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.

Loss of Right Atrial Pacing Lead Capture Due to Myocardial Infarction Obscuring Diagnosis on Electrocardiogram.

Right coronary artery occlusion can lead to failure to capture from the right atrial pacing lead. In this case, acute infarction resulted in failure of the right atrial lead to capture and thus increased right ventricular pacing. The new ventricular pacing masked the diagnosis of acute myocardial infarction. (Level of Difficulty: Intermediate.).

Racial and Ethnic Disparities in the Trends and Outcomes of Cardiogenic Shock Complicating Peripartum Cardiomyopathy.

Importance: Cardiogenic shock (CS) is a recognized complication of peripartum cardiomyopathy (PPCM) associated with poor prognosis. Although racial and ethnic disparities have been described in the occurrence and outcomes of PPCM, it is unclear if these disparities persist among patients with PPCM and CS. Objectives: To evaluate the temporal trends in CS incidence among hospitalized patients with PPCM stratified by race and ethnicity and to investigate the racial and ethnic differences in hospital mortality, mechanical circulatory support (MCS) use, and heart transplantation (HT). Design, Setting, and Participants: This multicenter retrospective cohort study included hospitalized patients with PPCM complicated by CS in the US from 2005 to 2019 identified from the National Inpatient Sample (NIS). Data analysis was conducted in November 2021. Exposure: PPCM complicated by CS. Main Outcomes and Measures: The main outcome was incidence of CS in PPCM stratified by race and ethnicity. The secondary outcome was racial and ethnic differences in hospital mortality, MCS use, and HT. Results: Of 55 804 hospitalized patients with PPCM, 1945 patients had CS, including 947 Black patients, 236 Hispanic patients, and 702 White patients, translating to an incidence rate of 35 CS events per 1000 patients with PPCM. The mean (SD) age was 31 (9) years. Black and Hispanic patients had higher CS incidence rates (39 events per 1000 patients with PPCM) compared with White patients (33 events per 1000 patients with PPCM). CS incidence rates significantly increased across all races and ethnicities over the study period. Overall, the odds of developing CS were higher in Black patients (aOR, 1.17 [95% CI, 1.15-1.57]; P < .001) and Hispanic patients (aOR, 1.37 [95% CI, 1.17-1.59]; P < 001) compared with White patients during the study period. Compared with White patients, the odds of in-hospital mortality were higher in Black (adjusted odds ratio [aOR], 1.67 [95% CI, 1.21-2.32]; P = .002) and Hispanic (aOR, 2.20 [95% CI, 1.45-3.33]; P < .001) patients. Hispanic patients were more likely to receive any type of MCS device (aOR, 2.23 [95% CI, 1.60-3.09]; P < .001), intraaortic balloon pump (aOR, 1.65 [95% CI, 1.11-2.44]; P < .001), and ventricular assisted device (aOR, 4.45 [95% CI, 2.45-8.08]; P < .001), compared with White patients. Black patients were more likely to receive VAD (aOR, 2.69 [95% CI, 1.63-4.42]; P < .001) compared with White patients. Black and Hispanic patients were significantly less likely to receive HT compared with White patients (Black patients: aOR, 0.51 [95% CI, 0.33-0.78]; P = .02; Hispanic patients: aOR, 0.15 [95% CI, 0.06-0.42]; P < .001). Conclusions and Relevance: These findings highlight significant racial disparities in mortality and HT among hospitalized patients with PPCM complicated by CS in the US. More research to identify factors of racial and ethnic disparities is needed to guide interventions to improve outcomes of patients with PPCM.

Trends, Predictors and Outcomes of Ischemic Stroke Among Patients Hospitalized with Takotsubo Cardiomyopathy.

