Impact of the number of modifiable risk factors on clinical outcomes after percutaneous coronary intervention: An analysis from the e-Ultimaster registry.

Aims: A substantial proportion of the patients undergoing percutaneous coronary intervention (PCI) have none of the of standard modifiable cardiovascular risk factors (SMuRFs): hypertension, diabetes, hypercholesterolaemia and smoking. The aim of this analysis was to compare clinical outcomes after PCI according to the number of SMuRFs. Methods: Patients with an indication for a PCI were stratified based upon the number of SMuRFs: 0, 1, 2 or 3-4. The primary outcome was target lesion failure (TLF), a composite of cardiac death, target vessel-related myocardial infarction or clinically driven target lesion revascularization at 1-year. Inverse weighted propensity score (IWPS) adjustment was performed to adjust for differences in baseline characteristics. Results: The prevalence of SMuRFs was: 0 SMuRF 16.4 %; 1 SMuRF 27.8 %; 2 SMuRFs 34.7 % and 3-4 SMuRFs 21.1 %. Patients without SMuRFs were younger, more likely to be male and had less complex coronary artery disease. The incidence of TLF increased with the number of SMuRFs: 2.65 %, 2.75 %, 3.23 %, and 4.24 %, Ptrend < 0.001. The relative risk (RR) for a TLF was 60 % higher (95 % confidence interval 1.32-1.93, p < 0.01) for patients with 3-4 SMuRFs compared to patients without SMuRFs. The trend remained (Ptrend < 0.01) after IWPS with TLF rates of 2.88 %, 2.64 %, 2.88 % and 3.65 %. The RR for a TLF was 27 % higher (95 % CI 1.05-1.53, p < 0.01). Conclusion: The incidence of clinical events at 1-year increased with the number of SMuRFs. While patients without SMuRFs have a relatively favourable risk profile, more research is needed to optimize therapeutic management in the majority of patients.

Repeat Coronary Angiography in Patients Aged over 50 Years with Previously Normal/Non-Obstructive Coronary Angiogram-Insights from a Retrospective Study.

(1) Introduction: A significant proportion of patients undergoing coronary angiography (CAG) have normal (NCA) or non-obstructive coronary artery disease (NOCAD). This study retrospectively tested the incidence of re-catheterization, and long-term outcomes of this population in patients aged over 50 years. (2) Methods: We identified all patients above 50 years of age with NOCAD who underwent their first CAG at our center between January 2008 and December 2019. Patients were evaluated for their baseline characteristics, risk factors profile, and indication for CAG. Patients undergoing repeat CAG after the index procedure were assessed for the above, including the primary preventive pharmacotherapy prescribed. (3) Results: A total of 1939 patients were reported to have NOCAD. Of these, 1756 (90%) patients (62% males, median age 66 (56-75) years) had no repeat angiography (group 1). Repeat angiography was performed in 10%: 136 (7%) proved futile (median time for repeat angiography 5 (3-8) years) (group 3), and 47 (3%) ended with angioplasty (median time for repeat angiography 4 (3-6) years) (group 2). Male gender, BMI above 30 (23% vs. 13%), hypertension (68% vs. 57%), diabetes (28% vs. 17%) and smoking (36% vs. 19%) were significantly higher in the interventional group. Regression analysis showed both paroxysmal atrial fibrillation and hyperlipidemia were significantly associated with repeat CAG. The indication for the first CAG was mainly symptoms related. In the interventional repeat angiography (n = 47) the incidence of troponin positive cases increased from 8.2% before intervention to 57.5%, 50% being ST elevation cases. The symptoms-related cases went from 36.7% to 18.4%. Intriguingly, 85% of the interventional group were not prescribed statin and/or aspirin on a regular basis, and/or did not adhere to treatment. (4) Conclusions: NOCAD is a frequent occurrence. The threshold for repeat angiography must be higher, better reserved to troponin positive cases. Moreover, patients must be handled according to their risk profile, not being mistakenly reassured by a snapshot benign coronary angiography.

Human Neutrophil α-Defensins 1-3 Are Upregulated in the Microenvironment of Fibrotic Liver.

