Inflammation as A Precursor of Atherothrombosis, Diabetes and Early Vascular Aging

Vascular disease was for a long time considered a disease of the old age, but it is becoming increasingly clear that a cumulus of factors can cause early vascular aging (EVA). Inflammation plays a key role in vascular stiffening and also in other pathologies that induce vascular damage. There is a known and confirmed connection between inflammation and atherosclerosis. However, it has taken a long time to prove the beneficial effects of anti-inflammatory drugs on cardiovascular events. Diabetes can be both a product of inflammation and a cofactor implicated in the progression of vascular disease. When diabetes and inflammation are accompanied by obesity, this ominous trifecta leads to an increased incidence of atherothrombotic events. Research into earlier stages of vascular disease, and documentation of vulnerability to premature vascular disease, might be the key to success in preventing clinical events. Modulation of inflammation, combined with strict control of classical cardiovascular risk factors, seems to be the winning recipe. Identification of population subsets with a successful vascular aging (supernormal vascular aging—SUPERNOVA) pattern could also bring forth novel therapeutic interventions.

Thrombotic vs. Bleeding Events of Interruption of Dual Antiplatelet Therapy within 12 Months among Patients with Stent-Driven High Ischemic Risk Definition following PCI

Background. There is a paucity of real-world data regarding the clinical impact of dual antiplatelet therapy (DAPT) interruption (temporary or permanent) among patients at high ischemic risk. The aim of this study was to assess the risk of cardiovascular events after interruption of DAPT in high-risk PCI population. Methods. This study used data from the Fuwai PCI registry, a large, prospective cohort of consecutive patients who underwent PCI. We assessed 3,931 patients with at least 1 high ischemic risk criteria of stent-related recurrent ischemic events proposed in the 2017 ESC guidelines for focused update on DAPT who were free of major cardiac events in the first 12 months. The primary ischemic endpoint was 30-month major adverse cardiac and cerebrovascular events, and the key safety endpoints were BARC class 2, 3, or 5 bleeding and net adverse clinical events. Results. DAPT interruption within 12 months occurred in 1,122 patients (28.5%), most of which were due to bleeding events or patients’ noncompliance to treatment. A multivariate Cox regression model, propensity score (PS) matching, and inverse probability of treatment weighting (IPTW) based on the propensity score demonstrated that DAPT interruption significantly increased the risk of primary ischemic endpoint compared with prolonged DAPT (3.9% vs. 2.2%; Cox-adjusted hazard ratio (HR): 1.840; 95% confidence interval (CI): 1.247 to 2.716; PS matching-HR: 2.049 [1.236–3.399]; IPTW-adjusted HR: 1.843 [1.250–2.717]). This difference was driven mainly by all-cause death (1.8% vs. 0.7%) and MI (1.3% vs. 0.5%). Furthermore, the rate of net adverse clinical events (4.9% vs. 3.2%; Cox-adjusted HR: 1.581 [1.128–2.216]; PS matching-HR: 1.639 [1.075–2.499]; IPTW-adjusted HR: 1.554 [1.110–2.177]) was also higher in patients with DAPT interruption (≤12 months), whereas no significant differences between groups were observed in terms of BARC 2, 3, or 5 bleeding. These findings were consistent across various stent-driven high-ischemic risk subsets with respect to the primary ischemic endpoints, with a greater magnitude of harm among patients with diffuse multivessel diabetic coronary artery disease. Conclusions. In patients undergoing high-risk PCI, interruption of DAPT in the first 12 months occurred infrequently and was associated with a significantly higher adjusted risk of major adverse cardiovascular events and net adverse clinical events. 2017 ESC stent-driven high ischemic risk criteria may help clinicians to discriminate patient selection in the use of long-term DAPT when the ischemic risk certainly overcomes the bleeding one.

Incidence and Predictors of Infections and All-Cause Death in Patients with Cardiac Implantable Electronic Devices: The Italian Nationwide RI-AIAC Registry

Background: The incidence of infections associated with cardiac implantable electronic devices (CIEDs) and patient outcomes are not fully known. Aim: To provide a contemporary assessment of the risk of CIEDs infection and associated clinical outcomes. Methods: In Italy, 18 centres enrolled all consecutive patients undergoing a CIED procedure and entered a 12-months follow-up. CIED infections, as well as a composite clinical event of infection or all-cause death were recorded. Results: A total of 2675 patients (64.3% male, age 78 (70–84)) were enrolled. During follow up 28 (1.1%) CIED infections and 132 (5%) deaths, with 152 (5.7%) composite clinical events were observed. At a multivariate analysis, the type of procedure (revision/upgrading/reimplantation) (OR: 4.08, 95% CI: 1.38–12.08) and diabetes (OR: 2.22, 95% CI: 1.02–4.84) were found as main clinical factors associated to CIED infection. Both the PADIT score and the RI-AIAC Infection score were significantly associated with CIED infections, with the RI-AIAC infection score showing the strongest association (OR: 2.38, 95% CI: 1.60–3.55 for each point), with a c-index = 0.64 (0.52–0.75), p = 0.015. Regarding the occurrence of composite clinical events, the Kolek score, the Shariff score and the RI-AIAC Event score all predicted the outcome, with an AUC for the RI-AIAC Event score equal to 0.67 (0.63−0.71) p < 0.001. Conclusions: In this Italian nationwide cohort of patients, while the incidence of CIED infections was substantially low, the rate of the composite clinical outcome of infection or all-cause death was quite high and associated with several clinical factors depicting a more impaired clinical status.

