Gut microbiota, blood metabolites, and left ventricular diastolic dysfunction in US Hispanics/Latinos.

BACKGROUND: Left ventricular diastolic dysfunction (LVDD) is an important precursor of heart failure (HF), but little is known about its relationship with gut dysbiosis and microbial-related metabolites. By leveraging the multi-omics data from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), a study with population at high burden of LVDD, we aimed to characterize gut microbiota associated with LVDD and identify metabolite signatures of gut dysbiosis and incident LVDD. RESULTS: We included up to 1996 Hispanic/Latino adults (mean age: 59.4 years; 67.1% female) with comprehensive echocardiography assessments, gut microbiome, and blood metabolome data. LVDD was defined through a composite criterion involving tissue Doppler assessment and left atrial volume index measurements. Among 1996 participants, 916 (45.9%) had prevalent LVDD, and 212 out of 594 participants without LVDD at baseline developed incident LVDD over a median 4.3 years of follow-up. Using multivariable-adjusted analysis of compositions of microbiomes (ANCOM-II) method, we identified 7 out of 512 dominant gut bacterial species (prevalence > 20%) associated with prevalent LVDD (FDR-q < 0.1), with inverse associations being found for Intestinimonas_massiliensis, Clostridium_phoceensis, and Bacteroide_coprocola and positive associations for Gardnerella_vaginali, Acidaminococcus_fermentans, Pseudomonas_aeruginosa, and Necropsobacter_massiliensis. Using multivariable adjusted linear regression, 220 out of 669 circulating metabolites with detection rate > 75% were associated with the identified LVDD-related bacterial species (FDR-q < 0.1), with the majority being linked to Intestinimonas_massiliensis, Clostridium_phoceensis, and Acidaminococcus_fermentans. Furthermore, 46 of these bacteria-associated metabolites, mostly glycerophospholipids, secondary bile acids, and amino acids, were associated with prevalent LVDD (FDR-q < 0.1), 21 of which were associated with incident LVDD (relative risk ranging from 0.81 [p = 0.001, for guanidinoacetate] to 1.25 [p = 9 × 10-5, for 1-stearoyl-2-arachidonoyl-GPE (18:0/20:4)]). The inclusion of these 21 bacterial-related metabolites significantly improved the prediction of incident LVDD compared with a traditional risk factor model (the area under the receiver operating characteristic curve [AUC] = 0.73 vs 0.70, p = 0.001). Metabolite-based proxy association analyses revealed the inverse associations of Intestinimonas_massilliensis and Clostridium_phoceensis and the positive association of Acidaminococcus_fermentans with incident LVDD. CONCLUSION: In this study of US Hispanics/Latinos, we identified multiple gut bacteria and related metabolites linked to LVDD, suggesting their potential roles in this preclinical HF entity. Video Abstract.

Lactobacillus plantarum probiotic induces Nrf2-mediated antioxidant signaling and eNOS expression resulting in improvement of myocardial diastolic function.

Yorkshire swine were fed standard diet (n = 7) or standard diet containing applesauce rich in caffeic acid with Lactobacillus plantarum (n = 7) for 3 wk. An ameroid constrictor was next placed around the left coronary circumflex artery, and the dietary regimens were continued. At 14 wk, cardiac function, myocardial perfusion, vascular density, and molecular signaling in ischemic myocardium were evaluated. The L. plantarum-applesauce augmented NF-E2-related factor 2 (Nrf2) in the ischemic myocardium and induced Nrf2-regulated antioxidant enzymes heme oxygenase-1 (HO-1), NADPH dehydrogenase quinone 1 (NQO-1), and thioredoxin reductase (TRXR-1). Improved left ventricular diastolic function and decreased myocardial collagen expression were seen in animals receiving the L. plantarum-applesauce supplements. The expression of endothelial nitric oxide synthase (eNOS) was increased in ischemic myocardial tissue of the treatment group, whereas levels of asymmetric dimethyl arginine (ADMA), hypoxia inducible factor 1α (HIF-1α), and phosphorylated MAPK (pMAPK) were decreased. Collateral-dependent myocardial perfusion was unaffected, whereas arteriolar and capillary densities were reduced as determined by α-smooth muscle cell actin and CD31 immunofluorescence in ischemic myocardial tissue. Dietary supplementation with L. plantarum-applesauce is a safe and effective method of enhancing Nrf2-mediated antioxidant signaling cascade in ischemic myocardium. Although this experimental diet was associated with a reduction in hypoxic stimuli, decreased vascular density, and without any change in collateral-dependent perfusion, the net effect of an increase in antioxidant activity and eNOS expression resulted in improvement in diastolic function.NEW & NOTEWORTHY Colonization of the gut microbiome with certain strains of L. Plantarum has been shown to convert caffeic acid readily available in applesauce to 4-vinyl-catechol, a potent activator of the Nrf2 antioxidant defense pathway. In this exciting study, we show that simple dietary supplementation with L. Plantarum-applesauce-mediated Nrf2 activation supports vascular function, ameliorates myocardial ischemic diastolic dysfunction, and upregulates expression of eNOS.

