Empagliflozin and Dapagliflozin Therapies Favorably Alter QRS-T Angle and Cardiac Repolarization Parameters in Patients with Heart Failure.

Recent randomized clinical trials demonstrated that treatment with sodium-glucose cotransporter-2 inhibitors (SGLT2is) reduces the risk of cardiac mortality due to sudden cardiac death and progressive pump failure in patients with heart failure (HF). Mechanisms underlying the potential anti-arrhythmic effects of SGLT2is are not well understood. We aimed to examine the effect of SGLT2i treatment on the frontal-plane QRS-T (f[QRS-T]) angle, a novel marker of myocardial repolarization and an independent predictor of adverse cardiac outcomes. The study included 106 patients with HF with reduced ejection fraction (HFrEF) who received an SGLT2i, empagliflozin, or dapagliflozin. All study participants underwent screening 12-lead electrocardiography (ECG) before and ∼90 days after treatment. We compared ECG repolarization parameters before and after treatment. During study enrollment, there were statistically significant decreases in the Tp-e/QT ratio (P ≤ .0001), Tp-e/corrected QT ratio (P = .0002), Tp-e interval (P < .0001), and f(QRS-T) angle (P = .04) in response to SGLT2i therapy. In addition, study participants experienced an improvement in functional capacity (2.06 ± 0.6 vs. 1.82 ± 0.6, P = .0001) and reduced N-terminal pro-b-type natriuretic peptide values. In this retrospective cohort study, SGLT2i therapy was associated with improved cardiac repolarization parameters in patients with HFrEF. More comprehensive studies are needed to evaluate the impact of SGLT2i on cardiac repolarization and its potential relation to cardiac arrhythmia and sudden cardiac death risk.

Microcystic lymphatic malformations in Turner syndrome are due to somatic mosaicism of PIK3CA.

Turner syndrome (45,X) is caused by a complete or partial absence of a single X chromosome. Vascular malformations occur due to abnormal development of blood and/or lymphatic vessels. They arise from either somatic or germline pathogenic variants in the genes regulating growth and apoptosis of vascular channels. Aortic abnormalities are a common, known vascular anomaly of Turner syndrome. However, previous studies have described other vascular malformations as a rare feature of Turner syndrome and suggested that vascular abnormalities in individuals with Turner syndrome may be more generalized. In this study, we describe two individuals with co-occurrence of Turner syndrome and vascular malformations with a lymphatic component. In these individuals, genetic testing of the lesional tissue revealed a somatic pathogenic variant in PIK3CA-a known and common cause of lymphatic malformations. Based on this finding, we conclude that the vascular malformations presented here and likely those previously in the literature are not a rare part of the clinical spectrum of Turner syndrome, but rather a separate clinical entity that may or may not co-occur in individuals with Turner syndrome.

Genomic profiling informs diagnoses and treatment in vascular anomalies.

Vascular anomalies are malformations or tumors of the blood or lymphatic vasculature and can be life-threatening. Although molecularly targeted therapies can be life-saving, identification of the molecular etiology is often impeded by lack of accessibility to affected tissue samples, mosaicism or insufficient sequencing depth. In a cohort of 356 participants with vascular anomalies, including 104 with primary complex lymphatic anomalies (pCLAs), DNA from CD31+ cells isolated from lymphatic fluid or cell-free DNA from lymphatic fluid or plasma underwent ultra-deep sequencing thereby uncovering pathogenic somatic variants down to a variant allele fraction of 0.15%. A molecular diagnosis, including previously undescribed genetic causes, was obtained in 41% of participants with pCLAs and 72% of participants with other vascular malformations, leading to a new medical therapy for 63% (43/69) of participants and resulting in improvement in 63% (35/55) of participants on therapy. Taken together, these data support the development of liquid biopsy-based diagnostic techniques to identify previously undescribed genotype-phenotype associations and guide medical therapy in individuals with vascular anomalies.

Mosaic pathogenic variants in AKT3 cause capillary malformation and undergrowth.

