Cangrelor vs. Ticagrelor in Patients Treated with Primary Percutaneous Coronary Intervention: Impact on Platelet Activity, Myocardial Microvascular Function and Infarct Size: A randomized controlled trial

This is an accepted manuscript of an article published by Thieme in Thrombosis and Haemostasis on 26/05/2019, available online: https://doi.org/10.1055/s-0039-1688789 The accepted version of the publication may differ from the final published version.Background Oral P2Y12 inhibitors take more than 2 hours to achieve full effect in healthy subjects and this action is further delayed in patients with acute myocardial infarction. Intravenous P2Y12 inhibition might lead to more timely and potent anti-platelet effect in the context of emergency primary angioplasty, improving myocardial recovery. Objectives This article compares the efficacy of intravenous cangrelor versus ticagrelor in a ST-elevation myocardial infarction (STEMI) population treated with primary percutaneous coronary intervention (PPCI). Materials and Methods In an open-label, prospective, randomized controlled trial, 100 subjects with STEMI were assigned 1:1 to intravenous cangrelor or oral ticagrelor. The co-primary endpoints were platelet P2Y12 inhibition at infarct vessel balloon inflation time, 4 and 24 hours. Secondary endpoints included indices of coronary microcirculatory function: index of microvascular resistance (IMR), initial infarct size (troponin at 24 hours) and final infarct size at 12 weeks (cardiac magnetic resonance). Secondary endpoints included indices of coronary microcirculatory function (index of microvascular resistance [IMR]), initial infarct size (troponin at 24 hours), final infarct size at 12 weeks (cardiac magnetic resonance), corrected thrombolysis in myocardial infarction (TIMI) frame count, TIMI flow grade, myocardial perfusion grade, and ST-segment resolution (ClinicalTrials.gov NCT02733341). Results P2Y12 inhibition at first balloon inflation time was significantly greater in cangrelor-treated patients (cangrelor P2Y12 reaction unit [PRU] 145.2 ± 50.6 vs. ticagrelor 248.3 ± 55.1). There was no difference in mean PRU at 4 and 24 to 36 hours post-dosing. IMR, final infarct size, angiographic and electrocardiographic measures of reperfusion were all similar between groups. Conclusion Cangrelor produces more potent P2Y12 inhibition at the time of first coronary balloon inflation time compared with ticagrelor. Despite this enhanced P2Y12 inhibition, coronary microvascular function and final infarct size did not differ between groups.This work was supported by the South Staffordshire Medical Foundation, the Rotha Abraham Bequest and the Royal Wolverhampton Trust (RE/2015005). This study was sponsored by the Royal Wolverhampton NHS Trust. C.B. and T.F. received funding support from the British Heart Foundation (PG/17/2532884; RE/13/5/30177; RE/18/6134217)

Percutaneous closure of postinfarction ventricular septal defect: in-hospital outcomes and long-term follow-up of UK experience.

Background— Postinfarction ventricular septal defect carries a grim prognosis. Surgical repair offers reasonable outcomes in patients who survive a healing phase. Percutaneous device implantation represents a potentially attractive early alternative. Methods and Results— Postinfarction ventricular septal defect closure was attempted in 53 patients from 11 centers (1997–2012; aged 72±11 years; 42% female). Nineteen percent had previous surgical closure. Myocardial infarction was anterior (66%) or inferior (34%). Time from myocardial infarction to closure procedure was 13 (first and third quartiles, 5–54) days. Devices were successfully implanted in 89% of patients. Major immediate complications included procedural death (3.8%) and emergency cardiac surgery (7.5%). Immediate shunt reduction was graded as complete (23%), partial (62%), or none (15%). Median length of stay after the procedure was 5.0 (2.0–9.0) days. Fifty-eight percent survived to discharge and were followed up for 395 (63–1522) days, during which time 4 additional patients died (7.5%). Factors associated with death after postinfarction ventricular septal defect closure included the following: age (hazard ratio [HR]=1.04; P =0.039), female sex (HR=2.33; P =0.043), New York Heart Association class IV (HR=4.42; P =0.002), cardiogenic shock (HR=3.75; P =0.003), creatinine (HR=1.007; P =0.003), defect size (HR=1.09; P =0.026), inotropes (HR=4.18; P =0.005), and absence of revascularization therapy for presenting myocardial infarction (HR=3.28; P =0.009). Prior surgical closure (HR=0.12; P =0.040) and immediate shunt reduction (HR=0.49; P =0.037) were associated with survival. Conclusions— Percutaneous closure of postinfarction ventricular septal defect is a reasonably effective treatment for these extremely high-risk patients. Mortality remains high, but patients who survive to discharge do well in the longer term. </jats:sec

Association of comorbid burden with clinical outcomes after transcatheter aortic valve implantation

