New Advances in Pharmacologic and Non-pharmacologic Therapy in Heart Failure and Heart Transplant

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

Deadline for manuscript submissions: closed (20 December 2023) | Viewed by 45171

Special Issue Editors


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Guest Editor
Heart Failure Unit, Department of Cardiology, AORN dei Colli-Monaldi Hospital, Naples, Italy
Interests: chronic heart failure; acute heart failure; advanced heart failure; left ventricular assist device; heart transplant

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Guest Editor
Cardiology Unit, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, Brescia, Italy
Interests: chronic heart failure; acute heart failure; advanced heart failure; pharmacological treatment; biomarkers; pulmonary hypertension

Special Issue Information

Dear Colleagues,

In recent years, treatment strategies for patients with heart failure have expanded, with new pharmacological (sacubitril/valsartan, SGLT2-i, vericiguat, omecamtiv mecarbil, ferric carboxymaltose) and non-pharmacological (cardiac contractility modulation, baroreceptor stimulation) options becoming available.

Despite these advances, the mortality and morbidity of heart failure patients are still high. In the upcoming ESC 2021 guidelines for the diagnosis and treatment of acute and chronic heart failure, the current challenge is to develop targeted therapies according to the etiology (e.g., amyloidosis, peripartum cardiomyopathy, inflammatory dilated cardiomyopathy) and the clinical phenotype of the patient (renal failure, bradycardia, low arterial pressure) and to the presence of comorbidities (iron deficiency, sleep-disordered breathing, diabetes). This tailored approach aims to prevent functional deterioration and to reduce morbidity and mortality.

Heart transplantation is the gold standard surgical approach to treating advanced heart failure. Recent advances have attempted to expand the pool of donor hearts; ameliorate the heart transplantation allocation policy; and better manage antibody sensitization.

This Special Issue aims to highlight new opportunities for improved treatments for heart failure and heart transplant patients.

Dr. Daniele Masarone
Dr. Carlo Lombardi
Guest Editors

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Keywords

  • chronic heart failure
  • acute heart failure
  • advanced heart failure
  • cardiac amyloidosis
  • SGLT2-i
  • cardiac contractility modulation
  • levosimendan
  • tafamidis
  • vericiguat
  • omecamtiv mecarbil
  • heart transplantation
  • graft dysfunction
  • antibody sensitization

Published Papers (18 papers)

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Editorial

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5 pages, 163 KiB  
Editorial
Recent Advances across the Spectrum of Heart Failure and Heart Transplant
by Daniele Masarone, Carlo Lombardi, Luigi Falco, Enrico Coscioni and Marco Metra
J. Clin. Med. 2024, 13(5), 1427; https://doi.org/10.3390/jcm13051427 - 01 Mar 2024
Viewed by 476
Abstract
In recent years, remarkable progress has been accomplished in the heart failure (HF) landscape, with novel drugs and groundbreaking device approaches [...] Full article

