Pasha, Ahmed K.

Introduction: Severe hypertriglyceridemia (SHTG), defined as plasma triglyceride (TG) level ≥ 500 mg/dl, is a risk factor for cardiovascular disease. In the NHANES dataset (2001 - 2006), the prevalence of SHTG was 1.7%. However, the prevalence of primary SHTG in the community is unknown. We conducted a community-based study to estimate the prevalence of primary SHTG, in Olmsted County, Minnesota. Methods: We used the Rochester Epidemiology Project (REP) records linkage system to identify individuals with TG ≥ 500 mg/dl between 1998-2015. Index date was defined as the first documentation of TG ≥500 mg/dl during the study period. We excluded individuals with mixed hyperlipidemia (TG ≥500 mg/dl and non-high density lipoprotein (HDL) cholesterol ≥190 mg/dl). HTG was defined as secondary in the presence of hypothyroidism, biliary obstruction, nephrotic syndrome, uncontrolled diabetes, pregnancy, liver disease, renal failure, BMI ≥35 and medication use (isotretinoin, tetracyclines, anti-retrovirals). Primary HTG was defined as absence of an identifiable secondary etiology. Characteristics of the primary SHTG individuals were ascertained from the electronic health record. Results: SHTG was identified in 3802 individuals of whom 2511 had mixed hyperlipidemia, 743 had a secondary cause for SHTG and the remaining 548 had primary SHTG. Using the 2015 population census of 151,436 for Olmsted County, the prevalence of SHTG was 2.5%, of secondary SHTG was 0.49% and of primary SHTG was 0.36%. Only half of the primary SHTG group had a diagnosis of dyslipidemia in the electronic health record and 44.3% were on lipid-lowering therapy on index date. Characteristics of individuals with primary SHTG are summarized in Table 1. Conclusions: These data highlight that primary SHTG is relatively common (≈1 in 300, similar to the prevalence of familial hypercholesterolemia), underdiagnosed and undertreated.

Introduction: The Safety and efficacy of DOACs is unknown in patients with left ventricular thrombus as these patients were excluded from DOAC trials. Hypothesis: The safety and efficacy of DOACs is comparable to vitamin K antagonists Methods: Databases including Medline, Scopus and Cochrane Central Registration of Controlled Trials were queried from inception to March 30 th 2022. Studies reporting efficacy and safety outcomes were selected for the analysis. Results: We included 11 studies comprising 1920 patients with left ventricular thrombus. The mean age in the DOAC group was 57.5 years (SD 12.8) and 58.6 years (SD 13.0) in the VKA group; 26.8% were females. Pooled results showed no difference in mortality (RR, 0.64 [95% CI, 0.16-2.52]) embolic events (RR, 0.94 [95% CI, 0.59-1.50]) or major bleeding (RR, 0.95[95% CI, 0.66-1.36]) in the DOACs compared to VKA groups. Event rate for DOAC group compared to VKA group was 12.7 vs 17.5 per 100 patient-years (mean follow up of 4.0 months) for mortality, 19.5 vs 26.5 per 100 patient-years (mean follow up of 8.9 months) for embolic events and 8.0 vs 10.0 per 100 patient-years (mean follow up of 9.5 months) for major bleeding. Conclusions: These data, from observational and randomized studies, demonstrate promising safety and efficacy of DOACs for treatment of left ventricular thrombus. Elevated embolic and mortality rates regardless of anticoagulant choice emphasize the need for further research to improve outcomes for patients with this complication.

