Chronic Myocardial Damage Research Articles

Interpretation of elevated baseline concentrations and serial changes of high-sensitivity cardiac troponin T in confirmed muscular dystrophies.

Concentrations of high-sensitivity cardiac troponin T (hs-cTnT) are frequently elevated in stable patients with confirmed muscle dystrophies. However, sparse information is available on the interpretation of serial concentration changes. Hs-cTnT was collected in 35 stable outpatients with confirmed skeletal muscle dystrophies at 0 and 1h and after 6-12months during scheduled outpatient visits. We simulated the effectiveness of the European Society of Cardiology (ESC) 0/1h algorithm and assessed biological variation at 6-12months using two established methods: reference change value (RCV) and minimal important difference (MID). Median baseline hs-cTnT concentrations were 34.4ng/L [inter-quartile range (IQR): 17.5-46.2], and values > 99th percentile upper limit of normal were present in 34 of 35 patients. All patients were stable without cardiovascular adverse events during a follow-up of 6.6months (IQR: 6-7). Median concentration change was 1.9ng/L (IQR: 0.7-3.2) and 0.8ng/L (IQR: 0-7.0) at 60min and 6-9months, respectively. Applying the criteria of the ESC 0/1h algorithm for triage of suspected acute coronary syndrome (ACS) showed poor overall effectiveness of baseline hs-cTnT values. No patient would qualify for rule-out based on hs-cTnT less than the limit of detection, whereas five cases would qualify for rule-in based on hs-cTnT≥52ng/L. Biological variabilities at 6-12months per MID and RCV were 1.2ng/L [95% confidence interval (CI): 0.7-2.1] and 28.6% (95% CI: 27.9-29.6), respectively. A total of 8 (22.9%) and 25 (71.4%) cases exceeded the biological variation range, suggesting some additional myocardial damage. The high prevalence of elevated hs-cTnT could negatively impact the effectiveness of rule-out and rule-in strategies based on a single hs-cTnT value. Knowledge of the physiological and biological variation of hs-cTnT after 6-12months is helpful to detect the progression of cardiac involvement or to search for cardiac complications including but not limited to arrhythmias that may trigger acute or chronic myocardial damage.

Clinical Utility of Strain Imaging in Assessment of Myocardial Fibrosis.

Myocardial fibrosis (MF) is a non-reversible process that occurs following acute or chronic myocardial damage. MF worsens myocardial deformation, remodels the heart and raises myocardial stiffness, and is a crucial pathological manifestation in patients with end-stage cardiovascular diseases and closely related to cardiac adverse events. Therefore, early quantitative analysis of MF plays an important role in risk stratification, clinical decision, and improvement in prognosis. With the advent and development of strain imaging modalities in recent years, MF may be detected early in cardiovascular diseases. This review summarizes the clinical usefulness of strain imaging techniques in the non-invasive assessment of MF.

Acute myocardial infarction in the elderly with anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA): A case report and literature review

Anomalous left coronary artery from the pulmonary artery (ALCAPA) is a rare congenital coronary artery malformation, with a fatality rate of 90% at 1 year of age; only 10% to 15% of patients are diagnosed in adulthood. However, elderly survivors are particularly rare. Here, we report a case of elderly ALCAPA presented with acute myocardial infarction. A 64-years-old female, complained of acute precordial pain in our hospital for 2 days. She was diagnosed with an acute non-ST-segment elevation myocardial infarction. Aortic angiography revealed emptiness of the left coronary sinus, and coronary angiography showed that the tortuous right coronary artery supplied blood to the left coronary artery through collateral circulation, and the contrast medium spilled from the opening of the left coronary artery. It was suspected that the left coronary artery was opened in the pulmonary artery. This finding was subsequently confirmed by coronary artery CT. The patient refused surgery to restore double coronary circulation and was administered standardized drug treatment. There was no chest pain during the 6-month follow-up. ALCAPA should be considered in patients with Myocardial Infarction with Non-obstructive Coronary Arteries, and surgical intervention is the first choice for such patients; However, chronic myocardial damage persists regardless of surgical treatment, prophylactic implantation of an ICD may be an important means of preventing sudden cardiac death and such patients should be followed up for a lifetime.

