Evidence Of Cardiac Disease Research Articles

Clinical features of pediatric Danon disease and the importance of early diagnosis

Successful therapy in a cohort with early onset Danon disease (DD) highlights the potential importance of earlier disease recognition. We present experience from the largest National Pediatric Center in Russia for cardiomyopathy patients. This report focuses on identification of early clinical features of DD in the pediatric population by detailed pedigree analysis and review of medical records. ResultsNine patients (3 females) were identified with DD at the Russian National Medical Research Center of Children's Health (“National Pediatric Center”) aged birth to 16 years. At presentation/evaluation: all patients had left ventricular hypertrophy (LVH), ECG features of Wolff-Parkinson-White (WPW), and an increase in hepatic enzymes (particularly lactate dehydrogenase (LDH)); three had marked increase in NT-proBNP; two had HCM with impaired LV function; one had LVH with LV noncompaction; five had arrhythmia with paroxysmal supraventricular and/or ventricular tachycardia. Two teenagers died at ages 16–17 from refractory heart failure and two underwent heart transplantation. All patients were found to have a pathogenic/likely pathogenic variant in the LAMP2 gene, six patients had no family history and a de novo evolvement was documented in 4/6 of those available for genetic tested. Retrospective review related to family background and earlier clinical evaluations revealed a definitive or highly suspicious family history of DD in 3, early clinical presentation with cardiac abnormalities (ECG, echo) in 3, and cerebral, hepatic and/or neuromuscular symptoms in 5. Abnormalities were detected 9,5 months to 5,8 years, median 3,5 years prior to referral to the National Pediatric Center. ConclusionThe earliest clinical manifestations of Danon disease occur in the first 12 years of life with symptoms of skeletal muscle and cerebral disease, raised hepatic enzymes, and evidence of cardiac disease on ECG/echo.

C61 RAREFACTION OF MYOCARDIAL LYMPHATIC VESSELS IN PATIENTS WITH CARDIAC AMYLOIDOSIS

Abstract Introduction In cardiac amyloidosis (CA), amyloid fibers accumulate in the extracellular spaces of the heart, causing a compression and obliteration of lymphatic vessels, and possibly their disappearance. As lympathic drainage removes proteins from the interstitial spaces, including amyloid precursors, an impairment of lympathic vessels could exacerbate amyloid accumulation, triggering a vicious circle. Methods Lymphatic vessels were visualized by immunohistochemistry using a monoclonal antibody against podoplanin (D2–40, a marker of lymphatic endothelial cells) and the immunopreroxidase technique. We investigated 3 groups of cases: 1) as a reference standard, endomyocardial specimens from the left ventricular (LV) endomyocardium of 10 heart valve donors, deceased for trauma and/or cerebral hemorrhage, with no evidence of cardiac disease on gross and microscopic examination; 2) 15 consecutive LV endomyocardial biopsies (EMBs) from patients with CA, where cardiac amyloid was detected and typed by Congo red staining, immunohistochemistry and proteomics, and 3) 13 surgical endomyocardial biopsies from patients with septal LV hypertrophy, undergoing aortic valve surgery and with CA excluded by histology. Results In donor hearts (n=10), lymphatic vessels were mostly distributed in the subendocardial and subepicardial layers, with some intra–myocardial lymphatic vessels near larger blood vessels. We then examined 15 patients with CA (amyloid transthyretin [ATTR]–CA, n=10; amyloid light–chain [AL]–CA, n=5; 50% men, median age 75 years [interquartile range 71–78]), and 13 patients with CA excluded (55% men, median age 68 years [59–71]). The density of lymphatic vessels in patients with CA was 0.52 vessels/mm2 (0–3.32), vs. 10.90 vessels/mm2 (3.10–26.25) in those without CA (p=0.001). No significant differences were found in LV mass index (p=0.170) or LV ejection fraction (p=0.262). Three patients with ATTR–CA and 2 patients with AL–CA showed no lymphatic vessels on EMB. The density of lymphatic vessels did not differ significantly in patients with ATTR– or AL–CA. Conclusions Patients with CA have significantly decreased endo–myocardial lymphatic vessels as compared to patients without CA, despite no significant difference in the degree of LV wall thickening or LV ejection fraction. These results support the hypothesis that the lymphatic drainage is deranged in patients with CA, possibly promoting further amyloid deposition.