Capillary malformations are slow-flow vascular malformations that affect the microcirculation including capillaries and post capillary venules and can be associated with growth differences. Specifically, the association of capillary malformations with undergrowth is a vastly understudied vascular syndrome with few reports of genetic causes including PIK3CA, GNAQ, and GNA11. Recently, a somatic pathogenic variant in AKT3 was identified in one child with a cutaneous vascular syndrome similar to cutis marmorata telangiectatica congenita, undergrowth, and no neurodevelopmental features. Here, we present a male patient with a capillary malformation and undergrowth due to a somatic pathogenic variant in AKT3 to confirm this association. It is essential to consider that mosaic pathogenic variants in AKT3 can cause a wide spectrum of disease. There is a need for future studies focusing on capillary malformations with undergrowth to understand the underlying mechanism.

Allergic Polysensitization Clusters: Newly Recognized Severity Marker in Urban Asthmatic Adults.

INTRODUCTION: While reliable, quantitative in vitro testing for sensitivity to aeroallergens has been available for decades, such information has largely been ignored in clustering analyses of asthma. Our aim is to explore allergic polysensitization as a possible marker of asthma severity and, as such, to be considered as an integral marker in future asthma clustering analyses. METHODS: We constructed a database of sensitizations to the 25 aeroallergens in our geographic area (zone 1, Northeastern US) using the ImmunoCAP® in vitro assay. We used the Scikit-Learn® machine learning library for model-based clustering to identify allergic polysensitization clusters. Clusters were compared for differences in common office-based clinical markers of asthma. RESULTS: The database consisted of 509 patients. Unbiased machine learning identified ten clusters of increasing allergic polysensitization of varying sizes (n = 1-339) characterized by significant increases in mean serum immunoglobulin E (p < 0.001), peripheral blood eosinophil count (p < 0.001), and DLCO (p = 0.02). There was a significant decline in mean age at presentation (p < 0.001), FEV1/FVC (p = 0.01), and FEF25-75 (p = 0.002) with increasing allergic polysensitization. Finally, we identified two divergent paths for the poly-atopic march, one driven by perennial and the other by seasonal allergens. CONCLUSION: This pilot study showed that allergic polysensitization, using readily available qualitative and quantitative in vitro sensitization data, largely ignored in cluster analyses to date, may add further clinical precision in cluster analyses of asthma. We suggest the methods used here can be applied and tested using larger databases and aeroallergens present in diverse geographic regions.

Multicompartment Dynamic Contrast Magnetic Resonance Lymphangiography in Diagnosis of Complicated Lymphatic Anomaly.

Background: To describe the dynamic contrast magnetic resonance lymphangiography (DCMRL) findings of three patients with complicated lymphatic anomaly (CLA) and protein losing enteropathy. We further discuss the importance of a multicompartment (intrahepatic [IH], intramesenteric [IM], and intranodal [IN]) DCMRL in delineating central lymphatic flow pathologies. Methods and Results: This is a retrospective study of three patients-one adult and two children who individually underwent the three-compartment DCMRL, namely IN-DCMRL, IH-DCMRL, and IM-DCMCRL. Findings from the results of the DCMRL for these three patients were obtained from the medical records and compared. Using the multicompartment imaging modalities, chylous fluid leakage into the peritoneum was observed using IM-DCMRL and IH-DCMRL but not IN-DCMRL for one of the patients in the case series. In contrast, leakage of chyle into the mediastinum was noted using IN-DCMRL but not IH-DCMRL and IM-DCMRL on another patient in this case series. Conclusion: Owing to the variability in outlining lymphatic flow pathologies, multicompartment imaging gives a more global picture of individual conduction disorders, has the potential to improve clinical assessment, and in some cases leads to a diagnosis of the abnormality and thus provides a better understanding of lymphatic flow anomalies in patients with CLAs.

Percutaneous Coronary Intervention Outcomes Among Patients With Alcoholic Cardiomyopathy: An Analysis of the National Inpatient Sample.