The Pharmacogenetics of Statin Therapy on Clinical Events: No Evidence that Genetic Variation Affects Statin Response on Myocardial Infarction

Background: The pharmacogenetic effect on cardiovascular disease reduction in response to statin treatment has only been assessed in small studies. In a pharmacogenetic genome wide association study (GWAS) analysis within the Genomic Investigation of Statin Therapy (GIST) consortium, we investigated whether genetic variation was associated with the response of statins on cardiovascular disease risk reduction.Methods: The investigated endpoint was incident myocardial infarction (MI) defined as coronary heart disease death and definite and suspect non-fatal MI. For imputed single nucleotide polymorphisms (SNPs), regression analysis was performed on expected allelic dosage and meta-analysed with a fixed-effects model, inverse variance weighted meta-analysis. All SNPs with p-values &lt;5.0 × 10−4 in stage 1 GWAS meta-analysis were selected for further investigation in stage-2. As a secondary analysis, we extracted SNPs from the Stage-1 GWAS meta-analysis results based on predefined hypotheses to possibly modifying the effect of statin therapy on MI.Results: In stage-1 meta-analysis (eight studies, n = 10,769, 4,212 cases), we observed no genome-wide significant results (p &lt; 5.0 × 10−8). A total of 144 genetic variants were followed-up in the second stage (three studies, n = 1,525, 180 cases). In the combined meta-analysis, no genome-wide significant hits were identified. Moreover, none of the look-ups of SNPs known to be associated with either CHD or with statin response to cholesterol levels reached Bonferroni level of significance within our stage-1 meta-analysis.Conclusion: This GWAS analysis did not provide evidence that genetic variation affects statin response on cardiovascular risk reduction. It does not appear likely that genetic testing for predicting effects of statins on clinical events will become a useful tool in clinical practice.

Casirivimab-imdevimab neutralizing SARS-CoV-2: post-infusion clinical events and their risk factors

Background Casirivimab-imdevimab has been developed to neutralize SARS-CoV-2. The global clinical trials in outpatients documented several adverse effects (AE), which mandate caution in Japan where part of patients return home. To investigate post-infusion clinical events and their risk factors, we attempted a retrospective study. Main body Subjects were a consecutive series of inpatients with COVID-19 undergoing an infusion of casirivimab-imdevimab in our institute. The criteria for administration were in accordance with previous clinical trials, e.g., exclusion of patients necessitating oxygen supply. In Japan, however, SARS-CoV-2 vaccinees were eligible. Methods were review of background factors of status, imaging, and laboratory findings for the outcome of post-infusion events such as temperature increase (Temp+), pulse oximetry below 94%, and other events. Also, we documented the drug efficacy. Of a total of 96 patients with a median follow-up of 54 days, one (1.0%) died who alone was an exception demanding oxygen supply. Other 95 patients (99.0%) recovered from fever and hypoxia by Day 4 and later had no worsening of COVID-19. Median increase of body temperature was 1.0 degrees Celsius, which was used for computation of Temp+. Multivariate analysis showed that for Temp+ (n = 47), white blood cell counts more than 4.3 × 103/microliter (Odds Ratio [OR] 2.593, 95% Confidence Interval [CI] 1.060–6.338, P = 0.037) was at risk, whereas 2-time vaccination for SARS-CoV-2 (OR 0.128, 95% CI 0.026–0.636, P = 0.012) was a preventing factor. Likewise for lowered oximetry (n = 21), CT showing bilateral ground glass attenuation (OR 5.544, CI 1.599–19.228, P = 0.007) was a significant risk factor. Two patients (2.1%) showed bradycardia (asymptomatic, intervention not indicated) on Day 3 and recovery on Day 5. Limitations for this study included the difficulty distinguishing AE from worsening of COVID-19, thus we documented as clinical events. Conclusions For 24 h after infusion of casirivimab-imdevimab, COVID-19 patients with increased white blood cell counts may be predisposed to temperature elevation more than 1.0 degrees centigrade, as may bilateral ground glass opacity to lowered oximetry. Thus, patients with leukocytosis and bilateral ground glass attenuation may need precaution for transient fever and hypoxia, respectively.

