Sex differences in heart failure patients assessed by combined echocardiographic and cardiopulmonary exercise testing

BackgroundWe aimed to test the differences in peak VO2 between males and females in patients diagnosed with heart failure (HF), using combined stress echocardiography (SE) and cardiopulmonary exercise testing (CPET).MethodsPatients who underwent CPET and SE for evaluation of dyspnea or exertional intolerance at our institution, between January 2013 and December 2017, were included and retrospectively assessed. Patients were divided into three groups: HF with preserved ejection fraction (HFpEF), HF with mildly reduced or reduced ejection fraction (HFmrEF/HFrEF), and patients without HF (control). These groups were further stratified by sex.ResultsOne hundred seventy-eight patients underwent CPET-SE testing, of which 40% were females. Females diagnosed with HFpEF showed attenuated increases in end diastolic volume index (P = 0.040 for sex × time interaction), significantly elevated E/e' (P < 0.001), significantly decreased left ventricle (LV) end diastolic volume:E/e ratio (P = 0.040 for sex × time interaction), and lesser increases in A-VO2 difference (P = 0.003 for sex × time interaction), comparing to males with HFpEF. Females diagnosed with HFmrEF/HFrEF showed diminished increases in end diastolic volume index (P = 0.050 for sex × time interaction), mostly after anaerobic threshold was met, comparing to males with HFmrEF/HFrEF. This resulted in reduced increases in peak stroke volume index (P = 0.010 for sex × time interaction) and cardiac output (P = 0.050 for sex × time interaction).ConclusionsCombined CPET-SE testing allows for individualized non-invasive evaluation of exercise physiology stratified by sex. Female patients with HF have lower exercise capacity compared to men with HF. For females diagnosed with HFpEF, this was due to poorer LV compliance and attenuated peripheral oxygen extraction, while for females diagnosed with HFmrEF/HFrEF, this was due to attenuated increase in peak stroke volume and cardiac output. As past studies have shown differences in clinical outcomes between females and males, this study provides an essential understanding of the differences in exercise physiology in HF patients, which may improve patient selection for targeted therapeutics

Valvular Heart Disease following Anthracycline Therapy—Is It Time to Look beyond Ejection Fraction?

The association between anthracycline (ANT) and left ventricle (LV) dysfunction is well known; however, data regarding its direct effect on cardiac valve function is limited. We aimed to evaluate how ANT therapy affected valvular function in patients diagnosed with breast cancer. Data were prospectively collected as part of the Israel Cardio-Oncology Registry (ICOR). Patients underwent echocardiography exams at baseline (T1), during ANT therapy (T2), and after completion within 3 months (T3) and 6 months (T4). A total of 141 female patients were included, with a mean age of 51 ± 12 years. From T1 to T4, we observed a significant deterioration in LV ejection fraction (60.2 ± 1.5 to 59.2 ± 2.7%, p = 0.0004) and LV global longitudinal strain (−21.6 (−20.0–−23.0) to −20.0 (−19.1–−21.1)%, p < 0.0001)), and an increase in LV end-systolic diameter (25 (22–27) to 27 (24–30) mm, p < 0.0001). We observed a significant increase in the incidence of new mitral regurgitation (MR) development (4 to 19%, p < 0.0001), worsening with concomitant trastuzumab therapy (6% to 31%, p = 0.003), and a trend for tricuspid regurgitation development (4% to 8%, p = 0.19). ANT therapy is associated with the development of a new valvular disease, mainly MR, which may imply the need for a valvular focus in the monitoring of cancer patients

Immune Checkpoint Inhibitor-Induced Myocarditis vs. COVID-19 Vaccine-Induced Myocarditis—Same or Different?

Immune checkpoint inhibitor (ICI) and coronavirus disease 2019 (COVID-19) vaccine-induced myocarditis possibly share common mechanisms secondary to overactivation of the immune system. We aimed to compare the presenting characteristics of ICIs and COVID-19 vaccine-induced myocarditis. We performed a retrospective analysis of characteristics of patients diagnosed with either ICIs or COVID-19 vaccine-induced myocarditis and compared the results to a control group of patients diagnosed with acute viral myocarditis. Eighteen patients diagnosed with ICIs (ICI group) or COVID-19 vaccine (COVID-19 vaccine group)-induced myocarditis, and 20 patients with acute viral myocarditis (Viral group) were included. The ICI group presented mainly with dyspnea vs. chest pain and fever among the COVID-19 vaccine and Viral groups. Peak median high sensitivity Troponin I was markedly lower in the ICI group (median 619 vs. 15,527 and 7388 ng/L, p = 0.004). While the median left ventricular (LV) ejection fraction was 60% among all groups, the ICI group had a lower absolute mean LV global longitudinal strain (13%) and left atrial conduit strain (17%), compared to the COVID-19 vaccine (17% and 30%) and Viral groups (18% and 37%), p = 0.016 and p = 0.001, respectively. Despite a probable similar mechanism, ICI-induced myocarditis’s presenting characteristics differed from COVID-19 vaccine-induced myocarditis

The Mechanism of Effort Intolerance in Patients with Peripheral Arterial Disease: A Combined Stress Echocardiography and Cardiopulmonary Exercise Test

