Citations

Introduction: Sepsis and its associated systemic inflammatory response syndrome in the heart can lead to septic cardiomyopathy. We aim to explore new onset cardiac dysfunction in septic shock patients and its association of right heart dysfunction with hospital outcomes. Hypothesis: Early development of correct ventricular abnormalities due to septic shock may lead to worse hospital outcomes. Methods: We conducted a retrospective study of 102 patients who were hospitalized at the Mayo Clinic between August 2018 and September 2022 with septic shock and had at least one pre-sepsis echo (within one year before admission) and one post-sepsis echo (within seven days of access). Information on patient demographics, comorbidities, echo parameters, and outcomes was collected from our sepsis database and retrospective chart review. Categorical variables were described as percentages and compared by Chi-square test, and continuous variables as medians and compared using an independent sample t-test. Statistical analysis was performed using BlueSky Statistics v10.3.1. Results: Our study included 102 patients with a median age of 68 (55, 78) years, the majority being men (68%) and Caucasians (80%). Between pre- and post-sepsis echos, there was a noticeable decrease in LVEF (60% vs 50.5 %; p=0.002). Moreover, there was an increase in reduced RV function (31.6% vs. 62.6%, p<0.001), reduced LV function (56.5% vs. 85.2%, p=0.048), and RV dilatation (35.8% vs. 51.5%, p=0.03). There was also a noticeable decrease in IVC collapsibility of more than 50% (65.9% vs 22.9%, p<0.001). There was no significance in terms of demographics, comorbidities, and baseline vitals and labs among patients with RV dysfunction and without RV dysfunction except for a lower LVEF (49% vs 62 %, p= 0.004) and decreased >50 % IVC collapsibility (14.5% vs 48%, p=0.005) in RV dysfunction group. We found no differences in hospital mortality, ICU and hospital LOS, or mechanical ventilation requirements amongst patients with RV abnormalities in function and size. Conclusions: Our retrospective study shows that abnormalities in RV function and RV size are commonly observed in the initial week of septic shock. However, such RV abnormalities did not translate into worse hospital outcomes.

Background: Heart failure (HF) is a complex trait influenced by environmental and genetic factors. Genome-wide association studies (GWAS) have found common genetic variants associated with HF risk, but the extent that common and rare variants explain risk and implicate similar genes and pathways in HF remains less understood. Methods: For common variants, we meta-analyze existing GWAS of all-cause HF with data from the Million Veteran Program, including 207,346 individuals with HF and 2,151,210 without in diverse populations. We examine rare coding variants in the Penn Medicine BioBank (PMBB) using gene-collapsing association studies and burden heritability regression. We test for an interaction between a polygenic risk score (PRS) based on our GWAS meta-analysis and truncating variants in TTN (TTNtv). Results: GWAS meta-analysis identified 176 risk loci (146 previously unreported), implicating known risk factors for HF and genes involved in cardiac development. New signals at GIPR/ GLP1R highlight potential contributions of dysregulated glucose homeostasis and metabolism in HF. Gene collapsing studies identified associations between HF and rare loss-of-function variants in TTN (OR 2.94, 95% CI 2.43-3.56) and MYBPC3 (OR 7.71, 95% CI 3.97-14.97) at exome-wide significance. HF heritability mediated through common variants (4.5%) was significantly higher than for rare variants (1.8%), but rare variant heritability was further enriched in cardiomyopathy genes compared to common variants (27-fold vs. 3.4-fold). We found a significant interaction between a new multi-ancestry HF-associated PRS (AUC 0.72, 95% CI 0.72-0.73) and TTNtv carrier status (interaction OR 1.32, 95% CI 1.06-1.64). Conclusions: Common and rare variants contribute to HF heritability. Common variant HF heritability is highly polygenic, while rare variant burden heritability appears more concentrated in core cardiomyopathy genes. HF risk conferred by TTNtv carrier status is further increased by an individual’s polygenic contribution. Our results support the continued inclusion of cardiomyopathy genes in rare-variant genetic testing panels for HF but suggest a meaningful polygenic component to HF exists that is not currently captured by clinical genetic testing.

