Clinical and Angiographic Features in Three COVID-19 Patients with Takotsubo Cardiomyopathy. Case Report.

While coronavirus disease 2019 (COVID-19), caused by severe acute respiratory coronavirus 2 (SARS-CoV-2), has often been perceived as a predominantly respiratory condition, it is characterized by complications in multiple organ systems. Especially the involvement of the cardiovascular system, along with the possibly severe pulmonary injury, is crucial for prognosis. We identified three COVID-19 patients with takotsubo (TT) cardiomyopathy at our infectious diseases treatment center and present their clinical, laboratory, echocardiographic, electrocardiographic, and angiographic features. All patients were female (median age, 67 years); disease severity regarding COVID-19 ranged from asymptomatic to ARDS (adult respiratory syndrome) necessitating mechanical ventilation for 22 days. Angiography revealed normal coronary arteries in patient 1, severe three-vessel coronary artery disease (CAD) in patient 2, and insignificant bystander CAD in patient 3. All patients showed classic apical hypokinesia with basal hyperkinesia. In patient 3, TT cardiomyopathy resulted in transient cardiogenic shock. Twenty-eight-day mortality was 0% in this case series. In conclusion, takotsubo cardiomyopathy may be yet another clinical entity associated with SARS-CoV-2 infection.

Effects of pantoprazole and esomeprazole on platelet inhibition by clopidogrel.

BACKGROUND: Clopidogrel is activated by CYP2C19, which also metabolizes proton pump inhibitors (PPI). As proton pump inhibitors are metabolized to varying degrees by CYP2C19, we hypothesized that the reported negative omeprazole-clopidogrel drug interaction may not be a class effect. METHODS: Responsiveness to clopidogrel was assessed by the vasodilator-stimulated phosphoprotein phosphorylation (VASP) assay and aggregometry (Multiplate Analyzer) in 300 patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI). RESULTS: The mean platelet reactivity index (PRI, assessed by the VASP assay) was nearly the same in patients with (n = 226; PRI = 51%) or without PPI treatment (n = 74; PRI = 49%; P = .724). Likewise, the adenosine diphosphate-induced platelet aggregation did not differ significantly between patients with or without PPI treatment (45 vs. 41 U; P = .619). Similarly, there was no difference in the PRI or the adenosine diphosphate-induced platelet aggregation between patients with pantoprazole (n = 152; PRI = 50%; aggregation = 47 U), esomeprazole (n = 74; PRI = 54%; aggregation = 42 U), or without PPI (n = 74; PRI = 49%; aggregation = 41 U; P = .382). CONCLUSION: In contrast to the reported negative omeprazole-clopidogrel drug interaction, the intake of pantoprazole or esomeprazole is not associated with impaired response to clopidogrel.

Gender-related outcome following percutaneous coronary intervention for ST-elevation myocardial infarction: data from the Austrian acute PCI registry.

AIMS: Whether or not primary percutaneous coronary intervention (P-PCI) is equally effective and safe in women and men in a real world setting is still a matter of debate. The aim of this study was to evaluate the effect of gender on in-hospital outcome after P-PCI for ST-elevation myocardial infarction (STEMI) in a prospective national registry. METHODS AND RESULTS: This registry includes in-hospital outcome data from 19 PCI-performing hospitals. During 12 months, 1087 patients with STEMI were registered (mean age 62 +/- 13 years; 27% women). Women were older than men (67 +/- 13 vs. 60 +/- 13 years; p < 0.001) and more often had diabetes mellitus (21% vs. 13%; p < 0.001) or cardiogenic shock (15% vs. 9%; p=0.004). PCI was performed in 1004 patients (92.4%) and more frequently in men than in women (93.9 vs. 88.3%, p=0.002), whereas conservative treatment was more often decided in women (9.3% vs 4.3%; p=0.002). No differences were found between women and men in primary success rate (TIMI 2+3 flow, 92.9% vs. 93%; p=0.96). On univariate analysis, in-hospital mortality was higher in women than in men (13.7% vs. 7.2%; p=0.001). On multivariable analysis age, shock, diabetes and TIMI flow before PCI remained associated with mortality. CONCLUSIONS: Women have higher in-hospital mortality following PCI for STEMI. On multivariate analysis age, shock, diabetes and TIMI flow, but not gender, were associated with mortality in this national register. Older age and more comorbidity are likely to explain the higher mortality in female patients undergoing P-PCI.

