Hypertension and Brachydactyly Syndrome: Genetic Insights and a Novel Presentation.

Phosphodiesterase 3A (PDE3A) gene mutations have recently been associated with hypertension and brachydactyly syndrome (HTNB). This report shows how the recent recognition of the role of the PDE3A gene in HTNB facilitated the diagnosis of HTNB in a 20-year-old female who could not be diagnosed at her initial presentation at 6 years of age.

Carpal Tunnel Syndrome and Transthyretin Amyloidosis in the All of Us Research Program.

OBJECTIVE: To evaluate the association of carpal tunnel syndrome (CTS) with incident heart failure and incident amyloidosis and to assess the risk of CTS in pathogenic TTR genetic variant carriers. METHODS: This prospective cohort study included multiethnic US adults 18 years of age and older without prevalent heart failure and amyloidosis with available genotypic data from the All of Us Research Program. The primary outcomes were incident heart failure and incident amyloidosis. The association of incident heart failure and incident amyloidosis with CTS was assessed using multivariable adjusted Cox models accounting for age, sex, race and ethnicity, obesity, hypertension, diabetes, statin use, and smoking status. RESULTS: Of the 166,987 individuals included, the median age was 54 (38 to 66) years; 105,279 (63.0%) were female, and 92,780 (55.6%) were non-Hispanic White individuals; CTS was identified in 12,407 (7.4%) individuals. Compared with individuals without CTS, the adjusted hazard ratio for incident heart failure was 1.13 (95% CI, 1.02 to 1.26) in individuals with CTS. The risk of amyloidosis was ∼3-fold higher (adjusted hazard ratio, 2.86; 95% CI, 1.71 to 4.77) in individuals with CTS compared with those without CTS. Individuals carrying a pathogenic TTR variant had an approximately 40% higher risk (adjusted hazard ratio, 1.38; 95% CI, 1.16 to 1.65) for development of CTS compared with noncarriers. CONCLUSION: Cardiac amyloidosis screening programs may use CTS as a sentinel event and use genetic testing to identify individuals at a higher risk of TTR amyloidosis.

Trends of Lipid Concentrations, Awareness, Evaluation, and Treatment in Severe Dyslipidemia in US Adults.

OBJECTIVE: To evaluate the contemporary trends of lipid concentrations, cholesterol evaluation, hypercholesterolemia awareness, and statin use among individuals with severe dyslipidemia (low-density lipoprotein cholesterol [LDL-C] level ≥190 mg/dL) between 2011 and 2020. PATIENTS AND METHODS: This serial cross-sectional analysis included nonpregnant adults ≥20 years of age from the National Health and Nutrition Examination Survey between 2011 and 2020. Age-adjusted weighted trends of LDL-C, triglycerides, cholesterol evaluation in the past 5 years, hypercholesterolemia awareness, and documented statin use among individuals with severe dyslipidemia were estimated. RESULTS: Among 24,722 participants included, the prevalence of severe dyslipidemia was 5.4% (SE: 0.2%) which was stable across the study period (Ptrend=.78). Among individuals with severe dyslipidemia (mean age: 55.3 [SE: 0.7] years; 52.2% females; 68.8% non-Hispanic White), LDL-C (224.3 [SE: 4.2] mg/dL in 2011-2012 to 224.2 [SE: 4.6] mg/dL in 2017-2020; Ptrend =.83), and triglyceride (123.3 [SE: 1.1] mg/dL in 2011-2012 to 101.8 [SE: 1.1] mg/dL in 2017-2020; Ptrend=.13), levels remained stable from 2011 to 2020. The rates of cholesterol evaluation in the past 5 years (72.0% [SE: 5.7%] in 2011-2012 to 78.0% [SE: 4.8%] in 2017-2020; Ptrend=.91), hypercholesterolemia awareness (48.1% [SE: 5.5%] in 2011-2012 to 51.9% [SE: 5.8%] in 2017- 2020; Ptrend=.77), and documented statin use (34.7% [SE: 4.5%] in 2011-2012 to 33.4% [SE: 4.0%] in 2017-2020; Ptrend=.28) remained stagnant in individuals with severe dyslipidemia between 2011 and 2020. CONCLUSION: Among individuals with severe dyslipidemia, cholesterol evaluation and hypercholesterolemia awareness rates were stable at ∼75% and ∼50% in the past decade. Only ∼34% of individuals with severe dyslipidemia took statins between 2011 and 2020, which likely contributed to the stable LDL-C levels noted across the study period. Further investigations into the determinants of statin use and adherence to statins are needed.

