Randomized, Double-Blind, Active Comparator Pharmacodynamic Study of Platelet Inhibition with Crushed and Integral Formulations of Clopidogrel and Ticagrelor in Acute Coronary Syndrome.

BACKGROUND: Crushed formulations of specific antiplatelet agents produce earlier and stronger platelet inhibition. We studied the platelet inhibitory effect of crushed clopidogrel in patients with acute coronary syndrome (ACS) and its relative efficacy compared with integral clopidogrel, crushed and integral ticagrelor. OBJECTIVES: We aimed to compare the platelet inhibitory effect of crushed and integral formulations of clopidogrel and ticagrelor in patients with acute coronary syndrome (ACS). METHODS: Overall, 142 patients with suspected ACS were randomly assigned to receive crushed or integral formulations of clopidogrel or ticagrelor. Platelet inhibition at baseline and 1 and 8 h was assessed using the VerifyNow assay. High on-treatment platelet reactivity (HTPR) ≥ 235 P2Y12 reaction units (PRUs) 1 h after the medication loading dose was also determined. RESULTS: The PRU and percentage inhibition median (interquartile range) at 1 h for the different formulations were as follows: crushed clopidogrel: 196.50 (155.50, 246.50), 9.36 (- 1.79, 25.10); integral clopidogrel: 189.50 (159.00, 214.00), 2.32 (- 2.67, 19.89); crushed ticagrelor: 59.00 (10.00, 96.00), 75.53 (49.12, 95.18); and integral ticagrelor: 126.50 (50.00, 168.00), 40.56 (25.59, 78.69). There was no significant difference in PRU or percentage platelet inhibition between the crushed and integral formulations of clopidogrel (p = 0.990, p = 0.479); both formulations of ticagrelor were superior to the clopidogrel formulations (p < 0.05). On paired comparison, crushed ticagrelor showed robust early inhibition of platelets compared with the integral formulation (p = 0.03). Crushed clopidogrel exhibited the maximal HTPR of 34.3%, but was < 3% for both formulations of ticagrelor. CONCLUSIONS: The platelet inhibitory effect of crushed clopidogrel is not superior to integral preparation in patients with ACS. Crushed ticagrelor produced maximal platelet inhibition acutely. HTPR rates in ACS are similar and very low with both formulations of ticagrelor, and maximal with crushed clopidogrel. Clinical Trials Registry of India identifier number CTRI/2020/06/025647.

Do the predictors of right ventricular pacing-induced cardiomyopathy add up?

OBJECTIVE: Knowledge of factors causing pacing-induced cardiomyopathy (PICM) is incomplete. We sought to estimate the incidence and predisposing factors for PICM and evaluate if the risk they portend adds up. METHODS: Single centre retrospective study where consecutive patients with preserved LVEF undergoing pacemaker (PM) implantation between 2012 and 2018 were analysed. RESULTS: A total of 749 patients (68.4 % male; mean age 59.2 ± 14.08 years) were included in the analysis. PICM developed in 74 (9.9%) patients over a median follow up of 2.2 years (IQR 1.1-3.2). Pre-implant LVEF, paced QRS duration and RV pacing burden were independent predictors of PICM. Using 90 % specificity cut-off values for LVEF and paced QRS, and the value separating lowest tertile of RV pacing from the higher tertiles, three risk factors were identified: (i) baseline LVEF < 55 %, (ii) paced QRS duration > 160 msec, and (iii) RV pacing burden > 33 %. Patients with two or more risk factors were at the highest risk (OR 11.62, 95 % CI 4.62-29.21, p-value < 0.001) for developing PICM while those with one risk factor had an intermediate risk (OR 3.89, 95 % CI 1.62-9.34, p-value 0.002) when compared to those without any risk factors. CONCLUSION: Low-normal baseline LVEF, wider paced QRS and higher RV pacing burden independently predicted the development of PICM. The presence of ≥2 factors increased the odds of PICM, twelve-fold. A narrower paced QRS, the only modifiable risk factor may help mitigate development of PICM.

Endografts with mini-cuff-augmented fenestrations for endovascular repair of thoracoabdominal aortic and common iliac artery aneurysms.

OBJECTIVE: To report a technique of creating mini-cuff-augmented fenestrations in endografts for use in endovascular aneurysm repair. METHODS: Circular fenestrations are made in Dacron thoracic (Valiant Captivia, Medtronic) or tapered iliac limb (Endurant, Medtronic) endografts using thermal cautery and the edges are strengthened with radio-opaque wire sutured on with 6-0 polypropylene. Straight thin-wall expanded polytetrafluoroethylene vascular graft of the same diameter as the fenestration is affixed to its edge with nonlocking 5-0 polypropylene suture, everted, trimmed, balloon-dilated to its nominal diameter and prevented from invaginating by relaxed external stay sutures. Mini-cuff-augmented fenestrations are often pre-cannulated with looped or externalized nitinol guidewires to facilitate catheter crossing. Successful use of mini-cuff-augmented fenestrations is illustrated in a symptomatic patient with Crawford extent-3 thoracoabdominal aortic and bilateral common iliac artery aneurysm undergoing endovascular repair. Seven mini-cuff-augmented fenestrations were created to preserve flow into five visceral arteries (celiac, superior mesenteric, left and dual right renal; all arising from the aneurysm) and both internal iliac arteries (arising at the aneurysm edge). RESULTS: Effective sealing was achieved immediately at all mini-cuff-augmented fenestrations. At 6-month follow-up there were no endoleaks, all fenestration stents were patent and undistorted, and the aneurysm sac size had decreased. CONCLUSION: Mini-cuff-augmented fenestrations accomplish effective fenestration sealing, despite being in aneurysmal zones, while preserving the advantages of fenestrations over cuffed branches.

Leptomeningeal carcinomatosis in a patient with gallbladder carcinoma.

Carcinomatous meningitis is a rare manifestation of malignancy. It is increasingly being recognized in lung carcinoma, breast carcinoma, melanomas, gastrointestinal malignancies, lymphomas, and leukemia and it is almost never seen in gallbladder malignancies. We present a case whose primary presentation was as a carcinomatous meningitis that was subsequently found to be secondary to a gallbladder primary.