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JCM
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Current Challenges and Advances in Heart Failure and Heart Transplant
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Current Challenges and Advances 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 2021) | Viewed by 16857

Special Issue Editor

Dr. Rabea Asleh

E-Mail Website
Guest Editor
Department of Cardiology, Hadassah University Medical Center, Ein Kerem, P.O.B. 12000, Jerusalem 9112001, Israel
Interests: heart failure; heart transplantation; cardiac allograft vasculopathy; immunosuppression; left ventricular assist devices; diabetes; atherosclerosis; gut microbiota; pulmonary hypertension
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Heart failure (HF) is an overwhelming economic and public health burden with high morbidity and mortality. HF is not a single disease, as it represents a heterogeneous clinical syndrome with respect to the pathophysiology and mechanisms of myocardial disease leading to hemodynamic derangement and secondary organ dysfunction. Despite the therapeutic advances in treating patients with HF with reduced ejection fraction (HFrEF) through neurohormonal modulation, sodium–glucose cotransporter-2 (SGLT2) inhibition, and device therapies, the treatment options for HF with preserved EF (HFpEF) remain limited, as clinical trials have largely failed to identify effective therapies. Part of this failure may be related to the mechanistic heterogeneity of the various HFpEF phenotypes. There is thus an urgent need for effective interventions to reduce the burden of HFpEF, which currently accounts for approximately 50% of all heart failure cases. Over the last two decades, we have observed significant improvements in HF management and advances in our understanding of the underlying mechanisms of HF pathogenesis and progression. However, several challenges remain to be overcome, and further research is still needed in order to improve the care of HF patients and reduce adverse clinical outcomes. This includes, but is not limited to, improved HF monitoring and telemedicine, as well as the development of new medical and device therapies for patients with HFpEF based on specific disease phenotypes. Furthermore, there has been a remarkable improvement in the management of patients with stage D HF, which is generally associated with poor prognosis. Recent advances in mechanical circulatory support devices and in the postoperative management of heart transplant recipients have improved long-term survival in this population. However, device-related and post-transplant complications are common and may pose clinical challenges, including for the early diagnosis and treatment of these complications. The development of appropriate strategies for improving the selection of patients for advanced HF therapies and the early identification and management of related complications can be clinically meaningful for achieving better outcomes. For this Special Issue of JCM, “Current Challenges and Advances in Heart Failure and Heart Transplants”, we encourage the submission of primary research and comprehensive review articles covering topics focusing on advances and current challenges in the diagnosis, monitoring, and treatment of patients with HFrEF, HFpEF, or end-stage HF requiring advanced HF therapies.

Dr. Rabea Asleh
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Clinical Medicine is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Heart failure with preserved ejection fraction
  • Heart transplantation
  • Immunosuppression
  • Cardiac allograft vasculopathy
  • Post-transplant lymphoproliferative disease
  • Pulmonary hypertension
  • Left ventricular assist devices
  • Patient selection
  • Heart failure monitoring and telemedicine

Published Papers (8 papers)

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Research

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12 pages, 493 KiB  
Article
Sirolimus-Based Immunosuppression Is Associated with Decreased Incidence of Post-Transplant Lymphoproliferative Disorder after Heart Transplantation: A Double-Center Study
by Rabea Asleh, Darko Vucicevic, Tanya M. Petterson, Walter K. Kremers, Naveen L. Pereira, Richard C. Daly, Brooks S. Edwards, D. Eric Steidley, Robert L. Scott and Sudhir S. Kushwaha
J. Clin. Med. 2022, 11(2), 322; https://doi.org/10.3390/jcm11020322 - 10 Jan 2022
Cited by 5 | Viewed by 1896
Abstract
Mammalian target of rapamycin (mTOR) inhibitors have been shown to reduce proliferation of lymphoid cells; thus, their use for immunosuppression after heart transplantation (HT) may reduce post-transplant lymphoproliferative disorder (PTLD) risk. This study sought to investigate whether the sirolimus (SRL)-based immunosuppression regimen is [...] Read more.
