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A 66-year-old man with a history of apical variant hypertrophic cardiomyopathy, heart failure with preserved ejection fraction (HFpEF), severe pulmonary hypertension, and prior Group B streptococcal mitral valve endocarditis four months before, presented with generalized body shakes and urinary incontinence. Computed tomography angiography revealed an acute left M1 occlusion. The patient underwent mechanical thrombectomy. Within 24 hours of presentation, he developed hypotension, tachycardia, and fever. Infectious workup revealed a leukocytosis. One out of two sets of blood cultures revealed bacteremia with Shewanella algae. A transthoracic echocardiogram revealed a large mitral valve vegetation with multiple mobile components portending a high thromboembolic risk, as evidenced by his acute presentation with multiple embolic infarcts. He was diagnosed with infectious endocarditis caused by Shewanella algae, a rare marine environment pathogen. He was treated with ciprofloxacin 750 mg twice daily orally and meropenem 2 g every eight hours intravenously with an initial decrease in the mitral valve vegetation size. He was discharged on ceftriaxone 2g and ciprofloxacin 750mg every 12 hours for a total of six weeks from his first negative blood cultures. He was monitored through transthoracic echocardiography as he continued medical management with levofloxacin 750 mg daily. Six months after his discharge from the hospital he developed worsening heart failure and elected to pursue comfort measures only.

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Acute Myeloid Leukemia (AML) is a life-threatening illness that requires prompt diagnosis and often immediate treatment. It can present in a variety of manners but most commonly is associated with fevers, fatigue, shortness of breath, or infection. Extramedullary leukemia is a less common finding upon initial presentation, but includes dermatologic manifestations, including leukemia cutis, and rarely, large mass-like presentations known as myeloid sarcomas. While leukemic infiltration of organ systems is a well-described phenomenon, cardiac tamponade is a rare form of presentation. Herein we describe a 58-year-old man with a recent hospitalization for idiopathic cardiac tamponade who re-presented to the hospital with worsening dyspnea and fevers. He was found to have a recurrent pericardial effusion with features concerning for tamponade, as well as worsening thrombocytopenia and macrocytic anemia. Bone marrow biopsy revealed 24% myeloblasts, confirming the diagnosis of AML. Notably, his cardiac symptoms improved with treatment of his leukemia. To our knowledge, this is one of only a few cases of AML with cardiac tamponade as the initial presentation.

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AIMS: Heart failure (HF) is a clinical syndrome with no definitive diagnostic tests. HF registries are often based on manual reviews of medical records of hospitalized HF patients identified using International Classification of Diseases (ICD) codes. However, most HF patients are not hospitalized, and manual review of big electronic health record (EHR) data is not practical. The US Department of Veterans Affairs (VA) has the largest integrated healthcare system in the nation, and an estimated 1.5 million patients have ICD codes for HF (HF ICD-code universe) in their VA EHR. The objective of our study was to develop artificial intelligence (AI) models to phenotype HF in these patients. METHODS AND RESULTS: The model development cohort (n = 20 000: training, 16 000; validation 2000; testing, 2000) included 10 000 patients with HF and 10 000 without HF who were matched by age, sex, race, inpatient/outpatient status, hospital, and encounter date (within 60 days). HF status was ascertained by manual chart reviews in VA's External Peer Review Program for HF (EPRP-HF) and non-HF status was ascertained by the absence of ICD codes for HF in VA EHR. Two clinicians annotated 1000 random snippets with HF-related keywords and labelled 436 as HF, which was then used to train and test a natural language processing (NLP) model to classify HF (positive predictive value or PPV, 0.81; sensitivity, 0.77). A machine learning (ML) model using linear support vector machine architecture was trained and tested to classify HF using EPRP-HF as cases (PPV, 0.86; sensitivity, 0.86). From the 'HF ICD-code universe', we randomly selected 200 patients (gold standard cohort) and two clinicians manually adjudicated HF (gold standard HF) in 145 of those patients by chart reviews. We calculated NLP, ML, and NLP + ML scores and used weighted F scores to derive their optimal threshold values for HF classification, which resulted in PPVs of 0.83, 0.77, and 0.85 and sensitivities of 0.86, 0.88, and 0.83, respectively. HF patients classified by the NLP + ML model were characteristically and prognostically similar to those with gold standard HF. All three models performed better than ICD code approaches: one principal hospital discharge diagnosis code for HF (PPV, 0.97; sensitivity, 0.21) or two primary outpatient encounter diagnosis codes for HF (PPV, 0.88; sensitivity, 0.54). CONCLUSIONS: These findings suggest that NLP and ML models are efficient AI tools to phenotype HF in big EHR data to create contemporary HF registries for clinical studies of effectiveness, quality improvement, and hypothesis generation.

