Journal of Clinical Medicine

Editorial

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2 pages, 175 KiB

Open AccessEditorial

Heart Failure with Preserved Ejection Fraction Is a Still Big Unmet Need in Cardiology

by Nobuyuki Ohte

J. Clin. Med. 2021, 10(11), 2460; https://doi.org/10.3390/jcm10112460 - 1 Jun 2021

Cited by 1 | Viewed by 2083

Abstract

Miñana and Núñez wrote an editorial to introduce the contents in a Special Issue of the Journal of Clinical Medicine focused on “Epidemiology, Diagnosis, Pathophysiology, Risk Stratification, and Therapy of Heart Failure with Preserved Ejection Fraction” [...] Full article

(This article belongs to the Special Issue Epidemiology, Diagnosis, Pathophysiology, Risk Stratification, and Therapy of Heart Failure with Preserved Ejection Fraction)

2 pages, 187 KiB

Open AccessEditorial

Heart Failure with Preserved Ejection Fraction: An Urgent Need for Precision Medicine

by Gema Miñana and Julio Núñez

J. Clin. Med. 2021, 10(9), 1801; https://doi.org/10.3390/jcm10091801 - 21 Apr 2021

Cited by 3 | Viewed by 1488

Abstract

Heart failure with preserved (HFpEF) and mid-range ejection fraction (HFmrEF) constitute two heart failure categories, representing about 50–70% of the total [...] Full article

(This article belongs to the Special Issue Epidemiology, Diagnosis, Pathophysiology, Risk Stratification, and Therapy of Heart Failure with Preserved Ejection Fraction)

Research

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15 pages, 1260 KiB

Open AccessArticle

What Type of Patients Did PARAGON-HF Select? Insights from a Real-World Prospective Cohort of Patients with Heart Failure and Preserved Ejection Fraction

by René Rettl, Theresa-Marie Dachs, Franz Duca, Christina Binder, Fabian Dusik, Benjamin Seirer, Johannes Schönauer, Christina Kronberger, Luciana Camuz Ligios, Christian Hengstenberg, Nina Derkits, Johannes Kastner, Roza Badr Eslam and Diana Bonderman

J. Clin. Med. 2020, 9(11), 3669; https://doi.org/10.3390/jcm9113669 - 15 Nov 2020

Cited by 8 | Viewed by 2389

Abstract

The PARAGON-HF clinical trial suggested that sacubitril/valsartan may become a treatment option for particular subgroups of patients with heart failure and preserved ejection fraction (HFpEF). However, the proportion of real-world HFpEF patients who are theoretically superimposable with the PARAGON-HF population is yet unknown. [...] Read more.

The PARAGON-HF clinical trial suggested that sacubitril/valsartan may become a treatment option for particular subgroups of patients with heart failure and preserved ejection fraction (HFpEF). However, the proportion of real-world HFpEF patients who are theoretically superimposable with the PARAGON-HF population is yet unknown. The present study was performed to define the proportion of real-world PARAGON-HF-like patients and to describe their clinical characteristics and long-term prognosis in comparison with those who would not meet PARAGON-HF criteria. We systematically applied PARAGON-HF inclusion and exclusion criteria to a total of 427 HFpEF patients who have been participating in a prospective national registry between December 2010 and December 2019. In total, only 170 (39.8%) registry patients were theoretically eligible for PARAGON-HF. Patients not meeting inclusion criteria (41.0%) were less impaired with respect to exercise capacity (median 6-min walk distance: 385 m (IQR: 300–450) versus 323 m (IQR: 240–383); p < 0.001) had lower pulmonary pressures (mean pulmonary artery pressure (mPAP): 31.2 mmHg, standard deviation (SD): ±10.2 versus 32.8 mmHg, SD: ±9.7; p < 0.001) and better outcomes (log-rank: p < 0.001) as compared to the PARAGON-like cohort. However, patients theoretically excluded from the trial (19.2%) were those with most advanced heart failure symptoms (median 6-min walk test: 252 m (IQR: 165–387); p < 0.001), highest pulmonary pressures (mPAP: 38.2 mmHg, SD: ±12.4; p < 0.001) and worst outcome (log-rank: p = 0.037). We demonstrate here that < 40% of real-world HFpEF patients meet eligibility criteria for PARAGON-HF. We conclude that despite reasons for optimism after PARAGON-HF, a large proportion of HFpEF patients will remain without meaningful treatment options. Full article