Mammalian target of rapamycin (mTOR) inhibitors have been shown to reduce proliferation of lymphoid cells; thus, their use for immunosuppression after heart transplantation (HT) may reduce post-transplant lymphoproliferative disorder (PTLD) risk. This study sought to investigate whether the sirolimus (SRL)-based immunosuppression regimen is associated with a decreased risk of PTLD compared with the calcineurin inhibitor (CNI)-based regimen in HT recipients. We retrospectively analyzed 590 patients who received HTs at two large institutions between 1 June 1988 and 31 December 2014. Cox proportional-hazard modeling was used to examine the association between type of primary immunosuppression and PTLD after adjustment for potential confounders, including Epstein–Barr virus (EBV) status, type of induction therapy, and rejection. Conversion from CNI to SRL as primary immunosuppression occurred in 249 patients (42.2%). During a median follow-up of 6.3 years, 30 patients developed PTLD (5.1%). In a univariate analysis, EBV mismatch was strongly associated with increased risk of PTLD (HR 10.0, 95% CI: 3.8–26.6; p < 0.001), and conversion to SRL was found to be protective against development of PTLD (HR 0.19, 95% CI: 0.04–0.80; p = 0.02). In a multivariable model and after adjusting for EBV mismatch, conversion to SRL remained protective against risk of PTLD compared with continued CNI use (HR 0.12, 95% CI: 0.03–0.55; p = 0.006). In conclusion, SRL-based immunosuppression is associated with lower incidence of PTLD after HT. These findings provide evidence of a benefit from conversion to SRL as maintenance therapy for mitigating the risk of PTLD, particularly among patients at high PTLD risk. Full article
(This article belongs to the Special Issue Current Challenges and Advances in Heart Failure and Heart Transplant)
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12 pages, 265 KiB  
Article
The Impact of Advance Directive Perspectives on the Completion of Life-Sustaining Treatment Decisions in Patients with Heart Failure: A Prospective Study
by JinShil Kim, Seongkum Heo, Bong Roung Kim, Soon Yong Suh, Jae Lan Shim, Minjeong An and Mi-Seung Shin
J. Clin. Med. 2021, 10(24), 5962; https://doi.org/10.3390/jcm10245962 - 19 Dec 2021
Cited by 2 | Viewed by 2071
Abstract
Evidence for non-modifiable and modifiable factors associated with the utilization of advance directives (ADs) in heart failure (HF) is lacking. The purpose of this study was to examine baseline-to-3-month changes in knowledge, attitudes, and benefits/barriers regarding ADs and their impact on the completion [...] Read more.
Evidence for non-modifiable and modifiable factors associated with the utilization of advance directives (ADs) in heart failure (HF) is lacking. The purpose of this study was to examine baseline-to-3-month changes in knowledge, attitudes, and benefits/barriers regarding ADs and their impact on the completion of life-sustaining treatment (LST) decisions at 3-month follow-up among patients with HF. Prospective, descriptive data on AD knowledge, attitudes, and benefits/barriers and LSTs were obtained at baseline and 3-month follow-up after outpatient visits. Of 64 patients (age, 68.6 years; male, 60.9%; New York Heart Association (NYHA) classes I/II, 70.3%), 53.1% at baseline and 43.8% at 3-month follow-up completed LST decisions. Advanced age (odds ratio (OR) = 0.91, p = 0.012) was associated with less likelihood of the completion of LST decisions at 3-month follow-up, while higher education (OR = 1.19, p = 0.025) and NYHA class III/IV (OR = 4.81, p = 0.049) were associated with more likelihood. In conclusion, advanced age predicted less likelihood of LST decisions at 3 months, while higher education and more functional impairment predicted more likelihood. These results imply that early AD discussion seems feasible in mild symptomatic HF patients with poor knowledge about ADs, considering the non-modifiable and modifiable factors. Full article
(This article belongs to the Special Issue Current Challenges and Advances in Heart Failure and Heart Transplant)
14 pages, 1432 KiB  
Article
Altered mRNA Expression of Interleukin-1 Receptors in Myocardial Tissue of Patients with Left Ventricular Assist Device Support
by Naima Niazy, Linus Mrozek, Mareike Barth, Moritz Benjamin Immohr, Nikolaos Kalampokas, Diyar Saeed, Hug Aubin, Yukiharu Sugimura, Ralf Westenfeld, Udo Boeken, Artur Lichtenberg and Payam Akhyari
J. Clin. Med. 2021, 10(21), 4856; https://doi.org/10.3390/jcm10214856 - 22 Oct 2021
Cited by 2 | Viewed by 1497
Abstract
Serum levels of cytokines interleukin 1 beta ( IL-1β) and interleukin 33 (IL-33) are highly abnormal in heart failure and remain elevated after mechanical circulatory support (MCS). However, local cytokine signaling induction remains elusive. Left (LV) and right ventricular (RV) myocardial tissue [...] Read more.
