The natural history of latent rheumatic heart disease in a 5 year follow-up study: a prospective observational study.

BACKGROUND: Latent rheumatic heart disease (RHD) occurs in asymptomatic individuals with echocardiographic evidence of RHD and no history of acute rheumatic fever. The natural history of latent RHD is unclear but has important clinical and economic implications about whether these children should receive penicillin prophylaxis or not. We performed a 5-year prospective study of this question. METHODS: In August 2013 through September 2014, we conducted a follow-up study of latent RHD among school pupils using the World Heart Federation (WHF) echocardiographic criteria. Contingency tables were used to assess progression, persistence or regression of latent RHD. RESULTS: Forty two borderline and 13 definite cases of RHD (n 55) were identified, 44 (80%; mean age 13.8 ± 4.0 years; 29 (65.9%) female) of whom were available for echocardiographic examination at a median follow-up of 60.8 months (interquartile range 51.3-63.5). Over the follow-up period, half the participants (n = 23; 52.3%) improved to normal or better WHF category (regressors), a third (n = 14, 31.8%) remained in the same category (persistors), while seven others (15.9%) progressed from borderline to definite RHD (progressors). In total, 21 subjects (47.7%) reverted to a normal status, nine (20.4%) either improved from definite to borderline or remained in the borderline category, and 14 (31.8%) either remained definite or progressed from borderline to a definite status. Two cases (20%) progressed to symptomatic disease. CONCLUSIONS: Latent RHD has a variable natural history that ranges from regression to normal in nearly half of cases, to persistence, progression or development of symptoms in the remainder of subjects.

A 12 week longitudinal study of microbial translocation and systemic inflammation in undernourished HIV-infected Zambians initiating antiretroviral therapy.

BACKGROUND: Undernourished, HIV-infected adults in sub-Saharan Africa have high levels of systemic inflammation, which is a risk factor for mortality and other adverse health outcomes. We hypothesized that microbial translocation, due to the deleterious effects of HIV and poor nutrition on intestinal defenses and mucosal integrity, contributes to heightened systemic inflammation in this population, and reductions in inflammation on antiretroviral therapy (ART) accompany reductions in translocation. METHODS: HIV-infected, Zambian adults with a body mass index <18.5 kg/m2 were recruited for a pilot study to assess the relationships between microbial translocation and systemic inflammation over the first 12 weeks of ART. To assess microbial translocation we measured serum lipopolysaccharide binding protein (LBP), endotoxin core IgG and IgM, and soluble CD14, and to assess intestinal permeability we measured the urinary excretion of an oral lactulose dose normalized to urinary creatinine (Lac/Cr ratio). Linear mixed models were used to assess within-patient changes in these markers relative to serum C-reactive protein (CRP), tumor necrosis factor-α receptor 1 (TNF-α R1), and soluble CD163 over 12 weeks, in addition to relationships between variables independent of time point and adjusted for age, sex, and CD4+ count. RESULTS: Thirty-three participants had data from recruitment and at 12 weeks: 55% were male, median age was 36 years, and median baseline CD4+ count was 224 cells/µl. Over the first 12 weeks of ART, there were significant decreases in serum levels of LBP (median change -8.7 µg/ml, p = 0.01), TNF-α receptor 1 (-0.31 ng/ml, p < 0.01), and CRP (-3.5 mg/l, p = 0.02). The change in soluble CD14 level over 12 weeks was positively associated with the change in CRP (p < 0.01) and soluble CD163 (p < 0.01). Pooling data at baseline and 12 weeks, serum LBP was positively associated with CRP (p = 0.01), while endotoxin core IgM was inversely associated with CRP (p = 0.01) and TNF-α receptor 1 (p = 0.04). The Lac/Cr ratio was not associated with any serum biomarkers. CONCLUSIONS: In undernourished HIV-infected adults in Zambia, biomarkers of increased microbial translocation are associated with high levels of systemic inflammation before and after initiation of ART, suggesting that impaired gut immune defenses contribute to innate immune activation in this population.

Electrophysiology in the Developing World: Challenges and Opportunities.