Aim: We used a combined stress echocardiography and cardiopulmonary exercise test (CPET) to explore effort intolerance in peripheral arterial disease (PAD) patients. Methods: Twenty-three patients who had both PAD and coronary artery disease (CAD) were compared with twenty-four sex- and age-matched CAD patients and fifteen normal controls using a symptom-limited ramp bicycle CPET on a tilting dedicated ergometer. Echocardiographic images were obtained concurrently with gas exchange measurements along predefined stages of exercise. Oxygen extraction was calculated using the Fick equation at each activity level. Results: Along the stages of exercise (unloaded; anaerobic threshold; peak), in PAD + CAD patients compared with CAD or controls, diastolic function worsened (p = 0.051 and p = 0.013, respectively), and oxygen consumption (p p p = 0.0024 and p = 0.0027, respectively) were reduced. Notably, oxygen pulse was blunted due to an insufficient increase in both stroke volume (p = 0.025 and p = 0.028, respectively) and peripheral oxygen extraction (p = 0.031 and p = 0.038, respectively). Chronotropic incompetence was more prevalent in PAD patients and persisted after correction for beta-blocker use (62% vs. 42% and 11%, respectively). Conclusions: In PAD patients, exercise limitation is associated with diastolic dysfunction, chronotropic incompetence and peripheral factors

Prevalence of Right Ventricle Strain Changes following Anthracycline Therapy

Background: Anthracycline (ANT) is the most recognized therapy known to cause cardiotoxicity, mainly left ventricle (LV) dysfunction. Global Longitudinal Strain (GLS) is the optimal tool for assessment of subclinical LV dysfunction. Right ventricle (RV) function has been recognized as an independent factor for cardiac outcomes; however, data evaluating RV GLS is limited. We aimed to evaluate the change in RV GLS following ANT therapy. Methods: The study cohort is part of the Israel Cardio-Oncology Registry (ICOR). All patients performed echocardiography before (T1) and at the end (T3) of ANT therapy. A significant reduction was defined as a relative reduction of ≥10% in RV GLS values. Results: The study included 40 female patients with breast cancer treated with ANT. During follow-up, both RV GLS and free wall longitudinal strain systolic peak (RV FWLS PK) decreased significantly (p < 0.001 and p = 0.002). Altogether, 30 (75%) and 23 (58%) patients showed RV GLS and RV FWLS PK ≥ 10% relative reduction. At T3, LV ejection fraction and LV GLS were within normal range. Conclusions: RV GLS and RV FWLS PK reduction following ANT exposure is extremely frequent, comparing to LV GLS reduction

Sex-related differences in the association between septal wall thickness and survival

Background: In many conditions characterised by septal hypertrophy, females have been shown to have worse outcomes compared to males. In clinical practice and research, similar cutoff points for septal hypertrophy are still used for both sexes. Here, we explore the association between different cutoff points for septal hypertrophy and survival in relation to sex. Methods and results: We performed a retrospective analysis of consecutive patients undergoing echocardiography between March 2010 and February 2021 in a large tertiary referral centre. A total of 70,965 individuals were included. Over a mean follow-up period of 59.1 ± 37 months, 9631 (25 %) males and 8429 (26 %) females died. When the same cutoff point for septal hypertrophy was used for both sexes, females had worse prognosis than males. The impact of septal hypotrophy on survival became statistically significant at a lower threshold in females compared to males: 11.1 mm (HR 1.13, CI 95 %:1.03–1.23, p = 0.01) vs 13.1 mm (HR 1.21, CI 95 %: 1.12–1.32, p < 0.001). However, when indexed wall thickness was used, the cutoff points were 6 mm/body surface area (BSA) (HR 1.08, CI 95 %: 1–1.18, p = 0.04) and 6.2 mm/BSA (HR 1.07, CI 95 %: 1–1.15, p = 0.05) for females and males, respectively. Conclusions: Septal hypertrophy is associated with increased mortality at a lower threshold in females than in males. This may account for the worse prognosis reported in females in many conditions characterised by septal hypertrophy. Applying a lower absolute value or using indexed measurements may facilitate early diagnosis and improve prognostication in females

Artificial intelligence modelling to assess the risk of cardiovascular disease in oncology patients

AIMS: There are no comprehensive machine learning (ML) tools used by oncologists to assist with risk identification and referrals to cardio-oncology. This study applies ML algorithms to identify oncology patients at risk for cardiovascular disease for referrals to cardio-oncology and to generate risk scores to support quality of care. METHODS AND RESULTS: De-identified patient data were obtained from Vanderbilt University Medical Center. Patients with breast, kidney, and B-cell lymphoma cancers were targeted. Additionally, the study included patients who received immunotherapy drugs for treatment of melanoma, lung cancer, or kidney cancer. Random forest (RF) and artificial neural network (ANN) ML models were applied to analyse each cohort: A total of 20 023 records were analysed (breast cancer, 6299; B-cell lymphoma, 9227; kidney cancer, 2047; and immunotherapy for three covered cancers, 2450). Data were divided randomly into training (80%) and test (20%) data sets. Random forest and ANN performed over 90% for accuracy and area under the curve (AUC). All ANN models performed better than RF models and produced accurate referrals. CONCLUSION: Predictive models are ready for translation into oncology practice to identify and care for patients who are at risk of cardiovascular disease. The models are being integrated with electronic health record application as a report of patients who should be referred to cardio-oncology for monitoring and/or tailored treatments. Models operationally support cardio-oncology practice. Limited validation identified 86% of the lymphoma and 58% of the kidney cancer patients with major risk for cardiotoxicity who were not referred to cardio-oncology