INVESTIGATION OF THE USE OF SERUM BIOMARKERS FOR THE DETECTION OF CARDIAC DISEASE IN MARINE MAMMALS.

Cardiac disease has been extensively documented in marine mammals; however, it remains difficult to diagnose antemortem. Assays measuring cardiac troponin I (cTnI) and N-terminal pro-brain natriuretic peptide (NT-proBNP) are used as sensitive and specific biomarkers of cardiac disease in many species, but have not been widely investigated in marine mammals. This study aimed to provide a set of reference values for cTnI and NT-proBNP in belugas (BW) (Delphinapterus leucas), sea otters (SO) (Enhydra lutris), Steller sea lions (SSL) (Eumetopias jubatus), and California sea lions (CSL) (Zalophus californianus) with and without cardiac disease, and to determine if these biomarkers are useful indicators of cardiac disease in these species. First, existing immunoassays for cTnI and NT-proBNP were successfully validated utilizing species-specific heart lysate spiked serum. Cohorts were defined by histopathology as animals with no evidence of cardiac disease ("control"), with confirmed cardiac disease ("disease"), and with concurrent renal and cardiac disease ("renal") for which serum samples were then analyzed. Serum concentration ranges for cTnI (ng/ml) and NT-proBNP (pmol/L) were determined for control and disease cohorts. There was significantly higher cTnI (P= 0.003) and NT-proBNP (P= 0.004) concentrations in the CSL disease cohort, as well as positive trends in BW, SO, and SSL disease cohorts that did not reach statistical significance. NT-proBNP concentrations were significantly higher in the CSL renal cohort compared with the control (P < 0.001) and disease (P= 0.007) cohorts. These results suggest that cTnI and NT-proBNP may be clinically useful in the antemortem diagnosis of cardiac disease in CSL, and warrant further investigation in BW, SO, and SL.

Scapular renal cell carcinoma metastasis as a cause of high-output heart failure: a case report

BackgroundHigh-output heart failure is a rare condition that occurs when the heart is unable to respond to a sustained increase in blood demand. On echocardiography, a cardiac index of > 4 L/min/m2 (or 6 L/min) is a clear indicator of this disorder. The causes of high-output heart failure vary, but they all involve peripheral vasodilation or arteriovenous shunting. Renal cell carcinoma is well known for producing high levels of angiogenic growth factors that induce arteriovenous shunts. The decrease in peripheral arterial resistance and the increase in venous return result in a permanent high cardiac output, followed by congestive heart failure. Single bone metastases of renal clear cell carcinoma tumours causing high cardiac output and heart failure symptoms have been reported less than ten times in the medical literature.Case presentationBefore a right-shoulder painful lump with a murmur when auscultated, magnetic resonance imaging revealed a large scapular mass, which was biopsied and found to be a bone metastasis of renal cell carcinoma. Two months later, the patient developed heart failure for the first time. There was no evidence of cardiac disease on echocardiography. The cardiac output was 9.8 L/min and the cardiac index was 5.1 L/min/m2. Doppler ultrasound revealed numerous arteriovenous shunts in the large scapular metastasis and a right axillary artery flow of 24% of cardiac output. Sustained lower cardiac output was obtained following lesion-focused radiotherapy and systemic antiangiogenic treatment with axitinib and pembrolizumab.ConclusionsHerein, we present a unique case of high-output heart failure in a 70-year-old man diagnosed by echocardiography and upper-limb Doppler ultrasound in the context of metastatic renal cell carcinoma without pre-existing cardiac disease. We stress the potentially life-threatening hemodynamic consequences of hypervascularity associated with arteriovenous shunts within a single metastatic renal cell carcinoma implant, the importance of auscultating any progressing bone mass, and the utility of non-invasive Doppler ultrasound assessment in this setting.

EFFECT OF BODY POSITION ON ECHOCARDIOGRAPHIC PARAMETERS IN PRAIRIE RATTLESNAKES (CROTALUS VIRIDIS).

