Citations

Background Heart failure (HF) is a complex disease that contributes to a high number of hospitalizations, deaths, and economic health care costs each year. However, among patients with HF, there is a lack of awareness of their HF diagnosis that has not been fully examined. Methods and Results Residents from 3 counties of southeast Minnesota with a first‐ever International Classification of Diseases, Ninth Revision ( ICD‐9 ) code 428 or Tenth Revision ( ICD‐10 ) code I50 between January 1, 2013 and March 31, 2016 (N=2461) were prospectively surveyed to measure HF self‐awareness. A total of 1114 patients returned the survey (response rate, 45%), and 787 had validated HF upon medical record review. Among these 787 patients with HF (mean age, 76 years; 53% men), 37% (n=293) were aware of their HF diagnosis. After adjustment, being a woman (odds ratio [OR], 1.56 [95% CI, 1.10–2.22]), having HF with reduced ejection fraction (OR, 1.58 [95% CI, 1.13–2.22]), attending the HF clinic (OR, 4.07 [95% CI, 2.25–7.36]), and having coronary artery disease (OR, 1.65 [95% CI, 1.16–2.37]) were all associated with increased awareness of an HF diagnosis. Conversely, having diabetes was associated with decreased awareness of an HF diagnosis (adjusted OR, 0.69 [95% CI, 0.50–0.95]). Conclusions Awareness of an HF diagnosis is low in a community population of patients with HF. Strategies to improve patient awareness of their diagnosis should be implemented to improve self‐care behaviors and outcomes in patients with HF.

Abstract Aims Cardiotoxicity is a serious side effect of anthracycline treatment, most commonly manifesting as a reduction in left ventricular ejection fraction (EF). Early recognition and treatment have been advocated, but robust, convenient, and cost-effective alternatives to cardiac imaging are missing. Recent developments in artificial intelligence (AI) techniques applied to electrocardiograms (ECGs) may fill this gap, but no study so far has demonstrated its merit for the detection of an abnormal EF after anthracycline therapy. Methods and results Single centre consecutive cohort study of all breast cancer patients with ECG and transthoracic echocardiography (TTE) evaluation before and after (neo)adjuvant anthracycline chemotherapy. Patients with HER2-directed therapy, metastatic disease, second primary malignancy, or pre-existing cardiovascular disease were excluded from the analyses as were patients with EF decline for reasons other than anthracycline-induced cardiotoxicity. Primary readout was the diagnostic performance of AI-ECG by area under the curve (AUC) for EFs < 50%. Of 989 consecutive female breast cancer patients, 22 developed a decline in EF attributed to anthracycline therapy over a follow-up time of 9.8 ± 4.2 years. After exclusion of patients who did not have ECGs within 90 days of a TTE, 20 cases and 683 controls remained. The AI-ECG model detected an EF < 50% and ≤ 35% after anthracycline therapy with an AUC of 0.93 and 0.94, respectively. Conclusion These data support the use of AI-ECG for cardiotoxicity screening after anthracycline-based chemotherapy. This technology could serve as a gatekeeper to more costly cardiac imaging and could enable patients to monitor themselves over long periods of time.

Introduction and importance: Edward syndrome is a severe chromosomal defect that occurs as a result of non-disjunction through meiosis. It presents with cardiac septal defects, horseshoe kidneys, patent ductus arteriosus, central nervous system dysgenesis, distinctive craniofacial deformities, and overriding or overlapping fingers. Klinefelter syndrome (47, XXY) is found in 1 in 660 newborn males. It is considered to be one of the most common genetic causes of infertility. It manifests with small firm testes, androgen insufficiency, and azoospermia. Case presentation: A 2-month-old male infant with a history of weakness in feeding, frequent convulsions, and an increase in cyanosis two days ago. There were multiple skeletal deformities and a tendency to spasm in the extremities, left ventricular atrophy, mitral atresia, atrial septal defect, ventricular septal defect with dilated right cavities, tricuspid valve regurgitation, pulmonary valve stenosis; and the aorta exits in the right ventricle. There is a widening of the subdural space, which was observed in the left frontal-parietal side with cortical atrophy in that area and a widening of the Sylvian fissure. A karyotype test confirmed the presence of Edward and Klinefelter syndromes. Clinical discussion: Aneuploidy is a chromosomal issue characterized by an abnormal number of a chromosome copies. The coexistence of two aneuploidies is called “double aneuploidy” which is a rare occurrence. Herein, we report a case of a 2-month-old male with Edward syndrome and Klinefelter syndrome. Conclusion: This publication aims to highlight the challenges in diagnosing and treating a complicated genetic disease.

