Heart failure 'the cancer of the heart': the prognostic role of the HLM score.

AIMS: The multi-systemic effects of heart failure (HF) resemble the spread observed during cancer. We propose a new score, named HLM, analogous to the TNM classification used in oncology, to assess the prognosis of HF. HLM refers to H: heart damage, L: lung involvement, and M: systemic multiorgan involvement. The aim was to compare the HLM score to the conventional New York Heart Association (NYHA) classification, American College of Cardiology/American Heart Association (ACC/AHA) stages, and left ventricular ejection fraction (LVEF), to assess the most accurate prognostic tool for HF patients. METHODS AND RESULTS: We performed a multicentre, observational, prospective study of consecutive patients admitted for HF. Heart, lung, and other organ function parameters were collected. Each patient was classified according to the HLM score, NYHA classification, ACC/AHA stages, and LVEF assessed by transthoracic echocardiography. The follow-up period was 12 months. The primary endpoint was a composite of all-cause death and rehospitalization due to HF. A total of 1720 patients who completed the 12 month follow-up period have been enrolled in the study. 520 (30.2%) patients experienced the composite endpoint of all-cause death and rehospitalization due to HF. 540 (31.4%) patients were female. The mean age of the study population was 70.5 ± 12.9. The mean LVEF at admission was 42.5 ± 13%. Regarding the population distribution across the spectrum of HLM score stages, 373 (21.7%) patients were included in the HLM-1, 507 (29.5%) in the HLM-2, 587 (34.1%) in the HLM-3, and 253 (14.7%) in the HLM-4. HLM was the most accurate score to predict the primary endpoint at 12 months. The area under the receiver operating characteristic curve (AUC) was greater for the HLM score compared with the NYHA classification, ACC/AHA stages, or LVEF, regarding the composite endpoint (HLM = 0.645; NYHA = 0.580; ACC/AHA = 0.589; LVEF = 0.572). The AUC of the HLM score was significantly better compared with the LVEF (P = 0.002), ACC/AHA (P = 0.029), and NYHA (P = 0.009) AUC. CONCLUSIONS: The HLM score has a greater prognostic power compared with the NYHA classification, ACC/AHA stages, and LVEF assessed by transthoracic echocardiography in terms of the composite endpoint of all-cause death and rehospitalization due to HF at 12 months of follow-up.

Treatment of corticosteroid refractory immune checkpoint inhibitor myocarditis with Infliximab: a case series.

BACKGROUND: Glucocorticoid treatment remains the cornerstone of therapy for immune checkpoint inhibitor (ICI) myocarditis, but data supporting the use of additional immunotherapy for steroid refractory cases remains limited. We investigate the safety and efficacy of infliximab in patients with ICI myocarditis who are refractory to corticosteroids. Additionally, we highlight the importance of a multi-disciplinary approach in the care for these complex patients. METHODS: We retrospectively identified consecutive patients who developed ICI myocarditis at our institution between January 2017 and January 2020. Baseline characteristics, laboratory data and clinical outcomes were compared between patients who received infliximab and those who did not. RESULTS: Of a total of 11 patients who developed ICI myocarditis, 4 were treated with infliximab. Aside from age, there were no significant differences in baseline patient characteristics between the two groups including total number of ICI doses received and duration from initial ICI dose to onset of symptoms. The time to troponin normalization was 58 vs. 151.5 days (p = 0.25). The duration of prednisone taper was longer in the infliximab group (90 vs. 150 days p = 0.32). All patients survived initial hospital admission. Over a median follow-up period of 287 days, two of the 4 patients died from sepsis 2 and 3 months after initial treatment of their myocarditis; one of these patients was on a steroid taper and the other patient had just completed a steroid taper. CONCLUSIONS: Infliximab, despite its black box warning in patients with heart failure, may be a safe and effective treatment for ICI myocarditis.

Ethical Challenges in Care of Patients on Mechanical Circulatory Support at End-of-Life.

PURPOSE OF REVIEW: Although the utilization of mechanical circulatory support (MCS) devices is increasing, ethical dilemmas regarding device deactivation and dying process persist, potentially complicating delivery of optimal and compassionate care at end-of-life (EOL). This review aims to study EOL challenges, left ventricular assist devices (LVADs) as a nuanced life support treatment, legal history in the US impacting EOL care, and suggestions to improve EOL care for patients on MCS support. RECENT FINDINGS: Recent studies have demonstrated challenging aspects of EOL care for patients on LVAD support: low use of advanced directives, high rates of surrogate decision-making due to lack of patient capacity, difficult decision-making involving LVAD deactivation even with cooperating patients, and high rates of death in the hospital and ICU settings. Recent studies also suggest lack of consensus even among clinicians in approaching LVAD deactivation as beliefs equating LVAD deactivation with physician-assisted suicide and/or euthanasia remain. Optimal care at EOL will likely require collaborative efforts among multiple specialties, caregivers, and patients. In light of the complex medical, logistical, and ethical challenges in EOL care for LVAD patients, there is room for improvement by multidisciplinary efforts to reach consensus about LVAD deactivation and best practices for EOL care, development and implementation of LVAD-specific advance planning, and protocols for LVAD deactivation. Programmatic involvement of hospice and palliative care in the continuum of care of LVAD patients has the potential to increase and improve advance care planning, support surrogate decision-making, improve EOL compassionate care, and to support caregivers.