Natriuretic Peptide Normative Levels and Deficiency: The National Health and Nutrition Examination Survey.

BACKGROUND: Natriuretic peptides (NPs) are hormones with a range of key functions vital for cardiometabolic health. However, the reference ranges of NPs and the prevalence of NP deficiency in the healthy United States population remains poorly defined. OBJECTIVES: This study aims to establish the reference range for N-terminal pro-B-type natriuretic peptide (NT-proBNP) values and to assess the prevalence of NP deficiency in a nationally representative healthy United States population. METHODS: Healthy participants with NT-proBNP measurements from the 1999-2004 National Health and Nutrition Examination Survey were included. Weighted multivariable-adjusted linear regression models were used to assess the adjusted percentage difference of NT-proBNP concentrations by sex and race and ethnicity. NP deficiency was defined as concentrations <2.5th percentile in the study cohort. RESULTS: Among 18,145 individuals (median age: 33.9 years [IQR: 17.1-49.0 years], 49.8% males, and 68.5% non-Hispanic White individuals), females had similar NT-proBNP concentrations in the 1-10 years group (4.2% [95% CI: -3.3% to 12.2%]), and highest differences in the 20-30 years group (150.5% [95% CI: 123.5%-180.8%]) compared with males in their respective age groups. Compared with non-Hispanic White individuals, non-Hispanic Black individuals had lower NT-proBNP concentrations in the 1- to 10-years group (19.6% [95% CI: 10.7%-27.6%]), and these differences were most pronounced in the 30-40 years group (40.2% [95% CI: 33.7%-46.0%]). An estimated 9.1 million United States individuals had NP deficiency. NP deficiency was associated with a higher risk of cardiometabolic diseases such as hypertension, dyslipidemia, obesity, and insulin resistance. CONCLUSIONS: This study establishes the normative NP concentrations across the lifespan of a healthy United States population.

Incident Heart Failure Risk Reclassification With Race-Independent Estimated Glomerular Filtration Rate: A National Heart, Lung, and Blood Institute Pooled Cohorts Analysis.

BACKGROUND: This study compared the predictive value of the race-independent creatinine- and cystatin C-based estimated glomerular filtration rate (eGFRcr-cys) and the race-dependent creatinine-based eGFR (eGFRcr) for incident heart failure (HF). METHODS: This study combined the participant-level data from ARIC (Atherosclerosis Risk in Communities) (visit 4) and MESA (Multi-Ethnic Study of Atherosclerosis) (visit 1) to calculate eGFRcr-cys and eGFRcr. The primary outcome of the study was adjudicated incident HF over a follow-up period of 10 years. Multivariable Cox models were used to assess the risk of incident HF with the quartiles of eGFRcr-cys and eGFRcr. RESULTS: Among 15,615 individuals (median age: 62 [57-68] years; 55.0% females; 23.9% Black), the median eGFRcr-cys and eGFRcr were 91.4 (79.4, 102.0) mL/min/1.73m2 and 84.7 (72.0, 94.7) mL/min/1.73m2, respectively. Compared with the fourth quartile of eGFRcr-cys, the hazard ratio for incident HF was 1.02 (95% CI:0.80-1.30) in the third quartile, 1.02 (95% CI:0.80-1.30) in the second quartile, and 1.47 (95% CI:1.16-1.86) in the first quartile. Compared with the 4th quartile of the eGFRcr, the risk of incident HF was similar in the 3rd (HRadj:0.90 [95% CI:0.73-1.12]), 2nd (HRadj: 0.96 [95% CI:0.77-1.20]), and 1st (HRadj:1.15 [95% CI:0.93-1.44]) quartiles. C-statistics were similar for the multivariable-adjusted Cox models for incident HF using eGFRcr (0.80 [0.79-0.81]) and eGFRcr-cys (0.80 [0.79-0.82]). CONCLUSION: The eGFRcr and eGFRcr-cys had comparable predictive values for incident HF.

