P2Y12 platelet inhibition in clinical practice

Platelet adhesion, activation and aggregation play a pivotal role in atherothrombosis. Intracoronary atherothrombosis is the most common cause of the development of acute coronary syndrome (ACS), and plays a central role in complications occurring around percutaneous coronary intervention (PCI) including recurrent ACS, procedure-related myocardial infarction or stent thrombosis. Inhibition of platelet aggregation by medical treatment impairs formation and progression of thrombotic processes and is therefore of great importance in the prevention of complications after an ACS or around PCI. An essential part in the platelet activation process is the interaction of adenosine diphosphate (ADP) with the platelet P2Y12 receptor. The P2Y12 receptor is the predominant receptor involved in the ADP-stimulated activation of the glycoprotein IIb/IIIa receptor. Activation of the glycoprotein IIb/IIIa receptor results in enhanced platelet degranulation and thromboxane production, and prolonged platelet aggregation. The objectives of this review are to discuss the pharmacological limitations of the P2Y12 inhibitor clopidogrel, and describe the novel alternative P2Y12 inhibitors prasugrel and ticagrelor and the clinical implications of the introduction of these new medicines

Leadless pacemaker implantation after explantation of infected conventional pacemaker systems: A viable solution?

Background: Conventional cardiac device infections are increasing in incidence, causing significant morbidity and mortality. Leadless pacemaker (LP) therapy may provide new opportunities for the management of pacemaker (PM) infections as it does not require implantation of transvenous leads and a pectoral pocket. Objective: We sought to evaluate the effect of early and late LP implantation in patients diagnosed with device infection. Methods: Patients receiving an LP at our center after conventional PM lead extraction due to infection between December 2013 and November 2017 were included. Results: A total of 17 patients (mean age 77.4 ± 7.77 years) underwent LP implantation (ie, 11 with Nanostim leadless cardiac pacemaker [Abbott, Chicago, IL] and 6 with Micra transcatheter pacing system [Medtronic, Minneapolis, MN]) after successful PM system explantation. In 9 PM-dependent patients, a temporary transvenous pacing system was placed as a bridge to permanent LP implantation. Early LP implantation was performed in 6 patients (1 week). All patients experienced no LP infection during a mean follow-up of 16 ± 12 months, including 7 patients with a history of recurrent device infections with a mean follow-up of 20 ± 14 months. Conclusion: Early and late LP placement after infected conventional pacing system explantation was a viable option in our case series. This therapy may provide an alternative strategy in the management of device infection, if confirmed by subsequent prospective randomized trials, particularly for patients who are PM dependent or have a history of recurrent device infections

Impact of early, late, and no ST-segment resolution measured by continuous ST Holter monitoring on left ventricular ejection fraction and infarct size as determined by cardiovascular magnetic resonance imaging

Background: The goal of this study is to determine the predictive value of ST-segment resolution (STR) early after percutaneous coronary intervention (PCI), late STR, and no STR for left ventricular ejection fraction (LVEF) and infarct size (IS) by cardiovascular magnetic resonance (CMR) at follow-up in patients with ST-segment elevation myocardial infarction. Methods: The analysis included 199 patients who were enrolled in the PRoximal Embolic Protection in Acute myocardial infarction and Resolution of ST-Elevation trial and in whom both continuous ST Holter and CMR at follow-up were available. Patients were stratified into 3 groups: (1) early complete (≥70%) STR measured immediately after last contrast injection (n = 113); (2) late complete STR (n = 52), defined as complete STR from 30 to 240 minutes after PCI; and (3) no complete STR after 240 minutes (n = 34). Results: Patients with early STR had more preserved LVEF and smaller IS compared to patients with late STR or no STR (LVEF: early STR, 54% ± 8%; late STR, 46% ± 13%; no STR, 43% ± 11%; and IS: 3.9 ± 3.3 g/m2; 8.0 ± 6.9 g/m2; 12.0 ± 6.0 g/m2; respectively; all P < .0001). Early STR was independently predictive for LVEF (β = 8.5; P = .0005) and IS (β = -7.0; P < .0001). Late STR was not predictive for LVEF (β = 1.6; P = .51) but predictive for IS (β = -3.5; P = .003). Conclusions: Patients with early complete STR after primary PCI have better preserved LVEF and smaller IS. Patients with late complete STR do not have better preserved LVEF but do have smaller IS. ST-segment resolution is a strong, independent predictor of LVEF and IS as assessed by CMR

Impact of Leadless Pacemaker Therapy on Cardiac and Atrioventricular Valve Function Through 12 Months of Follow-Up

BACKGROUND: Endocardial pacemaker leads and right ventricular (RV) pacing are well-known causes of tricuspid valve, mitral valve, and cardiac dysfunction. Lead-related adverse consequences can potentially be mitigated by leadless pacemaker (LP) therapy by eliminating the presence of a transvalvular lead. This study assessed the impact of LP placement on cardiac and valvular structure and function. METHODS: Echocardiographic studies before and 12±1 months after LP implantation were performed between January 2013 and May 2018 at our center and compared with age- and sex-matched controls of dual-chamber transvenous pacemaker recipients. RESULTS: A total of 53 patients receiving an LP were included, of whom 28 were implanted with a Nanostim and 25 with a Micra LP device. Tricuspid valve regurgitation was graded as being more severe in 23 (43%) patients at 12±1 months compared with baseline ( P<0.001). Compared with an apical position, an RV septal position of the LP was associated with increased tricuspid valve incompetence (odds ratio, 5.20; P=0.03). An increase in mitral valve regurgitation was observed in 38% of patients ( P=0.006). LP implantation resulted in a reduction of RV function, according to a lower tricuspid annular plane systolic excursion ( P=0.003) and RV tricuspid lateral annular systolic velocity ( P=0.02), and a higher RV Tei index ( P=0.04). LP implantation was further associated with a reduction of left ventricular ejection fraction ( P=0.03) and elevated left ventricular Tei index ( P=0.003). The changes in tricuspid valve regurgitation in the LP group were similar to the changes in the dual-chamber transvenous pacemaker control group (43% versus 38%, respectively; P=0.39). CONCLUSIONS: LP therapy is associated with an increase in tricuspid valve dysfunction through 12 months of follow-up; yet it was comparable to dual-chamber transvenous pacemaker systems. Furthermore, LP therapy seems to adversely impact mitral valve and biventricular function

