Prolonged PR Research Articles

The Case of Flecainide Toxicity: What to Look For and How to Treat

Introduction: Flecainide is a class Ic antiarrhythmic agent used to prevent and treat both ventricular and supraventricular tachycardias including atrial fibrillation, AV nodal re-entrant tachycardia (AVNRT), and Wolff- Parkinson-White syndrome (WPW). Flecainide can cause serious side effects include cardiac arrest, arrhythmias, and heart failure. Despite its growing use, the presenting signs and symptoms of flecainide toxicity are not familiar to most clinicians. Case description: This was a 58 year-old female who presented from her skilled nursing facility due to hypoxia and altered mental status. Past medical history was notable for paroxysmal atrial fibrillation for which she was on flecainide. At the nursing facility the patient was noted to be obtunded, whereas at baseline she was reportedly alert and oriented. On presentation to the Emergency Department EKG demonstrated wide-complex tachycardia. Subsequent lab results were notable for hypokalemia and an acute kidney injury (AKI). A repeat EKG was concerning for ischemia in leads II, III, aVF and cardiology was emergently consulted. They noted the EKG changes were consistent with flecainide toxicity, specifically a prolonged PR interval and QRS. She was eventually admitted to the medical intensive care unit. Her wide complex tachycardia on admission was ultimately attributed to flecainide toxicity in setting of AKI. Six days after presentation, it was found that her flecainide level was in the toxic range at 2.02 ug/mL (normal range: 0.20-1.00 ug/mL, toxic>1.50 ug/mL). Discussion: Flecainide intoxication is rare but serious due to the potential for cardiogenic shock. Its diagnosis can be difficult as the flecainide serum level may take days to result and there are no pathognomonic clinical signs. This case demonstrates the necessity of keeping flecainide toxicity on the physician’s differential for patients who are taking the drug, as well as what ECG and laboratory findings can suggest it as the etiology. A heightened suspicion is warranted in the patient with new renal impairment. Treatment can be lifesaving if initiated promptly.

CCL3/Macrophage Inflammatory Protein-1α Is Dually Involved in Parasite Persistence and Induction of a TNF- and IFNγ-Enriched Inflammatory Milieu in Trypanosoma cruzi-Induced Chronic Cardiomyopathy.

CCL3, a member of the CC-chemokine family, has been associated with macrophage recruitment to heart tissue and parasite control in the acute infection of mouse with Trypanosoma cruzi, the causative agent of Chagas disease. Here, we approached the participation of CCL3 in chronic chagasic cardiomyopathy (CCC), the main clinical form of Chagas disease. We induced CCC in C57BL/6 (ccl3+/+) and CCL3-deficient (ccl3−/−) mice by infection with the Colombian Type I strain. In ccl3+/+ mice, high levels of CCL3 mRNA and protein were detected in the heart tissue during the acute and chronic infection. Survival was not affected by CCL3 deficiency. In comparison with ccl3+/+, chronically infected ccl3−/− mice presented reduced cardiac parasitism and inflammation due to CD8+ cells and macrophages. Leukocytosis was decreased in infected ccl3−/− mice, paralleling the accumulation of CD8+ T cells devoid of activated CCR5+ LFA-1+ cells in the spleen. Further, T. cruzi-infected ccl3−/−mice presented reduced frequency of interferon-gamma (IFNγ)+ cells and numbers of parasite-specific IFNγ-producing cells, while the T. cruzi antigen-specific cytotoxic activity was increased. Stimulation of CCL3-deficient macrophages with IFNγ improved parasite control, in a milieu with reduced nitric oxide (NOx) and tumor necrosis factor (TNF), but similar interleukin-10 (IL-10), concentrations. In comparison with chronically T. cruzi-infected ccl3+/+ counterparts, ccl3−/− mice did not show enlarged heart, loss of left ventricular ejection fraction, QTc prolongation and elevated CK-MB activity. Compared with ccl3+/+, infected ccl3−/− mice showed reduced concentrations of TNF, while IL-10 levels were not affected, in the heart milieu. In spleen of ccl3+/+ NI controls, most of the CD8+ T-cells expressing the CCL3 receptors CCR1 or CCR5 were IL-10+, while in infected mice these cells were mainly TNF+. Lastly, selective blockage of CCR1/CCR5 (Met-RANTES therapy) in chronically infected ccl3+/+ mice reversed pivotal electrical abnormalities (bradycardia, prolonged PR, and QTc interval), in correlation with reduced TNF and, mainly, CCL3 levels in the heart tissue. Therefore, in the chronic T. cruzi infection CCL3 takes part in parasite persistence and contributes to form a CD8+ T-cell and macrophage-enriched cardiac inflammation. Further, increased levels of CCL3 create a scenario with abundant IFNγ and TNF, associated with cardiomyocyte injury, heart dysfunction and QTc prolongation, biomarkers of severity of Chagas' heart disease.

