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Clinical Challenges in Advanced Heart Failure, Heart Transplantation and Mechanical Circulatory Support

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

Deadline for manuscript submissions: closed (29 October 2024) | Viewed by 10645

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Prof. Dr. Jürgen R. Sindermann

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Guest Editor

Interdisciplinary Heart Failure Section, University Hospital Muenster, Albert Schweitzer Campus 1, A1, 48149 Muenster, Germany
Interests: advanced heart failure; worsening heart failure; heart transplantation; left ventricular assist device; mechanical circulatory support

Special Issue Information

Dear Colleagues,

Heart failure is continuing to increase, particularly in the aging population. While the early stages of heart failure are usually well managed by medical therapy and additional supportive means, worsening or advanced heart failure may require further steps. According to American College of Cardiology (ACC), Stage D heart failure patients are at an increased risk and are characterized by refractory heart failure symptoms, despite optimized guideline-directed medical treatment. In selected cases, heart transplantation or mechanical circulatory support have to be taken into account. While heart transplantation entered the scene in the 1960s, mechanical circulatory support in terms of left ventricular assist devices have traditionally gained importance due to a shortage of donor organs. In the meantime, they have overcome the role of bridge to transplant devices. Now, left ventricular assist devices are often implanted as bridge to decision or destination therapy. This, in turn, assigns heart failure units a role in the long-term follow-up of heart transplant recipients or patients utilizing ventricular assist devices. The aim of this Special Issue is to present original scientific research addressing the identification of patients at risk of experiencing worsening or advanced heart failure, and to mirror the challenging therapeutic scenario of heart transplantation and temporary or permanent mechanical circulatory support.

Prof. Dr. Jürgen R. Sindermann
Guest Editor

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Keywords

advanced heart failure
worsening heart failure
heart transplantation
immunosuppression
left ventricular assist device
temporary mechanical circulatory support
risk stratification

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Published Papers (7 papers)

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11 pages, 587 KiB

Open AccessArticle

Postoperative, but Not Preoperative, MELD-3.0 Prognosticates 3-Month Procedural Success in Patients Undergoing Orthotopic Heart Transplantation

by Jakub Ptak, Mateusz Sokolski, Joanna Gontarczyk, Roksana Mania, Piotr Byszuk, Dominik Krupka, Paulina Makowska, Magdalena Cielecka, Anna Boluk, Mateusz Rakowski, Mateusz Wilk, Maciej Bochenek, Roman Przybylski and Michał Zakliczyński

J. Clin. Med. 2024, 13(19), 5816; https://doi.org/10.3390/jcm13195816 - 28 Sep 2024

Viewed by 847

Abstract

Background/Objectives: Multi-organ failure (MOF) often complicates advanced heart failure (HF), contributing to a poor prognosis. The Model of End-Stage Liver Disease 3.0 (MELD-3.0) scale incorporates liver and kidney function parameters. This study aims to evaluate the prognostic significance of the MELD-3.0 score in patients with advanced HF who have undergone heart transplantation (HTx). Methods: The MELD-3.0 score was computed using the average values of the international normalized ratio and bilirubin, creatinine, sodium, and albumin levels during a hospital stay following HTx. The average MELD-3.0 scores from the period of 1 month preceding HTx and 1 week after HTx were analyzed. The primary endpoint of the study was the 6-month total mortality, and the secondary endpoint was ICU hospitalization time after HTx. Results: The analysis included 106 patients undergoing HTx, with a median age of 53 years (44–63), 81% of whom were male. Within 6 months post-HTx, 17 patients (16%) died; those patients had a higher 1-week post-HTx MELD-3.0 score of 18.3 (14.5–22.7) in comparison to survivors, whose average score was 13.9 (9.5–16.4), p < 0.01. There was no difference in MELD 3.0 score in the pre-HTx period: 16.6 (11.4–17.8) vs. 12.3 (8.6–17.1), p = 0.36. The post-HTx MELD-3.0 score independently predicted death: RR 1.17 (95% CI 1.05–1.30), p < 0.01. A Receiver Operating Characteristic (ROC) determined the cut-off value of the MELD-3.0 score as 17.3 (AUC = 0.83; sensitivity—67%; specificity—86%). Survivors with scores above this value had a longer ICU hospitalization time: 7 (5.0–11.0) vs. 12 (8–20) days (p = 0.01). Conclusions: The post-HTx MELD-3.0 score serves as an independent predictor of an unfavorable prognosis in patients with advanced HF undergoing HTx. The evaluation of MELD-3.0 scores provides additional prognostic information in this population. Full article

