Efficacy and safety of a four-drug, quarter-dose treatment for hypertension: the QUARTET USA randomized trial.

New approaches are needed to lower blood pressure (BP) given persistently low control rates. QUARTET USA sought to evaluate the effect of four-drug, quarter-dose BP lowering combination in patients with hypertension. QUARTET USA was a randomized (1:1), double-blinded trial conducted in federally qualified health centers among adults with hypertension. Participants received either a quadpill of candesartan 2 mg, amlodipine 1.25 mg, indapamide 0.625 mg, and bisoprolol 2.5 mg or candesartan 8 mg for 12 weeks. If BP was >130/>80 mm Hg at 6 weeks in either arm, then participants received open label add-on amlodipine 5 mg. The primary outcome was mean change in systolic blood pressure (SBP) at 12 weeks, controlling for baseline BP. Secondary outcomes included mean change in diastolic blood pressure (DBP), and safety included serious adverse events, relevant adverse drug effects, and electrolyte abnormalities. Among 62 participants randomized between August 2019-May 2022 (n = 32 intervention, n = 30 control), mean (SD) age was 52 (11.5) years, 45% were female, 73% identified as Hispanic, and 18% identified as Black. Baseline mean (SD) SBP was 138.1 (11.2) mmHg, and baseline mean (SD) DBP was 84.3 (10.5) mmHg. In a modified intention-to-treat analysis, there was no significant difference in SBP (-4.8 mm Hg [95% CI: -10.8, 1.3, p = 0.123] and a -4.9 mmHg (95% CI: -8.6, -1.3, p = 0.009) greater mean DBP change in the intervention arm compared with the control arm at 12 weeks. Adverse events did not differ significantly between arms. The quadpill had a similar SBP and greater DBP lowering effect compared with candesartan 8 mg. Trial registration number: NCT03640312.

Evaluation of Primary Healthcare Centers' Service Availability and Readiness for Implementing Diabetes Care in Abuja, Nigeria: A Cross-Sectional, Formative Assessment.

Introduction: Noncommunicable diseases (NCDs) are associated with a high and rising burden of morbidity and mortality in sub-Saharan Africa, including Nigeria. Diabetes mellitus (DM) is among the leading causes of NCD-related deaths worldwide and is a foremost public health problem in Nigeria. As part of the National Multi-Sectoral Action Plan for the Prevention and Control of NCDs, Nigeria has committed to implementing the World Health Organization (WHO) Package of Essential NCD control interventions. Implementing the intervention requires the availability of essential elements, including guidelines, trained staff, health management information systems, equipment, and medications, in primary healthcare centers (PHCs). This study assessed the availability of the WHO package components and the readiness of PHCs to implement a DM screening, evaluation, and management program. Methods: This cross-sectional formative assessment adapted the WHO Service Availability and Readiness Assessment (SARA) tool to survey 30 PHCs selected by multistage sampling for readiness to deliver DM diagnosis and care in Abuja, Nigeria, between August 2021 and October 2021. The service availability and readiness indicator scores were calculated based on the proportion of PHCs with available DM care services, minimum staff requirement, diagnostic tests, equipment, medications, and national guidelines/protocols for DM care within the defined SARA domain. Results: All 30 PHCs reported the availability of at least two full-time staff (median [interquartile range] staff = 5 [4-9]), which were mostly community health extension workers (median [interquartile range]) = 3 [1-4]. At least one staff member was recently trained in DM care in only 11 (36%) of the PHCs. The study also reported high availability (100%) of paper-based health management information systems (HMIS) and DM screening services using a glucometer (87%), but low availability of DM treatment (23%), printed job aids (27%), and national guidelines/protocols (0%). Conclusion: This systematic assessment of PHCs' readiness to implement a DM screening, evaluation, and management program in Abuja demonstrated readiness to integrate DM care into PHCs in terms of equipment, paper-based HMIS, and nonphysician health workers' availability. However, strategies are needed to promote DM health workforce training, provide DM management guidelines, and ensure a reliable supply of essential DM medications.

