Alabdaljabar, Mohamad S.

Introduction: Tricuspid regurgitation is a common echocardiographic finding leading to excess morbidity and mortality in adult population. Hypothesis: Racial and ethnic disparities have been observed in various cardiovascular disorders’ prevalence and natural course, including valvular lesions. However, little is known about the epidemiology and clinical correlations of TR among non-Hispanic Black adults. Methods: To examine risk factors and clinical outcomes in non-Hispanic Black adults with moderate or more severe TR, 685 patients (7%) self-identified as non-Hispanic Black and 9127 (93%) self-identified as non-Hispanic White with a first echocardiographic report of moderate or more severe TR between 2005-2016 were studied. Results: Non-Hispanic Black patients had more severe TR when compared to white patients (25% vs. 20%, p<0.001). After adjusting for age and sex, non-Hispanic Black patients had significantly higher 10-year all-cause mortality (HR=1.34 (1.18, 1.52), p<0.001). Black race remained a risk factor for all-cause mortality even after adjustment for comorbidities like CHF, COPD, DM, CKD, hypertension, and ischemic heart disease (HR=1.23 (1.08, 1.40), p=0.002). Conclusions: Significant racial disparities exist in demographic, clinical and echocardiographic characteristics between non-Hispanic Black and White patients with moderate or more severe TR. Black race is a potential disease modifier leading to excess mortality.

BACKGROUND: Alcohol septal ablation (ASA) is a minimally invasive treatment for drug-refractory obstructive hypertrophic cardiomyopathy. Detailed assessment of pressure changes and predictors of mortality and procedure success are not well defined. METHODS: This is a single-center study evaluating pressure changes and predictors of mortality and procedure success in transseptal ASA. Survival analysis and predictors of mortality were assessed using the Kaplan-Meier analysis and Cox regression, respectively. RESULTS: A total of 156 patients were included (mean age, 67.3 years; 46.8% women). Left atrial (LA) pressure and left ventricular outflow tract (LVOT) gradient decreased, whereas aortic pulse pressure (PP) increased post-ASA. Patients with lower baseline mean LA pressure (<median, 19 mm Hg), LVOT gradient reduction >82% (gradient change median), and PP increase >19% (PP change median) had superior survival. On Cox univariable regression, baseline mean LA pressure >median (19 mm Hg; hazard ratio [HR], 2.09 [95% CI, 1.05–4.18]; P =0.036), residual LVOT gradient (HR, 1.02 [95% CI, 1.01–1.03]; P =0.003), and LVOT gradient percent reduction <median (82%; HR, 2.92 [95% CI, 1.46–5.83]; P =0.002) were predictors of mortality. When adjusting for age and sex, baseline LA v wave >median (28 mm Hg; HR, 2.36 [95% CI, 1.17–4.76]; P =0.016), baseline mean LA pressure >median (19 mm Hg; HR, 2.70 [95% CI, 1.33–5.50]; P =0.006), percentage reduction in gradient <median (82%; HR, 2.74 [CI, 1.37–5.50]; P =0.005), and percentage increase in PP <median (19.3%; HR, 2.09 [CI, 1.05–4.16]; P =0.035) predicted survival free of all-cause mortality. CONCLUSIONS: ASA is associated with an acute decrease in the LVOT gradient and LA pressures and increase in aortic PP. Mean LA pressure, percentage decrease in LVOT gradient, and increase in PP are strong predictors of survival free of all-cause mortality following ASA and are important variables for procedural guidance.

Transcatheter valve replacement (TAVR) is a rapidly developing modality to treat patients with aortic stenosis (AS). Conduction disease post TAVR is one of the most frequent and serious complications experienced by patients. Multiple factors contribute to the risk of conduction disease, including AS and the severity of valve calcification, patients’ pre-existing conditions (i.e., conduction disease, anatomical variations, and short septum) in addition to procedure-related factors (e.g., self-expanding valves, implantation depth, valve-to-annulus ratio, and procedure technique). Detailed evaluation of risk profiles could allow us to better prevent, recognize, and treat this entity. Available evidence on management of conduction disease post TAVR is based on expert opinion and varies widely. Currently, conduction disease in TAVR patients is managed depending on patient risk, with minimal-to-no inpatient/outpatient observation, inpatient monitoring (24–48 h) followed by ambulatory monitoring, or either prolonged inpatient and outpatient monitoring or permanent pacemaker implantation. Herein, we review the incidence and risk factors of TAVR-associated conduction disease and discuss its management.

