ABSTRACT
Gut microbiome (GMB) has been increasingly recognized as a contributor to development and progression of heart failure (HF), immune-mediated subtypes of cardiomyopathy (myocarditis and anthracycline-induced cardiotoxicity), response to certain cardiovascular drugs, and HF-related comorbidities, such as chronic kidney disease, cardiorenal syndrome, insulin resistance, malnutrition, and cardiac cachexia. Gut microbiome is also responsible for the "gut hypothesis" of HF, which explains the adverse effects of gut barrier dysfunction and translocation of GMB on the progression of HF. Furthermore, accumulating evidence has suggested that gut microbial metabolites, including short chain fatty acids, trimethylamine N-oxide (TMAO), amino acid metabolites, and bile acids, are mechanistically linked to pathogenesis of HF, and could, therefore, serve as potential therapeutic targets for HF. Even though there are a variety of proposed therapeutic approaches, such as dietary modifications, prebiotics, probiotics, TMAO synthesis inhibitors, and fecal microbial transplant, targeting GMB in HF is still in its infancy and, indeed, requires further preclinical and clinical evidence. In this review, we aim to highlight the role gut microbiome plays in HF pathophysiology and its potential as a novel therapeutic target in HF.
Subject(s)
Gastrointestinal Microbiome , Heart Failure/pathology , Animals , Comorbidity , Heart Failure/epidemiology , Heart Failure/microbiology , HumansABSTRACT
BACKGROUND: Patients with heart failure (HF) are frequently hospitalized with common bacterial infections. It is unknown whether they experience concomitant Clostridium difficile infection (CDI) more frequently than patients without HF, and whether CDI affects their mortality. METHODS: We used 2012 National Inpatient Sample data to determine the rate of CDI and associated in-hospital mortality for hospitalized patients with comorbid HF and urinary tract infection (UTI), pneumonia (PNA), or sepsis. Univariate and multivariate analyses were performed. Weighted data are presented. RESULTS: There were an estimated 5,851,582 patient hospitalizations with discharge diagnosis of UTI, PNA, or sepsis in 2012 in the United States. Of these, 23.4% had discharge diagnosis of HF. Patients with HF were on average older and had more comorbidities. CDI rates were higher in hospitalizations with discharge diagnosis of HF compared with those without HF (odds ratio 1.13, 95% confidence interval 1.10-1.16) after controlling for patient demographics and comorbidities and hospital characteristics. Among HF hospitalizations with UTI, PNA, or sepsis, those with concomitant CDI had a higher in-hospital mortality than those without concomitant CDI (odds ratio 1.81, 95% confidence interval 1.71-1.92) after controlling for the covariates outlined previously. CONCLUSIONS: HF is associated with higher CDI rates among hospitalized patients with other common bacterial infections, even when adjusting for other known risk factors for CDI. Among these patients with comorbid HF, CDI is associated with markedly higher in-hospital mortality. These findings may suggest an opportunity to improve outcomes for hospitalized patients with HF and common bacterial infections, possibly through improved Clostridium difficile screening and prophylaxis protocols.
Subject(s)
Clostridium Infections/drug therapy , Clostridium Infections/epidemiology , Heart Failure/drug therapy , Heart Failure/epidemiology , Hospital Mortality , Aged , Analysis of Variance , Anti-Bacterial Agents/therapeutic use , Bacterial Infections/diagnosis , Bacterial Infections/drug therapy , Bacterial Infections/epidemiology , Cause of Death , Clostridioides difficile/pathogenicity , Clostridium Infections/diagnosis , Cohort Studies , Comorbidity , Databases, Factual , Diuretics/therapeutic use , Female , Follow-Up Studies , Heart Failure/diagnosis , Hospitalization/statistics & numerical data , Humans , Incidence , Kaplan-Meier Estimate , Male , Middle Aged , Multivariate Analysis , Reference Values , Retrospective Studies , Survival Analysis , Treatment OutcomeABSTRACT
Despite therapeutic advances, chronic heart failure (HF) is still associated with significant risk of morbidity and mortality. The course of disease and responses to therapies vary widely among individuals with HF, highlighting the need for precision medicine approaches. Gut microbiome stands to be an important aspect of precision medicine in HF. Exploratory clinical studies have revealed shared patterns of gut microbiome dysregulation in this disease, with mechanistic animal studies providing evidence for active involvement of the gut microbiome in development and pathophysiology of HF. Deeper insights into gut microbiome-host interactions in patients with HF promise to deliver novel disease biomarkers, preventative and therapeutic targets, and improve disease risk stratification. This knowledge may enable a paradigm shift in how we care for patients with HF, and pave the path toward improved clinical outcomes through personalized HF care.
