Chronic Heart Failure: Diagnosis and Management beyond LVEF Classification

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

Deadline for manuscript submissions: closed (15 December 2022) | Viewed by 31489

Special Issue Editors


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Guest Editor
Department of Cardiology, University of Thessaly, Larissa University General Hospital, Box 1425, 411 10 Larissa, PO, Greece
Interests: invasive cardiology; heart failure; intensive care

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Guest Editor
Heart Failure and Cardiac Transplant Medicine, Department of Cardiovascular Medicine, Kaufman Center for Heart Failure, Cleveland Clinic, Cleveland, OH 44195, USA
Interests: biventricular pacemaker; cardiac transplant; cardiac transplantation; endomyocardial biopsy; heart failure management; mechanical circulatory support

Special Issue Information

Dear Colleagues,

We invite you to participate in this Special Issue of JCM on “Chronic Heart Failure: Diagnosis and Management beyond LVEF Classification”. As you well know, heart failure (HF) is now recognised as a major and escalating public health problem in industrialized countries with aging populations. Data suggest that the incidence of HF is mostly flat or declining but that mortality and hospitalization rates remains virtually unabated despite significant ongoing efforts to manage HF. These disturbing trends reflect the complexity of the HF syndrome and the insufficient mechanistic understanding of its various manifestations and presentations. Further, classification and management, of HF has been based on the left ventricular ejection fraction (LVEF), which has emerged as the reigning dogma based on the practicalities of clinical trial design and may be too simplistic for a multifaceted and complex syndrome, such as HF. In this Special Issue of JCM, we seek clinical and experimental studies with emphasis on HF diagnosis, pathogenesis, and management, including advanced HF. Both original research papers and comprehensive review papers are welcome.

Prof. Dr. Filippos Triposkiadis
Prof. Dr. Randall Starling
Guest Editors

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Keywords

  • chronic disease
  • heart failure
  • diagnosis
  • management
  • pathogenesis

Published Papers (10 papers)

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Editorial

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2 pages, 175 KiB  
Editorial
Chronic Heart Failure: Diagnosis and Management beyond LVEF Classification
by Filippos Triposkiadis and Randall C. Starling
J. Clin. Med. 2022, 11(6), 1718; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm11061718 - 19 Mar 2022
Cited by 6 | Viewed by 2053
Abstract
The classification, phenotyping, and management of heart failure (HF) has been based on the left ventricular (LV) ejection fraction (LVEF) [...] Full article