Cardiac Structural and Functional Remodeling After Transcatheter Mitral Valve in Valve Implantation: Early Changes and Prognostic Significance.

Background: Transcatheter mitral valve-in-valve (MViV) replacement has emerged as an alternative to redo mitral valve (MV) surgery for the management of failed bioprosthetic MVs. The degree of cardiac remodeling assessed by echocardiography has been shown to have prognostic implications in degenerative mitral regurgitation patients undergoing MV surgery. The impact of transcatheter MViV in patients with degenerative bioprosthetic MV failure on cardiac remodeling and its associated prognosis remains undescribed. Objectives: The aim of this study is to describe the early anatomic and functional changes of the left-sided chambers and right ventricle by echocardiography posttranscatheter MViV intervention and their impact on mortality outcomes. Additionally, we sought to analyze the outcome of heart failure in bioprosthetic MV failure patients undergoing transcatheter MViV replacement. Methods: We analyzed consecutive patients undergoing MViV intervention for symptomatic bioprosthetic MV failure. Echocardiograms before intervention and within 100 days postintervention were analyzed. A chart review was performed to obtain baseline characteristics, follow-up visits, 30-day heart failure and 1-year all-cause mortality outcomes. Results: A total of 62 patients (mean age 69 ± 13 years, 61% male) were included in the study. Most patients were undergoing MViV intervention for prosthetic mitral stenosis n = 48 (77.4%) and the rest for mitral regurgitation or mixed disease. Compared with baseline, significant reductions were observed in median left atrial volume (LAV; 103 [81-129] ml vs. 95.2 [74.5-117.5] ml, p < 0.01) and mean (SD) left atrial conduit strain (9.1% ± 5.2% vs. 10.8% ± 4.8%, p = 0.039) within 100 days postintervention. Early reduction in right ventricular free wall global longitudinal strain and fractional area change also occurred postintervention. No significant change in left ventricular chamber dimensions or ejection fraction was observed. During the 1-year follow up period, 5 (8%) patients died. While baseline LAV was not associated with 1-year all-cause mortality (OR 0.98 CI 0.95-1.01; p = 0.27), a change in LAV in the follow up period was associated with all-cause mortality at 1 year (OR 1.06 CI 1.01-1.12; p = 0.023). At 30 days postintervention, 65% of patients had an improvement in their New York Heart Association functional class. Conclusion: In this retrospective study of patients undergoing transcatheter MViV intervention for failed bioprosthetic MVs, early reverse remodeling of the left atrium occurs within 100 days postintervention and reduction in LAV is associated with reduced all-cause mortality at 1 year. In addition, there is significant improvement in heart failure symptoms at 30 days following intervention but further investigation into the longitudinal remodeling changes and long-term outcomes is needed.

Interventions and contextual factors to improve retention in care for patients with hypertension in primary care: Hermeneutic systematic review.

BACKGROUND: Regular engagement over time in hypertension care, or retention, is a crucial but understudied step in optimizing patient outcomes. This systematic review leverages a hermeneutic methodology to identify, evaluate, and quantify the effects of interventions and contextual factors for improving retention for patients with hypertension. METHODS: We searched for articles that were published between 2000 and 2022 from multiple electronic databases, including MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, clinicaltrials.gov, and WHO International Trials Registry. We followed the latest version of the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guideline to report the findings for this review. We also synthesized the findings using a hermeneutic methodology for systematic reviews, which used an iterative process to review, integrate, analyze, and interpret evidence. RESULTS: From 4686 screened titles and abstracts, 18 unique studies from 9 countries were identified, including 10 (56%) randomized controlled trials (RCTs), 3 (17%) cluster RCTs, and 5 (28%) non-RCT studies. The number of participants ranged from 76 to 1562. The overall mean age range was 41-67 years, and the proportion of female participants ranged from 0% to 100%. Most (n = 17, 94%) studies used non-physician personnel to implement the proposed interventions. Fourteen studies (78%) implemented multilevel combinations of interventions. Education and training, team-based care, consultation, and Short Message Service reminders were the most common interventions tested. CONCLUSIONS: This review presents the most comprehensive findings on retention in hypertension care to date and fills the gaps in the literature, including the effectiveness of interventions, their components, and contextual factors. Adaptation of and implementing HIV care models, such differentiated service delivery, may be more effective and merit further study. REGISTRATION: CRD42021291368. PROTOCOL REGISTRATION: PROSPERO 2021 CRD42021291368. Available at: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=291368.