(This article belongs to the Special Issue Clinical Challenges in Advanced Heart Failure, Heart Transplantation and Mechanical Circulatory Support)

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13 pages, 3345 KiB

Open AccessArticle

An Exercise Immune Fitness Test to Unravel Disease Mechanisms—A Proof-of-Concept Heart Failure Study

by Galyna Bondar, Abhinandan Das Mahapatra, Tra-Mi Bao, Irina Silacheva, Adrian Hairapetian, Thomas Vu, Stephanie Su, Ananya Katappagari, Liana Galan, Joshua Chandran, Ruben Adamov, Lorenzo Mancusi, Isabel Lai, Anca Rahman, Tristan Grogan, Jeffrey J. Hsu, Monica Cappelletti, Peipei Ping, David Elashoff, Elaine F. Reed and Mario C. Deng Show full author list Hide full author list

J. Clin. Med. 2024, 13(11), 3200; https://doi.org/10.3390/jcm13113200 - 29 May 2024

Viewed by 1526

Abstract

Background: Cardiorespiratory fitness positively correlates with longevity and immune health. Regular exercise may provide health benefits by reducing systemic inflammation. In chronic disease conditions, such as chronic heart failure and chronic fatigue syndrome, mechanistic links have been postulated between inflammation, muscle weakness, frailty, catabolic/anabolic imbalance, and aberrant chronic activation of immunity with monocyte upregulation. We hypothesize that (1) temporal changes in transcriptome profiles of peripheral blood mononuclear cells during strenuous acute bouts of exercise using cardiopulmonary exercise testing are present in adult subjects, (2) these temporal dynamic changes are different between healthy persons and heart failure patients and correlate with clinical exercise-parameters and (3) they portend prognostic information. Methods: In total, 16 Heart Failure (HF) patients and 4 healthy volunteers (HV) were included in our proof-of-concept study. All participants underwent upright bicycle cardiopulmonary exercise testing. Blood samples were collected at three time points (TP) (TP1: 30 min before, TP2: peak exercise, TP3: 1 h after peak exercise). We divided 20 participants into 3 clinically relevant groups of cardiorespiratory fitness, defined by peak VO₂: HV (n = 4, VO₂ ≥ 22 mL/kg/min), mild HF (HF1) (n = 7, 14 < VO₂ < 22 mL/kg/min), and severe HF (HF2) (n = 9, VO₂ ≤ 14 mL/kg/min). Results: Based on the statistical analysis with 20–100% restriction, FDR correction (p-value 0.05) and 2.0-fold change across the three time points (TP1, TP2, TP3) criteria, we obtained 11 differentially expressed genes (DEG). Out of these 11 genes, the median Gene Expression Profile value decreased from TP1 to TP2 in 10 genes. The only gene that did not follow this pattern was CCDC181. By performing 1-way ANOVA, we identified 8/11 genes in each of the two groups (HV versus HF) while 5 of the genes (TTC34, TMEM119, C19orf33, ID1, TKTL2) overlapped between the two groups. We found 265 genes which are differentially expressed between those who survived and those who died. Conclusions: From our proof-of-concept heart failure study, we conclude that gene expression correlates with VO₂ peak in both healthy individuals and HF patients, potentially by regulating various physiological processes involved in oxygen uptake and utilization during exercise. Multi-omics profiling may help identify novel biomarkers for assessing exercise capacity and prognosis in HF patients, as well as potential targets for therapeutic intervention to improve VO₂ peak and quality of life. We anticipate that our results will provide a novel metric for classifying immune health. Full article

