Sheba Meymandi

An unfolding tragedy of Chagas disease in North America.

In North America, Chagas disease (American trypanosomiasis caused by Trypanosoma cruzi) was first reported in Mexico in 1940 [1] and in the United States in Texas in 1955 [2]. However, based on ancient mummified remains discovered in the Rio Grande Valley, human T. cruzi infection has been present in North America since prehistoric times [3].

Neglected Parasitic Infections in the United States: Chagas Disease

Chagas disease, which is caused by the protozoan parasite Trypanosoma cruzi, can lead to severe cardiac and gastrointestinal disease. Most persons acquire this infection through contact with vector bugs carrying T. cruzi in endemic areas of Latin America. Infection can also be acquired by congenital, transfusion, transplantation, and foodborne transmission. Although an estimated 300,000 persons with Chagas disease live in the United States, little is known about the burden of chagasic heart disease. It is not known how often congenital or vector-borne transmission of T. cruzi occurs in the United States, although it is known that infected mothers and infected vector bugs are found in this country. Better diagnostic tests and treatment drugs are needed to improve patient care, and research is needed to define transmission risks and develop strategies to prevent new infections and reduce the burden of disease.

Cardiovascular and endothelial effects of fish oil supplementation in healthy volunteers.

Consumption of fish oil (FO) is associated with reduced adverse cardiovascular events. In a randomized, blinded, placebo-controlled trial, 26 subjects (17 men and 9 women; mean age [± SD] 31 ± 3.7 years) received 1 g FO capsule (n = 14) or placebo (1 g of corn oil, n = 12) for 14 days. At day 0 and day 14, heart rate (HR), blood pressure, endothelium-dependent brachial artery flow-mediated vasodilation (EDV), and endothelium-independent nitroglycerin-mediated vasodilation (EIDV) were assessed with ultrasound. FO supplementation resulted in a significant increase in EDV (20.4% ± 13.2% vs 9.9% ± 5.4%; P = .036) and EIDV (32.6% ± 16.8% vs 18.0% ± 14.9%; P = .043). Resting HR decreased by a mean of 5.9 ± 9.4 bpm (FO) compared with placebo (mean increase of 0.73 ± 4.8 bpm [P = .05]). FO supplementation in healthy subjects is associated with improved endothelial function and decreased resting HR.

n-3 Fatty acids (fish oil) for epilepsy, cardiac risk factors, and risk of SUDEP: Clues from a pilot, double-blind, exploratory study

OBJECTIVE The goal of the work described here was to determine the effect of high-dose n-3 fatty acids (eicosapentanoic acid+docosahexanoic acid, fish oil) on several outcomes in subjects with refractory epilepsy, including seizure severity, seizure frequency, cardiac risk factors, and heart rate variability, in a pilot, exploratory planning trial. METHODS Pilot, randomized, double-blind two-period crossover clinical trial of high-dose fish oil (9600 mg of fish oil/day, 2880 mg of n-3 fatty acids) in 11 subjects with refractory seizures. Outcomes included seizure frequency, seizure severity, lipid panel, and heart rate variability as measured by SDNN and SDANN (defined as the standard deviation of all normal R-R intervals for 1h, and the standard deviation of all R-R intervals in each successive 5-min epoch, respectively). RESULTS Preliminary data identified trends towards lower seizure severity, lower triglycerides, higher HDL, and increased SDNN/SDANN in those with low SDNN/SDANN at baseline (Spearmans correlation=-0.65, P=0.03). No positive effect on seizure frequency was identified. CONCLUSIONS Further study of the effect of n-3 fatty acids is indicated in people with epilepsy, as favorable trends were identified on cardiac risk factors (triglycerides) and in a subgroup with low heart rate variability (low SDNN/SDANN), a marker of sudden death risk. To our knowledge, this is the first trial to explore the beneficial effects of n-3 fatty acids on cardiac risk factors and heart rate variability in people with epilepsy.

