Variant Angina and Cannabis-Induced Myocarditis: A Rare Presentation of Myocardial Inflammation.

Myocarditis is a rare but serious inflammatory disease of the myocardium, often caused by viral infections. We present a unique case of myocarditis in a previously healthy 29-year-old male who developed symptoms and electrocardiography changes of variant angina following cannabis use. This case report discusses the patient's atypical presentation, diagnostic evaluation, management, and outcome.

Real-World Adherence and Persistence to Direct Oral Anticoagulants in Patients With Atrial Fibrillation: A Systematic Review and Meta-Analysis.

BACKGROUND: Stroke reduction with direct oral anticoagulants (DOACs) in atrial fibrillation (AF) is dependent on adherence and persistence in the real-world setting. Individual study estimates of DOAC adherence/persistence rates have been discordant. Our aims were to characterize real-world observational evidence for DOAC adherence/persistence and evaluate associated clinical outcomes in patients with AF. METHODS AND RESULTS: PubMed, EMBASE, and CINAHL were searched from inception to June 2018. Observational studies that reported real-world DOAC adherence/persistence in patients with AF were included. Study quality was assessed using the Newcastle-Ottawa Scale. Meta-analyses for pooled estimates were performed using DerSimonian and Laird random-effects models. Outcomes included DOAC mean proportion of days covered or medication possession ratio, proportion of good adherence (proportion of days covered/medication possession ratio ≥80%), persistence, DOAC versus vitamin K antagonists persistence, and clinical outcomes associated with nonadherence/nonpersistence. Forty-eight observational studies with 594 784 unique patients with AF (59% male; mean age 71 years) were included. The overall pooled mean proportion of days covered/medication possession ratio was 77% (95% CI, 75%-80%), proportion of patients with good adherence was 66% (95% CI, 63%-70%), and proportion persistent was 69% (95% CI, 65%-72%). The pooled proportion of patients with good adherence was 71% (95% CI, 64%-78%) for apixaban, 60% (95% CI, 52%-68%) for dabigatran, and 70% (95% CI, 64%-75%) for rivaroxaban. Similar patterns were found for pooled persistence by agent. The pooled persistence was higher with DOACs than vitamin K antagonists (odds ratio, 1.44 [95% CI, 1.12-.86]). DOAC nonadherence was associated with an increased risk of stroke (hazard ratio, 1.39 [95% CI, 1.06-1.81]). CONCLUSIONS: Suboptimal adherence and persistence to DOACs was common in patients with AF, with 1 in 3 patients adhering to their DOAC <80% of the time, which was associated with poor clinical outcomes in nonadherent patients. Although it is convenient that DOACs do not require laboratory monitoring, greater effort in monitoring for and interventions to prevent nonadherence may be necessary to optimize stroke prevention. Increased clinician awareness of DOAC nonadherence may help identify at-risk patients.

Thiamine and Heart Failure: Challenging Cases of Modern-Day Cardiac Beriberi.

Cardiac beriberi, or heart failure due to thiamine deficiency, is considered rare in the developed world. The diagnosis is often only considered in limited populations such as those with chronic alcoholism. Alternatively, the disease can be mislabeled as "alcoholic cardiomyopathy" or "nonischemic cardiomyopathy." The following 2 cases illustrate the need to expand our vigilance to other at-risk populations.

Cangrelor Bridging Within 6 Months of a Drug-Eluting Stent in a Patient for Emergency Cervical Spine Surgery: A Case Report.

The recommended duration of dual antiplatelet therapy after drug-eluting stent placement presents a dilemma for patients with recent stenting who require urgent or emergency noncardiac surgery. We present the case of a patient with recent drug-eluting stent placement (<6 months) on dual antiplatelet therapy who underwent successful emergency cervical spine surgery with antiplatelet therapy bridged using cangrelor, an intravenous P2Y12 inhibitor antiplatelet agent. Our experience illustrates the multidisciplinary approach to a patient with high thrombotic and bleeding risk who underwent neurosurgery off both aspirin and a P2Y12 inhibitor.