Background: Chemotherapeutic agents have been associated with cardiotoxicity; thus, they require close monitoring. Several echocardiographic variables have been investigated as early predictors of symptomatic cardiotoxicity in patients undergoing chemotherapy. Objective: To identify if global longitudinal strain (GLS) is a better predictor of symptomatic cardiotoxicity compared to left ventricular ejection fraction (LVEF) in patients receiving chemotherapy. Methods: MEDLINE, Scopus, and Cochrane Central Register of Controlled Trials were searched from inception through December 2020. Adults who developed symptomatic cardiotoxicity (New York Heart Association [NYHA] Class III–IV heart failure, cardiac arrest, or cardiac death) after undergoing chemotherapy with pre- and postchemotherapy echocardiographic measures of cardiac function were included. The primary focus was on the prediction of symptomatic cardiotoxicity. Estimates were reported as random effects hazard ratios (HR) with 95% confidence intervals (CI). Results: Four studies met inclusion criteria. The most common malignancy identified in the included studies was breast cancer, and the most common chemotherapeutic agent utilized was anthracyclines. Most studies utilized the Simpson biplane method to measure echocardiographic parameters. Pooled results demonstrated no significant association between LVEF and the prediction of symptomatic cardiotoxicity (HR 1.48; 95% CI, 0.96–2.27; P = 0.07). However, 2 studies that analyzed GLS found it to be a strong predictor of symptomatic cardiotoxicity (HR 1.46; 95% CI, 1.34–1.58; P < .001). There was no significant association between symptomatic cardiotoxicity and baseline left ventricular end diastolic volume, end systolic volume, or end diastolic volume index. Conclusions: GLS may predict symptomatic cardiotoxicity and be used to monitor patients on chemotherapy for symptomatic cardiac dysfunction. While the pooled results for baseline LVEF identified that it is not a predictor of symptomatic cardiotoxicity, this differs from the findings of the only randomized trial included in this meta-analysis. The data for baseline GLS as a predictor of symptomatic cardiotoxicity is encouraging, but definite evidence that GLS may be superior to LVEF is lacking. Prospective randomized, blinded trials are required to identify if 1 echocardiographic parameter may be superior to the other.

Background: Catheter ablation for atrial fibrillation is a proven alternative to pharmacologic rhythm control in patients with heart failure with reduced ejection fraction (HFrEF). Whether outcomes differ in patients with heart failure with preserved ejection fraction (HFpEF) is of interest. Methods: Medline, Scopus, and Cochrane Central Register of Controlled Trials were systematically searched to identify relevant studies. We extracted or calculated a risk ratio (RR) and 95% confidence intervals (CI) from each study. Primary outcomes of interest include atrial arrythmia recurrence and repeat ablation. Harm outcomes of interest include all-cause mortality, all-cause hospitalizations, cardiovascular hospitalizations, stroke/transient ischemic attack, and cardiac tamponade. Results: We included 7 observational studies comprising 2,525 patients with HFpEF who underwent catheter ablation for atrial fibrillation. There were no significant differences in primary and harm outcomes when comparing catheter ablation for atrial fibrillation in patients with HFpEF to patients with no heart failure. Similarly, there were no significant differences in outcomes when comparing catheter ablation for patients with HFpEF to HFrEF. The certainty in these estimates was low. Conclusions: Non-randomized studies suggest that catheter ablation for atrial fibrillation in patients with HFpEF is associated with similar arrythmia free survival and safety profile when compared to patients with HFrEF and without heart failure. This suggests that patients with AF and HFpEF may benefit equally from catheter ablation as those with AF and HFrEF.