Echocardiography is a noninvasive diagnostic tool that can provide instantaneous information about cardiac function, but it is uncommonly used by veterinarians to assess reptilian patients. Echocardiograms were performed on 14 clinically healthy, adult prairie rattlesnakes (Crotalus viridis), and cardiac measurements were taken in a horizontal and vertical position. Cardiac parameters including ventricular volume in systole and diastole, as well as the diameter of the left atrium, pulmonary artery, and paired left and right aortic arches were obtained. No evidence of cardiac disease was noted in any of the study animals. Males had a greater percentage of ventricular volume change (VVC) than females in the vertical position (P = 0.043). The percentage of ventricular volume change was significantly lower in the horizontal compared with the vertical position (P = 0.032) and was not different by sex. For the short-axis views, the right atrial diameter and short-axis ventricular area in diastole and systole were significantly smaller in snakes in the vertical compared with the horizontal position. This study is the first to obtain echocardiographic measurements in North American vipers and adds to the understanding of techniques used to evaluate the cardiac function of these species.

Arrhythmogenic right ventricular cardiomyopathy in patients with biallelic JUP-associated skin fragility

Arrhythmogenic right ventricular cardiomyopathy (ARVC), with skin manifestations, has been associated with mutations in JUP encoding plakoglobin. Genotype–phenotype correlations regarding the penetrance of cardiac involvement, and age of onset have not been well established. We examined a cohort of 362 families with skin fragility to screen for genetic mutations with next-generation sequencing-based methods. In two unrelated families, a previously unreported biallelic mutation, JUP: c.201delC; p.Ser68Alafs*92, was disclosed. The consequences of this mutation were determined by expression profiling both at tissue and ultrastructural levels, and the patients were evaluated by cardiac and cutaneous work-up. Whole-transcriptome sequencing by RNA-Seq revealed JUP as the most down-regulated gene among 21 skin fragility-associated genes. Immunofluorescence showed the lack of plakoglobin in the epidermis. Two probands, 2.5 and 22-year-old, with the same homozygous mutation, allowed us to study the cross-sectional progression of cardiac involvements in relation to age. The older patient had anterior T wave inversions, prolonged terminal activation duration (TAD), and RV enlargement by echocardiogram, and together with JUP mutation met definite ARVC diagnosis. The younger patient had no evidence of cardiac disease, but met possible ARVC diagnosis with one major criterion (the JUP mutation). In conclusion, we identified the same biallelic homozygous JUP mutation in two unrelated families with skin fragility, but cardiac findings highlighted age-dependent penetrance of ARVC. Thus, young, phenotypically normal patients with biallelic JUP mutations should be monitored for development of ARVC.

Clinical characteristics of cats referred for evaluation of subclinical cardiac murmurs.

The aim of this study was to define the clinical characteristics of cats referred for evaluation of subclinical cardiac murmurs, and, secondarily, to identify predictors of echocardiographic identification of cardiac disease. One hundred and sixty-three apparently healthy cats with subclinical murmurs were retrospectively enrolled. Medical records of cats older than 1 year of age referred for the evaluation of subclinical murmurs were reviewed. Cats were considered healthy if clinical signs of systemic disease or cardiac disease were not reported and cats were not receiving cardiac medications. Logistic regression was used to identify clinical variables that predict echocardiographic identification of cardiac disease. One hundred and eight cats (66.3%) had echocardiographic evidence of cardiac disease with hypertrophic cardiomyopathy being the most common (80.5%). Left atrial enlargement was uncommon; in 90% of cats with echocardiographically identified cardiac disease, the left atrial aortic ratio from two-dimensional echocardiography was <1.51. Cats with cardiac disease were more likely to be male (P = 0.016), weigh more (P <0.01) and have a murmur of intensity ⩾3/6 (P = 0.019) than cats without cardiac disease. Murmur intensity ⩾grade 3/6 (P = 0.01) and male sex (P = 0.01) were independent predictors of echocardiographic evidence of cardiac disease in multivariable analysis. The majority of cats referred for evaluation of subclinical cardiac murmurs have cardiac disease. Based on left atrial dimensions, cardiac disease is generally mild. Male sex and a loud cardiac murmur are associated with the identification of cardiac disease.