Treatment of Chagas Disease in the United States.

PURPOSE OF REVIEW: Chagas disease (CD) is endemic to much of Latin America, but also present in the United States (U.S.). Following a lengthy asymptomatic period, CD produces serious cardiac or gastrointestinal complications in 30-40% of people. Less than 1% of the estimated six million cases in the Americas, including 326,000-347,000 in the U.S., are diagnosed. Infected persons are typically unaware and the bulk of clinicians are unfamiliar with current treatment guidelines. This review provides U.S. and other clinicians with the latest knowledge of CD treatment. RECENT FINDINGS: Chagas cardiomyopathy (CCM) causes severe fibrosis and autonomic damage in the myocardium. Eliminating the parasite through antitrypanosomal therapy with benznidazole, a nitroimidazole derivative or nifurtimox, a nitrofuran compound, potentially prevents heart failure and other sequelae of advanced CCM. Benznidazole, recently approved by the U.S. Food and Drug Administration (FDA) for children 2-12 years old, is the first-line therapy; optimal dosages are currently being studied. Antitrypanosomal therapy prevents congenital transmission; produces high cure rates for acute, congenital, and early chronic cases; and improves clinical outcomes in adult chronic indeterminate cases. However, this benefit was not observed in a large clinical trial that included patients with advanced CCM. SUMMARY: Treatment with antitrypanosomal drugs can cure CD in acute, congenital, and early chronic cases and provides improved clinical outcomes for chronic indeterminate cases. This treatment should be offered as early as possible, before advanced CCM develops.

The Prevalence of Chagas Disease Among Latin American Immigrants with Pacemakers in Los Angeles, California.

AbstractChagas disease (CD), with associated conduction abnormalities, is a common indication for pacemaker implantation in Latin America. The prevalence of CD in Latin American immigrants with pacemakers residing in the United States has never been studied. This single-center cross-sectional study included pacemaker patients who were aged 18 years or more with a previous residence in Latin America for at least 6 months. Patients with an implantable cardioverter-defibrillator, cardiac resynchronization therapy, or iatrogenic and/or congenital heart block were excluded. Serological testing for Trypanosoma cruzi was performed at enrollment. A total of 80 patients were enrolled, and CD was diagnosed in six patients (7.5%). Patients with CD were more likely to be from El Salvador (P = 0.001). Other clinical, therapeutic, electrocardiographic, and echocardiographic variables were similar between the CD and non-CD groups. There is a high prevalence of CD among Latin American immigrants with pacemakers in Los Angeles.

The degree of breath methane production in IBS correlates with the severity of constipation.

BACKGROUND: Recent work has demonstrated that among irritable bowel syndrome (IBS) subjects, methane on lactulose breath test (LBT) is nearly universally associated with constipation predominance. This work has been based on subjective constipation outcomes. In this study, methane is compared to constipation in another population of IBS subjects with constipation being determined both subjectively and objectively. METHODS: A nested study was conducted in subjects enrolled in a double-blind randomized placebo-controlled study. After consent, subjects were asked to complete a stool diary for 7 days. This included logging of all bowel movements that week as well as documenting the stool consistency for each during the same period using the Bristol Stool Score. After 7 days, subjects were asked to rate their symptoms on a visual analogue scale (VAS) score (0-100 mm) for diarrhea and constipation. They then had an LBT to evaluate both methane and hydrogen profiles over 180 min. Subjects with methane were compared to those without methane for Bristol Stool Score, stool frequency, as well as VAS scores for diarrhea and constipation. The degree of constipation was then compared to the quantity of methane production on LBT based on area under the curve. RESULTS: Among 87 subjects, 20 (23.8%) produced methane. IBS subjects with methane had a mean constipation severity of 66.1 +/- 36.7 compared to 36.2 +/- 30.8 for nonmethane producers (P < 0.001). The opposite was noted for diarrhea (P < 0.01). On LBT, the quantity of methane seen on breath test was directly proportional to the degree of constipation reported (r = 0.60, P < 0.01). In addition, greater methane production correlated with a lower stool frequency (r =-0.70, P < 0.001) and Bristol Stool Score (r =-0.58, P < 0.01). CONCLUSION: Methane on LBT is associated with constipation both subjectively and objectively. The degree of methane production on breath test appears related to the degree of constipation.