Abstract Background Over the past decades, cytomegalovirus has stood out as one of the most common viruses to cause acute infection in kidney transplantation patients, especially during the first six months, noting that the causes of late and very late infection are still not sufficiently studied. Symptoms of cytomegalovirus infection range from asymptomatic to end-organ infection that may cause graft rejection, which makes it an important factor for investigation and further study. Cytomegalovirus infection showed an increase in the morbidity and mortality of patients in addition to life-threatening complications associated with hypercoagulability and deep vein thrombosis, such as pulmonary embolism. Case presentation A65-year-old man with a history of kidney transplant 15 years ago due to idiopathic chronic renal failure, hypertension, diabetes type 2, and ischemic heart disease presented to the emergency department with a complaint of fatigue and hematemesis. His vital signs were normal, and initial tests showed an increase in creatine numbers. An upper gastrointestinal endoscopy was performed, and a biopsy was taken from the superior side of the pylorus, which later revealed signs of chronic gastritis. A cytomegalovirus-polymerase chain reaction was made, which came back positive, and the patient was diagnosed with chronic cytomegalovirus gastritis and treated with ganciclovir. The patient was discharged later with no signs of deep venous thrombosis. Five days after the discharge, the patient was admitted with signs of deep venous thrombosis only in the right lower limb and, after a few days, developed superficial vein thrombosis in his right arm. He was treated for both and left to rest. Conclusion Cytomegalovirus can cause deep venous thrombosis through an unknown mechanism that needs to be studied and analyzed. It is important to note that there is only one case report in the medical literature similar to ours (33) to the best of our knowledge, which makes our case considered to be a very rare case. In addition, CMV infection is a predisposing factor for thrombosis that needs to be considered in kidney transplant patients. Therefore, physicians should be aware of this complication and consider using prophylactic anticoagulants for high-risk patients.

Introduction: The carotid artery rim sign on CTA is characterized by soft-plaque components surrounded by a rind of thin, adventitial calcification and its role in plaque instability is not established yet. Intraplaque hemorrhage (IPH) and the inflammatory microenvironment in carotid atheroma are considered features of atherosclerotic plaque vulnerability leading to cerebrovascular events. Hypothesis: The association between rim sign on CTA and carotid IPH and inflammation remains scantly investigated. In this study, we aimed to determine whether rim sign is associated with IPH on MRA and with the extent of IPH and inflammation on histology. We hypothesized that rim sign may be a radiological predictor of carotid IPH and inflammation. Methods: We retrospectively enrolled 100 consecutive patients who underwent carotid endarterectomy (CEA) and neck CTA before CEA. On CTA, the ipsilateral rim sign was defined as the presence of adventitial calcifications with internal soft-tissue plaque of ≥2 mm in maximum thickness. Of the included patients, 25 had MRA with 3D magnetization-prepared rapid acquisition with gradient echo (MPRAGE) sequence. Carotid plaque specimens were collected and stained with H&E to quantify IPH (%). Histologically, we defined IPH as an area of carotid plaque with blood elements, and inflammatory microenvironment as the presence of lymphocytes and plasma cells (chronic inflammation) and foam cells. Results: The rim sign on CTA was present in 56 (56%) of patients. IPH on MRA was present in 11 (44%) patients. The rim sign was significantly associated with the presence of IPH on MRA [9 (81.8%) vs 2 (14.3%); p=0.003]. On histology, the rim sign was associated with a higher extent of IPH [5.0 % (IQR 2.0-25.0) vs 5.0% (IQR 0.0-10.0); p=0.017], with chronic inflammation [44 (78.6%) vs 12 (21.4%); p=0.003], and foam cells [51 (91.1%) vs 5 (8.9%); p<0.001]. Conclusions: These findings suggest that rim sign on CTA may be proposed as a potential imaging marker of IPH as well as a histologic predictor of IPH extent and carotid plaque inflammatory microenvironment.