Research

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14 pages, 785 KiB  
Article
Oral Anticoagulants after Heart Transplantation—Comparison between Vitamin K Antagonists and Direct Oral Anticoagulants
by Fabrice F. Darche, Lisa C. Fabricius, Matthias Helmschrott, Ann-Kathrin Rahm, Philipp Ehlermann, Tom Bruckner, Wiebke Sommer, Gregor Warnecke, Norbert Frey and Rasmus Rivinius
J. Clin. Med. 2023, 12(13), 4334; https://doi.org/10.3390/jcm12134334 - 28 Jun 2023
Viewed by 1159
Abstract
Aims: Patients after heart transplantation (HTX) often require oral anticoagulants (OACs) due to atrial arrhythmias or thromboembolic events but little is known about the post-transplant use of direct oral anticoagulants (DOACs). We investigated the frequency, indications, and complications of DOACs and vitamin K [...] Read more.
Aims: Patients after heart transplantation (HTX) often require oral anticoagulants (OACs) due to atrial arrhythmias or thromboembolic events but little is known about the post-transplant use of direct oral anticoagulants (DOACs). We investigated the frequency, indications, and complications of DOACs and vitamin K antagonists (VKAs) after HTX. Methods: We screened all adult patients for the use of post-transplant OACs who underwent HTX at Heidelberg Heart Center between 2000 and 2021. Patients were stratified by type of OAC (DOAC or VKA) and by DOAC agents (apixaban, dabigatran, edoxaban, or rivaroxaban). Indications for OACs comprised atrial fibrillation, atrial flutter, pulmonary embolism, upper and lower extremity deep vein thrombosis, as well as intracardiac thrombus. Results: A total of 115 of 459 HTX recipients (25.1%) required OACs, including 60 patients with DOACs (52.2%) and 55 patients with VKAs (47.8%). Concerning DOACs, 28 patients were treated with rivaroxaban (46.7%), 27 patients with apixaban (45.0%), and 5 patients with edoxaban (8.3%). We found no significant differences between both groups concerning demographics, immunosuppressive drugs, concomitant medications, indications for OACs, ischemic stroke, thromboembolic events, or OAC-related death. Patients with DOACs after HTX had a significantly lower one-year rate of overall bleeding complications (p = 0.002) and a significantly lower one-year rate of gastrointestinal hemorrhage (p = 0.011) compared to patients with VKAs after HTX in the Kaplan–Meier estimator. Conclusions: DOACs were comparable to VKAs concerning the risk of ischemic stroke, thromboembolic events, or OAC-related death but were associated with significantly fewer bleeding complications in HTX recipients. Full article
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9 pages, 840 KiB  
Article
Temporary Mechanical Circulatory Support in Patients with Cardiogenic Shock: Clinical Characteristics and Outcomes
by Michael Abiragi, Tahli Singer-Englar, Robert M. Cole, Dominic Emerson, Fardad Esmailian, Dominick Megna, Jaime Moriguchi, Jon A. Kobashigawa and Michelle M. Kittleson
J. Clin. Med. 2023, 12(4), 1622; https://doi.org/10.3390/jcm12041622 - 17 Feb 2023
Cited by 3 | Viewed by 1215
Abstract
Patients with cardiogenic shock may require stabilization with temporary mechanical circulatory support (tMCS) to assess candidacy for definitive therapy, including heart transplantation (HTx) or durable MCS, and/or maintain stability while on the HTx waiting list. We describe the clinical characteristics and outcomes of [...] Read more.
Patients with cardiogenic shock may require stabilization with temporary mechanical circulatory support (tMCS) to assess candidacy for definitive therapy, including heart transplantation (HTx) or durable MCS, and/or maintain stability while on the HTx waiting list. We describe the clinical characteristics and outcomes of patients with cardiogenic shock who underwent intra-aortic balloon pump (IABP) vs. Impella [Abiomed, Danvers, MA, USA] placement at a high-volume advanced heart failure center. We assessed patients ≥ 18 years who received IABP or Impella support for cardiogenic shock from 1 January 2020 to 31 December 2021. Ninety patients were included, 59 (65.6%) with IABP and 31 (34.4%) with Impella. Impella was used more frequently in less stable patients, as evidenced by higher inotrope scores, greater ventilator support, and worse renal function. While patients on Impella support had higher in-hospital mortality, despite the worse cardiogenic shock in patients for whom clinicians chose Impella support, over 75% were successfully stabilized to recovery or transplantation. Clinicians elect Impella support over IABP for less stable patients, though a high proportion are successfully stabilized. These findings demonstrate the heterogeneity of the cardiogenic shock patient population and may inform future trials to assess the role of different tMCS devices. Full article
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8 pages, 824 KiB  
Article
Blood Type A1 Mismatch Does Not Affect Heart Transplant Outcomes at One Year
by Louie Cao, Seongkyu Kim, Ellen Klapper, Jon A. Kobashigawa and Michelle M. Kittleson
J. Clin. Med. 2023, 12(4), 1337; https://doi.org/10.3390/jcm12041337 - 08 Feb 2023
Viewed by 1372
Abstract
There are subtypes within blood type A, termed non-A1, that have reduced expression of A antigen on cell surfaces. This can result in the development of anti-A1 antibodies. There is limited information regarding the impact of this in heart transplant (HTx) recipients. We [...] Read more.
