Echocardiographic Outcomes With Transcatheter Edge-to-Edge Repair for Degenerative Mitral Regurgitation in Prohibitive Surgical Risk Patients.

BACKGROUND: The CLASP IID randomized trial (Edwards PASCAL TrAnScatheter Valve RePair System Pivotal Clinical Trial) demonstrated the safety and effectiveness of the PASCAL system for mitral transcatheter edge-to-edge repair (M-TEER) in patients at prohibitive surgical risk with significant symptomatic degenerative mitral regurgitation (DMR). OBJECTIVES: This study describes the echocardiographic methods and outcomes from the CLASP IID trial and analyzes baseline variables associated with residual mitral regurgitation (MR) ≤1+. METHODS: An independent echocardiographic core laboratory assessed echocardiographic parameters based on American Society of Echocardiography guidelines focusing on MR mechanism, severity, and feasibility of M-TEER. Factors associated with residual MR ≤1+ were identified using logistic regression. RESULTS: In 180 randomized patients, baseline echocardiographic parameters were well matched between the PASCAL (n = 117) and MitraClip (n = 63) groups, with flail leaflets present in 79.2% of patients. Baseline MR was 4+ in 76.4% and 3+ in 23.6% of patients. All patients achieved MR ≤2+ at discharge. The proportion of patients with MR ≤1+ was similar in both groups at discharge but diverged at 6 months, favoring PASCAL (83.7% vs 71.2%). Overall, patients with a smaller flail gap were significantly more likely to achieve MR ≤1+ at discharge (adjusted OR: 0.70; 95% CI: 0.50-0.99). Patients treated with PASCAL and those with a smaller flail gap were significantly more likely to sustain MR ≤1+ to 6 months (adjusted OR: 2.72 and 0.76; 95% CI: 1.08-6.89 and 0.60-0.98, respectively). CONCLUSIONS: The study used DMR-specific echocardiographic methodology for M-TEER reflecting current guidelines and advances in 3-dimensional echocardiography. Treatment with PASCAL and a smaller flail gap were significant factors in sustaining MR ≤1+ to 6 months. Results demonstrate that MR ≤1+ is an achievable benchmark for successful M-TEER. (Edwards PASCAL TrAnScatheter Valve RePair System Pivotal Clinical Trial [CLASP IID]; NCT03706833).

Effects of terguride, ropinirole, and acetyl-L-carnitine on methamphetamine withdrawal in the rat.

Withdrawal from psychostimulants, including methamphetamine, induces a depressive state associated with lethargy, dysphoria, hyperphagia and psychomotor retardation. Previous work with repeated administration of amphetamine in rats has shown that amphetamine withdrawal produces decreased motivation to work for a non-drug reward, and this withdrawal is reversed by administration of a dopamine partial agonist. The purpose of the present study was to examine decreased motivation to work for a non-drug reward during methamphetamine withdrawal and explore the effects of a dopamine agonist, dopamine partial agonist, and indirect monoamine agonist on methamphetamine withdrawal. During withdrawal from repeated methamphetamine administration, rats showed reduced responding for a sweet solution in a progressive-ratio schedule of reinforcement, and this effect was significantly more pronounced than previously observed with amphetamine. Repeated systemic treatment with the dopamine partial agonist terguride (0.2 and 0.4 mg/kg, i.p., twice daily), the full dopamine agonist ropinirole (1 mg/kg, i.p., twice daily), and acetyl-L-carnitine (60 and 100 mg/kg, i.p.), a compound with a potential antidepressant effect, during methamphetamine withdrawal restored responding for the sweet solution, suggesting that these drugs may represent potential therapeutic strategies for the treatment of methamphetamine addiction during the withdrawal phase.