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.

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.

Dichotomous Relationship Between Age and 30-Day Death or Rehospitalization in Heart Failure Patients Admitted With Acute Decompensated Heart Failure: Results From the ASCEND-HF Trial.

BACKGROUND: Younger age as an independent predictor of death or all-cause rehospitalization at 30 days post-randomization for hospitalized heart failure (HF) patients has not been well described. METHODS AND RESULTS: ASCEND-HF enrolled 7141 hospitalized acute HF patients (categorized by age: <45, 45 to <55, 55 to <65, 65 to <75, and ≥75 years) and followed them for 30 days to assess clinical outcomes, which included death or rehospitalization. Patients 45 to <55 years had the lowest percentages of death (1.4%) and total rehospitalizations (10.7%); percentages increased for younger (3.0% and 12.2%, respectively, for age <45 y) and older (5.8% and 12.5%, respectively, for age ≥75 y) patients. For those rehospitalized, the total HF-induced readmissions were highest in the youngest (68%) and declined with increasing age (P = .03). Although patients ≥55 years of age were more likely to die or be rehospitalized within 30 days of randomization for each additional 10 years of life, those <55 years of age had a significant reduction in death or HF rehospitalization for each 10-year increase in age (similar findings for death and HF rehospitalization). CONCLUSIONS: There is a dichotomous relationship between age and risk of death or rehospitalization, and death or HF rehospitalization-risk decreases as age increases up to age 55 years, then increases after age 55 years.

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.

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.

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.

Implantable cardiac defibrillators and sudden death in recent onset nonischemic cardiomyopathy: results from IMAC2.

BACKGROUND: Given the potential for recovery in recent onset nonischemic cardiomyopathy (ROCM), the timing and need for implantable cardioverter-defibrillator (ICDs) remains controversial. We examined the utilization of ICDs and the impact on survival for subjects with ROCM. METHODS AND RESULTS: An National Heart, Lung, and Blood Institute sponsored registry enrolled 373 subjects with ROCM, all with a left ventricular ejection fraction (LVEF) ≤0.40 and ≤6 months of symptoms. The mean age was 45 ± 14 years, 38% were female, 21% black, 75% New York Heart Association II/III, and the mean LVEF was 0.24 ± 0.08. Survival was comparable for subjects with an ICD within 1 month of entry (n = 43, 1/2/3 year % survival = 97/97/92) and those with no ICD at 1 month (n = 330, % survival = 98/97/95, P = .30) and between those with and without an ICD at 6 months (ICD, n = 73, 1/2/3 year % survival = 98/98/95; no ICD, n = 300, % survival = 98/96/95, P = .95). There were only 6 sudden cardiac deaths (SCD) noted (% survival free from SCD = 99/98/97) and these occurred in 1.9% of subjects without ICD and 0.9% of those with a device (P = .50). CONCLUSIONS: In a multicenter cohort of ROCM the risk of SCD was low at 1% per year. Early ICD placement did not impact survival and can be deferred while assessing potential for myocardial recovery.

Myocardial recovery in peripartum cardiomyopathy: prospective comparison with recent onset cardiomyopathy in men and nonperipartum women.

BACKGROUND: Whether myocardial recovery occurs more frequently in peripartum cardiomyopathy (PPCM) than in recent onset cardiomyopathies in men and nonperipartum women has not been prospectively evaluated. This was examined through an analysis of outcomes in the Intervention in Myocarditis and Acute Cardiomyopathy 2 (IMAC2) registry. METHODS AND RESULTS: IMAC2 enrolled 373 subjects with recent onset nonischemic dilated cardiomyopathy. Left ventricular ejection fraction (LVEF) was assessed at entry and 6 months, and subjects followed for up to 4 years. Myocardial recovery was compared between men (group 1), nonperipartum women (group 2) and subjects with PPCM (group 3). The cohort included 230 subjects in group 1, 104 in group 2, and 39 in group 3. The mean LVEF at baseline in groups 1, 2, and 3 was 0.23 ± 0.08, 0.24 ± 0.08, and 0.27 ± 0.07 (P = .04), and at 6 months was 0.39 ± 0.12, 0.42 ± 0.11, and 0.45 ± 0.14 (P = .007). Subjects in group 3 had a much greater likelihood of achieving an LVEF >0.50 at 6 months than groups 1 or 2 (19 %, 34%, and 48% respectively, P = .002). CONCLUSIONS: Prospective evaluation confirms myocardial recovery is greatest in women with PPCM, poorest in men, and intermediate in nonperipartum women. On contemporary therapy, nearly half of women with PPCM normalize cardiac function by 6 months.

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.).

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).

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.

Sepsis-induced cardiomyopathy: a review of pathophysiologic mechanisms.

Cardiac dysfunction is a well-recognized complication of severe sepsis and septic shock. Cardiac dysfunction in sepsis is characterized by ventricular dilatation, reduction in ejection fraction and reduced contractility. Initially, cardiac dysfunction was considered to occur only during the "hypodynamic" phase of shock. But we now know that it occurs very early in sepsis even during the "hyperdynamic" phase of septic shock. Circulating blood-borne factors were suspected to be involved in the evolution of sepsis induced cardiomyopathy, but it is not until recently that the cellular and molecular events are being targeted by researchers in a quest to understand this enigmatic process. Septic cardiomyopathy has been the subject of investigation for nearly half a century now and yet controversies exist in understanding it's pathophysiology. Here, we discuss our understanding of the pathogenesis of septic cardiomyopathy and the complex roles played by nitric oxide, mitochondrial dysfunction, complements and cytokines.

