Use of Coronary Artery Calcium Quantification and Distribution for Coronary Vascular Disease Risk Reclassification in a Primary Prevention Setting.

In a large screening program of asymptomatic middle-aged individuals, we sought to assess the degree of risk reclassification provided by comparing multiethnic study on subclinical atherosclerosis coronary artery calcium scoring (CACS) versus atherosclerotic cardiovascular disease (ASCVD) and Reynolds risk score (RRS) score. All 5,324 consecutive patients (aged 57 ± 8 years, 76% male) who underwent CACS screening at the Cleveland Clinic as part of a primary prevention executive health between March 16 and October 21 were included. The 10-year ASCVD, RRS, and multiethnic study on subclinical atherosclerosis CACS (MESA-CACS) risk scores were calculated and categorized as <1, 1 to 4.99, 5 to 9.99, and ≥10%. Compared with ASCVD, using MESA-CACS resulted in a downgraded risk in 1,667 subjects (31%), whereas 738 (14%) had an upgrade in risk (total of 45% reclassification). Similarly, compared with RRS, using MESA-CACS resulted in an upgraded risk in 797 (15%) and a downgrade in 1,380 (26%) subjects (total of 41% reclassification). However, by further dividing by the distribution of the coronary calcification, ASCVD overestimates the risk only for patients with coronary artery calcium (CAC) in 0 or 1 coronary artery only, whereas MESA-CACS overestimates if the CAC was noted in ≥2 arteries. Similarly, RRS only overestimates the risk for patients with 0 CAC, whereas it underestimates the risk for patients with any CAC. In conclusion, the use of MESA-CACS, along with CAC distribution in primary prevention clinics, results in differential and significant reclassification of traditional scores when calculating the 10-years coronary vascular disease risk. Overall, RRS underestimates and ASCVD overestimates the cardiovascular disease risk compared with MESA-CACS.

A Novel Approach to Detect IDH Point Mutations in Gliomas Using Nanopore Sequencing: Test Validation for the Clinical Laboratory.

The use of standard next-generation sequencing technologies to detect key mutations in IDH genes for glioma diagnosis imposes several challenges, including high capital cost and turnaround delays associated with the need for batch testing. For both glioma testing and testing in other tumor types where highly specific mutation identification is required, the high-throughput nature of next-generation sequencing limits the feasibility of using it as a primary approach in clinical laboratories. We hypothesized that third-generation nanopore sequencing by Oxford Nanopore Technologies has the capability to overcome these limitations. This study aimed to develop and validate a nanopore-based IDH mutation detection assay for clinical practice using glioma formalin-fixed, paraffin-embedded (FFPE) tissue. Glioma FFPE (n = 66) samples with confirmed IDH gene mutational status were sequenced on the MinION device using an amplicon-based approach. All cases were concordant when compared with the reference results. Limit of blank and limit of detection for the variant allele fraction were 1.5% and 3.3%, respectively, at 500× read depth per gene. Total sequencing cost per sample was CAD$50 to CAD$134 with results being available in 9 to 15 hours. These findings demonstrate that nanopore-sequencing technology can be leveraged to develop low-cost, high-performance clinical sequencing-based assays with quick turnaround times to support the detection of targeted mutations in FFPE tumor tissue.

Quantitative Echocardiographic Assessment and Optimal Criteria for Early Intervention in Asymptomatic Tricuspid Regurgitation.