There are subtypes within blood type A, termed non-A1, that have reduced expression of A antigen on cell surfaces. This can result in the development of anti-A1 antibodies. There is limited information regarding the impact of this in heart transplant (HTx) recipients. We conducted a single-center cohort study of 142 Type A HTx recipients in which we compared outcomes of a match group (an A1/O heart into an A1 recipient or a non-A1/O heart into a non-A1 recipient) with a mismatch group (an A1 heart into a non-A1 recipient or a non-A1 heart into an A1 recipient). At one year post-transplant, there were no differences between the groups in survival, freedom from non-fatal major adverse cardiovascular events, freedom from any treated rejection, or freedom from cardiac allograft vasculopathy. There was an increased hospital length of stay in the mismatch group (13.5 vs. 17.1 days, p = 0.04). Our study showed that A1 mismatch was not associated with worse outcomes at one year post-HTx. Full article
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10 pages, 1326 KiB  
Article
Effects of Cardiac Contractility Modulation Electrodes on Tricuspid Regurgitation in Patients with Heart Failure with Reduced Ejection Fraction: A Pilot Study
by Daniele Masarone, Michelle M. Kittleson, Stefano De Vivo, Antonio D’Onofrio, Ishu Rao, Ernesto Ammendola, Vittoria Errigo, Maria L. Martucci, Gerardo Nigro and Giuseppe Pacileo
J. Clin. Med. 2022, 11(24), 7442; https://doi.org/10.3390/jcm11247442 - 15 Dec 2022
Cited by 2 | Viewed by 1364
Abstract
Background: Cardiac contractility modulation (CCM) is an innovative therapy for heart failure with reduced ejection fraction delivered by a cardiac implantable device (Optimizer Smart®). One of the most prominent periprocedural complications common to all cardiac implantable devices (CIDs) is tricuspid regurgitation [...] Read more.
Background: Cardiac contractility modulation (CCM) is an innovative therapy for heart failure with reduced ejection fraction delivered by a cardiac implantable device (Optimizer Smart®). One of the most prominent periprocedural complications common to all cardiac implantable devices (CIDs) is tricuspid regurgitation (TR) due to the placement of the right ventricular endocardial leads. To date, no published studies have assessed the changes in the TR degree in patients with heart failure with reduced ejection fraction (HFrEF) who received an implantable cardioverter-defibrillator (ICD) after the implantation of cardiac contractility modulation therapy devices. Objective: This study aimed to evaluate the effect of the implantation of the trans-tricuspid leads required to deliver CCM therapy on the severity of TR in patients with HFrEF who previously underwent ICD implantation. Methods: We enrolled 30 HFrEF patients who underwent CCM therapy between November 2020 and October 2021. For all the patients, echocardiographic evaluations of TR were performed according to current guidelines 24 h before and six months after the Optimizer Smart® implant was applied. Results: At the 6-month follow-up, the grade of TR remained unchanged compared to the preimplant grade. The value of the vena contracta (VC) of TR was 0.40 ± 0.19 cm in the preimplant period and 0.45 ± 0.21 cm at the 6-month follow-up (p = 0.33). Similarly, the TR proximal isovelocity surface area (PISA) radius value was unchanged at follow-up (0.54 ± 0.22 cm vs. 0.62 ± 0.20 cm; p = 0.18). No statistically significant difference existed between the preimplant VC and PISA radius values, irrespective of the device type. Conclusions: The implantation of right ventricular electrodes for the delivery of CCM therapy did not worsen tricuspid regurgitation in patients with HFrEF and ICD. Full article
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7 pages, 516 KiB  
Article
Dapsone-Associated Anemia in Heart Transplant Recipients with Normal Glucose-6-Phosphate Dehydrogenase Activity
by Kevin W. Lor, Evan P. Kransdorf, Jignesh K. Patel, David H. Chang, Jon A. Kobashigawa and Michelle M. Kittleson
J. Clin. Med. 2022, 11(21), 6378; https://doi.org/10.3390/jcm11216378 - 28 Oct 2022
Cited by 2 | Viewed by 1171
Abstract
Dapsone is considered an alternative for pneumocystis jirovecii pneumonia (PJP) prophylaxis in sulfa-allergic or -intolerant transplant patients with normal glucose-6-phosphate dehydrogenase (G6PD) activity. Despite normal G6PD activity, anemia can still occur while on dapsone therapy. We retrospectively reviewed heart transplant patients transplanted at [...] Read more.
Dapsone is considered an alternative for pneumocystis jirovecii pneumonia (PJP) prophylaxis in sulfa-allergic or -intolerant transplant patients with normal glucose-6-phosphate dehydrogenase (G6PD) activity. Despite normal G6PD activity, anemia can still occur while on dapsone therapy. We retrospectively reviewed heart transplant patients transplanted at our center between January 2016 and June 2018 and identified those taking dapsone prophylaxis. There were 252 heart transplant recipients at our center between January 2016 and June 2018. 36 patients received dapsone prophylaxis. All had normal G6PD activity assessed prior to dapsone initiation. 8 (22%) patients developed significant anemia attributed to dapsone: 2 were hospitalized for anemia, 1 of whom required blood transfusion. These patients had a median reduction in hemoglobin of 2.1 g/dL from baseline prior to dapsone initiation. Overt evidence of hemolysis was present in six patients. Once dapsone was discontinued, Hgb increased by at least 2 g/dL in a median of 30 days. Anemia from dapsone may occur in a significant proportion of patients despite normal G6PD activity and resulting in significant morbidity. Careful monitoring of transplant recipients on dapsone prophylaxis is warranted, as well as consideration of alternative agents. Full article
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10 pages, 2458 KiB  
Article
The Effects of Device-Based Cardiac Contractility Modulation Therapy on Left Ventricle Global Longitudinal Strain and Myocardial Mechano-Energetic Efficiency in Patients with Heart Failure with Reduced Ejection Fraction