(This article belongs to the Special Issue Epidemiology, Diagnosis, Pathophysiology, Risk Stratification, and Therapy of Heart Failure with Preserved Ejection Fraction)

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10 pages, 1832 KiB

Open AccessArticle

Mitral Valve Repair of Atrial Functional Mitral Regurgitation in Heart Failure with Preserved Ejection Fraction

by Zsuzsanna Balogh, Takuya Mizukami, Jozef Bartunek, Carlos Collet, Monika Beles, Marzia Albano, Asim Katbeh, Filip Casselman, Marc Vanderheyden, Guy Van Camp, Frank Van Praet and Martin Penicka

J. Clin. Med. 2020, 9(11), 3432; https://doi.org/10.3390/jcm9113432 - 26 Oct 2020

Cited by 13 | Viewed by 2297

Abstract

Our objective was to describe the long-term effects of endoscopic mitral valve (MV) repair on outcome in patients with heart failure with preserved ejection fraction (HFpEF) and atrial functional mitral regurgitation (AFMR). In patients with HFpEF, even mild AFMR has been associated with [...] Read more.

Our objective was to describe the long-term effects of endoscopic mitral valve (MV) repair on outcome in patients with heart failure with preserved ejection fraction (HFpEF) and atrial functional mitral regurgitation (AFMR). In patients with HFpEF, even mild AFMR has been associated with poor outcome. The study population consisted of consecutive patients with HFpEF (left ventricular ejection fraction (LVEF) ≥ 50%, H₂FPEF score ≥ 5) and AFMR, who underwent isolated, minimally invasive endoscopic MV repair (MVRepair group) (n = 131) or remained on standard of care (StanCare group) (n = 139). Patients with coronary artery disease or organic mitral regurgitation (MR) were excluded. Patients were matched using inverse probability of treatment weighting. Endpoints were all-cause mortality and a composite of all-cause mortality and HFpEF readmissions. The median follow-up was 5.03 years (interquartile range (IQR) 2.6–7.9 years). In the MVRepair group, the perioperative, 30-day, 1-year, and 5-year mortality were 0, 1%, 1%, and 12%, respectively. Additionally, 13 (10%) patients were readmitted for worsening HFpEF, while 2 (1%) individuals underwent redo MV surgery for recurrent MR. MVRepair compared with StanCare showed 21–29% (Standard Error (SE) 6–8%) and 19–26% (SE 6–8%) absolute risk reduction of all-cause mortality and HFpEF readmissions, respectively (all p < 0.05). MVRepair emerged as the strongest independent predictor of all-cause mortality (Hazard Ratio (HR) 0.16, 95% (Confidence Interval (CI) 0.07–0.34, p < 0.001) and HFpEF readmissions (HR 0.21, 95% CI 0.09–0.51, p < 0.001). At 5-year follow-up, in the MVRepair group, a total of 88% were alive and 80% were alive without readmission for HFpEF. We can conclude that endoscopic MV repair is associated with low perioperative mortality as well as high long-term efficacy, and appears to improve clinical outcome in patients with AFMR and HFpEF. Full article

(This article belongs to the Special Issue Epidemiology, Diagnosis, Pathophysiology, Risk Stratification, and Therapy of Heart Failure with Preserved Ejection Fraction)

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12 pages, 1260 KiB

Open AccessArticle

Iron Deficiency: Impact on Functional Capacity and Quality of Life in Heart Failure with Preserved Ejection Fraction

by Alex Alcaide-Aldeano, Alberto Garay, Lídia Alcoberro, Santiago Jiménez-Marrero, Sergi Yun, Marta Tajes, Elena García-Romero, Carles Díez-López, José González-Costello, Gemma Mateus-Porta, Miguel Cainzos-Achirica, Cristina Enjuanes, Josep Comín-Colet and Pedro Moliner