May Strenuous Endurance Sports Activity Damage the Cardiovascular System of Healthy Athletes? A Narrative Review.

The positive effects of physical activity are countless, not only on the cardiovascular system but on health in general. However, some studies suggest a U-shape relationship between exercise volume and effects on the cardiovascular system. On the basis of this perspective, moderate-dose exercise would be beneficial compared to a sedentary lifestyle, while very high-dose physical activity would paradoxically be detrimental. We reviewed the available evidence on the potential adverse effects of very intense, prolonged exercise on the cardiovascular system, both acute and chronic, in healthy athletes without pre-existing cardiovascular conditions. We found that endurance sports activities may cause reversible electrocardiographic changes, ventricular dysfunction, and troponin elevation with complete recovery within a few days. The theory that repeated bouts of acute stress on the heart may lead to chronic myocardial damage remains to be demonstrated. However, male veteran athletes with a long sports career show an increased prevalence of cardiovascular abnormalities such as electrical conduction delay, atrial fibrillation, myocardial fibrosis, and coronary calcifications compared to non-athletes. It must be underlined that the cause–effect relationship between such abnormalities and the exercise and, most importantly, the prognostic relevance of such findings remains to be established.

Severe myocarditis as a cause of the formation of cardiorenal syndrome in a patient with refractory rheumatoid arthritis

According to modern concepts, myocarditis is an inflammatory disease of the myocardium, diagnosed on the basis of generally accepted histological, immunological, immunohistochemical criteria. Previously, most researchers believed that the most common cardiac extra-articular manifestation of rheumatoid arthritis (RA) is pericarditis. In the last decade, using magnetic resonance imaging (MRI) of the heart, it turned out that myocarditis in patients with rheumatoid arthritis is not a rare manifestation of the disease. Recently, there is increasing evidence that inflammatory cytokines in RA can also directly cause chronic myocardial damage, further contributing to the development of chronic heart failure (CHF). In our clinical case, myocarditis developed in a patient with active refractory rheumatoid arthritis. The myocardial lesion in the patient was characterized by pronounced echocardiographic signs of restrictive cardiomyopathy, a significant decrease in the ejection fraction with the development of heart failure, various rhythm disturbances in combination with acute renal dysfunction, which led to the formation of cardiorenal syndrome (CRS). Complete regression of myocarditis and cattle occurred precisely against the background of effective treatment of refractory rheumatoid arthritis (RA) with basic antirheumatic drugs and the successful use of biological therapy.

Sufentanil ameliorates oxygen-glucose deprivation/reoxygenation-induced endothelial barrier dysfunction in HCMECs via the PI3K/Akt signaling pathway.

Ischemic heart disease, a chronic myocardial damage disease caused by coronary artery ischemia, is the leading cause of death worldwide. The aim of the present study was to explore the efficacy of sufentanil in myocardial ischemia/reperfusion (I/R) injury. Oxygen and glucose deprivation/reoxygenation (OGD/R) was utilized to induce human cardiac microvascular endothelial cells (HCMECs) to simulate myocardial I/R injury in vitro. The Cell Counting Kit-8 assay was used to detect the effects of sufentanil on HCMECs and OGD/R-induced HCMECs. The TUNEL, lactate dehydrogenase (LDH) activity, immunofluorescence and in vitro permeability assays, were used to assess apoptosis, LDH activity, VE-cadherin protein expression levels and endothelial barrier function in OGD/R-induced HCMECs, respectively. Moreover, western blotting was performed to assess the protein expression levels of apoptosis, endothelial barrier function and phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt)-related proteins. The results demonstrated that sufentanil had no significant influence on the viability of HCMECs but increased the viability of OGD/R-induced HCMECs in a dose-dependent manner. Furthermore, sufentanil inhibited cell apoptosis and permeability of OGD/R-induced HCMECs but enhanced the protein expression levels of tight junction proteins, including ZO-1, Occludin, VE-cadherin and Claudin-5. Sufentanil was also demonstrated to activate the PI3K/Akt signaling pathway. In addition, the use of LY294002, an inhibitor of the PI3K/Akt signaling pathway, partially abolished the protective effects of sufentanil on apoptosis, permeability and tight junction protein expression levels. These results indicated that sufentanil ameliorated OGD/R-induced endothelial barrier dysfunction in HCMECs, potentially via the PI3K/Akt signaling pathway. The present study therefore suggested that sufentanil may serve as a novel therapeutic option for the improvement of myocardial I/R injury.