by Daniele Masarone, Michelle M. Kittleson, Stefano De Vivo, Antonio D’Onofrio, Ernesto Ammendola, Gerardo Nigro, Carla Contaldi, Maria L. Martucci, Vittoria Errigo and Giuseppe Pacileo
J. Clin. Med. 2022, 11(19), 5866; https://doi.org/10.3390/jcm11195866 - 04 Oct 2022
Cited by 6 | Viewed by 1606
Abstract
Background: Virtually all patients with heart failure with reduced ejection fraction have a reduction of myocardial mechano-energetic efficiency (MEE). Cardiac contractility modulation (CCM) is a novel therapy for the treatment of patients with HFrEF, in whom it improves the quality of life and [...] Read more.
Background: Virtually all patients with heart failure with reduced ejection fraction have a reduction of myocardial mechano-energetic efficiency (MEE). Cardiac contractility modulation (CCM) is a novel therapy for the treatment of patients with HFrEF, in whom it improves the quality of life and functional capacity, reduces hospitalizations, and induces biventricular reverse remodeling. However, the effects of CCM on MEE and global longitudinal strain (GLS) are still unknown; therefore, this study aims to evaluate whether CCM therapy can improve the MEE of patients with HFrEF. Methods: We enrolled 25 patients with HFrEF who received an Optimizer Smart implant (the device that develops CCM therapy) between January 2018 and January 2021. Clinical and echocardiographic evaluations were performed in all patients 24 h before and six months after CCM therapy. Results: At six months, follow-up patients who underwent CCM therapy showed an increase of left ventricular ejection fraction (30.8 ± 7.1 vs. 36.1 ± 6.9%; p = 0.032) as well a rise of GLS 10.3 ± 2.7 vs. −12.9 ± 4.2; p = 0.018), of MEE (32.2 ± 10.1 vs. 38.6 ± 7.6 mL/s; p = 0.013) and of MEE index (18.4 ± 6.3 vs. 24.3 ± 6.7 mL/s/g; p = 0.022). Conclusions: CCM therapy increased left ventricular performance, improving left ventricular ejection fraction, GLS, as well as MEE and MEEi. Full article
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7 pages, 797 KiB  
Article
Levosimendan as a “Bridge to Optimization” in Patients with Advanced Heart Failure with Reduced Ejection—A Single-Center Study
by Daniele Masarone, Michelle M. Kittleson, Maria L. Martucci, Fabio Valente, Rita Gravino, Marina Verrengia, Ernesto Ammendola, Carla Contaldi, Vito Di Palma, Angelo Caiazzo, Andrea Petraio, Piero Pollesello and Giuseppe Pacileo
J. Clin. Med. 2022, 11(14), 4227; https://doi.org/10.3390/jcm11144227 - 21 Jul 2022
Cited by 5 | Viewed by 2063
Abstract
Background: Patients with advanced heart failure with reduced ejection fraction often cannot tolerate target doses of guideline-directed medical therapy due to symptomatic hypotension, renal dysfunction, and associated electrolyte abnormalities. While levosimendan can facilitate the titration of β-blockers in patients with advanced HFrEF, [...] Read more.
Background: Patients with advanced heart failure with reduced ejection fraction often cannot tolerate target doses of guideline-directed medical therapy due to symptomatic hypotension, renal dysfunction, and associated electrolyte abnormalities. While levosimendan can facilitate the titration of β-blockers in patients with advanced HFrEF, it is unclear whether ambulatory levosimendan infusions would offer the same benefit. In this prospective study, we investigate the effects of intermittent ambulatory levosimendan infusions on the uptitration of disease-modifying drugs. Methods: We enrolled 37 patients with advanced HFrEF who received repeated ambulatory infusions of levosimendan between January 2018 and January 2021. The demographic, clinical, and laboratory data were acquired 24 h before the first and the last ambulatory levosimendan infusion. Results: At the 1 year follow-up, the enrolled patients were on significantly higher doses of guideline-directed medical therapy, including bisoprolol (3.2 ± 2.8 mg vs. 5.9 ± 4.1 mg; p = 0.02), sacubitril/valsartan (41.67 ± 32.48 mg vs. 68.5 ± 35.72 mg; p = 0.01), and eplerenone (12.7 ± 8.5 mg vs. 22.8 ± 13.6 mg; p = 0.03). Furthermore, a substantial decrease in the furosemide dose was observed (123.2 ± 32.48 mg vs. 81.6 ± 19.47 mg; p < 0.0001). Conclusions: Levosimendan facilitates the optimization of disease-modifying heart failure medications in previously intolerant advanced HFrEF patients. Full article
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9 pages, 681 KiB  
Article
Effects of Sacubitril/Valsartan on the Renal Resistance Index
by Margherita Ilaria Gioia, Giuseppe Parisi, Dario Grande, Miriam Albanese, Gianmarco Alcidi, Michele Correale, Natale Daniele Brunetti, Marco Matteo Ciccone and Massimo Iacoviello
J. Clin. Med. 2022, 11(13), 3683; https://doi.org/10.3390/jcm11133683 - 26 Jun 2022
Cited by 3 | Viewed by 1810
Abstract
Background: Sacubitril/valsartan plays a key role in improving left ventricular remodeling and prognosis in patients with heart failure with a reduced ejection fraction (HFrEF). Moreover, some data support its role in preserving renal function. In order to better clarify the effects of sacubitril/valsartan [...] Read more.