(This article belongs to the Special Issue Clinical Challenges in Advanced Heart Failure, Heart Transplantation and Mechanical Circulatory Support)

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14 pages, 1913 KiB

Open AccessEditor’s ChoiceArticle

BMI-Stratified Exploration of the ‘Obesity Paradox’: Heart Failure Perspectives from a Large German Insurance Database

by Anastasia J. Hobbach, Jannik Feld, Wolfgang A. Linke, Jürgen R. Sindermann, Patrik Dröge, Thomas Ruhnke, Christian Günster and Holger Reinecke

J. Clin. Med. 2024, 13(7), 2086; https://doi.org/10.3390/jcm13072086 - 3 Apr 2024

Cited by 5 | Viewed by 1294

Abstract

Background: The global rise of obesity and its association with cardiovascular risk factors (CVRF) have highlighted its connection to chronic heart failure (CHF). Paradoxically, obese CHF patients often experience better outcomes, a phenomenon known as the ‘obesity paradox’. This study evaluated the ‘obesity paradox’ within a large cohort in Germany and explored how varying degrees of obesity affect HF outcome. Methods: Anonymized health claims data from the largest German insurer (AOK) for the years 2014–2015 were utilized to analyze 88,247 patients hospitalized for myocardial infarction. This analysis encompassed baseline characteristics, comorbidities, interventions, complications, and long-term outcomes, including overall survival, freedom from CHF, and CHF-related rehospitalization. Patients were categorized based on body mass index. Results: Obese patients encompassed 21.3% of our cohort (median age 68.69 years); they exhibited a higher prevalence of CVRF (p < 0.001) and comorbidities than non-obese patients (median age 70.69 years). Short-term outcomes revealed lower complication rates and mortality (p < 0.001) in obese compared to non-obese patients. Kaplan–Meier estimations for long-term analysis illustrated increased incidences of CHF and rehospitalization rates among the obese, yet with lower overall mortality. Multivariable Cox regression analysis indicated that obese individuals faced a higher risk of developing CHF and being rehospitalized due to CHF but demonstrated better overall survival for those classified as having low-level obesity (p < 0.001). Conclusions: This study underscores favorable short-term outcomes among obese individuals. The ‘obesity paradox’ was confirmed, with more frequent CHF cases and rehospitalizations in the long term, alongside better overall survival for certain degrees of obesity. Full article

(This article belongs to the Special Issue Clinical Challenges in Advanced Heart Failure, Heart Transplantation and Mechanical Circulatory Support)

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10 pages, 1155 KiB

Open AccessArticle

Durability of Tricuspid Valve Repair in Patients Undergoing Left Ventricular Assist Device Implantation

by Gloria Färber, Imke Schwan, Hristo Kirov, Marcel Rose, Sophie Tkebuchava, Ulrich Schneider, Tulio Caldonazo, Mahmoud Diab and Torsten Doenst

