Close Cardiovascular Monitoring during the Early Stages of Treatment for Patients Receiving Immune Checkpoint Inhibitors.

Background: There is an unmet medical need for the early detection of immune checkpoint inhibitor (ICI)-induced cardiovascular (CV) adverse events due to a lack of adequate biomarkers. This study aimed to provide insights on the incidence of troponin elevations and echocardiographic dynamics during ICI treatment in cancer patients and their role as potential biomarkers for submyocardial damage. In addition, it is the first study to compare hs-TnT and hs-TnI in ICI-treated patients and to evaluate their interchangeability in the context of screening. Results: Among 59 patients, the mean patient age was 68 years, and 76% were men. Overall, 25% of patients received combination therapy. Although 10.6% [95% CI: 5.0-22.5] of the patients developed troponin elevations, none experienced a CV event. No significant changes were found in 3D left ventricular (LV) ejection fraction nor in global longitudinal strain f (56 ± 6% vs. 56 ± 6%, p = 0.903 and -17.8% [-18.5; -14.2] vs. -17.0% [-18.8; -15.1], p = 0.663) at 3 months. There were also no significant changes in diastolic function and right ventricular function. In addition, there was poor agreement between hs-TnT and hs-TnI. Methods: Here, we present a preliminary analysis of the first 59 patients included in our ongoing prospective clinical trial (NCT05699915) during the first three months of treatment. All patients underwent electrocardiography and echocardiography along with blood sampling at standardized time intervals. This study aimed to investigate the incidence of elevated hs-TnT levels within the first three months of ICI treatment. Elevations were defined as hs-TnT above the upper limit of normal (ULN) if the baseline value was normal, or 1.5 ≥ times baseline if the baseline value was above the ULN. Conclusions: Hs-TnT elevations occurred in 10.6% of the patients. However, no significant changes were found on 3D echocardiography, nor did any of the patients develop a CV event. There were also no changes found in NT-proBNP. The study is still ongoing, but these preliminary findings do not show a promising role for cardiac troponins nor for echocardiographic dynamics in the prediction of CV events during the early stages of ICI treatment.

Extensive CArdioVAscular Characterization and Follow-Up of Patients Receiving Immune Checkpoint Inhibitors: A Prospective Multicenter Study.

BACKGROUND: The increasing use of immune checkpoint inhibitors (ICIs) in the treatment of both advanced and early stages of various malignancies has resulted in a substantial increase in the incidence of cardiovascular (CV) immune-related adverse events (irAEs). The current follow-up guidelines are based on anecdotal evidence and expert opinions, due to a lack of solid data and prospective studies. As many questions remain unanswered, cardiac monitoring, in patients receiving ICIs, is not always implemented by oncologists. Hence, an urgent need to investigate the possible short- and long-term CV effects of ICIs, as ICI approval is continuing to expand to the (neo)adjuvant setting. METHODS: We have initiated a prospective, multicenter study, i.e., the CAVACI trial, in which a minimum of 276 patients with a solid tumor, eligible for ICI treatment, will be enrolled. The study consists of routine investigations of blood parameters (troponin and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, in particular) and a thorough CV follow-up (electrocardiograms, transthoracic echocardiograms, and coronary calcium scoring) at fixed time points for a total period of two years. The primary endpoint is the cumulative incidence of troponin elevation in the first three months of ICI treatment, compared to baseline levels. Furthermore, secondary endpoints include incidence above the upper limit of normal of both troponin and NT-proBNP levels, evolution in troponin and NT-proBNP levels, the incidence of CV abnormalities/major adverse cardiac events, evaluation of associations between patient characteristics/biochemical parameters and CV events, transthoracic echocardiography parameters, electrocardiography parameters, and progression of coronary atherosclerosis. Recruitment of patients started in January 2022. Enrolment is ongoing in AZ Maria Middelares, Antwerp University Hospital, AZ Sint-Vincentius Deinze, and AZ Sint-Elisabeth Zottegem. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05699915, registered 26 January 2023.

Statin-induced myopathy: a case report.

