P2Y12 Inhibitor Loading Time Before Elective PCI and the Prevention of Myocardial Necrosis.

BACKGROUND: There are dated and conflicting data about the optimal timing of initiation of P2Y12 inhibitors in elective percutaneous coronary intervention (PCI). Peri-PCI myocardial necrosis is associated with poor outcomes. We aimed to assess the impact of the P2Y12 inhibitor loading time on periprocedural myocardial necrosis in the population of the randomized Assessment of Loading With the P2Y12 Inhibitor Ticagrelor or Clopidogrel to Halt Ischemic Events in Patients Undergoing Elective Coronary Stenting (ALPHEUS) trial, which compared ticagrelor with clopidogrel in high-risk patients who received elective PCI. METHODS: The ALPHEUS trial divided 1809 patients into quartiles of loading time. The ALPHEUS primary outcome was used (type 4 [a or b] myocardial infarction or major myocardial injury) as well as the main secondary outcome (type 4 [a or b] myocardial infarction or any type of myocardial injury). RESULTS: Patients in the first quartile group (Q1) presented higher rates of the primary outcome (P = 0.01). When compared with Q1, incidences of the primary outcome decreased in patients with longer loading times (adjusted odds ratio [adjOR], 0.70 [0.52.-0.95]; P = 0.02 for Q2; adjOR 0.65 [0.48-0.88]; P < 0.01 for Q3; adjOR 0.66 [0.49-0.89]; P < 0.01 for Q4). Concordant results were found for the main secondary outcome. There was no interaction with the study drug allocated by randomization (clopidogrel or ticagrelor). Bleeding complications (any bleeding ranging between 4.9% and 7.3% and only 1 major bleeding at 48 hours) and clinical ischemic events were rare and did not differ among groups. CONCLUSIONS: In elective PCI, administration of the oral P2Y12 inhibitor at the time of PCI could be associated with more frequent periprocedural myocardial necrosis than an earlier administration. The long-term clinical consequences remain unknown.

Ventricular septal rupture: insights into an old disease.

Ventricular septal rupture (VSR) is a serious complication of ST-elevation myocardial infarction (STEMI) and surgery is the reference treatment. We aimed at describing trends in management and mortality during the last four decades and reporting mortality predictors in these patients. We conducted a single-center retrospective study of patients sustaining a VSR from 1981 to 2020. We screened 274 patients and included 265 for analysis. The number of patients decreased over the years: 80, 88, 56, and 50 in each 10-year time span. In-hospital mortality decreased significantly since 1990 (logrank 0.007). The median age was 72.0 years IQR [66-78] and 188 patients (70.9%) were operated on. IABP was used more routinely (p < 0.0001). In-hospital mortality was assessed at 66.8% (177 patients) and main predictors of death were a time from MI to surgery < 8 days HR 2.7 IC95% [1.9-3.8] p < 0.0001, a Killip class > 2 HR 2.5 IC [1.9-3.4] p < 0.0001 and Euroscore 2 > 20 HR 2.4 IC [1.8-3.2] p < 0.0001. A "time from MI to surgery" of 8 days offers the best ability to discriminate between patients with or without mortality. The ability of "Euroscore 2 and Killip" to detect the patients most likely to wait 8 days for surgery was at 0.81 [0.73-0.89] p < 0.0001. Mortality remains high over the years. Euroscore 2, Killip class, and time from MI to surgery are the main mortality predictors. Patients with a Killip < 3 and a Euroscore < 20 should be monitored at least 8 days since MI before being referred to surgery.

Fractional Flow Reserve to Guide Treatment of Patients With Multivessel Coronary Artery Disease.