Abstract Background: Reduced or low-dose direct oral anticoagulants (DOACs) have been studied in randomized control trials for the extended prevention of venous thromboembolism (VTE) after 6 months of treatment at the therapeutic doses. The real-world effectiveness as well as utilization of this approach in clinical practice compared to continuing at therapeutic doses is unknown. Aims: Evaluate the efficacy of reduced-dose DOACs compared to standard therapeutic anticoagulation in patients with extended anticoagulation. Methods: Consecutive patients with VTE were identified using the Mayo Clinic VTE Registry from March 1st , 2013 to December 31st, 2020. Patients were followed prospectively for outcomes of VTE recurrence, death, major bleeding and clinically relevant non major bleeding (CRNMB) either in person or by survey. Type of anticoagulation and dose changes were recorded, and progressing to a low dose was treated as an endpoint. In the models relating it to the outcome, it was treated as a time-dependent covariate in the cox models. After completing standard anticoagulation treatment for 3 months with any anticoagulant, patients continuing anticoagulation were divided into two groups: standard therapeutic anticoagulation (any drug) vs those who transitioned to rivaroxaban 10 mg daily or apixaban 2.5mg twice daily any time after 3 months. Patients with recurrent VTE, major or CRNMB during the first 3 months were excluded from further analysis. Results: 219 patients (153 on Apixaban and 66 on Rivaroxaban) were identified in the low dose DOAC and 2521 in the standard anticoagulation group. The mean age was 60.7 years, mean weight was 93.2 Kg and 55.9% were males (Table 1). Patients on low dose DOACs were about the same age and weight compared to standard anticoagulation group. Among all diagnosis categories, patients with active cancer were less likely to be prescribed low dose DOACs (HR 0.56; 95%CI 0.42-0.73; P&lt;0.001), while low dose DOACs prescription was more likely in patients with pulmonary embolism (HR 1.45; 95%CI 1.11-1.89; P=0.007). The median months to start a low dose DOAC after completing the 3 months was 3.1 months with standard deviation of 6.6 months and interquartile range 2.8 months. There was no statistically significant association in the likelihood of going to a low dose group in relation to VTE recurrence (HR 1.36; 95%CI 0.42-4.45; P=0.61) or major bleeding (HR 0.59; 95%CI 0.08-4.37; P=0.61). However, transitioning to low dose DOAC was associated with reduced mortality (HR 0.53; 95%CI 0.35-0.80; P=0.003). Also, patients on low dose DOACs were more likely to have a CRNMB (HR 2.76; 95%CI 1.15-6.62; P=0.02). Conclusion: In this study of patients continuing anticoagulation past 3 months for an initial acute venous thromboembolic event, transitioning to low dose DOACs was not associated with any statistically significant association with VTE recurrence or major bleeding. However, mortality was lower and CRNMB was higher in this unadjusted analysis. Our results show that physicians are not always waiting until 6 months to transition to low doses and low doses are being utilized in cancer patients. Further research is needed to better understand the higher risk for CRNMB identified in this group. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Background Hypertriglyceridemia is associated with increased risk of coronary heart disease but the association is often attributed to concomitant metabolic abnormalities. We investigated the epidemiology of primary isolated hypertriglyceridemia (PIH) and associated cardiovascular risk in a population‐based setting. Methods and Results We identified adults with at least one triglyceride level ≥500 mg/dL between 1998 and 2015 in Olmsted County, Minnesota. We also identified age‐ and sex‐matched controls with triglyceride levels <150 mg/dL. There were 3329 individuals with elevated triglyceride levels; after excluding those with concomitant hypercholesterolemia, a secondary cause of high triglycerides, age <18 years or an incomplete record, 517 patients (49.4±14.0 years, 72.0% men) had PIH (triglyceride 627.6±183.6 mg/dL). The age‐ and sex‐adjusted prevalence of PIH in adults was 0.80% (0.72–0.87); the diagnosis was recorded in 60%, 46% were on a lipid‐lowering medication for primary prevention and a triglyceride level <150 mg/dL was achieved in 24.1%. The association of PIH with coronary heart disease was attenuated but remained significant after adjustment for demographic, socioeconomic, and conventional cardiovascular risk factors (hazard ratio [HR], 1.53; 95% CI, 1.06‐2.20; P = 0.022). There was no statistically significant association between PIH and cerebrovascular disease (HR, 1.06; 95% CI, 0.65‐1.73, P = 0.813), peripheral artery disease (HR, 1.27; 95% CI, 0.43‐3.75; P = 0.668), or the composite end point of all 3 (HR, 1.28; 95% CI, 0.92‐1.80; P =0.148) in adjusted models. Conclusions PIH was associated with incident coronary heart disease events (although there was attenuation after adjustment for conventional risk factors), supporting a causal role for triglycerides in coronary heart disease. The condition is relatively prevalent but awareness and control are low.