Background and Objectives: Neutrophil infiltration is an established signature of Non-Alcoholic Fatty Liver Disease (NAFLD) and Steatohepatitis (NASH). The most abundant neutrophilic peptide, alpha-defensin, is considered a new evolving risk factor in the inflammatory milieu, intimately involved in lipid mobilization. Our objective is to assess for potential association between alpha-defensin immunostains and NAFLD severity. Materials and Methods: We retrospectively investigated the liver biopsies of NAFLD/NASH patients, obtained at Hillel Yaffe Medical center between the years 2012 and 2016. Patients' characteristics were recorded, including relevant blood tests at the time of biopsy. Each biopsy was semi-quantitatively scored using NAFLD Activity Score (NAS) and NASH fibrosis stage. The biopsies were immunostained for alpha-defensin. The precipitation of alpha-defensin was correlated to NAS and fibrosis. Results: A total of 80 biopsies were evaluated: male ratio 53.2%, mean age 44.9 ± 13.2 years, 54 had fibrosis grades 0-2, and 26 were grade 3-4. Conventional metabolic risk factors were more frequent in the high-grade fibrosis group. Immunostaining for alpha-defensin disclosed higher intensity (a.u.) in grade 3-4 fibrosis relative to grades 0-2, 25% vs. 6.5%, p < 0.05, respectively. Moreover, alpha-defensin staining was nicely co-localized with fibrosis. Conclusions: In our group of NASH/NAFLD patients, higher metabolic risk profile was associated with higher fibrosis grade. Immunostaining for alpha-defensin showed patchy intense staining concordant with high fibrosis, nicely co-localized with histological fibrosis. Whether alpha-defensin is a profibrotic risk factor or merely risk marker for fibrosis must be clarified in future studies.

Remote Surgical Discussion of Multivessel Coronary Artery Disease Patients without Surgery on Site-Retrospective Insights.

OBJECTIVE: The heart team approach is highly advocated for in treatment decision making in patients with multivessel disease (MVD). Nevertheless, many centers lack on-site cardiac surgical services (CSS)/formal heart team. Our local alternative is of remote surgical consultation without a structured image sharing platform. In our understanding, the incidence of anatomical complete revascularization (ACR) under this daily practice, and its clinical impact, has not been discussed before. METHODS: We analyzed 477 consecutive patients who were surgically revascularized between January 2009 and March 2018 for MVD, after remote surgical consultation. Unstable, late arrival, and ST elevation patients were excluded (n = 163). ACR was considered grafting all anatomic lesions > 50%. Syntax score (SS) calculation and ACR categorization were determined by an independent interventionalist using diagnostic angiograms and available operative reports (n = 267). Patients' outcomes were assessed in relation to multiple clinical variables including troponin result and the revascularization status. RESULTS: Three hundred and fourteen patients were included. Mean age was 64 years, and mean SS-II was 27.3 ± 11. At the 4-year follow-up, the observed mortality (11.8% and 12.9%, with troponin-positive and -negative groups, respectively), myocardial infarction (11.8%), and repeat revascularization (9.8%) were higher than those predicted using a nomogram depicting the predicted 4-year mortality as a function of the SYNTAX II Score (5.3%, 8.8%, and 3.5%, respectively, p = 0.02). ACR was reported in 33% of 267 available patients' reports. After multivariate adjustment ACR was the only variable associated with a significant increase in 4-year mortality (12.3% vs. 6.7%, p < 0.05). CONCLUSIONS: Partial revascularization in the absence of on-site CSS and a structured heart team platform is a frequent occurrence. Not surprisingly, this occurrence was associated with a higher risk for mid-term mortality. An upfront, structured, virtual, heart team interface is mandatory to particularly prioritize the completeness of revascularization when considering the optimal revascularization mode.

Divergent impacts of tocilizumab and colchicine in COVID-19-associated coagulopathy: the role of alpha-defensins.

Patients who are severely affected by coronavirus disease 2019 (COVID-19) may develop a delayed onset 'cytokine storm', which includes an increase in interleukin-6 (IL-6). This may be followed by a pro-thrombotic state and increased D-dimers. It was anticipated that tocilizumab (TCZ), an anti-IL-6 receptor monoclonal antibody, would mitigate inflammation and coagulation in patients with COVID-19. However, clinical trials with TCZ have recorded an increase in D-dimer levels. In contrast to TCZ, colchicine reduced D-dimer levels in patients with COVID-19. To understand how the two anti-inflammatory agents have diverse effects on D-dimer levels, we present data from two clinical trials that we performed. In the first trial, TCZ was administered (8 mg/kg) to patients who had a positive polymerase chain reaction test for COVID-19. In the second trial, colchicine was given (0·5 mg twice a day). We found that TCZ significantly increased IL-6, α-Defensin (α-Def), a pro-thrombotic peptide, and D-dimers. In contrast, treatment with colchicine reduced α-Def and Di-dimer levels. In vitro studies show that IL-6 stimulated the release of α-Def from human neutrophils but in contrast to colchicine, TCZ did not inhibit the stimulatory effect of IL-6; raising the possibility that the increase in IL-6 in patients with COVID-19 treated with TCZ triggers the release of α-Def, which promotes pro-thrombotic events reflected in an increase in D-dimer levels.

Alpha-defensins: risk factor for thrombosis in COVID-19 infection.

