Usefulness of cardiac screening in patients with systemic lupus erythematosus and anti-Ro/SSA antibodies.

OBJECTIVES: Recent data suggest that some adult patients with autoimmune rheumatic diseases may develop cardiac conduction and repolarization abnormalities mediated by anti-Ro/SSA antibodies. We aim to investigate the utility of a cardiac screening in patients with systemic lupus erythematous (SLE) and anti-Ro/SSA positivity. METHODS: SLE patients who consecutively attended a Rheumatology clinic during 1 year where evaluated for the presence and levels of anti-Ro/SSA antibodies, and clinical and biological markers of organ damage and disease activity. All participants underwent a cardiovascular anamnesis and physical examination, ECG, echocardiography, and 24-hour Holter. RESULTS: Of the 145 recruited patients, 49 (32%) had anti-Ro/SSA positivity. None had any degree of atrioventricular block in the ECG or Holter monitoring. No significant differences were observed between anti-Ro/SSA-positive vs. negative patients in terms of PR, QRS or QTc intervals. No clinically significant arrhythmias were recorded during Holter monitoring and no differences in average heart rate, heart rate variability, or atrial or ventricular ectopy burden were observed. Finally, no differences were found in echocardiographic measurements. CONCLUSIONS: In this study of SLE patients, anti-Ro/SSA positivity was not associated with significant alterations in ECG, echocardiography, or 24-hour Holter. These findings do not support ordinary cardiac evaluation in these patients. (Clinicaltrials.gov registration number: NCT02162992).

Malignant Arrhythmogenic Role Associated with RBM20: A Comprehensive Interpretation Focused on a Personalized Approach.

The RBM20 gene encodes the muscle-specific splicing factor RNA-binding motif 20, a regulator of heart-specific alternative splicing. Nearly 40 potentially deleterious variants in RBM20 have been reported in the last ten years, being found to be associated with highly arrhythmogenic events in familial dilated cardiomyopathy. Frequently, malignant arrhythmias can be a primary manifestation of disease. The early recognition of arrhythmic genotypes is crucial in avoiding lethal episodes, as it may have an impact on the adoption of personalized preventive measures. Our study performs a comprehensive update of data concerning rare variants in RBM20 that are associated with malignant arrhythmogenic phenotypes with a focus on personalized medicine.

Association Between Norepinephrine Levels and Abnormal Iron Status in Patients With Chronic Heart Failure: Is Iron Deficiency More Than a Comorbidity?

Background Mechanisms underlying iron homeostasis dysregulation in patients with chronic heart failure remain unsettled. In cardiomyocyte models, norepinephrine may lead to intracellular iron depletion, but the potential association between catecholamines (sympathetic activation markers) and iron metabolism biomarkers in chronic heart failure is unknown. Methods and Results In this cross-sectional analysis, we studied the association between plasma norepinephrine levels and serum iron status biomarkers indicating iron storage (ferritin), iron transport (transferrin saturation), and iron demand (soluble transferrin receptor) in a prospective cohort of 742 chronic heart failure patients (mean age, 72±11 years; 56% male). Impaired iron status was defined as ferritin <100 µg/L or transferrin saturation <20%. Impaired iron status was observed in 69% of patients. In multivariate models, greater norepinephrine levels were associated with impaired iron transport (transferrin saturation <20%, odds ratio=2.28; 95% CI [1.19-4.35]; P=0.013), but not with impaired iron storage (ferritin <100 µg/L, odds ratio=1.25; 95% CI [0.73-2.16]; P=0.415). Norepinephrine was a significant predictor of increased iron demand (soluble transferrin receptor, standardized ß-coefficient=0.12; P=0.006) and low transferrin saturation (standardized ß-coefficient=-0.12; P=0.003). However, norepinephrine levels were not associated with iron or ferritin levels ( P>0.05). Adjusted norepinephrine marginal means were significantly higher in patients with impaired iron status compared with those with normal iron status (528 pg/mL [505-551] versus 482 pg/mL [448-518], respectively; P=0.038). Conclusions In chronic heart failure patients, increased sympathetic activation estimated with norepinephrine levels is associated with impaired iron status and, particularly, dysregulation of biomarkers suggesting impaired iron transport and increased iron demand. Whether the relationship between norepinephrine and iron metabolism is bidirectional and entails causality need to be elucidated in future research.

Reduced levels of vasopressin, an independent mechanism in the obesity paradox in patients with chronic heart failure: Insights from the DAMOCLES study.

BACKGROUND: An "obesity paradox" has been described in patients with chronic heart failure (CHF), obese patients having a better survival. Vasopressin is elevated in patients with CHF, and higher levels are associated with worsening severity of the disease. We aimed at evaluating the relationship between body mass index (BMI), obesity (BMI ≥30 kg/m2), and vasopressin in patients with CHF, as well as the prognostic implications of vasopressin across the full spectrum of BMI values. METHODS: We included 1132 consecutive CHF patients referred to a multidisciplinary CHF unit. BMI and vasopressin levels were measured at baseline, and their association was evaluated using multivariable linear and logistic regression models. Death was evaluated after a median follow-up of 2.93 years and using Cox regression analyses. RESULTS: Mean age was 73 years, 43% women, mean BMI 28 kg/m2. Vasopressin levels were independently associated with all-cause death across the whole spectrum of BMI values, and were significantly lower in obese as compared to non-obese patients (median adjusted estimated levels of log-vasopressin in obese patients 2.57 [95% CI 1.5-3.67], in non-obese patients 3.16 [95% CI 2.11-4.23]; p < 0.001). Also, the higher the BMI, the lower the vasopressin levels, at least for patients with BMI <35 kg/m2. Subgroup analyses stratifying by left ventricle ejection fraction and sensitivity analyses further adjusting for norepinephrin levels yielded similar findings. CONCLUSIONS: Reduced levels of vasopressin may represent an independent mechanism in the survival paradox in obese patients with CHF. Studies including larger samples of patients BMI ≥35 kg/m2 are needed.