Adverse myocardial and vascular side effects of immune checkpoint inhibitors: a prospective multimodal cardiovascular assessment.

BACKGROUND: Immune checkpoint inhibitors (ICIs) can induce cardiovascular toxicities. OBJECTIVES: To prospectively assess the incidence of major cardiovascular events (MACE) on ICIs in solid cancer patients: myocarditis, pericarditis, acute coronary syndrome, heart failure, high-degree conduction abnormalities or sustained ventricular arrhythmias, or cardiovascular death at 6 weeks (early MACE), including asymptomatic clinical changes by an independent adjudication committee using current recommended diagnostic criteria. The secondary objective was the incidence of the above-mentioned events adding atrial fibrillation (AF) at 6 months (late MACE). RESULTS: Participants underwent pre-ICIs and repeated multimodality cardiac imaging (echocardiogram, cardiac magnetic resonance (CMR)), serum biomarkers (ultrasensitive troponin I), and rhythm surveillance (ambulatory ECG monitoring) at 6 weeks and 6 months. Forty-nine patients (38 (77.6%) male; mean age 64.3 (SD 11.0) years old) were included (June 2020-December 2021). Early MACE were observed in 9 (18.4%) patients at mean 40.1 (SD 5.9) days, with heart failure (HF) in 5 (10.2%), ventricular arrhythmias, or new conduction disorders in 4 (8.2%) patients. History of AF (HR 4.49 (CI 1.11-18.14), P = 0.035) predicted early MACE. At 6 months follow-up, 18 MACE were observed in 15/49 (31%) patients, with 6 (12.2%) HF events, 5 (10.2%) significant ventricular arrhythmias, or conduction disorders, and 4 (8.2%) AF. There was a significant decline in LVEF (P < 0.001) in patients with no MACE (P = 0.003) or HF (P = 0.0028). Higher creatinine at inclusion (HR 0.99 [0.98-1.00], P = 0.006) predicted HF on multivariate analysis. There were no significant T1 or T2 mapping changes in our study cohort on repeated CMR. CONCLUSIONS: Cardiotoxicity on ICIs is more frequent than previously described when using a thorough detection strategy, consisting mainly in HF and asymptomatic rhythm disorders.

Toxicological Analysis Unveiling the Low Rate of Self-Reporting of Addictive/Recreative Substances in Acute Severe Drug Overdose Cases.

OBJECTIVE: Toxicological analysis (TA) is advised when assessing the prognosis and the treatment of drug overdose patients. Apart from this use, the value of TA has remained unclear. This study aimed at defining the value of TA regarding the toxicological diagnosis in severe overdose cases that involved addictive or recreational drugs (ARDs) that were used either alone or in combination with medicinal drugs. METHODS: The patients who were enrolled in the study had been admitted to our intensive care unit for the treatment of poisoning. TA was performed using advanced technologies such as mass spectrometry of blood/urine on admission. An occurrence indicated the supposed ingestion of a defined substance. Patients were included in a group depending on the combination of the occurrences of supposed ingested drugs (SID) and the results of the 1) TA: SID+, TA+; 2) SID+, not searched by TA; 3) SID-, TA+. RESULTS: There were 224 occurrences of 90 substances in 70 patients. ARDs were present in 30 patients (43%). ARD accounted for 24 occurrences in the SID+, TA+ group, 10 occurrences in the SID+, not searched group and 196 occurrences in the SID-, TA+ group. In the SID+, TA+ group, 9 occurrences (69%) of ethanol were confirmed by TA. Ingestion of ethanol was invalidated in 4 occurrences (31%). In the patients who denied ethanol ingestion, TA confirmed the non-ingestion of ethanol using 30 blood measures (81%). Ethanol was involved in 57% of the patients, being the lone substance in only 1 case. CONCLUSION: In drug overdose instances that result in organ failure(s) and involve ARDs, self-reporting is of limited value in assessing the patients' exposure to ARD. Multiple consumptions expose patients to unexpected drug interactions.