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BACKGROUND: Percutaneous left atrial appendage occlusion (LAAO) devices have emerged as alternatives to anticoagulation for embolic stroke prevention in patients with non-valvular atrial fibrillation (NVAF). The left atrial appendage is known to produce vasoactive neuroendocrine hormones involved in cardiovascular homeostasis. The hemodynamic impact of LAA occlusion on cardiac function remains poorly characterized. METHODS: This is a single-center, retrospective study of sixty-seven consecutive patients who received LAAO utilizing the WATCHMAN device from May 2017 to June 2019. All patients received a comprehensive 2D transthoracic echocardiogram (TTE) prior to the procedure and a post-procedural TTE. 2D echocardiographic pre-/post-procedural measurements including left ventricular ejection fraction, tricuspid regurgitation, estimated pulmonary artery pressure, diastolic parameters, and left atrial and right ventricular strain were statistically analyzed using the paired t-test. RESULTS: Seventy percent of study patients were male with an overall mean age of 73.0 ± 9.0 years. Analysis of post-procedural LAAO revealed statistically significant improvement in left ventricular ejection fraction (52.4 ± 12.6 vs. 56.7 ± 12.7, p < 0.001), an increase in mitral E/e' (14.1 ± 6.5 vs. 18.3 ± 10.8, p < 0.001), and a decrease right ventricular global longitudinal strain (RVGLS) (- 17.5 ± 4.6 vs. - 19.6 ± 5.7, p = 0.027) as compared to pre-procedural TTE. Peak left atrial longitudinal strain (PALS) improved post-LAAO (20.6 ± 12.2 to 22.9 ± 12.9, p = 0.040) with adjustment for cardiac arrhythmias. Post-LAAO, heart failure hospitalizations occurred in 23.9% of patients. CONCLUSIONS: Percutaneous LAAO results in real-time atrial and ventricular hemodynamic changes as assessed by echocardiographic evaluation of LV filling pressures (E/e'), PALS, RVGLS, and LVEF.

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BACKGROUND: Randomized clinical trial data have demonstrated catheter ablation (CA) as a viable treatment modality for atrial fibrillation (AF). Patients with heart failure (HF) undergoing AF CA appear to derive improvements in quality of life and mortality compared to those treated with medical therapy (MT). Contemporary national data on 30-day readmissions after CA compared to MT among patients with HF are lacking. METHODS: From the 2016 Nationwide Readmissions Databases, 749 776 (weighted national estimate: 1 421 673) AF HF patients were identified of which 2204 (0.3%) underwent CA and 747 572 (99.7%) received MT. Propensity matching balanced baseline clinical characteristics. Thirty-day readmission rates, causes, predictors, and costs of 30-day readmission were compared. RESULTS: Among both the unmatched and matched cohorts, 30-day readmissions were lower for patients treated with CA compared to MT (16.8% vs 20.1%, P < .001 and 16.8% vs 18.8%, P = .020). CA was associated with reduced risk of readmission compared to MT (odds ratio 0.86, 95% confidence interval [CI]: 0.77-0.97). HF exacerbation and arrhythmias were the most common cause for 30-day readmission after CA. CA costs were higher during index hospitalization but similar to MT during readmission among the matched cohort ($15 858 ± $21 636 vs $16 505 ± $29 171, P = .67). Predictors of readmission were largely nonmodifiable risk factors among both the CA and MT groups. CONCLUSIONS: Nearly one in six patients with HF is readmitted within 30-days after undergoing CA. In propensity matched analyses, CA was associated with decreased rate and risk for readmission compared to MT. CA has higher index hospitalization costs, but lower readmission costs.