Circular Network of Coregulated Sphingolipids Dictates Chronic Hypoxia Damage in Patients With Tetralogy of Fallot.

Background: Tetralogy of Fallot (TOF) is the most common cyanotic heart disease. However, the association of cardiac metabolic reprogramming changes and underlying molecular mechanisms in TOF-related chronic myocardial hypoxia damage are still unclear.Methods: In this study, we combined microarray transcriptomics analysis with liquid chromatography tandem-mass spectrometry (LC–MS/MS) spectrum metabolomics analysis to establish the metabolic reprogramming that occurs in response to chronic hypoxia damage. Two Gene Expression Omnibus (GEO) datasets, GSE132176 and GSE141955, were downloaded to analyze the metabolic pathway in TOF. Then, a metabolomics analysis of the clinical samples (right atrial tissue and plasma) was performed. Additionally, an association analysis between differential metabolites and clinical phenotypes was performed. Next, four key genes related to sphingomyelin metabolism were screened and their expression was validated by real-time quantitative PCR (QT-PCR).Results: The gene set enrichment analysis (GSEA) showed that sphingolipid metabolism was downregulated in TOF and the metabolomics analysis showed that multiple sphingolipids were dysregulated. Additionally, genes related to sphingomyelin metabolism were identified. We found that four core genes, UDP-Glucose Ceramide Glucosyltransferase (UGCG), Sphingosine-1-Phosphate Phosphatase 2 (SGPP2), Fatty Acid 2-Hydroxylase (FA2H), and Sphingosine-1-Phosphate Phosphatase 1 (SGPP1), were downregulated in TOF.Conclusion: Sphingolipid metabolism was downregulated in TOF; however, the detailed mechanism needs further investigation.

Prognostic Role of Myocardial Edema as Evidenced by Early Cardiac Magnetic Resonance in Survivors of Out-of-Hospital Cardiac Arrest: A Multicenter Study.

BackgroundSudden cardiac arrest (SCA) may be caused by an acute and reversible myocardial injury, a chronic and irreversible myocardial damage, or a primary ventricular arrhythmia. Cardiac magnetic resonance imaging may identify myocardial edema (ME), which denotes acute and reversible myocardial damage. We evaluated the arrhythmic outcome of SCA survivors during follow‐up and tested the prognostic role of ME.Methods and ResultsWe included a consecutive series of 101 (71% men, median age 47 years) SCA survivors from 9 collaborative centers who underwent early (<1 month) cardiac magnetic resonance imaging and received an implantable cardioverter‐defibrillator (ICD). On T2‐weighted sequences, ME was found in 18 of 101 (18%) patients. According to cardiac magnetic resonance imaging findings, the arrhythmic SCA was ascribed to acute myocardial injury (either ischemic [n=10] or inflammatory [n=8]), to chronic structural heart diseases (ischemic heart disease [n=11], cardiomyopathy [n=20], or other [n=23]), or to primarily arrhythmic syndrome (n=29). During a follow‐up of 47 months (28 to 67 months), 24 of 101 (24%) patients received an appropriate ICD intervention. ME was associated with a significantly higher survival free from both any ICD interventions (log‐rank=0.04) and ICD shocks (log‐rank=0.03) and remained an independent predictor of better arrhythmic outcome after adjustment for left ventricular ejection fraction and late gadolinium enhancement. The risk of appropriate ICD intervention was unrelated to the type of underlying heart disease.ConclusionsME on early cardiac magnetic resonance imaging, which denotes an acute and transient arrhythmogenic substrate, predicted a favorable long‐term arrhythmic outcome of SCA survivors. These findings may have a substantial impact on future guidelines on the management of SCA survivors.

