Cardiovascular Concerns, Cancer Treatment, and Biological and Chronological Aging in Cancer: JACC Family Series.

Cardiovascular disease (CVD) and cancer are leading causes of death globally, particularly among the rapidly growing population of older adults (OAs). CVD is a leading cause of mortality among cancer survivors, often accelerated by cancer treatments associated with short- or long-term cardiotoxicity. Moreover, there is a dynamic relationship among CVD, cancer, and aging, characterized by shared risk factors and biological hallmarks, that plays an important role in caring for OAs, optimizing treatment approaches, and developing preventive strategies. Assessment of geriatric domains (eg, functional status, comorbidities, cognition, polypharmacy, nutritional status, social support, psychological well-being) is critical to individualizing treatment of OAs with cancer. The authors discuss considerations in caring for an aging population with cancer, including methods for the assessment of OAs with CVD and/or cardiovascular risk factors planned for cancer therapy. Multidisciplinary care is critical in optimizing patient outcomes and maintaining quality of life in this growing vulnerable population.

Non-Cardiac Amyloidosis Findings Are Not Increased in African American Carriers of TTR V142I with Heart Failure and/or Arrhythmia.

Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive systemic disease involving the extracellular deposition of misfolded transthyretin protein. The hereditary subtype is caused by mutations in the transthyretin (TTR) gene. An estimated 2-3% of individuals of African American (AA) ancestry carry the p.Val142Ile (V142I, also referred to as V122I) TTR pathogenic variant. The non-specific clinical nature of ATTR-CM makes it challenging to diagnose clinically, and the high allele frequency of TTR V142I suggests that many patients with hereditary ATTR-CM may not have been tested. An analysis of electronic health record data from over 13,000 AA patients with a diagnostic code for heart disease or arrhythmia who also had additional amyloid-related findings were not diagnosed with amyloidosis at higher rates than those with heart failure or arrhythmia who did not have additional amyloid-related clinical diagnoses. Similarly, after genotyping 666 AA patients with heart failure or arrhythmia, TTR V142I carriers appeared to be clinically indistinguishable based on amyloid-related non-cardiac diagnoses from those who did not carry the allele. No additional TTR gene sequence variants were found in the TTR wildtype V142V patients with heart failure or arrhythmia who had additional amyloid-related diagnoses. Genetic testing for ATTR-CM may be important for timely diagnosis.

Improved Graft Function following Desensitization of Anti-AT1R and Autoantibodies in a Heart Transplant Recipient Negative for Donor-Specific Antibodies with Antibody-Mediated Rejection: A Case Report.

HLA donor-specific antibodies (DSAs) pre and post transplant increase the risk of antibody-mediated rejection (AMR) and lead to poor graft survival. Increasing data exist to support the involvement of non-HLA antibodies in triggering an immunological response. The development of non-HLA antibodies specific for AT1R is associated with poor clinical outcomes in orthotopic heart transplant recipients. This case presents an investigation of non-HLA antibodies in a 56-year-old female heart transplant recipient diagnosed with AMR in the absence of DSAs.

Heart Transplant Human Leukocyte Antigen Matching in the Modern Era.

BACKGROUND: Although numerous reports have studied the consequences of human leukocyte antigen (HLA) mismatching in renal transplantation, there are limited and outdated data analyzing this association in thoracic organ transplantation. Therefore, our study reviewed the impact of HLA mismatching at both the total and the loci levels in the modern-era heart-transplant procedure on survival and chronic rejection outcomes. METHODS: We performed a retrospective analysis of adult patients after heart transplant by using the United Network for Organ Sharing database from January 2005-July 2021. Total HLA and HLA-A, HLA-B and HLA-DR mismatches were analyzed. Survival and cardiac allograft vasculopathy were the outcomes of interest during a 10-year follow-up period using Kaplan-Meier curves, log-rank tests and multivariable regression models. RESULTS: A total of 33,060 patients were included in this study. Recipients with a high degree of HLA mismatching had increased incidences of acute organ rejection. There were no significant differences in mortality rates among any of the total or loci level groups. Similarly, there were no significant differences between total HLA mismatch groups in time to first cardiac allograft vasculopathy, though mismatching at the HLA-DR locus was associated with an increased risk of cardiac allograft vasculopathy. CONCLUSION: Our analysis suggests that HLA mismatch is not a significant predictor of survival in the modern era. Overall, the clinical implications of this study provide reassuring data for the continued use of non-HLA-matched donors in an effort to increase the donor pool. If HLA matching is to be considered for heart transplant donor-recipient selection, matching at the HLA-DR locus should take priority due to its association with cardiac allograft vasculopathy.