Massive Thrombosis of the Transplanted Heart in the Early Postoperative Period.

We experienced a case with the left atrium almost completely filled with a thrombus after orthotopic heart transplantation while the patient was supported on extracorporeal membrane oxygenation for primary graft failure. The patient had recurrent thrombosis even after successful surgical thrombectomy and appropriate anticoagulation. The cardiac thrombosis resolved only after starting plasmapheresis.

Obstructive Sleep Apnea in Obese Hospitalized Patients: A Single Center Experience.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is an important health problem associated with significant morbidity and mortality. This condition often is underrecognized in hospitalized patients. The aim of this study was to conduct a clinical pathway evaluation (CPE) among obese patients admitted to a tertiary care hospital. We also assessed oxygen desaturation index (ODI, measured by overnight pulse oximetry) as a potential low-cost screening tool for identifying OSA. METHODS: This was a prospective study of 754 patients admitted to an academic medical center between February 2013 and February 2014. Consecutive obese patients (body mass index ≥ 30) admitted to the hospital (medical services) were screened and evaluated for OSA with the snoring, tiredness during daytime, observed apnea, high blood pressure (STOP) questionnaire. The admitting team was advised to perform follow-up evaluation, including polysomnography, if the test was positive. RESULTS: A total of 636 patients were classified as high risk and 118 as low risk for OSA. Within 4 w of discharge, 149 patients underwent polysomnography, and of these, 87% (129) were shown to have OSA. An optimal screening cutoff point for OSA (apnea-hypopnea index ≥ 10/h) was determined to be ODI ≥ 10/h [Matthews correlation coefficient = 0.36, 95% confidence interval = 0.24-0.47]. Significantly more hospitalized patients were identified and underwent polysomnography compared with the year prior to introduction of the CPE. CONCLUSIONS: Our results indicate that the CPE increased the identification of OSA in this population. Furthermore, ODI derived from overnight pulse oximetry may be a cost-effective strategy to screen for OSA in hospitalized patients.

Current insights: use of Immuknow in heart transplant recipients.

Despite the advances in medical management of congenital and acquired cardiac disease, heart transplant remains the only curative option for certain patients. Transplant physicians aim to maintain a fine balance between too much and too little immunosuppression, so as to prevent complications such as infections, malignant growths, and toxic effects of drugs on one hand and acute or chronic rejection of the graft on the other hand. The ImmuKnow assay (by Cylex, recently acquired by Viracor-IBT Laboratories, Inc) was first introduced in 2002 by the Food and Drug Administration for detecting cell-mediated global immunity, thus providing an additional tool to help identify patients at risk for infection and rejection. All studies done to date are reviewed to examine the use of ImmuKnow in heart transplant recipients, both adults and children. Advantages and disadvantages are described, as well as areas in need of further investigation and improvement.

S100A1 genetically targeted therapy reverses dysfunction of human failing cardiomyocytes.

OBJECTIVES: This study investigated the hypothesis whether S100A1 gene therapy can improve pathological key features in human failing ventricular cardiomyocytes (HFCMs). BACKGROUND: Depletion of the Ca²âº-sensor protein S100A1 drives deterioration of cardiac performance toward heart failure (HF) in experimental animal models. Targeted repair of this molecular defect by cardiac-specific S100A1 gene therapy rescued cardiac performance, raising the immanent question of its effects in human failing myocardium. METHODS: Enzymatically isolated HFCMs from hearts with severe systolic HF were subjected to S100A1 and control adenoviral gene transfer and contractile performance, calcium handling, signaling, and energy homeostasis were analyzed by video-edge-detection, FURA2-based epifluorescent microscopy, phosphorylation site-specific antibodies, and mitochondrial assays, respectively. RESULTS: Genetically targeted therapy employing the human S100A1 cDNA normalized decreased S100A1 protein levels in HFCMs, reversed both contractile dysfunction and negative force-frequency relationship, and improved contractile reserve under beta-adrenergic receptor (ß-AR) stimulation independent of cAMP-dependent (PKA) and calmodulin-dependent (CaMKII) kinase activity. S100A1 reversed underlying Ca²âº handling abnormalities basally and under ß-AR stimulation shown by improved SR Ca²âº handling, intracellular Ca²âº transients, diastolic Ca²âº overload, and diminished susceptibility to arrhythmogenic SR Ca²âº leak, respectively. Moreover, S100A1 ameliorated compromised mitochondrial function and restored the phosphocreatine/adenosine-triphosphate ratio. CONCLUSIONS: Our results demonstrate for the first time the therapeutic efficacy of genetically reconstituted S100A1 protein levels in HFCMs by reversing pathophysiological features that characterize human failing myocardium. Our findings close a gap in our understanding of S100A1's effects in human cardiomyocytes and strengthen the rationale for future molecular-guided therapy of human HF.

