Trends in Cancer and Heart Failure related mortality in adult US population: A CDC WONDER database analysis from 1999 to 2020.

BACKGROUND: With the advent of novel chemotherapy, survival of patients with cancer has improved. However, people with cancer have an increased risk of heart failure (HF). Conversely, HF-related mortality may undermine survival among people with cancer. We aim to analyze the trends of mortality in people with HF and cancer in the adult US population. METHODS: We conducted an examination of death certificates sourced from the CDC WONDER (Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research) database, from the years 1999 to 2020. Mortality in adults with HF and cancer was assessed. Age-adjusted mortality rates (AAMRs) per 100,000 persons and annual percent change were reported. RESULTS: Between 1999 and 2020, 621,783 deaths occurred from HF in people with cancer. The AAMR declined from 16.4 in 1999 to 11.9 in 2017, after which an increase to 14.5 was observed in 2020. Men had consistently higher overall AAMR as compared to women (men = 18.1 vs women = 9.9). Similar AAMR was observed between non-Hispanic (NH) Blacks/African Americans (13.9) and NH Whites (13.3), with lower in American Indian/Alaska Native (9.6) and Hispanics (7.4). Asian/Pacific Islanders reported the lowest AAMR (5.7). The Midwestern region reported the highest AAMR (14.8). We observed the highest AAMR amongst the older population (61.4). CONCLUSION: The mortality rates of people with HF and cancer are increasing in the adult U.S. POPULATION: This underscores the need for increased screening, aggressive management, and subsequent surveillance of people at risk or with manifested HF in people with cancer.

Anthracycline Therapy Modifies Immune Checkpoint Signaling in the Heart.

Cancer survival rates have increased significantly because of improvements in therapy regimes and novel immunomodulatory drugs. Recently, combination therapies of anthracyclines and immune checkpoint inhibitors (ICIs) have been proposed to maximize neoplastic cell removal. However, it has been speculated that a priori anthracycline exposure may prone the heart vulnerable to increased toxicity from subsequent ICI therapy, such as an anti-programmed cell death protein 1 (PD1) inhibitor. Here, we used a high-dose anthracycline mouse model to characterize the role of the PD1 immune checkpoint signaling pathway in cardiac tissue using flow cytometry and immunostaining. Anthracycline treatment led to decreased heart function, increased concentration of markers of cell death after six days and a change in heart cell population composition with fewer cardiomyocytes. At the same time point, the number of PD1 ligand (PDL1)-positive immune cells and endothelial cells in the heart decreased significantly. The results suggest that PD1/PDL1 signaling is affected after anthracycline treatment, which may contribute to an increased susceptibility to immune-related adverse events of subsequent anti-PD1/PDL1 cancer therapy.

Clonal hematopoiesis confers an increased mortality risk in orthotopic heart transplant recipients.

Novel risk stratification and non-invasive surveillance methods are needed in orthotopic heart transplant (OHT) to reduce morbidity and mortality post-transplant. Clonal hematopoiesis (CH) refers to the acquisition of specific gene mutations in hematopoietic stem cells linked to enhanced inflammation and worse cardiovascular outcomes. The purpose of this study was to investigate the association between CH and OHT. Blood samples were collected from 127 OHT recipients. Error-corrected sequencing was used to detect CH-associated mutations. We evaluated the association between CH and acute cellular rejection, CMV infection, cardiac allograft vasculopathy (CAV), malignancies, and survival. CH mutations were detected in 26 (20.5%) patients, mostly in DNMT3A, ASXL1, and TET2. Patients with CH showed a higher frequency of CAV grade 2 or 3 (0% vs. 18%, p < .001). Moreover, a higher mortality rate was observed in patients with CH (11 [42%] vs. 15 [15%], p = .008) with an adjusted hazard ratio of 2.9 (95% CI, 1.4-6.3; p = .003). CH was not associated with acute cellular rejection, CMV infection or malignancies. The prevalence of CH in OHT recipients is higher than previously reported for the general population of the same age group, with an associated higher prevalence of CAV and mortality.

Muscle Wasting and Sarcopenia in Heart Failure-The Current State of Science.

Sarcopenia is primarily characterized by skeletal muscle disturbances such as loss of muscle mass, quality, strength, and physical performance. It is commonly seen in elderly patients with chronic diseases. The prevalence of sarcopenia in chronic heart failure (HF) patients amounts to up to 20% and may progress into cardiac cachexia. Muscle wasting is a strong predictor of frailty and reduced survival in HF patients. Despite many different techniques and clinical tests, there is still no broadly available gold standard for the diagnosis of sarcopenia. Resistance exercise and nutritional supplementation represent the currently most used strategies against wasting disorders. Ongoing research is investigating skeletal muscle mitochondrial dysfunction as a new possible target for pharmacological compounds. Novel agents such as synthetic ghrelin and selective androgen receptor modulators (SARMs) seem promising in counteracting muscle abnormalities but their effectiveness in HF patients has not been assessed yet. In the last decades, many advances have been accomplished but sarcopenia remains an underdiagnosed pathology and more efforts are needed to find an efficacious therapeutic plan. The purpose of this review is to illustrate the current knowledge in terms of pathogenesis, diagnosis, and treatment of sarcopenia in order to provide a better understanding of wasting disorders occurring in chronic heart failure.

Cardiac cachexia.

Cachexia is a multifactorial disease characterized by a pathologic shift of metabolism towards a more catabolic state. It frequently occurs in patients with chronic diseases such as chronic heart failure and is especially common in the elderly. In patients at risk, cardiac cachexia is found in about 10% of heart failure patients. The negative impact of cardiac cachexia on mortality, morbidity, and quality of life demonstrates the urgent need to find new effective therapies against cardiac cachexia. Furthermore, exercise training and nutritional support can help patients with cardiac cachexia. Despite ongoing efforts to find new therapies for cachexia treatment, also new preventive strategies are needed.

Detectable troponin below the 99th percentile predicts survival in patients undergoing coronary angiography.

Background: Cardiac troponin I (cTnI) above the 99th percentile is associated with an increased risk of major adverse events. Patients with detectable cTnI below the 99th percentile are a heterogeneous group with a less well-defined risk profile. The purpose of this study is to investigate the prognostic relevance of detectable cTnI below the 99th percentile in patients undergoing coronary angiography. Methods: The study included 14,776 consecutive patients (mean age of 65.4 ± 12.7 years, 71.3 % male) from the Essen Coronary Artery Disease (ECAD) registry. Patients with cTnI levels above the 99th percentile and patients with ST-segment elevation acute myocardial infarction were excluded. All-cause mortality was defined as the primary endpoint. Results: Detectable cTnI below the 99th percentile was present in 2811 (19.0 %) patients, while 11,965 (81.0 %) patients were below detection limit of the employed assay. The mean follow-up was 4.25 ± 3.76 years. All-cause mortality was 20.8 % for patients with detectable cTnI below the 99th percentile and 15.0 % for those without detectable cTnI. In a multivariable Cox regression analysis, detectable cTnI was independently associated with all-cause mortality with a hazard ratio of 1.60 (95 % CI 1.45-1.76; p < 0.001). There was a stepwise relationship with increasing all-cause mortality and tertiles of detectable cTnI levels with hazard ratios of 1.63 (95 % CI 1.39-1.90) for the first tertile to 2.02 (95 % CI 1.74-2.35) for the third tertile. Conclusions: Detectable cTnI below the 99th percentile is an independent predictor of mortality in patients undergoing coronary angiography with the risk of death growing progressively with increasing troponin levels.