SARS-CoV-2, myocardial injury and inflammation: insights from a large clinical and autopsy study

ObjectiveDespite growing evidence about myocardial injury in hospitalized COronaVIrus Disease 2019 (COVID-19) patients, the mechanism behind this injury is only poorly understood and little is known about its association with SARS-CoV-2-mediated myocarditis. Furthermore, definite evidence of the presence and role of SARS-CoV-2 in cardiomyocytes in the clinical scenario is still lacking.MethodsWe histologically characterized myocardial tissue of 40 patients deceased with severe SARS-CoV-2 infection during the first wave of the pandemic. Clinical data were also recorded and analyzed. In case of findings supportive of myocardial inflammation, histological analysis was complemented by RT-PCR and immunohistochemistry for SARS-CoV-2 viral antigens and in situ RNA hybridization for the detection of viral genomes.ResultsBoth chronic and acute myocardial damage was invariably present, correlating with the age and comorbidities of our population. Myocarditis of overt entity was found in one case (2.5%). SARS-CoV-2 genome was not found in the cardiomyocytes of the patient with myocarditis, while it was focally and negligibly present in cardiomyocytes of patients with known viral persistence in the lungs and no signs of myocardial inflammation. The presence of myocardial injury was not associated with myocardial inflammatory infiltrates.ConclusionsIn this autopsy cohort of COVID-19 patients, myocarditis is rarely found and not associated with SARS-CoV-2 presence in cardiomyocytes. Chronic and acute forms of myocardial damage are constantly found and correlate with the severity of COVID-19 disease and pre-existing comorbidities.Graphic abstract

Chronic cardiac structural damage, diastolic and systolic dysfunction following acute myocardial injury due to bromine exposure in rats.

Accidental bromine spills are common and its large industrial stores risk potential terrorist attacks. The mechanisms of bromine toxicity and effective therapeutic strategies are unknown. Our studies demonstrate that inhaled bromine causes deleterious cardiac manifestations. In this manuscript we describe mechanisms of delayed cardiac effects in the survivors of a single bromine exposure. Rats were exposed to bromine (600ppm for 45min) and the survivors were sacrificed at 14 or 28days. Echocardiography, hemodynamic analysis, histology, transmission electron microscopy (TEM) and biochemical analysis of cardiac tissue were performed to assess functional, structural and molecular effects. Increases in right ventricular (RV) and left ventricular (LV) end-diastolic pressure and LV end-diastolic wall stress with increased LV fibrosis were observed. TEM images demonstrated myofibrillar loss, cytoskeletal breakdown and mitochondrial damage at both time points. Increases in cardiac troponin I (cTnI) and N-terminal pro brain natriuretic peptide (NT-proBNP) reflected myofibrillar damage and increased LV wall stress. LV shortening decreased as a function of increasing LV end-systolic wall stress and was accompanied by increased sarcoendoplasmic reticulum calcium ATPase (SERCA) inactivation and a striking dephosphorylation of phospholamban. NADPH oxidase 2 and protein phosphatase 1 were also increased. Increased circulating eosinophils and myocardial 4-hydroxynonenal content suggested increased oxidative stress as a key contributing factor to these effects. Thus, a continuous oxidative stress-induced chronic myocardial damage along with phospholamban dephosphorylation are critical for bromine-induced chronic cardiac dysfunction. These findings in our preclinical model will educate clinicians and public health personnel and provide important endpoints to evaluate therapies.

Soluble uric acid induces myocardial damage through activating the NLRP3 inflammasome.