Dynamic changes in lymphocyte GRK2 levels in cardiac transplant patients: a biomarker for left ventricular function.

G protein-coupled receptor kinase 2 (GRK2), which is upregulated in the failing human myocardium, appears to have a role in heart failure (HF) pathogenesis. In peripheral lymphocytes, GRK2 expression has been shown to reflect myocardial levels. This study represents an attempt to define the role for GRK2 as a potential biomarker of left ventricular function in HF patients. We obtained blood from 24 HF patients before and after heart transplantation and followed them for up to 1 year, also recording hemodynamic data and histological results from endomyocardial biopsies. We determined blood GRK2 protein by Western blotting and enzyme-linked immunosorbent assay. GRK2 levels were obtained before transplant and at first posttransplant biopsy. GRK2 levels significantly declined after transplant and remained low over the course of the study period. After transplantation, we found that blood GRK2 significantly dropped and remained low consistent with improved cardiac function in the transplanted heart. Blood GRK2 has potential as a biomarker for myocardial function in end-stage HF.

Cardiac transplantation across a positive prospective lymphocyte cross-match in sensitized recipients.

BACKGROUND: Although there is an increasing body of evidence for a deleterious effect of mismatched donor HLA antigens on the outcome of human cardiac transplantation, the role of anti-HLA lymphocytotoxic antibodies remains controversial. Thus, their appearance after cardiac transplantation has been associated with poor outcome by some groups; whereas others have reported them to be of no clinical significance. Furthermore, their presence prior to cardiac transplantation has also been the subject of similarly conflicting reports. The deleterious effect of such pre-existing antibodies has been predicted by a positive lymphocyte cross-match (LCM), which, for most patients awaiting renal transplantation and in many requiring a cardiac allograft, leads to cancellation of the operation. The reason for undertaking the current study was to test the hypothesis that the constraints which a positive LCM result impose in preventing renal transplantation may not apply to orthotopic heart transplantation (OHT). PATIENTS AND METHODS: Four sensitized patients underwent OHT across a positive prospective LCM. Three were females, and one of those females also underwent cadaveric renal transplantation at the time of OHT. All four patients received aggressive early post-transplant immunosuppressive therapy, which included plasmapheresis, intravenous immunoglobulin (IVIg), antiproliferative agents (cyclophosphamide, basiliximab) and cytokine down-regulators (calcineurin inhibitors, muromonab-CD3) and anticell antibodies (OKT3, ATG). They also received standard immunosuppressive therapy which included corticosteroids. Complement-dependent cytotoxicity (CDC) was used for the identification of anti-HLA lymphocytotoxic antibodies. Reactivity of the latter against more than 10% of a panel of well-characterized T cells was considered sensitization, and required LCM to be performed prospectively, which test was also performed using the CDC technique. RESULTS: Three of the patients exhibited evidence suggestive of acute or hyperacute rejection in endomyocardial biopsy specimens by postoperative day (POD) 7. Two of the three patients with rejection also exhibited haemodynamic instability (elevated filling pressures and reduced cardiac index) on POD 1, which improved with inotropic support. One patient sustained a cardiac arrest on POD 7, and was successfully resuscitated without sequelae. All patients are now doing well, postoperatively (follow-up: 17-57 months) post-transplant. Two patients have normal left ventricular function and one patient has mild left ventricular dysfunction. Two have no further evidence of sensitization (PRA < 10%). CONCLUSIONS: Although the number of patients in this study is small, the long-term successful outcome of OHT following positive prospective cross-matches suggests that such a test result, in contrast to the restraints it imposes on renal transplantation, may not be a contra-indication to transplantation of the human heart. If OHT proceeds after the LCM is reported positive, aggressive immunotherapy should not only be initiated early, but should also be targeted at humoral-vascular rejection in particular.