Studying the overlap between IBS and GERD: a systematic review of the literature.

Evidence points to a significant overlap between irritable bowel syndrome (IBS) and gastroesophageal reflux disease (GERD). In this study, we evaluate this overlap by conducting a systematic review of the literature. Six electronic databases from 1966 through January 2005 were screened by multiple search terms to identify all epidmiological evidence linking IBS and GERD. In addition, AGA meeting abstracts for 2003 and 2004 were also screened. All studies were validated by the authors and data extracted according to predefined criteria. As a separate search strategy, studies evaluating the prevalence of IBS and GERD in the general population were sought. These articles were obtained to compare the prevalence of IBS and GERD in the community to the degree of overlap. The search identified 997 original titles with 15 publications that fulfilled our eligibility criteria. Among the 15 studies, 7 determined the GERD maximum mean prevalence in patients already diagnosed with IBS to be 39.3% and the weighted mean 30.3%. The other 7 studies examined the prevalence of IBS in patients already diagnosed with GERD. The maximum mean prevalence of IBS in subjects with known GERD was 48.8% and the weighted mean 60.5%. Based on the prevalence of IBS (12.1%) and GERD (19.4%) in the community, the rate of IBS in the non-GERD community was calculated to be only 5.1%. There is a strong overlap between GERD and IBS that exceeds the individual presence of each condition. In the absence of GERD, IBS is relatively uncommon.

The effect of a nonabsorbed oral antibiotic (rifaximin) on the symptoms of the irritable bowel syndrome: a randomized trial.

BACKGROUND: Alterations in gut flora may be important in the pathophysiology of the irritable bowel syndrome (IBS). OBJECTIVE: To determine whether the nonabsorbed antibiotic rifaximin is more effective than placebo in reducing symptoms in adults with IBS. DESIGN: Double-blind, randomized, placebo-controlled study. SETTING: 2 tertiary care medical centers. PARTICIPANTS: 87 patients who met Rome I criteria for IBS and were enrolled from December 2003 to March 2005. INTERVENTIONS: Participants who met enrollment criteria were randomly assigned to receive 400 mg of rifaximin 3 times daily for 10 days (n = 43) or placebo (n = 44). Eighty participants completed rifaximin therapy or placebo, and follow-up data were available for at least 34 participants per study group at any time point thereafter. MEASUREMENTS: A questionnaire was administered before treatment and 7 days after treatment. The primary outcome was global improvement in IBS. Patients were then asked to keep a weekly symptom diary for 10 weeks. RESULTS: Over the 10 weeks of follow-up, rifaximin resulted in greater improvement in IBS symptoms (P = 0.020). In addition, rifaximin recipients had a lower bloating score after treatment. LIMITATIONS: The major limitations of the study were its modest sample size and short duration and that most patients were from 1 center. CONCLUSIONS: Rifaximin improves IBS symptoms for up to 10 weeks after the discontinuation of therapy.

Neomycin improves constipation-predominant irritable bowel syndrome in a fashion that is dependent on the presence of methane gas: subanalysis of a double-blind randomized controlled study.