Perspective on AHFTC Specialty by Women in Heart Transplant and MCS (WiTMCS).

BACKGROUND: The advanced heart failure (HF) and transplant cardiology specialty has seen a decrease in applicants seeking training in the field. Data are needed to identify principal reform areas to generate and maintain interest in the field for sustainability. METHODS: Women in Transplant and Mechanical Circulatory support conducted a survey across their membership group investigating the barriers to attracting new talent and areas that need reform to improve the status of the specialty. A Likert scale was used to assess various perceived barriers to attracting new trainees and reform needed to improve the specialty. RESULTS: A total of 131 women physicians in transplant and mechanical circulatory support responded to the survey. Five principal areas in need of reform were identified: need for practice model variety (86.9%), inadequate compensation for non-revenue value unit activities and total compensation (86.4% and 79.1%, respectively), challenging work-life balance (78.5%), need for curriculum reform and specialized pathways (73.1% and 65.4%, respectively), and exposure during general cardiology fellowship (65.1%). CONCLUSION: Given the increasing number of patients with HF and the increased demand for more HF specialists, reform is needed to restructure the 5 areas identified in our survey to increase interest in the field of advanced HF and transplant cardiology and maintain the current talent.

Sex Differences in Circulating Biomarkers of Heart Failure.

PURPOSE OF REVSIEW: Evidence is scaling up for sex differences in heart failure; however, clinical relevance of sex-specific differential thresholds for biomarkers is not clearly known. Current ambiguity warrants a further look into the sex-specific studies on cardiac biomarkers and may facilitate understanding of phenotypic presentations, clinical manifestations, and pathophysiologic pathway differences in men and women. RECENT FINDINGS: Recent studies have confirmed the fact that females have differential threshold for biomarkers, with lower troponin and higher NT proBNP levels. Ambiguity continues to exist in the clinical relevance of ST-2, Galectin 3, and other biomarkers. Novel biomarkers, proteomic biomarkers, and circulating micro RNAs with machine learning are actively being explored. Biomarkers in HFpEF patients with higher female representation are evolving. In recent clinical trials, sex-related difference in biomarkers is not seen despite therapeutic intervention being more effective in females compared to males. Sex-related difference exists in the expression of biomarkers in health and in various disease states of heart failure. However, this differentiation has not effectively translated into the clinical practice in terms of diagnostic studies or prognostication. Active exploration to bridge the knowledge gap and novel technologies can shed more light in this area.

Cardiovascular Toxicities of Radiation Therapy and Recommended Screening and Surveillance.

Radiation therapy is a key part of treatment for many cancers. Vast advancements in the field of radiation oncology have led to a decrease in malignancy-related mortality, which has uncovered some of the long-term side effects of radiation therapy. Specifically, there has been an increase in research looking into the cardiovascular side effects of chest radiation therapy for cancers of the esophagus, breast, and lung tissue as well as lymphomas. The manifestations of cardiac injury from irradiation range from short-term complications, such as pericarditis, to long-term damage including cardiomyopathy, valvular disease, and conduction disturbances. The aims of this article are to describe the cardiovascular side effects and the associated risk factors, to discuss risk reduction strategies, and to provide guidance in pre-radiation screening, post-radiation surveillance, and the management of these conditions.

Adequacy of Size Matching With Predicted Heart Mass Ratio in Diverse Types of Cardiomyopathies.