Myocardial strain is associated with adverse cardiac events in patients treated with chimeric antigen receptor (CAR) T-cell therapy.

BACKGROUND: Cardiovascular events, including heart failure and arrhythmias, following chimeric antigen receptor (CAR) T-cell therapy are increasingly recognized. Although global longitudinal strain (GLS) has demonstrated prognostic utility for other cancer therapy-related cardiac dysfunction, less is known regarding the association of GLS with adverse cardiac events following CAR T-cell therapy. OBJECTIVES: To determine the association of baseline GLS with adverse cardiovascular events in adults receiving CAR-T cell therapy. METHODS: Patients who had an echocardiogram within 6 months prior to receiving CAR T-cell therapy were retrospectively identified. Clinical data and cardiac events were collected via chart review. Echocardiograms were analyzed offline for GLS, left ventricular ejection fraction, and Doppler parameters. Multivariable logistic regression was used to determine the association between adverse cardiovascular events and echocardiographic parameters. RESULTS: Among 75 CAR T-cell therapy patients (mean age 63.9, 34.7% female), nine patients (12%) experienced cardiac events (CEs) including cardiovascular death, new/worsening heart failure, and new/worsening arrhythmia within 1 year of treatment. In univariable models, higher baseline GLS (OR 0.78 [0.63, 0.96], p = .021) was associated with a lower risk of CE and higher baseline mitral E/e' (OR 1.40 [1.08, 1.81], p = .012) was associated with a higher risk of CE. After adjusting for age and LDH, higher baseline GLS (OR 0.65 [0.48-0.88], p = <.01) was associated with a lower risk of CE and higher baseline mitral E/e' (OR 1.56 [1.06, 2.29], p = .024) was associated with a higher risk of CE. CONCLUSION: Lower GLS and higher mitral E/e' on a baseline echocardiogram were associated with higher risk for CEs in patients receiving CAR T-cell therapy.

The risk vs. benefit calculus of anticoagulation in patients with ibrutinib-related atrial fibrillation.

For ibrutinib-related atrial fibrillation (IRAF), guidelines for anticoagulation do not exist. We sought to describe stroke, bleeding, and anticoagulation rates among patients with IRAF. We performed a single-center retrospective review of 168 patients treated with ibrutinib followed from 2013 to 2022. Over a median follow-up of 6.4 years, 44 (26.0%) patients developed IRAF of which 38 (86.4%) had a CHA2DS2-VASc ≥2 and 7 (15.9%) had a HAS-BLED ≥3. Anticoagulation was initiated in 20 (45.5%) without a clear pattern in scores, risk factors, or cumulative dose, besides having another reason for anticoagulation. Few patients with IRAF developed non-hemorrhagic CVA (n = 3, 6.8%) or significant bleeding (n = 3, 6.8%). Among those with each adverse outcome, 2 in each group were anticoagulated and all were older than 65 years old. In conclusion, decisions for anticoagulation vary widely and patients who are elderly or with HTN may be most at risk for CVA or significant bleed.

Anticoagulation Bridging in Patients With Left Ventricular Assist Device: A Regional Analysis of HeartMate 3 Recipients.

