Dataset Information

Gut-dependent microbial translocation induces inflammation and cardiovascular events after ST-elevation myocardial infarction.

ABSTRACT: BACKGROUND:Post-infarction cardiovascular remodeling and heart failure are the leading cause of myocardial infarction (MI)-driven death during the past decades. Experimental observations have involved intestinal microbiota in the susceptibility to MI in mice; however, in humans, identifying whether translocation of gut bacteria to systemic circulation contributes to cardiovascular events post-MI remains a major challenge. RESULTS:Here, we carried out a metagenomic analysis to characterize the systemic bacteria in a cohort of 49 healthy control individuals, 50 stable coronary heart disease (CHD) subjects, and 100 ST-segment elevation myocardial infarction (STEMI) patients. We report for the first time higher microbial richness and diversity in the systemic microbiome of STEMI patients. More than 12% of post-STEMI blood bacteria were dominated by intestinal microbiota (Lactobacillus, Bacteroides, and Streptococcus). The significantly increased product of gut bacterial translocation (LPS and D-lactate) was correlated with systemic inflammation and predicted adverse cardiovascular events. Following experimental MI, compromised left ventricle (LV) function and intestinal hypoperfusion drove gut permeability elevation through tight junction protein suppression and intestinal mucosal injury. Upon abrogation of gut bacterial translocation by antibiotic treatment, both systemic inflammation and cardiomyocyte injury in MI mice were alleviated. CONCLUSIONS:Our results provide the first evidence that cardiovascular outcomes post-MI are driven by intestinal microbiota translocation into systemic circulation. New therapeutic strategies targeting to protect the gut barrier and eliminate gut bacteria translocation may reduce or even prevent cardiovascular events post-MI.

SUBMITTER: Zhou X

PROVIDER: S-EPMC5883284 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Gut-dependent microbial translocation induces inflammation and cardiovascular events after ST-elevation myocardial infarction.

Zhou Xin X Li Jing J Guo Junli J Geng Bin B Ji Wenjie W Zhao Qian Q Li Jinlong J Liu Xinlin X Liu Junxiang J Guo Zhaozeng Z Cai Wei W Ma Yongqiang Y Ren Dong D Miao Jun J Chen Shaobo S Zhang Zhuoli Z Chen Junru J Zhong Jiuchang J Liu Wenbin W Zou Minghui M Li Yuming Y Cai Jun J

Microbiome 20180403 1

<h4>Background</h4>Post-infarction cardiovascular remodeling and heart failure are the leading cause of myocardial infarction (MI)-driven death during the past decades. Experimental observations have involved intestinal microbiota in the susceptibility to MI in mice; however, in humans, identifying whether translocation of gut bacteria to systemic circulation contributes to cardiovascular events post-MI remains a major challenge.<h4>Results</h4>Here, we carried out a metagenomic analysis to char ...[more]

PMID: 29615110

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Project description:Background Early systolic lengthening (ESL) may occur in ischemic myocardial segments with reduced contractile force. We sought to evaluate the prognostic potential of ESL in patients with ST-segment-elevation myocardial infarction treated with primary percutaneous coronary intervention. Methods and Results We prospectively enrolled 373 patients with ST-segment-elevation myocardial infarction treated with primary percutaneous coronary intervention. All patients underwent a speckle tracking echocardiographic examination a median of 2 days (interquartile range, 1-3 days) after the percutaneous coronary intervention. We assessed a novel viability index, the ESL index, defined as follows: [-100×(peak positive systolic strain/peak negative strain in cardiac cycle)]. We also calculated ESL duration, defined as time from onset of QRS complex on the ECG to time of peak positive systolic strain. Both parameters were averaged from 18 myocardial segments. During a median follow-up of 5.3 years (interquartile range, 2.5-6.0 years), 145 (39%) experienced major adverse cardiovascular events, a composite of incident heart failure, new myocardial infarction, and all-cause mortality. The ESL index and ESL duration were significantly increased in culprit lesion areas (6.7±6.2% versus 5.0±4.1% and 43±33 ms versus 33±24 ms, respectively; P<0.001 for both). In Cox proportional hazard models, the ESL index (hazard ratio, 1.27 per 1% increase; 95% CI, 1.13-1.43; P<0.001) and ESL duration (hazard ratio, 1.49 per 1-ms increase; 95% CI, 1.15-1.92; P=0.002) yielded prognostic information on major adverse cardiovascular events. Both associations remained significant after adjusting for clinical, echocardiographic, and invasive confounders. Conclusions Assessment of ESL after primary percutaneous coronary intervention in patients with ST-segment-elevation myocardial infarction yields independent and significant prognostic information on the future risk of cardiovascular events.

Project description:ImportanceChallenges to improving ST-segment elevation myocardial infarction (STEMI) care are formidable in low- to middle-income countries because of several system-level factors.ObjectiveTo examine access to reperfusion and percutaneous coronary intervention (PCI) during STEMI using a hub-and-spoke model.Design, setting, and participantsThis multicenter, prospective, observational study of a quality improvement program studied 2420 patients 20 years or older with symptoms or signs consistent with STEMI at primary care clinics, small hospitals, and PCI hospitals in the southern state of Tamil Nadu in India. Data were collected from the 4 clusters before implementation of the program (preimplementation data). We required a minimum of 12 weeks for the preimplementation data with the period extending from August 7, 2012, through January 5, 2013. The program was then implemented in a sequential manner across the 4 clusters, and data were collected in the same manner (postimplementation data) from June 12, 2013, through June 24, 2014, for a mean 32-week period.ExposuresCreation of an integrated, regional quality improvement program that linked the 35 spoke health care centers to the 4 large PCI hub hospitals and leveraged recent developments in public health insurance schemes, emergency medical services, and health information technology.Main outcomes and measuresPrimary outcomes focused on the proportion of patients undergoing reperfusion, timely reperfusion, and postfibrinolysis angiography and PCI. Secondary outcomes were in-hospital and 1-year mortality.ResultsA total of 2420 patients with STEMI (2034 men [84.0%] and 386 women [16.0%]; mean [SD] age, 54.7 [12.2] years) (898 in the preimplementation phase and 1522 in the postimplementation phase) were enrolled, with 1053 patients (43.5%) from the spoke health care centers. Missing data were common for systolic blood pressure (213 [8.8%]), heart rate (223 [9.2%]), and anterior MI location (279 [11.5%]). Overall reperfusion use and times to reperfusion were similar (795 [88.5%] vs 1372 [90.1%]; P = .21). Coronary angiography (314 [35.0%] vs 925 [60.8%]; P < .001) and PCI (265 [29.5%] vs 707 [46.5%]; P < .001) were more commonly performed during the postimplementation phase. In-hospital mortality was not different (52 [5.8%] vs 85 [5.6%]; P = .83), but 1-year mortality was lower in the postimplementation phase (134 [17.6%] vs 179 [14.2%]; P = .04), and this difference remained consistent after multivariable adjustment (adjusted odds ratio, 0.76; 95% CI, 0.58-0.98; P = .04).Conclusions and relevanceA hub-and-spoke model in South India improved STEMI care through greater use of PCI and may improve 1-year mortality. This model may serve as an example for developing STEMI systems of care in other low- to middle-income countries.

Dataset Information

Gut-dependent microbial translocation induces inflammation and cardiovascular events after ST-elevation myocardial infarction.

Publications

Gut-dependent microbial translocation induces inflammation and cardiovascular events after ST-elevation myocardial infarction.

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