J. Clin. Med. 2020, 9(4), 1199; https://doi.org/10.3390/jcm9041199 - 22 Apr 2020

Cited by 42 | Viewed by 4104

Abstract

The effects of iron deficiency (ID) have been widely studied in heart failure (HF) with reduced ejection fraction. On the other hand, studies in HF with preserved ejection fraction (HFpEF) are few and have included small numbers of participants. The aim of this [...] Read more.

The effects of iron deficiency (ID) have been widely studied in heart failure (HF) with reduced ejection fraction. On the other hand, studies in HF with preserved ejection fraction (HFpEF) are few and have included small numbers of participants. The aim of this study was to assess the role that ID plays in functional capacity and quality of life (QoL) in HFpEF while comparing several iron-related biomarkers to be used as potential predictors. ID was defined as ferritin <100 ng/mL or transferrin saturation <20%. Submaximal exercise capacity, measured by the 6-min walking test (6MWT), and QoL, assessed by the Minnesotta Living with Heart Failure Questionnaire (MLHFQ), were compared between iron deficient patients and patients with normal iron status. A total of 447 HFpEF patients were included in the present cross-sectional study, and ID prevalence was 73%. Patients with ID performed worse in the 6MWT compared to patients with normal iron status (ID 271 ± 94 m vs. non-ID 310 ± 108 m, p < 0.01). They also scored higher in the MLHFQ, denoting worse QoL (ID 49 ± 22 vs. non-ID 43 ± 23, p = 0.01). Regarding iron metabolism biomarkers, serum soluble transferrin receptor (sTfR) was the strongest independent predictor of functional capacity (β = −63, p < 0.0001, R² 0.39) and QoL (β = 7.95, p < 0.0001, R² 0.14) in multivariate models. This study postulates that ID is associated with worse functional capacity and QoL in HFpEF as well, and that sTfR is the best iron-related biomarker to predict both. Our study also suggests that the effects of ID could differ among HFpEF patients by left ventricular ejection fraction. Full article

(This article belongs to the Special Issue Epidemiology, Diagnosis, Pathophysiology, Risk Stratification, and Therapy of Heart Failure with Preserved Ejection Fraction)

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14 pages, 1676 KiB

Open AccessArticle

Right Ventricular Dysfunction Staging System for Mortality Risk Stratification in Heart Failure with Preserved Ejection Fraction

by Enrique Santas, Rafael De la Espriella, Francisco Javier Chorro, Patricia Palau, Gema Miñana, Raquel Heredia, Martina Amiguet, Héctor Merenciano, Juan Sanchis, Josep Lupón, Antoni Bayés-Genís and Julio Núñez

J. Clin. Med. 2020, 9(3), 831; https://doi.org/10.3390/jcm9030831 - 18 Mar 2020

Cited by 17 | Viewed by 3461

Abstract

Right ventricular dysfunction (RVD) parameters are increasingly important features in heart failure with preserved ejection fraction (HFpEF). We sought to evaluate the prognostic impact of a progressive RVD staging system by combining the tricuspid annular plane systolic excursion (TAPSE) to pulmonary artery systolic [...] Read more.