Advances in left ventricular assist device technologies have led to an improvement in pump hemocompatibility and outcomes. Because of concerns of thromboembolic complications in prior generations of left ventricular assist devices, bridging with parenteral anticoagulants was routinely. Management strategies of subtherapeutic INRs and their effects on the current generation of devices deserve review. We performed analysis of the MOMENTUM 3 trial including 6 centers in the mid-America region. Patients with subtherapeutic INRs (INR < 2) occurring after the index admission underwent chart review to determine the management strategies taken by clinicians. Strategies were divided into two groups, bridging or nonbridging. Of the 225 patients included in the analysis, 130 (58%) patients had a total of 235 subtherapeutic international normalized ratio (INR) events. Most (n = 179, 76.2%) of these INRs were not bridged (n = 100 warfarin dose adjustment, n = 79 no change in warfarin dose). Among those INRs (n = 56, 23.8%) treated with bridging, approximately half (n = 30, 53.6%) were treated with subcutaneous agents and other half (n = 26, 46.4%) were treated with intravenous agents. There was no difference in individual outcomes or composite endpoints of death, rehospitalization, CVA, or bleeding events between the groups.

Process Evaluation of a Double-Blind Randomized Controlled Trial to Assess the Efficacy and Safety of a Quadruple Ultra-Low-Dose Treatment for Hypertension Within a Federally Qualified Health Center Network (QUARTET USA).

BACKGROUND: This convergent parallel-design mixed-methods process evaluation of the QUARTET USA (Quadruple Ultra-Low-Dose Treatment for Hypertension USA) clinical trial (NCT03640312) explores patient and health care professional perceptions about the use of low-dose quadruple therapy (LDQT) as a novel strategy for hypertension management. METHODS AND RESULTS: A survey of all 62 patients enrolled in the QUARTET USA trial was conducted. A subsample of 13 patients and 11 health care professionals, recruited via purposive sampling, took part in semistructured interviews. At enrollment, 68% of participants (mean [SD] age, 51.7 [11.5] years; 56% self-identified as Hispanic: Mexican ethnicity, 16% as Hispanic: other ethnicity, 16% as Black race, 8% as White race, and 1.6% as South Asian race) reported that their current health depended on blood pressure medications, and 48% were concerned about blood pressure medications. At trial completion, 80% were satisfied with LDQT, 96% were certain the benefits of taking LDQT outweighed the disadvantages, and 96% reported that LDQT was convenient to take. Both patients and health care professionals found LDQT acceptable because it reduced patients' perceived pill burden and facilitated medication adherence. Health care professionals stated that a perceived limitation of LDQT was the inability to titrate doses. Steps to facilitate LDQT implementation include introducing stepped-care combinations and treatment protocols, inclusion in clinical practice guidelines, and eliminating patient cost barriers. CONCLUSIONS: LDQT was an acceptable strategy for hypertension treatment among patients and health care professionals involved in the QUARTET USA clinical trial. Although LDQT was generally perceived as beneficial for maintaining patients' blood pressure control and facilitating adherence, some clinicians perceived limitations in titration inflexibility, adverse effects, and costs. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03640312.

Formative Evaluation and Adaptation of a Hypertension Extension for Community Health Outcomes Program for Healthcare Workers within the Federal Capital Territory, Nigeria.

Background: The Extension for Community Health Outcomes (ECHO) model has been used extensively to link care providers in rural communities with experts with the aim of improving local patient care. Objective: The aim of this qualitative research study was to assess the feasibility, acceptability, perceived needs, and contextual factors to guide implementation of a hypertension focused ECHO program for Community Health Extension Workers (CHEWs) in the Federal Capital Territory, Nigeria. Methods: From September 2020 to December 2020, key informant interviews were performed with seven global organizations (hubs) providing ECHO training focused on cardiovascular disease or nephrology to identify contextual factors and implementation strategies used by each hub. In February 2022, seven focus group discussions were performed with 42 frontline healthcare workers in the Federal Capital Territory to inform local adaptation of a hypertension ECHO program. Directed content analysis identified major themes which were mapped to the Consolidated Framework for Implementation Research. Qualitative analyses were performed using Dedoose, and results were synthesized using the Implementation Research Logic Model. Results: We found both barriers and facilitators across the Consolidated Framework for Implementation Research domains that mapped to a number of constructs in each one. The results of these analyses confirmed that the core components of the ECHO model are a feasible and appropriate intervention for hypertension education of healthcare workers. However, implementing the ECHO program within the Federal Capital Territory may require strategies such as utilizing communications resources effectively, developing incentives to motivate initial participation, and providing rewards or recognition for ongoing engagement. Conclusions: These results provide valuable formative insights to guide implementation of our proposed hypertension ECHO program for CHEWs in the Federal Capital Territory, Nigeria. This information was used for key decisions around: 1) scope and content of training, 2) format and frequency, 3) selection of implementation strategies, and 4) building a community of practice.

