Background Patients with lung cancer face a heightened risk of atherosclerosis-related cardiovascular events. Despite the strong scientific rationale, there is currently a lack of clinical evidence examining the impact of immune checkpoint inhibitors (ICIs) on the advancement of atherosclerosis in patients with lung cancer. The objective of our study was to investigate whether there is a correlation between ICIs and the accelerated progression of atherosclerosis among individuals with lung cancer. Methods In this case–control (2:1 matched by age and gender) study, total, non-calcified, and calcified plaque volumes were measured in the thoracic aorta using sequential contrast-enhanced chest CT scans. Univariate and multivariate rank-based estimation regression models were developed to estimate the effect of ICI therapy on plaque progression in 40 cases (ICI) and 20 controls (non-ICI). Results The patients had a median age of 66 years (IQR: 58–69), with 50% of them being women. At baseline, there were no significant differences in plaque volumes between the groups, and their cardiovascular risk profiles were similar. However, the annual progression rate for non-calcified plaque volume was 7 times higher in the ICI group compared with the controls (11.2% vs 1.6% per year, p=0.001). Conversely, the controls showed a greater progression in calcified plaque volume compared with the ICI group (25% vs 2% per year, p=0.017). In a multivariate model that considered cardiovascular risk factors, the use of an ICI was associated with a more substantial progression of non-calcified plaque volume. Additionally, individuals treated with combination ICI therapy exhibited greater plaque progression. Conclusions ICI therapy was associated with more non-calcified plaque progression. These findings underscore the importance of conducting studies aimed at identifying the underlying mechanisms responsible for plaque advancement in patients undergoing ICI treatment. Trial registration number NCT04430712 .

Introduction: Type 2 diabetes mellitus (T2DM) and obstructive sleep apnea (OSA) are independently associated with adverse left (LV) and right (RV) ventricular remodeling. However, the effect of continuous positive airway pressure (CPAP) is unknown. Hypothesis: CPAP prevents adverse remodeling in T2DM+OSA overlap. Methods: In this prospective study, 141 participants (Control: 28; T2DM only: 27; OSA only: 29; T2DM+OSA: 57) were recruited and underwent home sleep testing and cardiac magnetic resonance. Subsequently, 53 adults from the T2DM+OSA group were enrolled in a 3-month, parallel-arm, randomized, placebo-controlled trial comparing active and sham CPAP. The measures of interest were LV and RV remodeling indices (mass/volume). Kruskal-Wallis for multiple groups and Wilcoxon rank-sum and signed-rank tests for paired samples for two groups were applied. Results: Groups were of similar sex [Control (males): 54%; T2DM: 44%; OSA only: 52%; T2DM+OSA: 65%; p=0.31)]; OSA and T2DM+OSA participants were older (age in years: 46± 15; 51±7.8; 53±10; 56±9.1* # ; respectively p=0.001; *p<0.05 vs. control, # p<0.05 vs. T2DM only) and had higher BMI (29.8±6.3; 31±4.8; 34±6.3*; 35.2±6.6* # kg/m 2 , respectively p=0.001). At baseline, LV remodeling index (g/ml) was higher in T2DM+OSA (0.67±0.12; 0.71±0.10; 0.75±0.13; 0.78±0.16*; respectively, p=0.01), whereas RV remodeling index was similar (0.19±0.03; 0.20±0.03; 0.20±0.03; 0.21±0.04; p=0.33). The difference in LV remodeling index persisted after adjustment for age, sex and BMI (p<0.001). CPAP treatment over 3 months prevented progression of adverse LV remodeling compared with sham [difference: CPAP: -0.01 (-0.08, 0.08) g/ml; sham: 0.11 (-0.03, 0.17) g/ml; p=0.03)] but not of RV remodeling index [difference: CPAP: 0.01 (-0.04, 0.08) g/ml; sham: 0.003 (-0.02, 0.04) g/ml; p=0.82)]. Conclusion: T2DM and OSA increased adverse LV but not RV remodeling. CPAP prevented the progression of adverse LV but not RV remodeling.

This study aims to evaluate the efficacy of the Pooled Cohort Equation (PCE), U.S. Preventative Services Task Force (USPSTF), and Framingham Risk Score (FRS) models in predicting ASCVD events among patients receiving radiation therapy (RT) for head and neck cancer (HNCA). From a large cohort of HNCA patients treated with RT, ASCVD events were adjudicated. Observed vs. predicted ASCVD events were compared. We compared rates by statin eligibility status. Regression models and survival analysis were used to identify the relationship between predicted risk and post-RT outcomes. Among the 723 identified patients, 274 (38%) were statin-eligible based on USPSTF criteria, 359 (49%) based on PCE, and 234 (32%) based on FRS. During follow-up, 17% developed an ASCVD, with an event rate of 27 per 1000 person-years, 68% higher than predicted (RR 1.68 (95% CI: 1.02, 2.12), p < 0.001). In multivariable regression, there was no difference in event rates by statin eligibility status (p > 0.05). Post-RT, the observed event rate was higher than the predicted ASCVD risk across all grades of predicted risk (p < 0.05) and the observed risk of an ASCVD event was high even among patients predicted to have a low risk of ASCVD. In conclusion, current ASCVD risk calculators significantly underestimate the risk for ASCVD among patients receiving RT for HNCA.