Abstract Aims Tricuspid valve regurgitation (TR) is a common valvular disease associated with increased mortality. There is a need for tools to assess the interaction between the pulmonary artery (PA) circulation and the right ventricle in patients with TR and to investigate their association with outcomes. The pulmonary artery pulsatility index (PAPi) has emerged as a haemodynamic risk predictor in left heart disease and pulmonary hypertension (PH). Whether PAPi discriminates risk in unselected patients with greater than or equal to moderate TR is unknown. Methods and results In 5079 patients with greater than or equal to moderate TR (regardless of aetiology) and PA systolic and diastolic pressures measured on their first echocardiogram, we compared all-cause mortality at 5 years based on the presence or absence of PH and PAPi levels. A total of 2741 (54%) patients had PH. The median PAPi was 3.0 (IQR 1.9, 4.4). Both the presence of PH and decreasing levels of PAPi were associated with larger right ventricles, worse right ventricular systolic function, higher NT-pro BNP levels, greater degrees of right heart failure, and worse survival. In a subset of patients who had an echo and right heart catheterization within 24 h, the correlation of non-invasive to invasive PA pressures and PAPi levels was very good (r = 0.76). Conclusion In patients with greater than or equal to moderate TR with and without PH, lower PAPi is associated with right ventricular dysfunction, right heart failure, and worse survival. Incorporating PA pressure and PAPi may help stratify disease severity in patients with greater than or equal to moderate TR regardless of aetiology.

Nephrotic syndrome (NS) is a kidney illness characterized by excessive proteinuria, hypoalbuminemia, edema, and hyperlipidemia, which may lead to kidney failure and necessitate renal transplantation. End-stage renal disease, cardiovascular issues, and mortality are much more common in those with NS. Therefore, the present study aimed to identify potential new biomarkers associated with the pathogenesis and diagnosis of NS. The liquid chromatography–mass spectrometry (LC–MS) metabolomics approach was applied to profile the metabolome of human serum of patients with NS. A total of 176 metabolites were significantly altered in NS compared to the control. Arginine, proline, and tryptophan metabolism; arginine, phenylalanine, tyrosine, and tryptophan biosynthesis were the most common metabolic pathways dysregulated in NS. Furthermore, alanyl-lysine and isoleucyl-threonine had the highest discrimination between NS and healthy groups. The candidate biomarkers may lead to understanding the possible metabolic alterations associated with NS and serve as potential diagnostic biomarkers.

AbstractThe number of non‐Hodgkin lymphoma (NHL) survivors is increasing. With the advancement of NHL therapies, it is crucial to focus on the challenges these survivors may face. Three main categories are to be considered in NHL survivorship, including quality of life and uncertainty about the future, possible physical health complications (including cardiovascular disease, infertility, and subsequent neoplasms), and the impact of novel NHL treatments and their potential complications. The latter includes CAR T‐cell therapy, monoclonal antibodies, checkpoint inhibitors, and hematopoietic stem cell transplantation. In this report, we aim to shed the light on these aspects and to discuss survivorship care plan for NHL.

In cardiomyocytes, the endoplasmic reticulum (ER) plays a dynamic role in excitation‐contraction coupling by regulating cytosolic Ca 2+ concentration ([Ca 2+ ] cyt ). Under pathological conditions the ER accumulates unfolded proteins triggering a homeostatic ER stress response to minimize and limit protein unfolding (via chaperone proteins) and accumulation (by decreasing synthesis and increasing degradation). The interactions between ER stress, [Ca 2+ ] cyt regulation and downstream contractile responses remain unknown, although such interactions may underlie the etiology of various cardiovascular diseases. We hypothesized that in cardiomyocytes ER stress alters the regulation of [Ca 2+ ] cyt and reduces cardiac contractility by decreasing myofilament Ca 2+ sensitivity. In isolated rat cardiomyocytes, ER stress was induced by tunicamycin, a naturally occurring antibiotic that induces ER stress by inhibiting N‐linked glycosylation. In one set of experiments, we used Western blotting techniques to evaluate the effects of ER stress on phosphorylation of cTnI at Ser23/24. In a second set of experiments, we evaluated the impact of tunicamycin on excitation‐contraction coupling by simultaneously measuring [Ca 2+ ] cyt (using Fura‐2 AM ratiometric imaging) and contractile (sarcomere length (SL) shortening) responses to electrical field stimulation using an IonOptix system. Tunicamycin induced an increase in phosphorylation of cTnI by 3–6 h. The evoked [Ca 2+ ] cyt transient was relatively unaffected by tunicamycin while the contractile response was markedly reduced. This resulted in a rightward shift in the phase loop relationship between [Ca 2+ ] cyt and SL shortening indicating reduced myofilament Ca 2+ sensitivity. We conclude that ER stress may underlie contractile dysfunction in a variety of cardiac diseases. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .