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Background: Inflammatory heart disease can be triggered by a variety of causes, both infectious and noninfectious in nature. We hypothesized that inflammatory cardiomyopathy is potentially related to microbial infection., Methods: In this retrospective study, we used deep RNA sequencing on formalin-fixed paraffin-embedded heart tissue specimens to detect pathogenic agents. We first investigated 4 single-sample cases to test the feasibility of this diagnostic protocol and further 3 control-sample paired cases to improve the protocol with differential metatranscriptomics next-generation sequencing (mtNGS) analysis., Results: We demonstrate that differential mtNGS allows identification of various microbials as potentially pathogenic, for example, Cutibacterium acnes , Corynebacterium aurimucosum , and Pseudomonas denitrificans , which are usually commensal in healthy individuals. Differential mtNGS also allows characterization of human host response in each individual by profiling alterations of gene expression, networked pathways, and inferred immune cell compositions, information of which is beneficial for us to understand different etiologies and immunity roles in each case. Additionally, differential mtNGS allows the identification of genetic variants in patients that may contribute to their susceptibility to particular microbial infections., Conclusions: The demonstrated power of differential mtNGS in simultaneous capture of both the infectious microbial(s) and the status of human host immune response could help us better understand the pathogenesis of complex inflammatory cardiomyopathy, if conducted on a larger scale of the population. The developed differential mtNGS method could also shed light on its translation and adoption of such a laboratory test in clinic practice, allowing for a more effective diagnosis to guide therapeutic treatment of the disease., Competing Interests: Dr Dimitrova was an employee of Philips Healthcare North America. Dr Fallon received research funding from Philips Healthcare North America. The other authors report no conflicts.

Sepsis is a life-threatening organ dysfunction caused by the host's dysfunctional response to infection. Sepsis-induced cardiomyopathy (SICM), as a serious complication of sepsis, is an acute reversible cardiac dysfunction syndrome unrelated to myocardial ischemia, which affects the outcome and prognosis of sepsis. As a complex microbial system, gut microbiota has been confirmed to be involved in the development of coronary heart disease, hypertension, heart failure and other cardiovascular diseases, and is also related to the occurrence and development of sepsis. However, there are few studies on the relationship between gut microbiota and SICM. This paper reviews the current research progress on gut microbiota and SICM, aiming at provide a new idea for clinical treatment of SICM.

Increasing evidence indicates that patients or experimental animals exposure to endotoxin (lipopolysaccharides, LPS) exert deleterious cardiac functions that greatly contribute to morbidity and mortality. The pathophysiologic processes, including NLRP3 inflammasome overactivation and cardiac inflammatory injury, are complicated. Sodium tanshinone IIA sulfonate (STS), a water-soluble derivative of tanshinone IIA, is a naturally occurring compound extracted from Salvia miltiorrhiza and has anti-inflammatory and cardioprotective properties. In this study we examined the effect of STS on endotoxin-induced cardiomyopathy and investigated the underlying mechanisms. An endotoxemic mouse model was established by injecting LPS (10 mg/kg). Different doses of STS were administered intraperitoneally (5, 10, or 50 mg/kg) at different time points (2/12 h, 4/12 h, and 8/12 h) after LPS challenge to assess its effect on survival of mice with endotoxemia. In parallel, cardiac function, myocardial inflammatory cytokines, cardiomyocyte pyroptosis and autophagy were evaluated to determine the extent of myocardial damage due to sepsis in the presence and absence of STS at the optimal dose (10 mg/kg) and time-point (2/12 h). The results demonstrated that STS increased the survival rates, improved the compromised cardiac function and reduced myocardial inflammatory injury associated with enhanced autophagy and mitigated NLRP3 inflammasome activation. Moreover, inhibiting of autophagy or blocking the AMPK pathway reversed STS-elicited prevention of cardiomyopathy and activated the NLRP3 inflammasome in endotoxemic mice. Collectively, our study demonstrates that STS attenuates endotoxemia-induced mortality and cardiomyopathy, which may be associated with promotion of autophagy and inhibition of NLRP3 inflammasome overactivation., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background People living with HIV are at increased risk of developing diastolic dysfunction, heart failure, and sudden cardiac death, all of which have been characterized by higher levels of myocardial fibrosis. Transmethylamine-N-oxide (TMAO), a dietary gut metabolite, is linked to the development of myocardial fibrosis in animal models. However, it is unclear whether TMAO plays a role in the development of myocardial fibrosis in people living with HIV. Methods and Results The study population consisted of participants enrolled in the multisite cross-sectional study called CHART-HIV (Characterizing Heart Function on Anti-Retroviral Therapy). Participants underwent echocardiography, cardiac magnetic resonance imaging, biomarker analysis, and targeted assessment of gut-related circulating metabolites; diastolic dysfunction was determined by study-specific criteria. Multivariable linear regression models were performed to examine the relationship of gut-related metabolites with serum and imaging measures of myocardial fibrosis. Models were adjusted for traditional cardiovascular, inflammatory, and HIV-related risk factors. Diastolic dysfunction was present in 94 of 195 individuals (48%) in CHART-HIV; this cohort demonstrated higher prevalence of hypertension, hyperlipidemia, and chronic kidney disease as well as higher plasma levels of both TMAO and choline. TMAO levels were associated with parameters reflecting increased left ventricular filling pressures and with a marker of the innate immune system. TMAO levels correlated with diffuse myocardial fibrosis ( R =0.35; P <0.05) as characterized by myocardial extracellular volume fraction as well as biomarkers reflective of myocardial fibrosis. Conclusions In this study of people living with HIV, the gut metabolite TMAO was associated with underlying diffuse myocardial fibrosis and found to be a potential marker of early structural heart disease. The mechanistic role of the gut microbiome in HIV-associated cardiovascular disease warrants further investigation. Registration URL: https://clinicaltrials.gov; Unique identifier: NCT02860156.