PURPOSE:Conventional photon radiation therapy (RT) for breast cancer is associated with a reduction in global longitudinal strain (GLS) and an increase in troponin, N-terminal pro hormone B-type natriuretic peptide (NT-proBNP), and incident heart failure. The cardiac radiation exposure with proton-RT is much reduced and thus may be associated with less cardiotoxicity. The objective was to test the effect of proton-RT on GLS, troponin, and NT-proBNP. METHODS AND MATERIALS:We conducted a prospective, observational, single-center study of 70 women being treated with proton-RT for breast cancer. Serial measurements of GLS, high-sensitivity troponin I, and NT-proBNP were performed at prespecified intervals (before proton-RT, 4 weeks after completion of proton-RT, and again at 2 months after proton-RT). RESULTS:The mean age of the patients was 46 ± 11 years, and the mean body mass index was 25.6 ± 5.2 kg/m2; 32% of patients had hypertension, and the mean radiation doses to the heart and the left ventricle (LV) were 0.44 Gy and 0.12 Gy, respectively. There was no change in left ventricular ejection fraction (65 ± 5 vs 66 ± 5 vs 64 ± 4%; P = .15), global GLS (-21.7 ± 2.7 vs -22.7 ± 2.3 vs -22.8 ± 2.1%; P = .24), or segmental GLS from before to after proton-RT. Similarly, there was no change in either high-sensitivity troponin or NT-proBNP with proton-RT. However, in a post hoc subset analysis, women with hypertension had a greater decrease in GLS after proton-RT compared with women without hypertension (-21.3 ± 3.5 vs -24.0 ± 2.4%; P = .006). CONCLUSIONS:Proton-RT did not affect LV function and was not associated with an increase in biomarkers. These data support the potential cardiac benefits of proton-RT compared with conventional RT.

BACKGROUND Sodium-glucose co-transporter-2 (SGLT2) inhibitors improve outcomes among patients with estab-lished heart failure. Despite supportive basic science studies, there are no data on the value of SGLT2 inhibitors among patients treated with anthracyclines.OBJECTIVES This study sought to test the cardiac efficacy and overall safety of SGLT2 inhibitors in patients treated with anthracyclines.METHODS This study identified 3,033 patients with diabetes mellitus (DM) and cancer who were treated with anthracyclines. Cases were patients with cancer and DM who were on SGLT2 inhibitor therapy during anthracycline treatment (n = 32). Control participants (n = 96) were patients with cancer and DM who were also treated with anthracyclines, but were not on an SGLT2 inhibitor. The primary cardiac outcome was a composite of cardiac events (heart failure incidence, heart failure admissions, new cardiomyopathy [>10% decline in ejection fraction to <53%], and clinically significant arrhythmias). The primary safety outcome was overall mortality.RESULTS Age, sex, ethnicity, cancer type, cancer stage, and other cardiac risk factors were similar between groups. There were 20 cardiac events over a median follow-up period of 1.5 years. The cardiac event incidence was lower among case patients in comparison to control participants (3% vs 20%; P = 0.025). Case patients also experienced lower overall mortality when compared with control participants (9% vs 43%; P < 0.001) and a lower composite of sepsis and neutropenic fever (16% vs 40%; P = 0.013). CONCLUSIONS SGLT2 inhibitors were associated with lower rate of cardiac events among patients with cancer and DM who were treated with anthracyclines. Additionally, SGLT2 inhibitors appeared to be safe. These data support the con-ducting of a randomized clinical trial testing SGLT2 inhibitors in patients at high cardiac risk treated with anthracyclines. (J Am Coll Cardiol HF 2022;10:559-567) (c) 2022 by the American College of Cardiology Foundation.