Echocardiographic reference intervals with allometric scaling of 823 clinically healthy rhesus macaques (Macaca mulatta)

BackgroundEchocardiography is commonly used for assessing cardiac structure and function in various species including non-human primates. A few previous studies reported normal echocardiographic reference intervals of clinically healthy rhesus macaques under sedation. However, these studies were under-powered, and the techniques were not standardized. In addition, body weight, age, and sex matched reference intervals should be established as echocardiographic measurements are commonly influenced by these variables. The purpose of this study was to establish reference intervals for complete echocardiographic parameters based on a large cohort of clinically healthy rhesus macaques with wide ranges of weight and age distributions using allometric scaling.ResultsA total of 823 rhesus macaques (ages 6 months to 31 years old; body weights 1.4 to 22.6 kg) were enrolled. Of these rhesus macaques, 421 were males and 402 were females. They were assessed with a complete echocardiographic examination including structural and functional evaluation under sedation with ketamine hydrochloride. The reference intervals of the key echocardiographic parameters were indexed to weight, age, and sex by calculating the coefficients of the allometric eq. Y = aMb. On correlation matrix, body weight, age, sex, and heart rate were significantly correlated with various echocardiographic parameters and some of the parameters were strongly correlated with body weight and age. Multiple regression analysis revealed that heart rate and body weight statistically significantly predicted several echocardiographic parameters. Valve regurgitation including tricuspid, aortic, pulmonic, and mitral regurgitations without other cardiac structural and functional abnormalities are common in clinically healthy rhesus macaques under ketamine sedation.ConclusionsIn this study, the reference intervals of echocardiographic parameters were established by performing complete echocardiographic examinations on a large number of clinical healthy rhesus macaques. In addition, allometric scaling was performed based on their weight, and further indexed to age and sex. These allometrically scaled reference intervals can be used to accurately evaluate echocardiographic data in rhesus macaques and diagnose structural and functional evidence of cardiac disease.

Use of cardiac sphericity index and manubrium heart scores to assess radiographic cardiac silhouettes in large-and small-breed dogs with and without cardiac disease.

To evaluate the usefulness of manubrium heart scores (MHSs) in distinguishing between dogs with and without cardiac disease. 184 client-owned dogs with (n = 64) and without (120) cardiac disease. Medical records, including thoracic radiographic images, of dogs that either had echocardiographically confirmed moderate to severe cardiac disease with cardiomegaly (case dogs) or were healthy and without evidence of cardiac disease (control dogs) were retrospectively reviewed. From right lateral thoracic radiographic images, the lengths of the cardiac short and long axes and the manubrium were measured and cardiac sphericity indices (CSIs), MHSs, and vertebral heart scores were determined. Dogs were grouped on the basis of whether they did or did not have cardiac disease (case dogs vs control dogs), breed size (large-breed dogs vs small-breed dogs), and whether cardiac disease affected the right side of the heart (right-sided cardiac disease) or the left side of heart (left-sided cardiac disease). Results were compared across groups. The mean CSI was greatest in case dogs with right-sided cardiac disease, compared with other groups. In dogs of the present study, a combination of high short-, long-, and overall-MHSs was more suggestive of left-sided cardiac disease, whereas a high short-MHS without high long- and overall-MHSs was more suggestive of right-sided cardiac disease. Results indicated that MHSs could be useful, objective values to help assess dogs for potential heart disease, and we recommend that MHSs be added to the diagnostic tools used by veterinarians when screening for heart disease in dogs.

Echocardiographic assessment of diastolic function in asymptomatic systemic lupus erythematosus (SLE) patients

Cardiac disease is common among patients with systemic lupus erythematosus (SLE) even when clinically asymptomatic but diastolic dysfunction is infrequently reported. The aim of our study was to assess diastolic left ventricular dysfunction at a subclinical stage and to compare the obtained results with a control population. We conducted a prospective study over a period of seven years from 2008 to 2015 in the echocardiography laboratory of the adult cardiology department of La Rabta Hospital. Thirty consecutive SLE patients without evidence of cardiac disease were enrolled (group A), and were compared with 30 age-matched healthy control subjects (group B). The average age of our patients was 41 ± 8 years old. There were 25 women (83.3%) and 5 men (16.66%). All had normal LV systolic function; There were no statistically significant differences between SLE patients and controls in such parameters as; peak early diastolic filling velocity (E) LV between the 2 groups A and B (90 ± 12 cm/s vs. 85 ± 10 cm/s), the peak late diastolic velocity A, (66 ± 9 cm/s vs. 60 ± 9 cm/s), the Ratio of Peak Early to Late Diastolic Filling Velocity of Transmitral Flow E/A (1.32 ± 0.3 vs. 1.4 ± 0.4) and the E wave deceleration (181 ± 8ms vs. 200 ± 22 ms). Early diastolic mitral annular velocity (Ea) was decreased in lupus patients compared to controls (7.0 ± 0.5 cm/s vs. 11.5 ± 2.4 cm/s, P < 0.01).The difference in the duration between the pulmonary venous atrial reversal and the mitral inflow A wave Ar-Am was longer in group B, and the E/Ea ratio was significantly higher in lupus patients than in healthy subjects (13.1 ± 1.1 vs. 7.6 ± 1.2, P < 0.01) ( Table 1 ). Echocardiography seems to be an excellent non-invasive tool for early detection of subclinical impaired diastolic cardiac function. So we suggest that patients with SLE, should better undergo an echocardiographic evaluation, and be followed periodically.