Background: Sacubitril/valsartan plays a key role in improving left ventricular remodeling and prognosis in patients with heart failure with a reduced ejection fraction (HFrEF). Moreover, some data support its role in preserving renal function. In order to better clarify the effects of sacubitril/valsartan in cardiorenal syndrome, this study evaluated its effects on the renal resistance index (RRI). Methods: A group of patients with HFrEF was enrolled. The RRI was assessed with renal echo-color Doppler at enrollment and again after at least six months of sacubitril/valsartan treatment. In a subgroup of patients, the RRI was also evaluated at least six months before enrollment. The variations in echocardiographic parameters reflecting the left and right ventricular function, as well as creatinine and the estimated glomerular filtration rate, were also evaluated. Results: After treatment with sacubitril/valsartan, significant improvements in the left ventricular ejection fraction, and a decrease in the left atrial and ventricular volumes were observed. The RRI also showed a significant decrease. No relationship was found between the improvements in the parameters reflecting cardiac function and changes in the RRI. Conclusions: Treatment with sacubitril/valsartan is associated with improvements in both left ventricular function and renal perfusion, through decreasing the renal resistance. These data help to clarify the effects of the drug on cardiorenal syndrome progression. Full article
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6 pages, 467 KiB  
Communication
Early Hemodynamic Changes following Surgical Ablation of the Right Greater Splanchnic Nerve for the Treatment of Heart Failure with Preserved Ejection Fraction
by Piotr Gajewski, Marat Fudim, Veraprapas Kittipibul, Zoar J. Engelman, Jan Biegus, Robert Zymliński and Piotr Ponikowski
J. Clin. Med. 2022, 11(4), 1063; https://doi.org/10.3390/jcm11041063 - 18 Feb 2022
Cited by 3 | Viewed by 1875
Abstract
Background: Permanent ablation of the right greater splanchnic nerve (GSN) has previously been demonstrated to improve quality of life and functional outcomes, as well as reduce abnormally high intracardiac filling pressures, in patients with heart failure with preserved ejection fraction (HFpEF) at 1, [...] Read more.
Background: Permanent ablation of the right greater splanchnic nerve (GSN) has previously been demonstrated to improve quality of life and functional outcomes, as well as reduce abnormally high intracardiac filling pressures, in patients with heart failure with preserved ejection fraction (HFpEF) at 1, 3 and 12 months following the procedure. We hypothesize that hemodynamic changes that ensue from surgical right GSN ablation would be apparent as early as 24 h after the medical intervention. Methods and Results: This is a prespecified analysis of a single-arm, two-center, open-label study evaluating the effects of right GSN ablation via thoracoscopic surgery in HFpEF patients with pulmonary capillary wedge pressure (PCWP) ≥15 mmHg at rest or ≥25 mmHg with supine cycle ergometry. A total of seven patients (median age 67 years, 29% female) underwent GSN removal followed by invasive right heart catheterization within 24 h. GSN ablation resulted in a significant reduction in PCWP 24 h after the procedure compared to baseline for both 20 W exercise (baseline (28.0 ± 4.3 mmHg) to 24 h (19.6 ± 6.9 mmHg); p = 0.0124) and peak exercise (baseline (25.6 ± 2.4 mmHg) to 24 h (17.4 ± 5.9 mmHg); p = 0.0025). There were no significant changes in resting or leg-up hemodynamics. Conclusions: Permanent right GSN ablation leads to a reduction in intracardiac filling pressures during exercise, apparent as early as 24 h following the procedure. Full article
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11 pages, 538 KiB  
Article
Prognostic Benefit of New Drugs for HFrEF: A Systematic Review and Network Meta-Analysis
by Matteo Pagnesi, Luca Baldetti, Alberto Aimo, Riccardo Maria Inciardi, Daniela Tomasoni, Enrico Vizzardi, Giuseppe Vergaro, Michele Emdin and Carlo Mario Lombardi
J. Clin. Med. 2022, 11(2), 348; https://doi.org/10.3390/jcm11020348 - 11 Jan 2022
Cited by 5 | Viewed by 2648
Abstract
Background: The new heart failure (HF) therapies of sodium-glucose cotransporter 2 inhibitors (SGLT2i), vericiguat, and omecamtiv mecarbil do not act primarily through the neuro-hormonal blockade, but have shown clinical benefits in patients with HF with reduced ejection fraction (HFrEF). However, their respective efficacies [...] Read more.
Background: The new heart failure (HF) therapies of sodium-glucose cotransporter 2 inhibitors (SGLT2i), vericiguat, and omecamtiv mecarbil do not act primarily through the neuro-hormonal blockade, but have shown clinical benefits in patients with HF with reduced ejection fraction (HFrEF). However, their respective efficacies remain unclear. Our aim was to evaluate the relative efficacy of new drugs for HFrEF. Methods: We performed a network meta-analysis (NMA) of randomized controlled trials (RCTs) comparing SGLT2i, vericiguat, omecamtiv mecarbil, and placebo in HFrEF patients. The primary endpoint was the composite of cardiovascular death (CVD) or HF hospitalization (CVD-HF); secondary endpoints were CVD, all-cause death, and HF hospitalization (HFH). Results: Twelve RCTs (n = 23,861 patients) were included. A significant reduction in CVD-HF was observed with SGLT2i compared with placebo (risk ratio (RR) 0.77, 95% confidence interval (CI) 0.71–0.83), vericiguat (RR 0.84, 95% CI 0.75–0.93), and omecamtiv mecarbil (RR 0.80, 95% CI 0.72–0.88). No significant difference was observed between vericiguat and omecamtiv mecarbil (RR 0.95, 95% CI 0.87–1.04). SGLT2i were superior to placebo and omecamtiv mecarbil for all individual secondary endpoints (CVD, all-cause death, and HFH), and also to vericiguat for HFH. SGLT2i ranked as the most effective therapy for all endpoints, and vericiguat, omecamtiv mecarbil, and placebo ranked as the second, third, and last options, respectively, for the primary endpoint. Conclusions: In patients with HFrEF on standard-of-care therapy, SGLT2i therapy was associated with a reduced risk of CVD-HF compared to placebo, vericiguat, and omecamtiv mecarbil. Furthermore, SGLT2i were superior to placebo and omecamtiv mecarbil for CVD, all-cause death, and HFH, and also to vericiguat for HFH. Full article
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Review