High-Dose Inhaled Nitric Oxide in Acute Hypoxemic Respiratory Failure Due to COVID-19: A Multicenter Phase II Trial.

Rationale: The effects of high-dose inhaled nitric oxide on hypoxemia in coronavirus disease (COVID-19) acute respiratory failure are unknown. Objectives: The primary outcome was the change in arterial oxygenation (PaO2/FiO2) at 48 hours. The secondary outcomes included: time to reach a PaO2/FiO2.300mmHg for at least 24 hours, the proportion of participants with a PaO2/FiO2.300mmHg at 28 days, and survival at 28 and at 90 days. Methods: Mechanically ventilated adults with COVID-19 pneumonia were enrolled in a phase II, multicenter, single-blind, randomized controlled parallel-arm trial. Participants in the intervention arm received inhaled nitric oxide at 80 ppm for 48 hours, compared with the control group receiving usual care (without placebo). Measurements and Main Results: A total of 193 participants were included in the modified intention-to-treat analysis. The mean change in PaO2/FiO2 ratio at 48 hours was 28.3mmHg in the intervention group and 21.4mmHg in the control group (mean difference, 39.1mmHg; 95% credible interval [CrI], 18.1 to 60.3). The mean time to reach a PaO2/FiO2.300mmHg in the interventional group was 8.7 days, compared with 8.4 days for the control group (mean difference, 0.44; 95% CrI, 23.63 to 4.53). At 28 days, the proportion of participants attaining a PaO2/FiO2.300mmHg was 27.7% in the inhaled nitric oxide group and 17.2% in the control subjects (risk ratio, 2.03; 95% CrI, 1.11 to 3.86). Duration of ventilation and mortality at 28 and 90 days did not differ. No serious adverse events were reported. Conclusions: The use of high-dose inhaled nitric oxide resulted in an improvement of PaO2/FiO2 at 48 hours compared with usual care in adults with acute hypoxemic respiratory failure due to COVID-19.

Trends of cardiovascular health in Asian American individuals: A national health and nutrition examination survey study.

Objective: Oversampling of Asian American individuals in the National Health and Nutrition Examination Survey (NHANES) provides a unique opportunity to assess the population-level cardiovascular health (CVH) in the fastest-growing racial group in the US. Methods: The Life's Essential 8 (LE8) score and its components were calculated in self-reported Asian American individuals ≥20 years of age and free of cardiovascular disease in the NHANES cycles from 2011-March 2020. Multivariable adjusted linear and logistic regression models were used for analysis. Results: Among 2,059 Asian American individuals, the weighted mean LE8 score was 69.1 (0.4) with US-born [69.0 (0.8)] and foreign-born individuals [69.1 (0.4)] having similar CVH. From 2011 to March 2020, CVH in the overall population [69.7 (0.8) to 68.1 (0.8); Ptrend: 0.009] and foreign-born individuals [69.7 (0.8) to 67.7 (0.8); Ptrend: 0.005] declined. Decreasing trends were noted in the body mass index score irrespective of stratification and in the blood pressure scores in the overall population and foreign-born Asian American individuals. Compared with US-born individuals, the odds of ideal levels of smoking [ORadj:<5 years: 2.23 (95%CI: 1.45-3.44); 5-15 years: 1.97 (95%CI: 1.27-3.05); 15-30 years: 1.61 (95%CI: 1.11-2.34); ≥30 years: 1.69(95%CI:1.20-2.36)] and diet [ORadj: <5 years: 1.87 (95%CI: 1.26-2.79); 5-15 years: 2.00 (95%CI: 1.38-2.89); 15-30 years: 1.74 (95%CI: 1.14-2.68)] were higher in foreign-born individuals. Foreign-born individuals had lower odds of ideal physical activity levels [ORadj: 5-15 years: 0.55 (95%CI: 0.39-0.79); 15-30 years: 0.68 (95%CI: 0.49-0.95)] and ideal cholesterol levels [ORadj: 5-15 years: 0.59 (95%CI: 0.42-0.82); 15-30 years: 0.54 (95%CI :0.38-0.76); ≥30 years: 0.52 (95%CI: 0.38-0.76)]. Conclusion: The CVH in Asian American individuals declined from 2011 to March 2020. The odds of ideal CVH decreased with increasing duration of stay in the US, with foreign-born individuals residing in the US for ≥30 years having ∼28% lower odds of ideal CVH compared with US-born individuals.