Health Status in Heart Failure and Cancer: Analysis of the Medicare Health Outcomes Survey 2016-2020.

BACKGROUND: People with heart failure (HF) and cancer experience impaired physical and mental health status. However, health-related quality of life (HRQOL) has not been directly compared between these conditions in a contemporary population of older people. OBJECTIVES: The authors sought to compare HRQOL in people with HF vs those with lung, colorectal, breast, and prostate cancers. METHODS: The authors performed a pooled analysis of Medicare Health Outcomes Survey data from 2016 to 2020 in participants ≥65 years of age with a self-reported history of HF or active treatment for lung, colon, breast, or prostate cancer. They used the Veterans RAND-12 physical component score (PCS) and mental component score (MCS), which range from 0-100 with a mean score of 50 (based on the U.S. general population) and an SD of 10. The authors used pairwise Student's t-tests to evaluate for differences in PCS and MCS between groups. RESULTS: Among participants with HF (n = 71,025; 54% female, 16% Black), mean PCS was 29.5 and mean MCS 47.9. Mean PCS was lower in people with HF compared with lung (31.2; n = 4,165), colorectal (35.6; n = 4,270), breast (37.7; n = 14,542), and prostate (39.6; n = 17,670) cancer (all P < 0.001). Participants with HF had a significantly lower mean MCS than those with lung (31.2), colon (50.0), breast (52.0), and prostate (53.0) cancer (all P < 0.001). CONCLUSIONS: People with HF experience worse HRQOL than those with cancer actively receiving treatment. The pervasiveness of low HRQOL in HF underscores the need to implement evidence-based interventions that target physical and mental health status and scale multidisciplinary clinics.

Should mitral valve replacement age guidelines be lowered due to better bioprosthetic mitral valve durability?

OBJECTIVE: Guideline recommendations for mechanical or bioprosthetic valve for mitral valve replacement by age remains controversial. We sought to determine bovine pericardial valve durability by age and risk of reintervention. METHODS: This retrospective study between 2 large university-based cardiac surgery programs examined patients who underwent bioprosthetic mitral valve replacement from 2004 to 2020. Follow-up was obtained through June 2022. Durability outcomes involving structural valve deterioration were compared by age decile. RESULTS: Of 1544 available patients, mean age was 66 ± 13 years and 652 (42%) were aged less than 65 years. Indications for mitral valve replacement were as follows: mitral regurgitation greater than 2+ in 53% (n = 813), mitral stenosis in 44% (n = 650), endocarditis in 18% (n = 277), and reoperation in 39% (n = 602). Concomitant procedures were aortic valve replacement in 28% (n = 426), tricuspid valve in 36% (n = 550), and coronary artery bypass in 19% (n = 290). Thirty-day mortality was 5.4%. In follow-up (clinical: median [interquartile range] 75 [25-129] months), reoperation for endocarditis and new stroke were low (0.30 and 1.06 per 100 patient/years, respectively). The cumulative incidence of mitral valve reintervention for structural valve deterioration among all patients was 6.2% at 10 years and 9.0% at 12 years with no statistical difference in structural valve deterioration in patients aged 40 to 70 years (P = .1). In 90 patients with mitral valve reintervention, 30-day mortality after reintervention was 4.7% (n = 2) for 43 with mitral valve-in-valve and 6.4% (n = 3) for 47 with reoperation. CONCLUSIONS: Bovine pericardial mitral valve replacement is a durable option for younger patients. The opportunity to avoid anticoagulation and the associated risks with mechanical mitral valve replacement may be of benefit to patients. These insights may provide data needed to revise the current guidelines.