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15 pages, 1508 KiB  
Review
Functional Mitral and Tricuspid Regurgitation across the Whole Spectrum of Left Ventricular Ejection Fraction: Recognizing the Elephant in the Room of Heart Failure
by Valeria Cammalleri, Giorgio Antonelli, Valeria Maria De Luca, Myriam Carpenito, Annunziata Nusca, Maria Caterina Bono, Simona Mega, Gian Paolo Ussia and Francesco Grigioni
J. Clin. Med. 2023, 12(9), 3316; https://doi.org/10.3390/jcm12093316 - 06 May 2023
Cited by 2 | Viewed by 1464
Abstract
Functional mitral regurgitation (FMR) and tricuspid regurgitation (FTR) occur due to cardiac remodeling in the presence of structurally normal valve apparatus. Two main mechanisms are involved, distinguishing an atrial functional form (when annulus dilatation is predominant) and a ventricular form (when ventricular remodeling [...] Read more.
Functional mitral regurgitation (FMR) and tricuspid regurgitation (FTR) occur due to cardiac remodeling in the presence of structurally normal valve apparatus. Two main mechanisms are involved, distinguishing an atrial functional form (when annulus dilatation is predominant) and a ventricular form (when ventricular remodeling and dysfunction predominate). Both affect the prognosis of patients with heart failure (HF) across the entire spectrum of left ventricle ejection fraction (LVEF), including preserved (HFpEF), mildly reduced (HFmrEF), or reduced (HFrEF). Currently, data on the management of functional valve regurgitation in the various HF phenotypes are limited. This review summarizes the epidemiology, pathophysiology, and treatment of FMR and FTR within the different patterns of HF, as defined by LVEF. Full article
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25 pages, 4636 KiB  
Review
Acute Heart Failure: Diagnostic–Therapeutic Pathways and Preventive Strategies—A Real-World Clinician’s Guide
by Ciro Mauro, Salvatore Chianese, Rosangela Cocchia, Michele Arcopinto, Stefania Auciello, Valentina Capone, Mariano Carafa, Andreina Carbone, Giuseppe Caruso, Rossana Castaldo, Rodolfo Citro, Giulia Crisci, Antonello D’Andrea, Roberta D’Assante, Maria D’Avino, Francesco Ferrara, Antonio Frangiosa, Domenico Galzerano, Vincenzo Maffei, Alberto Maria Marra, Rahul M. Mehta, Rajendra H. Mehta, Fiorella Paladino, Brigida Ranieri, Monica Franzese, Giuseppe Limongelli, Salvatore Rega, Luigia Romano, Andrea Salzano, Chiara Sepe, Olga Vriz, Raffaele Izzo, Filippo Cademartiri, Antonio Cittadini and Eduardo Bossoneadd Show full author list remove Hide full author list
J. Clin. Med. 2023, 12(3), 846; https://doi.org/10.3390/jcm12030846 - 20 Jan 2023
Cited by 5 | Viewed by 6684
Abstract
Acute heart failure (AHF) is the most frequent cause of unplanned hospital admission in patients of >65 years of age and it is associated with significantly increased morbidity, mortality, and healthcare costs. Different AHF classification criteria have been proposed, mainly reflecting the clinical [...] Read more.
Acute heart failure (AHF) is the most frequent cause of unplanned hospital admission in patients of >65 years of age and it is associated with significantly increased morbidity, mortality, and healthcare costs. Different AHF classification criteria have been proposed, mainly reflecting the clinical heterogeneity of the syndrome. Regardless of the underlying mechanism, peripheral and/or pulmonary congestion is present in the vast majority of cases. Furthermore, a marked reduction in cardiac output with peripheral hypoperfusion may occur in most severe cases. Diagnosis is made on the basis of signs and symptoms, laboratory, and non-invasive tests. After exclusion of reversible causes, AHF therapeutic interventions mainly consist of intravenous (IV) diuretics and/or vasodilators, tailored according to the initial hemodynamic status with the addition of inotropes/vasopressors and mechanical circulatory support if needed. The aim of this review is to discuss current concepts on the diagnosis and management of AHF in order to guide daily clinical practice and to underline the unmet needs. Preventive strategies are also discussed. Full article
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15 pages, 2131 KiB  
Review
Efficacy of the New Inotropic Agent Istaroxime in Acute Heart Failure
by Imma Forzano, Pasquale Mone, Gaetano Mottola, Urna Kansakar, Luigi Salemme, Antonio De Luca, Tullio Tesorio, Fahimeh Varzideh and Gaetano Santulli
J. Clin. Med. 2022, 11(24), 7503; https://doi.org/10.3390/jcm11247503 - 18 Dec 2022
Cited by 7 | Viewed by 2739
Abstract
Current therapeutic strategies for acute heart failure (AHF) are based on traditional inotropic agents that are often associated with untoward effects; therefore, finding new effective approaches with a safer profile is dramatically needed. Istaroxime is a novel compound, chemically unrelated to cardiac glycosides, [...] Read more.
Current therapeutic strategies for acute heart failure (AHF) are based on traditional inotropic agents that are often associated with untoward effects; therefore, finding new effective approaches with a safer profile is dramatically needed. Istaroxime is a novel compound, chemically unrelated to cardiac glycosides, that is currently being studied for the treatment of AHF. Its effects are essentially related to its inotropic and lusitropic positive properties exerted through a dual mechanism of action: activation of the sarcoplasmic reticulum Ca2+ ATPase isoform 2a (SERCA2a) and inhibition of the Na+/K+-ATPase (NKA) activity. The advantages of istaroxime over the available inotropic agents include its lower arrhythmogenic action combined with its capability of increasing systolic blood pressure without augmenting heart rate. However, it has a limited half-life (1 hour) and is associated with adverse effects including pain at the injection site and gastrointestinal issues. Herein, we describe the main mechanism of action of istaroxime and we present a systematic overview of both clinical and preclinical trials testing this drug, underlining the latest insights regarding its adoption in clinical practice for AHF. Full article