Subject(s)
Gastrointestinal Microbiome , Heart Failure , Heart Failure/therapy , Precision Medicine , Humans , Animals , Lipopolysaccharides , Fatty Acids, Volatile , Bile Acids and SaltsABSTRACT
Consumer wearable devices that continuously measure vital signs have been used to monitor the onset of infectious disease. Here, we show that data from consumer smartwatches can be used for the pre-symptomatic detection of coronavirus disease 2019 (COVID-19). We analysed physiological and activity data from 32 individuals infected with COVID-19, identified from a cohort of nearly 5,300 participants, and found that 26 of them (81%) had alterations in their heart rate, number of daily steps or time asleep. Of the 25 cases of COVID-19 with detected physiological alterations for which we had symptom information, 22 were detected before (or at) symptom onset, with four cases detected at least nine days earlier. Using retrospective smartwatch data, we show that 63% of the COVID-19 cases could have been detected before symptom onset in real time via a two-tiered warning system based on the occurrence of extreme elevations in resting heart rate relative to the individual baseline. Our findings suggest that activity tracking and health monitoring via consumer wearable devices may be used for the large-scale, real-time detection of respiratory infections, often pre-symptomatically.
Subject(s)
COVID-19/diagnosis , COVID-19/prevention & control , Pandemics/prevention & control , Adult , Asymptomatic Diseases , Female , Humans , Male , Monitoring, Physiologic/methods , Retrospective Studies , SARS-CoV-2/pathogenicity , Wearable Electronic DevicesSubject(s)
Cardiovascular Diseases , Gastrointestinal Microbiome , Heart Failure , Hypertension , HumansABSTRACT
OBJECTIVE: Interplay of baseline physiologic status, case complexity, technical performance, and outcomes in high-acuity operations has been poorly defined. This study explored these interactions to determine whether a technically optimal operation can mitigate effects of baseline physiology and high case-complexity on outcomes for the stage I Norwood procedure. METHODS: Technical performance was categorized as optimal, adequate, or inadequate from adequacy of the anatomic repair of the stage I subprocedures according to anatomic areas where intervention is performed. Physiological illness severity statuses in preoperative and postoperative periods were determined with Pediatric Risk of Mortality III system, which uses 17 physiologic variables. Case complexity was calculated with Aristotle comprehensive system. All patients undergoing stage I procedure from January 2004 to December 2007 were retrospectively studied. RESULTS: One hundred thirty-five procedures were included. Five were excluded from the technical performance assessment because of inadequate postoperative data. Eighty-one (62.3%), 26 (20%), and 23 (17.7%), respectively, were scored as optimal, adequate, and inadequate. Overall hospital mortality was 14.1%. Inadequate technical performance, high-complexity Aristotle comprehensive scores, and high preoperative illness severity scores correlated with significantly higher hospital mortality, longer stay, and greater frequency of major postoperative complications. In subgroup analysis of patients with optimal technical performance, outcomes were favorable irrespective of high or low preoperative physiologic illness severity or case complexity. CONCLUSIONS: In stage I Norwood procedures, optimal technical performance attenuated effects of poor preoperative physiologic status and high case complexity, with reduced hospital mortality. Inadequate technical performance resulted in poor outcomes regardless of preoperative status.