Background: Septic cardiomyopathy has been observed in association with influenza, indicating that not only bacteria but also other infective agents can cause this condition. There has been no systematic study as to whether Treponema pallidum infection induces septic cardiomyopathy, and we are the first to report this possibility., Case Presentation: We report two cases of a 48-year-old man and a 57-year-old man who were diagnosed with syphilis-related septic cardiomyopathy. The diagnosis of cardiomyopathy was made based on elevation of cardiogenic markers and decrease in ejection fraction evaluated by echocardiography. Screen for infective pathogens was negative except for syphilis, which supported our diagnosis. The two patients recovered following effective anti-syphilis treatment and advanced life support technology. Syphilis serology became negative after treatment., Conclusion: Syphilis has the potential to cause septic cardiomyopathy. Clinicians should consider Treponema pallidum in cases of septic cardiomyopathy with unknown pathogens. However, the specific pathophysiological mechanism of syphilis-associated septic cardiomyopathy has not been elucidated, and more specific studies are needed.

Lyme carditis is an extracutaneous manifestation of Lyme disease characterized by episodes of atrioventricular block of varying degrees and additional, less reported cardiomyopathies. The molecular changes associated with the response to Borrelia burgdorferi over the course of infection are poorly understood. Here, we identify broad transcriptomic and proteomic changes in the heart during infection that reveal a profound down-regulation of mitochondrial components. We also describe the long-term functional modulation of macrophages exposed to live bacteria, characterized by an augmented glycolytic output, increased spirochetal binding and internalization, and reduced inflammatory responses. In vitro, glycolysis inhibition reduces the production of tumor necrosis factor (TNF) by memory macrophages, whereas in vivo, it produces the reversion of the memory phenotype, the recovery of tissue mitochondrial components, and decreased inflammation and spirochetal burdens. These results show that B. burgdorferi induces long-term, memory-like responses in macrophages with tissue-wide consequences that are amenable to be manipulated in vivo., Competing Interests: The authors have declared that no competing interests exist.

Background: Keshan disease is an endemic cardiomyopathy of undefined causes. Being involved in the unclear pathogenesis of Keshan disease, a clear diagnosis, and effective treatment cannot be initiated. However, the rapid development of gut flora in cardiovascular disease combined with omics and big data platforms may promote the discovery of new diagnostic markers and provide new therapeutic options. This study aims to identify biomarkers for the early diagnosis and further explore new therapeutic targets for Keshan disease., Methods: This cohort study consists of two parts. Though the first part includes 300 participants, however, recruiting will be continued for the eligible participants. After rigorous screening, the blood samples, stools, electrocardiograms, and ultrasonic cardiogram data would be collected from participants to elucidate the relationship between gut flora and host. The second part includes a prospective follow-up study for every 6 months within 2 years. Finally, deep mining of big data and rapid machine learning will be employed to analyze the baseline data, experimental data, and clinical data to seek out the new biomarkers to predict the pathogenesis of Keshan disease., Discussion: Our study will clarify the distribution of gut flora in patients with Keshan disease and the abundance and population changes of gut flora in different stages of the disease. Through the big data platform analyze the relationship between environmental factors, clinical factors, and gut flora, the main factors affecting the occurrence of Keshan disease were identified, and the changed molecular pathways of gut flora were predicted. Finally, the specific gut flora and molecular pathways affecting Keshan disease were identified by metagenomics combined with metabonomic analysis., Trial Registration: ChiCTR1900026639. Registered on 16 October 2019.