Prognostic Role of Left Ventricular Systolic Function Measured by Speckle Tracking Echocardiography in Septic Shock.

BACKGROUND: Left ventricular (LV) systolic dysfunction is common in septic shock. Global longitudinal strain (GLS) measured by speckle tracking echocardiography (STE) is a useful marker of intrinsic left ventricular systolic function. However, the association between left ventricular GLS and outcome in septic patients is not well understood. We performed this prospective study to investigate the prognostic value of LV systolic function utilizing speckle tracking echocardiography in patients with septic shock. METHODS: All the patients with septic shock based on sepsis-3 definition admitted to the intensive care unit were prospectively studied with STE within 24 hours after the onset of septic shock. Baseline clinical and echocardiographic variables were collected. The primary outcome was in-hospital mortality. RESULTS: During a 19-month period, 90 consecutive patients were enrolled in the study. The in-hospital mortality rate was 43.3%. Compared with survivors, nonsurvivors exhibited significantly less negative GLS (-13.1 ± 3.3% versus -15.8 ± 2.9%; p < 0.001), which reflected worse LV systolic function. The area under the ROC curves of GLS for the prediction of mortality was 0.76 (95% CI 0.67 to 0.87). Patients with GLS > -14.1% showed a significantly higher mortality rate (67.7% versus 15.6%; p < 0.0001; log-rank = 23.3; p < 0.0001). In the multivariate analysis, GLS (HR, 1.27; 95% CI 1.07 to 1.50, p = 0.005) and SOFA scores (HR, 1.27; 95% CI 1.08 to 1.50, p = 0.004) were independent predictors of in-hospital mortality. CONCLUSIONS: Our study indicated that LV systolic function measured by STE might be associated with mortality in patients with septic shock.

Age-dependent cardiac function during experimental sepsis: effect of pharmacological activation of AMP-activated protein kinase by AICAR.

Age represents a major risk factor for multiple organ failure, including cardiac dysfunction, in patients with sepsis. AMP-activated protein kinase (AMPK) is a crucial regulator of energy homeostasis that controls mitochondrial biogenesis by activation of peroxisome proliferator-activated receptor-γ coactivator-1α and disposal of defective organelles by autophagy. We investigated whether AMPK dysregulation contributes to age-dependent cardiac injury in young (2-3 mo) and mature adult (11-13 mo) male mice subjected to sepsis by cecal ligation and puncture and whether AMPK activation by 5-amino-4-imidazole carboxamide riboside affords cardioprotective effects. Plasma proinflammatory cytokines and myokine follistatin were similarly elevated in vehicle-treated young and mature adult mice at 18 h after sepsis. However, despite equivalent troponin I and T levels compared with similarly treated young mice, vehicle-treated mature adult mice exhibited more severe cardiac damage by light and electron microscopy analyses with more marked intercellular edema, inflammatory cell infiltration, and mitochondrial derangement. Echocardiography revealed that vehicle-treated young mice exhibited left ventricular dysfunction after sepsis, whereas mature adult mice exhibited a reduction in stroke volume without apparent changes in load-dependent indexes of cardiac function. At molecular analysis, phosphorylation of the catalytic subunits AMPK-α1/α2 was associated with nuclear translocation of peroxisome proliferator-activated receptor-γ coactivator-1α in vehicle-treated young but not mature adult mice. Treatment with 5-amino-4-imidazole carboxamide riboside ameliorated cardiac architecture derangement in mice of both ages. These cardioprotective effects were associated with attenuation of the systemic inflammatory response and amelioration of cardiac dysfunction in young mice only, not in mature adult animals. NEW & NOTEWORTHY Our data suggest that sepsis-induced cardiac dysfunction manifests with age-dependent characteristics, which are associated with a distinct regulation of AMP-activated protein kinase-dependent metabolic pathways. Consistent with this age-related deterioration, pharmacological activation of AMP-activated protein kinase may afford cardioprotective effects allowing a partial recovery of cardiac function in young but not mature age.