BACKGROUND: There is limited evidence that fractional flow reserve (FFR) is effective in guiding therapeutic strategy in multivessel coronary artery disease (CAD) beyond prespecified percutaneous coronary intervention or coronary graft surgery candidates. OBJECTIVES: The FUTURE (FUnctional Testing Underlying coronary REvascularization) trial aimed to evaluate whether a treatment strategy based on FFR was superior to a traditional strategy without FFR in the treatment of multivessel CAD. METHODS: The FUTURE trial is a prospective, randomized, open-label superiority trial. Multivessel CAD candidates were randomly assigned (1:1) to treatment strategy based on FFR in all stenotic (≥50%) coronary arteries or to a traditional strategy without FFR. In the FFR group, revascularization (percutaneous coronary intervention or surgery) was indicated for FFR ≤0.80 lesions. The primary endpoint was a composite of major adverse cardiac or cerebrovascular events at 1 year. RESULTS: The trial was stopped prematurely by the data safety and monitoring board after a safety analysis and 927 patients were enrolled. At 1-year follow-up, by intention to treat, there were no significant differences in major adverse cardiac or cerebrovascular events rates between groups (14.6% in the FFR group vs 14.4% in the control group; hazard ratio: 0.97; 95% confidence interval: 0.69-1.36; P = 0.85). The difference in all-cause mortality was nonsignificant, 3.7% in the FFR group versus 1.5% in the control group (hazard ratio: 2.34; 95% confidence interval: 0.97-5.18; P = 0.06), and this was confirmed with a 24 months' extended follow-up. FFR significantly reduced the proportion of revascularized patients, with more patients referred to exclusively medical treatment (P = 0.02). CONCLUSIONS: In patients with multivessel CAD, we did not find evidence that an FFR-guided treatment strategy reduced the risk of ischemic cardiovascular events or death at 1-year follow-up. (Functional Testing Underlying Coronary Revascularisation; NCT01881555).

Serum Soluble Tumor Necrosis Factor Receptors 1 and 2 Are Early Prognosis Markers After ST-Segment Elevation Myocardial Infarction.

Background: As inflammation following ST-segment elevation myocardial infarction (STEMI) is both beneficial and deleterious, there is a need to find new biomarkers of STEMI severity. Objective: We hypothesized that the circulating concentration of the soluble tumor necrosis factor α receptors 1 and 2 (sTNFR1 and sTNFR2) might predict clinical outcomes in STEMI patients. Methods: We enrolled into a prospective cohort 251 consecutive STEMI patients referred to our hospital for percutaneous coronary intervention revascularization. Blood samples were collected at five time points: admission and 4, 24, 48 h, and 1 month after admission to assess sTNFR1 and sTNFR2 serum concentrations. Patients underwent cardiac magnetic resonance imaging at 1 month. Results: sTNFR1 concentration increased at 24 h with a median of 580.5 pg/ml [95% confidence interval (CI): 534.4-645.6]. sTNFR2 increased at 48 h with a median of 2,244.0 pg/ml [95% CI: 2090.0-2,399.0]. Both sTNFR1 and sTNFR2 peak levels were correlated with infarct size and left ventricular end-diastolic volume and inversely correlated with left ventricular ejection fraction. Patients with sTNFR1 or sTNFR2 concentration above the median value were more likely to experience an adverse clinical event within 24 months after STEMI [hazards ratio (HR): 8.8, 95% CI: 4.2-18.6, p < 0.0001 for sTNFR1; HR: 6.1, 95% CI: 2.5 -10.5, p = 0.0003 for sTNFR2]. Soluble TNFR1 was an independent predictor of major adverse cardiovascular events and was more powerful than troponin I (p = 0.04 as compared to the troponin AUC). Conclusion: The circulating sTNFR1 and sTNFR2 are inflammatory markers of morphological and functional injury after STEMI. sTNFR1 appears as an early independent predictor of clinical outcomes in STEMI patients.

Association of myocardial hemorrhage and persistent microvascular obstruction with circulating inflammatory biomarkers in STEMI patients.