Research

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10 pages, 1311 KiB  
Article
Sex-Specific Predictors of Long-Term Mortality in Elderly Patients with Ischemic Cardiomyopathy
by Hyun Ju Yoon, Kye Hun Kim, Nuri Lee, Hyukjin Park, Hyung Yoon Kim, Jae Yeong Cho, Youngkeun Ahn and Myung Ho Jeong
J. Clin. Med. 2023, 12(5), 2012; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm12052012 - 03 Mar 2023
Viewed by 1117
Abstract
Ischemic heart failure (HF) is one of the most common causes of morbidity and mortality in the world-wide, but sex-specific predictors of mortality in elderly patients with ischemic cardiomyopathy (ICMP) have been poorly studied. A total of 536 patients with ICMP over 65 [...] Read more.
Ischemic heart failure (HF) is one of the most common causes of morbidity and mortality in the world-wide, but sex-specific predictors of mortality in elderly patients with ischemic cardiomyopathy (ICMP) have been poorly studied. A total of 536 patients with ICMP over 65 years-old (77.8 ± 7.1 years, 283 males) were followed for a mean of 5.4 years. The development of death during clinical follow up was evaluated, and predictors of mortality were compared. Death was developed in 137 patients (25.6%); 64 females (25.3%) vs. 73 males (25.8%). Low-ejection fraction was only an independent predictor of mortality in ICMP, regardless of sex (HR 3.070 CI = 1.708–5.520 in female, HR 2.011, CI = 1.146–3.527 in male). Diabetes (HR 1.811, CI = 1.016–3.229), elevated e/e’ (HR 2.479, CI = 1.201–5.117), elevated pulmonary artery systolic pressure (HR 2.833, CI = 1.197–6.704), anemia (HR 1.860, CI = 1.025–3.373), beta blocker non-use (HR2.148, CI = 1.010–4.568), and angiotensin receptor blocker non-use (HR 2.100, CI = 1.137–3.881) were bad prognostic factors of long term mortality in female, whereas hypertension (HR 1.770, CI = 1.024–3.058), elevated Creatinine (HR 2.188, CI = 1.225–3.908), and statin non-use (HR 3.475, CI = 1.989–6.071) were predictors of mortality in males with ICMP independently. Systolic dysfunction in both sexes, diastolic dysfunction, beta blocker and angiotensin receptor blockers in female, and statins in males have important roles for long-term mortality in elderly patients with ICMP. For improving long-term survival in elderly patients with ICMP, it may be necessary to approach sex specifically. Full article
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11 pages, 3443 KiB  
Article
Inward Displacement: A Novel Method of Regional Left Ventricular Functional Assessment for Left Ventriculoplasty Interventions in Heart Failure with Reduced Ejection Fraction (HFrEF)
by Romy R. M. J. J. Hegeman, Sean McManus, Jan-Peter van Kuijk, Serge C. Harb, Martin J. Swaans, Patrick Klein and Rishi Puri
J. Clin. Med. 2023, 12(5), 1997; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm12051997 - 02 Mar 2023
Cited by 2 | Viewed by 2613
Abstract
Background: Hybrid minimally invasive left ventricular reconstruction is used to treat patients with ischemic heart failure with reduced ejection fraction (HFrEF) and antero-apical scar. Pre- and post-procedural regional functional left ventricular assessment with current imaging techniques remains limited. We evaluated ‘inward displacement’ as [...] Read more.
Background: Hybrid minimally invasive left ventricular reconstruction is used to treat patients with ischemic heart failure with reduced ejection fraction (HFrEF) and antero-apical scar. Pre- and post-procedural regional functional left ventricular assessment with current imaging techniques remains limited. We evaluated ‘inward displacement’ as a novel technique of assessing regional left ventricular function in an ischemic HFrEF population who underwent left ventricular reconstruction with the Revivent System. Methods: Inward displacement adopts three standard long-axis views obtained during cardiac MRI or CT and assesses the degree of inward endocardial wall motion towards the true left ventricular center of contraction. For each of the standard 17 left ventricular segments, regional inward displacement is measured in mm and expressed as a percentage of the maximal theoretical distance each segment can contract towards the centerline. The left ventricle was divided into three regions, obtaining the arithmetic average of inward displacement or speckle tracking echocardiographic strain at the left ventricular base (segments 1–6), mid-cavity (segments 7–12) and apex (segments 13–17). Inward displacement was measured using computed tomography or cardiac magnetic resonance imaging and compared pre- and post-procedurally in ischemic HFrEF patients who underwent left ventricular reconstruction with the Revivent System (n = 36). In a subset of patients who underwent baseline speckle tracking echocardiography, pre-procedural inward displacement was compared with left ventricular regional echocardiographic strain (n = 15). Results: Inward displacement of basal and mid-cavity left ventricular segments increased by 27% (p < 0.001) and 37% (p < 0.001), respectively, following left ventricular reconstruction. A significant overall decrease in both the left ventricular end systolic volume index and end diastolic volume index of 31% (p < 0.001) and 26% (p < 0.001), respectively, was detected, along with a 20% increase in left ventricular ejection fraction (p = 0.005). A significant correlation between inward displacement and speckle tracking echocardiographic strain was noted within the basal (R = −0.77, p < 0.001) and mid-cavity left ventricular segments (R = −0.65, p = 0.004), respectively. Inward displacement resulted in relatively larger measurement values compared to speckle tracking echocardiography, with a mean difference of absolute values of −3.33 and −7.41 for the left ventricular base and mid-cavity, respectively. Conclusions: Obviating the limitations of echocardiography, inward displacement was found to highly correlate with speckle tracking echocardiographic strain to evaluate regional segmental left ventricular function. Significant improvements in basal and mid-cavity left ventricular contractility were demonstrated in ischemic HFrEF patients following left ventricular reconstruction of large antero-apical scars, consistent with the concept of reverse left ventricular remodeling at a distance. Inward displacement holds significant promise in the HFrEF population being evaluated pre- and post-left ventriculoplasty procedures. Full article
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18 pages, 763 KiB  
Article
Kinematic Parameters That Can Discriminate in Levels of Functionality in the Six-Minute Walk Test in Patients with Heart Failure with a Preserved Ejection Fraction
by Iván José Fuentes-Abolafio, Manuel Trinidad-Fernández, Adrian Escriche-Escuder, Cristina Roldán-Jiménez, José María Arjona-Caballero, M. Rosa Bernal-López, Michele Ricci, Ricardo Gómez-Huelgas, Luis Miguel Pérez-Belmonte and Antonio Ignacio Cuesta-Vargas
J. Clin. Med. 2023, 12(1), 241; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm12010241 - 28 Dec 2022
Cited by 1 | Viewed by 1681
Abstract
It is a challenge to manage and assess heart failure with preserved left ventricular ejection fraction (HFpEF) patients. Six-Minute Walk Test (6MWT) is used in this clinical population as a functional test. The objective of the study was to assess gait and kinematic [...] Read more.
It is a challenge to manage and assess heart failure with preserved left ventricular ejection fraction (HFpEF) patients. Six-Minute Walk Test (6MWT) is used in this clinical population as a functional test. The objective of the study was to assess gait and kinematic parameters in HFpEF patients during the 6MWT with an inertial sensor and to discriminate patients according to their performance in the 6MWT: (1) walk more or less than 300 m, (2) finish or stop the test, (3) women or men and (4) fallen or did not fall in the last year. A cross-sectional study was performed in patients with HFpEF older than 70 years. 6MWT was carried out in a closed corridor larger than 30 m. Two Shimmer3 inertial sensors were used in the chest and lumbar region. Pure kinematic parameters analysed were angular velocity and linear acceleration in the three axes. Using these data, an algorithm calculated gait kinematic parameters: total distance, lap time, gait speed and step and stride variables. Two analyses were done according to the performance. Student’s t-test measured differences between groups and receiver operating characteristic assessed discriminant ability. Seventy patients performed the 6MWT. Step time, step symmetry, stride time and stride symmetry in both analyses showed high AUC values (>0.75). More significant differences in velocity and acceleration in the maximum Y axis or vertical movements. Three pure kinematic parameters obtained good discriminant capacity (AUC > 0.75). The new methodology proved differences in gait and pure kinematic parameters that can distinguish two groups according to the performance in the 6MWT and they had discriminant capacity. Full article
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Review