His bundle pacing in heart failure: A review of current literature

Biventricular (BiV) pacing revolutionized the heart failure management in patients with sinus rhythm and left bundle branch block; however, left ventricular-lead placement is not always technically possible. Also, BiV pacing does not fully normalize ventricular activation and, therefore, the ventricular resynchronization is imperfect. On the other hand, right ventricular pacing for bradycardia may cause or worsen heart failure in some patients by causing dyssynchronous ventricular activation. His bundle pacing comes as an alternative to current approaches as it activates the ventricles via the native His-Purkinje system, resulting in true physiological pacing, and, therefore, is a promising site for pacing in bradycardia and traditional CRT indications in cases where it can overcome left bundle branch block. Furthermore, it has the potential to open up new indications for pacing therapy in heart failure, such as targeting patients with PR prolongation, but a narrow QRS duration. In this article we explore the history, clinical evidence, proposed mechanisms, procedural characteristics, and the role in current therapy of His bundle pacing in the prevention and treatment of heart failure.

A CASE OF LIFE-THREATENING FLECAINIDE INDUCED VENTRICULAR TACHYCARDIA

The class 1C antiarrhythmic agent flecainide is considered a first-line rhythm control option for atrial fibrillation (AF) in patients without LV dysfunction or coronary artery disease. However, due to its blockade of sodium channels, its use carries the risk of PR and QRS prolongation and life-

A CASE OF FULMINANT CARDIAC SARCOIDOSIS RESEMBLING GIANT CELL MYOCARDITIS

Severe cardiac sarcoidosis (CS) can share clinical and histopathologic features with giant cell myocarditis (GCM). A 56 year old female presented with 1 week of exertional chest pressure and dyspnea. EKG revealed prolonged PR interval, bifascicular block and frequent PVCs. Echocardiogram

CAPE COD, CHEST PAIN, AND HEART BLOCK … IT’S NOT LYME!

Myopericarditis, inflammation of pericardium and cardiac muscle, is often caused by a virus. Lyme is considered when concurrent conduction abnormalities are present. 18 year old male presented with 1 day of pleuritic chest pain. ECG demonstrated marked PR prolongation and diffuse ST elevation (Fig

Real-world behavior of CRT pacing using the AdaptivCRT algorithm on patient outcomes: Effect on mortality and atrial fibrillation incidence.

BackgroundThe AdaptivCRT (aCRT) algorithm continuously adjusts cardiac resynchronization therapy (CRT) according to intrinsic atrioventricular conduction, providing synchronized left ventricular pacing in patients with normal PR interval and adaptive BiV pacing in patients with prolonged PR interval. Previous analyses demonstrated an association between aCRT and clinical benefit. We evaluated the incidence of patient mortality and atrial fibrillation (AF) with aCRT compared with standard CRT in a real‐world population.Methods and ResultsPatients enrolled in the Medtronic Personalized CRT Registry and implanted with a CRT from 2013‐2018 were divided into aCRT ON or standard CRT groups based upon device‐stored data. A Frailty survival model was used to evaluate the potential survival benefit of aCRT, accounting for patient heterogeneity and center variability. Daily AF burden and first device‐detected AF episodes of various durations were recorded by the device during follow‐up.A total of 1814 CRT patients with no reported long‐standing AF history at implant were included. Mean follow‐up time was 26.1 ± 16.5 months and 1162 patients (64.1%) had aCRT ON. Patient survival probability at 36 months was 88.3% for aCRT ON and 83.7% for standard CRT (covariate‐adjusted hazard ratio [HR] = 0.71, 95% CI: 0.53‐0.96, P = .028). Mean AF burden during follow‐up was consistently lower in aCRT ON patients compared with standard CRT. At 36 months, the probability of AF was lower in patients with aCRT ON, regardless of which AF definition threshold was applied (6 minutes‐30 days, all P < .001).ConclusionUse of the AdaptivCRT algorithm was associated with improved patient survival and lower incidence of AF in a real‐world, prospective, nonrandomized registry.

