A Review of the Cardiovascular Safety of Prucalopride in Patients With Chronic Idiopathic Constipation

Prokinetic agents, specifically 5-hydroxytryptamine type 4 (5-HT 4 ) receptor agonists, have been shown to provide relief in chronic idiopathic constipation (CIC). The first-generation 5-HT 4 agonists were initially withdrawn from use owing to associations with serious cardiovascular (CV) events. This review summarizes CV safety data for prucalopride, a high-affinity 5-HT 4 agonist approved in the United States in 2018 for adults with CIC. No significant effects of prucalopride on CV safety were observed in animal models or early-phase clinical studies, including a thorough QT study at therapeutic (2 mg) or supratherapeutic (10 mg) doses. Among 1,750 patients with CIC who received prucalopride (2-4 mg) in 5 phase 3 studies, no trends in CV adverse events, electrocardiogram parameters, or blood pressure were documented; ≤1.0%-2.0% of patients had prolonged QT interval corrected for heart rate (HR) using Fridericia formula after placebo or prucalopride treatment, and low HR occurred in ≤6.1% and ≤3.3% of these patients, respectively. In two 24-month observational studies among 2,468 patients, changes in electrocardiogram parameters over time were minor, except at occasional time points when significant changes from baseline were reported for HR or QT interval. In a real-world European CV safety study among 35,087 patients (prucalopride, 5,715; polyethylene glycol 3350 [PEG3350], 29,372), results were consistent for no evidence of increased risk of major adverse CV events among patients treated with prucalopride vs PEG3350 (incidence rate ratio = 0.64; 95% confidence interval 0.36-1.14). Studies to date have not raised concerns regarding the impact of prucalopride treatment on CV parameters

The Role of Fatty Acid-Binding Protein 4 in the Characterization of Atrial Fibrillation and the Prediction of Outcomes after Catheter Ablation

Aims: The utility of biomarkers in characterizing atrial cardiomyopathy is unclear. We aim to test the ability of biomarkers of fibrosis (galectin-3 (Gal-3)) and adiposity (fatty acid-binding protein 4 (FABP4) and leptin) to predict: (1) the presence of low-voltage areas (LVA) in the electroanatomic voltage mapping; and (2) the recurrence of atrial fibrillation (AF) after pulmonary vein isolation (PVI). Methods: Patients referred for PVI were enrolled. Areas of bipolar voltage 20 ng/mL) was developed. Results: 299 patients were included. AF was paroxysmal in 100 (33%), persistent in 130 (43%) and long-standing persistent in 69 (23%). Multivariable analysis revealed age, left atrium area, and the proposed score as independent predictors of LVA. During a mean follow-up period of 972 ± 451 days, freedom from AF recurrence was 63%. The score incorporating AF pattern and FABP4 levels accurately predicted freedom from AF recurrence, stratifying risk into ranges from 28% (score of 1) to 68% (score of 3). Cox regression models identified the score including AF pattern + FABP4 as the best model for AF recurrence (hazard ratio 2.32; 95% CI, 1.19 to 4.5; p = 0.014). Conclusions: Traditional clinical classification of atrial cardiomyopathy may be improved by markers of adiposity (FABP4). The combination allows better prediction of the presence of LVA and AF recurrence post-PVI. Gal-3 provided no added predictive value

Long-term prognosis of patients with life-threatening ventricular arrhythmias induced by coronary artery spasm.

AIMS: Coronary artery spasm (CAS) is associated with ventricular arrhythmias (VA). Much controversy remains regarding the best therapeutic interventions for this specific patient subset. We aimed to evaluate the clinical outcomes of patients with a history of life-threatening VA due to CAS with various medical interventions, as well as the need for ICD placement in the setting of optimal medical therapy. METHODS AND RESULTS: A multicentre European retrospective survey of patients with VA in the setting of CAS was aggregated and relevant clinical and demographic data was analysed. Forty-nine appropriate patients were identified: 43 (87.8%) presented with VF and 6 (12.2%) with rapid VT. ICD implantation was performed in 44 (89.8%). During follow-up [59 (17-117) months], appropriate ICD shocks were documented in 12. In 8/12 (66.6%) no more ICD therapies were recorded after optimizing calcium channel blocker (CCB) therapy. SCD occurred in one patient without ICD. Treatment with beta-blockers was predictive of appropriate device discharge. Conversely, non-dihydropyridine CCB therapy was significantly protective against VAs. CONCLUSION: Patients with life-threatening VAs secondary to CAS are at particularly high-risk for recurrence, especially when insufficient medical therapy is administered. Non-dihydropyridine CCBs are capable of suppressing episodes, whereas beta-blocker treatment is predictive of VAs. Ultimately, in spite of medical intervention, some patients exhibited arrhythmogenic events in the long-term, suggesting that ICD implantation may still be indicated for all