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18 pages, 994 KiB  
Review
Prognostic Role of Metabolic Exercise Testing in Heart Failure
by Arianne Clare Agdamag, Erik H. Van Iterson, W. H. Wilson Tang and J. Emanuel Finet
J. Clin. Med. 2023, 12(13), 4438; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm12134438 - 30 Jun 2023
Cited by 1 | Viewed by 1758
Abstract
Heart failure is a clinical syndrome with significant heterogeneity in presentation and severity. Serial risk-stratification and prognostication can guide management decisions, particularly in advanced heart failure, when progression toward advanced therapies or end-of-life care is warranted. Each currently utilized prognostic marker carries its [...] Read more.
Heart failure is a clinical syndrome with significant heterogeneity in presentation and severity. Serial risk-stratification and prognostication can guide management decisions, particularly in advanced heart failure, when progression toward advanced therapies or end-of-life care is warranted. Each currently utilized prognostic marker carries its own set of challenges in acquisition, reproducibility, accuracy, and significance. Left ventricular ejection fraction is foundational for heart failure syndrome classification after clinical diagnosis and remains the primary parameter for inclusion in most clinical trials; however, it does not consistently correlate with symptoms and functional capacity, which are also independently prognostic in this patient population. Utilizing the left ventricular ejection fraction as the sole basis of prognostication provides an incomplete characterization of this condition and is prone to misguide medical decision-making when used in isolation. In this review article, we survey and exposit the important role of metabolic exercise testing across the heart failure spectrum, as a complementary diagnostic and prognostic modality. Metabolic exercise testing, also known as cardiopulmonary exercise testing, provides a comprehensive evaluation of the multisystem (i.e., neurological, respiratory, circulatory, and musculoskeletal) response to exercise performance. These differential responses can help identify the predominant contributors to exercise intolerance and exercise symptoms. Additionally, the aerobic exercise capacity (i.e., oxygen consumption during exercise) is directly correlated with overall life expectancy and prognosis in many disease states. Specifically in heart failure patients, metabolic exercise testing provides an accurate, objective, and reproducible assessment of the overall circulatory sufficiency and circulatory reserve during physical stress, being able to isolate the concurrent chronotropic and stroke volume responses for a reliable depiction of the circulatory flow rate in real time. Full article
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13 pages, 830 KiB  
Review
Structural Interventions in Heart Failure: Mending a Broken Heart
by David Katzianer and Chonyang Albert
J. Clin. Med. 2023, 12(9), 3243; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm12093243 - 01 May 2023
Viewed by 1326
Abstract
Advanced heart failure is often accompanied by perturbations in cardiac chamber or valve geometries which result in worsening cardiac function and hemodynamics. Once limited to surgical procedures, recent developments in minimally invasive percutaneous techniques have demonstrated efficacy in patients with both reduced and [...] Read more.
Advanced heart failure is often accompanied by perturbations in cardiac chamber or valve geometries which result in worsening cardiac function and hemodynamics. Once limited to surgical procedures, recent developments in minimally invasive percutaneous techniques have demonstrated efficacy in patients with both reduced and preserved ejection fraction who are at an elevated surgical risk for perioperative events. This review highlights a subset of the interventions available in clinical practice or in development for the treatment of these valvular and structural alterations. Full article
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16 pages, 1324 KiB  
Review
Does the Measurement of Ejection Fraction Still Make Sense in the HFpEF Framework? What Recent Trials Suggest
by Alberto Palazzuoli, Michele Correale, Massimo Iacoviello and Edoardo Gronda
J. Clin. Med. 2023, 12(2), 693; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm12020693 - 15 Jan 2023
Cited by 4 | Viewed by 4889
Abstract
Left ventricular ejection fraction (LVEF) is universally accepted as a cardiac systolic function index and it provides intuitive interpretation of cardiac performance. Over the last two decades, it has erroneously become the leading feature used by clinicians to characterize the left ventricular function [...] Read more.