The relationship of the prolonged PR interval with the long-term survival in patients with heart failure undergoing cardiac resynchronization therapy

Aim. To assess the relationship between the prolonged PR interval (≥200 ms) and the long-term survival of patients undergoing cardiac resynchronization therapy (CRT).Material and methods. A total of 85 patients (mean age — 55,1Ѓ}9,9 years; men — 81,2%) with NYHA class II-IV heart failure (HF) were examined. The mean follow-up was 34,0Ѓ}21,2 months. Patients with PR&lt;200 ms (n=52) made up group I, with PR≥200 ms (n=33) — group II. Then the patients were divided into subgroups depending on the QRS duration: ≥150 ms (n=33 in group I and n=14 in group II, respectively) &lt;150 ms (n=19 in group I and n=19 in group II, respectively).Results. In patients of group II, a history of myocardial infarction (MI) was more often registered (p=0,005), left ventricular ejection fraction (LVEF) was lower (p=0,032). In a multivariate analysis, MI (OR 3,217; CI 95% 1,188-8,712; p=0,022) and LVEF value (OR 0,869; CI 95% 0,780-0,968; p=0,011) had a significant relationship with the PR interval prolongation (≥200 ms). The survival of patients of group I was 59,6%, group II — 18,2% (Log-rank test p&lt;0,001). According to Cox regression model, the initial left ventricle end-systolic volume (OR 1,012; 95% CI 1,006-1,017; p&lt;0,001), inferior wall MI (OR 1,690; 95% CI 1,131-2,527; p=0,011) and PR interval ≥200 ms (OR 2,179; 95% CI 1,213–3,915; p=0,009) were associated with long-term mortality. In patients with PR≥200 ms, survival rate was low, regardless of the QRS duration (21,4% in patients with QRS≥150 ms, 15,8% in patients with QRS&lt;150 ms; Log-rank test p=0,698) In patients with PR&lt;200 ms, the survival rate of patients with QRS≥150 ms was 72,7%, and for patients with QRS&lt;150 ms — 36,8% (Log-rank test p=0,031).Conclusion. In HF patients, PR interval prolongation (≥200 ms) is associated with long-term mortality increase. The highest survival rates were observed in patients with PR&lt;200 ms and QRS≥150 ms. In patients with QRS≥150 ms, the presence of PR≥200 ms should be considered as an additional criterion for CRT.

Abstract WP255: Can Normal Electrocardiogram Rule Out Newly Diagnosed Atrial Fibrillation in Ischemic Stroke Patients

Introduction: Electrocardiogram (ECG) findings of premature atrial contraction and prolonged PR interval are associated with risk of onset atrial fibrillation (AF) in cryptogenic stroke. We sought to see if normal ECG and AF incidence is incompletely understood. Methods: From a prospective single-hospital stroke registry from 2018, we identified ischemic stroke patients who had ECG done on admission for review. We excluded patients with AF on admission ECG, history of AF, and implanted device with cardiac monitoring capability. Normal ECG was interpreted based on the standardized reporting guidelines for ECG studies evaluating risk stratification of emergency department patients. Stroke subtype was diagnosed according to the TOAST classification: large artery atherosclerosis (LAA), small vessel occlusion (SVO), cardioembolism, others/undetermined and embolic stoke of undetermined source (ESUS) criteria. We compared the incidence of newly diagnosed AF during hospitalization and from outpatient cardiac event monitoring between normal and abnormal ECG. Results: Of the 558 consecutive acute ischemic stroke patients, we excluded 135 with AF on admission ECG or history of AF and 9 with implanted devices. Of the remaining 414 patients that were included in the study, ESUS (31.2%) was the most frequent stroke subtype, followed by LAA (30.0%), SVO (14.0%), others/undetermined (15.7%), and cardioembolism (9.2%). Normal ECG was observed in 125 patients (30.2%). Cardioembolic subtype was less frequent in the normal versus abnormal ECG group (1.6% vs. 12.5%, p&lt;0.001). New AF was detected in 17/414 patients (4.1%) during hospitalization. Of these 17 patients, none had normal ECG (0/125) and all had abnormal ECG (17/289, 5.9%) (p=0.002). After discharge, of 111 patients undergoing 4-week outpatient cardiac monitoring, new AF was detected in 16 (14.4%). Of these 16 patients, only 1 had a normal ECG (1/35, 2.9%) while 15 had abnormal ECG (15/76, 19.7%) (p=0.02). Conclusions: Normal ECG at admission for acute ischemic stroke is associated with low likelihood of detection of new atrial fibrillation in either the inpatient or outpatient setting.