OBJECTIVES: This study assessed the temporal trends in the incidence of ischemic stroke among patients hospitalized with takotsubo cardiomyopathy (TCM) stratified by the subtypes of ischemic stroke (cardioembolic versus thrombotic). Predictors of each stroke subtype, the association with atrial fibrillation (AF), the occurrence of ventricular fibrillation/ventricular tachycardia (VF/VT), cardiogenic shock (CS), in-hospital mortality, length of stay (LOS), and total healthcare cost were also assessed. BACKGROUND: Ischemic stroke in TCM is thought to be primarily cardioembolic from left ventricular mural thromboembolism. Limited data are available on the incidence of thrombotic ischemic stroke in TCM. MATERIALS AND METHODS: We identified 27,970 patients hospitalized with the primary diagnosis of TCM from the 2008 to 2017 National Inpatient Sample, of which 751 (3%) developed ischemic stroke. Of those with ischemic stroke, 571 (76%) had thrombotic stroke while 180 (24%) had cardioembolic stroke. Cochrane armitage test was used to assess the incidence of thrombotic and cardioembolic strokes and multivariate regression was used to identify risk factors associated with each stroke subtype. We compared the incidence of AF, VF/VT, CS, LOS, in-hospital mortality and total cost between hospitalized patients with TCM alone to those with cardioembolic and thrombotic strokes. RESULTS: From 2008 - 2017, the incidence of thrombotic stroke (4.7%-9.5% (p< 0.0001) increased while it was unchanged for cardioembolic stroke (0.5%-0.7% P=0.5). In the multivariate regression, peripheral artery disease, prior history of stroke, and hyperlipidemia were significantly associated with thrombotic stroke, while CS, AF, and Asian race (compared to White race) were associated with cardioembolic stroke. Both cardioembolic and thrombotic strokes were associated with higher odds of IHM, AF, CS, longer LOS and increased cost. Trends in in-hospital mortality and the utilization of thrombolysis, cerebral angiography, and mechanical thrombectomy among patients with TCM and ischemic stroke were unchanged from 2008 to 2017. CONCLUSION: Among patients with TCM and ischemic stroke, thrombotic stroke was more common compared to cardioembolic stroke. Ischemic stroke was associated with poorer outcomes, including higher in-hospital mortality and increased healthcare resource utilization in TCM.

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.

The dawn of the four-drug era? SGLT2 inhibition in heart failure with reduced ejection fraction.

Sodium-glucose cotransporter type 2 (SGLT2) inhibitors are a relatively new class of antihyperglycemic drug with salutary effects on glucose control, body weight, and blood pressure. Emerging evidence now indicates that these drugs may have a beneficial effect on outcomes in heart failure with reduced ejection fraction (HFrEF). Post-approval cardiovascular outcomes data for three of these agents (canagliflozin, empagliflozin, and dapagliflozin) showed an unexpected improvement in cardiovascular endpoints, including heart failure hospitalization and mortality, among patients with type 2 diabetes mellitus (T2DM) and established cardiovascular disease or risk factors. These studies were followed by a placebo controlled trial of dapagliflozin in patients with HFrEF both with and without T2DM, showing a reduction in all-cause mortality comparable to current guideline-directed HFrEF medical therapies such as angiotensin-converting enzyme inhibitors and beta-blockers. In this review, we discuss the current landscape of evidence, safety and adverse effects, and proposed mechanisms of action for use of these agents for patients with HFrEF. The United States (US) and European guidelines are reviewed, as are the current US federally approved indications for each SGLT2 inhibitor. Use of these agents in clinical practice may be limited by an uncertain insurance environment, especially in patients without T2DM. Finally, we discuss practical considerations for the cardiovascular clinician, including within-class differences of the SGLT2 inhibitors currently available on the US market (217/300).

Clinical outcomes in patients with native valve infective endocarditis and diabetes mellitus.

