Cao, Jenny Jia Ling

Abstract Human genomic studies link reduced CUB domain-containing protein 1 (CDCP1) expression with myocardial recovery in heart failure. While CDCP1 regulates cardiac fibroblast proliferation in vitro, it’s in vivo role in cardiac fibrosis remains unclear. Using a Cdcp1 -knockout (KO) angiotensin II/phenylephrine mouse model, we show that Cdcp1 deletion reduces echocardiographic left ventricular mass, histologic cardiac fibrosis, and pro-fibrotic gene expression, along with decreased fibroblast activation and inflammatory markers. Spatial transcriptomics identified a pressure overload–expanded fibroblast subpopulation enriched for growth factor and TGF-β signaling (FB5), which was markedly attenuated in Cdcp1 -KO hearts, alongside reduction of a pro-inflammatory cardiomyocyte subtype (CM4). Complementary studies in human ventricular fibroblasts demonstrate that CDCP1 knockdown reduced extracellular matrix gene expression and collagen I deposition. These findings establish CDCP1 as a regulator of cardiac fibrotic remodeling in vivo and open avenues for its further investigation as a potential therapeutic target.

Abstract Background The incidence, epidemiology, and clinical characteristics of enterococcal bloodstream infection (BSI) have not previously been studied on a population-based level in the United States. Methods We utilized the Expanded Rochester Epidemiology Project medical records linkage system to conduct a contemporary 5-year, retrospective, population-based study of monomicrobial enterococcal (ME) BSI among adult residents of 8 counties in southeast Minnesota from January 1, 2018 to December 31, 2022. Results A total of 109 cases of ME-BSI were identified. The overall age- and sex-adjusted incidence rate was 6.7 per 100 000 person-years (95% confidence interval, 5.4–7.9). Multivariable analysis revealed that male sex (P < .001) and older age (P < .001) were each independently associated with increased incidence, whereas no temporal association was demonstrated (year effect, P = .475). The median age of incident cases was 76.8 years (interquartile range, 65.0–83.3). Urinary tract source was the most common presumed source (42.2%), and Enterococcus faecalis was the predominant (83.5%) pathogen. Overall, 14.4% of patients met modified Duke criteria for definite infective endocarditis. Cumulative mortality was 28.4% at 12 weeks and 43.1% at 1 year. Conclusions In this population-based study, ME-BSI was significantly associated with older age and male sex. There was a high rate of mortality at 12 weeks and 1 year, with ∼1 out of 7 cases complicated by definite infective endocarditis. These findings underscore the importance of ongoing investigation of this syndrome.

ABSTRACTBackgroundEsophageal‐pericardial fistula (EPF) is rare with an incidence of 0.016%–0.04%. With novel procedures involving intracardiac or esophageal instrumentation in the last few decades, including atrial fibrillation (AF) ablation, further understanding of this unique entity is warranted. In this systematic review, we summarize the etiology, diagnostic features, management, and outcomes of EPF.MethodsA librarian conducted a systematic literature review of case reports/series describing adults diagnosed with EPF through 7 major databases/registries from inception to 7/30/2024.ResultsOne hundred twenty patients from 115 papers met the inclusion criteria. Median age(IQR) was 57(44–67) years, with a male predominance (73.7%). The primary etiology of EPF shifted from benign esophageal diseases before 2000 to AF ablation on/after 2000. Median time(IQR) from AF ablation to EPF presentation/diagnosis was 17(13–23) days. Chest pain (70.8%) and pneumopericardium (90.0%) were, respectively, the most common presenting symptom and pericardial finding. Water‐soluble contrast esophagram (WSCE) had the highest diagnostic sensitivity (82.8%). Management included surgery (47.5%), stent placement (22.5%), combined surgery/stenting (19.2%), and conservative (10.8%). Overall mortality was 37.5%; median(IQR) time to death was 20(9–41) days. EPF from malignancy had poorer survival than those from benign esophageal causes (HR 2.65 [1.36–5.17]; p = 0.004) and cardiac ablation (HR 5.74 [2.41–13.65]; p < 0.0001). Patients who received any intervention (HR 0.28 [0.13‐0.57]; p = 0.0005) or had confirmed EPF resolution (HR 0.27 [0.12–0.59]; p = 0.0009) demonstrated better survival. There was no difference in survival between surgery and stenting alone (p = 0.91).ConclusionsAF ablation is now the leading etiology of EPF. Given its high mortality, a high degree of clinical suspicion is essential in those presenting with key signs/symptoms following AF ablation to enable urgent diagnosis and multi‐disciplinary management. WSCE may be the diagnostic modality to perform, given its high sensitivity. Future studies are warranted to investigate whether stenting should be the primary management given possible non‐inferiority to surgery.