BACKGROUND: Significant tricuspid regurgitation (TR) is associated with poor outcome and high operative mortality resulting from late presentation. Yet, the optimal timing for intervention is unknown. OBJECTIVES: The purpose of this study was to evaluate the prognostic value of echocardiographic parameters to inform early intervention in asymptomatic TR. METHODS: Using the Cleveland Clinic echocardiography database 2004 to 2018, the authors identified a consecutive cohort of asymptomatic patients with moderate to severe (3+) or severe (4+) TR. Quantitative TR and right heart parameters were retrospectively determined, and their prognostic utility for all-cause mortality was assessed. RESULTS: In 325 asymptomatic patients (mean age: 67.9 years; 79.4% female) with at least 3+ TR, there were 132 deaths (40.6%), with a median survival time of 9.9 years (95% CI: 7.9-12.7 years). By contrast, the median survival time in an age- and sex-matched cohort of symptomatic TR patients was 4.4 years (95% CI: 2.8-5.9 years). Among all the echocardiographic parameters evaluated, right ventricle free wall strain (RVFWS) and tricuspid regurgitant volume (RVol) were the strongest predictors of mortality in asymptomatic TR. The optimal discriminatory thresholds for these parameters were RVFWS <-19% and RVol >45 mL. The 5-year survival rates by number of risk factors (RF) were 93% (95% CI: 86%-96%), 65% (95% CI: 55%-74%), and 38% (95% CI: 26%-49%) for no RF, 1 RF, and both RFs, respectively. Compared with symptomatic TR, mortality was lower for asymptomatic TR with no RF (HR: 0.10; 95% CI: 0.04-0.29) or 1 RF (HR: 0.29; 95% CI: 0.14-0.58), but similar for asymptomatic TR with both RFs (HR: 1.11; 95% CI: 0.56-2.19). CONCLUSIONS: RVFWS and RVol are key prognostic markers that can be serially monitored to inform optimal timing of intervention for severe asymptomatic TR.

Association Between Psychosocial Risk Factors and Readmissions After Acute Myocardial Infarction: Role of COVID-19 Pandemic.

Psychosocial risk factors (PSRFs) are known to be associated with worse cardiovascular (CV) outcomes. However, there are limited data on the impact of PSRFs on readmissions after acute myocardial infarction (AMI) before and during the COVID-19 (Coronavirus Disease 2019) pandemic. Therefore, we aimed to examine this association and whether the effects of PSRFs were amplified during the COVID-19 pandemic. We queried the 2019 and 2020 Nationwide Readmissions Database for adult (age ≥18 years) index admissions with AMI as the primary diagnosis. They were then divided into 2 cohorts based on the presence or absence of ≥1 PSRF and compared across non-COVID-19 (2019) and COVID-19 (2020) time periods. The primary outcome was 30-day all-cause readmissions. Secondary outcomes included cause-specific readmissions (cardiac, noncardiac, AMI, heart failure). Multivariable hierarchical logistic regression was conducted to evaluate differences in outcomes. The study included 380,820 patients with index AMI, of which 214,384 (56%) had ≥1 PSRFs. Patients with PSRFs were younger, more likely to be female, and had a higher prevalence of CV risk factors. Of 30-day all-cause readmissions were higher in patients with PSRFs in both eras. Moreover, noncardiac and heart failure readmissions were also higher in patients with PSRFs admitted with AMI in 2019 and 2020. This study of a nationally representative population magnifies the association of PSRF with more unplanned readmissions after AMI in both pre-COVID-19 and COVID-19 times.

Association of Psychosocial Risk Factors and Outcomes in Heart Failure: Does COVID-19 Affect Outcomes?