Clinical outcome after surgical or percutaneous revascularization in coronary bypass graft failure

Aims To describe long-term outcome following surgical and percutaneous revascularization in graft failure. Methods We analyzed consecutive patients with graft failure after heart-team assignment to percutaneous coronary intervention (PCI) or redo coronary artery bypass grafting (CABG) between 2003 and 2008. The primary endpoint was the composite of death, myocardial infarction (MI) or target vessel revascularization (TVR). Kaplan-Meier event rate estimates were calculated up to a 5-year follow-up. Independent predictors for outcomes were identified by backward selection in a multivariable Cox proportional hazard model. Results We identified 287 patients treated for graft failure: 243 with PCI and 44 with redo CABG. Patients undergoing PCI more frequently presented with ST-elevated myocardial infarction (STEMI) (P <0.001), multivessel disease (P <0.001), vein graft failure (P = 0.04), a history of MI (P <0.001) and shorter time-to-graft failure (P = 0.001). Bare-metal stents (BMS) were used in 81.3% of the PCI-treated lesions and drug-eluting stents (DES) in 18.7%. The median follow-up was 3.9 years. Five-year rate of composite all-cause death, MI or TVR was 57.6% after PCI and 51% after CABG (P = 0.51). Repeat revascularization [TVR and target lesion revascularization (TLR)] was 30.7 and 21.3% after PCI, and 8.0 and 3.2% following CABG (P = 0.009; P = 0.008). In the PCI group, BMS was associated with higher rates of TVR (35.1 vs. 12.6%; P = 0.04) and TLR (24.8 vs. 7.6%; P = 0.04), but similar rate of death or MI compared with DES. Independent predictors for the primary outcome were creatinine [hazard ratio 1.008 per mu mol/l, 95% confidence interval (CI) 1.005-1.011, P <0.001] and peak creatine kinase MB (hazard ratio 1.001 per U/l, 95% CI 1.000-1.002, P = 0.027). Conclusion Clinical outcomes are similarly poor after heart-team triage for surgical or percutaneous intervention in patients with graft failure. Repeat revascularization occurred more frequent after PCI, particularly following BMS implantatio

Early ST-segment recovery after primary percutaneous coronary intervention accurately predicts long-term prognosis after acute myocardial infarction

Background Several ancillary studies reported on the prognostic value of ST-segment recovery (STR) with measurement at 30 to 240 minutes after primary percutaneous coronary intervention (PCI). We determined the long-term prognostic value of early STR, assessed at the end of primary PCI, in unselected patients after ST-segment elevation myocardial infarction (STEMI). Methods We analyzed 12-lead electrocardiograms, recorded in the catheterization laboratory before arterial puncture and at the time of the end of PCI, from 2,124 STEMI patients who underwent primary PCI at our institution between 2000 and 2007. ST-segment recovery was categorized as complete (>= 70%), partial (30%-70%), or absent ( <30%). Median follow-up was 4.1 years. Results The estimated 5-year mortality was 8.3% in patients with complete STR, 14.4% in patients with partial STR, and 22.8% in patients with absent STR (P <.001). Multivariable-adjusted hazard ratios for 1-year death of patients with partial and absent STR, as compared with patients with complete STR, were 2.1 (95% CI 1.2-3.8, P=.014) and 3.2 (95% CI 1.8-5.8, P <.001), respectively. In a landmark analysis restricted to 1-year survivors, early STR was significantly predictive of 5-year mortality, even after multivariable adjustment. Conclusions Early STR assessment has strong, long-term prognostic properties in all-comer STEMI patients. Moreover, the prognostic power of early STR is not restricted to the early recovery phase after STEMI, but identifies high-risk subgroups among 1-year survivors. (Am Heart J 2010; 159: 1005-11.

Short- and long-term prognostic value of the TIMI risk score after primary percutaneous coronary intervention for ST-segment elevation myocardial infarction

We investigated the short- and long-term predictive value of the TIMI risk score regarding mortality for patients treated with primary percutaneous coronary intervention (PPCI) for ST-elevation myocardial infarction (STEMI). Data on the long-term predictive value of the TIMI risk score is sparse. We used data from 3,609 STEMI patients undergoing PPCI in a high-volume PCI center in The Netherlands. Cumulative event rates according to TIMI score variables were estimated with the Kaplan-Meier method and compared with the log-rank test. The original TIMI risk score was modified based on the availability of the data in the single center registry. Higher TIMI scores were associated with significantly higher mortality at short- and long-term follow-up (P 100 beats per minute, or systolic blood pressure <100 mmHG had a worse short-term prognosis compared to those who had not. However, long-term mortality was nonsignificantly different. The presence of a history of diabetes/hypertension and weight had only long-term prognostic value. Time to PPCI did not have any prognostic value. Our current report shows that the TIMI risk score has both short- and long-term discriminative value. The different variables contained in the TIMI risk score predict short-term prognosis, others predominantly long-term mortality, whereas some are predictive for bot