Calcium-channel blockers reduce the antiplatelet effect of clopidogrel.

OBJECTIVES: Because of the known CYP3A4 inhibition by calcium-channel blockers (CCBs), we hypothesized that there might be a drug-drug interaction between clopidogrel and dihydropyridines in patients with coronary artery disease. BACKGROUND: Clopidogrel is activated by CYP3A4, which also metabolizes CCBs of the dihydropyridine class. METHODS: Responsiveness to clopidogrel was assessed by the vasodilator-stimulated phosphoprotein (VASP) phosphorylation assay and aggregometry in 200 patients with coronary artery disease undergoing percutaneous coronary intervention. RESULTS: The platelet reactivity index (PRI) (in the VASP assay, normal range 69% to 100%) was higher in patients receiving both clopidogrel and CCBs (61%) as compared with patients receiving clopidogrel without CCBs (48%). The absolute difference was 13% (95% confidence interval: 6% to 20%; p = 0.001), and the relative difference approached 21%. A decreased platelet inhibition by clopidogrel (PRI >69%) was seen in 40% of patients with concomitant CCB treatment and in 20% of patients without concomitant treatment (chi-square test, p = 0.008). Intake of CCB remained an independent predictor of reduced platelet inhibition by clopidogrel after adjustment for cardiovascular risk factors. Adenosine diphosphate-induced platelet aggregation was 30% higher in patients on concomitant CCB treatment compared with patients without CCBs (p = 0.046). Moreover, intake of CCBs was associated with adverse clinical outcome. In vitro incubation with CCBs (nimodipine, verapamil, amlodipine, and diltiazem) did not alter the PRI or the adenosine diphosphate-induced platelet aggregation of patients taking clopidogrel. This finding indicates that the negative effect occurs in vivo, conceivably at the level of the CYP3A4 cytochrome. CONCLUSIONS: Coadministration of CCBs is associated with decreased platelet inhibition by clopidogrel.

Parameters of the tissue factor pathway with coumadin/dipyridamole versus ticlopidine as adjunct antithrombotic-drug regimen in coronary artery stenting.

A different rate and timing of subacute stent thrombosis after percutaneous coronary intervention was reported with various peri-interventional antithrombotic regimens. Next to platelet activation, coagulation triggered by tissue factor (TF) may play a key role in this process. Thirty-one consecutive patients with stable and unstable angina undergoing coronary stenting were randomly assigned to adjunct oral anticoagulation/anti-platelet therapy (coumadin, dipyridamole, aspirin and heparin; n = 16) or adjunct anti-platelet therapy with thienopyridin (ticlopidine, aspirin and heparin; n = 15). Antigen levels of plasma TF, total tissue factor pathway inhibitor (TFPI) and TFPI/ activated factor X (TFPI/FXa) complex were determined before and for up to 6 days after intervention by immunoassay. At baseline, significantly higher levels of plasma TF and TFPI/FXa were found in patients with unstable angina [TF, 161 pg/ml (126-191 pg/ml); TFPI/FXa, 7.8 ng/ml (6.1-9.6 ng/ml)] compared with stable angina [TF, 62 pg/ml (46-82 pg/ml), P < 0.0001; TFPI/FXa, 4.5 ng/ml (3-7.6 ng/ml), P= 0.003]. One hour after intervention, an increase of plasma TF and TFPI/FXa was seen in both treatment groups. In unstable angina patients, plasma levels of TF, TFPI and TFPI/FXa were more efficiently reduced by adjunct ticlopidine therapy compared with adjunct coumadin/dipyridamole. These data suggest reduced release of circulating TF by combined anti-platelet therapy with ticlopidine and aspirin after coronary artery stenting, which may-contribute to the lower incidence of subacute stent thrombosis previously observed.