Improved endothelial function after short-term therapy with evolocumab.

BACKGROUND: The reduction of cholesterol levels with cholesterol-lowering therapy may improve endothelial function. Lipid-lowering therapy has been greatly enhanced by the introduction of proprotein convertase subtilisin/kexin type 9 (PCSK9) antibodies. Less is known of the effect of PCSK9 inhibitors on endothelial function of subjects with hypercholesterolemia. OBJECTIVE: To assess whether treatment with PCSK9 inhibitors may improve endothelial function evaluated by brachial artery vasoreactivity test. METHODS: Brachial artery vasoreactivity test was performed in 14 consecutive patients with previous myocardial infarction before and after 2 months of therapy with evolocumab 140 mg twice in a month. Mean brachial artery diameter, velocity time integral, flow-mediated dilation (FMD) and low-density lipoprotein (LDL) cholesterol levels were also evaluated. RESULTS: After 2 months of treatment with evolocumab, mean total cholesterol levels decreased from 245 ± 41 to 128 ± 30 mg/dL (P < .001, -48%), and LDL levels from 176 ± 43 to 71 ± 26 mg/dL (P = .001, -59%); FMD conversely increased from 6.3 ± 4.1% to 8.8 ± 6.3% (P = .004, +40%). Improvement in FMD was proportional to reduction of LDL levels (r = 0.69, P = .006). Therapy with evolocumab increased brachial artery diameter during vasoreactivity test (peak values 0.39 ± 0.09 vs 0.36 ± 0.11 cm, P = .010; final values 0.36 ± 0.10 vs 0.34 ± 0.10 cm, P = .001), and velocity time integral (peak levels 96 ± 1 vs 85 ± 9 cm, P = .045). CONCLUSIONS: Two months of treatment with evolocumab 140 mg may improve endothelial function in subjects with increased cardiovascular risk. The improvement in endothelial function is proportional to LDL reduction.

Fast 'wandering' Takotsubo syndrome: atypical mixed evolution from apical to mid-ventricular ballooning.

We report the case of a 53-year-old woman admitted for typical chest pain and a diagnosis of Takotsubo syndrome (TTS). Initial echocardiographic presentation was characterized by apical and mid-ventricular akinesis and basal hyper-kinesis. Unexpectedly, later after admission, echocardiography showed recovered apical akinesis with an apparent 'migration' of systolic dysfunction to mid-ventricular segment and hyper-kinesis of apical and basal segments. One week after admission, left ventricular contractility completely recovered and cardiac magnetic resonance imaging did not show signs of subendocardial late-enhancement and myocardial edema. Cases of TTS may therefore occasionally rapidly 'wander' within left ventricular segments, raising doubts over the so far used classification of left ventricular patterns of ballooning in subjects with TTS (typical/atypical). Apparently, different patterns can rapidly evolve into each other. The absence of late-enhancement at cardiac magnetic resonance imaging could hypothetically identify rapidly 'wandering' cases.

Maximal hyperemia in the assessment of fractional flow reserve: intracoronary adenosine versus intracoronary sodium nitroprusside versus intravenous adenosine: the NASCI (Nitroprussiato versus Adenosina nelle Stenosi Coronariche Intermedie) study.

OBJECTIVES: This study sought to compare increasing doses of intracoronary (i.c.) adenosine or i.c. sodium nitroprusside versus intravenous (i.v.) adenosine for fractional flow reserve (FFR) assessment. BACKGROUND: Maximal hyperemia is the critical prerequisite for FFR assessment. Despite i.v. adenosine currently representing the recommended approach, i.c. administration of adenosine or other coronary vasodilators constitutes a valuable alternative in everyday practice. However, it is surprisingly unclear which i.c. strategy allows the achievement of FFR values comparable to i.v. adenosine. METHODS: Fifty intermediate coronary stenoses (n = 45) undergoing FFR measurement were prospectively and consecutively enrolled. Hyperemia was sequentially induced by incremental boli of i.c. adenosine (ADN) (60 µg ADN60, 300 µg ADN300, 600 µg ADN600), by i.c. sodium nitroprusside (NTP) (0.6 µg/kg bolus) and by i.v. adenosine infusion (IVADN) (140 µg/kg/min). FFR values, symptoms, and development of atrioventricular block were recorded. RESULTS: Incremental doses of i.c. adenosine and NTP were well tolerated and associated with fewer symptoms than IVADN. Intracoronary adenosine doses (0.881 ± 0.067, 0.871 ± 0.068, and 0.868 ± 0.070 with ADN60, ADN300, and ADN600, respectively) and NTP (0.892 ± 0.072) induced a significant decrease of FFR compared with baseline levels (p < 0.001). Notably, ADN600 only was associated with FFR values similar to IVADN (0.867 ± 0.072, p = 0.28). Among the 10 patients with FFR values ≤0.80 with IVADN, 5 were correctly identified also by ADN60, 6 by ADN300, 7 by ADN600, and 6 by NTP. CONCLUSIONS: Intracoronary adenosine, at doses higher than currently suggested, allows obtaining FFR values similar to i.v. adenosine. Intravenous adenosine, which remains the gold standard, might thus be reserved for those lesions with equivocal FFR values after high (up to 600 µg) i.c. adenosine doses.