Serum levels of cytokines interleukin 1 beta ( IL-1β) and interleukin 33 (IL-33) are highly abnormal in heart failure and remain elevated after mechanical circulatory support (MCS). However, local cytokine signaling induction remains elusive. Left (LV) and right ventricular (RV) myocardial tissue specimens of end-stage heart failure (HF) patients without (n = 24) and with MCS (n = 39; 594 ± 57 days) were analyzed for cytokine mRNA expression level of IL-1B, interleukin 1 receptor 1/2 (IL-1R1/2), interleukin 1 receptor-like 1 (IL-1RL1), IL-33 and interleukin-1 receptor accessory protein (IL-1RaP). MCS patients showed significantly elevated IL-1B expression levels (LV: 2.0 fold, p = 0.0058; RV: 3.3 fold, p < 0.0001). Moreover, IL-1R1, IL-1RaP and IL-33 expression levels strongly correlated with each other. IL-1RL1 and IL-1R2 expression levels were significantly higher in RV myocardial tissue (RV/LV ratio IL-1R2 HF: 4.400 ± 1.359; MCS: 4.657 ± 0.655; IL-1RL1 HF: 3.697 ± 0.876; MCS: 4.529 ± 0.5839). In addition, IL1-RaP and IL-33 RV expression levels were significantly elevated in MCS. Furthermore, IL-33 expression correlates with C-reactive protein (CRP) plasma levels in HF, but not in MCS patients. Increased expression of IL-1B and altered correlation patterns of IL-1 receptors indicate enhanced IL-1β signaling in MCS patients. Correlation of IL-1 receptor expression with IL-33 may hint towards a link between both pathways. Moreover, diverging expression in LV and RV suggests specific regulation of local cytokine signaling. Full article
(This article belongs to the Special Issue Current Challenges and Advances in Heart Failure and Heart Transplant)
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12 pages, 954 KiB  
Article
Impact of the Pre-Transplant Circulatory Supportive Strategy on Post-Transplant Outcome: Double Bridge May Work
by Nai-Kuan Chou, Heng-Wen Chou, Chuan-I Tsao, Chih-Hsien Wang, Kevin Po-Hsun Chen, Nai-Hsin Chi, Shu-Chien Huang, Hsi-Yu Yu and Yih-Sharng Chen
J. Clin. Med. 2021, 10(20), 4697; https://doi.org/10.3390/jcm10204697 - 13 Oct 2021
Cited by 3 | Viewed by 1394
Abstract
Background: The number of waitlisted patients requiring mechanical circulatory support (MCS) as a bridge to heart transplantation is increasing. The data concerning the results of the double-bridge strategy are limited. We sought to investigate the post-transplant outcomes across the different bridge strategies. Methods: [...] Read more.
Background: The number of waitlisted patients requiring mechanical circulatory support (MCS) as a bridge to heart transplantation is increasing. The data concerning the results of the double-bridge strategy are limited. We sought to investigate the post-transplant outcomes across the different bridge strategies. Methods: We retrospectively reviewed a heart transplantation database from Jan 2009 to Jan 2019. Intra-aortic balloon pump (IABP), extracorporeal membrane oxygenation (ECMO), and ventricular assist devices (VAD) were the MCS that we investigated. The pre- and post-transplant characteristics and variables of patients bridged with the different types of MCS were collected. The post-transplant survival was compared using Kaplan–Meier survival analysis. Results: A total of 251 heart transplants were reviewed; 115 without MCS and 136 with MCS. The patients were divided to five groups: Group 1 (no MCS): n = 115; Group 2 (IABP): n = 15; Group 3 (ECMO): n = 33; Group 4 (ECMO-VAD): double-bridge (n = 59); Group 5 (VAD): n = 29. Survival analysis demonstrated that the 3-year post-transplant survival rates were significantly different among the groups (Log-rank p < 0.001). There was no difference in survival between group 4(ECMO-VAD) and group 1(no MCS)1 (p = 0.136), or between group 4(ECMO-VAD) and group 5(VAD) (p = 0.994). Group 3(ECMO) had significantly inferior 3-year survival than group 4(ECMO-VAD) and group 5(VAD). Conclusion: Double bridge may not lead to worse mid-term results in patients who could receive a transplantation. Initial stabilization with ECMO for critical patients before implantation of VAD might be considered as a strategy for obtaining an optimal post-transplant outcome. Full article
(This article belongs to the Special Issue Current Challenges and Advances in Heart Failure and Heart Transplant)
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12 pages, 1909 KiB  
Article
Comparative Analysis of the Kinetic Behavior of Systemic Inflammatory Markers in Patients with Depressed versus Preserved Left Ventricular Function Undergoing Transcatheter Aortic Valve Implantation
by Haitham Abu Khadija, Gera Gandelman, Omar Ayyad, Lion Poles, Michael Jonas, Offir Paz, Sorel Goland, Sara Shimoni, Valery Meledin, Jacob George and Alex Blatt
J. Clin. Med. 2021, 10(18), 4148; https://doi.org/10.3390/jcm10184148 - 15 Sep 2021
Cited by 4 | Viewed by 1520
Abstract
Background: Prior studies have proven the safety and efficacy of transcatheter aortic valve implantation (TAVI) in patients with reduced left ventricular (LV) function. This study’s aim was to investigate periprocedural inflammatory responses after TAVI. Methods: Patients with severe symptomatic aortic stenosis and reduced [...] Read more.