Uric acid crystal is known to activate the NLRP3 inflammasome and to cause tissue damages, which can result in many diseases, such as gout, chronic renal injury and myocardial damage. Meanwhile, soluble uric acid (sUA), before forming crystals, is also related to these diseases. This study was carried out to investigate whether sUA could also activate NLRP3 inflammasome in cardiomyocytes and to analyse the mechanisms. The cardiomyocyte activity was monitored, along with the levels of mature IL‐1β and caspase‐1 from H9c2 cells following sUA stimulus. We found that sUA was able to activate NLRP3 inflammasome, which was responsible for H9c2 cell apoptosis induced by sUA. By elevating TLR6 levels and then activating NF‐κB/p65 signal pathway, sUA promoted NLRP3, pro‐caspase 1 and pro‐IL‐1β production and provided the first signal of NLRP3 inflammasome activation. Meanwhile, ROS production regulated by UCP2 levels also contributed to NLRP3 inflammasome assembly and subsequent caspase 1 activation and mature IL‐1β secretion. In addition, the tlr6 knockdown rats suffering from hyperuricemia showed the lower level of IL‐1β and an ameliorative cardiac function. These findings suggest that sUA activates NLRP3 inflammasome in cardiomyocytes and they may provide one therapeutic strategy for myocardial damage induced by sUA.

Parameters used in the control of ventricular rate in patients with permanent atrial fibrillation

Purpose. To analyze the possibility of using high-sensitivity cardiac troponin I (hsTnI), N-terminal pro-B type natriuretic peptide (NT-proBNP), tissue hemodynamics parameters, echocardiographic data and the quality of life for selection of the individual regimen for ventricular rate (VR) control drug therapy in patients with permanent atrial fibrillation (AF). Methods. The study included 120 patients aged &gt;60 years old with the diagnosis of permanent AF, who gave the informed consent. Patients were randomized into 2 groups according to the target range of VR at rest: 60-79 bpm (first group, n=60) and 80-100 bpm (second group, n=60). Patients in both groups were prescribed a selective beta1 -adrenoceptors blocker bisoprolol for VR control. The following parameters were determined before randomization and after 6 months of VR control in the target ranges: atrial and ventricular remodeling with transthoracic echocardiography; biochemical markers hsTnI and NT-proBNP; the tissue hemodynamics by the mean flow velocity (Vm) and the value of the pulsatility index (PI) using high-frequency ultrasound Doppler flowmetry; the patients’ quality of life with the “Atrial Fibrillation Effect on QualiTy-of-life (AFEQT) Questionnaire” and the “EQ-5D-5L” system with a scale EQ-VAS.Results. VR at rest after 6 months was 70±3 and 88±4 bpm (p1, p2˂0.001) in the first and second groups, respectively (p1 - comparing the initial and achieved values, p2 - values of the first and second groups). The level of hsTnI significantly decreased in both groups, but it was more pronounced in the 60-79 bpm range group (p˂0.001). Spearman’s correlation coefficients between the degree of decrease in VR and decrease in the level of hsTnI were 0.45 (p˂0.001) and 0.44 (p˂0.001) in the first and second groups, respectively. AFEQT and EQ VAS scores of quality of life improved after 6 months in both groups: the increase in the total AFEQT score in the first group -56.2±17.0% (M±SD), in the second - 42.6±15.3% (p˂0.001); EQ VAS values also increased, but differences between groups were not significant (p=0.078). In both the first and second groups, a strong positive correlation was found between the degree of decrease in VR and increase in the total score of the AFEQT questionnaire. The tendency toward an increase in Vm and a decrease in PI observed in both groups was more pronounced in the group with VR of 80-100 bpm, where Vm increased by more than 10% (p1, p2˂0.001). Changes in NT-proBNP under the influence of therapy for the reported observation period did not reach statistical significance in both groups (p1 =0.092, p2 =0.063). There was no significant dynamics of echocardiographic parameters of myocardial remodeling.Conclusion. The degree of chronic myocardial damage caused by arrhythmia (estimated by hsTnI), as well as the tissue hemodynamic parameters Vm and PI, can be the basis for individualized selection of the target VR range. This approach will allow to find a balance between cardioprotection and improvement of tissue blood flow. In creating the algorithm of selecting the target VR for patients older than 60 years with permanent AF, it is advisable to use such parameter as the degree of the initial VR change and quality of life data from the “AFEQT Questionnaire”.