Predicted heart mass ratio (PHMr) has been proposed as an optimal size metric in the selection of a donor heart for transplant; however, it is not known if the same size matching criteria pertains uniformly to all types of cardiomyopathies. Heart transplant recipients in the United Network for Organ Sharing registry database were categorized into 6 groups based on the type of cardiomyopathy, dilated, coronary artery disease, hypertrophic, restrictive, valvular and adult congenital heart disease. Patients in each group of etiology were stratified based on the PHMr into 5 groups: severely undersized <0.86, moderately undersized 0.86 to 0.94, matched 0.95 to 1.04, moderately oversized 1.05 to 1.24, and severely oversized >1.25. The survival and cause of death of patients in each etiology group were reviewed. The United Network for Organ Sharing registry database from January 1987 to July 2021 included 53,573 patients who received a heart transplant. Compared with patients with size matched hearts, recipients with dilated (hazard ratio 1.17, p = 0.001) and valvular (hazard ratio 1.79, p = 0.032) cardiomyopathy who had an undersized heart with PHMr <0.86 had decreased survival. In addition, the survival of patients with hypertrophic or restrictive cardiomyopathy and adult congenital heart disease was not affected by size matching based on the PHMr (0.601 and 0.079, respectively, p = 0.873). In conclusion, our analysis suggests that the size matching criteria based on PHMr may not be uniform to all patients across various etiologies of cardiomyopathy. Therefore, the data can be used to increase the acceptance rate of donor hearts, particularly, for patients with hypertrophic, restrictive cardiomyopathy and congenital heart disease in which size matching is less significant for survival outcome.

LVAD therapy as a catalyst to heart failure remission and myocardial recovery.

The management of chronic heart failure over the past decade has witnessed tremendous strides in medical optimization and device therapy including the use of left ventricular assist devices (LVAD). What we once thought of as irreversible damage to the myocardium is now demonstrating signs of reverse remodeling and recovery. Myocardial recovery on the structural, molecular, and hemodynamic level is necessary for sufficient recovery to withstand explant and achieve sustained recovery post-LVAD. Guideline-directed medical therapy and unloading have been shown to aid in recovery with the potential to successfully explant the LVAD. This review will summarize medical optimization, assessment for recovery, explant methodologies and outcomes post-recovery with explant of durable LVAD.

Predictors of protein losing enteropathy after Fontan completion: An 8-year retrospective study at Sheikh Khalifa Medical City.

BACKGROUND: The Fontan procedure is the final stage of a three-stage palliation process in patients born with a univentricular heart as part of hypoplastic left heart syndrome (HLHS) or other pathologies with a univentricular heart. As essential as this procedure has proven to be for such cases, the Fontan physiology diminishes cardiac output and expands systemic venous pressure, which then leads to venous congestion that can be complicated by protein-losing enteropathy (PLE). This retrospective study aimed to identify the predictors of such complications in all patients who underwent completion of the Fontan procedure at our center (Sheikh Khalifa Medical City/SKMC) in the past eight years. METHODS: This study examined the medical records of patients who underwent completion of Fontan repair at our center since the inauguration of the cardiac surgery program of SKMC in the United Arab Emirates (UAE) - 01 Jan 2012 to 31 Dec 2020. Exclusion criteria included the absence of any of the undermentioned data in patient files. Patients were divided into two groups: those who developed PLE and those who did not. For each group, the following data were collected: demographics data (current age and age at completion of Fontan), clinical and laboratory data (oxygen saturation, serum albumin), echocardiographic data (classification of original cardiac diagnosis, degree of atrio-ventricular valve regurgitation, ventricular functions), hemodynamic data (mean pressures of superior vena cava and pulmonary arteries before Fontan completion), operative data (type of initial palliation, type of Fontan, presence of fenestrations and its size) and the need for any cardiac intervention prior to Fontan completion, such as atrio-ventricular valve repair, peripheral pulmonary stenting and arch balloon dilatation. RESULTS: Of the 48 included patients,13 (25%) developed PLE. Multivariate regression analysis proved that the best predictors of PLE were superior vena cava mean pressure (P = 0.012) and the degree of atrio-ventricular valve regurgitation (P = 0.013). An oxygen saturation <83% prior to Fontan completion was 92% sensitive in predicting PLE after Fontan completion. CONCLUSION: This is a single-center study of the predictors of PLE after Fontan procedure and, as expected from similar studies, SVC pressure higher than 11 mmHg and moderate-to-severe atrio-ventricular valve regurgitation were predictors of Fontan failure. The higher prevalence of PLE in our cohort, as well as lower cut-offs of SVC pressure that can predict complications, may be related to the predominance of hypoplastic left heart in the operated patients, which has been the main referral center for cardiac surgeries in UAE in the last decade.