Sex-Associated Differences in the Clinical Outcomes of Left Ventricular Assist Device Recipients: Insights From Interagency Registry for Mechanically Assisted Circulatory Support.

BACKGROUND: Sex-associated differences in clinical outcomes among left ventricular assist device recipients in the United States have been recognized. However, an investigation of the social and clinical determinants of sex-associated differences is lacking. METHODS: Left ventricular assist device receiving patients enrolled in Interagency Registry for Mechanically Assisted Circulatory Support between 2005 and 2017 were included. The primary outcome was all-cause mortality. Secondary outcomes included heart transplantation and postimplantation adverse event rates. The cohort was stratified by the social subgroup of race and ethnicity (non-Hispanic White, non-Hispanic Black, non-Hispanic Asian, and Hispanic), and clinical subgroups of device strategy (destination therapy, bridge to transplant, and bridge to candidacy), and implantation center volume (low [≤20 implants/y], medium [21-30 implants/y], and high [>30 implants/y]). A multivariable-adjusted Cox proportional hazard model was used to assess the risk of death and heart transplantation with prespecified interaction testing. Poisson regression was used to estimate adverse events by sex across the various subgroups. RESULTS: Among 18 525 patients, there were 3968 (21.4%) females. Compared with their male counterparts, Hispanic (adjusted hazard ratio [HRadj], 1.75 [1.23-2.47]) females had the highest risk of death followed by non-Hispanic White females (HRadj, 1.15 [1.07-1.25]; Pinteraction=0.02). Hispanic (HRadj, 0.60 [0.40-0.89]) females had the lowest cumulative incidence of heart transplantation followed by non-Hispanic Black females (HRadj, 0.76 [0.67-0.86]), and non-Hispanic White females (HRadj, 0.88 [0.80-0.96]) compared with their male counterparts (Pinteraction<0.001). Compared with their male counterparts, females on the bridge to candidacy strategy (HRadj, 1.32 [1.18-1.48]) had the highest risk of death (Pinteraction=0.01). The risk of death (Pinteraction=0.44) and cumulative incidence of heart transplantation (Pinteraction=0.40) did not vary by sex in the center volume subgroup. A higher incidence rate of adverse events after left ventricular assist device implantation was also seen in females compared with the males, overall, and across all subgroups. CONCLUSIONS: Among left ventricular assist device recipients, the risk of death, the cumulative incidence of heart transplantation, and adverse events differ by sex across the social and clinical subgroups.

Vitamin D receptor genetic polymorphisms in severe and recurrent tuberculosis in children.

AIM: To analyze the genetic polymorphisms of vitamin D receptor FokI, TaqI, ApaI and BsmI gene polymorphisms in children with severe and recurrent tuberculosis (TB). METHODS: A prospective, observational study was conducted in 35 children with severe and recurrent TB referred to our Pediatric TB clinic at a tertiary referral center for children. The blood samples were analysed for genetic polymorphisms of Vitamin D receptor with respect to FokI, TaqI, ApaI and BsmI genotypes and their individual alleles and association of various clinical and laboratory parameters were analysed. RESULT: Ten (28.6%) children had recurrent TB and 26 (74.3%) had severe TB. The severity of TB was not associated with Ff and ff polymorphism of FokI (Odd's ratio 7.88) as compared to no FokI polymorphism. Absence of FokI polymorphism was associated with recurrent lymph node TB (Odds ratio 3.429). Presence of Tt polymorphism of TaqI (p = 0.04) and Fok1 Polymorphism [Odds ratio 7.88] were not associated with recurrent TB. CONCLUSION: Recurrent TB was absent in presence of Tt polymorphism of TaqI. Severe TB was not associated polymorphism of Vitamin D receptor polymorphisms.

AHA Life's essential 8 and ideal cardiovascular health among young adults.