J. Clin. Med. 2024, 13(5), 1411; https://doi.org/10.3390/jcm13051411 - 29 Feb 2024

Cited by 1 | Viewed by 1163

Abstract

Objectives: Benefits of tricuspid valve repair (TVR) in left ventricular assist device (LVAD) patients have been questioned. High TVR failure rates have been reported. Remaining or recurring TR was found to be a risk factor for right heart failure (RHF). Therefore, we assessed our experience. Methods: Since 12/2010, 195 patients have undergone LVAD implantation in our center. Almost half (n = 94, 48%) received concomitant TVR (LVAD+TVR). These patients were included in our analysis. Echocardiographic and clinical data were assessed. Median follow-up was 2.8 years (7 days–0.6 years). Results were correlated with clinical outcomes. Results: LVAD+TVR patients were 59.8 ± 11.4 years old (89.4% male) and 37.3% were INTERMACS level 1 and 2. Preoperative TR was moderate in 28 and severe in 66 patients. RV function was severely impaired in 61 patients reflected by TAPSE-values of 11.2 ± 2.9 mm (vs. 15.7 ± 3.8 mm in n = 33; p < 0.001). Risk for RHF according to EUROMACS-RHF risk score was high (>4 points) in 60 patients, intermediate (>2–4 points) in 19 and low (0–2 points) in 15. RHF occurred in four patients (4.3%). Mean duration of echocardiographic follow-up was 2.8 ± 2.3 years. None of the patients presented with severe and only five (5.3%) with moderate TR. The vast majority (n = 63) had mild TR, and 26 patients had no/trace TR. Survival at 1, 3 and 5 years was 77.4%, 68.1% and 55.6%, 30-day mortality was 11.7% (n = 11). Heart transplantation was performed in 12 patients (12.8%). Conclusions: Contrary to expectations, concomitant TVR during LVAD implantation may result in excellent repair durability, which appears to be associated with low risk for RHF. Full article

(This article belongs to the Special Issue Clinical Challenges in Advanced Heart Failure, Heart Transplantation and Mechanical Circulatory Support)

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13 pages, 818 KiB

Open AccessArticle

Complications and Outcomes in 39,864 Patients Receiving Standard Care Plus Mechanical Circulatory Support or Standard Care Alone for Infarct-Associated Cardiogenic Shock

by Jan-Sören Padberg, Jannik Feld, Leonie Padberg, Jeanette Köppe, Lena Makowski, Joachim Gerß, Patrik Dröge, Thomas Ruhnke, Christian Günster, Stefan Andreas Lange and Holger Reinecke

J. Clin. Med. 2024, 13(4), 1167; https://doi.org/10.3390/jcm13041167 - 19 Feb 2024

Cited by 1 | Viewed by 1671

Abstract

Background: Temporary mechanical circulatory support devices (tMCS) are increasingly being used in patients with infarct-associated cardiogenic shock (AMICS). Evidence on patient selection, complications and long-term outcomes is lacking. We aim to investigate differences in clinical characteristics, complications and outcomes between patients receiving no tMCS or either intra-aortic balloon pump (IABP), veno-arterial extracorporeal membrane oxygenation (V-A ECMO) or Impella^® for AMICS, with a particular focus on long-term outcomes. Methods: Using health claim data from AOK—Die Gesundheitskasse (local health care funds), we retrospectively analysed complications and outcomes of all insured patients with AMICS between 1 January 2010 and 31 December 2017. Results: A total of 39,864 patients were included (IABP 5451; Impella 776; V-A ECMO 833; no tMCS 32,804). In-hospital complications, including renal failure requiring dialysis (50.3% V-A ECMO vs. 30.5% Impella vs. 29.2 IABP vs. 12.1% no tMCS), major bleeding (38.1% vs. 20.9% vs. 18.0% vs. 9.3%) and sepsis (22.5% vs. 15.9% vs. 13.9% vs. 9.3%) were more common in V-A ECMO patients. In a multivariate analysis, the use of both V-A ECMO (HR 1.57, p < 0.001) and Impella (HR 1.25, p < 0.001) were independently associated with long-term mortality, whereas use of IABP was not (HR 0.89, p < 0.001). Kaplan–Meier estimates showed better survival for patients on IABP compared with Impella, V-A ECMO and no-tMCS. Short- and long-term mortality was high across all groups. Conclusions: Our data show noticeably more in-hospital complications in patients on tMCS and higher mortality with V-A ECMO and Impella. The use of both devices is an independent risk factor for mortality, whereas the use of IABP is associated with a survival benefit. Full article

(This article belongs to the Special Issue Clinical Challenges in Advanced Heart Failure, Heart Transplantation and Mechanical Circulatory Support)