P6455Differences in cardiac phenotype and natural history of laminopathies with and without neuromuscular presentation

Abstract Aim To look for differences in cardiac phenotype and natural history of patients affected by laminopathy, according to the presence or less of neuromuscular involvement at clinical presentation. Methods We prospectively analyzed 47 consecutive pts with a genetic diagnosis of laminopathy followed at a single centre between 1994 and 2017. Additionally, reports of clinical and instrumental evaluations before referral at our centre were retrospectively evaluated. Results Neuromuscular presentation, mainly as Emery-Dreifuss muscular dystrophy (EDMD), was present in 21 (46%) cases (14 LMNA and 7 EMD gene mutations). These pts had symptoms earlier (9 vs 39 years, p&lt;0.001) in life compared to pts without neuromuscular onset (26 LMNA gene mutations), and clinical manifestations anticipated the first evidence of cardiac disease by a mean time of 15±8 years (maximum time gap of 38 years). Despite a similar prevalence of atrial fibrillation/flutter (AF) (71% vs 65%, p=0.758) and atrio-ventricular blocks (48% vs 65%, p=0.250), pts with neuromuscular onset experienced AF and pace-maker implantation at a significantly younger age (27 vs 41 yrs, p=0.015 and 23 vs 44 yrs, p=0.027 respectively). Differently a higher prevalence of sinus node dysfunction (33% vs 4%; p=0.015) and atrial paralysis (14% vs 4%; p=0.311) was reported in pts with neuromuscular onset. Prevalence of cardiomyopathy (CMP) (73% vs 33%, p=0.008) and sustained ventricular tachyarrhythmias were higher among pts with cardiac onset (23% vs 4%, p=0.111) whereas the prevalence of heart transplantations and median age of recipients were similar in the two groups (24% vs 20%, p=1.000 and 46 vs 43, p=0.592 years respectively). All pts with neuromuscular onset who received a diagnosis of CMP had a previous history of rhythm disturbance except 2 cases, where a concomitant diagnosis of the 2 disorders was formulated. On the contrary a strict temporal progression from rhythm disturbances to CMP (or viceversa) was not appreciable in the other group: AF and AVBs could precede the diagnosis of CMP be diagnosed at the same time or later. Conclusions In pts affected by laminopathy neuromuscular involvement, when present, was most often the first clinical manifestation and preceded cardiological involvement, with a long time frame in some cases. Except for sinus node dysfunction, much more frequent in patients with EDMD, a similar prevalence of rhythm disturbances was reported, although pts with neuromuscular clinical onset were younger at diagnosis of AF and at PM implantation. Pts without neuromuscular presentation had a higher prevalence of CMP and ventricular arrhythmias, albeit a similar rate of heart transplantation. In pts with neuromuscular onset, cardiac involvement was characterized by a stepwise progression from rhythm disturbances to CMP, where a strict temporal progression from rhythm disturbances to CMP was not observed in the group of pts without neuromuscular clinical onset.

Norwich terriers possess a greater vertebral heart scale than the canine reference value.

Previous studies have demonstrated evidence that normal reference ranges for radiographic vertebral heart scale values can vary among dog breeds. The purpose of this retrospective, observational study was to determine whether the normal vertebral heart scale values published by Buchanan and Bücheler for lateral radiographs are applicable to the Norwich terrier. Secondary objectives were to determine if clinical signs of respiratory disease, age, sex, weight, body condition score, recumbency, or thoracic depth-to-width ratio had any influence on vertebral heart scale measurements in this breed. The electronic medical record systems of two universities were reviewed and Norwich terriers were included in the study if they had orthogonal thoracic radiographs performed and no historical or radiographic evidence of cardiopulmonary disease. A vertebral heart scale was calculated for each patient. Sixty-one client-owned, Norwich terrier dogs with no clinical signs of cardiovascular disease were evaluated. The vertebral heart scale for Norwich terriers without evidence of cardiac disease (10.6 ± 0.6) was found to be significantly greater than the canine reference value of 9.7 ± 0.5 initially established by Buchanan and Bücheler. No significant correlation was found between clinical signs of respiratory disease, sex, age, thoracic depth-to-width ratio or lateral recumbency, and vertebral heart scale. Norwich terriers with a body condition score ≥6 had a significantly higher vertebral heart scale than those with a body condition score ≤5. Breed-specific ranges and body condition scores need to be considered when interpreting vertebral heart scale values for Norwich terriers.

