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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) | Viewed by 76698

Special Issue Editors


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Guest Editor
Department of Cardiology & Pneumology, Universitätsmedizin Göttingen, D-37099 Göttingen, Germany
Interests: heart failure; comorbidities; biomarkers; pharmacotherapy; exercise capacity; quality of life
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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

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Published Papers (14 papers)

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Research

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10 pages, 596 KiB  
Article
The Effects of Sacubitril/Valsartan on Clinical, Biochemical and Echocardiographic Parameters in Patients with Heart Failure with Reduced Ejection Fraction: The “Hemodynamic Recovery”
by Giuseppe Romano, Giuseppe Vitale, Laura Ajello, Valentina Agnese, Diego Bellavia, Giuseppa Caccamo, Egle Corrado, Gabriele Di Gesaro, Calogero Falletta, Eluisa La Franca, Chiara Minà, Salvatore Antonio Storniolo, Filippo Maria Sarullo and Francesco Clemenza
J. Clin. Med. 2019, 8(12), 2165; https://doi.org/10.3390/jcm8122165 - 6 Dec 2019
Cited by 25 | Viewed by 5397
Abstract
Background: Sacubitril/valsartan has been shown to be superior to enalapril in reducing the risks of death and hospitalization for heart failure (HF). However, knowledge of the impact on cardiac performance remains limited. We sought to evaluate the effects of sacubitril/valsartan on clinical, biochemical [...] Read more.
Background: Sacubitril/valsartan has been shown to be superior to enalapril in reducing the risks of death and hospitalization for heart failure (HF). However, knowledge of the impact on cardiac performance remains limited. We sought to evaluate the effects of sacubitril/valsartan on clinical, biochemical and echocardiographic parameters in patients with heart failure and reduced ejection fraction (HFrEF). Methods: Sacubitril/valsartan was administered to 205 HFrEF patients. Results: Among 230 patients (mean age 59 ± 10 years, 46% with ischemic heart disease) 205 (89%) completed the study. After a follow-up of 10.49 (2.93 ± 18.44) months, the percentage of patients in New York Heart Association (NYHA) class III changed from 40% to 17% (p < 0.001). Median N–Type natriuretic peptide (Nt-proBNP) decreased from 1865 ± 2318 to 1514 ± 2205 pg/mL, (p = 0.01). Furosemide dose reduced from 131.3 ± 154.5 to 120 ± 142.5 (p = 0.047). Ejection fraction (from 27± 5.9% to 30 ± 7.7% (p < 0.001) and E/A ratio (from 1.67 ± 1.21 to 1.42 ± 1.12 (p = 0.002)) improved. Moderate to severe mitral regurgitation (from 30.1% to 17.4%; p = 0.002) and tricuspid velocity decreased from 2.8 ± 0.55 m/s to 2.64 ± 0.59 m/s (p < 0.014). Conclusions: Sacubitril/valsartan induce “hemodynamic recovery” and, consistently with reduction in Nt-proBNP concentrations, improve NYHA class despite diuretic dose reduction. Full article
(This article belongs to the Special Issue Acute and Chronic Heart Failure)
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12 pages, 1371 KiB  
Article
CMR Tissue Characterization in Patients with HFmrEF
by Patrick Doeblin, Djawid Hashemi, Radu Tanacli, Tomas Lapinskas, Rolf Gebker, Christian Stehning, Laura Astrid Motzkus, Moritz Blum, Elvis Tahirovic, Aleksandar Dordevic, Robin Kraft, Seyedeh Mahsa Zamani, Burkert Pieske, Frank Edelmann, Hans-Dirk Düngen and Sebastian Kelle
J. Clin. Med. 2019, 8(11), 1877; https://doi.org/10.3390/jcm8111877 - 5 Nov 2019
Cited by 33 | Viewed by 4209
Abstract
The characteristics and optimal management of heart failure with a moderately reduced ejection fraction (HFmrEF, LV-EF 40–50%) are still unclear. Advanced cardiac MRI offers information about function, fibrosis and inflammation of the myocardium, and might help to characterize HFmrEF in terms of adverse [...] Read more.