Characterization of Screen Failures Among Patients Evaluated for Transcatheter Tricuspid Valve Repair (TriSelect-Study).

BACKGROUND: Transcatheter tricuspid valve repair (TTVr) has significantly expanded treatment options for tricuspid regurgitation (TR). However, a sizeable proportion of patients are still declined for TTVr and little is known about their clinical characteristics and cardiac morphology. OBJECTIVES: This study sought to characterize patients who screen fail for TTVr with respect to their clinical characteristics and cardiac morphology. METHODS: A total of 547 patients were evaluated for TTVr between January 2016 to December 2021 from 3 centers in the United States and Germany. Clinical records and echocardiographic studies were used to assess medical history and right ventricular (RV) and tricuspid valve (TV) characteristics. RESULTS: Median age was 80 (IQR: 74-83) years and 60.0% were female. Over half (58.1%) were accepted for TTVr. Of those who were deemed unsuitable for TTVr (41.9%), the most common exclusion reasons were anatomical criteria (56.8%). In the regression analysis, RV and right atrial size, TV coaptation gap, and tethering area were identified as independent screen failure predictors. Other rejection reasons included clinical futility (17.9%), low symptom burden (12.7%), and technical limitations (12.7%). Most of the excluded patients (71.6%) were managed conservatively with medical therapy, while a small number either proceeded to TV surgery (22.3%) or subsequently became eligible for transcatheter tricuspid valve replacement in later available clinical trials in the United States (6.1%). CONCLUSIONS: The majority of TTVr screen failure patients are excluded due to TV, right atrial, and RV enlargement. However, a significant proportion is excluded due to clinical futility. These identifiable anatomical and clinical characteristics emphasize the importance of earlier referral and intervention of TR and the need for continued innovation of Transcatheter tricuspid valve interventions.

Clinical characteristics and treatment patterns of pregnant women with hypertension in primary care in the Federal Capital Territory of Nigeria: cross-sectional results from the hypertension treatment in Nigeria Program.

BACKGROUND: Hypertensive disorders of pregnancy, including hypertension, are a leading cause of maternal mortality in Nigeria. However, there is a paucity of data on pregnant women with hypertension who receive care in primary health care facilities. This study presents the results from a cross-sectional analysis of pregnant women enrolled in the Hypertension Treatment in Nigeria Program which is aimed at integrating and strengthening hypertension care in primary health care centres. METHODS: A descriptive analysis of the baseline results from the Hypertension Treatment in Nigeria Program was performed. Baseline blood pressures, treatment and control rates of pregnant women were analysed and compared to other adult women of reproductive age. A complete case analysis was performed, and a two-sided p value < 0.05 was considered statistically significant. RESULTS: Between January 2020 to October 2022, 5972 women of reproductive age were enrolled in the 60 primary healthcare centres participating in the Hypertension Treatment in Nigeria Program and 112 (2%) were pregnant. Overall mean age (SD) was 39.6 years (6.3). Co-morbidities were rare in both groups, and blood pressures were similar amongst pregnant and non-pregnant women (overall mean (SD) first systolic and diastolic blood pressures were 157.4 (20.6)/100.7 (13.6) mm Hg and overall mean (SD) second systolic and diastolic blood pressures were 151.7 (20.1)/98.4 (13.5) mm Hg). However, compared to non-pregnant women, pregnant women had a higher rate of newly diagnosed hypertension (65.2% versus 54.4% p = 0.02) and lower baseline walk-in treatment (32.1% versus 42.1%, p = 0.03). The control rate was numerically lower among pregnant patients (6.3% versus 10.2%, p = 0.17), but was not statistically significant. Some pregnant patients (8.3%) were on medications contraindicated in pregnancy, and none of the pregnant women were on aspirin for primary prevention of preeclampsia. CONCLUSIONS: These findings indicate significant gaps in care and important areas for future studies to improve the quality of care and outcomes for pregnant women with hypertension in Nigeria, a country with the highest burden of maternal mortality globally.