INTRODUCTION: Myocardial hemorrhage (IMH) and persistent microvascular obstruction (MVO) are associated with impaired myocardial recovery and adverse clinical outcomes in STEMI patients. However, their relationship with circulating inflammatory biomarkers is unclear in human patients. METHODS AND RESULTS: Twenty consecutive patients referred for primary percutaneous coronary intervention of first STEMI were included in a prospective study. Blood sampling was performed at admission, 4, 12, 24, 48 hours, 7 and 30 days after reperfusion for inflammatory biomarker (C reactive protein, fibrinogen, interleukin-6 (IL-6) and neutrophils count) assessment. At seven days, cardiovascular magnetic resonance (CMR) was performed for infarct size, MVO and IMH assessment. Median infarct size was 24.6% Interquartile range (IQR) [12.0-43.5] of LV mass and edema was 13.2% IQR [7.7-36.1] of LV mass. IL-6 reached a peak at H24 (5.6 pg/mL interquartile range (IQR) [2.5-17.5]), CRP at H48 (11.7 mg/L IQR [7.1-69.2]), fibrinogen one week after admission (4.4 g/L IQR [3.8-6.7]) and neutrophils at H12 (9.0 G/L IQR [6.5-12.7]). MVO was present in 11 patients (55% of the study population) and hemorrhage in 7 patients (35%). Patients with IMH had significantly higher IL-6, CRP, fibrinogen, and neutrophils levels compared to patients without IMH. Patients with persistent MVO had significantly higher CRP, fibrinogen and neutrophils level compared to patients without MVO, but identical IL-6 kinetics. CONCLUSION: In human patients with acute myocardial infarction, intramyocardial hemorrhage appears to have a stronger relationship with inflammatory biomarker release compared to persistent MVO. Attenuating myocardial hemorrhage may be a novel target in future adjunctive STEMI treatments.

National French registry of spontaneous coronary artery dissections: prevalence of fibromuscular dysplasia and genetic analyses.

BACKGROUND: Spontaneous coronary artery dissection (SCAD) is an increasingly reported but poorly understood condition. Few European data are available. AIMS: The aims of this study were to obtain European data on SCAD, determine the prevalence of fibromuscular dysplasia (FMD) and enable genetic analyses in this population. METHODS: Data from a national French registry of SCAD cases were analysed prospectively and retrospectively. Clinical and angiographic data and management strategy were collected. Major adverse cardiovascular events (MACE) were analysed after one year of follow-up. Subjects were screened for FMD and blood was collected for DNA extraction. RESULTS: From June 2016 to August 2018, 373 SCAD cases were confirmed by the core lab. Mean age was 51.5 years. Patients were mostly women (90.6%) and 54.7% of cases had less than two cardiovascular risk factors. At one year, 295 patients (79.1%) were treated conservatively, the MACE rate was 12.3%, and there were no cases of mortality. The recurrence rate of SCAD was 3.3%. FMD was found at ≥1 arterial site in 45.0% of cases. We also confirmed the genetic association between the PHACTR1 locus and SCAD (odds ratio=1.66, p=7.08×10-8). CONCLUSIONS: Here we describe the DISCO registry, the largest European SCAD cohort where FMD was found in 45% of cases and the genetic association with PHACTR1 was confirmed. This nationwide cohort is a valuable resource for future clinical and genetic investigation to understand SCAD aetiology.

Hypertrophic cardiomyopathy: the edge-to-edge secures the correction of the systolic anterior motion.

Objectives: Although septal myectomy is the technique of choice for hypertrophic cardiomyopathy, the surgical management of concomitant mitral valve lesions is controversial. Various complex surgeries have been proposed to address mitral valve lesions. We propose a simple option using an edge-to-edge mitral valve repair through the aortic valve in addition to the septal myectomy. Methods: We performed an observational analysis of our prospectively collected database. The clinical follow-up was done by telephone contact with each patient. The echocardiographic follow-up was performed in our Department of Cardiology or by the referring cardiologist. Results: Between January 2009 and March 2016, we operated 22 symptomatic patients (mean age 48.5 years, males 59%). The mean interventricular septum diameter and resting intraventricular gradient were 25.8 mm and 75.4 mmHg, respectively. The systolic anterior motion was present in every patient. The mean mitral regurgitation grade was 2.4. There were no in-hospital deaths. Two (9%) patients required a pacemaker. After a mean follow-up of 26.3 months, the mean New York Heart Association functional class decreased from 2.5 to 1.2 ( P < 0.001). The echocardiographic follow-up showed a sustained significant reduction of the septal thickness ( P < 0.001), resting intraventricular gradient ( P < 0.001), presence of systolic anterior motion ( P < 0.001) and grade of mitral regurgitation ( P = 0.002). Conclusions: Septal myectomy remains the gold standard of any surgery for hypertrophic cardiomyopathy owing to its good clinical and echocardiographic results. The edge-to-edge mitral valve repair is an additional simple option to avoid the systolic anterior motion and effectively reduce the grade of mitral regurgitation.