Nitric oxide in patients with chronic chagas disease

Among the main causes of death around the world, we can highlight those caused by cardiovascular diseases, which have been growing significantly. The knowledge of the pathophysiology of cardiovascular diseases evidences the involvement of inflammatory processes, acute or chronic, with action of pro-inflammatory and vasoactive factors. One of these factors is nitric oxide (NO), a potent vasodilator that acts on the physiological regulation of vascular tone and has its serum levels altered in the presence of cardiovascular event, representing a physiological compensatory mechanism, to be included in Chagas disease. Method: Peripheral blood samples from 2 patients (men, mean age 65 years) with positive Chagas; disease serology (cardiac form, chronic phase) were collected at the cardiology outpatient service of the Hospital Electro Bonini (UNAERP). Two healthy volunteer participants were used as a negative control. NO (NO 2- / NO 3-) levels were determined by a quantitative detection kit for nitrate and nitrite concentrations using colorimetric assay. Absorbance was read at 540 nm. Partial Results: The median NO activity was 1.4 umol/L in chagasic patients and 1.0 umol/L in healthy participants (p &amp;lt;0.001). Discussion and conclusion of the results: The cardiac form of Chagas Disease, a condition caused by the chronic infection of the protozoan Trypanossoma cruzi and marked by chronic inflammation and progressive myocardial cell damage, has progressed with new endemic areas throughout the world, although its incidence has decreased last years. The parasite compromises the energetic synthesis of cardiac myocytes without altering the mitochondrial ultrastructure. It is reported that the parasite can control the central structure of the organelle in order to obtain substrate for its proliferation. Therefore, it has become relevant to investigate the relationship of serum NO concentration with cardiovascular diseases, due to the importance of vasoactive factor and the subject for public health. Developing knowledge that allows better understanding of oxidative stress in the presence of T. cruzi infection and associating them with inflammatory mechanisms culminates in the elucidation of this chronic pathology.

Irisin ameliorates septic cardiomyopathy via inhibiting DRP1-related mitochondrial fission and normalizing the JNK-LATS2 signaling pathway.

Irisin plays a protective effect in acute and chronic myocardial damage, but its role in septic cardiomyopathy is unclear. The aim of our study was to explore the in vivo and in vitro effects of irisin using an LPS-induced septic cardiomyopathy model. Our results demonstrated that irisin treatment attenuated LPS-mediated cardiomyocyte death and myocardial dysfunction. At the molecular level, LPS application was associated with mitochondrial oxidative injury, cardiomyocyte ATP depletion and caspase-related apoptosis activation. In contrast, the irisin treatment sustained mitochondrial function by inhibiting DRP1-related mitochondrial fission and the reactivation of mitochondrial fission impaired the protective action of irisin on inflammation-attacked mitochondria and cardiomyocytes. Additionally, we found that irisin modulated DRP1-related mitochondrial fission through the JNK-LATS2 signaling pathway. JNK activation and/or LATS2 overexpression abolished the beneficial effects of irisin on LPS-mediated mitochondrial stress and cardiomyocyte death. Altogether, our results illustrate that LPS-mediated activation of DRP1-related mitochondrial fission through the JNK-LATS2 pathway participates in the pathogenesis of septic cardiomyopathy. Irisin could be used in the future as an effective therapy for sepsis-induced myocardial depression because it corrects DRP1-related mitochondrial fission and normalizes the JNK-LATS2 signaling pathway.