Predictive Value of Relative Apical Sparing of Longitudinal Strain on Echocardiography for Cardiac Amyloidosis.

Relative apical longitudinal sparing (RALS) on echocardiography has become an increasingly used tool to evaluate for cardiac amyloidosis (CA), but the predictive value of this finding remains unclear. This is a retrospective analysis at a single tertiary care center across 3 years. Patients were included if they had RALS, defined by strain ratio ≥2.0 on echocardiography, and sufficient laboratory, imaging, or histopathologic workup to indicate their likelihood of CA. Patients were stratified by their likelihood of CA, and contributions of other co-morbidities previously shown to be associated with RALS. Of the 220 patients who had adequate workup to determine their likelihood of having CA, 50 (22.7%) had confirmed CA, 35 (15.9%) had suspicious CA, 83 (37.7%) had unlikely CA, and 52 (23.7%) had ruled-out CA. The positive predictive value of RALS for CA was 38.6% for confirmed or suspicious CA. The remaining 61.4% of patients who were unlikely or ruled out for CA had other co-morbidities such as hypertension, chronic kidney disease, malignancy, or aortic stenosis, 17.0% of this group had none of these co-morbidities. In our tertiary care cohort of patients with RALS pattern on echocardiography, we found that fewer than half of patients with RALS were likely to have CA. Given the increasing use of strain technology, further studies are warranted to determine the optimal strategy for assessing CA in a patient with RALS.

Nigeria healthcare worker SARS-CoV-2 serology study: Results from a prospective, longitudinal cohort.

Healthcare workers, both globally and in Nigeria, have an increased risk for SARS-CoV-2 infection compared with the general population due to higher risk contacts, including occupational exposures. In addition, primary healthcare workers represent an important group for estimating prior infection to SARS-CoV-2 because they work at the first point-of-contact for most patients yet have not been included in prior COVID-19 seroepidemiology research in Nigeria. We sought to evaluate baseline seroprevalence, rates of seroconversion (IgG- to IgG+) and seroreversion (IgG+ to IgG-), change in IgG concentration at 3- and 6-month follow-up, and factors associated with seropositivity. From June 2020 to December 2020, we conducted a longitudinal seroepidemiology study among frontline health care workers in Nigeria using a validated dried blood spot assay. Among 525 participants, mean (SD) age was 39.1 (9.7) years, 61.0% were female, and 45.1% were community health workers. The six-month follow-up rate was 93.5%. Seropositivity rates increased from 31% (95% CI: 27%, 35%) at baseline to 45% (95% CI: 40%, 49%) at 3-month follow-up, and 70% (95% CI: 66%, 74%) at 6-month follow-up. There was a corresponding increase in IgG levels from baseline (median = 0.18 ug/mL) to 3-month (median = 0.35 ug/mL) and 6-month follow-up (median = 0.59 ug/mL, Ptrend < .0001). A minority of participants reported symptoms from February 2020 until baseline (12.2%) or during 3-month (6.6%) or 6-month (7.5%) follow-up. only 1 participant was hospitalized. This study demonstrated high baseline, 3-month and 6-month follow-up prevalence of IgG antibodies to SARS-CoV-2 during the first two waves of the COVID-19 pandemic in Nigeria among a cohort of unvaccinated frontline healthcare workers, including primary healthcare workers despite low symptomatology. These results may have implications in state- and national-level disease pandemic modeling. Trial registration: NCT04158154.

Investigating Gene-Diet Interactions Impacting the Association Between Macronutrient Intake and Glycemic Traits.