Background: Tuberculosis of the myocardium is an extremely rare entity with few published case reports. Diagnosis is often delayed, and outcomes are unfavorable: particularly when cardiac involvement has been the presenting entity., Methods: Four patients, aged 24-51 years, presented with life-threatening ventricular arrhythmia (VA). None had a previous history of tuberculosis or any structural heart disease. Electrocardiogram during sinus rhythm and Echocardiography did not show any gross abnormality. All patients underwent contrast-enhanced computer tomography of thorax and cardiac magnetic resonance imaging. Attempts to obtain tissue (cardiac or associated mediastinal lymph nodes) were associated with increased risk to the patients thus indirect evidence of Mantoux skin test and interferon gamma release assay results were used to aid diagnosis., Results: Based on clinicoradiological findings, patients were put on antitubercular therapy (ATT). Supportive therapy included antiarrhythmic drugs (all patients), catheter ablation (two patients), and implantable cardioverter defibrillator (one patient). Arrhythmia suppression was achieved in all patients predischarge. On a follow-up of 2-24 months, none of the patients has had any recurrence of arrhythmia. ATT and antiarrhythmic drug therapy have been stopped in two patients who have completed the 6 months of ATT. Their radiological lesions showed resolution., Conclusions: Myocardial tuberculosis presenting as life-threatening VA in a rare but definite clinical entity. A high index of suspicion and cardiac imaging can lead to early diagnosis and appropriate treatment that ensures survival in all patients., (© 2020 Wiley Periodicals, Inc.)

Prolonged intermittent hypoxia (IH) has been shown to impair myocardial function (mainly via oxidative stress and inflammation) and modify gut microbiota in mice. Gut microbiota plays an important role in health and disease, including obesity and cardiovascular disease (CVD). Probiotics refer to live microorganisms that confer health benefits on the host after administration in adequate amounts. Research on novel probiotics related therapies has evoked much attention. In our previous study, both Lactobacillus rhamnosus GG (LGG) and LGG cell-free supernatant (LGGs) were found to protect against alcohol-induced liver injury and steatosis; however, the effects of LGG and LGGs on cardiac tissues of obese mice exposed to IH have not been determined. Here we exposed high-fat high-fructose diet (HFHFD)-induced obese mice to IH, to establish a model of obesity with obstructive sleep apnea (OSA). Mice were divided into four groups: (1) HFHFD for 15 weeks; (2) HFHFD for 15 weeks with IH in the last 12 weeks (HFHFD/IH); (3) and (4) HFHFD/IH plus oral administration of either LGG (10 9 CFU bacteria/day) or LGGs (dose equivalent to 10 9 CFU bacteria/day) over the 15 weeks, respectively. Compared to HFHFD mice, HFHFD/IH-mice showed heart dysfunction with significant cardiac remodeling and inflammation; all these pathological and functional alterations were prevented by treatment with both LGG and LGGs (no significant difference between LGG and LGGs in this respect). The cardioprotective effect of LGG and LGGs against IH/HFHFD was associated with up-regulation of nuclear factor erythroid 2-related factor 2(Nrf2)-mediated antioxidant pathways. Our findings suggest a cardioprotective effect of LGG and LGGs in obese mice with OSA., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

LPS-induced septic cardiomyopathy has been found to be connected with mitochondrial stress through unknown mechanisms. Mitochondrial fission is an early event in mitochondrial dysfunction. The aim of our study was to determine the role and regulatory mechanism of mitochondrial fission in the progression of LPS-induced septic cardiomyopathy, with a particular focus on Mst1 and F-actin. Our data demonstrated that Mst1 expression was rapidly upregulated in LPS-treated hearts and that increased Mst1 promoted cardiomyocyte death by inducing mitochondrial stress. Mechanistically, elevated expression of Mst1 upregulated Drp1, and the latter initiated mitochondrial fission. Excessive mitochondrial fission caused mitochondrial oxidative injury, mitochondrial membrane potential reduction, mitochondrial proapoptotic element translocation into the cytoplasm/nucleus, mitochondrial energy dysfunction and mitochondrial apoptosis activation. Inhibition of mitochondrial fission sustained mitochondrial function and favored cardiomyocyte survival. Furthermore, we identified F-actin degradation as an apparent downstream event of mitochondrial fission activation in the context of LPS-induced septic cardiomyopathy. Stabilization of F-actin attenuated fission-mediated cardiomyocyte death. Altogether, our results define the Mst1/Drp1/mitochondrial fission/F-actin axis as a new signaling pathway that mediates LPS-related septic cardiomyopathy by inducing mitochondrial stress and cardiomyocyte death. Therefore, Mst1 expression, mitochondrial fission modification and F-actin stabilization may serve as potential therapeutic targets for sepsis-related myocardial injury.

Rationale: Takotsubo syndrome (TTS) most commonly occurs in postmenopausal women who have been exposed to a triggering event such as acute physical or emotional distress. Sepsis-induced TTS in young premenopausal women were rarely reported. In particular, the relationship between sepsis-induced TTS and sepsis-induced cardiomyopathy (SIC) remains to be illuminated., Patient Concerns: Two young premenopausal women were admitted to the hospital with sepsis and myocardial involvement., Diagnosis: Both patients fully met the Mayo Clinic criteria for TTS., Interventions: Both patients received anti-infection and fluid infusion treatment., Outcomes: Both patients were discharged without complications and the follow-up ultrasonic echocardiography showed normal results., Lessons: In this report, we describe 2 young premenopausal women with sepsis-induced TTS. There is an overlap between sepsis-induced TTS and SIC, and SIC could be a special type of TTS, which occurs under the stress of sepsis.