Chronic myocardial damage in idiopathic pulmonary arterial hypertension: a clinical case

Chronic myocardial injury, determined by a constantly elevated cardiac troponin (cTn) value, may occur in patients with pulmonary arterial hypertension (PAH), indicating the severity of the disease and associated with an adverse prognosis. Increasing of cTn among patients with PAH was registered prior to 2018, but after the Fourth universal definition of myocardial infarction (2018) was released the understanding of this phenomenon has been changed. One of the causes of chronic myocardial injury in patients with PAH is the compression of coronary arteries. Left main coronary artery (LMCA) compression is an uncommon and probably underestimated cause for angina-like chest pain and ventricular dysfunction in patients with severe pulmonary artery hypertension. LMCA compression by an enlarged pulmonary artery trunk has been associated with angina, but appropriate diagnostic and treatment approaches remain poorly defined. This is a case report on a woman with idiopathic PAH and compression of the LMCA by an enlarged pulmonary artery. The diagnosis of LMCA stenosis was confirmed by multi-slice computed tomography and coronary angiography. Biomarkers such as cTn and brain natriuretic peptide have also been identified as criteria of optimal treatment. Percutaneous coronary intervention in conjunction with PAH-specific therapy appears to be a feasible, safe, and effective treatment option for patients with extrinsic compression of the LMCA from pulmonary artery enlargement

Synthesis and structure of (het)arylglutamic acids and pyroglutamic acid hydrazides

Hydrochlorides of (2R*,3R*)-3-(het)arylglutamic acid diesters were synthesized by esterification of the corresponding glutamic acids (Glu). Diesters reacted with hydrazine hydrate to give (4R*,5R*)-2-pyrrolidone-5-carboxylic acid hydrazides. Hydrochlorides of glutamic acids diesters were found to exhibit cardioprotective properties against acute and chronic stress myocardial damage.

Physical Activity, Obesity, and Subclinical Myocardial Damage

ObjectivesThis study sought to evaluate the association of physical activity with chronic myocardial damage, assessed by elevated high-sensitivity cardiac troponin T (hs-cTnT), in individuals with and without obesity. BackgroundPhysical activity is associated with reduced risk of heart failure (HF), particularly among obese people. The role of chronic myocardial damage in this association is uncertain. MethodsWe studied 9,427 participants in the Atherosclerosis Risk in Communities Study without cardiovascular disease, with body mass index >18.5 kg/m2. Physical activity was categorized per American Heart Association guidelines as recommended, intermediate, or poor. We evaluated cross-sectional associations of physical activity and obesity with elevated hs-cTnT (≥14 ng/l). In prospective analyses, we quantified the association of elevated hs-cTnT with HF risk within cross-categories of baseline physical activity and obesity. ResultsPeople with poor physical activity were more likely to have elevated hs-cTnT than those with recommended levels (odds ratio [OR]: 1.39; 95% confidence interval [CI]: 1.15 to 1.68). In cross-categories of physical activity and obesity, using the non-obese/recommended activity group as the reference, individuals with obesity and poor activity were most likely to have elevated hs-cTnT (OR: 2.46; 95% CI: 1.91 to 3.19), whereas the obese/recommended activity group had a weaker association (OR: 1.68; 95% CI: 1.28 to 2.21; p < 0.001 for interaction between physical activity and obesity). In prospective analyses, elevated hs-cTnT was strongly associated (p < 0.001) with incident HF in all obesity/physical activity cross-categories (p > 0.20 for interaction). ConclusionsPhysical activity is inversely associated with chronic subclinical myocardial damage. Physical activity might lessen the association between obesity and subclinical myocardial damage, which could represent a mechanism by which physical activity reduces HF risk.

Immune-Mediated Heart Disease.

The heart involvement in systemic autoimmune diseases represents a growing burden for patients and health systems. Cardiac function can be impaired as a consequence of systemic conditions and manifests with threatening clinical pictures or chronic myocardial damage. Direct injuries are mediated by the presence of inflammatory infiltrate which, even though unusual, is one of the most danger manifestations requiring prompt recognition and treatment. On the other hand, a not well-managed inflammatory status leads to accelerated atherosclerosis that precipitates ischemic disease. All cardiac structures may be damaged with different grades of intensity; moreover, lesions can appear simultaneously or more frequently at a short distance from each other leading to the onset of varied clinical pictures. The pathogenesis of heart damages in systemic autoimmune conditions is not yet completely understood for the great part of situations, even if several mechanisms have been investigated. The principal biochemical circuits refer to the damaging role of autoantibodies on cardiac tissues and the precipitation of immune complexes on endocardium. These events are finally responsible of inflammatory infiltration which leads to subsequent worsening of the previous damage. For these reasons, it appears of paramount importance a regular and deepened cardiovascular assessment to prevent a progressive evolution toward heart failure in patient affected by autoimmune diseases.