The characteristics and optimal management of heart failure with a moderately reduced ejection fraction (HFmrEF, LV-EF 40–50%) are still unclear. Advanced cardiac MRI offers information about function, fibrosis and inflammation of the myocardium, and might help to characterize HFmrEF in terms of adverse cardiac remodeling. We, therefore, examined 17 patients with HFpEF, 18 with HFmrEF, 17 with HFrEF and 17 healthy, age-matched controls with cardiac MRI (Phillips 1.5 T). T1 and T2 relaxation time mapping was performed and the extracellular volume (ECV) was calculated. Global circumferential (GCS) and longitudinal strain (GLS) were derived from cine images. GLS (−15.7 ± 2.1) and GCS (−19.9 ± 4.1) were moderately reduced in HFmrEF, resembling systolic dysfunction. Native T1 relaxation times were elevated in HFmrEF (1027 ± 40 ms) and HFrEF (1033 ± 54 ms) compared to healthy controls (972 ± 31 ms) and HFpEF (985 ± 32 ms). T2 relaxation times were elevated in HFmrEF (55.4 ± 3.4 ms) and HFrEF (56.0 ± 6.0 ms) compared to healthy controls (50.6 ± 2.1 ms). Differences in ECV did not reach statistical significance. HFmrEF differs from healthy controls and shares similarities with HFrEF in cardiac MRI parameters of fibrosis and inflammation. Full article
(This article belongs to the Special Issue Acute and Chronic Heart Failure)
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9 pages, 269 KiB  
Article
Better Myocardial Function in Aortic Stenosis with Low Left Ventricular Mass: A Mechanism of Protection against Heart Failure Regardless of Stenosis Severity?
by Bernadeta Chyrchel, Klaudiusz Bolt, Dorota Długosz, Anna Urbańska, Małgorzata Nowak-Kępczyk, Joanna Bałata, Agnieszka Rożanowska, Ewa Czestkowska, Olga Kruszelnicka and Andrzej Surdacki
J. Clin. Med. 2019, 8(11), 1836; https://doi.org/10.3390/jcm8111836 - 1 Nov 2019
Cited by 1 | Viewed by 2266
Abstract
About one-tenth to one-third of patients with severe aortic stenosis (AS) do not develop left ventricular hypertrophy (LVH). Intriguingly, the absence of LVH despite severe AS is associated with lower prevalence of heart failure (HF), which challenges the classical notion of LVH as [...] Read more.
About one-tenth to one-third of patients with severe aortic stenosis (AS) do not develop left ventricular hypertrophy (LVH). Intriguingly, the absence of LVH despite severe AS is associated with lower prevalence of heart failure (HF), which challenges the classical notion of LVH as a beneficial compensatory response. Notably, the few studies that have attempted to characterize AS subjects with inadequately low left ventricular (LV) mass relative to LV afterload (i-lowLVM) described better prognosis and enhanced LV performance in AS associated with i-lowLVM, but those reports were limited to severe AS. Our aim was to compare myocardial function between moderate and severe AS with i-lowLVM. We retrospectively analyzed in-hospital records of 225 clinically stable nondiabetic patients with isolated moderate or severe degenerative AS in sinus rhythm, free of coexistent diseases. Subjects with i-lowLVM were compared to those with appropriate or excessive LVM (a/e-LVM), defined on the basis of the ratio of a measured LVM to the LVM predicted from an individual hemodynamic load. Patients with i-lowLVM and a/e-LVM did not differ in aortic valve area, LV end-diastolic diameter (LVd, a measure of LV preload), and circumferential end-systolic LV wall stress (cESS), an estimate of LV afterload. Compared to a/e-LVM, patients with i-lowLVM had increased LV ejection fraction (EF) and especially higher LV midwall fractional shortening (a better index of LV myocardial function than EF in concentric LV geometry) (p < 0.001–0.01), in both moderate and severe AS. LVd and cESS were similar in the four subgroups of the study subjects, i.e., moderate AS with i-lowLVM, moderate AS with a/e-LVM, severe AS with i-lowLVM, and severe AS with a/e-LVM (p > 0.6). Among patients with i-lowLVM, LVM did not differ significantly between moderate and severe AS (p > 0.4), while in those with a/e-LVM, LVM was increased in severe versus moderate AS (p < 0.001). In conclusion, the association of the low-LVM phenotype with better myocardial contractility may already develop in moderate AS. Additionally, cESS appears to be a controlled variable, which is kept constant over AS progression irrespective of LVM category, but even when controlled (by increasing LVM), is not able to prevent deterioration of LV function. Whether improved myocardial performance contributes to favorable prognosis and the preventive effect against HF in AS without LVH, remains to be studied. Full article