Atherosclerotic and high-risk plaques are predominantly localized to vessel wall regions with non-laminar disturbed blood flow (d-flow), leading to the principle that d-flow-, but not laminar flow (l-flow)-driven endothelial cells (EC) dysfunction plays a role in this process. LATS1/2 and YAP are components of the Hippo signaling pathway that are involved in cellular responses to l-flow. The l-flow-mediated inhibition of LATS1/2 activity triggers YAP activation and maintains vascular structure. However, the role of Hippo signaling under d-flow remains unclear. Although both l- and d-flow increased YAP activity, only d-flow decreased LATS1/2 expression. Since the effects of l- and d-flow on EC differ, we studied the role of EC LATS1/2 using EC-specific Lats1 and 2 knock-out (EKO) mice. Within 14 days after inducing Lats1/2 deletion in tamoxifen-inducible Lats1 homo / Lats2 homo EKO mice, all the mice (27/27) died of severe systemic edema, accompanied by increased EC apoptosis and vascular permeability. We generated Lats1 he t / Lats2 homo -EKO mice ( Lats1 het /2 homo -EKO) and induced hypercholesteremia with AAV8-PCSK9 injections and a high-fat diet (HFD). After HFD, we detected plaque erosion-like plaque lesions at the d-flow areas, which revealed strongly fibrin/fibrinogen-positive organized thrombus (OTh) formation without sizeable necrotic cores. In Lats1 het /2 homo -EKO, we found significant increases in 1) EC proliferation, 2) EC apoptosis with senescent phenotype, 3) tissue factor (TF) expression, and 4) inflammation. Therefore, the phenotype observed in Lats1 het /2 homo -EKO represents a unique senescence-associated stemness (SAS) phenotype, which allows EC to escape senescence-induced cell cycle arrest. The EC proliferation induced by depletion of LATS1/2 was YAP-dependent. In contrast, EC senescence induced by CD38-mediated NAD + depletion was YAP-independent. These findings indicate that downregulating LATS1/2 expression-induced SAS leads to OTh via both YAP-dependent and independent mechanisms. OTh plays a key role in human atherosclerosis but is rarely observed in the mouse atherosclerosis model. Lats1 het /2 homo -EKO can provide a valuable platform for studying the mechanism and unique role of EC SAS-induced OTh formation.

Background: The gap between electrocardiogram (ECG) artificial intelligence-derived age (ECG-Age) and chronological age (Age-Gap) predicts cardiovascular (CV) comorbidities and mortality reflecting physiologic age. Adverse childhood experiences (ACEs) are traumatic and harmful events that impact adulthood CV outcomes. We hypothesized that ACEs would be associated with physiologic age as determined by the Age-Gap. Methods: We applied a previously validated ECG-Age algorithm to the ECGs of 1,988 consecutive individuals aged ≥18, that within 2 years completed an ACEs questionnaire as part of psychological evaluations for weight management. The ACE questionnaire assesses 3 psychosocial domains (i) childhood abuse (psychological, physical or sexual), (ii) household dysfunction (substance abuse, mental illness, female figure treated violently, criminal behavior and parental separation/divorce) and (iii) neglect (emotional or physical) before age 18; results ranged 0 to 10 and were categorized as burden (0, 1-3, and ≥4) and presence (abuse, household dysfunction, neglect). Age-Gap was operationalized as (≤mean or > mean) positive values reflect physiological aging. Logistic regression analyses tested the association between ACE and Age-Gap. Results: Mean ± SD chronological age was 49±13 yr, ECG-Age 54±12 yr, Age-Gap 4.26±8.95 yr,75% women, average ACE 2±2, 32% experienced 0, 44% 1-3, and 24% ≥4 ACEs. Age-Gap was 1.4 years higher in those who experienced at least 1 ACE. Compared to those who didn’t experience ACE those who faced 1-3 ACE were more likely to have an Age-Gap >mean (OR 1.28 95%CI 1.57-1.04) independent of sex and the age-adjusted Charlson comorbidity index Fig A. Also, they were more prone to experiencing neglect and household dysfunction Fig B. Conclusions: Age-gap was associated with ACEs burden and domains, underscoring the need to identify ACEs during clinical evaluations to prevent ACEs at the individual, family, and community levels.