Alcohol Consumption and Cardiac Biomarkers: The Atherosclerosis Risk in Communities (ARIC) Study.

The role of alcohol in the development of subclinical cardiovascular disease is unclear. We examined the association between alcohol consumption and markers of subclinical cardiac damage and wall stress. We studied the cross-sectional and prospective associations of alcohol consumption with high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro B-type natriuretic peptide (NT-proBNP) measured at 2 time points, 6 years apart (baseline, 1990-1992; follow-up, 1996-1998), in over 11000 participants of the Atherosclerosis Risk in Communities (ARIC) Study with no history of cardiovascular disease. Alcohol consumption was categorized as follows: never, former, current: ≤1, 2-7, 8-14, and ≥15 drinks/week. Compared to never drinkers, persons who consumed 2-7 drinks per week were less likely to have increased hs-cTnT (≥14 ng/L) at baseline (odds ratio = 0.67, 95% CI, 0.46-0.96), and had a lower risk of incident increases in hs-cTnT at follow-up (relative risk = 0.70, 95% CI, 0.49-1.00). Conversely, there was a positive association between alcohol intake and NT-proBNP concentrations at baseline. Consumption of ≥15 drinks/week was positively associated with incident increases in NT-proBNP (≥300 pg/mL) at the 6-year follow-up visit (relative risk = 2.38, 95% CI, 1.43-3.96). In this community-based study of middle-aged adults without a history of cardiovascular disease, moderate drinking was associated with lower concentrations of hs-cTnT, a marker of chronic subclinical myocardial damage, and positively associated with NT-proBNP, a biomarker of cardiac wall stress. Our results suggest that the cardiac effects of alcohol are complex. Cardiac biomarkers may help improve our understanding of the full cardiovascular effects of alcohol consumption.

Association of a Biomarker of Glucose Peaks, 1,5-Anhydroglucitol, With Subclinical Cardiovascular Disease

1,5-Anhydroglucitol (1,5-AG) is a biomarker of glucose peaks and has been associated with clinical cardiovascular disease. However, the association between 1,5-AG and subclinical cardiovascular disease is unknown. We investigated the association of 1,5-AG with subclinical myocardial damage (assessed by high-sensitivity cardiac troponin T [hs-cTnT]) and atherosclerosis (assessed by carotid intima-media thickness [CIMT] and carotid plaque). We measured 1,5-AG, hs-cTnT, CIMT, and carotid plaque among 10,072 people without diabetes and 681 with diabetes who attended the second examination of the Atherosclerosis Risk in Communities (ARIC) Study (baseline, 1990-1992). We used Poisson regression to characterize the associations between 1,5-AG and prevalent elevated hs-cTnT, thick CIMT, or carotid plaque. Among 9,145 people with a second hs-cTnT measurement 6 years later, we used multinomial logistic regression to assess associations with incident elevation in hs-cTnT. We found that in people with diabetes, lower 1,5-AG (<6 μg/mL) was cross-sectionally associated with elevated hs-cTnT (prevalence ratio 2.06, 95% CI 1.23-3.46) compared with higher 1,5-AG (≥10 μg/mL). Associations in people without diabetes and with thick CIMT or the presence of carotid plaque were less robust. Low 1,5-AG was prospectively associated with the 6-year incident elevation in hs-cTnT (relative risk 2.90, 95% CI 1.23-6.85) in people with diabetes. All associations were strongly attenuated with further adjustment for HbA1c. In people with diabetes, 1,5-AG was associated with subclinical cardiovascular disease, particularly chronic subclinical myocardial damage. Nonetheless, whether observed associations are truly independent of average glycemia is unclear.