Left ventricular ejection fraction (LVEF) is universally accepted as a cardiac systolic function index and it provides intuitive interpretation of cardiac performance. Over the last two decades, it has erroneously become the leading feature used by clinicians to characterize the left ventricular function in heart failure (HF). Notably, LVEF sets the basis for structural and functional HF phenotype classification in current guidelines. However, its diagnostic and prognostic role in patients with preserved or mildly reduced contractile function is less clear. This is related to several concerns due to intrinsic technical, methodological and hemodynamic limitations entailed in LVEF measurement that do not describe the chamber’s real contractile performance as expressed by pressure volume loop relationship. In patients with HF and preserved ejection fraction (HFpEF), it does not reflect the effective systolic function because it is prone to preload and afterload variability and it does not account for both longitudinal and torsional contraction. Moreover, a repetitive measurement could be assessed over time to better identify HF progression related to natural evolution of disease and to the treatment response. Current gaps may partially explain the causes of negative or neutral effects of traditional medical agents observed in HFpEF. Nevertheless, recent pooled analysis has evidenced the positive effects of new therapies across the LVEF range, suggesting a potential role irrespective of functional status. Additionally, a more detailed analysis of randomized trials suggests that patients with higher LVEF show a risk reduction strictly related to overall cardiovascular (CV) events; on the other hand, patients experiencing lower LVEF values have a decrease in HF-related events. The current paper reports the main limitations and shortcomings in LVEF assessment, with specific focus on patients affected by HFpEF, and it suggests alternative measurements better reflecting the real hemodynamic status. Future investigations may elucidate whether the development of non-invasive stroke volume and longitudinal function measurements could be extensively applied in clinical trials for better phenotyping and screening of HFpEF patients. Full article
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11 pages, 1048 KiB  
Review
Reshaping Treatment of Heart Failure with Preserved Ejection Fraction
by Nikolaos Karamichalakis, Andrew Xanthopoulos, Filippos Triposkiadis, Ioannis Paraskevaidis and Elias Tsougos
J. Clin. Med. 2022, 11(13), 3706; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm11133706 - 27 Jun 2022
Cited by 2 | Viewed by 3029
Abstract
Current data indicate that in the community, approximately 50% of patients with heart failure (HF) have preserved left ventricular (LV) ejection fraction (LVEF)—the so-called HFpEF. Treatment of HFpEF has been considered an unmet need for decades. We believe that the main underlying reasons [...] Read more.
Current data indicate that in the community, approximately 50% of patients with heart failure (HF) have preserved left ventricular (LV) ejection fraction (LVEF)—the so-called HFpEF. Treatment of HFpEF has been considered an unmet need for decades. We believe that the main underlying reasons have been (a) the ever-changing LVEF cut-offs used for HF classification; (b) controversies regarding the definition of the LVEF normal range; (c) the fact that HFpEF does not represent a phenotype, but a category of diseases with entirely different characteristics (hypertensive heart disease, valvular heart disease (VHD), hypertrophic cardiomyopathy (HCM) etc.); (d) the lack of recognition that hypertensive HFpEF is the most common and important HFpEF phenotype; (e) the assumption that neurohormonal overactivity is absent in HF patients with a LVEF > 45–50% which has been proven to be wrong. Current HFpEF trials, in which the vast majority of the participants suffered from hypertension (HTN), whereas VHD and HCM were absent, demonstrated that neurohormonal and sodium-glucose cotransporter 2 (SGLT2) inhibitors are effective in HF patients over a wide LVEF range. Thus, restricting these lifesaving treatments to HF patients with reduced LVEF is not justified anymore and it should be additionally considered for HFpEF patients suffering from HTN. Full article
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14 pages, 2041 KiB  
Review
The Interventricular Septum: Structure, Function, Dysfunction, and Diseases
by Filippos Triposkiadis, Andrew Xanthopoulos, Konstantinos Dean Boudoulas, Grigorios Giamouzis, Harisios Boudoulas and John Skoularigis
J. Clin. Med. 2022, 11(11), 3227; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm11113227 - 06 Jun 2022
Cited by 6 | Viewed by 6100
Abstract
Vertebrates developed pulmonary circulation and septated the heart into venous and arterial compartments, as the adaptation from aquatic to terrestrial life requires more oxygen and energy. The interventricular septum (IVS) accommodates the ventricular portion of the conduction system and contributes to the mechanical [...] Read more.
Vertebrates developed pulmonary circulation and septated the heart into venous and arterial compartments, as the adaptation from aquatic to terrestrial life requires more oxygen and energy. The interventricular septum (IVS) accommodates the ventricular portion of the conduction system and contributes to the mechanical function of both ventricles. Conditions or diseases that affect IVS structure and function (e.g., hypertrophy, defects, other) may lead to ventricular pump failure and/or ventricular arrhythmias with grave consequences. IVS structure and function can be evaluated today using current imaging techniques. Effective therapies can be provided in most cases, although definitions of underlying etiologies may not always be easy, particularly in the elderly due to overlap between genetic and acquired causes of IVS hypertrophy, the most common being IVS abnormality. In this review, state-of-the-art information regarding IVS morphology, physiology, physiopathology, and disease is presented. Full article
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Other