Fish oil (n-3 fatty acids) in drug resistant epilepsy: a randomised placebo-controlled crossover study

Abstract Background n-3 fatty acids inhibit neuronal excitability and reduce seizures in animal models. High-dose fish oil has been explored in two randomised trials in drug resistant epilepsy with negative results. We performed a phase II randomised controlled crossover trial of low-dose and high-dose fish oil in participants with drug resistant epilepsy to explore whether low-dose or high-dose fish oil reduces seizures or improves cardiovascular health. Methods Randomised placebo-controlled trial of low-dose and high-dose fish oil versus placebo (corn oil, linoleic acid) in 24 participants with drug resistant epilepsy. A three-period crossover design was utilised lasting 42 weeks, with three 10-week treatment periods and two 6-week washout periods. All participants were randomised in double-blind fashion to receive placebo, high dose or low dose in different sequences. The primary outcome was per cent change in total seizure frequency. Findings Low-dose fish oil (3 capsules/day, 1080 mg eicosapentaenoic acid+docosahexaenoic acid) was associated with a 33.6% reduction in seizure frequency compared with placebo. Low-dose fish oil was also associated with a mild but significant reduction in blood pressure. High-dose fish oil was no different than placebo in reducing seizures or improving cardiac risk factors. Interpretation In this phase II randomised crossover trial, low-dose fish oil was effective in reducing seizures compared with placebo. The magnitude of improvement is similar to that of recent antiepileptic drug trials in drug resistant epilepsy (DRE). The results indicate that low-dose fish oil may reduce seizures and improve the health of people with epilepsy. These findings justify a large multicentre randomised trial of low-dose fish oil (n-3 fatty acids <1080 mg/day) in drug resistant epilepsy. Trial registration number NCT00871377.

Risk Assessment for Sudden Death in Epilepsy: The SUDEP-7 Inventory

Background Sudden unexpected death in epilepsy (SUDEP) is a major cause of death in those with drug-resistant epilepsy (DRE). There is a need for inventories and biomarkers associated with the risk for SUDEP. Objective To explore the revised SUDEP Risk Inventory (SUDEP-7) in a cohort with DRE and determine the association with Heart Rate and other covariates. Methods Twenty-five subjects with severe DRE were enrolled in a clinical trial for epilepsy. Baseline demographics, duration of epilepsy, seizure types, seizure frequency, seizure severity, AEDs, and vital signs were collected. Heart rate variability (HRV) was calculated from 1-h recordings of ECG. A SUDEP Risk Inventory (SUDEP-7) was administered, which included seven validated and weighted risk factors initially identified by Walczak et al. as factors associated with SUDEP risk. Results The total score on the revised SUDEP-7 ranged from 1 to 7, mean = 3.4 (SD 1.8). The SUDEP Risk Inventory score was inversely correlated with RMSSD (Pearson r = −0.45, p = 0.027). The following variables were significantly associated with RMSSD: epilepsy duration (p = 0.02), age (p = 0.03), and developmental intellectual disability (p < 0.001). The correlation between RMSSD and SUDEP-7 tended to persist also after the adjustment for patient age (r = −0.40, p = 0.05). Two subjects died of SUDEP: their SUDEP-7 scores were above average and in the upper twenty-fifth and fiftieth percentiles, respectively (6 and 4, mean = 3.4). Conclusion RMSSD, a measure of low frequency HRV, was significantly associated with SUDEP Risk Inventory (SUDEP-7) scores. Using a multivariate model, the covariates of developmental intellectual disability, age, and duration of epilepsy were also significantly associated with decreased HRV. The correlation between decreased HRV and a higher SUDEP-7 score remained unchanged even after the adjustment for patient age. The results suggest that older age, greater duration of epilepsy, and the presence of developmental intellectual disability may increase the risk of SUDEP through their direct influence on decreasing the vagus nerve-mediated HRV. Further validation of the SUDEP-7 inventory is indicated. Trial Registration ClinicalTrials.gov, NCT00871377.

Prevalence and Impact of Chagas Disease Among Latin American Immigrants With Nonischemic Cardiomyopathy in Los Angeles, California

Background—Chagas disease is a well-known cause of cardiomyopathy in Latin America; however, 300 000 individuals are estimated to have Chagas disease in the United States. This study examined the prevalence and impact of Chagas cardiomyopathy (CCM) in a US population. We hypothesized that patients with CCM would have increased morbidity and mortality when compared with patients with non-CCM. Methods and Results—This is a single-center, prospective cohort study. Enrollment criteria were new diagnosis of nonischemic cardiomyopathy (left ventricular ejection fraction ⩽40%) and previous residence in Latin America for at least 12 months. Serological testing for Trypanosoma cruzi was performed at enrollment. The primary end point was all-cause mortality or heart transplantation. The secondary end point was heart failure–related hospitalization. A total of 135 patients were enrolled, with a median of 43 months of follow-up. Chagas disease was diagnosed in 25 (19%) patients. The primary end point occurred in 9 patients (36%) in the CCM group and in 11 patients (10%) in the non-CCM group (hazard ratio [HR], 4.46; 95% confidence interval, 1.8–10.8; P=0.001). The secondary end point occurred in 13 patients (52%) in the CCM group and in 35 patients (32%) in the non-CCM group (HR, 2.22; 95% confidence interval, 1.2–4.2; P=0.01). Conclusions—There is a high prevalence of Chagas disease among Latin American immigrants diagnosed with nonischemic cardiomyopathy in Los Angeles. Advanced CCM portends a poor prognosis and is associated with increased all-cause mortality/heart transplantation and heart failure–related hospitalization.