Diffuse large B-cell lymphoma (DLBCL) is the most prevalent and aggressive subtype of non-Hodgkin lymphoma comprising 30% to 40% of cases. While DLBCL frequently arises in the lymph nodes, up to 40% of cases originate in extranodal tissues. Primary splenic DLBCL is extremely rare comprising only ~1% of DLBCL cases and can be complicated by rare entities including gastrosplenic fistula (GSF). In contrast to DLBCL, polycythemia vera (PV) is a myeloproliferative malignancy. Polycythemia vera can transform into other hematologic malignancies including post-polycythemia myelofibrosis, but associations with DLBCL are uncommon. We present the first case of PV with concomitant primary splenic DLBCL complicated by GSF. While the majority of splenic lesions are benign, they have a broad differential diagnosis including malignant etiologies. Cystic or solid morphology, the number of lesions, and vascularity on imaging heavily guide further management. Due to concern for imminent massive upper gastrointestinal bleeding in the setting of GSF, our patient was diagnosed and managed with prompt splenectomy and gastrectomy. Percutaneous splenic biopsy is also a safe and effective diagnostic modality, but was deferred in our case given increased bleeding risk with PV. In conclusion, primary splenic lymphoma should be in the differential for a splenic mass regardless of whether the patient has a prior hematologic malignancy, and management should be prompt especially if complicated by a GSF.

Background: Patients with normal resting left ventricular ejection fraction (LVEF) without either coronary artery disease (CAD) or a hypertensive response can paradoxically develop reduced LVEF during exercise stress echocardiography (ESE). The clinical phenotype and outcomes of these patients is unknown. Hypothesis: Patients who paradoxically develop reduced LVEF during exercise may represent a sub-phenotype of heart failure with preserved LVEF (HFpEF). Aims: To describe the baseline characteristics and clinical outcomes of this unique patient population. Methods: Among all ESE performed between January 2003 and December 2022, patients without a hypertensive response to exercise and without CAD by angiogram within 90 days of ESE, who had a resting LVEF ≥50% with a ≥5% LVEF decrease during ESE were identified. All-cause mortality, HF hospitalization, and atrial fibrillation (AF) outcomes were assessed. Kaplan-Meier and Cox regression methods were used to analyze time-to-event outcomes. Results: Among 213,643 stress echocardiograms performed, 134 patients met eligibility criteria (Table 1). The mean age of the population was 66±10 years, 76% were women, and 16% had AF at baseline. Mean LVEF was 58±4% at rest and 43±4% at peak stress. Stress electrocardiogram met criteria for ischemia in 14%. The 10-year all-cause mortality risk was 12.9% (95% CI 5.5-20.3) with 10 (37%) of 27 deaths due to cancer (Figure 1, Panel A). The 10-year estimated risk of HF hospitalization was 17.6% (95% CI 9.0-26.2) (Figure 1, Panel B). Among 112 patients without AF at baseline, the 10-year risk of developing AF was 23.4% (95% CI 13.4-33.4). Conclusions: Patients with exercise-induced reduced LVEF in the absence of obstructive CAD have a high incidence of HF hospitalizations and AF. Given the preponderance of women, risk for AF, HF hospitalizations, and cancer-related deaths, the possibility that this condition is an early sub-phenotype of HFpEF should be investigated.