Background: Prior studies have proven the safety and efficacy of transcatheter aortic valve implantation (TAVI) in patients with reduced left ventricular (LV) function. This study’s aim was to investigate periprocedural inflammatory responses after TAVI. Methods: Patients with severe symptomatic aortic stenosis and reduced LV function who underwent transfemoral TAVI were enrolled. A paired-matched analysis (1:2 ratio) was performed using patients with preserved LV function. Whole white blood cells (WBC) and subpopulation dynamics as well as the neutrophil to lymphocyte ratio (NLR) were evaluated at different times. Results: A total of 156 patients were enrolled, including 52 patients with LVEF < 40% 35.00 [30.00, 39.25] and 104 with LVEF > 50% 55.00 [53.75, 60.0], p < 0.001. Baseline NLR in the reduced LV function group was significantly higher compared to the preserved LV function group, 2.85 [2.07, 4.78] vs. 3.90 [2.67, 5.26], p < 0.04. After a six-month follow-up, the inflammatory profile was found to be similar in the two groups, NLR 2.94 [2.01, 388] vs. 3.30 [2.06, 5.35], p = 0.288. No significant mortality differences between the two groups were observed in the long-term outcome. Conclusions: TAVI for severe symptomatic aortic stenosis, with reduced LV function, was associated with an improvement in the inflammatory profile that may account for some of the observable benefits of the procedure in this subset of patients. Full article
(This article belongs to the Special Issue Current Challenges and Advances in Heart Failure and Heart Transplant)
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13 pages, 2894 KiB  
Article
Use of Extracorporeal Life Support for Heart Transplantation: Key Factors to Improve Outcome
by Jun Ho Lee, Nayeon Choi, Yun Jin Kim, Kiick Sung, Wook Sung Kim, Darae Kim, Jeong Hoon Yang, Eun-Seok Jeon, Sung Ho Shinn, Jin-Oh Choi and Yang Hyun Cho
J. Clin. Med. 2021, 10(12), 2542; https://doi.org/10.3390/jcm10122542 - 08 Jun 2021
Cited by 1 | Viewed by 1507
Abstract
Although patients receiving extracorporeal life support (ECLS) as a bridge to transplantation have demonstrated worse outcomes than those without ECLS, we investigated the key factors in the improvement of their posttransplant outcome. From December 2003 to December 2018, 257 adult patients who underwent [...] Read more.