Psychosocial risk factors (PSRFs) have emerged as crucial nontraditional risk factors affecting outcomes in patients with heart failure (HF). There is a paucity of data studying these risk factors in HF nationally. Additionally, whether the COVID-19 pandemic impacted outcomes remains unexplored, given the increased psychosocial risk during these times. Our objective is to assess the impact of PSRFs on the outcomes of HF and their comparison across non-COVID-19 and COVID-19 eras. Patients with a diagnosis of HF were selected using the 2019-2020 Nationwide Readmissions Database. Two cohorts were created based on the presence or absence of PSRFs and compared across non-COVID-19 and COVID-19 eras. We examined the association using hierarchical multivariable logistic regression models. A total of 305,955 patients were included, of which 175,348 (57%) had PSRFs. Patients with PSRFs were younger, less likely to be female, and had a higher prevalence of cardiovascular risk factors. All-cause readmissions were higher in patients with PSRFs in both the eras. All-cause mortality [odds ratio, OR 1.15 (1.04-1.27), P = 0.005] and composite of MACE [OR 1.11 (1.06-1.16), P < 0.001] were higher in patients in the non-COVID-19 era. Compared to 2019, patients with PSRFs and HF in 2020 had significantly higher all-cause mortality [OR 1.13 (1.03-1.24), P = 0.009]; however, the composite of MACE was comparable [OR 1.04 (1.00-1.09), P = 0.03]. In conclusion, the presence of PSRFs in patients with HF is associated with a significant increase in all-cause readmissions in COVID-19 and non-COVID-19 eras. The worse outcomes evident in the COVID-19 era highlights the importance of multidisciplinary care in this vulnerable population.

Persistence of Cryoglobulinemic Vasculitis after DAA Induced HCV Cure.

Treatment with a direct acting antiviral (DAA) has revolutionized HCV therapy, as more than 95% of patients achieve a sustained virological response (SVR). Cryoglobulinemic vasculitis (CryoVas), however, can persist and recur after the HCV cure. In this systematic review, we include data from 19 studies that provided information on the persistence and recurrence of CryoVas after the HCV cure with DAAs. A complete clinical response (CR) was reported in 63.7% to 90.2% of the DAA-treated patients after achieving SVR. Relapse of CryoVas symptoms was reported in 4% to 18% of the patients. Neuropathy, nephropathy, and dermatological complications were the most common manifestations of CryoVas. B-cell clones persisted in 31-40% of the patients and could contribute to CryoVas relapse. INFL3-rs12979860, ARNTL-rs648122, RETN-rs1423096, and SERPINE1-rs6976053 were associated with a higher incidence of persistence and recurrence of CryoVas. Prospective multicenter studies with diverse patient populations are needed to validate these findings for the timely and effective management of this challenging condition.

Outcomes Following Acute Coronary Syndrome in Patients With and Without Rheumatic Immune-Mediated Inflammatory Diseases.

Background Rheumatic immune mediated inflammatory diseases (IMIDs) are associated with high risk of acute coronary syndrome. The long-term prognosis of acute coronary syndrome in patients with rheumatic IMIDs is not well studied. Methods and Results We identified Medicare beneficiaries admitted with a primary diagnosis of myocardial infarction (MI) from 2014 to 2019. Outcomes of patients with MI and concomitant rheumatic IMIDs including systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis, dermatomyositis, or psoriasis were compared with propensity matched control patients without rheumatic IMIDs. One-to-three propensity-score matching was done for exact age, sex, race, ST-segment-elevation MI, and non-ST-segment-elevation MI variables and greedy approach on other comorbidities. The study primary outcome was all-cause mortality. The study cohort included 1 654 862 patients with 3.6% prevalence of rheumatic IMIDs, the most common of which was rheumatoid arthritis, followed by systemic lupus erythematosus. Patients with rheumatic IMIDs were younger, more likely to be women, and more likely to present with non-ST-segment-elevation MI. Patients with rheumatic IMIDs were less likely to undergo coronary angiography, percutaneous coronary intervention or coronary artery bypass grafting. After propensity-score matching, at median follow up of 24 months (interquartile range 9-45), the risk of mortality (adjusted hazard ratio [HR], 1.15 [95% CI, 1.14-1.17]), heart failure (HR, 1.12 [95% CI 1.09-1.14]), recurrent MI (HR, 1.08 [95% CI 1.06-1.11]), and coronary reintervention (HR, 1.06 [95% CI, 1.01-1.13]) (P<0.05 for all) was higher in patients with versus without rheumatic IMIDs. Conclusions Patients with MI and rheumatic IMIDs have higher risk of mortality, heart failure, recurrent MI, and need for coronary reintervention during follow-up compared with patients without rheumatic IMIDs.