Introduction: Venoarterial extracorporeal membrane oxygenation (VA ECMO) provides full hemodynamic support for cardiogenic shock (CS), but optimal timing of ECMO initiation remains uncertain. Hypothesis: We hypothesized that earlier initiation of ECMO would be associated with improved survival in CS patients. Methods: We analyzed adult patients with CS who received VA ECMO from the Extracorporeal Life Support Organization (ELSO) Registry from 2009 - 2019, excluding those cannulated following an operation. Multivariable logistic regression evaluated the association between time from admission to ECMO initiation and in-hospital mortality. Results: Among 8619 patients (median 56.7 years; 33.5% females), the duration from admission to ECMO initiation was 14 (5, 32) hours. Patients who had ECMO initiated within 24 hours (n = 5882 [68.2%]) differed from those who had ECMO initiated after 24 hours, with younger age, more preceding cardiac arrest, and worse acidosis. After adjustment, patients with ECMO initiated more than 24 hours after admission had higher risk of adjusted in-hospital mortality (adjusted OR 1.20, 95% CI 1.06-1.36, p = 0.004) (Figure 1). Each 12-hour increase in the time from admission to ECMO initiation was incrementally associated with higher adjusted in-hospital mortality (adjusted OR 1.06, 95% CI 1.03-1.10, p < 0.001). The association between longer time to ECMO and worse outcomes appeared stronger in patients with lower shock severity. Among patients who were cannulated within 24 hours, those cannulated during the same day shift had lower mortality than those who were admitted at night and cannulated the following day (adjusted OR adjusted OR 0.81, 95% CI 0.66-0.99, p = 0.04). Conclusions: Longer delays from admission to ECMO initiation were associated with higher mortality in a large-scale, international registry. Our analysis supports optimization of door-to-support time and the avoidance of inappropriately delayed ECMO initiation.

Case: A 65-year-old patient presented 4 months after mitral valve repair (annuloplasty band, commissuroplasty, neo-chordae to the anterior mitral leaflet (AL)). At follow up, he developed significant hemolytic anemia (Hemoglobin 10.1g/dL, LDH 650U/L, Bilirubin 1.4mg/dL and haptoglobin<14 mg/dL). TEE revealed the substrate for hemolysis: moderate-severe mitral regurgitation (MR) starting at the coaptation of A2 and P2 scallops due to AL overriding the posterior (PL). The jet was then directed posteriorly to a small (3 x 6 mm confirmed by cardiac CT) area of annuloplasty band dehiscence at the base of the P2 scallop, with the band in direct path of the flow. The unique feature was that AL retained coaptation with the annuloplasty band, thus forming a small tunnel from the A2-P2 coaptation defect to the dehisced area. Given that redo surgery early after initial intervention would be challenging, the Heart Team decided to pursue percutaneous closure at the level of the dehisced annuloplasty to reduce regurgitation and mitigate hemolysis. Under 3D TEE guidance closure with a 12mm AVP plug was attempted but resulted in interference with PL motion with a new jet of regurgitation laterally. Using two 8mm AVP plugs was successful in closing the dehiscence with minimal impact on PL. Overall regurgitation was reduced to mild. Within a week hemolysis labs improved: LDH337 U/L, Bilirubin0.7 mg/dL. Discussion: Annuloplasty band dehiscence is a known cause of recurrent MR after repair. As regurgitation occurs at the leaflet coaptation zone, percutaneous closure of these defects is usually futile. In this patient we took advantage of the maintained coaptation between the AL and annuloplasty band.