Impact of donor ventricular function on heart transplantation outcomes.

BACKGROUND: Some heart transplant (HTx) centers have expanded their donor eligibility criteria in response to the organ shortage; one area of active interest involves utilizing hearts with ventricular dysfunction. Our study seeks to identify if a relationship exists between donor left ventricular ejection fraction (LVEF) and ischemic time or donor age on HTx outcomes. METHODS: We performed a retrospective analysis on adult patients who had a HTx between 1996 and 2021 (n = 46,936). Donor LVEF (dLVEF) values were categorized into three groups: <50%, 50%-70%, and >70%. Ischemic time and donor age were stratified into four groups: ≤2.0, 2.1-3.0, 3.1-4.0, >4.0 h, and ≤30, 31-40, 41-50, >50 years, respectively. The outcome of interest was long-term survival. RESULTS: Multivariable survival analysis found a slight increase in overall mortality risk for patients with donor ejection fractions <50% (HR = 1.16, p = .013). However, subsequent subgroup investigation discovered that this elevated hazard was only applicable when ischemic time was prolonged to >3.0 h (3.1-4.0 h: HR = 1.23, p = .024; > 4.0 h: HR = 1.52, p < .001). There was no significant difference in survival between dLVEF groups when ischemic time was limited to ≤3.0 h or when stratified by donor age. CONCLUSION: HTx patients with a low donor ejection fraction have comparable survival to recipients with a normal dLVEF when ischemic time is limited to ≤3.0 h. Reduced dLVEF does not appear to be sensitive to advanced donor age. The clinical implications of our study may encourage the recruitment of more donor hearts for transplantation.

Correlation between severity of obesity and mortality in cardiogenic shock.

INTRODUCTION: Cardiogenic shock (CS) is associated with high mortality despite the development of risk stratification tools and new treatment strategies. Obesity, although a risk factor for cardiovascular disease, is not included in current risk stratification tools for CS. A relationship between mortality and obesity has only been shown in subsets populations of CS; there is not yet a clear relationship between severity of obesity and all-cause CS. OBJECTIVES: In this study we evaluate the relationship between rising body mass index (BMI) and mortality in all-cause CS. METHODS: All patients with BMI measurements and hospitalizations complicated by CS from 2014 to 2019 at a single quaternary care institution were identified. Patients were grouped by obesity classification. Multivariate logistic regression was performed to determine a relationship between higher obesity classifications with 30-day mortality in patients with CS. RESULTS: Seventy-two patients were available for analysis. Mean BMI for those who survived compared to those who did not was 29.7 ± 8 kg/m2 vs 33.7 ± 7.6 kg/m2 (p = 0.04). The odds ratio for mortality with incremental increase in obesity classification was 1.6 (95% CI 1.1 - 2.6, p = 0.03) after adjusting for etiology of CS and other common associations with CS mortality. CONCLUSION: This study suggests that the higher mortality risk with incremental increases in BMI should be taken into account when risk stratifying these patients.

Giant ventral hernia following left ventricular assist device bridge to heart transplantation.

Ventral hernias following left ventricular assist device (LVAD) placement are rare. With the improvement in technology, and miniaturization of devices associated with intrapericardial placement, these complications have largely been abolished. The mere presence of a large ventral hernia should not exclude recipients from being candidates for orthotopic heart transplantation.

Special Considerations in the Care of Women With Advanced Heart Failure.