Aberrant fecal flora observed in guinea pigs with pressure overload is mitigated in animals receiving vagus nerve stimulation therapy.

Altered gut microbial diversity has been associated with several chronic disease states, including heart failure. Stimulation of the vagus nerve, which innervates the heart and abdominal organs, is proving to be an effective therapeutic in heart failure. We hypothesized that cervical vagus nerve stimulation (VNS) could alter fecal flora and prevent aberrations observed in fecal samples from heart failure animals. To determine whether microbial abundances were altered by pressure overload (PO), leading to heart failure and VNS therapy, a VNS pulse generator was implanted with a stimulus lead on either the left or right vagus nerve before creation of PO by aortic constriction. Animals received intermittent, open-loop stimulation or sham treatment, and their heart function was monitored by echocardiography. Left ventricular end-systolic and diastolic volumes, as well as cardiac output, were impaired in PO animals compared with baseline. VNS mitigated these effects. Metagenetic analysis was then performed using 16S rRNA sequencing to identify bacterial genera present in fecal samples. The abundance of 10 genera was significantly altered by PO, 8 of which were mitigated in animals receiving either left- or right-sided VNS. Metatranscriptomics analyses indicate that the abundance of genera that express genes associated with ATP-binding cassette transport and amino sugar/nitrogen metabolism was significantly changed following PO. These gut flora changes were not observed in PO animals subjected to VNS. These data suggest that VNS prevents aberrant gut flora following PO, which could contribute to its beneficial effects in heart failure patients.

TandemHeart as a Bridge to Recovery in Legionella Myocarditis.

Legionnaires' disease is the designation for pneumonia caused by the Legionella species. Among the rare extrapulmonary manifestations, cardiac involvement is most prevalent, in the forms of myocarditis, pericarditis, postcardiotomy syndrome, and prosthetic valve endocarditis. Mechanical circulatory support has proved to be a safe and effective bridge to myocardial recovery in patients with acute fulminant myocarditis; however, to our knowledge, this support has not been used in infectious myocarditis specifically related to Legionellosis. We describe a case of Legionella myocarditis associated with acute left ventricular dysfunction and repolarization abnormalities in a 48-year-old man. The patient fully recovered after left ventricular unloading with use of a TandemHeart percutaneous ventricular assist device. In addition, we review the English-language medical literature on Legionella myocarditis and focus on cardiac outcomes.

Pneumonia and purulent pericarditis caused by Streptococcus pneumoniae: an uncommon association in the antibiotic era.

Bacterial pericarditis in children has become a rare entity in the modern antibiotic era. The most common pathogen is Staphylococcus aureus, being Streptococcus pneumoniae an exceptional cause. We present 2 children, who were diagnosed of pneumonia complicated with a pleural effusion that developed a purulent pericarditis with signs of cardiac tamponade. One of them had received 4 doses of the 7-valent conjugated pneumococcal vaccine. Systemic antibiotics and pericardial and pleural drainages were used. Pneumococcal antigens were positive in pleural and pericardial fluids in both cases, and S. pneumoniae was isolated from pleural effusion in one of them. Both children fully recovered, and none of them developed constrictive pericarditis, although 1 case presented a transient secondary left ventricular dysfunction. Routine immunization with 10- and 13-valent vaccines including a wider range of serotypes should further decrease the already low incidence.

Diphtheroids as a cause of endocarditis in a haemodialysis patient.

The authors report a fatal case of Corynebacterium sp. endocarditis. Corynebacterium spp. are non-sporulating, pleomorphic Gram-positive bacilli. In particular the authors have identified a species of Corynebacterium very closely related to C striatum. This is C simulans. The authors were able to identify the genus and species using various phenotypic tests. Highlighted here is the importance of identifying diphtheroids as a significant pathogen in the appropriate setting and the need to start antibiotic therapy if this is suspected.