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11 pages, 915 KiB  
Review
Use of Levosimendan in Patients with Advanced Heart Failure: An Update
by Daniele Masarone, Michelle M. Kittleson, Piero Pollesello, Marco Marini, Massimo Iacoviello, Fabrizio Oliva, Angelo Caiazzo, Andrea Petraio and Giuseppe Pacileo
J. Clin. Med. 2022, 11(21), 6408; https://doi.org/10.3390/jcm11216408 - 29 Oct 2022
Cited by 1 | Viewed by 2934
Abstract
Levosimendan is an inodilator drug that, given its unique pharmacological actions and safety profile, represents a viable therapeutic option in patients with heart failure with reduced ejection fraction in the advanced stage of the disease (advHFrEF). Pulsed levosimendan infusion in patients with advHFrEF [...] Read more.
Levosimendan is an inodilator drug that, given its unique pharmacological actions and safety profile, represents a viable therapeutic option in patients with heart failure with reduced ejection fraction in the advanced stage of the disease (advHFrEF). Pulsed levosimendan infusion in patients with advHFrEF improves symptoms and clinical and hemodynamic status, prevents recurrent hospitalizations, and enables optimization of guidelines-directed medical therapy. Furthermore, considering its proprieties on right ventricular function and pulmonary circulation, levosimendan could be helpful for the prevention and treatment of the right ventricular dysfunction post-implanting a left ventricular assist device. However, to date, evidence on this issue is scarce and has yielded mixed results. Finally, preliminary experiences indicate that treatment with levosimendan at scheduled intervals may serve as a “bridge to transplant” strategy in patients with advHFrEF. In this review, we summarized the clinical pharmacology of levosimendan, the available evidence in the treatment of patients with advHFrEF, as well as a hypothesis for its use in patients with advanced heart failure with preserved ejection fraction. Full article
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15 pages, 604 KiB  
Review
Novel Therapeutic Devices in Heart Failure
by Mateusz Guzik, Szymon Urban, Gracjan Iwanek, Jan Biegus, Piotr Ponikowski and Robert Zymliński
J. Clin. Med. 2022, 11(15), 4303; https://doi.org/10.3390/jcm11154303 - 25 Jul 2022
Cited by 5 | Viewed by 1928
Abstract
Heart failure (HF) constitutes a significant clinical problem and is associated with a sizeable burden for the healthcare system. Numerous novel techniques, including device interventions, are investigated to improve clinical outcome. A review of the most notable currently studied devices targeting pathophysiological processes [...] Read more.
Heart failure (HF) constitutes a significant clinical problem and is associated with a sizeable burden for the healthcare system. Numerous novel techniques, including device interventions, are investigated to improve clinical outcome. A review of the most notable currently studied devices targeting pathophysiological processes in HF was performed. Interventions regarding autonomic nervous system imbalance, i.e., baroreflex activation therapy; vagus, splanchnic and cardiopulmonary nerves modulation; respiratory disturbances, i.e., phrenic nerve stimulation and synchronized diaphragmatic therapy; decongestion management, i.e., the Reprieve system, transcatheter renal venous decongestion system, Doraya, preCardia, WhiteSwell and Aquapass, are presented. Each segment is divided into subsections: potential pathophysiological target, existing evidence and weaknesses or unexplained issues. Novel therapeutic devices represent great potential in HF therapy management; however, further evidence is necessary to fully evaluate their utility. Full article
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20 pages, 1146 KiB  
Review
The Treatment of Heart Failure in Patients with Chronic Kidney Disease: Doubts and New Developments from the Last ESC Guidelines
by Matteo Beltrami, Massimo Milli, Lorenzo Lupo Dei and Alberto Palazzuoli
J. Clin. Med. 2022, 11(8), 2243; https://doi.org/10.3390/jcm11082243 - 17 Apr 2022
Cited by 6 | Viewed by 9256
Abstract
Patients with heart failure (HF) and associated chronic kidney disease (CKD) are a population less represented in clinical trials; additionally, subjects with more severe estimated glomerular filtration rate reduction are often excluded from large studies. In this setting, most of the data come [...] Read more.
Patients with heart failure (HF) and associated chronic kidney disease (CKD) are a population less represented in clinical trials; additionally, subjects with more severe estimated glomerular filtration rate reduction are often excluded from large studies. In this setting, most of the data come from post hoc analyses and retrospective studies. Accordingly, in patients with advanced CKD, there are no specific studies evaluating the long-term effects of the traditional drugs commonly administered in HF. Current concerns may affect the practical approach to the traditional treatment, and in this setting, physicians are often reluctant to administer and titrate some agents acting on the renin angiotensin aldosterone system and the sympathetic activity. Therefore, the extensive application in different HF subtypes with wide associated conditions and different renal dysfunction etiologies remains a subject of debate. The role of novel drugs, such as angiotensin receptor blocker neprilysin inhibitors and sodium glucose linked transporters 2 inhibitors seems to offer a new perspective in patients with CKD. Due to its protective vascular and hormonal actions, the use of these agents may be safely extended to patients with renal dysfunction in the long term. In this review, we discussed the largest trials reporting data on subjects with HF and associated CKD, while suggesting a practical stepwise algorithm to avoid renal and cardiac complications. Full article
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Other