BACKGROUND: There is a lack of data on the clinical outcomes in patients with native valve infective endocarditis (NVIE) and diabetes mellitus (DM). AIM: To investigate (1) trends in the prevalence of DM among patients with NVIE; and (2) the impact of DM on NVIE outcomes. METHODS: We identified 76385 with NVIE from the 2004 to 2014 National Inpatient Sample, of which 22284 (28%) had DM. We assessed trends in DM from 2004 to 2014 using the Cochrane Armitage test. We compared baseline comorbidities, microorganisms, and in-patients procedures between those with vs without DM. Propensity match analysis and multivariate logistic regression were used to investigate study outcomes in in-hospital mortality, stroke, acute heart failure, cardiogenic shock, septic shock, and atrioventricular block. RESULTS: Crude rates of DM increased from in 22% in 2004 to 30% in 2014. There were significant differences in demographics, comorbidities and NVIE risk factors between the two groups. Staphylococcus aureus was the most common organism identified with higher rates in patients with DM (33.1% vs 35.6%; P < 0.0001). After propensity matching, in-hospital mortality (11.1% vs 11.9%; P < 0.0001), stroke (2.3% vs 3.0%; P < 0.0001), acute heart failure (4.6% vs 6.5%; P = 0.001), cardiogenic shock (1.5% vs 1.9%; P < 0.0001), septic shock (7.2% vs 9.6%; P < 0.0001), and atrioventricular block (1.5% vs 2.4%; P < 0.0001), were significantly higher in patients with DM. Independent predictors of mortality in NVIE patients with DM include hemodialysis, congestive heart failure, atrial fibrillation, staphylococcus aureus, and older age. CONCLUSION: There is an increasing prevalence of DM in NVIE and it is associated with poorer outcomes. Further studies are crucial to identify the clinical, and sociodemographic contributors to this trend and develop strategies to mitigate its attendant risk.

The effect of transfusion of blood products on ventricular assist device support outcomes.

AIMS: Perioperative blood transfusions are common among patients undergoing left ventricular assist device (LVAD) implantation. The association between blood product transfusion at the time of LVAD implantation and mortality has not been described. METHODS AND RESULTS: This was a retrospective cohort study of all patients who underwent continuous flow LVAD implantation at a single, large, tertiary care, academic centre, from 2008 to 2014. We assessed used of packed red blood cells (pRBCs), platelets, and fresh frozen plasma (FFP). Outcomes of interest included all-cause mortality and acute right ventricular (RV) failure. Standard regression techniques were used to examine the association between blood product exposure and outcomes of interest. A total of 170 patients were included in this study (mean age: 56.5 ± 15.5 years, 79.4% men). Over a median follow-up period of 11.2 months, for every unit of pRBC transfused, the hazard for mortality increased by 4% [hazard ratio (HR) 1.04; 95% CI 1.02-1.07] and odds for acute RV failure increased by 10% (odds ratio 1.10; 95% CI 1.05-1.16). This association persisted for other blood products including platelets (HR for mortality per unit 1.20; 95% CI 1.08-1.32) and FFP (HR for mortality per unit 1.08; 95% CI 1.04-1.12). The most significant predictor of perioperative blood product exposure was a lower pre-implant haemoglobin. CONCLUSIONS: Perioperative blood transfusions among patients undergoing LVAD implantation were associated with a higher risk for all-cause mortality and acute RV failure. Of all blood products, FFP use was associated with worst outcomes. Future studies are needed to evaluate whether pre-implant interventions, such as intravenous iron supplementation, will improve the outcomes of LVAD candidates by decreasing need for transfusions.

CHA2DS2-VASc Is Associated With In-Hospital Mortality in Patients With Infective Endocarditis: A Cross-Sectional Cohort Study.