5163Predictors of adverse cardiovascular events in patients with truncating variants in the filamin c (flnc) gene

Abstract Background Truncating variants in Filamin C (FLNCtv) are associated with arrhythmogenic (AC) and dilated cardiomyopathies (DCM). Affected patients are reported to demonstrate a high incidence of arrhythmic and heart-failure related cardiovascular events. The aim of this study was to determine factors that predict adverse events in mutation carriers. Methods The study cohort comprised 168 FLNCtv carriers followed at 19 European centres. Baseline and longitudinal follow-up clinical data were collected. The primary endpoint was a composite of sudden cardiac death (SCD), aborted SCD, appropriate implantable cardioverter-defibrillator (ICD) shock, cardiac transplantation (HTx) and mortality from end-stage heart failure (ESHF). Results 47 different pathogenic or likely-pathogenic FLNCtv were identified in 60 unrelated probands. In those with baseline and longitudinal data (160 patients; 57 probands), 114 (71.3%) patients exhibited evidence of cardiac disease at initial evaluation. Gene penetrance was 85% by the age of 40 years. During a median follow-up of 1.5 years (IQR 4.1), 24 individuals (15%) reached the primary endpoint – 16 arrhythmic (SCD/aborted SCD/ICD shock) and 8 heart failure (ESHF/HTx) related-events. Univariable predictors at baseline evaluation of the composite primary endpoint included proband status (HR 4.0, 95% CI: 1.5–10.9, p=0.01), symptoms of dyspnoea (HR 2.8, 95% CI: 1.2–6.4, p=0.02), LV systolic dysfunction (LVSD) (HR 12.4, 95% CI: 2.9–53.2, p=0.001), frequent ventricular ectopy (VE&gt;500) on 24-hour Holter (HR 9.3, 95% CI: 1.2–74.7, p=0.04) and the presence of late gadolinium enhancement on CMR (HR 8.9, 95% CI: 1.2–68.5, p=0.04). Multivariable analysis identified LVSD (LVEF &lt;50%) at baseline as an independent predictor of the primary endpoint with a hazard ratio of 8.6 (95% CI: 1.8–41.5, p=0.007). ROC analysis using LV systolic dysfunction to predict the primary endpoint demonstrated an area under the curve of 0.84 (95% CI: 0.76–0.91, p&lt;0.001) and identified an optimal LVEF “cut-off” of 47% for predicting adverse events with a Youden's index of 0.61 (sensitivity 0.91; specificity 0.70). Kaplan-Meier plot to demonstrate freedom Conclusions LVSD is associated with an over 8-fold increase in the hazard of a primary endpoint event in FLNCtv gene carriers indicating that these patients should be considered for implantable cardioverter-defibrillator (ICD) implantation, optimal heart failure medical therapy and close clinical follow-up. Acknowledgement/Funding NIHR Biomedical Research Centre; Instituto de Salud Carlos III; DETECTIN-HF project; Wellcome Trust;CIBERCV; EU Regional Development Fund; FEDER.

MYOTONIC DYSTROPHY: P.22Subclinical myocardial dysfunction in patients with myotonic dystrophy type 1 and type 2 detected by cardiac magnetic resonance