Streptococcus pneumoniae is an opportunistic Gram-positive pathogen that can cause invasive disease. Recent studies have shown that S. pneumoniae is able to invade the myocardium and kill cardiomyocytes, with one-in-five adults hospitalized for pneumococcal pneumonia having a pneumonia-associated adverse cardiac event. Furthermore, clinical reports have shown up to a 10-year increased risk of adverse cardiac events in patients formerly hospitalized for pneumococcal bacteremia. In this study, we investigated the ability of nine S. pneumoniae clinical isolates, representing eight unique serotypes, to cause cardiac damage in a mouse model of invasive disease. Following intraperitoneal challenge of C57BL/6 mice, four of these strains (D39, WU2, TIGR4, and 6A-10) caused high-grade bacteremia, while CDC7F:2617-97 and AMQ16 caused mid- and low-grade bacteremia, respectively. Three strains did not cause any discernible disease. Of note, only the strains capable of high-grade bacteremia caused cardiac damage, as inferred by serum levels of cardiac troponin-I. This link between bacteremia and heart damage was further corroborated by Hematoxylin & Eosin and Trichrome staining which showed cardiac cytotoxicity only in D39, WU2, TIGR4, and 6A-10 infected mice. Finally, hearts infected with these strains showed varying histopathological characteristics, such as differential lesion formation and myocytolysis, suggesting that the mechanism of heart damage varied between strains., Competing Interests: The authors have declared that no competing interests exist.

Background: Septic cardiomyopathy represents cardiac impairment in sepsis and is a part of systemic involvement in sepsis. Cytokine storm is responsible for septic shock and for myocardial dysfunction of potentially reversible septic cardiomyopathy. Several case reports and case series demonstrated successful removal of circulating cytokines by combined blood purification techniques. In this way, septic shock and survival of septic patients improved. However, the evidences for reversal of myocardial dysfunction are rare., Case Presentation: We present a patient with a history of chemotherapy for coat cell lymphoma, splenectomy and autologous bone marrow transplantation, who suffered severe pneumococcal sepsis, septic shock and septic cardiomyopathy, resistant to pharmacological therapy. Combined blood purification techniques 36 h after the start of treatment successfully decreased Interleukin-6 level, lactacidosis, the need for vasopressors to maintain normotension, improved systolic function of the left ventricle and clinical outcome., Conclusions: Our case suggests that combined blood purification techniques initiated even 36 h after the start of treatment successfully removed inflammatory cytokines, reversed circulatory failure and improved left ventricular systolic function in pneumococcal sepsis.

Background: We report a case of recurrent post-partum pyoderma gangrenosum (PG) complicated by post-partum cardiomyopathy (PPCM)., Patients and Methods: A 23-year-old woman presented with a previous medical history of aseptic abscess of the left breast in her fourth pregnancy, which developed after surgical drainage of an inflammatory ulceration treated by atraumatic topical care. During her fifth pregnancy, the patient presented a large and painful ulceration in relation to the scar of the Caesarean section, despite the introduction of broad-spectrum antibiotic therapy. Bacteriological samples were negative. Histological examination militated in favor of PG. One week after initiation of corticosteroid therapy, the patient suddenly showed signs of heart failure. Based on trans-thoracic echocardiography PPCM was diagnosed, and the outcome was fatal., Discussion: This observation raises the question of the relationship between PG and pregnancy and describes the association of PG and PPCM. PG occurs rarely during pregnancy and it may be induced by the rise in G-CSF levels found in pregnant women. The association with PPCM seen in our patient could have been due to the development of an anti-angiogenic climate at the end of pregnancy, together with inflammatory myocardial aggression linked to the PG., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Current scientific consensus about the physiopathology in the progression from severe sepsis to septic shock and death focuses on myocardial contractile dysfunction. Nevertheless, objective parameters to establish a pathological correlate of a fatal outcome are lacking; then a cause of death due to sepsis can remain an unsolved problem. We first reviewed all death cases recorded at our institutions during the period from 2007 until 2015. Then, we conducted a retrospective study of a selected autopsy series of people who had received "sepsis" as cause of death. Two pathologists re-examined the heart sections while the most suitable myocardial sample for each case was stained for immunohistochemistry with antibodies targeted for specific inflammatory-related molecules. We used specific antibodies for the following markers: alpha-smooth muscle actin (alpha-SMA); fibronectin; matrix metallopeptidase 9 (MMP-9); intercellular adhesion molecule 1 (ICAM-1); caspase-3; lactoferrin (LF); cluster differentiation 15 (CD15). The statistical significance of differences was assessed using student's t-test for unpaired data or non-parametric Mann-Whitney or Wilcoxon tests for skewed variables or one-way analysis of variance and post hoc Scheffe's test for continuous variables and Pearson's χ 2 -test for discrete variables. Linear regression analysis was used to determine the presence of a correlation between continuous variables. At our institutions, 2220 deaths have been recorded during the period study. Sepsis accounted as a cause of death for the 20% of total. We finally enrolled 56 cases; of these, only 20 were positive for microbiological analysis. At histological examination, clear inflammation was detectable in the 32% of cases; otherwise, immunohistochemical reaction showed a positive reaction for LF and CD15 in more than a half cases (56%). We still ignore all the underlying mechanisms of sepsis and all its pathophysiological connections with cardiac metabolism; in this sense, we aim to corroborate the diagnostic value of anti-LF and anti-CD15 staining for the post-mortem detection of myocardial inflammation.