Background and objective The CHA2DS2-VASc score is a stroke risk stratification tool that is used in patients with atrial fibrillation (AF). Most of its clinical variables have been associated with poor outcomes in patients with infective endocarditis (IE). In this study, we aimed to determine its utility in predicting outcomes in IE patients. Methods We included 35,570 patients with IE from the National Inpatient Sample (NIS), 2009-2012. The CHA2DS2-VASc score was calculated for each patient. Hierarchical logistic regression was used to estimate the adjusted odds ratio for in-hospital mortality for CHA2DS2-VASc scores from 1 to 9, using a score of 0 as the reference score. All clinical characteristics were defined using the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes. Results The mean age of the sample was 57.81 ±14 years. Higher CHA2DS2-VASc scores were associated with increased mortality, and the scores among the sample ranged from 0 for 8.1% to 8 for 21.7%. In the hierarchical logistic regression, after adjusting for age, sex, and relevant comorbidities, as the score increased, so did the odds for overall mortality. Conclusion In patients with IE, the CHA2DS2-VASc score may serve as a risk assessment tool with which to predict outcomes. Further studies are needed to replicate these findings.

Reduction in heart failure hospitalization rate during coronavirus disease 19 pandemic outbreak.

AIMS: The recent coronavirus disease 19 (COVID-19) pandemic outbreak forced the adoption of restraint measures, which modified the hospital admission patterns for several diseases. The aim of the study is to investigate the rate of hospital admissions for heart failure (HF) during the early days of the COVID-19 outbreak in Italy, compared with a corresponding period during the previous year and an earlier period during the same year. METHODS AND RESULTS: We performed a retrospective analysis on HF admissions number at eight hospitals in Italy throughout the study period (21 February to 31 March 2020), compared with an inter-year period (21 February to 31 March 2019) and an intra-year period (1 January to 20 February 2020). The primary outcome was the overall rate of hospital admissions for HF. A total of 505 HF patients were included in this survey: 112 during the case period, 201 during intra-year period, and 192 during inter-year period. The mean admission rate during the case period was 2.80 admissions per day, significantly lower compared with intra-year period (3.94 admissions per day; incidence rate ratio, 0.71; 95% confidence interval [CI], 0.56-0.89; P = 0.0037), or with inter-year (4.92 admissions per day; incidence rate ratio, 0.57; 95% confidence interval, 0.45-0.72; P < 0.001). Patients admitted during study period were less frequently admitted in New York Heart Association (NYHA) Class II compared with inter-year period (P = 0.019). At covariance analysis NYHA class was significantly lower in patients admitted during inter-year control period, compared with patients admitted during case period (P = 0.014). CONCLUSIONS: Admissions for HF were significantly reduced during the lockdown due to the COVID-19 pandemic in Italy.

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.

Advanced Heart Failure and End-Stage Heart Failure: Does a Difference Exist.

Advanced heart failure (AdHF) represents a challenging aspect of heart failure patients. Because of worsening clinical symptoms, high rates of re-hospitalization and mortality, AdHF represents an unstable condition where standard treatments are inadequate and additional interventions must be applied. A heart transplant is considered the optimal therapy for AdHF, but the great problem linked to the scarcity of organs and long waiting lists have led to the use of mechanical circulatory support with ventricular-assist device (VAD) as a destination therapy. VAD placement improves the prognosis, functional status, and quality of life of AdHF patients, with high rates of survival at 1 year, similar to transplant. However, the key element is to select the right patient at the right moment. The complete assessment must include a careful clinical evaluation, but also take into account psychosocial factors that are of crucial importance in the out-of-hospital management. It is important to distinguish between AdHF and end-stage HF, for which advanced therapy interventions would be unreasonable due to severe and irreversible organ damage and, instead, palliative care should be preferred to improve quality of life and relief of suffering. The correct selection of patients represents a great issue to solve, both ethically and economically.

Elevated Body Mass Index Is Not a Risk Factor for Adverse Outcomes Following Ventricular Assist Device Implantation.