Myotonic dystrophies (DM) represent the most common hereditary multi-systemic muscle diseases in adults characterized by progressive skeletal muscle degeneration, muscle wasting, myotonia, and multi-organ involvement. Cardiac affection is common, and premature death often occurs due to arrhythmic events. We examined whether signs of cardiac involvement in patients without clinically evident cardiac disease can be detected by a comprehensive cardiac magnetic resonance (CMR) approach. Thirty-five DM patients (13 DM type 1 and 22 DM type 2) without cardiac symptoms and normal ECG and echocardiography findings underwent CMR. The control group consisted of 31 healthy subjects. Our CMR protocol allowed for the determination of late gadolinium enhancement (LGE), myocardial edema, T1 relaxation times, T2 relaxation times, extracellular volume (ECV) and myocardial strain. When compared with controls, DM patients showed alterations of left ventricular function as demonstrated by lower systolic longitudinal and circumferential strain values. Visible myocardial fibrosis was prevalent in 28.6% of DM patients. Markers of diffuse myocardial fibrosis were also significantly elevated (T1 relaxation, ECV). Also, T2 relaxation times indicative of edema-like changes were significantly elevated in DM patients. In conclusion, asymptomatic DM patients had a subclinical impairment of myocardial function and elevated markers of myocardial fibrosis and edema when compared to healthy controls. These findings may indicate a high burden of subclinical myocardial disease in our DM patients with normal routine heart checkup results and an unremarkable history of cardiac disease. To summarize, CMR might be a useful tool to improve cardiac monitoring and outcome in DM1 and DM2 patients especially at early disease stages.

Levels of creatine kinase MB-mass in chronic kidney disease patients on maintenance hemodialysis without coronary complications

Introduction: A triad of clinical evaluation, electrocardiography and biomarkers of acute cardio necrosis are basis for diagnosing acute coronary syndrome (ACS). Evaluation of ACS by electrocardiography can be inconclusive in patients on maintenance hemodialysis; thereby making cardiac biomarkers better indicators. Hemodialysis is known to alter troponin I values with studies suggesting high false positives but not for the values of CKMB mass. Aim: The aim of the study was to estimate the levels of cardiac CKMB-mass in patients with stage IV/stage V renal failure on maintenance hemodialysis (MHD) with no evidence of cardiac disease, and to correlate these values with manufactures guidelines for healthy individuals (cut off of Materials and Methods: The study was conducted on 23 patients between age group 20 to 70 years, diagnosed with stage IV or V Chronic Kidney disease (CKD) (confirmed biochemically and ultrasonographically). These patients were undergoing regular biweekly regime of maintenance hemodialysis for more than 3 months at dialysis unit PESIMSR, Kuppam. CKMB mass levels were measured in these patients. Results and Conclusion: The kidney function tests and electrolyte values were deranged in patients with CKD, however as the patients were on calcium supplementation, mineral levels were within normal range. Liver function tests of these patients were found to be normal. The hemoglobin and RBC levels were lower due to CKD associated anemia. CKMB-mass levels of these patients were done in Biomerieux Vidas analyzer using Enzyme linked fluorescent assay (ELFA) method. The values were within manufacturer’s cutoff range of 5ng/ml with mean value of 3.0±1.69 ng/ml. The patients were followed up either until death or for 24 months for any cardiac related events and follow up rate was 99%. The overall survival rates of the patients were found to be 77% and none of the patients were found to have developed cardiac related events and specifically myocardia

Echocardiographic assessment of diastolic function in asymptomatic systemic lupus erythematosus (SLE) patients

Cardiac disease is common among patients with systemic lupus erythematosus (SLE) even when clinically asymptomatic but diastolic dysfunction remains infrequently reported. The aim of our study was to assess diastolic left ventricular dysfunction at a subclinical stage and to compare the obtained results with a control population. We conducted a prospective study over a period of seven years from 2008 to 2015 in the adult cardiology department of La Rabta Hospital. Thirty consecutive SLE patients without evidence of cardiac disease (group A) were enrolled, and were compared with 30 age-matched healthy control subjects (group B). The average age of our patients was 41 ± 8 years old. There were 25 women (83.33%) and 5 men (16.66%). All had normal LV systolic function. There were no statistically significant differences between SLE patients and controls in such parameters as: – peak early diastolic filling velocity (E) (90 ± 12 cm/s vs. 85 ± 10 cm/s); – the peak of teleastolic velocity A, (66 ± 9 cm/s) versus (60 ± 9 cm/s); – the Ratio of Peak Early to Late Diastolic Filling Velocity of Transmitral Flow E/A (1.32 ± 0.3 vs. 1.4 ± 0.4); – the E wave deceleration (181 ± 8ms vs. 200 ± 22 ms). Early diastolic mitral annular velocity (Ea) was decreased in lupus patients compared to controls (7 ± 0.5 cm/s vs. 11.5 ± 2.4 cm/s, P < 0.01). The E/VP ratio was higher in group A compared to group B (2.4 ± 0.3 vs. 1.2 ± 0.3, P < 0.01), The difference in the duration between the pulmonary venous atrial reversal and the mitral inflow A wave Ar-Am was longer in group B, and the E/Ea ratio was significantly higher in lupus patients than in healthy subjects (13.1 ± 1.1 vs. 7.6 ±1.2, P < 0.01). Echocardiography seems to be an excellent non-invasive tool for early dectection of subclinical impaired diastolic cardiac function. So we suggest that patients with SLE, should better undergo an echocardiographic evaluation, and be followed periodically.