Endotoxemia decreases matching of regional blood flow and O2 delivery to O2 uptake in the porcine left ventricle.

Heterogeneity of regional coronary blood flow is caused in part by heterogeneity in O(2) demand in the normal heart. We investigated whether myocardial O(2) supply/demand mismatching is associated with the myocardial depression of sepsis. Regional blood flow (microspheres) and O(2) uptake ([(13)C]acetate infusion and analysis of resultant NMR spectra) were measured in about nine contiguous tissue samples from the left ventricle (LV) in each heart. Endotoxemic pigs (n = 9) showed hypotension at unchanged cardiac output with a fall in LV stroke work and first derivative of LV pressure relative to controls (n = 4). Global coronary blood flow and O(2) delivery were maintained. Lactate accumulated in arterial blood, but net lactate extraction across the coronary bed was unchanged during endotoxemia. When LV O(2) uptake based on blood gas versus NMR data were compared, the correlation was 0.73 (P = 0.007). While stable over time in controls, regional blood flows were strongly redistributed during endotoxin shock, with overall flow heterogeneity unchanged. A stronger redistribution of blood flow with endotoxin was associated with a larger fall in LV function parameters. Moreover, the correlation of regional O(2) delivery to uptake fell from r = 0.73 (P < 0.001) in control to r = 0.18 (P = 0.25, P = 0.009 vs. control) in endotoxemic hearts. The results suggest a redistribution of LV regional coronary blood flow during endotoxin shock in pigs, with regional O(2) delivery mismatched to O(2) demand. Mismatching may underlie, at least in part, the myocardial depression of sepsis.

Presence of Borrelia burgdorferi in endomyocardial biopsies in patients with new-onset unexplained dilated cardiomyopathy.

Dilated cardiomyopathy (DCM) represents the third most common cause of heart failure and the most frequent cause of heart transplantation. Infectious, mostly viral, and autoimmune mechanisms, together with genetic abnormalities, have been reported as three major causes of DCM. We hypothesized that Lyme disease (LD), caused by spirochete Borrelia burgdorferi (Bb), might be an important cause of new-onset unexplained DCM in patients living in a highly endemic area for LD such as the Czech Republic. We performed endomyocardial biopsy (EMB) in 39 consecutive patients presenting with symptomatic unexplained left ventricular (LV) systolic dysfunction lasting no more than 12 months. In eight subjects (21%), Bb was detected in the EMB sample by polymerase chain reaction or by electron microscopy. None of these patients exhibited any form of atrioventricular block or other extracardiac manifestation of Bb infection. Serological testing identified IgG antibodies against Bb in only two cases and IgM antibodies in none. All affected patients were treated with intravenous ceftriaxone for 3 weeks. At 6 months follow-up, LV morphology and function as well as functional status of these patients significantly improved. In conclusion, Bb infection may represent an important cause of new-onset unexplained DCM in patients living in endemic regions such as the Czech Republic. Because the antibiotic treatment appears to be markedly effective and serological examination does not provide a tool for diagnosing the disease, EMB focused on the detection of Bb should be performed in all patients from endemic areas with new-onset unexplained DCM not responding to conventional therapy.

Medical treatment of a Salmonella-infected left ventricular pseudoaneurysm: a case report.

Here, we present a case of Salmonella infection in a post-myocardial infarction patient with a left ventricular aneurysm and mural thrombus. This is a rare case that was successfully treated with medicinal therapy alone. Our experience with this case documents the early spontaneous drainage of the myocardial abscess by 8 weeks of antibiotic therapy under serial two- and three-dimensional echocardiography to monitor the clinical outcomes and guide the decision-making process. This approach may be a viable alternative for intolerant, high-risk surgical aneurysmectomy patients.

A case of tuberculous endocarditis with acute aortic valve insufficiency and annular subvalvular left ventricular aneurysm.