BACKGROUND: Despite ventricular assist devices (VADs) becoming more common in heart failure (HF) treatment, it is still uncertain which patients are more prone to complications. One potential risk factor is increased body mass index (BMI), which is known to increase both all-cause mortality and mortality from ischemic heart disease; however, the role of the BMI in predicting morbidity and mortality following device implantation is unclear. METHODS: The study population for this single-institution retrospective chart review consisted of 136 patients with HF, who underwent VAD implantation between 2004 and 2015. Patients were divided into 2 groups based on their BMI: a nonobese group (18.5 < BMI < 30.0; n = 82) or an obese group (BMI >30.0; n = 54). These groups were compared at baseline and after implantation for survival, hospital readmission, and adverse events. RESULTS: No significant difference was found in initial hospital length of stay, number or length of readmissions, or readmission diagnosis. At 1 year, rates of ongoing device support, orthotopic heart transplant (OHT), and death were not significantly different between groups ( P = .89, P = .90, and P = .70, respectively). Multivariate analysis did not identify obesity as an independent predictor of mortality ( P = .90); only biventricular assist device implantation was associated with decreased survival (hazard ratio [HR] = 5.90, P = .002). CONCLUSION: Obesity in itself should not preclude the use of VAD support in patients with HF, as carefully selected obese patients were shown to have similar rates of hospital readmission, 1-year outcomes, and survival following device implantation compared to nonobese patients.

Obesity and heart failure with preserved ejection fraction: A growing problem.

Heart Failure with Preserved Ejection Fraction (HFpEF) is increasing in prevalence due to the aging of the United States population as well as the current obesity epidemic. While obesity is very common in patients with HFpEF, obesity may represent a specific phenotype of HFpEF characterized by unique hemodynamics and structural abnormalities. Obesity induces a systemic inflammatory response that may contribute to myocardial fibrosis and endothelial dysfunction. The most obese patients continue to be excluded from HFpEF clinical trials, and thus ongoing research is needed to determine the role of pharmacologic and interventional approaches in this growing population.

Circulating T-Cell Subsets, Monocytes, and Natural Killer Cells in Peripartum Cardiomyopathy: Results From the Multicenter IPAC Study.

OBJECTIVE: The aim of this work was to evaluate the hypothesis that the distribution of circulating immune cell subsets, or their activation state, is significantly different between peripartum cardiomyopathy (PPCM) and healthy postpartum (HP) women. BACKGROUND: PPCM is a major cause of maternal morbidity and mortality, and an immune-mediated etiology has been hypothesized. Cellular immunity, altered in pregnancy and the peripartum period, has been proposed to play a role in PPCM pathogenesis. METHODS: The Investigation of Pregnancy-Associated Cardiomyopathy (IPAC) study enrolled 100 women presenting with a left ventricular ejection fraction of <0.45 within 2 months of delivery. Peripheral T-cell subsets, natural killer (NK) cells, and cellular activation markers were assessed by flow cytometry in PPCM women early (<6 wk), 2 months, and 6 months postpartum and compared with those of HP women and women with non-pregnancy-associated recent-onset cardiomyopathy (ROCM). RESULTS: Entry NK cell levels (CD3-CD56+CD16+; reported as % of CD3- cells) were significantly (P < .0003) reduced in PPCM (6.6 ± 4.9% of CD3- cells) compared to HP (11.9 ± 5%). Of T-cell subtypes, CD3+CD4-CD8-CD38+ cells differed significantly (P < .004) between PPCM (24.5 ± 12.5% of CD3+CD4-CD8- cells) and HP (12.5 ± 6.4%). PPCM patients demonstrated a rapid recovery of NK and CD3+CD4-CD8-CD38+ cell levels. However, black women had a delayed recovery of NK cells. A similar reduction of NK cells was observed in women with ROCM. CONCLUSIONS: Compared with HP control women, early postpartum PPCM women show significantly reduced NK cells, and higher CD3+CD4-CD8-CD38+ cells, which both normalize over time postpartum. The mechanistic role of NK cells and "double negative" (CD4-CD8-) T regulatory cells in PPCM requires further investigation.