(This article belongs to the Special Issue Acute and Chronic Heart Failure)
12 pages, 375 KiB  
Article
Prognostic Value of the Echocardiographic Probability of Pulmonary Hypertension in Patients with Acute Decompensated Heart Failure
by Sebastian Carballo, Philippe Musso, Nicolas Garin, Hajo Müller, Jacques Serratrice, François Mach, David Carballo and Jérôme Stirnemann
J. Clin. Med. 2019, 8(10), 1684; https://doi.org/10.3390/jcm8101684 - 15 Oct 2019
Cited by 5 | Viewed by 2844
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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11 pages, 420 KiB  
Article
Iron Deficiency in Acute Decompensated Heart Failure
by Anna Beale, David Carballo, Jerome Stirnemann, Nicolas Garin, Thomas Agoritsas, Jacques Serratrice, David Kaye, Philippe Meyer and Sebastian Carballo
J. Clin. Med. 2019, 8(10), 1569; https://doi.org/10.3390/jcm8101569 - 1 Oct 2019
Cited by 15 | Viewed by 3371
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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19 pages, 9131 KiB  
Article
Autophagy and Inflammasome Activation in Dilated Cardiomyopathy
by Angela Caragnano, Aneta Aleksova, Michela Bulfoni, Celeste Cervellin, Irene Giulia Rolle, Claudia Veneziano, Arianna Barchiesi, Maria Chiara Mimmi, Carlo Vascotto, Nicoletta Finato, Sandro Sponga, Ugolino Livi, Miriam Isola, Carla Di Loreto, Rossana Bussani, Gianfranco Sinagra, Daniela Cesselli and Antonio Paolo Beltrami
J. Clin. Med. 2019, 8(10), 1519; https://doi.org/10.3390/jcm8101519 - 21 Sep 2019
Cited by 35 | Viewed by 5854
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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12 pages, 1408 KiB  
Article
Patients with Heart Failure and Preserved Ejection Fraction Are at Risk of Gastrointestinal Bleeding
by Lore Schrutka, Benjamin Seirer, Franz Duca, Christina Binder, Daniel Dalos, Andreas Kammerlander, Stefan Aschauer, Lorenz Koller, Alberto Benazzo, Asan Agibetov, Marianne Gwechenberger, Christian Hengstenberg, Julia Mascherbauer and Diana Bonderman
J. Clin. Med. 2019, 8(8), 1240; https://doi.org/10.3390/jcm8081240 - 17 Aug 2019
Cited by 11 | Viewed by 4018
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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11 pages, 1008 KiB  
Article
Antiarrhythmic Effect of Sacubitril-Valsartan: Cause or Consequence of Clinical Improvement?
by António Valentim Gonçalves, Tiago Pereira-da-Silva, Ana Galrinho, Pedro Rio, Luísa Moura Branco, Rui Soares, Joana Feliciano, Rita Ilhão Moreira and Rui Cruz Ferreira
J. Clin. Med. 2019, 8(6), 869; https://doi.org/10.3390/jcm8060869 - 18 Jun 2019
Cited by 29 | Viewed by 4629
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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13 pages, 1570 KiB  
Article
Heterogeneous Metabolic Response to Exercise Training in Heart Failure with Preserved Ejection Fraction
by Martin Bahls, Nele Friedrich, Maik Pietzner, Rolf Wachter, Kathrin Budde, Gerd Hasenfuß, Matthias Nauck, Axel Pressler, Stephan B. Felix, Frank Edelmann, Martin Halle and Marcus Dörr
J. Clin. Med. 2019, 8(5), 591; https://doi.org/10.3390/jcm8050591 - 29 Apr 2019
Cited by 5 | Viewed by 4139
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 (ISRCTN42524037). 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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15 pages, 1675 KiB  
Article
The Predictivity of N-Terminal Pro b-Type Natriuretic Peptide for All-Cause Mortality in Various Follow-Up Periods among Heart Failure Patients
by Min-Yu Lai, Wei-Chih Kan, Ya-Ting Huang, John Chen and Chih-Chung Shiao
J. Clin. Med. 2019, 8(3), 357; https://doi.org/10.3390/jcm8030357 - 13 Mar 2019
Cited by 8 | Viewed by 4167
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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17 pages, 931 KiB  
Review
Comparison of Hemodynamic Factors Predicting Prognosis in Heart Failure: A Systematic Review
by Margot Aalders and Wouter Kok
J. Clin. Med. 2019, 8(10), 1757; https://doi.org/10.3390/jcm8101757 - 22 Oct 2019
Cited by 17 | Viewed by 4314
Abstract
Objectives: We systematically reviewed the literature to address the question of which of the three hemodynamic factors predicts prognosis best in heart failure patients when directly compared to each other: cardiac output, preload or afterload. Methods: Prognostic studies in heart failure (HF) were [...] Read more.