Advanced heart failure (AHF) is associated with increased morbidity and mortality, and greater healthcare utilization. Recognition requires a thorough clinical assessment and appropriate risk stratification. There are persisting inequities in the allocation of AHF therapies. Women are less likely to be referred for evaluation of candidacy for heart transplantation or left ventricular assist device despite facing a higher risk of AHF-related mortality. Sex-specific risk factors influence progression to advanced disease and should be considered when evaluating women for advanced therapies. The purpose of this review is to discuss the role of sex hormones on the pathophysiology of AHF, describe the clinical presentation, diagnostic evaluation and definitive therapies of AHF in women with special attention to pregnancy, lactation, contraception and menopause. Future studies are needed to address areas of equipoise in the care of women with AHF.

Adverse Effects of Immunosuppression: Nephrotoxicity, Hypertension, and Metabolic Disease.

The use of Immunosuppression has led to the tremendous improvement in graft survival. However, immunosuppressants have been found to cause a variety of metabolic derangements including but not limited to: insulin resistance and diabetes, hyperlipidemia, hypertension, and weight gain after transplantation. This combination of metabolic risk factors may be associated with increased cardiovascular disease (Grundy et al., Circulation 112(17):2735, 2005). In addition many transplant recipients may have many of these risk factors pre-transplant that are exacerbated by immunosuppression. These facts emphasize the need for rigorous follow-up and management of these risk factors post-transplant.The most common immune suppressant regimens may include different combinations of these agents: Corticosteroids, Calcineurin inhibitors (CNIs), Mammalian Target of Rapamycin (mTOR) Inhibitors, Antimetabolite.

Healthcare disparities in cardio oncology: patients receive same level of surveillance regardless of race at a safety net hospital.

BACKGROUND: Cardiotoxicity remains a dreaded complication for patients undergoing chemotherapy with human epidermal growth factor (HER)-2 receptor antagonists and anthracyclines. Though many studies have looked at racial disparities in heart failure patients, minimal data is present for the cardio-oncology population. METHODS: We queried the echocardiogram database at a safety net hospital, defined by a high proportion of patients with Medicaid or no insurance, for patients who received HER2 receptor antagonists and/or anthracyclines from January 2016 to December 2018. Patient demographics, clinical characteristics, and treatment outcomes were collected. Based on US census data in 2019, home ZIP codes were used to group patients into quartiles based on median annual household income. The primary end point studied was referral rate to cardiology for patients undergoing chemotherapy. RESULTS: We identified 149 patients who had echocardiograms and also underwent treatment with HER2 receptor antagonists and/or anthracyclines, of which 70 (47.0%) were referred to the cardio-oncology program at our institution. Basic demographics were similar, but white patients were more likely to live in ZIP codes with higher income quartiles (p < 0.00001). Comparing between racial groups, there was no statistical difference in the percentage of patients that had a reduction in ejection fraction (EF) (p = 0.75). There was no statistical difference between racial groups in the number of cardiology or oncology appointments attended, number of appointments cancelled, average number of echocardiograms received, additional cardiac imaging received. Black patients were more likely to receive ACEI/ARB post chemotherapy (p = 0.047). A logistic regression model was created using race, age, gender, insurance, income quartile by home ZIP code, comorbidities (hypertension, hyperlipidemia, coronary artery disease, arrhythmia, diabetes mellitus, smoking, family history, age > 65), procedures (coronary stents, cardiac surgery), medications pre-chemotherapy, cancer type, cancer stage, and chemotherapy. This model found that there was an increased referral rate among patients from higher income quartiles (p = 0.017 for quartile 3, p = 0.049 for quartile 4), patients with a history of hypertension (p < 0.0001), and patients with breast cancer (p = 0.02). CONCLUSIONS: The results of this study suggest that patients of our cardio-oncology population at a safety net hospital receive the same level of surveillance and treatment, and develop drop in ejection fraction at similar rates regardless of their race. However, patients that reside in ZIP codes associated with higher income quartiles, with hypertension, and with breast cancer, are associated with increased rate of referral.