Different dynamics of new-onset electrocardiographic changes after balloon- and self-expandable transcatheter aortic valve replacement: Implications for prolonged heart rhythm monitoring

BackgroundNew onset electrocardiographic (ECG) changes after transcatheter aortic valve replacement (TAVR) are used to assess the risk for late atrioventricular block. However, the time of ECG evaluation remains controversial. We aimed to compare the time course and dynamics of new onset ECG changes according to valve design in balloon- (BEV) and self-expandable (SEV) TAVR. Methods and resultsThis single center study enrolled 133 consecutive TAVR patients (28.6% SEV, 71.4% BEV). Patients with pre-existent permanent pacemaker implant (PPMI), procedural death or incomplete ECG registration were excluded. Standard 12‑lead ECG was performed before the procedure, at 1, 24, 48 and 120 h and 1 month. In BEV patients, no significant PR prolongation occurred, whereas in SEV patients the PR interval prolonged significantly with 33.7 ± 22.0 ms (p < 0.001, compared to pre-TAVR) but only after 48 h after TAVR. Widening of QRS duration was comparable among both BEV and SEV patients (6.7 ± 21.5 versus 17.0 ± 26.9 ms, p = 0.061) and occurred immediately after TAVR. New-onset left bundle branch block was seen in 18.5% of BEV and 30.8% of SEV patients (p = 0.120) and occurred within 24 h after TAVR in both groups. Late PPMI (>24 h after TAVR) was higher in SEV compared to BEV patients (15.3% versus 1.5%, p = 0.008). ConclusionSelf-expandable valves cause more impairment in atrioventricular conduction with a delayed time course compared to balloon expandable valves. This might explain the higher pacemaker need beyond 24 h after TAVR. Our findings suggest that patients with self-expandable valves require at least 48 h ECG monitoring post TAVR.

Biophysical mechanisms for QRS- and QTc-interval prolongation in mice with cardiac expression of expanded CUG-repeat RNA

Myotonic dystrophy type 1 (DM1), the most common form of muscular dystrophy in adults, results from the expression of toxic gain-of-function transcripts containing expanded CUG-repeats. DM1 patients experience cardiac electrophysiological defects, including prolonged PR-, QRS-, and QT-intervals, that increase susceptibility to sudden cardiac death (SCD). However, the specific biophysical and molecular mechanisms that underlie the electrocardiograph (ECG) abnormalities and SCD in DM1 are unclear. Here, we addressed this issue using a novel transgenic mouse model that exhibits robust cardiac expression of expanded CUG-repeat RNA (LC15 mice). ECG measurements in conscious LC15 mice revealed significantly prolonged QRS- and corrected QT-intervals, but a normal PR-interval. Although spontaneous arrhythmias were not observed in conscious LC15 mice under nonchallenged conditions, acute administration of the sodium channel blocker flecainide prolonged the QRS-interval and unveiled an increased susceptibility to lethal ventricular arrhythmias. Current clamp measurements in ventricular myocytes from LC15 mice revealed significantly reduced action potential upstroke velocity at physiological pacing (9 Hz) and prolonged action potential duration at all stimulation rates (1-9 Hz). Voltage clamp experiments revealed significant rightward shifts in the voltage dependence of sodium channel activation and steady-state inactivation, as well as a marked reduction in outward potassium current density. Together, these findings indicate that expression of expanded CUG-repeat RNA in the murine heart results in reduced sodium and potassium channel activity that results in QRS- and QT-interval prolongation, respectively.