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11 pages, 883 KiB

Open AccessArticle

Pulmonary Vascular Resistance to Predict Right Heart Failure in Patients Undergoing Left Ventricular Assist Device Implantation

by René Schramm, Johannes Kirchner, Mohamad Ibrahim, Sebastian V. Rojas, Michiel Morshuis, Volker Rudolph, Jan F. Gummert and Henrik Fox

J. Clin. Med. 2024, 13(2), 462; https://doi.org/10.3390/jcm13020462 - 14 Jan 2024

Viewed by 1163

Abstract

Right heart failure (RHF) is associated with poor outcomes, especially in patients undergoing left ventricular assist device (LVAD) implantation. The aim of this study was to identify predictors of RHF after LVAD implantation. Of 129 consecutive patients (mean age 56 ± 11 years, 89% male) undergoing LVAD implantation, 34 developed RHF. Compared to patients without RHF, those with RHF required longer invasive mechanical ventilation and had longer intensive care unit and hospital stays (p < 0.01). One-year all-cause mortality was significantly higher in patients with versus without RHF after LVAD implantation (29.4% vs. 1.2%; hazard ratio 35.4; 95% confidence interval 4.5–277; p < 0.001). Mortality was highest in patients with delayed RHF after initial LVAD-only implantation (66.7%). Patients who did versus did not develop RHF had significantly higher baseline pulmonary vascular resistance (PVR; 404 ± 375 vs. 234 ± 162 dyn/s/cm⁵; p = 0.01). PVR > 250 dyn/s/cm⁵ was a significant predictor of survival in patients with RHF after LVAD implantation. These data confirm the negative impact of RHF on morbidity and mortality after LVAD implantation. Preoperative PVR > 250 dyn/s/cm⁵ determined using invasive right heart catheterization was an independent predictor of developing RHF after LVAD implantation, and of subsequent mortality, and could be used for risk stratification in the setting for deciding between single or biventricular support strategy. Full article

(This article belongs to the Special Issue Clinical Challenges in Advanced Heart Failure, Heart Transplantation and Mechanical Circulatory Support)

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Review

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18 pages, 1049 KiB

Open AccessReview

De Novo Donor-Specific Antibodies after Heart Transplantation: A Comprehensive Guide for Clinicians

by Irene Marco, Juan Carlos López-Azor García, Javier González Martín, Andrea Severo Sánchez, María Dolores García-Cosío Carmena, Esther Mancebo Sierra, Javier de Juan Bagudá, Javier Castrodeza Calvo, Francisco José Hernández Pérez and Juan Francisco Delgado

J. Clin. Med. 2023, 12(23), 7474; https://doi.org/10.3390/jcm12237474 - 2 Dec 2023

Cited by 1 | Viewed by 2227

Abstract

Antibodies directed against donor-specific human leukocyte antigens (HLAs) can be detected de novo after heart transplantation and play a key role in long-term survival. De novo donor-specific antibodies (dnDSAs) have been associated with cardiac allograft vasculopathy, antibody-mediated rejection, and mortality. Advances in detection methods and international guideline recommendations have encouraged the adoption of screening protocols among heart transplant units. However, there is still a lack of consensus about the correct course of action after dnDSA detection. Treatment is usually started when antibody-mediated rejection is present; however, some dnDSAs appear years before graft failure is detected, and at this point, damage may be irreversible. In particular, class II, anti-HLA-DQ, complement binding, and persistent dnDSAs have been associated with worse outcomes. Growing evidence points towards a more aggressive management of dnDSA. For that purpose, better diagnostic tools are needed in order to identify subclinical graft injury. Cardiac magnetic resonance, strain techniques, or coronary physiology parameters could provide valuable information to identify patients at risk. Treatment of dnDSA usually involves plasmapheresis, intravenous immunoglobulin, immunoadsorption, and ritxumab, but the benefit of these therapies is still controversial. Future efforts should focus on establishing effective treatment protocols in order to improve long-term survival of heart transplant recipients. Full article

(This article belongs to the Special Issue Clinical Challenges in Advanced Heart Failure, Heart Transplantation and Mechanical Circulatory Support)

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