Tuberculous endocarditis is an exceptionally rare disease, and its surgical operation has been reported in only one case. This is a successful surgical report of acute aortic insufficiency caused by tuberculous endocarditis associated with annular subvalvular left ventricular aneurysm (ASLVA) beneath the aortic valve. This patient had acute left ventricular failure and cardiorespiratory arrest and suffered from multiple organ dysfunction and coagulopathy disorder. Urgent surgery was performed to replace the aortic valve with the approximation of ASLVA. Histopathological findings of the excised aortic cusps gave the diagnosis of tuberculous endocarditis, and antituberculous drug administration started on the first postoperative day. Postoperative recovery has been uneventful without relapse of tuberculosis for 7 postoperative years.

Left ventricular apical ballooning in mitral endocarditis.

Tako-tsubo cardiomyopathy is an enigmatic syndrome characterized by chest pain, transient left ventricular dysfunction and specific electrocardiographic changes induced by physical or emotional stress. We describe the first case of this syndrome associated with acute mitral regurgitation due to bacterial endocarditis: the reversible ventricular dysfunction might have been induced by altered catecholamine dynamics due to the pulmonary edema.

[Impact of chronic Chlamydia pneumoniae infection on left ventricular remodeling after myocardial infarction]. / Wplyw przewleklego zakazenia Chlamydia pneumoniae na remodeling lewej komory po zawale serca.

BACKGROUND: Postmyocardial infarction left ventricular remodeling is modified by inflammatory processes and structural changes in the myocardium. Chlamydia pneumoniae (Chp) causes chronic myocyte infection, affects apoptosis and TNF-alpha production, and may induce cross reactivity with alpha myosin. This is the way in which this intracellular pathogen may modulate remodeling on the cellular and organ level. MATERIAL AND METHODS: The study was conducted in 101 patients with a first myocardial infarction in whom we evaluated the serological features of Chp infection using the ELISA method and echocardiographic left ventricular volume at 10 days and 10 weeks after the infarction. RESULTS: Patients with chronic Chp infection had a tendency toward higher end-diastolic volume at 10 weeks after the infarction (123 +/- 32.9 ml vs. 134 +/- 34.7 ml, p = 0.09). In order to better define this relationship we used ROC analysis and measured levels of antibodies: IgG = 117 EIU and IgA = 15.6 EIU by which we divided the patients into two subgroups. Those with IgG > or = 117 EIU and IgA > or = 15.6 EIU belong to the subgroup with chronic and active Chp infection. These patients had larger left ventricular end-diastolic volumes (155.8 vs. 123.1 ml, p = 0.0005) and end-systolic volumes (77.4 vs. 59.5 ml, p = 0.006) at 10 weeks after the infarction. Both subgroups were similar with respect to age, gender, history of arterial hypertension, systolic and diastolic blood pressure values, infarct site, reperfusion, infarct size, left ventricular ejection fraction and left ventricular contractility index. Type of reperfusion therapy and pharmacological treatment at 10 days and at 10 weeks did not differ, either. CONCLUSIONS: Chronic Chlamydia pneumonie infection modifies the course of left ventricular remodeling.

Murine in vivo myocardial contractile dysfunction after burn injury is exacerbated by pneumonia sepsis.

We evaluated hemodynamic and cardiac contractile dysfunction in a murine model of 40% contact burn complicated by Streptococcus pneumoniae (1 x 10(5) CFU) sepsis. Male, 9- to 10-week-old C57/BL6 mice were divided into the following groups: sham burn, sham sepsis; 24 h after burn alone; 24 h after sepsis alone; 7 days after burn alone; and 7 days after burn followed by pneumonia sepsis. Hemodynamic and cardiac contractile function was assessed with carotid artery cannulation and left ventricular pressure-volume analysis. At 24 h after burn, there were significant decreases in all load-insensitive contractility variables including the end-systolic pressure volume relationship, preload-recruitable stroke work, and maximum elastance, but there were no changes in global hemodynamics. Twenty-four hours after sepsis, there was similar cardiac contractile dysfunction, along with a decrease in cardiac output, but mean arterial pressure was maintained with an increase in systemic vascular resistance. Late burn (7 days) was associated with a recovery of all contractility variables except the end-systolic pressure volume relationship. However, sepsis induced during the late burn period was associated with a significant decrease in heart rate and cardiac output, but mean arterial pressure was still maintained with increased systemic vascular resistance. With burn complicated by sepsis, all cardiac contractility variables showed profound contractile dysfunction. Our data indicate that burn complicated by sepsis is associated with more pronounced cardiac contractile dysfunction than burn alone or sepsis alone.