As a subset of the growing epidemic of cardiovascular morbidity and mortality in low-income and middle-income countries (LMICs), the significant burdens of heart rhythm disorders also increase. Effective diagnostic and treatment modalities exist, but financial resources and expertise are limited. Cost-effective strategies exist to address most of these limitations, but many surmountable barriers need to be overcome to introduce and improve electrophysiologic care in LMICs. In this article, current and potential solutions are offered for the diagnostic and therapeutic challenges of managing bradyarrhythmias and tachyarrhythmias.

Ictal asystole and ictal syncope: insights into clinical management.

BACKGROUND: Ictal asystole is a rare, serious, and often treatable cause of syncope. There are currently limited data to guide management. Characterization of ictal syncope predictors may aid in the selection of high-risk patients for treatments such as pacemakers. METHODS AND RESULTS: We searched our epilepsy monitoring unit database from October 2003 to July 2013 for all patients with ictal asystole events. Clinical, electroencephalogram, and ECG data for each of their seizures were examined for their relationships with ictal syncope events. In 10 patients with ictal asystole, we observed 76 clinical seizures with 26 ictal asystole episodes, 15 of which led to syncope. No seizure with asystole duration≤6 s led to syncope, whereas 94% (15/16) of seizures with asystole duration>6 s led to syncope (P=0.02). During ictal asystole events, 4 patients had left temporal seizure onset, 4 patients had right temporal seizure onset, and 2 patients had both. Syncope was more common with left temporal (40%) than with right temporal seizures (10%; P=0.002). Treatment options included antiepileptic drug changes, epilepsy surgery, and pacemaker implantation. Eight patients received pacemakers. During follow-up of 72±95 months, all patients remained syncope free. CONCLUSIONS: Ictal asystole>6 s is strongly associated with ictal syncope. Ictal syncope is more common in left than in right temporal seizures. A permanent pacemaker should be considered in patients with ictal syncope if they are not considered good candidates for epilepsy surgery.

Increased systemic inflammation is associated with cardiac and vascular dysfunction over the first 12 weeks of antiretroviral therapy among undernourished, HIV-infected adults in Southern Africa.

INTRODUCTION: Persistent systemic inflammation is associated with mortality among undernourished, HIV-infected adults starting antiretroviral therapy (ART) in sub-Saharan Africa, but the etiology of these deaths is not well understood. We hypothesized that greater systemic inflammation is accompanied by cardiovascular dysfunction over the first 12 weeks of ART. METHODS: In a prospective cohort of 33 undernourished (body mass index <18.5 kg/m2) Zambian adults starting ART, we measured C-reactive protein (CRP), tumor necrosis factor-α receptor 1 (TNF-α R1), and soluble CD163 and CD14 at baseline and 12 weeks. An EndoPAT device measured the reactive hyperemia index (LnRHI; a measure of endothelial responsiveness), peripheral augmentation index (AI; a measure of arterial stiffness), and heart rate variability (HRV; a general marker of autonomic tone and cardiovascular health) at the same time points. We assessed paired changes in inflammation and cardiovascular parameters, and relationships independent of time point (adjusted for age, sex, and CD4+ T-cell count) using linear mixed models. RESULTS: Serum CRP decreased (median change -3.5 mg/l, p=0.02), as did TNF-α R1 (-0.31 ng/ml, p<0.01), over the first 12 weeks of ART. A reduction in TNF-α R1 over 12 weeks was associated with an increase in LnRHI (p=0.03), and a similar inverse relationship was observed for CRP and LnRHI (p=0.07). AI increased in the cohort as a whole over 12 weeks, and a reduction in sCD163 was associated with a rise in the AI score (p=0.04). In the pooled analysis of baseline and 12 week data, high CRP was associated with lower HRV parameters (RMSSD, p=0.01; triangular index, p<0.01), and higher TNF- α R1 accompanied lower HRV (RMSSD, p=0.07; triangular index, p=0.06). CONCLUSIONS: Persistent inflammation was associated with impaired cardiovascular health over the first 12 weeks of HIV treatment among undernourished adults in Africa, suggesting cardiac events may contribute to high mortality in this population.