14 pages, 613 KiB  
Perspective
Heart Failure Pharmacological Management: Gaps and Current Perspectives
by Paolo Severino, Andrea D'Amato, Silvia Prosperi, Vincenzo Myftari, Elena Sofia Canuti, Aurora Labbro Francia, Claudia Cestiè, Viviana Maestrini, Carlo Lavalle, Roberto Badagliacca, Massimo Mancone, Carmine Dario Vizza and Francesco Fedele
J. Clin. Med. 2023, 12(3), 1020; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm12031020 - 28 Jan 2023
Cited by 8 | Viewed by 5733
Abstract
Proper therapeutic management of patients with heart failure (HF) is a major challenge for cardiologists. Current guidelines indicate to start therapy with angiotensin converting enzyme inhibitors/angiotensin receptor neprilysin inhibitors (ACEi/ARNI), beta blockers (BB), mineralocorticoid receptor antagonists (MRAs) and sodium glucose cotransporter 2 inhibitors [...] Read more.
Proper therapeutic management of patients with heart failure (HF) is a major challenge for cardiologists. Current guidelines indicate to start therapy with angiotensin converting enzyme inhibitors/angiotensin receptor neprilysin inhibitors (ACEi/ARNI), beta blockers (BB), mineralocorticoid receptor antagonists (MRAs) and sodium glucose cotransporter 2 inhibitors (SGLT2i) to reduce the risk of death and hospitalization due to HF. However, certain aspects still need to be defined. Current guidelines propose therapeutic algorithms based on left ventricular ejection fraction values and clinical presentations. However, these last do not always reflect the precise hemodynamic status of patients and pathophysiological mechanisms involved, particularly in the acute setting. Even in the field of chronic management there are still some critical points to discuss. The guidelines do not specify which of the four pillar drugs to start first, nor at what dosage. Some authors suggest starting with SGLT2i and BB, others with ACEi or ARNI, while one of the most recent approach proposes to start with all four drugs together at low doses. The aim of this review is to revise current gaps and perspectives regarding pharmacological therapy management in HF patients, in both the acute and chronic phase. Full article
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