BACKGROUND: Statins are one of the most frequently used drug groups among patients with cardiovascular disease. Muscle pain is very frequent among patients using statins. It is important to distinguish patients with benign muscle pain without significant biochemical correlates from patients with serious myopathies. CASE SUMMARY: We present the case of a 68-year-old woman taking atorvastatin in the past 8 months after a coronary bypass grafting, presenting with proximal muscle weakness and pain. Biochemical analysis showed a markedly elevated creatine kinase (CK) (24,159 U/L). Despite discontinuation of the statin and therapy for rhabdomyolysis (IV fluid, mannitol, and sodium bicarbonate), CK levels did not drop as much as expected. Muscle biopsy showed mild inflammatory changes and few necrotic muscle fibres, suggestive for an immune-mediated necrotizing myopathy (IMNM). Serology showed a high anti-HMG-CoA reductase antibody (anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase antibody) titre, diagnostic for an IMNM induced by statins. The patient was treated with corticosteroids and methotrexate. Creatine kinase levels, muscle weakness, and pain gradually improved over the following months. DISCUSSION: IMNM induced by statins is a relatively new entity. It is important to be recognized because it is not a self-limiting adverse effect such as the frequent benign muscle pains caused by statins. Beside discontinuation of the causative statin, aggressive immunosuppressive therapy is mandatory in IMNM. Therefore, it is important to test for anti-HMGCR antibodies and if necessary perform a muscle biopsy in patients taking statins, presenting with muscle weakness, and CK elevations not improving after discontinuation of the statin.

Impact of the preoperative risk and the type of surgery on exercise capacity and training after valvular surgery.

Information on exercise capacity and training in patients who underwent valvular surgery is scarce. The aim of this study is to evaluate postoperative exercise capacity and functional improvement after exercise training according to the preoperative risk and type of surgery. In this prospective study, 145 patients who underwent aortic valve surgery (AVS) or mitral valve surgery (MVS) and who were referred for cardiac rehabilitation were stratified according to the preoperative risk (European System for Cardiac Operative Risk Evaluation [EuroSCORE]) and type of surgery (sternotomy vs ministernotomy or port access). Exercise capacity was evaluated at the start and end of cardiac rehabilitation. Postoperative exercise capacity and the benefit from exercise training were compared between the groups. Patients with a higher preoperative risk had a worse postoperative exercise capacity, with a lower load, peak VO2, anaerobic threshold and 6-minute walking distance (all p<0.001), and a higher VE/VCO2 slope (p=0.01). In MVS, port access patients performed significantly better at baseline (all p<0.05), but in AVS, ministernotomy patients performed better than sternotomy patients with a concomitant coronary artery bypass graft (p<0.05). Training resulted in an improvement in exercise capacity in each risk group and each type of surgery (all p<0.05). This gain in exercise capacity was comparable for the EuroSCORE risk groups and for the types of surgery, for patients after AVS or MVS. In conclusion, exercise capacity after cardiac surgery is related to the preoperative risk and the type of surgery. Despite these differences in postoperative exercise capacity, a similar benefit from exercise training is obtained, regardless of their preoperative risk or type of surgery.

Carcinoid heart disease: typical findings on echocardiography and cardiac magnetic resonance.

Carcinoid syndrome is often complicated by carcinoid heart disease. Deposition of carcinoid plaques on the endocardium of the tricuspid and pulmonary valves causes the typical echocardiographic iconography with thickening of the leaflets and valvular insufficiency and/or stenosis leading to right heart failure. Additionally, the fibrous plaques can be visualized with cardiac magnetic resonance using delayed enhancement sequences. Accurate assessment of the dimensions of the dilated right ventricle by magnetic resonance implicates therapeutic options and defines prognosis. We report the case of a patient with advanced right heart failure as the clue to the diagnosis of carcinoid syndrome. Echocardiography was suggestive. Advanced investigation with magnetic resonance confirmed carcinoid plaque deposition on the tricuspid and the pulmonary valves, and we also had evidence of plaque deposition in the right ventricle. Multimodality imaging is essential in the investigation of this rare disorder.