Clinical evaluation and current trends in the diagnosis and treatment of Brugada syndrome

Brugada syndrome (BrS) is a cardiac channelopathy associated with an increased risk of unexplained syncope, life-threatening ventricular arrhythmia, or sudden cardiac death. The patients with BrS often have the arrhythmia at rest or while asleep. It could also be triggered by fever or medications. About 15% of those with BrS have a family history of this condition. BrS is diagnosed by identifying ST segment elevation in leads V1–V2 with a right bundle branch block-like appearance of standard 12-lead electrocardiogram (ECG) placed in the fourth intercostal space. The ST segment elevation could also be unmasked or become more obvious by placing lead V1–V2 in the second and third intercostal spaces. In some patients, the ECG shows a prolonged PR interval but normal QTc interval. The first-line therapy for patients with BrS presenting with prior cardiac arrest or documented ventricular tachycardia is an implantable cardioverter-defibrillator (ICD). In the cases with recurrent ventricular arrhythmia or electrical storm, pharmacological therapy with quinidine is recommended as an adjunct to an ICD. This article is an overview of the clinical evaluation and current trends in the diagnosis and treatment of BrS.

New guidelines for diagnosis of rheumatic fever; do they apply to all populations?

To evaluate the efficacy of recently updated Jones criteria for diagnosis of rheumatic fever in high incidence populations like Egypt. Clinical data of 891 Egyptian patients with rheumatic fever, aged 5-15 years in a highly specialized rheumatic fever clinic were reviewed retrospectively from March 2014 to March 2016. Discriminant analysis was used to detect the most effective predictors for diagnosis of rheumatic fever in our patients incorporating echocardiographic criteria. We compared our results to the most recent update by the American Heart Association. The most effective predictors of rheumatic fever included arthritis, carditis, chorea, aortic regurgitation, grades of mitral regurgitation ≥10mm length and velocity ≥2.5 m/s, thick anterior mitral valve leaflets, elevated acute phase reactants, positive family history and prolonged PR interval. Our predictors showed a high sensitivity of 93%, a specificity of 62% and an overall prediction accuracy of 81.4%. We concluded that strict application of updated Jones criteria may lead to under diagnosis of rheumatic fever in highly endemic countries. We recommend further studies to examine the sensitivity of the most recent update of Jones criteria on other highly endemic populations.

Prevalence of Electrocardiogram Abnormalities in Human Immunodeficiency Virus-Infected Children

HIV is an important cause of childhood morbidity and mortality affecting more than 1.3 million children worldwide, one of the morbidity is cardiac abnormalities. Cardiovascular abnormalities are still subclinical during childhood then become symtomatic in adulthood. Electrocardiography is effective to detect cardiac diseases. This study aimed to assess ECG changes in HIV infected children and describe ECG abnormalities in HIV-infected children with or without HAART. From 70 subjects, we found the most common abnormality was sinus tachycardia in 17 patients (24.3%), sinus bradycardia 1 patient (1.4%) and 2 patients with sinus arrhythmia (2.9%). The mean QTc interval was 0.42 seconds (±0.07) and 14 patients (20%) had prolongation. The mean PR interval was 0.12 seconds (±0.02), 11 patients (15.7%) experienced prolongation of PR interval. The mean QRS duration was 0.06 seconds (±0.09). Left ventricular enlargement was present in 6 patients (8.6%), conduction disturbance which is characterized by Bundle branch block was found in 2 patients (2.9%) and ST changes was seen in 2 patients (2.9%). Other ECG abnormalities are characterized by right ventricle hyperthropy in 4 patients and a patient had T tall. The prevalence of cardiac abnormalities based on ECG examination from this study was 51.3%, consist of heart rhythm abnormality, prolonged PR interval, prolonged QTc interval, bundle branch block, ventricle hypertrophy and ST changes.

Electrocardiographic findings in human immunodeficiency virus-infected children in Benin City, Nigeria.

