Early Effects of Ticagrelor Versus Clopidogrel on Peripheral Endothelial Function After Non-ST-Elevation Acute Coronary Syndrome and Assessment of Its Relationship With Coronary Microvascular Function.

Peripheral endothelial dysfunction is an independent predictor of adverse long-term prognosis after acute coronary syndrome. Data are lacking on the effects of oral P2Y12-inhibitors on peripheral endothelial function in non-ST-elevation acute coronary syndrome (NSTEACS). Furthermore, the relation between peripheral endothelial function and invasive indexes of coronary microvascular function in NSTEACS is unclear. Between March 2018 and July 2020, hospitalized patients with NSTEACS were randomized (1:1) to ticagrelor or clopidogrel. Peripheral endothelial function was assessed with brachial artery flow-mediated vasodilation (FMD). Invasive indexes of coronary microvascular function were obtained using an intracoronary pressure-temperature sensor-tipped wire. In 70 patients included, mean age was 58.6 years, 78.6% (n = 55) were male and 20% (n = 14) had diabetes mellitus. Compared with clopidogrel, ticagrelor significantly improved FMD (14.2 ± 5.4% vs 8.9 ± 5.3%, p <0.001) after a median treatment time of 41.2 hours. The FMD was significantly correlated with the index of microcirculatory resistance (IMR) measured in the infarct-related artery (r = -0.38, p = 0.001), with a stronger correlation found in those who did not have percutaneous coronary intervention (r = -0.52, p = 0.03). Using receiver operating characteristic curve analysis, an FMD of 8.2% identified an IMR of >34 as the threshold, with 77.6% sensitivity and 52.4% specificity. In patients who did not have a percutaneous coronary intervention, an FMD of 11.49% identified an IMR of >34 with 84.6% sensitivity and 80% specificity. In conclusion, ticagrelor significantly improved peripheral endothelial function compared with clopidogrel in patients with NSTEACS. There was a significant correlation between brachial artery FMD and IMR of the infarct-related artery.

Impact of Ticagrelor Versus Clopidogrel on Coronary Microvascular Function After Non-ST-Segment-Elevation Acute Coronary Syndrome.

BACKGROUND: Coronary microvascular dysfunction after acute coronary syndrome is an important predictor of long-term prognosis. Data is lacking on the effects of oral P2Y12-inhibitors on coronary microvascular function in non-ST-segment-elevation acute coronary syndrome. The aim of this study was to compare the acute effects of ticagrelor versus clopidogrel pretreatment on coronary microvascular function in non-ST-segment-elevation acute coronary syndrome patients. METHODS: Hospitalized non-ST-segment-elevation acute coronary syndrome patients were randomized (1:1) to ticagrelor or clopidogrel. The index of microcirculatory resistance, coronary flow reserve, and resistive reserve ratio were obtained using an intracoronary pressure-temperature sensor-tipped wire. RESULTS: In total, 128 patients were randomized between March 2018 and July 2020. Mean age 59.2±11.8 years, 84% were male, mean Global Registry of Acute Coronary Events score was 93.7±24.5. Intracoronary physiological measurements were obtained in 118 patients (60 ticagrelor, 58 clopidogrel). In the infarct-related artery, the ticagrelor group had lower baseline index of microcirculatory resistance (22.0 [13.0-34.9] versus 27.7 [19.3-29.8]; P=0.02) and higher baseline resistive reserve ratio (3.0 [2.3-4.4] versus 2.4 [1.7-3.4]; P=0.01) compared with the clopidogrel group. A total of 88 patients underwent percutaneous coronary intervention (PCI; 45 ticagrelor, 43 clopidogrel). The ticagrelor group had lower post-PCI index of microcirculatory resistance (22.0 [15.0-29.0] versus 27.0 [18.5-47.5]; P=0.02) and higher post-PCI resistive reserve ratio (3.0 [1.8-3.8] versus 1.8 [1.5-3.4]; P=0.006) compared with the clopidogrel group. The coronary flow reserve was not significantly different between the 2 groups at baseline or post-PCI. No between-group differences were seen in any of the indices in the non-infarct-related artery. CONCLUSIONS: In non-ST-segment-elevation acute coronary syndrome patients, ticagrelor significantly improved coronary microvascular function before and after PCI compared with clopidogrel. REGISTRATION: URL: https://www.anzctr.org.au; Unique identifier: ACTRN12618001610224.

Adverse diastolic remodeling after reperfused ST-elevation myocardial infarction: An important prognostic indicator.