Background: Electrocardiography-based artificial intelligence (AI-ECG) validated models that detect cardiac disease are increasingly being applied in clinical practice. The utility of such tools to detect insidious cardiac disease in patients with normal baseline left ventricular ejection fraction (LVEF) who paradoxically develop reduced LVEF during exercise stress echocardiography (ESE), and do not have coronary artery disease (CAD) or hypertension, is unknown. Hypothesis: AI-ECG is useful to diagnose insidious cardiac disease and predict clinical outcomes in patients with exercise-induced cardiomyopathy. Aims: To assess the utility of AI ECG in patients with exercise-induced cardiomyopathy. Methods: Among all ESE performed between January 2003 and December 2022, patients without a hypertensive response to exercise and without CAD (confirmed by coronary angiography within 90 days after ESE), with resting LVEF ≥50% and a paradoxical ≥5% LVEF decrease during ESE were identified. A previously validated AI-ECG algorithm that predicts atrial fibrillation (AF), reduced LVEF, and cardiac amyloidosis (CA) was applied to the baseline ECG closest to the time of ESE. The predicted probability of AF, reduced LVEF, and CA if above the published thresholds, was determined. Results: There were 134 patients with exercise-induced cardiomyopathy who were identified. The mean age of this cohort was 66±10 years, 76% were women and 16% had AF at baseline. Mean LVEF was 58±4% at rest and 43±4% at peak stress. The median follow-up period was 6.8 years (IQR 3.0-12.2). Among patients without a baseline history of AF (n=112), AI-ECG identified 29% with a significant probability of AF, which was associated with a subsequent AF diagnosis at univariable analysis (HR 2.505, 95%CI 1.016-6.177, p=0.046). There were 10 patients with an AI-ECG prediction of reduced LVEF among whom 3 were subsequently hospitalized with HF. AI-ECG was positive for CA in 8 and 3 amongst these had subsequent HF hospitalizations (Table). Conclusions: Baseline AI-ECG may help predict subsequent AF and diagnose preclinical amyloid cardiomyopathy in patients who by resting echocardiography do not seem to have cardiac disease but with exercise develop reduced LVEF.

Case Description: A 68-year-old man with end-stage renal disease on dialysis, peripheral vascular disease with metatarsal amputations, atrial fibrillation and type 1 diabetes was admitted for foot osteomyelitis secondary to MSSA bacteremia. Transesophageal echocardiogram revealed mobile mitral valve vegetations up to 1.8cm on the atrial aspect of the posterior mitral valve leaflet which prolapsed through the mitral valve during diastole. Ejection fraction was 60% and there was trivial-mild mitral regurgitation without valvular destruction or peri-annular extension into the mitral annulus. MRI brain showed bilateral cerebral and cerebellar hemispheric infarcts, consistent with acute embolic stroke. He was at high risk for both recurrent embolism and operative mortality (STS risk score 51%) due to his comorbidities and risk of hemorrhagic conversion of stroke. After shared decision making, percutaneous aspiration of the mitral vegetation was performed with AngioVac (Fig). Cerebral embolism protection devices were deployed prior to AngioVac evacuation of the mass. There was no residual mitral regurgitation and only a small vegetation strand remained (Fig). Surgical pathology confirmed MSSA endocarditis. Blood cultures remained negative, and the patient did not suffer from recurrent embolic events. The patient underwent revision metatarsal amputation and was discharged with a 6-week course of IV cefazolin. Discussion: Infective endocarditis with high embolic risk is life-threatening and challenging to treat in patients with high surgical risk. We illustrate a case of percutaneous vegetation aspiration using the AngioVac device in our patient who suffered from embolic strokes due to MSSA mitral valve endocarditis. Meta-analyses have shown clinically successful debulking in 90% of cases, with 82% of patients able to clear bacteremia with AngioVac. Although most commonly used in right-sided lesions, percutaneous debulking of left-sided endocarditis with AngioVac and cerebral protection can be considered as a treatment strategy in select patients with prohibitive surgical risk.