Objectives: We systematically reviewed the literature to address the question of which of the three hemodynamic factors predicts prognosis best in heart failure patients when directly compared to each other: cardiac output, preload or afterload. Methods: Prognostic studies in heart failure (HF) were searched that included at least two of the three hemodynamic variables: (1) cardiac output or cardiac index (CI), (2) preload represented by pulmonary capillary wedge pressure (PCWP) and (3) afterload simplified to systolic blood pressure (SBP). Critical appraisal was done according to the QUIPS format for prognostic studies. The main endpoint was all-cause mortality, which could be combined with other endpoints. We report the number of studies in which CI, PCWP and SBP remained significant prognostic predictors in multivariate analysis. We also assessed whether hemodynamic predictors of prognosis varied in four different HF-populations. Results: Included were 18 studies containing a multivariate analysis. PCWP was an independent predictor of prognosis in 10 of 18 studies, SBP in 3 of 14 studies and CI in none of 18 studies. Results were not specific for any of the HF-populations. Conclusions: A higher PCWP and lower SBP are independent predictors of poor prognosis in HF. In spite of the frequently used concept behind HF, this review demonstrates that CI is not an independent predictor of prognosis in HF. Full article
(This article belongs to the Special Issue Acute and Chronic Heart Failure)
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20 pages, 1597 KiB  
Review
The Endocrine Function of the Heart: Physiology and Involvements of Natriuretic Peptides and Cyclic Nucleotide Phosphodiesterases in Heart Failure
by Claire Lugnier, Alain Meyer, Anne Charloux, Emmanuel Andrès, Bernard Gény and Samy Talha
J. Clin. Med. 2019, 8(10), 1746; https://doi.org/10.3390/jcm8101746 - 21 Oct 2019
Cited by 32 | Viewed by 13566
Abstract
Besides pumping, the heart participates in hydro-sodium homeostasis and systemic blood pressure regulation through its endocrine function mainly represented by the large family of natriuretic peptides (NPs), including essentially atrial natriuretic (ANP) and brain natriuretic peptides (BNP). Under normal conditions, these peptides are [...] Read more.
Besides pumping, the heart participates in hydro-sodium homeostasis and systemic blood pressure regulation through its endocrine function mainly represented by the large family of natriuretic peptides (NPs), including essentially atrial natriuretic (ANP) and brain natriuretic peptides (BNP). Under normal conditions, these peptides are synthesized in response to atrial cardiomyocyte stretch, increase natriuresis, diuresis, and vascular permeability through binding of the second intracellular messenger’s guanosine 3′,5′-cyclic monophosphate (cGMP) to specific receptors. During heart failure (HF), the beneficial effects of the enhanced cardiac hormones secretion are reduced, in connection with renal resistance to NP. In addition, there is a BNP paradox characterized by a physiological inefficiency of the BNP forms assayed by current methods. In this context, it appears interesting to improve the efficiency of the cardiac natriuretic system by inhibiting cyclic nucleotide phosphodiesterases, responsible for the degradation of cGMP. Recent data support such a therapeutic approach which can improve the quality of life and the prognosis of patients with HF. Full article
(This article belongs to the Special Issue Acute and Chronic Heart Failure)
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14 pages, 810 KiB  
Review
Sex and Heart Failure with Preserved Ejection Fraction: From Pathophysiology to Clinical Studies
by Marijana Tadic, Cesare Cuspidi, Sven Plein, Evgeny Belyavskiy, Frank Heinzel and Maurizio Galderisi
J. Clin. Med. 2019, 8(6), 792; https://doi.org/10.3390/jcm8060792 - 4 Jun 2019
Cited by 38 | Viewed by 12971
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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17 pages, 272 KiB  
Review
Biomarkers in the Diagnosis, Management, and Prognostication of Perioperative Right Ventricular Failure in Cardiac Surgery—Are We There Yet?
by Habib Jabagi, Lisa M. Mielniczuk, Peter P. Liu, Marc Ruel and Louise Y. Sun
J. Clin. Med. 2019, 8(4), 559; https://doi.org/10.3390/jcm8040559 - 25 Apr 2019
Cited by 14 | Viewed by 3686
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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