9 pages, 3856 KiB  
Opinion
Cardiac Contractility Modulation Therapy in Patients with Amyloid Cardiomyopathy and Heart Failure, Case Report, Review of the Biophysics of CCM Function, and AMY-CCM Registry Presentation
by Procolo Marchese, Francesca Gennaro, Giovanni Mazzotta, Claudia Acciarri, Stenio Amabili, Carlo Bonanni, Antonella D’Antonio, Domenico Delfino, Luca Di Vito, Manrico Partemi, Riccardo Pascucci, Andrea Romandini, Giancarla Scalone, Simona Silenzi and Pierfrancesco Grossi
J. Clin. Med. 2023, 12(3), 1184; https://doi.org/10.3390/jcm12031184 - 02 Feb 2023
Cited by 2 | Viewed by 1546
Abstract
Cardiac amyloidosis may result in an aggressive form of heart failure (HF). Cardiac contractility modulation (CCM) has been shown to be a concrete therapeutic option in patients with symptomatic HF, but there is no evidence of its application in patients with cardiac amyloidosis. [...] Read more.
Cardiac amyloidosis may result in an aggressive form of heart failure (HF). Cardiac contractility modulation (CCM) has been shown to be a concrete therapeutic option in patients with symptomatic HF, but there is no evidence of its application in patients with cardiac amyloidosis. We present the case of TTR amyloidosis, where CCM therapy proved to be effective. The patient had a history of multiple HF hospitalizations due to an established diagnosis of wild type TTR-Amyloidosis with significant cardiac involvement. Since he was highly symptomatic, except during continuous dobutamine and diuretic infusion, it was opted to pursue CCM therapy device implantation. At follow up, a significant improvement in clinical status was reported with an increase of EF, functional status (6 min walk test improved from zero meters at baseline, to 270 m at 1 month and to 460 m at 12 months), and a reduction in pulmonary pressures. One year after device implantation, no other HF hospital admission was needed. CCM therapy may be effective in this difficult clinical setting. The AMY-CCM Registry, which has just begun, will evaluate the efficacy of CCM in patients with HF and diagnosed TTR amyloidosis to bring new evidence on its potential impact as a therapeutic option. Full article
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