Garcia-Arango, M

Abstract Introduction Anthracyclines (ACs) have been identified as cardiotoxic drugs. They are associated with contractile dysfunction of the heart, which can manifest as heart failure. However, differentiating between HFrEF (left ventricular ejection fractions [LVEF] ≤40%) or HFpEF (LVEF >40%) has been overlooked. Purpose Using a retrospective cohort of patients with breast cancer (BC), Hodgkin (HL) or non-Hodgkin lymphoma (NHL) and controls from the Rochester Epidemiology Project, we evaluated the association of ACs use with risk of HFrEF and/or HFpEF. Methods 797 subjects with BC, HL or NHL diagnosed from 1988 to 2010 were identified, 658 treated with ACs (ACs group) and 139 not treated with ACs (no-ACs group). Controls (n=1526) were subjects without cancer. The median (Q1, Q3) follow up was 11.5 years (7.4, 16.7). Cox proportional hazards regression was used to compare the risk of HFpEF and HFrEF in the three cohorts, adjustment for sex, CV comorbidities (type 2 diabetes [T2D], hypertension [HTN] and dyslipidemia), radiotherapy (RT), and ACs cumulative dose was performed. Results Baseline characteristics are shown in table 1. HFpEF occurred in 29/1526 subjects in the control group, 3/139 in the no-ACs group and in 14/658 in the ACs group. Compared to the control group, there was not an increased risk of developing HFpEF in the no-ACs group (HR 1.67, CI 95%: 0.5 – 5.53, p = 0.39) or in the ACs group (HR 1.83, CI 95%: 0.95 – 3.52, p = 0.06) (Figure 1). Compared with no-ACs group, the ACs group had a similar risk of developing HFpEF (HR 1.09, CI 95%: 0.3 – 3.87, p = 0.88). RT was associated with a lower risk of HFpEF (HR 0.21, CI 95%: 0.06 – 0.75, p = 0.01). In the multivariable analysis, T2D (HR 6.91, CI 95%: 3.07-15.56, p = <0.0001) was associated with higher risk of HFpEF. A cumulative dose of ACs > 250 mg/m2 was not associated with increased risk of HFpEF. HFrEF occurred in 25/1526 subjects in the control group, in 4/139 in the no-ACs group and in 31/658 in the ACs group. Compared to the control group, the ACs group had a significant increase in the risk of HFrEF (HR 4.77, CI 95%: 2.76 – 8.22, p < 0.0001), the no-ACs group did not (HR 2.81, CI 95%: 0.97 – 8.12, p = 0.055) (figure 2). RT was associated with lower risk of HFrEF (HR 0.29, CI 95%: 0.13 – 0.65, p = 0.002). In the multivariable analysis, ACs (HR 4.23, CI 95%: 2.4-7.47, p = < 0.0001) being male (HR 2.45, CI 95%: 1.43 – 4.15, p < 0.0001), smoking history (HR 2, CI 95%: 1.16 – 3.44, p < 0.01), and HTN (HR 3.23, CI 95%: 1.9 – 5.61, p < 0.0001), were associated with higher risk of HFrEF. A cumulative dose of ACs > 250 mg/m2 was not associated with increased risk of HFrEF. Conclusion To our knowledge this is the first study to differentiate between HFpEF and HFrEF in this cohort. ACs were not associated with increased risk of HFpEF. However, ACs were associated with increased risk of HFrEF, but not with a specific dose. These results should be validated in other population cohorts.

Abstract Background Obesity, defined by the World Health Organization (WHO) as a BMI greater than 30k g/m2, has reached epidemic proportions worldwide, related to approximately 2.8 million deaths/year as of June 2021. WHO sub-classifies obesity based on BMI in Class 1: 30–34.9 kg/m2, Class 2: 35–39.9 kg/m2, and Class 3: ≥40 kg/m2. This state of increased body weight is associated with an increased risk of cardiovascular disease. Cardiac remodeling can be affected by obesity and/or other cardiovascular risk factors (CVRF) as an adaptive physiological response. The remodeling patterns, Normal Geometry (NG), Concentric Remodeling (CR), Concentric Hypertrophy (CH), and Eccentric Hypertrophy, are classified by changes in Relative Wall Thickness (RWT), ≤ or >0.42, and/or Left Ventricular Mass Index (LVMI g/m2), ≤ or >88 for women and ≤ or >102 for men. Left Ventricular Ejection Fraction (LVEF) can remain within normal limits in patients with obesity with multiple CVRF and cardiac remodeling. Left Ventricular Global Longitudinal Strain (LV-GLS) and Right ventricular free wall strain (RV-FWS) can be useful to detect subclinical myocardial dysfunction. The aim of this study was to evaluate if these strain variables are affected in patients with obesity associated to other CVRF in relation to cardiac remodeling type when compared to controls. Methods 2859 patients with BMI ≥30 kg/m2 and 2616 normal-weight controls (BMI between 18.5 and 24.9 kg/m2), with normal and abnormal cardiac geometry, and normal ejection fraction by echocardiography performed between 01/01/2008 and 12/31/2018, were compared. Obesity was classified based on the World Health Organization. CVRF included were Hypertension (HTN), Diabetes Mellitus (DM), Dyslipidemia, history of Vascular Event (myocardial infarction and/or stroke), and Obstructive sleep apnea (OSA). Results BMI, cardiac geometry, CVRF, and the number of comorbidities independently affected GLS and RV-FWS (Figure 1 and Figure 2). LV-GLS and RV-FWS values [mean (SD)] in obesity classes 1, 2, and 3 were −19 (2.9), −18.9 (2.9), −18.7 (2.9) & −24.2 (5.2), −23.8 (6.2), −24.5 (5.9), respectively. In the control group LV-GLS and RV-FWS values [mean (SD)] were −20.1 (3.0) & −27 (5.6), respectively. CH was associated with the greatest decrease in LV-GLS and RV-FWS in males and females, regardless of BMI (Figure 2). LV-GLS values [mean (SD)] associated to CH for obesity class 1, 2, and 3, and controls in females were −18.4 (3.4), −18 (3.1) −17.6 (3.6), and −17.8 (4), respectively, and for obesity class 1, 2, and 3, and controls in males were −16.1 (3.5), 16.5 (3.2), −14.4 (2.7), and −16.6 (4.7), respectively (Figure 1). Conclusion Obesity associated to CVRF and CH have the lowest values of GLS in patients with normal ejection fraction. These values were exceedingly below average compared to other groups. These parameters should be used as reference values for this population. Funding Acknowledgement Type of funding sources: None.