OBJECTIVES: We sought to determine the relationship of adverse diastolic remodeling (ie, worsening diastolic or persistent restrictive filling) with infarct scar characteristics, and to evaluate its prognostic value after ST-segment elevation myocardial infarction (STEMI). BACKGROUND: Severe diastolic dysfunction (restrictive filling) has known prognostic value post STEMI. However, ongoing left ventricular (LV) remodeling post STEMI may alter diastolic function even if less severe. METHODS AND RESULTS: There were 218 prospectively recruited STEMI patients with serial echocardiograms (transthoracic echocardiography) and cardiac magnetic resonance imaging (CMR) performed, at a median of 4 days (early) and 55 days (follow-up). LV ejection fraction and infarct characteristics were assessed by CMR, and comprehensive diastolic function assessment including a diastolic grade was evaluated on transthoracic echocardiography. 'Adverse diastolic remodeling' occurred if diastolic function grade either worsened (≥1 grade) between early and follow-up imaging, or remained as persistent restrictive filling at follow-up. Follow-up infarct scar size (IS) predicted adverse diastolic remodeling (area under the curve 0.86) and persistent restrictive filling (area under the curve 0.89). The primary endpoint of major adverse cardiovascular events (MACE) occurred in 48 patients during follow-up (mean, 710±79 days). Kaplan-Meier analysis showed that adverse diastolic remodeling (n=50) and persistent restrictive filling alone (n=33) were significant predictors of MACE (both P<.001). Multivariate Cox analysis, when adjusted for TIMI risk score and CMR IS, microvascular obstruction, and LV ejection fraction, showed adverse diastolic remodeling (HR 3.79, P<.001) was an independent predictor of MACE, as was persistent restrictive filling alone (HR 2.61, P=.019). CONCLUSIONS: Larger IS is associated with adverse diastolic remodeling. Following STEMI, adverse diastolic remodeling is a powerful prognostic marker, and identifies a larger group of 'at-risk' patients, than does persistent restrictive filling alone.

High-sensitivity troponin T predicts infarct scar characteristics and adverse left ventricular function by cardiac magnetic resonance imaging early after reperfused acute myocardial infarction.

BACKGROUND: Late gadolinium enhancement cardiac magnetic resonance imaging (CMRI) is the current standard for evaluation of myocardial infarct scar size and characteristics. Because post-ST-segment elevation myocardial infarction (STEMI) troponin levels correlate with clinical outcomes, we sought to determine the sampling period for high-sensitivity troponin T (hs-TnT) that would best predict CMRI-measured infarct scar characteristics and left ventricular (LV) function. METHODS AND RESULTS: Among 201 patients with first presentation with STEMI who were prospectively recruited, we measured serial hs-TnT levels at admission, peak, 24 hours, 48 hours, and 72 hours after STEMI. Indexed LV volumes, LV ejection fraction (LVEF) and infarct scar characteristics (scar size, scar heterogeneity, myocardial salvage index, and microvascular obstruction) were evaluated by CMRI at a median of 4 days post-STEMI. Peak and serial hs-TnT levels correlated positively with early indexed LV volumes and infarct scar characteristics, and negatively correlated with myocardial salvage index and LVEF. Both 48- and 72-hour hs-TnT levels similarly predicted "large" total infarct scar size (odds ratios [ORs] 3.08 and 3.53, both P < .001), myocardial salvage index (ORs 1.68 and 2.30, both P < .001), and LVEF <40% (ORs 2.16 and 2.17, both P < .001) on univariate analyses. On multivariate analyses, 48- and 72-hour hs-TnT levels independently predicted large infarct scar size (ORs 2.05 and 2.31, both P < .001), reduced myocardial salvage index (OR 1.39 [P = .031] and OR 1.55 [P = .009]), and LVEF <40% (OR 1.47 [P = .018] and OR 1.43 [P = .026]). All measured hs-TnT levels had a modest association and similar capacity to predict microvascular obstruction. CONCLUSIONS: Levels of hs-TnT at 48 and 72 hours, measured during the "plateau phase" post-STEMI, predicted infarct scar size, poor myocardial salvage, and LVEF. These levels also correlated with scar heterogeneity and microvascular obstruction post-STEMI. Since ascertaining peak levels after STEMI is challenging in routine practice, based on the biphasic kinetics of hs-TnT, a measurement at 48 to 72 hours (during the plateau phase) provides a useful and simple method for early evaluation of LV function and infarct scar characteristics.