Few studies have demonstrated reproducible gene-diet interactions (GDIs) impacting metabolic disease risk factors, likely due in part to measurement error in dietary intake estimation and insufficient capture of rare genetic variation. We aimed to identify GDIs across the genetic frequency spectrum impacting the macronutrient-glycemia relationship in genetically and culturally diverse cohorts. We analyzed 33,187 participants free of diabetes from 10 National Heart, Lung, and Blood Institute Trans-Omics for Precision Medicine program cohorts with whole-genome sequencing, self-reported diet, and glycemic trait data. We fit cohort-specific, multivariable-adjusted linear mixed models for the effect of diet, modeled as an isocaloric substitution of carbohydrate for fat, and its interactions with common and rare variants genome-wide. In main effect meta-analyses, participants consuming more carbohydrate had modestly lower glycemic trait values (e.g., for glycated hemoglobin [HbA1c], -0.013% HbA1c/250 kcal substitution). In GDI meta-analyses, a common African ancestry-enriched variant (rs79762542) reached study-wide significance and replicated in the UK Biobank cohort, indicating a negative carbohydrate-HbA1c association among major allele homozygotes only. Simulations revealed that >150,000 samples may be necessary to identify similar macronutrient GDIs under realistic assumptions about effect size and measurement error. These results generate hypotheses for further exploration of modifiable metabolic disease risk in additional cohorts with African ancestry. ARTICLE HIGHLIGHTS: We aimed to identify genetic modifiers of the dietary macronutrient-glycemia relationship using whole-genome sequence data from 10 Trans-Omics for Precision Medicine program cohorts. Substitution models indicated a modest reduction in glycemia associated with an increase in dietary carbohydrate at the expense of fat. Genome-wide interaction analysis identified one African ancestry-enriched variant near the FRAS1 gene that may interact with macronutrient intake to influence hemoglobin A1c. Simulation-based power calculations accounting for measurement error suggested that substantially larger sample sizes may be necessary to discover further gene-macronutrient interactions.

Echocardiographic correlates of major adverse cardiac events at 1 year in patients with apical ballooning takotsubo syndrome.

INTRODUCTION: Takotsubo syndrome (TTS) is characterized by transient left ventricular dysfunction and associated with considerable morbidity and mortality. We sought to evaluate the association between change in cardiac mechanics after diagnosis of TTS with 1-year incidence of major adverse cardiovascular events (MACE). METHODS: We retrospectively identified 85 patients with apical TTS based on ICD 9/10 codes and chart adjudication, who had a follow-up echocardiogram within 6 months of diagnosis. Echocardiograms were analyzed for left ventricular ejection fraction (LVEF), global longitudinal strain (GLS), GLS ratio, global circumferential strain (GCS), and global radial strain (GRS). Multivariable logistic regression was performed to identify parameters associated with MACE (all-cause mortality, heart failure, stroke, and coronary artery disease [CAD] requiring percutaneous coronary intervention [PCI]) at 1 year. Event-free survival was assessed in patients with GLS (≤-18% vs. >18%) and LVEF (≥53% vs. <53%). RESULTS: Within 1 year of diagnosis, MACE occurred in 15 (18%) patients. Between baseline and follow-up echocardiogram (median 15 [range 1-151] days), there were significant differences in change in LVEF and GLS in patients with versus without incident MACE. In multivariate analysis, change in LVEF (odds ratio [OR] = .93 [.87, .98], p = .013) and change in GLS (OR = 1.32 [1.04, 1.67], p = .022) were independently associated with MACE; however, the association with change in GLS was attenuated (odds ratio [OR] = 1.13 [.94, 1.36], p = .21) after adjustment for baseline and change in LVEF. Among patients with normalized LVEF at follow-up, there were five (14.7%) MACE; whereas, there were no events among patients with normalized GLS. CONCLUSIONS: In patients with apical TTS, recovery in GLS and LVEF at follow-up was associated with significantly lower MACE at 1 year. Normalization of GLS at follow-up was better able to discriminate event-free survival than normalization of LVEF.