Introduction High consumption of alcohol has an enormous toll on the health status of individuals. A direct affectation of cardiac integrity concerns cardiologists, primary care physicians, and the healthcare system because this increases the disease burden. Alcoholic cardiomyopathy (ACM) results from the enormous consumption of alcohol over a long period of time. The prevalence varies between regions and sex and ranges between 4% and 40%. Viewing the entire spectrum of cardiomyopathies, ACM makes up about 4% of all cardiomyopathies. However, it causes dilated-type cardiomyopathy and is the second most common cause of dilated cardiomyopathy. We sought to explore the outcomes of percutaneous coronary intervention (PCI) among patients with ACM. Methods This was a retrospective, cross-sectional study of the National Inpatient Sample (NIS) for hospital discharges in the United States between 2012 and 2014. We identified the number of patients with a primary or secondary diagnosis of ACM using the International Classification of Diseases, Ninth Revision (ICD-9) code of 4.255. Using the ICD-9 codes for PCI (00.66, 36.01, 36.02, 36.05, 36.06, 36.07, and 17.55), we identified patients diagnosed with ACM who underwent a PCI (ACPCI). The racial and sexual prevalence, hospital length of stay (LOS), mortality, cost of hospitalization, and cardiovascular outcomes (ventricular fibrillation (VF) and atrial fibrillation (AF)) were compared between patients with and without ACM who underwent a PCI. Results A total of 2,488,293 PCIs were performed between 2012 and 2014. Of these, there were a total of 161 admissions for ACM. About 93% (151) of the ACM PCI group were men. Ethnic distribution revealed a majority of Caucasians with 69% (98), and blacks and Asians at 13.4% (19) and 11.3% (16), respectively. The mean age was 59.8 (SD = 9). The patients with ACPCI were likely to stay longer in the hospital, with an average stay of 6.6 days (SD = 6.2) compared to patients without ACM undergoing PCI (NOACPCI) (3.7 days; SD = 5.0) (p = 0.0001). The mean cost of hospital admission for patients with ACPCI was $120,225 (SD = 101,044), while that of those without ACM who underwent PCI (NOACPCI) was $87,936 (SD = 83,947) (p = 0.0001). A higher death rate during hospitalization (3.7%) was recorded in the ACPCI category vs. 2.3% in patients without ACM who underwent PCI (p = 0.0001). Patients with ACPCI had a higher prevalence of AF (30.4%) than VF (7.5%). Conclusion The ACPCI group had overall poorer hospital outcomes. The majority affected were older Caucasian men with an increased prevalence of AF, higher cost of hospitalization, and longer hospital stays. Further studies are needed to explore the burden of long-term alcohol consumption on cardiovascular disease treatment outcomes.

Gallbladder Disease and Risk of Type 2 Diabetes in Postmenopausal Women: A Women's Health Initiative Study.

Studies have suggested that adults with gallbladder disease have increased risk of type 2 diabetes. This prospective cohort study assessed the risk of type 2 diabetes in postmenopausal women with gallbladder disease. Data from women enrolled in the Women's Health Initiative from 1993 to 2005, aged 50-79 years (mean = 63.2; standard deviation, 7.2), were analyzed. Cox proportional hazards regression models were used to estimate the risk of type 2 diabetes associated with gallbladder disease. There were 8,896 new cases of type 2 diabetes after 1,025,486 person-years of follow-up. Gallbladder disease was significantly associated with type 2 diabetes (hazard ratio = 1.52; 95% confidence interval (CI): 1.38,1.67). The observed risk of type 2 diabetes in women with both gallbladder disease and central obesity was 37% higher than expected (relative excess risk due to interaction = 0.37, 95% CI: 0.11,0.63) on the additive scale. The hazard ratios for type 2 diabetes associated with gallbladder disease were 1.25 (95% CI: 1.19,1.32) and 1.48 (95% CI: 1.34,1.63) in women with and without central obesity, respectively, on the multiplicative scale. Results of this study support further studies to determine whether interventions in older women with gallbladder disease would reduce type 2 diabetes risk, especially among those with central obesity. Future research should examine the pathophysiological basis of the association between gallbladder disease and type 2 diabetes.

Sleep Deprivation Is Associated With Increased Risk for Hypertensive Heart Disease: A Nationwide Population-Based Cohort Study.

