Foley, T. Raymond

Background: Lung cancer is classified into small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC – including adenocarcinoma, squamous cell, and large cell carcinoma). The incidence of major adverse cardiovascular events (MACE)—defined as acute myocardial infarction, acute coronary syndrome/ischemic heart disease requiring revascularization, stroke, and cardiovascular death—have not been well defined in lung cancer patients following treatment. Coronary artery calcifications (CAC) and aortic calcifications (CA) are known cardiovascular risk markers in non-cancer populations. Purpose: To determine whether the presence of CAC or CA, as identified on baseline PET-CT (Positron Emission Tomography–Computed Tomography) or chest CT imaging, is predictive of MACE and all-cause mortality (ACM) in patients with lung cancer. Methods: We conducted a retrospective cohort study of patients diagnosed with SCLC or NSCLC who received chemotherapy, between January 1, 2010, and December 31, 2024. The baseline PET-CT or chest CT scans were reviewed for the presence of CAC and/or CA. Patients were excluded if they lacked baseline imaging or had experienced a MACE before treatment. Univariate and multivariate adjusted Cox regression models were employed to assess associations between CAC/CA and MACE or ACM. The Kaplan-Meier survival analyses was performed to evaluate event-free survival. Results: A total of 385 patients were included (mean age: 74 years, IQR: 67–79), predominantly female (158 [55%]) and white (279 [96.2%]). NSCLC was found in 255 (88%) and SCLC in 35 (12%). CAC was identified in 172 (60%) and CA in 87 (30%). Among patients with NSCLC, the presence of CAC was significantly associated with MACE (HR: 2.84 [95% CI: 1.6–4.8], p=0.0001) (Fig. a), particularly in those with adenocarcinoma (Fig. b). In SCLC, (HR: 1.56 [95% CI: 0.1–14.0], p=ns). On multivariable analysis, CAC remained the strongest predictor of MACE after adjusting for age, hypertension, diabetes, dyslipidemia, and smoking status (HR: 2.6 [95% CI: 1.5–4.4], p=0.0008) (Fig. d). No significant association was found between CA and MACE in either group (p>0.05). ACM was similar for SCLC, squamous cell, and NSCLC (Fig. c). Conclusion: In patients with NSCLC especially lung adenocarcinoma, the presence of CAC in the baseline PET/CT was an independent predictor of MACE. This finding supports the value of CAC as a non-invasive cardiovascular risk marker.

Background: Major adverse cardiovascular events (MACE), including myocardial infarction, acute coronary syndrome, ischemic heart disease requiring revascularization, stroke, and heart failure, have been documented as significant contributors to mortality in cancer survivors. Coronary artery calcium (CAC) can predict MACE in non-cancer populations, while calcium in the aorta (CA) has not been evaluated as a prognostic marker. Every patient diagnosed with cancer undergoes a standard-of-care Positron Emission Tomography-Computed Tomography (PET-CT) or a chest CT before the initiation of chemotherapy. Hypothesis: To determine whether the CAC or CA of patients with Hodgkin's or non-Hodgkin's lymphoma, derived from standard-of-care PET-CT/chest CT, can predict the incidence of MACE. Methods: Patients treated with anthracycline-based chemotherapy, diagnosed and followed from January 1, 2013, through June 30, 2023, were included. Patients who did not undergo a PET-CT or CT, and/or developed MACE before treatment initiation were excluded. Univariate and multivariate adjusted Cox regression models were employed to assess whether the presence of CAC, CA, or CAC-CA was associated with the development of MACE. Calcium was retrospectively quantified using TeraRecon software (Durham NC) and categorized as: 0, 1-99, and >100. Outcome analyses was estimated using the Kaplan-Meier method. Results: 326 patients were included, mean age of 55 years (range: 52-60), predominantly male 201 (61%) and white 314 (96%), CAC was found in 89 patients and CA in 140. In the univariate regression model, a statistically significant association was found with values >100 for CA, CAC and CAC-CA with the risk of MACE. (Fig 1a/b/c). CAC equal to 0 demonstrated a significant protective effect against MACE. (Fig 1a). In the multivariable analysis, these associations persisted even after adjusting for comorbidities. (Table 1). Conclusion: CAC, CA and CAC/CA >100 in the standard-of-care CT/PET CT are predictors of MACE in lymphoma patients undergoing anthracycline treatment, a CAC equal to 0 has protective effect, these relationships remained statistically significant after adjusting for comorbidities.

Importance In patients with severe aortic valve stenosis at intermediate surgical risk, transcatheter aortic valve replacement (TAVR) with a self-expanding supra-annular valve was noninferior to surgery for all-cause mortality or disabling stroke at 2 years. Comparisons of longer-term clinical and hemodynamic outcomes in these patients are limited. Objective To report prespecified secondary 5-year outcomes from the Symptomatic Aortic Stenosis in Intermediate Risk Subjects Who Need Aortic Valve Replacement (SURTAVI) randomized clinical trial. Design, Setting, and Participants SURTAVI is a prospective randomized, unblinded clinical trial. Randomization was stratified by investigational site and need for revascularization determined by the local heart teams. Patients with severe aortic valve stenosis deemed to be at intermediate risk of 30-day surgical mortality were enrolled at 87 centers from June 19, 2012, to June 30, 2016, in Europe and North America. Analysis took place between August and October 2021. Intervention Patients were randomized to TAVR with a self-expanding, supra-annular transcatheter or a surgical bioprosthesis. Main Outcomes and Measures The prespecified secondary end points of death or disabling stroke and other adverse events and hemodynamic findings at 5 years. An independent clinical event committee adjudicated all serious adverse events and an independent echocardiographic core laboratory evaluated all echocardiograms at 5 years. Results A total of 1660 individuals underwent an attempted TAVR (n = 864) or surgical (n = 796) procedure. The mean (SD) age was 79.8 (6.2) years, 724 (43.6%) were female, and the mean (SD) Society of Thoracic Surgery Predicted Risk of Mortality score was 4.5% (1.6%). At 5 years, the rates of death or disabling stroke were similar (TAVR, 31.3% vs surgery, 30.8%; hazard ratio, 1.02 [95% CI, 0.85-1.22]; P = .85). Transprosthetic gradients remained lower (mean [SD], 8.6 [5.5] mm Hg vs 11.2 [6.0] mm Hg; P < .001) and aortic valve areas were higher (mean [SD], 2.2 [0.7] cm 2 vs 1.8 [0.6] cm 2 ; P < .001) with TAVR vs surgery. More patients had moderate/severe paravalvular leak with TAVR than surgery (11 [3.0%] vs 2 [0.7%]; risk difference, 2.37% [95% CI, 0.17%- 4.85%]; P = .05). New pacemaker implantation rates were higher for TAVR than surgery at 5 years (289 [39.1%] vs 94 [15.1%]; hazard ratio, 3.30 [95% CI, 2.61-4.17]; log-rank P < .001), as were valve reintervention rates (27 [3.5%] vs 11 [1.9%]; hazard ratio, 2.21 [95% CI, 1.10-4.45]; log-rank P = .02), although between 2 and 5 years only 6 patients who underwent TAVR and 7 who underwent surgery required a reintervention. Conclusions and Relevance Among intermediate-risk patients with symptomatic severe aortic stenosis, major clinical outcomes at 5 years were similar for TAVR and surgery. TAVR was associated with superior hemodynamic valve performance but also with more paravalvular leak and valve reinterventions.