Human immunodeficiency virus (HIV) infection is a global pandemic affecting mostly sub-Saharan Africa. It is a multisystem disease. Cardiovascular involvement detected by electrocardiogram (ECG) has been described mostly in adult populations with few studies on children. In this study, the ECG findings of HIV-infected as against HIV-uninfected children were evaluated. This comparative cross-sectional study was conducted in two public hospitals in Benin City. Using convenience sampling, 200 each of HIV-positive children attending the HIV clinics of both hospitals and age- and sex-matched HIV-negative children attending follow-up clinics in the same hospitals were recruited. Biodata/sociodemographic information was obtained, while each participant underwent 12-channel ECG evaluation. The prevalence of abnormal ECG findings in HIV-positive children was 34.5% compared to 4.5% in HIV-negative children (P < 0.0001). The mean PR, QRS and QT intervals in the participants were 0.13 ± 0.02 s, 0.11 ± 0.15 s and 0.41 ± 0.03, respectively. They were statistically significantly longer than controls, 0.12 ± 0.02 s, 0.08 ± 0.09 s and 0.40 ± 0.02 s, respectively, P < 0.05, in each case. The prevalence of prolonged PR, QRS and QTc was significantly higher in the patients, 5%, 3.5% and 3.5%, respectively, than controls, 05, 0% and 0%, respectively (P < 0.05 in each case). A third of the HIV-infected children in the study had abnormal ECG changes. It is recommended that ECG be included in their routine management of HIV-positive children so as to better supervise the affected children, retard the deterioration and improve their quality of health.

Coronary artery aneurysm in Kawasaki disease.

A 3-year-old male presents to the emergency department with chief complaints of fever and vomiting. He had a positive rapid streptococcus throat test with cervical lymphadenopathy. The patient was started on antibiotics. On examination, there was diffuse erythematous macular rash on the chest. Laboratory tests revealed elevated white cell count and C-reactive protein. Electrocardiogram was notable for prolonged PR interval indicating 1st degree atrioventricular block. Echocardiogram revealed ectasia of the right coronary artery (RCA). A presumptive diagnosis of Kawasaki disease was made and the patient was started on high-dose aspirin and intravenous immunoglobulins. Cardiac computed tomography angiography (CTA) showed an aneurysm of the proximal RCA measuring up to 7.4 mm. The RCA immediately proximal to the aneurysm measured 3 mm in diameter. The Z score was 13.4. Oblique coronal image from cardiac CTA and volume rendered images demonstrated an aneurysm of the proximal RCA. The patient improved with treatment.

Association between prolonged PR intervals and significant coronary artery disease in patients with non-ST elevation myocardial infarction and unstable angina

Objectives: The purpose of this study was to assess the association between a prolonged PR interval and significant coronary artery disease (CAD) in patients who were acutely admitted with unstable angina or non-ST-segment elevation myocardial infarction (NSTEMI). Background: Prolongation of the electrocardiographic PR interval occurs frequently in clinical practice. Few studies to date have evaluated the association between prolonged PR intervals and significant CAD in hospitalized patients with NSTEMI and unstable angina. Methodology: PR interval was measured in 205 patients with NSTEMI or unstable angina, and the patients were divided into those with normal ( ([0-9]+)200 ms) was present in 96 patients (46.8%). This finding was statistically significantly associated with significant CAD (P = 0.024). In addition, these patients had a trend toward higher Gensini scores (P = 0.093) and a higher frequency of left main coronary artery or three-vessel CAD (P = 0.069). Conclusion: Our study showed that a prolonged PR interval is independently associated with significant CAD in patients with acute coronary syndrome, in contrast with earlier beliefs.

Electrocardiogram abnormalities in obese adolescents

Background Obesity in adolescents is a known risk factor for cardiovascular disease mortality and sudden cardiac death. Obesity is associated with a wide variety of electrocardiogram (ECG) abnormalities.&#x0D; Objective To assess prevalence and describe the ECG abnormalities in obese adolescents.&#x0D; Methods This cross-sectional study was conducted at Children’s Cardiology Clinic – Integrated Heart Center of Sanglah General Hospital, Denpasar, Bali, by recording ECGs of obese adolescents aged 11-15 years from several junior high schools from December 2016 to April 2017. The inclusion criteria were obese adolescents aged 11 to 15 years, who were willing to participate in the study and provided informed consent.&#x0D; Results A total of 78 ECGs of obese adolescents (60% male) were selected. Subjects’ mean weight and age were 82.6 (SD 15.2) kg and 13.2 (SD 1) years, respectively. Pre-hypertension was found in 25 (32%) subjects, while hypertension was found in 18 (23%) subjects. There were 29 (37%) subjects with abnormal ECGs. Sinus tachycardia was present in 13 (17%) subjects, and sinus arrhythmia was identified in 11 (14%) subjects. Eight (10%) patients experienced prolongation of QTc interval and 5 (6%) patients presented with prolongation of PR interval. There were no shifts of the P wave, QRS wave and T wave axes, changes of P wave morphology, low QRS voltage, T wave flattening, ventricular enlargement, or ST segment changes found in this study.&#x0D; Conclusion The prevalence of cardiac abnormalities based on ECG examination in obese adolescents is 37%, consisting of heart rhythm abnormalities, prolonged PR interval, and prolonged QTc interval.