Temperature Profile and Adverse Outcomes After Discharge From the Intensive Care Unit

Background A predictive model that uses the rhythmicity of core body temperature (CBT) could be an easily accessible clinical tool to ultimately improve outcomes among critically ill patients. Objectives To assess the relation between the 24-hour CBT profile (CBT-24) before intensive care unit (ICU) discharge and clinical events in the step-down unit within 7 days of ICU discharge. Methods This retrospective cohort study in a tertiary ICU at a single center included adult patients requiring acute invasive ventilation for more than 48 hours and assessed major clinical adverse events (MCAEs) and rapid response system activations (RRSAs) within 7 days of ICU discharge (MCAE-7 and RRSA-7, respectively). Results The 291 enrolled patients had a median mechanical ventilation duration of 139 hours (IQR, 50-862 hours) and at admission had a median Acute Physiology and Chronic Health Evaluation II score of 22 (IQR, 7-42). At least 1 MCAE or RRSA occurred in 64% and 22% of patients, respectively. Independent predictors of an MCAE-7 were absence of CBT-24 rhythmicity (odds ratio, 1.78 [95% CI, 1.07-2.98]; P = .03), Sequential Organ Failure Assessment score at ICU discharge (1.10 [1.00-1.21]; P = .05), male sex (1.72 [1.04-2.86]; P = .04), age (1.02 [1.00-1.04]; P = .02), and Charlson Comorbidity Index (0.87 [0.76-0.99]; P = .03). Age (1.03 [1.01-1.05]; P = .006), sepsis at ICU admission (2.02 [1.13-3.63]; P = .02), and Charlson Comorbidity Index (1.18 [1.02-1.36]; P = .02) were independent predictors of an RRSA-7. Conclusions Use of CBT-24 rhythmicity can assist in stratifying a patient’s risk of subsequent deterioration during general care within 7 days of ICU discharge.

Subclinical Leaflets Thrombosis After Transcatheter Replacement of Bicuspid vs. Tricuspid Aortic Valve

Background: Subclinical leaflet thrombosis (SLT) is an important sequela that compromises the durability of the bioprosthetic valve.Objectives: To better determine the effect of SLT in bicuspid aortic valve (BAV), we performed a retrospective assessment of CT-defined SLT in BAV and tricuspid aortic valve (TAV) stenotic patients.Methods: We consecutively collected patients undergoing the TAVR between August 2015 and March 2020 in our center. A total of 170 BAV and 201 TAV cases were enrolled. Multidetector computed tomography was performed within 30 days and at 1-year.Results: Twenty cases in the BAV group and 19 cases in the TAV group had hypoattenuated leaflet thickening (HALT) in 30 days (12.5 vs. 9.9%, p = 0.449), and 52 cases in BAV and 61 cases in TAV had the HALT (34.9 vs. 36.7%, p = 0.733) at 1-year follow-up. The mean aortic gradient (MAG) and effective orifice areas (EOA) values were comparable between the two groups at 30 days (HALT vs. no HALT; 10.8 ± 4.8 vs. 11.3 ± 6.0, p = 0.638; 1.6 ± 0.4 vs. 1.6 ± 0.3, p = 0.724), and still, no difference was observed in the MAG at 1-year (11.5 ± 5.6 vs. 10.6 ± 5.1, p = 0.164). However, the EOA at 1-year was statistically different between the two groups (1.5 ± 0.3 vs. 1.6 ± 0.4, p = 0.004). The multivariate logistic regression analysis demonstrated the anticoagulation and age as independent predictors both in the BAV and TAV groups at 1-year. There was no difference in clinical events between the HALT and no HALT group in relevant to BAV or TAV at 1-year follow-up.Conclusions: The presence of subclinical leaflet thrombosis defined by the CT was comparable between the BAV and TAV in the first year after the TAVR procedure. Age and anticoagulation were the independent predictors of the subclinical leaflet thrombosis at 1 year after the TAVR. There was no difference in relevant clinical events between the BAV and TAV groups at 1-year follow-up.

Psychosocial Risk and Health Behaviors as Predictors of Clinical Events in Patients Wait-Listed for a New Heart: Results from 7 Years of Follow-Up

We examined the long-term relationship of psychosocial risk and health behaviors on clinical events in patients awaiting heart transplantation (HTx). Psychosocial characteristics (e.g., depression), health behaviors (e.g., dietary habits, smoking), medical factors (e.g., creatinine), and demographics (e.g., age, sex) were collected at the time of listing in 318 patients (82% male, mean age = 53 years) enrolled in the Waiting for a New Heart Study. Clinical events were death/delisting due to deterioration, high-urgency status transplantation (HU-HTx), elective transplantation, and delisting due to clinical improvement. Within 7 years of follow-up, 92 patients died or were delisted due to deterioration, 121 received HU-HTx, 43 received elective transplantation, and 39 were delisted due to improvement. Adjusting for demographic and medical characteristics, the results indicated that frequent consumption of healthy foods (i.e., foods high in unsaturated fats) and being physically active increased the likelihood of delisting due improvement, while smoking and depressive symptoms were related to death/delisting due to clinical deterioration while awaiting HTx. In conclusion, psychosocial and behavioral characteristics are clearly associated with clinical outcomes in this population. Interventions that target psychosocial risk, smoking, dietary habits, and physical activity may be beneficial for patients with advanced heart failure waiting for a cardiac transplant.