Objectives To investigate the association of the CharlsonComorbidity Index (CCI) with clinical outcomes after transcatheter aortic valve implantation (TA VI).Background Patients undergoing TAVI have high comorbid burden; however, there is limited evidence of its impact on clinical outcomes.Methods Data from 1887 patients from the UK, Canada, Spain, Switzerland and Italy were collected between 2007 and 2016. The association of CCI with 30-day mortality, Valve Academic Research Consortium-2 (VARC-2) composite early safety, long-term survival and length of stay (LoS) was calculated using logistic regression and Cox proportional hazard models, as a whole cohort and at a country level, through a two-stage individual participant data (IPD) random effect meta-analysis.Results Most (60%) of patients had a CCI >= 3. A weak correlation was found between the total CCI and four different preoperative risks scores (rho=0.16 to 0.29), and approximately 50% of patients classed as low risk from four risk prediction models still presented with a CCI >= 3. Per-unit increases in total CCI were not associated with increased odds of 30-day mortality (OR 1.09, 95% CI 0.96 to 1.24) or VARC-2 early safety (OR 1.04, 95% CI 0.96 to 1.14) but were associated with increased hazard of long-term mortality (HR 1.10, 95% CI 1.05 to 1.16). The two-stage IPD meta-analysis indicated that CCI was not associated with LoS (HR 0.97, 95% CI 0.93 to 1.02).Conclusion In this multicentre international study, patients undergoing TA VI had significant comorbid burden. We found a weak correlation between the CCI and well-established preoperative risks scores. The CCI had a moderate association with long-term mortality up to 5 years post-TAVI

Initial experience of a second generation self expanding transcatheter aortic valve. The Uk & Ireland Evolut R Implanters' Registry

ABSTRACT Objectives This study presents the United Kingdom and Ireland real-world learning curve experience of the EvolutTM R (Medtronic, Minneapolis, Minnesota, USA) transcatheter heart valve. Background The EvolutTM R is a self-expanding, repositionable and fully recapturable second-generation transcatheter heart valve with several novel design features to improve outcome, and reduce complications. Methods Clinical, procedural, and 30-day outcome data were prospectively collected for the first 264 patients to receive an Evolut RTM valve in the United Kingdom and Ireland. Results 264 consecutive EvolutTM R implants were performed across 9 centers. Mean age was 81.1 ± 7.8 years and mean Logistic EuroScore was 19.9 ± 13.7%. Procedural indications included aortic stenosis (72.0%), mixed aortic valve disease (17.4%) and failing aortic valve bioprostheses (10.6%). Conscious sedation was used in 39.8% of cases and transfemoral access in 93.6%. The procedural success rate was 91.3%, and paravalvular leak immediately after implantation was mild or less in 92.3%. Major complications were rare: cardiac tamponade 0.4%; conversion to sternotomy 0.8%; annular rupture 0.0%; coronary occlusion 0.8%; major vascular 5.3%; acute kidney injury 6.1%; new permanent pacemaker implantation 14.7%; and procedural-related death 0.0%. At 30-day follow-up survival was 97.7%, paravalvular leak was mild or less in 92.3% and stroke rate was 3.8%. Conclusions This registry represents the largest published real-world experience of the EvolutTM R valve. Procedural success rate was high and safety was excellent, comparable to previous studies of the EvolutTM R valve and other second-generation devices. The low rate of complications represents an improvement on first-generation devices

Survival relative to pacemaker status after transcatheter aortic valve implantation

Objectives: To determine whether a permanent pacemaker (PPM) in situ can enhance survival after transcatheter aortic valve implantation (TAVI), in a predominantly inoperable or high risk cohort. Background: New conduction disturbances are the most frequent complication of TAVI, often necessitating PPM implantation before hospital discharge. Methods: We performed an observational cohort analysis of the UK TAVI registry (2007–2015). Primary and secondary endpoints were 30-day post-discharge all-cause mortality and long-term survival, respectively. Results: Of 8,651 procedures, 6,815 complete datasets were analyzed. A PPM at hospital discharge, irrespective of when implantation occurred (PPM 1.68% [22/1309] vs. no PPM 1.47% [81/5506], odds ratio [OR] 1.14, 95% confidence interval [CI] 0.71–1.84; p =.58), or a PPM implanted peri- or post-TAVI only (PPM 1.44% [11/763] vs. no PPM 1.47% [81/5506], OR 0.98 [0.51–1.85]; p =.95) did not significantly reduce the primary endpoint. Patients with a PPM at discharge were older, male, had right bundle branch block at baseline, were more likely to have received a first-generation self-expandable prosthesis and had experienced more peri- and post-procedural complications including bailout valve-in-valve rescue, bleeding and acute kidney injury. A Cox proportional hazards model demonstrated significantly reduced long-term survival in all those with a PPM, irrespective of implantation timing (hazard ratio [HR] 1.14 [1.02–1.26]; p =.019) and those receiving a PPM only at the time of TAVI (HR 1.15 [1.02–1.31]; p =.032). The reasons underlying this observation warrant further investigation. Conclusions: A PPM did not confer a survival advantage in the first 30 days after hospital discharge following TAVI.</p