Three therapeutic principles most substantially improve organ dysfunction and survival in sepsis: early, appropriate antimicrobial therapy; restoration of adequate cellular perfusion; timely source control. The new definitions of sepsis and septic shock reflect the inadequate sensitivity, specify, and lack of prognostication of systemic inflammatory response syndrome criteria. Sequential (sepsis-related) organ failure assessment more effectively prognosticates in sepsis and critical illness. Inadequate cellular perfusion accelerates injury and reestablishing perfusion limits injury. Multiple organ systems are affected by sepsis and septic shock and an evidence-based multipronged approach to systems-based therapy in critical illness results in improve outcomes., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Sepsis-associated cardiac arrest is a relatively common occurrence with especially poor outcomes. Of the greater than 200,000 in-hospital cardiac arrests that occur in the United States annually, between 30,000 and 60,000 occur in patients with underlying sepsis. These patients are less likely to survive than cardiac arrest victims without sepsis. In this review, we discuss the epidemiology of sepsis-associated in-hospital cardiac arrest in adults and children, the relevant physiology responsible for its pathogenesis and poor outcomes, and potential therapeutic interventions based on this pathophysiology. We postulate that persistence of sepsis pathophysiology during and after cardiac arrest is responsible for these poor outcomes. This includes derangements of vascular tone and intravascular volume status; myocardial dysfunction; hypoxemia, acidemia, and other metabolic derangements; and pulmonary hypertension. Potential interventions that specifically target this pathophysiology before, during, and after cardiac arrest may augment standard cardiopulmonary resuscitation and post-resuscitation care for patients with sepsis and septic shock., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Cardiomyopathy is a progressive disease of myocardium causing either mechanical or electrical disturbances. Sepsis-induced cardiomyopathy (SICM) is an entity of cardiomyopathy which is reversible in 1â€"2 weeks after recovery from sepsis or septic shock. SICM is thought to have unpredictable cumulative mortality towards sepsis but its exact mechanism remains elusive. We report a case of Escherichia coli SICM in a 63-year-old woman presented with sudden onset of dyspnoea on exertion and orthopnoea following nausea, vomiting and diarrhoea after consuming Chinese foods. Transthoracic echocardiogram revealed severely reduced global left ventricular ejection fraction (LVEF) of <20% which returned back to normal LVEF of 57% after 10 days. Subsequent cardiac catheterisation showed non-obstructive coronaries. No specific therapy intended for reversal of SICM presents to date despite current sepsis survival guideline available for haemodynamic support. Initiation of beta blockers after recovery from septic shock has been beneficial., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Although rare, cardiac sarcoidosis (CS) is potentially fatal. Early diagnosis and intervention are essential, but histopathologic diagnosis is limited. We aimed to detect Propionibacterium acnes, a commonly implicated etiologic agent of sarcoidosis, in myocardial tissues obtained from CS patients., Methods and Results: We examined formalin-fixed paraffin-embedded myocardial tissues obtained by surgery or autopsy and endomyocardial biopsy from patients with CS (n = 26; CS-group), myocarditis (n = 15; M-group), or other cardiomyopathies (n = 39; CM-group) using immunohistochemistry (IHC) with a P. acnes-specific monoclonal antibody. We found granulomas in 16 (62%) CS-group samples. Massive (≥14 inflammatory cells) and minimal (<14 inflammatory cells) inflammatory foci, respectively, were detected in 16 (62%) and 11 (42%) of the CS-group samples, 10 (67%) and 10 (67%) of the M-group samples, and 1 (3%) and 18 (46%) of the CM-group samples. P. acnes-positive reactivity in granulomas, massive inflammatory foci, and minimal inflammatory foci were detected in 10 (63%), 10 (63%), and 8 (73%) of the CS-group samples, respectively, and in none of the M-group and CM-group samples., Conclusions: Frequent identification of P. acnes in sarcoid granulomas of originally aseptic myocardial tissues suggests that this indigenous bacterium causes granuloma in many CS patients. IHC detection of P. acnes in massive or minimal inflammatory foci of myocardial biopsy samples without granulomas may be useful for differentiating sarcoidosis from myocarditis or other cardiomyopathies.