Intramuscular Immunization of Streptococcus pyogenes SF370 protein extract and identification of multiple virulence factors through proteomic profiling in RHD induced Balb/c mice

Group A streptococcus (GAS) and autoimmunity are associated with heart related mitral valve damage, in adults. In this study Balb/c mice were intramuscularly immunized with S. pyogenes SF370 for 4 weeks. Prior to euthanization, physiological parameters like body weight and electrical signalling of the heart were recorded. After euthanization, the heart tissue homogenate was prepared and proteomic alterations were studied using SDS-PAGE and 2D electrophoresis. The expression levels of inflammatory genes like TNFα, IFNγ and TGF-β were quantified using real time PCR. Insilico analysis was performed to identify the functions of hypothetical proteins and virulence factors involved in the induction of rheumatic carditis. The results showed a reduction in body weight, ulceration, inflammation, cardiac lesions and prolonged PR interval in mice immunized with S. pyogenes SF370, as a result of RHD. The heart related proteins like α-actinin, fatty acid binding protein-heart, myosin light chain 3, hemoglobin subunit alpha, myoglobin regulatory light chain 2, (ventricular/cardiac muscle isoform), myosin-6, troponin-1 were found to be up-regulated when compared with the control. The functional annotation of S. pyogenes (SF370) was carried out by retrieving 1696 identified proteins and 653 hypothetical protein sequences in NCBI genome database. The conserved domain was identified for 505 proteins. The pfam database documented that the super families of 279 sequences and 40 signal peptides enabled the classification of proteins in different categories like biological (20%), cellular (22%) and molecular functions (36%). Putative transcription repair coupling factor and putative lysine aminopeptidase N terminal are the two virulence factors identified by VICMPRED in S. pyogenes SF370. The two identified virulence factors are involved in altering the mice heart proteome and thereby controlling the streptococcus pyogenes infection. Thus, the results of the present study reveals the role of immunogenic proteins in induction of rheumatic carditis and to elucidate the molecular mechanisms leading to autoimmune reactions in Balb/c mice.

Effect of ghrelin on VEGF-B and connexin-43 in a rat model of doxorubicin-induced cardiomyopathy.

Background Since their discovery in the early 1960s, doxorubicin (DOX) remains the most effective anticancer drug. However, this drug has confirmed to be a double-edged sword because it causes a cardiomyopathy that leads to congestive heart failure. Ghrelin, a multi-functional peptide, plays an important role in cardiovascular protection. Therefore, we investigated the effects of ghrelin on vascular endothelial growth factor-beta (VEGF-B) and connexin-43 (Cx43) expression in DOX-induced cardiomyopathy. Methods Forty adult male rats were divided randomly into four groups: normal, normal + ghrelin, DOX-induced cardiomyopathy, and DOX-induced cardiomyopathy + ghrelin. Biochemical and histopathological analysis, electrocardiograph (ECG), heart rate, systolic blood pressure (SBP), and immunohistochemical staining of VEGF-B and Cx43 were assessed for all rats in heart tissue specimens. The duration of the study was 2 weeks. Results DOX-induced cardiomyopathy in rats showed significant ECG changes such as prolongation of PR, QT, QTC intervals and ST segment, a decrease in amplitude and an increase in the duration of QRS complex, bradycardia, and a decrease in SBP. Also, rats in the DOX group showed myocardial histopathological damage in the form of severe fibrosis with decreased expression of Cx43 and a non-significant difference in expression of VEGF-B when compared to normal rats. Treatment with ghrelin resulted in a significant improvement in all the studied parameters and was associated with an increase in VEGF-B and Cx43 expression. Conclusions Ghrelin has a beneficial effect against DOX-induced cardiomyopathy which may be mediated through VEGF-B and Cx43 expression in the myocardium. Ghrelin is a promising cardioprotective drug in DOX-induced cardiomyopathy patients, but further studies are needed to evaluate its use.