Pre-treatment high-sensitivity troponin T for the short-term prediction of cardiac outcomes in patients on immune checkpoint inhibitors.

BACKGROUND: Immune checkpoint inhibitors (ICIs) are an emerging option for several advanced metastatic cancers, but may have cardiotoxic effects. The prognostic value of high-sensitivity troponin T (hs-TnT) before treatment start has never been investigated. MATERIALS AND METHODS: Thirty consecutive patients underwent measurement of hs-TnT before starting ICI therapy (pembrolizumab, 23%; nivolumab, 12%; atezolizumab, 6%; durvalumab, 5%). The primary endpoint of cardiovascular death, stroke or transient ischaemic attack, pulmonary embolism and new-onset heart failure, and the secondary endpoint of progression of cardiac involvement according to the CARDIOTOX classification were evaluated after 3 months from the first cycle. RESULTS: Patients (median age 68 years, 77% men, 13% with coronary artery disease, 90% current or former smokers, 67% overweight or obese and 43% hypertensive) had a median hs-TnT of 12 ng/L (interquartile interval 8-23). The primary endpoint occurred only in patients with hs-TnT ≥ 14 ng/L at baseline. Therefore, only patients who had hs-TnT ≥ 14 ng/L before the first cycle died had a stroke/TIA or new-onset HF. Furthermore, nine out of 13 patients with the secondary endpoint (progression of cardiac disease) had hs-TnT ≥ 14 ng/L before the first cycle (P = .012). AUC values were 0.909 for the primary endpoint and 0.757 for the secondary endpoint. The best cut-off was 14 ng/L for both the primary (100% sensitivity, 73% specificity) and secondary endpoints (sensitivity 75%, specificity 77%). CONCLUSIONS: In patients on ICIs, baseline hs-TnT predicts a composite cardiovascular endpoint and the progression of cardiac involvement at 3 months, with 14 ng/L as the best cut-off.

[Oral anticoagulation in patients with atrial fibrillation and stage 4 or 5 chronic kidney disease]. / Prevenzione dell'ictus nel paziente con fibrillazione atriale e malattia renale cronica in stadio 4 o stadio 5.

Patients with chronic kidney disease (CKD) have a high prevalence of atrial fibrillation (AF). Stroke in patients with CKD and AF is frequent, and is usually more severe than in the absence of CKD. Current European Society of Cardiology guidelines recommend oral anticoagulant therapy in order to reduce thromboembolic risk in AF patients in general, and also in the presence of CKD, excluding however stage 4 and dialysis (stage 5) patients. Warfarin and other vitamin K antagonists are still the most frequently used drugs in these settings, despite the high bleeding risk. In the United States, the non-vitamin K antagonist oral anticoagulants, especially apixaban, are here used off-label, despite the absence of strong evidences of efficacy and safety. Several clinical trials are ongoing, and further evidence is needed before non-vitamin K antagonists can be recommended in these patients.

Growth Differentiation Factor 15 in Severe Aortic Valve Stenosis: Relationship with Left Ventricular Remodeling and Frailty.

Background: Frailty is an important outcome predictor in patients with aortic stenosis who are candidates for transcatheter or surgical aortic valve replacement (AVR). Growth/differentiation factor 15 (GDF15) is a cytokine playing a role in the pathophysiology of ventricular remodeling. We assessed its potential role as an independent soluble biomarker of frailty in these patients. Methods: We studied 62 patients (age, mean 79 years, 95% confidence interval (CI) 77-81; 54.8% female) with severe aortic valve stenosis and candidates for AVR. We systematically assessed pre-intervention GDF15 levels for their relationship with frailty (Katz score) and echocardiographic parameters of left ventricular dysfunction/remodeling. Fifteen hypertensive patients with left ventricular (LV) hypertrophy served as controls. Results: Patients with aortic valve stenosis featured higher GDF15 levels than controls (1773, 95% CI 1574-1971 pg/mL vs. 775, 95% CI 600-950 pg/mL, respectively, p < 0.0001). Subjects in the upper GDF15 tertile were older (p = 0.004), with a more advanced NYHA functional class (p = 0.04) and a higher prevalence of impaired renal function (p = 0.004). Such patients also showed a higher frailty score (p = 0.04) and higher indices of LV dysfunction, including reduced global longitudinal strain (p = 0.01) and a higher left ventricular mass (p = 0.001). GDF15 was significantly related to the Katz score, and predicted (OR 1.05; 95% CI 0.9-1.1; p = 0.03) a low (<5) Katz score, independent of the relationship with LV mass, age, renal function or indices of LV dysfunction. Conclusions: GDF15 is increased in patients with severe aortic stenosis and appears to be a soluble correlate of patients' frailty, independent of indices of left ventricular dysfunction.