A 53-year-old woman presented to our hospital with dizziness and low-grade fever. She underwent percutaneous coronary intervention to the obtuse marginal artery with a drug-eluting stent 20 months prior to this presentation. Physical examination was remarkable for bradycardia. Electrocardiogram showed a junctional rhythm with heart rate of 35 bpm. Blood and urine cultures were negative. Despite successful urgent pacemaker placement, she had cardiac arrest the following day with unsuccessful cardiopulmonary resuscitation attempt. Cardiac autopsy report revealed multiple abscesses involving the obtuse marginal and left anterior descending arteries as well as the adjacent myocardial regions., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objectives: The mechanism(s) for septic cardiomyopathy in humans is not known. To address this, we measured messenger RNA alterations in hearts from patients who died from systemic sepsis, in comparison to changed messenger RNA expression in nonfailing and failing human hearts., Design: Identification of genes with altered abundance in septic cardiomyopathy, ischemic heart disease, or dilated cardiomyopathy, in comparison to nonfailing hearts., Setting: ICUs at Barnes-Jewish Hospital, St. Louis, MO., Patients: Twenty sepsis patients, 11 ischemic heart disease, nine dilated cardiomyopathy, and 11 nonfailing donors., Interventions: None other than those performed as part of patient care., Measurements and Main Results: Messenger RNA expression levels for 198 mitochondrially localized energy production components, including Krebs cycle and electron transport genes, decreased by 43% ± 5% (mean ± SD). Messenger RNAs for nine genes responsible for sarcomere contraction and excitation-contraction coupling decreased by 43% ± 4% in septic hearts. Surprisingly, the alterations in messenger RNA levels in septic cardiomyopathy were both distinct from and more profound than changes in messenger RNA levels in the hearts of patients with end-stage heart failure., Conclusions: The expression profile of messenger RNAs in the heart of septic patients reveals striking decreases in expression levels of messenger RNAs that encode proteins involved in cardiac energy production and cardiac contractility and is distinct from that observed in patients with heart failure. Although speculative, the global nature of the decreases in messenger RNA expression for genes involved in cardiac energy production and contractility suggests that these changes may represent a short-term adaptive response of the heart in response to acute change in cardiovascular homeostasis.

Sepsis is one of the main causes of ICU hospitalization worldwide, with a high mortality rate, and is associated with a large number of comorbidities. One of the main comorbidities associated with sepsis is septic cardiomyopathy. This process occurs mainly due to mechanisms of damage in the cardiovascular system that will lead to changes in cardiovascular physiology, such as decreased Ca 2+ response, mitochondrial dysfunction and decreased β-adrenergic receptor response. Within this process the exosomes play an important role in the pathophysiology of this disease, in which the exosomal content is related to mechanisms that will trigger its development. After platelet activation through ROS exposition, exosomes containing high concentrations of NADPH are released in heart blood vessels, those exosomes will be internalized in endothelial cells leading to cell death and cardiac dysfunction. On the opposite, exosomes derived from mesenchymal stem cells contain miR-223, that have anti-inflammatory properties, are released in less quantities in septic patients causing an imbalance that leads to cardiac dysfunction.

Background: Cardiac involvement in Lyme disease, caused by the tick-borne spirochete Borrelia burgdorferi, has been reported to occur in 0.3-4 % of infected patients in Europe. Cardiac manifestations may include conduction disturbances, and also myocarditis, pericarditis, and left ventricular dysfunction. We investigated the prevalence of B. burgdorferi DNA in endomyocardial biopsies from patients with suspected inflammatory heart disease and positive serology for B. burgdorferi., Methods and Results: In 64 patients, endomyocardial biopsies were taken after exclusion of coronary heart disease by coronary angiography, and investigated with polymerase chain reaction (PCR) for the presence of B. burgdorferi and cardiotropic viruses. B. burgdorferi DNA was not detected in any of the endomyocardial biopsies. Viruses, particularly parvovirus B19, were detected as infectious agents in 19 (30 %) patients., Conclusion: The results of our study demonstrate that PCR analysis of endomyocardial biopsies from patients with suspected inflammatory heart disease, including individuals with dilated cardiomyopathy (DCM) and positive serology for B. burgdorferi, did not reveal the B. burgdorferi genome in any biopsy sample.