Recent studies have shown that normalization of the lactulose breath test (LBT) with neomycin leads to a significant reduction in irritable bowel syndrome (IBS) symptoms. This subanalysis was done on the constipation-predominant IBS subgroup of patients (C-IBS) to test the ability of neomycin to improve constipation and its correlation with the elimination of methane on breath test. IBS subjects underwent LBT in a blinded fashion. They were then randomly allocated to neomycin or placebo groups. For the purpose of this analysis, only the C-IBS subjects were identified. They were then evaluated for global improvement, abdominal pain, and constipation severity. The ability of neomycin to eliminate methane and its associated improvement in constipation was also determined. One hundred eleven subjects meeting Rome I criteria for IBS were included in the study. Thirty-nine of these had C-IBS. Of these, 20 received placebo and 19 received neomycin. With neomycin, a global improvement of 36.7+/-7.9% was seen, compared to 5.0+/-3.2% for placebo (P < .001) in the intention-to-treat analysis. Constipation was improved by 32.6+/-9.9% with neomycin compared to 18.7+/-7.2% for placebo (P=.26). Of the original 111 subjects, 12 demonstrated methane on breath test. All 12 of these patients were constipation predominant. In the methane producers receiving neomycin or placebo, improvement in constipation was significantly greater in those receiving neomycin (44.0+/-12.3%) compared to placebo (5.0+/-5.1%) (P < .05). Treatment with neomycin improves constipation in C-IBS. This improvement depends on the presence and elimination of methane on breath test.

Methane, a gas produced by enteric bacteria, slows intestinal transit and augments small intestinal contractile activity.

The presence of methane on lactulose breath test among irritable bowel syndrome (IBS) subjects is highly associated with the constipation-predominant form. Therefore, we set out to determine whether methane gas can alter small intestinal motor function. In dogs, small intestinal fistulae were created to permit measurement of intestinal transit. Using a radiolabel, we evaluated transit during infusion of room air and subsequently methane. In this model, small intestinal infusion of methane produced a slowing of transit in all dogs by an average of 59%. In a second experiment, guinea pig ileum was pinned into an organ bath for the study of contractile activity in response to brush strokes applied to the mucosa. The force of contraction was measured both orad and aborad to the stimulus. The experiment was repeated while the bath was gassed with methane. Contractile activities orad and aborad to the stimulus were significantly augmented by methane compared with room air (P < 0.05). In a third experiment, humans with IBS who had undergone a small bowel motility study were compared such that subjects who produced methane on lactulose breath test were compared with those producing hydrogen. The motility index was significantly higher in methane-producing IBS patients (1,851 +/- 861) compared with hydrogen producers (1,199 +/- 301) (P < 0.05). Therefore, methane, a gaseous by-product of intestinal bacteria, slows small intestinal transit and appears to do so by augmenting small bowel contractile activity.

A 14-day elemental diet is highly effective in normalizing the lactulose breath test.

Treatment of small intestinal bacterial overgrowth is frustrated by the low efficacy of antibiotics. Elemental diets have been shown to reduce enteric flora. In this study, we evaluate the ability of an elemental diet to normalize the lactulose breath test (LBT) in IBS subjects with abnormal breath test findings. Consecutive subjects with IBS and abnormal LBT suggesting the presence of bacterial overgrowth underwent a 2-week exclusive elemental diet. The diet consisted of Vivonex Plus (Novartis Nutrition Corp., Minneapolis, MN) in a quantity based on individual caloric requirement. On day 15 (prior to solid food), subjects returned for a follow-up breath test and those with an abnormal LBT were continued on the diet for an additional 7 days. The ability of an elemental diet to normalize the LBT was determined for days 15 and 21. A chart review was then conducted to evaluate any clinical benefit 1 month later. Of the 93 subjects available for analysis, 74 (80%) had a normal LBT on day 15 of the elemental diet. When those who continued to day 21 were included, five additional patients normalized the breath test (85%). On chart review, subjects who successfully normalized their breath test had a 66.4 +/- 36.1% improvement in bowel symptoms, compared to 11.9 +/- 22.0% in those who failed to normalize (P < 0.001). An elemental diet is highly effective in normalizing an abnormal LBT in IBS subjects, with a concomitant improvement in clinical symptoms.

IBS subjects with methane on lactulose breath test have lower postprandial serotonin levels than subjects with hydrogen.