Objective: This study assessed cardiovascular health (CVH) in young adults using the 2022 AHA Life's Essential 8 (LE8) score and compared it with the Life's Simple 7 (LS7) score. Methods: Individuals aged 18 to 44 years without a history of cardiovascular disease in the National Health and Nutrition Examination Survey (NHANES) cycles were included. Data from 2007-2008 to 2017-2018 were combined to create 3 groups (2007-2010, 2011-2014, and 2015-2018) for analysis. The LE8 score and its components were computed in the overall population and stratified by sex and race/ethnicity. Trends for the LE8 score were analyzed using adjusted linear regression models. Results: Among 12,197 young adults, representing an estimated 89.4 million individuals, from the NHANES 2007-2018, the CVH in the overall population and across all subgroups was stable (Ptrend >0.05). The blood lipid score improved across all subgroups (Ptrend:<0.05). The mean LE8 score was 69.2±0.3. Females (71.4±0.4) had better CVH compared with males (67.2±0.4). Non-Hispanic Black individuals (65.1± 0.3) had the lowest CVH compared with Non-Hispanic White individuals (69.9±0.5), Mexican American individuals (67.3±0.3), and other race individuals (71.2±0.4). Of the 46.1 million individuals categorized as intermediate CVH by the LS7 score, 8.1 million (17.6%) and 2.3 million (5.0%) were reclassified to poor and ideal CVH by the LE8 score, respectively. Of the 40.1 million individuals categorized as ideal CVH by the LS7 score, 18.9 million (47.1%) and 0.1 million (0.2%) were reclassified to poor CVH and intermediate CVH by the LE8 score, respectively. Conclusion: Among US young adults, there has been no improvement in CVH over the last decade with notable sex and race/ethnicity-associated differences in the LE8 score. Nearly 1 in 4 young adults had ideal CVH using the LE8 score compared with 1 in 2 individuals using the LS7 score.

Complications Associated With Transesophageal Echocardiography in Transcatheter Structural Cardiac Interventions.

BACKGROUND: Transesophageal echocardiograms (TEEs) performed during transcatheter structural cardiac interventions may result in greater complications than those performed in the nonoperative setting or even those performed during cardiac surgery. However, there are limited data on complications associated with TEE during these procedures. We evaluated the prevalence of major complications among these patients in the United States. METHODS: A retrospective cohort study was conducted using an electronic health record database (TriNetX Research Network) from large academic medical centers across the United States for patients undergoing TEE during transcatheter structural interventions from January 2012 to January 2022. Using the American Society of Echocardiography-endorsed International Statistical Classification of Diseases and Related Health Problems Clinical Modifications (10th edition) codes, patients undergoing TEE during a transcatheter structural cardiac intervention, including transaortic, mitral or tricuspid valve repair, left atrial appendage occlusion, atrial septal defect closure, patent foramen ovale closure, and paravalvular leak repair, were identified. The primary outcome was major complications within 72 hours of the procedure (composite of bleeding and esophageal and upper respiratory tract injury). The secondary aim was the frequency of major complications, death, or cardiac arrest within 72 hours in patients who completed intraoperative TEE during surgical valve replacement. RESULTS: Among 12,043 adult patients (mean age, 74 years old; 42% female) undergoing TEE for transcatheter structural cardiac interventions, 429 (3.6%) patients had a major complication. Complication frequency was higher in patients on anticoagulation or antiplatelet therapy compared with those not on therapy (3.9% vs 0.5%; risk ratio [RR] = 8.09, P < .001). Compared with those patients <65 years of age, patients ≥65 years of age had a higher frequency of major complications (3.9% vs 2.2%; RR = 1.75, P < .001). Complication frequency was similar among male and female patients (3.5% vs 3.7%; RR = 0.96, P = .67). Among 28,848 patients who completed surgical valve replacement with TEE guidance, 728 (2.5%) experienced a major complication. CONCLUSIONS: This study found that more than 3% of patients undergoing TEE during transcatheter structural cardiac interventions have a major complication, which is more common among those on anticoagulant or antiplatelet therapy or who are elderly. With a shift of poor surgical candidates to less invasive percutaneous procedures, the future of TEE-guided procedures relies on comprehensive risk discussion and updating practices beyond conventional methods to minimize risk for TEE-related complications.