Background: Clinical and experimental conflicting data have questioned the relationship between infectious agents, inflammation and dilated cardiomyopathy (DCM)., Objectives: The aim of this study was to determine the frequency of infectious agents and inflammation in endomyocardial biopsy (EMB) specimens from patients with idiopathic DCM, explanted hearts from different etiologies, including Chagas' disease, compared to donated hearts., Methods: From 2008 to 2011, myocardial samples from 29 heart donors and 55 patients with DCMs from different etiologies were studied (32 idiopathic, 9 chagasic, 6 ischemic and 8 other specific etiologies). Inflammation was investigated by immunohistochemistry and infectious agents by immunohistochemistry, molecular biology, in situ hybridization and electron microscopy., Results: There were no differences regarding the presence of macrophages, expression of HLA class II and ICAM-I in donors and DCM. Inflammation in Chagas' disease was predominant. By immunohistochemistry, in donors, there was a higher expression of antigens of enterovirus and Borrelia, hepatitis B and C in DCMs. By molecular biology, in all groups, the positivity was elevated to microorganisms, including co-infections, with a higher positivity to adenovirus and HHV6 in donors towards DCMs. This study was the first to demonstrate the presence of virus in the heart tissue of chagasic DCM., Conclusions: The presence of inflammation and infectious agents is frequent in donated hearts, in the myocardium of patients with idiopathic DCM, myocardial dysfunction related to cardiovascular diseases, and primary and secondary cardiomyopathies, including Chagas' disease. The role of co-infection in Chagas' heart disease physiopathology deserves to be investigated in future studies., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background: The cardiac dysfunction presented in cirrhotic patients is already known as cirrhotic cardiomyopathy. The pathogenesis of this entity is not fully understood., Aims: The aim of this study was to evaluate the frequency and characteristics of cirrhotic cardiomyopathy and to investigate the possible role of bacterial endotoxemia on its aggravation., Methods: Forty-five cirrhotics were studied by a tissue Doppler imaging echocardiography at rest and after stress. The diagnosis of left ventricular diastolic dysfunction was based on the latest guidelines of the American Society of Echocardiography, whereas its severity was defined by the E/e'av ratio. Endotoxemia was estimated by measuring the serum levels of lipopolysaccharide-binding protein (LBP) and cytokines., Results: None of the patients had systolic dysfunction, but 17/45 (37.8 %) had a diastolic one. Patients with grade II diastolic dysfunction had significantly longer QTc (p = 0.049), larger left atrium volume (p = 0.013), higher Brain Natriuretic Peptide levels (p = 0.007) and higher LBP levels (p = 0.02), compared to those with normal cardiac function, without differences in the systemic hemodynamics and the cytokines' levels. Moreover, the severity of diastolic dysfunction as reflected by the E/e'av. was significantly correlated with the LBP levels (p = 0.002). On the multivariate analysis, the LBP was independently associated with the presence of diastolic dysfunction., Conclusions: Cirrhosis is commonly complicated by cardiac dysfunction. Patients with severe cirrhotic cardiomyopathy have higher LBP levels, which are significantly correlated with the degree of diastolic dysfunction. Our findings support a potential role of bacterial endotoxemia on the aggravation of cardiomyopathy in cirrhotic patients.

We report a case of postpartum severe mitral regurgitation caused by papillary muscle rupture in a female with normal coronary arteries. The etiology of papillary muscle rupture was endocarditis from puerperal fever. Clinical stabilization was achieved with extracorporeal membrane oxygenation (ECMO) followed by mitral valve replacement two days later., (© 2012 Wiley Periodicals, Inc.)

The typical symptoms and signs of myocardial infarction are well known. Alterations in electrocardiogram (ECG), echocardiography or biochemical markers of myocardial necrosis are usually helpful to confirm the diagnosis. Some of these features, however, also occur in myocarditis, which is a potential differential diagnosis. We describe an unusual case of bacterial sepsis due to Escherichia coli that caused myocardial damage (myocarditis) with ECG changes mimicking acute myocardial infarction. The possible pathophysiological mechanisms of myocardial injury in sepsis are also reviewed.

Necrotizing fasciitis is a life-threatening infection of the fascia and subcutaneous tissues. We report on a 30-year-old man with history of intramuscular injection resulted in gluteal abscess that progressed to necrotizing fasciitis. On admission, the patient developed circulatory collapse, severe left ventricular dysfunction, and ST-segment elevation in the inferior leads. Wound and blood cultures indicated staphylococcal infection. The clinical, laboratory, echocardiographic, and electrocardiographic features are discussed.

A case of pacemaker infection complicated by bacteremia and myocardial abscess caused by Mycobacterium fortuitum is reported and 9 other cases of pacemaker infection associated with rapidly growing mycobacteria are reviewed. Most cases developed within 6 months from implantation suggesting nosocomial acquisition. Wound discharge, fever, and pain at generator site were the most common presenting features. At presentation they had a median duration of symptoms of 34 days. Concomitant bacteremia was present in half of the cases. Antibiotics therapy and removal of the pacemaker system were needed to achieve cure in the majority of cases. Clarithromycin and fluoroquinolones were the most commonly used antibiotics.

We report the case of a 48-year-old female patient who had a Crohn's disease treated by corticosteroids. The patient developed severe cardiac failure, which was refractory to treatment with inotropic agents. At necropsy, examination of the heart revealed myocardial abscesses. On microscopic study, we diagnosed an aspergillar myocarditis. Aspergillar myocarditis is a rare and fatal localisation in disseminated aspergillosis. Diagnosis is difficult and treatment, usually initiated late, is ineffective.