Right ventricular dysfunction (RVD) parameters are increasingly important features in heart failure with preserved ejection fraction (HFpEF). We sought to evaluate the prognostic impact of a progressive RVD staging system by combining the tricuspid annular plane systolic excursion (TAPSE) to pulmonary artery systolic pressure (TAPSE/PASP) ratio with functional tricuspid regurgitation (TR) severity. We prospectively included 1355 consecutive HFpEF patients discharged for acute heart failure (HF). Of them, in 471 (34.7%) patients, PASP could not be accurately measured, leaving the final sample size to be 884 patients. Patients were categorized as Stage 1: TAPSE/PASP ≥ 0.36 without significant TR; stage 2: TAPSE/PASP ≥ 0.36 with significant TR; stage 3: TAPSE/PASP < 0.36 without significant TR; and stage 4: TAPSE/PASP < 0.36 with significant TR. By the 1 year follow-up, 207 (23.4%) patients had died. We found a significant and graded association between RVD stages and mortality rates (15.8%, 25%, 31.2%, and 45.4% from stage 1 to stage 4, respectively; log-rank test, p < 0.001). After multivariable adjustment, and compared to stage 1, stages 3 and 4 were independently associated with mortality risk (HR: 1.8219; 95% CI 1.308–2.538; p < 0.001 and HR = 2.2632; 95% CI 1.540–3.325; p < 0.001, respectively). A RVD staging system, integrating TAPSE/PASP and TR, provides a comprehensive and widely available tool for risk stratification in HFpEF. Full article

(This article belongs to the Special Issue Epidemiology, Diagnosis, Pathophysiology, Risk Stratification, and Therapy of Heart Failure with Preserved Ejection Fraction)

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16 pages, 1801 KiB

Open AccessArticle

Neutrophil-Lymphocyte Ratio in Patients with Acute Heart Failure Predicts In-Hospital and Long-Term Mortality

by Jun Hwan Cho, Hyun-Jai Cho, Hae-Young Lee, You-Jeong Ki, Eun-Seok Jeon, Kyung-Kuk Hwang, Shung Chull Chae, Sang Hong Baek, Seok-Min Kang, Dong-Ju Choi, Byung-Su Yoo, Kye Hun Kim, Jae-Joong Kim and Byung-Hee Oh

J. Clin. Med. 2020, 9(2), 557; https://doi.org/10.3390/jcm9020557 - 18 Feb 2020

Cited by 49 | Viewed by 3303

Abstract

The application of a simple blood test to predict prognosis in acute heart failure (AHF) patients is not well established. Neutrophil-lymphocyte ratio (NLR) is inexpensive and easy to obtain in hospitalized patients using a routine blood test. We evaluate the prognostic implications of [...] Read more.

The application of a simple blood test to predict prognosis in acute heart failure (AHF) patients is not well established. Neutrophil-lymphocyte ratio (NLR) is inexpensive and easy to obtain in hospitalized patients using a routine blood test. We evaluate the prognostic implications of NLR as an independent predictor of in-hospital and long-term mortality in AHF patients. Among 5625 patients enrolled in the Korean Acute Heart Failure registry, 5580 patients were classified into quartiles by their NLR level, and analyzed for in-hospital and post-discharge three-year mortality. Patients in the highest NLR quartile had the highest in-hospital and post-discharge three-year mortality. The same results were seen by dividing the aggravating factor into the infection or ischemia group and the non-infection or non-ischemia group. For patients aggravated from infection or ischemia, a cut-off NLR value was 7.0 that increase the risk of in-hospital and post-discharge three-year mortality. In subgroups of patients not aggravated from infection or ischemia, a cut-off NLR value was 5.0 that increase the risk of in-hospital and post discharge three-year mortality. Elevated NLR in AHF patients at the index hospitalization is an independent predictor for in-hospital and post-discharge three-year mortality. Taken together, NLR is a marker for risk assessment of AHF patients. Full article

(This article belongs to the Special Issue Epidemiology, Diagnosis, Pathophysiology, Risk Stratification, and Therapy of Heart Failure with Preserved Ejection Fraction)

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Review

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13 pages, 272 KiB

Open AccessReview

Treatment of Heart Failure with Mid-Range Ejection Fraction: What Is the Evidence

by Eleni-Evangelia Koufou, Angelos Arfaras-Melainis, Sahil Rawal and Andreas P. Kalogeropoulos

J. Clin. Med. 2021, 10(2), 203; https://doi.org/10.3390/jcm10020203 - 8 Jan 2021

Cited by 6 | Viewed by 3715

Abstract

In this review, we briefly outline our current knowledge on the epidemiology, outcomes, and pathophysiology of heart failure (HF) with mid-range ejection fraction (HFmrEF), and discuss in more depth the evidence on current treatment options for this group of patients. In most studies, [...] Read more.

