review of RV specific biomarkers and their potential utilization in the clinical and perioperative setting in cardiac surgery. Based on current evidence, we suggest the potential utility of ST2, sST2, Gal-3, CRP, hs-cTn, and NT-proBNP in predicting and detecting RVF in cardiac surgery patients, as they encompass the multifaceted nature of perioperative RVF and warrant further investigation to establish their clinical utility. Full article
(This article belongs to the Special Issue Acute and Chronic Heart Failure)
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