Objectives: We sought to identify predictive factors for Lyme carditis in children and to characterize the clinical course of these patients., Methods: We reviewed all cases of early disseminated Lyme disease presenting to our institution from January 1994 through July 2008, and summarized the presentation and course of those patients with carditis. A case-control study was used to identify predictive factors for carditis. Controls were patients with early disseminated Lyme disease without carditis., Results: Of 207 children with early disseminated Lyme disease, 33 (16%) had carditis, 14 (42%) of whom had advanced heart block, including 9 (27%) with complete heart block. The median time to recovery of sinus rhythm in these 14 patients was 3 days (range: 1-7 days), and none required a permanent pacemaker. Four (12%) of 33 patients with carditis had depressed ventricular systolic function, 3 (9%) of whom required mechanical ventilation, temporary pacing, and inotropic support. Complete resolution of rhythm disturbances and myocardial dysfunction occurred in 24 (89%) of 27 patients for whom follow-up data were available. Most patients with carditis also had other systemic Lyme involvement. By using multivariate logistic regression analysis, we found that children >10 years of age, those with arthralgias, and those with cardiopulmonary symptoms were more likely to have carditis., Conclusions: The spectrum of presentation for children with Lyme carditis is broad, ranging from asymptomatic, first-degree heart block to fulminant myocarditis. Variable degrees of heart block are the most common manifestation and occasionally require temporary pacing. Transient myocardial dysfunction, although less common, can be life-threatening. Advanced heart block resolves within 1 week in most cases. In children with early disseminated Lyme disease, older age, arthralgias, and cardiopulmonary symptoms independently predict the presence of carditis.

In sub-Saharan Africa, pericardial tuberculosis is frequently diagnosed in HIV sero-positive patients. Myocardial involvement has only rarely been reported. We present an HIV sero-positive patient in whom both pericardial and myocardial tuberculosis were diagnosed, and highlight the value of cardiac magnetic resonance imaging in the diagnosis and management of this condition.

Francisella tularensis causes pulmonary tularemia and death in humans when left untreated. Here, using a novel aerosol infection model, we show that acute pulmonary Francisella novicida infection not only causes pneumonia and liver damage, but also induces dystrophic cardiac calcinosis (DCC) in BALB/c mice. C57BL/6 mice also develop pneumonia and hepatic damage, but fail to develop DCC. Development of DCC in BALB/c mice is associated with significant induction of RANKL but not osteopontin in their organs. Depletion of lung macrophages prior to infection markedly reduces pericarditis and calcification in BALB/c mice but does not increase their susceptibility to infection.

Background and Aim of the Study: The study aim was to assess the characteristics of bacterial endocarditis complicating mitral annulus calcification, and to evaluate the surgical results., Methods: Twenty-four patients (mean age 64 years) underwent surgery for mitral insufficiency secondary to mitral endocarditis with annulus calcification (acute, n = 18; healed, n = 6). Surgery was performed as an emergency in seven cases for septic (n = 3) or cardiogenic (n = 4) shock. An aortic prosthesis had previously been placed in three cases. Comorbidities noted included chronic renal insufficiency/dialysis (n = 8), cancer (n = 6), coronary disease (n = 6), and obstructive cardiomyopathy (n = 1). Nine patients suffered an embolic complication, such as stroke (n = 7, of which three had coma), splenic (n = 3), or lower limb (n = 1). The microorganism present was identified as Staphylococcus aureus (n = 9), Streptococcus/ Enterococcus sp. (n = 12), or others (n = 3). The left atrial diameter was 48 mm, the ejection fraction 63%, and the septal thickness 13 mm., Results: The mean severity score of annulus calcifications (range: 1 to 5) was 1.9. The anatomical lesions included: vegetations (n = 16, of which eight were > 10 mm), leaflet perforation (n = 9), chordae rupture (n = 9), aortic abscess (n = 2) and mitral annular abscess (n = 9), and one fistulation into the pericardium. The valve was repaired in 15 cases, and replaced in nine (seven bioprostheses, two mechanical). Associated procedures included aortic valve replacement (n = 7) and coronary artery bypass (n = 3). The in-hospital mortality was 29% (n = 7); all patients who died were operated on during the acute phase. All patients who presented with septic shock or coma died. After a mean follow up of 46 months, six patients had died (overall survival was 46% at 33 months), and 11 were in NYHA class I/II. One recurrence of endocarditis was treated medically., Conclusion: Bacterial endocarditis complicating mitral annulus calcification has a poor prognosis due to the frequent comorbidity and severity of the infectious complications. Patients in septic shock or coma do not appear to be suitable candidates for surgery. Valve repair was possible in two-thirds of the present patients; otherwise, a bioprosthetic replacement was the option of choice.

Propionibacterium acnes endocarditis is an uncommon infection in pediatrics. We describe a case of P. acnes endocarditis in a 16-year-old boy that occurred 6 months after recurrent surgery for a congenital cardiopathy. Molecular identification of P. acnes was obtained. He recovered from this infection after a surgical treatment and with a prolonged antibiotic regimen including ceftriaxone.