In this review, we briefly outline our current knowledge on the epidemiology, outcomes, and pathophysiology of heart failure (HF) with mid-range ejection fraction (HFmrEF), and discuss in more depth the evidence on current treatment options for this group of patients. In most studies, the clinical background of patients with HFmrEF is intermediate between that of patients with HF and reduced ejection fraction (HFrEF) and patients with HF and preserved ejection fraction (HFpEF) in terms of demographics and comorbid conditions. However, the current evidence, stemming from observational studies and post hoc analyses of randomized controlled trials, suggests that patients with HFmrEF benefit from medications that target the neurohormonal axes, a pathophysiological behavior that resembles that of HFrEF. Use of β-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, mineralocorticoid receptor antagonists, and sacubitril/valsartan is reasonable in patients with HFmrEF, whereas evidence is currently scarce for other therapies. In clinical practice, patients with HFmrEF are treated more like HFrEF patients, potentially because of history of systolic dysfunction that has partially recovered. Assessment of left ventricular systolic function with contemporary noninvasive modalities, e.g., echocardiographic strain imaging, is promising for the selection of patients with HFmrEF who will benefit from neurohormonal antagonists and other HFrEF-targeted therapies. Full article

(This article belongs to the Special Issue Epidemiology, Diagnosis, Pathophysiology, Risk Stratification, and Therapy of Heart Failure with Preserved Ejection Fraction)

19 pages, 1759 KiB

Open AccessReview

Transitioning from Preclinical to Clinical Heart Failure with Preserved Ejection Fraction: A Mechanistic Approach

by Antoni Bayes-Genis, Felipe Bisbal, Julio Núñez, Enrique Santas, Josep Lupón, Patrick Rossignol and Walter Paulus

J. Clin. Med. 2020, 9(4), 1110; https://doi.org/10.3390/jcm9041110 - 13 Apr 2020

Cited by 23 | Viewed by 5460

Abstract

To better understand heart failure with preserved ejection fraction (HFpEF), we need to better characterize the transition from asymptomatic pre-HFpEF to symptomatic HFpEF. The current emphasis on left ventricular diastolic dysfunction must be redirected to microvascular inflammation and endothelial dysfunction that leads to [...] Read more.

To better understand heart failure with preserved ejection fraction (HFpEF), we need to better characterize the transition from asymptomatic pre-HFpEF to symptomatic HFpEF. The current emphasis on left ventricular diastolic dysfunction must be redirected to microvascular inflammation and endothelial dysfunction that leads to cardiomyocyte remodeling and enhanced interstitial collagen deposition. A pre-HFpEF patient lacks signs or symptoms of heart failure (HF), has preserved left ventricular ejection fraction (LVEF) with incipient structural changes similar to HFpEF, and possesses elevated biomarkers of cardiac dysfunction. The transition from pre-HFpEF to symptomatic HFpEF also involves left atrial failure, pulmonary hypertension and right ventricular dysfunction, and renal failure. This review focuses on the non-left ventricular mechanisms in this transition, involving the atria, right heart cavities, kidneys, and ultimately the currently accepted driver—systemic inflammation. Impaired atrial function may decrease ventricular hemodynamics and significantly increase left atrial and pulmonary pressure, leading to HF symptoms, irrespective of left ventricle (LV) systolic function. Pulmonary hypertension and low right-ventricular function are associated with the incidence of HF. Interstitial fibrosis in the heart, large arteries, and kidneys is key to the pathophysiology of the cardiorenal syndrome continuum. By understanding each of these processes, we may be able to halt disease progression and eventually extend the time a patient remains in the asymptomatic pre-HFpEF stage. Full article

(This article belongs to the Special Issue Epidemiology, Diagnosis, Pathophysiology, Risk Stratification, and Therapy of Heart Failure with Preserved Ejection Fraction)

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