Measurement of plasma endothelin-1 concentration in healthy horses and horses with cardiac disease during rest and after exercise.

Cardiac biomarkers are important tools for monitoring disease progress and can monitor progression of therapy. Endothelin-1 (ET-1) has been studied for its use as a cardiac biomarker in human and small animal medicine while in horses with cardiac disease it has not been evaluated yet. The objective of the present study was to determine the concentration of plasma ET-1 in healthy horses and compare it with ET-1 concentration in horses with cardiac disease during rest and after exercise. Fifty four horses admitted to the Equine Clinic of Free University of Berlin were used in the present study, of which 15 horses were clinically healthy with no evidence of cardiac disease (Group 1), 22 horses suffered from cardiac disease with normal heart dimensions (Group 2) and 17 horses with cardiac disease and enlarged heart diameters (Group 3). Clinical examination, electrocardiography and echocardiography were performed. Endothelin-1 concentration was determined using ET-1 ELISA kit. The concentration of plasma ET-1 was significantly increased in horses with cardiac disease and normal cardiac dimensions (Group 2) and in horses with cardiac disease and enlargement of the left atrium (Group 3) compared to its concentration in clinically healthy horses (Group 1). In addition, the concentration of plasma ET-1 after exercise was significantly increased in diseased horses compared to its concentration at rest. Detection of ET-1 plasma concentration in horses at rest may be useful for detecting horses with changes in left atrial cardiac dimensions.

P4484Prognostic value of endothelial dysfunction in asymptomatic type 2 diabetic patients with no evidence of cardiac disease

P4484Prognostic value of endothelial dysfunction in asymptomatic type 2 diabetic patients with no evidence of cardiac disease

P3817Diagnostic yield of genetic testing in cardiac arrest survivors with or without clinical evidence of cardiac disease: A swiss experience

P3817Diagnostic yield of genetic testing in cardiac arrest survivors with or without clinical evidence of cardiac disease: A swiss experience

Elevated Cardiac Troponin T in Patients With Skeletal Myopathies

BackgroundCardiac troponins are often elevated in patients with skeletal muscle disease who have no evidence of cardiac disease. ObjectivesThe goal of this study was to characterize cardiac troponin concentrations in patients with myopathies and derive insights regarding the source of elevated troponin T measurements. MethodsCardiac troponin T (cTnT) and cardiac troponin I (cTnI) concentrations were determined by using high sensitivity assays in 74 patients with hereditary and acquired skeletal myopathies. Patients underwent comprehensive cardiac evaluation, including 12-lead electrocardiogram, 24-h electrocardiogram, cardiac magnetic resonance imaging, and coronary artery computed tomography. cTnT and cTnI protein expression was determined in skeletal muscle samples of 9 patients and in control tissues derived from autopsy using antibodies that are used in commercial assays. Relevant Western blot bands were subjected to liquid chromatography tandem mass spectrometry for protein identification. ResultsLevels of cTnT (median: 24 ng/l; interquartile range: 11 to 54 ng/l) were elevated (>14 ng/l) in 68.9% of patients; cTnI was elevated (>26 ng/l) in 4.1% of patients. Serum cTnT levels significantly correlated with creatine kinase and myoglobin (r = 0.679 and 0.786, respectively; both p < 0.001). Based on cTnT serial testing, 30.1% would have fulfilled current rule-in criteria for myocardial infarction. Noncoronary cardiac disease was present in 23%. Using cTnT antibodies, positive bands were found in both diseased and healthy skeletal muscle at molecular weights approximately 5 kDa below cTnT. Liquid chromatography tandem mass spectrometry identified the presence of skeletal troponin T isoforms in these bands. ConclusionsMeasured cTnT concentrations were chronically elevated in the majority of patients with skeletal myopathies, whereas cTnI elevation was rare. Our data indicate that cross-reaction of the cTnT immunoassay with skeletal muscle troponin isoforms was the likely cause.