BACKGROUND: Literature documenting the in-hospital cardiovascular outcomes of sleep deprivation (SD) patients is scarce. We aimed to compare inpatient cardiovascular outcomes in patients with sleep deprivation and those without sleep deprivation. METHOD: We queried the National Inpatient Sample (NIS) database from 2016 to 2019 to conduct a retrospective observational study. Using the International Classification of Diseases, Tenth Revision (ICD-10) codes, we identified patients with sleep deprivation (SD) diagnosis and compared them to their counterparts without sleep deprivation (NSD). The cardiovascular outcomes of interest were hypertensive heart disease (HHD), atrial fibrillation (AF), and ST-segment and non-ST-segment elevation myocardial infarction (STEMI and NSTEMI, respectively). We used multivariable regression analysis to unearth the relationship between sleep deprivation and cardiovascular disease. RESULTS: There were 28,484,087 patients admitted during the study period, among which 2.1% (6,08,059) with a mean age of 59 (sd=19) years had a sleep deprivation diagnosis unrelated to medical or psychiatric illness. Of these, 75.7% were Caucasians, 11.5% were Blacks, and 8% were Hispanics. Individuals with sleep deprivation had a higher odds ratio (OR) of HHD, i.e., OR=1.3 (1.29-1.31), p<0.0001. The odds of heart failure with reduced ejection fraction (HFrEF) was 0.9 (0.9-1.92), p=0.45; heart failure with preserved ejection fraction (HFpEF) was 0.98 (0.97-1.01), p=0.31; and the odds of the SD population for AF was 0.9 (0.89-1.03), p=0.11. CONCLUSION: Sleep deprivation seems to be more prevalent in the Caucasian population. Individuals with sleep deprivation have a higher risk of hypertensive heart disease but similar outcomes to the general population in terms of AF, HFrEF, and HFpEF.

Misdiagnosis of capillary malformations in darker skin phototypes.

In the dermatologic medical literature, there is an underrepresentation of conditions in individuals of color. Due to the lack of representation, it may be harder for clinicians to recognize certain diagnoses in patients with darker skin phototypes leading to misdiagnosis and affecting overall patient management, outcomes, and satisfaction. Here, we present four Black or Indigenous People of Color who were initially referred for hyperpigmentation, hemihyperplasia, or café au lait spots and found to have syndromic capillary malformations.

Occupations Associated With Poor Cardiovascular Health in Women: The Women's Health Initiative Observational Study.

INTRODUCTION: Research on the effect of occupation on cardiovascular health (CVH) among older women is limited. METHODS: Each of the seven American Heart Association's CVH metrics was scored as ideal (1) or non-ideal (0) and summed. Multivariable logistic regression was used to estimate the odds of poor overall CVH (CVH score of 0 to 2) comparing women employed in each of the top 20 occupational categories to those not employed in that category, adjusting for age, marital status, and race/ethnicity. RESULTS: (1) Bookkeeping, accounting, and auditing clerks; (2) first-line supervisors of sales workers; (3) first-line supervisors of office and administrative support workers; and (4) nursing, psychiatric, and home health aides were more likely to have poor overall CVH compared to women who did not work in these occupations. CONCLUSIONS: Several commonly held occupations among women were associated with poor CVH.

Occupations Associated with Poor Cardiovascular Health in Women: The Women's Health Initiative Observational Study.

INTRODUCTION: Research on the effect of occupation on cardiovascular health (CVH) among older women is limited. METHODS: Each of the 7 American Heart Association's CVH metrics was scored as ideal (1) or non-ideal (0) and summed. Multivariable logistic regression was used to estimate the odds of poor overall CVH (CVH score of 0-2) comparing women employed in each of the top 20 occupational categories to those not employed in that category, adjusting for age, marital status, and race/ethnicity. RESULTS: 1) Bookkeeping, accounting, and auditing clerks; 2) first-line supervisors of sales workers; 3) first-line supervisors of office and administrative support workers; and 4) nursing, psychiatric, and home health aides were more likely to have poor overall CVH compared to women who did not work in these occupations. CONCLUSIONS: Several commonly held occupations among women were associated with poor CVH.