Background— We prospectively evaluated the prevalence, pattern, and prognostic impact of left ventricular (LV) remodeling after acute myocardial infarction (AMI) successfully treated with primary PTCA. The prevalence, course, and prognostic value of LV remodeling after primary PTCA are still to be clarified. Methods and Results— In 284 consecutive patients with AMI treated with primary PTCA, serial echocardiographic and angiographic studies, within 24 hours (T1), at 1 (T2) and 6 months (T3) after AMI were performed. Long-term (61±14 months) clinical follow-up data were collected for 98.6% patients enrolled in the study. Overall, 85 (30%) patients showed LV dilation (>20% end-diastolic volume increase) at T3 as compared with T1. Early (from T1 to T2), late (from T2 to T3), and progressive dilation patterns (from T1 to T2 to T3) were detected in 42 (15%), 41 (14%), and 36 (13%) patients, respectively. Cardiac death and combined events rate was significantly higher among patients with than among those without LV dilation ( P =0.005 and P =0.025, respectively). The pattern of LV dilation during 6 months did not significantly affect survival. Cox survival analysis identified end-systolic volume at T1 and age as baseline predictors and end-systolic volume at T3 and age as 6-month predictors of cardiac death, respectively. Conclusions— LV remodeling after successful PTCA occurs despite sustained patency of the infarct-related artery and preservation of regional and global LV function. LV dilation at 6 months after AMI but not the specific pattern of LV dilation is clearly associated with worse long-term clinical outcome.

Background— We hypothesized that preserved microvascular integrity in the area at risk would favorably influence left ventricular (LV) remodeling and long-term outcome after acute myocardial infarction. Methods and Results— Before and after successful primary angioplasty (percutaneous transluminal coronary angioplasty [PTCA]), 124 patients with acute myocardial infarction underwent intracoronary myocardial contrast echo (MCE). An MCE score index (MCESI) was derived by averaging the single-segment score (0=not visible, 1=patchy, 2=homogeneous contrast effect) within the area at risk. An MCESI ≥1 was considered adequate reperfusion. Mean follow-up was 46±32 months. After PTCA, 100 patients showed adequate reperfusion (no microvascular dysfunction, NoMD), whereas 24 did not (MD). MD patients had a higher mean creatine kinase (4153±2422 versus 2743±1774 U/L; P =0.002) and baseline wall-motion score index (2.61±0.31 versus 2.25±0.42; P <0.001) and a lower baseline ejection fraction (33±8% versus 40±7%; P <0.001). From day 1 on, LV volumes progressively increased in the MD patients (n=19) and were larger than those of NoMD patients (n=85) at 6 months (end-diastolic volume 170±55 versus 115±29 mL; P <0.001). MCESI was the most important independent predictor of LV dilation (OR 0.61, 95% CI 0.52 to 0.71, P <0.000001). By Cox analysis, MD represented the only predictor of cardiac death (OR 0.26, 95% CI 0.09 to 0.72, P =0.010) and combined events (cardiac death, reinfarction, and heart failure; OR 0.44, 95% CI 0.23 to 0.85, P =0.014). MD patients showed worse survival in terms of cardiac death ( P <0.0001) and combined events ( P <0.0001). Conclusions— In reperfused acute myocardial infarction, MD within the risk area is an important predictor of both LV remodeling and unfavorable long-term outcome.

Brugada syndrome (BrS) is characterized by a unique electrocardiogram (ECG) pattern and life-threatening arrhythmias. However, the Type 1 Brugada ECG pattern is often transient, and a genetic cause is only identified in <25% of patients. We sought to identify an additional biomarker for this rare condition. As myocardial inflammation may be present in BrS, we evaluated whether myocardial autoantibodies can be detected in these patients. For antibody (Ab) discovery, normal human ventricular myocardial proteins were solubilized and separated by isoelectric focusing (IEF) and molecular weight on two-dimensional (2D) gels and used to discover Abs by plating with sera from patients with BrS and control subjects. Target proteins were identified by mass spectrometry (MS). Brugada syndrome subjects were defined based on a consensus clinical scoring system. We assessed discovery and validation cohorts by 2D gels, western blots, and ELISA. We performed immunohistochemistry on myocardium from BrS subjects (vs. control). All (3/3) 2D gels exposed to sera from BrS patients demonstrated specific Abs to four proteins, confirmed by MS to be α-cardiac actin, α-skeletal actin, keratin, and connexin-43, vs. 0/8 control subjects. All (18/18) BrS subjects from our validation cohorts demonstrated the same Abs, confirmed by western blots, vs. 0/24 additional controls. ELISA optical densities for all Abs were elevated in all BrS subjects compared to controls. In myocardium obtained from BrS subjects, each protein, as well as SCN5A, demonstrated abnormal protein expression in aggregates. A biomarker profile of autoantibodies against four cardiac proteins, namely α-cardiac actin, α-skeletal actin, keratin, and connexin-43, can be identified from sera of BrS patients and is highly sensitive and specific, irrespective of genetic cause for BrS. The four involved proteins, along with the SCN5A-encoded Nav1.5 alpha subunit are expressed abnormally in the myocardium of patients with BrS.

Aims: The five-item PRECISE-DAPT, integrating age, haemoglobin, white-blood-cell count, creatinine clearance, and prior bleeding, predicts bleeding risk in patients on dual antiplatelet therapy (DAPT) after stent implantation. We sought to assess whether the bleeding risk prediction offered by the PRECISE-DAPT remains valid among patients receiving ticagrelor monotherapy from 1 month onwards after coronary stenting instead of standard DAPT and having or not having centrally adjudicated bleeding endpoints. Methods and results: The PRECISE-DAPT was calculated in 14 928 and 7134 patients from GLOBAL LEADERS and GLASSY trials, respectively. The ability of the score to predict Bleeding Academic Research Consortium 3 or 5 bleeding was assessed and compared among patients on ticagrelor monotherapy (experimental strategy) or standard DAPT (reference strategy) from 1 month after drug-eluting stent implantation. Bleeding endpoints were investigator-reported or centrally adjudicated in GLOBAL LEADERS and GLASSY, respectively. At 2 years, the c-indexes for the score among patients treated with the experimental or reference strategy were 0.67 [95% confidence interval (CI): 0.63–0.71] vs. 0.63 (95% CI: 0.59–0.67) in GLOBAL LEADERS (P = 0.27), and 0.67 (95% CI: 0.61–0.73) vs. 0.66 (95% CI: 0.61–0.72) in GLASSY (P = 0.88). Decision curve analysis showed net benefit using the PRECISE-DAPT to guide bleeding risk assessment under both treatment strategies. Results were consistent between investigator-reported and adjudicated endpoints and using the simplified four-item PRECISE-DAPT. Conclusion: The PRECISE-DAPT offers a prediction model that proved similarly effective to predict clinically relevant bleeding among patients on ticagrelor monotherapy from 1 month after coronary stenting compared with standard DAPT and appears to be unaffected by the presence or absence of adjudicated bleeding endpoints.