Introduction: The impact of COVID-19 was felt across cardiology as resources were redirected to critical care, delaying elective cardiology procedures. Hypothesis: To evaluate differences in outcomes of cardiac implantable electronic device (CIED) procedures in 2020 (height of COVID) vs. 2016-2019 (pre-COVID). Methods: Adults >= 18 years undergoing CIED procedures were identified from National Inpatient Sample Databases (NIS) 2016-2020. Complications and mortality were assessed based on the type of device: Permanent Pacemaker (PPM); Implantable Cardioverter Defibrillator (ICD); Cardiac Resynchronization Therapy with Pacemaker (CRT-P) or defibrillator (CRT-D): Leadless PPM; Generator explant (GE), and Lead extraction (LE). Results: A 13.8% drop in CIED admissions was recorded between 2019 and 2020 (p<0.01). Fewer procedures involving PPM, ICD, CRT-P, CRT-D, LE, and GE were observed between 2019 and 2020. Leadless PPM utilization rose consistently between 2016-2020 (47.6% increase during 2020 vs 2019)(Figure). In 2020, a higher proportion of patients were classified with a Charlson Comorbidity Index score of ≥3 (severe) (47.4% in 2020 vs. 42.9% in 2016-2019, p<0.01). The table shows significantly higher complications during CIED implants with no changes in mortality related to procedures. Conclusions: Patients admitted for CIED implants in 2020 had more severe comorbidities and expressed considerable differences in complications than pre-COVID era (2016-2019), but mortality remained unchanged. Leadless PPM use increased during pandemic, as against a decrease in the use of other CIEDs.

Introduction: While Coronavirus disease 2019 (COVID-19) primarily affects the respiratory system but can impact the cardiovascular system can triggering various complications. Hypothesis: To investigate the trend in age-adjusted mortality rates (AAMRs) in patients with atrial fibrillation(AF) among COVID-19-positive patients (CPP) by race and sex. Methods: Trends in AAMRs (per 100,000) from all-cause in patients with AF between April to December 2016-2020 were evaluated via the National Inpatient Sample and the US Census Bureau. The AAMRs among CPP with AF in 2020 was also evaluated between racial and sex cohorts. Results: A gradual rise in AAMR(all causes) in patients with AF was observed between 2016-2019, with a 49.4% overall rise between 2019(271 per 100,000) and 2020(405 per 100,000) ( Table 1a and Figure ). Around 250475 COVID-19-positive patients had AF, and 24.2% of cases did not survive their hospitalization (vs. 10.9% in those without AF, p<0.01, aOR 1.457, 95% CI 1.438-1.477). Among CPP males and females with AF that died, White females and males were the oldest, while Black males and females reported the highest mean Charlson Comorbidity Index (CCI) score ( Table 1b ).Furthermore, among the CPP with AF in 2020, Hispanics reported a higher AAMR (119.6 per 100,000) than Whites(111.1 per 100,000) and Blacks(101.9 per 100,000). AAMRs in males were higher in Hispanic males (144.8 per 100,000), followed by White males (129.7 per 100,000), and Black males (110 per 100,000). However, the AAMRs in females were highest in Black females (91.3 per 100,000), followed by White females (88.3 per 100,000) and Hispanic females (87.0 per 100,000). ( Table 1c ) Conclusions: AAMRs in patients with AF are on the rise and a sharp growth was seen during the first year of the pandemic. AAMRs among CPP patients with AF were highest among Black females and Hispanic males, while White males and females were oldest and Black males and females reported the highest CCI scores.

Purpose: New 2022 European Society of Cardiology/European Respiratory Society PAH guidelines recommend treatment guided by a multi-parameter risk assessment. 1 Patients with low/intermediate risk without cardiopulmonary comorbidities should start dual PAH combination therapy; those with cardiopulmonary comorbidities should be reassessed early for rapid escalation to dual therapy. Initial triple therapy is recommended for high-risk patients. We examined use of dual and triple PAH therapy in the US (before guideline update). Methods: We used the Pulmonary Hypertension Association Registry (PHAR), a prospective US registry of pulmonary hypertension (PH) patients, enrolled within 6 months of their first outpatient visit at one of 54 participating PH care centers in the US, between Sep 2015-Jun 2022. We included adults (≥18 years at enrollment) with incident PAH (newly diagnosed and treated within 6 months of enrollment) and ≥1 follow-up clinic visit post baseline visit. Chronic thromboembolic PH patients were excluded. Results: We analyzed (descriptive statistics) 794 incident patients (baseline characteristics in Table 1). Treatment patterns at baseline (n=794)/last follow-up visit (n=610) were 289 (36.4%)/102 (16.7%) on monotherapy, 419 (52.8%)/314 (51.5%) on dual combination, 83 (10.5%)/179 (29.3%) on triple combination therapy, respectively. Mean time from enrollment to dual and triple combination therapy was 86.1 (standard deviation [SD]: 209.0) and 346.1 days (SD: 430.8), respectively. Conclusions: Among incident PHAR patients, half received initial dual and 10% triple upfront combination therapy. At last follow-up, most (>80%) patients had escalated to dual/triple combination therapies. Clinical Implications: At PH care centers, most incident PHAR patients are escalated to dual and triple therapy (at last follow-up) per current guidelines. Reference 1. Humbert M, et al. Eur Heart J. 2022;43:3618-731.