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.

AVP receptor antagonists in patients with CHF.

In the Adhere (Acute Decompensated Heart Failure Registry) National Registry, hyponatremia (serum sodium <130 mEq/l) at clinical presentation was noted in 5% of patients with HF. The enhanced release of arginine vasopressin (AVP) can lead to hyponatremia by binding to the V2 receptor results in free-water retention and hyponatremia. Given the central role of AVP in causing hyponatremia in patients with congestive heart failure, decreasing vasopressin activity has been a therapeutic focus. With no current therapy to decrease production of AVP, attention was turned to decreasing the effect of AVP by blocking the receptor.

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.

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.

Pharmacologic therapy of chronic heart failure.

Over the past 2 decades, investigators have learned more about the pathophysiologic changes that occur in systolic and diastolic dysfunction. Ironically, in some cases, the biologic pathways that have protected the heart during acute dysfunction are the same pathways that cause progressive deleterious effects with chronic activation. In particular, it is the activation of the neurohormonal system that has a significant impact on disease progression. As a result, the neurohormonal system has provided a key target for pharmacologic therapy in patients with heart failure secondary to systolic dysfunction. These targets include the renin-angiotensin-aldosterone system as well as the sympathetic nervous system. Neurohormonal manipulation, however, is often ineffective in the pharmacologic therapy of patients with endstage heart failure, therefore other treatment strategies - including the use of inotropic agents to improve pump function and diuretics to control fluid balance are needed.

Hyponatremia and vasopressin antagonism in congestive heart failure.

In a national heart failure registry, hyponatremia (serum sodium < 130 mEq/L) was initially reported in 5% of patients and considered a risk factor for increased morbidity and mortality. In a chronic heart failure study, serum sodium level on admission predicted an increased length of stay for cardiovascular causes and increased mortality within 60 days of discharge. Hyponatremia in patients with congestive heart failure (CHF) is associated with a higher mortality rate. Also, by monitoring and increasing serum sodium levels during hospitalization for CHF, patient outcomes may improve. This review describes the pathophysiology of hyponatremia in relation to CHF, including the mechanism of action of vasopressin receptors in the kidney, and assesses the preclinical and clinical trials of vasopressin receptor antagonists--agents recently developed to treat hyponatremia. In hospitalized patients with CHF, hyponatremia plays a major role in poor outcomes. Vasopressin receptor antagonists have been shown to be safe and effective in clinical trials in patients with hyponatremia.

A review of the association between congestive heart failure and cognitive impairment.

Heart failure is a growing epidemic with an estimated 5 million Americans suffering from this condition. Several clinical trials have demonstrated a high correlation between congestive heart failure (CHF) and cognitive impairment. The severity of cognitive impairment correlates positively with the degree of CHF. The underlying mechanism for cognitive impairment remains unclear but appears to be related to cerebral hypoperfusion and impaired cerebral reactivity with selective impairment of verbal memory and attention domains. Furthermore, cognitive dysfunction represents one aspect of frailty, a novel concept that encompasses a range of clinical conditions that results in functional impairment in patients with heart failure. In addition, frailty independently predicts mortality in CHF patients. Cognitive impairment is a common and predictable effect of CHF that contributes with social and behavioral problems to decreased compliance to prescribed therapy and increased hospital readmissions. A multidisciplinary approach is necessary to deal with the complexity of this clinical syndrome.

Sleep Overnight Monitoring for Apnea in Patients Hospitalized with Heart Failure (SOMA-HF Study).

INTRODUCTION: Sleep-disordered breathing (SDB) is highly prevalent in hospitalized patients with congestive heart failure (CHF) and the condition is diagnosed and treated in only a minority of these patients. Portable monitoring (PM) is a screening option, but due to costs and the expertise required, many hospitals may find it impractical to implement. We sought to test the utility of an alternative approach for screening hospitalized CHF patients for SDB, high-resolution pulse oximetry (HRPO). METHODS: We conducted a prospective controlled trial of 125 consecutive patients admitted to the hospital with CHF. Simultaneous PM and HRPO for a single night was performed. All but one patient were monitored on breathing room air. The HRPO-derived ODI (oxygen desaturation index) was compared with PM-derived respiratory event index (REI) using both receiver operator characteristic (ROC) curve analysis and a Bland-Altman plot. RESULTS: Of 105 consecutive CHF patients with analyzable data, 61 (58%) were males with mean age of 64.9 ± 15.1 years and mean body mass index of 30.3 ± 8.3 kg/m2. Of the 105 patients, 10 (9.5%) had predominantly central sleep apnea (central events > 50% of the total events), although central events were noted in 42 (40%) of the patients. The ROC analysis showed an area under the curve of 0.89 for REI > 5 events/h. The Bland-Altman plot showed acceptable agreement with 95% limits of agreement between -28.5 to 33.7 events/h and little bias. CONCLUSIONS: We conclude that high-resolution pulse oximetry is a simple and cost-effective screening tool for SDB in CHF patients admitted to the hospital. Such screening approaches may be valuable for large-scale implementation and for the optimal design of interventional trials.