We have previously shown that methane on lactulose breath test (LBT) is highly associated with constipation in IBS and that methane gas itself slows small bowel transit in dogs. Previous studies suggest that serotonin may have a role in the control of transit in IBS. In this study, we aim to evaluate the role of serotonin in methane producing IBS subjects. Rome I-positive IBS subjects were recruited into the study after exclusion criteria were met. A fasting LBT was performed after subjects filled out a questionnaire rating the degree of constipation and diarrhea. Within 7 days of this test, subjects returned fasting for determination of serotonin before and after a 75-g oral glucose meal. The serotonin response was compared between hydrogen and methane producing IBS subjects. After 2 subjects were excluded for inadequate blood samples, 18 subjects completed the study. Four of 18 subjects produced methane. The postprandial serotonin level in methane producing IBS subjects was lower than in hydrogen producers (P < 0.05). Methane producers had a reduction in serotonin after glucose. Methane producing IBS subjects have reduced postprandial serotonin. Whether methane is a surrogate marker of constipation or contributing to the reduced serotonin remains to be determined.

Breath testing to evaluate lactose intolerance in irritable bowel syndrome correlates with lactulose testing and may not reflect true lactose malabsorption.

OBJECTIVES: An increased prevalence of lactose intolerance is seen in irritable bowel syndrome (IBS). Recently, we demonstrated a high prevalence of abnormal lactulose breath test results in IBS suggesting bacterial overgrowth. Because symptoms of lactose intolerance result from bacterial fermentation, the purpose of this study was to determine whether an abnormal lactose breath test is reflective of malabsorption or early presentation to bacteria. METHODS: Subjects with diarrhea-predominant IBS were enrolled. On day 1, subjects underwent a lactulose breath test after an overnight fast. Within 1 wk, subjects returned after fasting for a lactose breath test with simultaneous blood glucose measurements every 15 min to complete a lactose tolerance test (LTT). Symptoms were evaluated 3 h after lactose administration. RESULTS: Twenty subjects completed the study. One subject inadvertently received dextrose through the intravenous and was excluded. Of the remaining 19 subjects, three (16%) had an abnormal LTT suggesting malabsorption. In all, 10 subjects (53%) had an abnormal lactose breath test, 14 (74%) had an abnormal lactulose breath test, and 11 (58%) had symptoms after lactose administration. The agreement with symptoms was moderate (kappa = 0.47) and fair (kappa = 0.24) when compared to the lactose breath test and LTT, respectively. There was a fair correlation between lactose breath test and LTT (kappa = 0.29). However, lactose breath test hydrogen levels >166 ppm were universally predictive of abnormal LTT. Finally, a significant correlation was seen between the hydrogen production on lactose and lactulose breath test (r = 0.56, p = 0.01). CONCLUSIONS: Lactose breath testing in IBS subjects does not seem to reflect malabsorption; it may be an indicator of abnormal lactulose breath test, suggesting bacterial overgrowth.

Methane production during lactulose breath test is associated with gastrointestinal disease presentation.

It has recently been determined that there is an increased prevalence of bacterial overgrowth in IBS. Since there are two gases (hydrogen and methane) measured on lactulose breath testing, we evaluated whether the different gas patterns on lactulose breath testing coincide with diarrhea and constipation symptoms in IBS and IBD. Consecutive patients referred to the gastrointestinal motility program at Cedars-Sinai Medical Center for lactulose breath testing were given a questionnaire to evaluate their gastrointestinal symptoms. Symptoms were graded on a scale of 0-5. Upon completion of the breath test, the results were divided into normal, hydrogen only, hydrogen and methane, and methane only positive breath tests. A comparison of all subjects and IBS subjects was undertaken to evaluate diarrhea and constipation with regards to the presence or absence of methane. This was further contrasted to Crohn's and ulcerative colitis (UC) patients in the database. After exclusion criteria, 551 subjects from the database were available for comparison. Of the 551 subjects (P < 0.05, one-way ANOVA) and in a subgroup of 296 IBS subjects (P < 0.05, one-way ANOVA), there was a significant association between the severity of reported constipation and the presence of methane. The opposite was true for diarrhea (P < 0.001). If a breath test was methane positive, this was 100% associated with constipation predominant IBS. Furthermore, IBS had a greater prevalence of methane production than Crohn's or UC. In fact, methane was almost nonexistent in the predominantly diarrheal conditions of Crohn's and UC. In conclusion, a methane positive breath test is associated with constipation as a symptom.