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BACKGROUND: Atrioventricular block requiring permanent pacemaker (PPM) implantation is a common complication of transcatheter aortic valve replacement (TAVR). The mechanism of atrioventricular (AV) block during TAVR is not fully understood, but it may be due to the mechanical stress of TAVR deployment, resulting in possible injury to the nearby compact AV node. Aortic valve calcification (AVC) may worsen this condition and has been associated with an increased risk for post-TAVR PPM implantation. We performed a retrospective analysis to determine if AVC is predictive for long-term right ventricular (RV) pacing in post-TAVR pacemaker patients at 30 days. METHODS: A total of 262 consecutive patients who underwent TAVR with a balloon-expandable valve were analyzed. AVC data were derived from contrast-enhanced computed tomography and characterized by leaflet sector and region. RESULTS: A total of 25 patients (11.1%) required post-TAVR PPM implantation. Seventeen patients did not require RV pacing at 30 days. Nine of these 17 patients had no RV pacing requirement within 10 days. The presence of intra-procedural heart block (P = 0.004) was the only significant difference between patients who did not require PPM and those who required PPM but they were not RV pacing-dependent at 30 days. Non-coronary cusp (NCC) calcium volume was significantly higher in patients who were pacemaker-dependent at 30 days (P = 0.01) and a calcium volume of > 239.2 mm3 in the NCC was strongly predictive of pacemaker dependence at 30 days (area under the curve (AUC) = 0.813). Pre-existing right bundle branch block (RBBB) (odds ratio (OR) 105.4, P = 0.004), bifascicular block (OR 12.5, P = 0.02), QRS duration (OR 70.43, P = 0.007) and intra-procedural complete heart block (OR 12.83, P = 0.03) were also predictive of pacemaker dependence at 30 days. CONCLUSIONS: In patients who required PPM after TAVR, quantification of AVC by non-coronary leaflet calcium volume was found to be a novel predictor for RV pacing dependence at 30 days. The association of NCC calcification and PPM dependence may be related to the proximity of the conduction bundle to the non-coronary leaflet. Further studies are necessary to improve risk prediction for long-term RV pacing requirements following TAVR.

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Coronary artery disease (CAD) is the number one cause of death among men and women in the USA. Genetic predisposition and environmental factors lead to the development of atherosclerotic plaques in the vessel walls of the coronary arteries, resulting in decreased myocardial perfusion. Treatment includes a combination of revascularization procedures and medical therapy. Because of the high surgical risk of many of the patients undergoing revascularization procedures, medical therapies to reduce ischemic disease are an area of active research. Small molecule, cytokine, endothelial progenitor cell, stem cell, gene, and mechanical therapies show promise in increasing the collateral growth of blood vessels, thereby reducing myocardial ischemia.

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BACKGROUND: Inflammation is central to the pathogenesis of transplant arteriosclerosis (TA). We questioned whether physiologic levels of anti-inflammatory A20 influence TA severity. METHODS: We performed major histocompatibility complex mismatched aorta to carotid artery interposition grafts, using wild type (WT) or A20 heterozygote (HET) C57BL/6 (H-2) donors and BALB/c (H-2) recipients, and conversely BALB/c donors and WT/HET recipients. We analyzed aortic allografts by histology, immunohistochemistry, immunofluorescence, and gene profiling (quantitative real-time reverse-transcriptase polymerase chain reaction). We validated select in vivo A20 targets in human and mouse smooth muscle cell (SMC) cultures. RESULTS: We noted significantly greater intimal hyperplasia in HET versus WT allografts, indicating aggravated TA. Inadequate upregulation of A20 in HET allografts after transplantation was associated with excessive NF-кB activation, gauged by higher levels of IkBα, p65, VCAM-1, ICAM-1, CXCL10, CCL2, TNF, and IL-6 (mostly localized to SMC). Correspondingly, cytokine-induced upregulation of TNF and IL-6 in human and mouse SMC cultures inversely correlated with A20 expression. Aggravated TA in HET versus WT allografts correlated with increased intimal SMC proliferation, and a higher number of infiltrating IFNγ and Granzyme B CD4 T cells and natural killer cells, and lower number of FoxP3 regulatory T cells. A20 haploinsufficiency in allograft recipients did not influence TA. CONCLUSIONS: A20 haploinsufficiency in vascular allografts aggravates lesions of TA by exacerbating inflammation, SMC proliferation, and infiltration of pathogenic T cells. A20 single nucleotide polymorphisms associating with lower A20 expression or function in donors of vascularized allografts may inform risk and severity of TA, highlighting the clinical implications of our findings.

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