Although patients receiving extracorporeal life support (ECLS) as a bridge to transplantation have demonstrated worse outcomes than those without ECLS, we investigated the key factors in the improvement of their posttransplant outcome. From December 2003 to December 2018, 257 adult patients who underwent heart transplantation (HTx) at our institution were included. We identified 100 patients (38.9%) who underwent HTx during ECLS (ECLS group). The primary outcome was 30-day mortality after HTx. The median duration of ECLS was 10.0 days. The 30-day mortality rate was 3.9% (9.2% in peripheral ECLS, 2.9% in central ECLS, and 1.9% in non-ECLS). The use of ECLS was not an independent predictor of 30-day and 1-year mortality (p = 0.248 and p = 0.882, respectively). Independent predictors of 30-day mortality were found to be higher ejection fraction (p < 0.001), Sequential Organ Failure Assessment score (p < 0.001), and total bilirubin level (p = 0.005). In a subgroup analysis, cannulation type was not a predictor of 30-day mortality (p = 0.275). Early ECLS application to prevent organ failure and sophisticated management of acute heart failure may be important steps in achieving favorable survival after HTx. Full article
(This article belongs to the Special Issue Current Challenges and Advances in Heart Failure and Heart Transplant)
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Review

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9 pages, 1202 KiB  
Review
Pathophysiology of Heart Failure: A Role for Peripheral Blood Mononuclear Cells Mitochondrial Dysfunction?
by François Sauer, Marianne Riou, Anne-Laure Charles, Alain Meyer, Emmanuel Andres, Bernard Geny and Samy Talha
J. Clin. Med. 2022, 11(3), 741; https://doi.org/10.3390/jcm11030741 - 29 Jan 2022
Cited by 7 | Viewed by 3360
Abstract
Heart failure (HF) is a leading cause of hospitalization in patients aged more than 65 years and is associated with high mortality rates. A better comprehension of its physiopathology is still needed, and, in addition to neurohormonal systems and sodium glucose co-transporter 2 [...] Read more.
Heart failure (HF) is a leading cause of hospitalization in patients aged more than 65 years and is associated with high mortality rates. A better comprehension of its physiopathology is still needed, and, in addition to neurohormonal systems and sodium glucose co-transporter 2 modulations, recent studies focus on the mitochondrial respiration of peripheral blood circulating cells (PBMCs). Thus, cardiovascular metabolic risk factors and cellular switch with an increased neutrophil/lymphocytes ratio might favor the decreased PBMC mitochondrial respiration observed in relation with HF severity. PBMCs are implicated in the immune system function and mitochondrial dysfunction of PBMC, potentially induced by their passage through a damaged heart and by circulating mitoDAMPs, which can lead to a vicious circle, thus sustaining negative cardiac remodeling during HF. This new approach of HF complex pathophysiology appears to be a promising field of research, and further studies on acute and chronic HF with reduced or preserved LVEF are warranted to better understand whether circulating PBMC mitochondrial function and mitoDAMPs follow-ups in HF patients might show diagnosis, prognosis or therapeutic usefulness. Full article
(This article belongs to the Special Issue Current Challenges and Advances in Heart Failure and Heart Transplant)
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15 pages, 1423 KiB  
Review
In Search of Clinical Impact: Advanced Monitoring Technologies in Daily Heart Failure Care
by Dean Nachman, Eldad Rahamim, Yotam Kolben, Bethlehem Mengesha, Gabby Elbaz-Greener, Offer Amir and Rabea Asleh
J. Clin. Med. 2021, 10(20), 4692; https://doi.org/10.3390/jcm10204692 - 13 Oct 2021
Cited by 2 | Viewed by 2782
Abstract
Despite significant advances in the management of heart failure (HF), further improvement in the outcome of this chronic and progressive disease is still considered a major unmet need. Recurrent hospitalizations due to decompensated HF frequently occur, resulting in increased morbidity and mortality rates. [...] Read more.
Despite significant advances in the management of heart failure (HF), further improvement in the outcome of this chronic and progressive disease is still considered a major unmet need. Recurrent hospitalizations due to decompensated HF frequently occur, resulting in increased morbidity and mortality rates. Past attempts at early detection of clinical deterioration were mainly based on monitoring of signs and symptoms of HF exacerbation, which have mostly given disappointing results. Extensive research of the pathophysiology of HF decompensation has indicated that hemodynamic alterations start days prior to clinical manifestation. Novel technologies aim to monitor these minute hemodynamic changes, allowing time for therapeutic interventions to prevent hemodynamic derangement and HF exacerbation. The latest noticeable advancements include assessment of lung fluid volume, wearable devices with integrated sensors, and microelectromechanical systems-based implantable devices for continuous measurement of cardiac filling pressures. This manuscript will review the rationale for monitoring HF patients and discuss previous and ongoing attempts to develop clinically meaningful monitoring devices to improve daily HF health care, with particular emphasis on the recent advances and clinical trials relevant to this evolving field. Full article
(This article belongs to the Special Issue Current Challenges and Advances in Heart Failure and Heart Transplant)
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