Tolerance of Benznidazole in a United States Chagas Disease Clinic

The US-based Center of Excellence for Chagas Disease performed an observational study on the safety and tolerance of benznidazole 5 mg/kg/day for 60 days in 30 adults with chronic Chagas disease. The side-effect profile was suboptimal, including 5 cases of debilitating neuropathy and an unusually high angioedema rate.

The Prevalence and Impact of Chagas Disease Among Latin American Immigrants With Non-Ischemic Cardiomyopathy in Los Angeles, California

Background—Chagas disease is a well-known cause of cardiomyopathy in Latin America; however, 300 000 individuals are estimated to have Chagas disease in the United States. This study examined the prevalence and impact of Chagas cardiomyopathy (CCM) in a US population. We hypothesized that patients with CCM would have increased morbidity and mortality when compared with patients with non-CCM. Methods and Results—This is a single-center, prospective cohort study. Enrollment criteria were new diagnosis of nonischemic cardiomyopathy (left ventricular ejection fraction ⩽40%) and previous residence in Latin America for at least 12 months. Serological testing for Trypanosoma cruzi was performed at enrollment. The primary end point was all-cause mortality or heart transplantation. The secondary end point was heart failure–related hospitalization. A total of 135 patients were enrolled, with a median of 43 months of follow-up. Chagas disease was diagnosed in 25 (19%) patients. The primary end point occurred in 9 patients (36%) in the CCM group and in 11 patients (10%) in the non-CCM group (hazard ratio [HR], 4.46; 95% confidence interval, 1.8–10.8; P=0.001). The secondary end point occurred in 13 patients (52%) in the CCM group and in 35 patients (32%) in the non-CCM group (HR, 2.22; 95% confidence interval, 1.2–4.2; P=0.01). Conclusions—There is a high prevalence of Chagas disease among Latin American immigrants diagnosed with nonischemic cardiomyopathy in Los Angeles. Advanced CCM portends a poor prognosis and is associated with increased all-cause mortality/heart transplantation and heart failure–related hospitalization.

Cardiac sympathetic denervation for intractable ventricular arrhythmias in Chagas disease

BACKGROUND Autonomic modulation is a valuable therapeutic option for the management of ventricular arrhythmias. Bilateral cardiac sympathetic denervation (BCSD) has shown promising results in the acute, intermediate, and long-term management of polymorphic and monomorphic ventricular tachycardia (VT) in patients with structural heart disease. Cardiomyopathy (CM) due to Chagas disease (CD), and associated VT, is thought to be in part due to autonomic neuronal destruction and dysfunction. OBJECTIVE The purpose of this study was to assess whether BCSD is a safe and effective treatment modality in patients with CD and VT storm or refractory VT. METHODS A retrospective analysis of data from patients with chagasic CM who underwent BCSD between 2009 and 2015 at 2 international centers was performed. RESULTS Of 75 patients who underwent BCSD for VT storm or refractory VT in the setting of CM, 7 (9.3%) patients had CD as the etiology of CM. All patients had monomorphic VT. Median follow-up was 7 months (range 1-46 months). All patients either underwent previous unsuccessful catheter ablation or were not candidates for ablation. The median number of implantable cardioverter-defibrillator (ICD) shocks 1 month before BCSD was 4 (range 2-30) and decreased to 0 (range 0-2) during available follow-up after BCSD. When antitachycardia pacing therapies were included in the analysis, the median number of ICD therapies (shocks + antitachycardia pacing) still decreased to 1 (range 0-3). CONCLUSION In patients with chagasic CM presenting with refractory monomorphic VT, early evidence suggests that BCSD reduces appropriate ICD therapy and may represent a valuable treatment option.