The inflammatory response to SARS/CoV-2 (COVID-19) infection may contribute to the risk of thromboembolic complications. α-Defensins, antimicrobial peptides released from activated neutrophils, are anti-fibrinolytic and prothrombotic in vitro and in mouse models. In this prospective study of 176 patients with COVID-19 infection, we found that plasma levels of α-defensins were elevated, tracked with disease progression/mortality or resolution and with plasma levels of interleukin-6 (IL-6) and D-dimers. Immunohistochemistry revealed intense deposition of α-defensins in lung vasculature and thrombi. IL-6 stimulated the release of α-defensins from neutrophils, thereby accelerating coagulation and inhibiting fibrinolysis in human blood, imitating the coagulation pattern in COVID-19 patients. The procoagulant effect of IL-6 was inhibited by colchicine, which blocks neutrophil degranulation. These studies describe a link between inflammation and the risk of thromboembolism, and they identify a potential new approach to mitigate this risk in patients with COVID-19 and potentially in other inflammatory prothrombotic conditions.

Characteristics, Management, and Outcome of Transient ST-elevation Versus Persistent ST-elevation and Non-ST-elevation Myocardial Infarction.

Patients with acute myocardial infarctions (AMIs) present as persistent ST-elevation myocardial infarction (STEMI) or as non-ST-segment elevation myocardial infarction (NSTEMI). In some patients with STEMI, ST elevations are transient and resolve before coronary intervention (transient ST-elevation myocardial infarction [TSTEMI]). We analyzed our registry comprising all consecutive patients with AMI admitted during 2009 to 2014, and compared the characteristics, management, and outcome of patients with TSTEMI with those of patients with STEMI and NSTEMI. Of 1,847 patients with AMI included in the registry, 1,073 patients sustained a STEMI (58%), 649 had a NSTEMI (35%), and 126 presented with TSTEMI (6.9%). Patients with TSTEMI were younger than patients with NSTEMI and STEMI (56.5 vs 62.8, p <0.001, and 59.5 years, p <0.02, respectively), smoked more (77.8 vs 54.0, p <0.001, and 62.1%, p <0.0005), and fewer were hypertensive (52.4 vs 74.2% and 58.8%, both p <0.001) and diabetic (26.2% vs 47.7%, p <0.0001, and 36.9%, p <0.02). The extent of coronary artery disease in patients with TSTEMI was similar to that of patients with STEMI except for less involvement of the left anterior descending artery (p <0.001), but less extensive than in NSTEMI patients. TSTEMI involved less myocardial damage by troponin-T level (p <0.005) with better cardiac function (LVEF 61% vs 55% and 49%, both p <0.0001). Mortality was lower among TSTEMI both in-hospital (0 vs 2.3% [p = NS] and 4.2% [p <0.01]) and long-term (4.8% vs 14.7% and 14.2%, both p <0.003) at a median of 36 months. In conclusion, TSTEMI is an acute coronary syndrome distinct from NSTEMI and STEMI, characterized by fewer risk factors, a similar extent of coronary artery disease to STEMI, but is associated with less myocardial damage and portends a better outcome.

Effects of estradiol and raloxifene on arterial thrombosis in ovariectomized mice.

OBJECTIVE: The effects of estrogen and selective estrogen receptor modulators (eg, raloxifene) on arterial thrombosis are not well defined. This study assessed the manner and mechanism by which estrogen and raloxifene affect homeostatic pathways in ovariectomized mice after acute arterial injury. DESIGN: Female mice (3 weeks old) underwent ovariectomy or sham operation. Five days after surgery, mice were assigned to treatment with estradiol (5.3 nmol/kg), raloxifene (2.7 micromol/kg), or placebo (n = 10-12/group). The biological effects of both treatments were assessed by measurements of bone mass and the degree of uterine atrophy. After 4 months of therapy, carotid artery thrombosis was induced by photochemical injury, and the time to vascular occlusion was measured. RESULTS: Both treatments increased bone mineral density (4.1%-7.85%). Reversal of macroscopic uterine atrophy was observed only in estrogen-treated mice. Ovariectomized mice had a shorter time to occlusion compared with sham-operated mice (70.8 +/- 7.4 vs 103 +/- 11.3 min), suggesting accelerated thrombosis. Both estradiol and raloxifene significantly inhibited intra-arterial thrombosis in ovariectomized mice, prolonging the time to occlusion to 136.33 +/- 13.5 and 141.43 +/- 9.26 min, respectively. Cyclooxygenase-2 levels in the lung tissue were significantly increased by both raloxifene and estradiol with endothelial nitric oxide synthase expression being unaltered. Platelet adhesion (measured by surface coverage under a shear rate of 1,800 s for 2 min) was significantly reduced in ovariectomized animals, being 4.63% +/- 1.47%, 5.78% +/- 1.58%, and 10.04% +/- 1.33% for raloxifene, estradiol, and placebo, respectively. CONCLUSIONS: Ovariectomy amplifies thrombosis. We found that 4 months of treatment with both estradiol and raloxifene attenuates intravascular thrombosis. The antithrombotic effect was accompanied by increased expression of cyclooxygenase-2 and suppression of platelet surface adhesion.