Introduction: Overlap of type 2 diabetes mellitus (T2DM) and obstructive sleep apnea (OSA) increases the risk of heart failure possibly mediated by myocardial fibrosis. Hypothesis: T2DM+OSA overlap increases myocardial fibrosis. Methods: This was a prospective study where 141 participants (Control: 28; T2DM only: 27; OSA only: 29; T2DM+OSA: 57) underwent a sleep study and cardiac magnetic resonance. The measures of interest were LV and RV extracellular volume (ECV), native T1 and cardiomyocyte size (tau). Differences were tested with Kruskal-Wallis. The groups 'T2DM only' and 'OSA only' were combined (Control; T2DM or OSA; T2DM+OSA) for trend analysis with Jonckheere-Terpstra test. Results: Groups had similar sex [Control (males): 54%; T2DM: 44%; OSA only: 52%; T2DM+OSA: 65%; p=0.31)]; OSA and OSA+T2DM participants were older (46± 15; 51±7.8; 53±10; 56±9.1* # years; respectively p=0.001; *p<0.05 vs. control, # p<0.05 vs. T2DM only) and had higher BMI (29.8±6.3; 31±4.8; 34±6.3*; 35.2±6.6* # kg/m 2 , respectively p=0.001). LV ECV increased progressively with highest values among subjects with T2DM and OSA (0.25±0.02%; 0.27±0.03%; 0.28±0.04%; 0.31±0.05%; respectively, p=0.001; p for trend<0.001). LV native T1 was similar across groups (995±91 ms; 986±112 ms; OSA: 977±132 ms; 1041±128 ms; respectively, p=0.39; p for trend=0.14), and the T2DM+OSA group had a marginally higher LV tau (0.15±0.04 s; 0.13±0.05 s; 0.12±0.04 s; 0.17±0.06 s; respectively, p= 0.05; p for trend=0.59). RV ECV (0.40±0.06%; 0.41±0.05%; 0.40±0.04%; 0.42±0.05%; respectively, p=0.70; p for trend=0.27) and RV native T1 (1105±164 ms; 1083±124 ms; 1063±189 ms; 1092±148 ms; p=0.85; p for trend=0.85) were similar. RV tau was similar but with a positive trend towards T2DM+OSA (0.087±0.029 s; 0.094±0.023 s; 0.990±0.033 s; 0.115±0.045 s; p= 0.17, p= 0.03). Conclusions: The overlap of T2DM and OSA has an incremental adverse effect on the LV ECV and may explain the increased risk of adverse cardiac events.

BackgroundGlobal circumferential strain (GCS) and global radial strain (GRS) are reduced with cytotoxic chemotherapy. There are limited data on the effect of immune checkpoint inhibitor (ICI) myocarditis on GCS and GRS.ObjectivesThis study aimed to detail the role of GCS and GRS in ICI myocarditis.MethodsIn this retrospective study, GCS and GRS from 75 cases of patients with ICI myocarditis and 50 ICI-treated patients without myocarditis (controls) were compared. Pre-ICI GCS and GRS were available for 12 cases and 50 controls. Measurements were performed in a core laboratory blinded to group and time. Major adverse cardiovascular events (MACEs) were defined as a composite of cardiogenic shock, cardiac arrest, complete heart block, and cardiac death.ResultsCases and controls were similar in age (66 ± 15 years vs 63 ± 12 years; P = 0.20), sex (male: 73% vs 61%; P = 0.20) and cancer type (P = 0.08). Pre-ICI GCS and GRS were also similar (GCS: 22.6% ± 3.4% vs 23.5% ± 3.8%; P = 0.14; GRS: 45.5% ± 6.2% vs 43.6% ± 8.8%; P = 0.24). Overall, 56% (n = 42) of patients with myocarditis presented with preserved left ventricular ejection fraction (LVEF). GCS and GRS were lower in myocarditis compared with on-ICI controls (GCS: 17.5% ± 4.2% vs 23.6% ± 3.0%; P < 0.001; GRS: 28.6% ± 6.7% vs 47.0% ± 7.4%; P < 0.001). Over a median follow-up of 30 days, 28 cardiovascular events occurred. A GCS (HR: 4.9 [95% CI: 1.6-15.0]; P = 0.005) and GRS (HR: 3.9 [95% CI: 1.4-10.8]; P = 0.008) below the median was associated with an increased event rate. In receiver-operating characteristic (ROC) curves, GCS (AUC: 0.80 [95% CI: 0.70-0.91]) and GRS (AUC: 0.76 [95% CI: 0.64-0.88]) showed better performance than cardiac troponin T (cTnT) (AUC: 0.70 [95% CI: 0.58-0.82]), LVEF (AUC: 0.69 [95% CI: 0.56-0.81]), and age (AUC: 0.54 [95% CI: 0.40-0.68]). Net reclassification index and integrated discrimination improvement demonstrated incremental prognostic utility of GRS over LVEF (P = 0.04) and GCS over cTnT (P = 0.002).ConclusionsGCS and GRS are lower in ICI myocarditis, and the magnitude of reduction has prognostic significance.