Proteomic analysis of coronary sinus serum reveals leucine-rich α2-glycoprotein as a novel biomarker of ventricular dysfunction and heart failure

BACKGROUND: Heart failure (HF) prevention strategies require biomarkers that identify disease manifestation. Increases in B-type natriuretic peptide (BNP) correlate with increased risk of cardiovascular events and HF development. We hypothesize that coronary sinus serum from a high BNP hypertensive population reflects an active pathological process and can be used for biomarker exploration. Our aim was to discover differentially expressed disease-associated proteins that identify patients with ventricular dysfunction and HF.

METHODS AND RESULTS: Coronary sinus serum from 11 asymptomatic, hypertensive patients underwent quantitative differential protein expression analysis by 2-dimensional difference gel electrophoresis. Proteins were identified using mass spectrometry and then studied by enzyme-linked immunosorbent assay in sera from 40 asymptomatic, hypertensive patients and 105 patients across the spectrum of ventricular dysfunction (32 asymptomatic left ventricular diastolic dysfunction, 26 diastolic HF, and 47 systolic HF patients). Leucine-rich α2-glycoprotein (LRG) was consistently overexpressed in high BNP serum. LRG levels correlate significantly with BNP in hypertensive, asymptomatic left ventricular diastolic dysfunction, diastolic HF, and systolic HF patient groups (P≤0.05). LRG levels were able to identify HF independent of BNP. LRG correlates with coronary sinus serum levels of tumor necrosis factor-α (P=0.009) and interleukin-6 (P=0.021). LRG is expressed in myocardial tissue and correlates with transforming growth factor-βR1 (P<0.001) and α-smooth muscle actin (P=0.025) expression.

CONCLUSIONS: LRG was identified as a serum biomarker that accurately identifies patients with HF. Multivariable modeling confirmed that LRG is a stronger identifier of HF than BNP and this is independent of age, sex, creatinine, ischemia, β-blocker therapy, and BNP.

Natural history of markers of collagen turnover in patients with early diastolic dysfunction and impact of eplerenone

OBJECTIVES: This study was designed to evaluate the impact of eplerenone on collagen turnover in preserved systolic function heart failure (HFPSF).

BACKGROUND: Despite growing interest in abnormal collagen metabolism as a feature of HFPSF with diastolic dysfunction, the natural history of markers of collagen turnover and the impact of selective aldosterone antagonism on this natural history remains unknown.

METHODS: We evaluated 44 patients with HFPSF, randomly assigned to control (n = 20) or eplerenone 25 mg daily (n = 24) for 6 months, increased to 50 mg daily from 6 to 12 months. Serum markers of collagen turnover and inflammation were analyzed at baseline and at 6 and 12 months and included pro-collagen type-I and -III aminoterminal peptides, matrix metalloproteinase type-2, interleukin-6 and -8, and tumor necrosis factor-alpha. Doppler-echocardiographic assessment of diastolic filling indexes and tissue Doppler analyses were also obtained.

RESULTS: The mean age of the patients was 80 +/- 7.8 years; 46% were male; 64% were receiving an angiotensin-converting enzyme inhibitor, 34% an angiotensin-II receptor blocker, and 68% were receiving beta-blocker therapy. Pro-collagen type-III and -I aminoterminal peptides, matrix metalloproteinase type-2, interleukin-6 and -8, and tumor necrosis factor-alpha increased with time in the control group. Eplerenone treatment had no significant impact on any biomarker at 6 months but attenuated the increase in pro-collagen type-III aminoterminal peptide at 12 months (p = 0.006). Eplerenone therapy was associated with modest effects on diastolic function without any impact on clinical variables or brain natriuretic peptide.

CONCLUSIONS: This study demonstrates progressive increases in markers of collagen turnover and inflammation in HFPSF with diastolic dysfunction. Despite high background utilization of renin-angiotensin-aldosterone modulators, eplerenone therapy prevents a progressive increase in pro-collagen type-III aminoterminal peptide and may have a role in management of this disease. (The Effect of Eplerenone and Atorvastatin on Markers of Collagen Turnover in Diastolic Heart Failure; NCT00505336).

Miocardiopatia hipertrófica: estudo ultrassonográfico

Mestrado em Tecnologias de Diagnóstico e Intervenção Cardiovascular - Área de especialização: Ultrassonografia Cardiovascular.

Oclusão percutânea do apêndice auricular esquerdo e estrutura auricular: efeito na função mecânica e endócrina auricular

Mestrado em Tecnologia de Diagnóstico e Intervenção Cardiovascular - Área de especialização: Intervenção Cardiovascular.

Impact du phénotype de la valve aortique et de l’âge sur la relation entre la calcification valvulaire aortique et la sévérité hémodynamique de la sténose aortique - Étude PROGRESSA

L’évaluation de la sténose aortique (SA) par échocardiographie Doppler aboutit à une classification discordante de la sévérité chez environ 30 % des patients. La tomodensitométrie qui mesure la calcification valvulaire aortique, un indice de sévérité anatomique, peut alors être utile pour corroborer la sévérité de la SA. De précédentes études ont montré une bonne corrélation entre la sévérité hémodynamique mesurée par échocardiographie Doppler et la sévérité anatomique définie par la calcification valvulaire aortique mesurée par tomodensitométrie. Cependant, l’impact du phénotype de la valve aortique (bicuspide versus tricuspide) et de l’âge sur cette relation entre sévérité hémodynamique et sévérité anatomique reste inconnu. Or, ces deux facteurs sont hautement impliqués dans le développement de la SA. En effet, les patients ayant une valve aortique bicuspide ont une prédisposition à développer une SA, et ce, généralement plus tôt que les patients avec une valve aortique tricuspide. L’hypothèse principale de l’étude est que le phénotype de la valve aortique et l’âge influencent la relation entre la sévérité hémodynamique et la calcification valvulaire aortique de la SA. L’objectif principal de l’étude est d’évaluer l’impact du phénotype de la valve aortique et de l’âge sur la relation entre la sévérité hémodynamique et la calcification valvulaire aortique de la SA.

Two cases of right atrial myxoma in redo patients. A mere coincidence?

We describe two cases of right atrial myxoma in redo patients who had previously undergone to coronary artery by-pass grafting (CABGs) and mitral valve replacement respectively. Both of patients experienced effort dyspnea and were assessed by trans-thoracic echocardiography, revealing the right atrial masses. They were operated on for myxoma resection and postoperative course was uneventful. Our report deals with the interesting topic of the location of benign masses that are usually more common in the left atrium. Should we hypothesize that the right atrial manipulation during the previous surgery induces the onset of the right atrial mass? It is an interesting matter to debate.

Free-Floating Thrombi in the Right Atrium Causing Pulmonary Embolism

A 74-year-old man presented to our Emergency Department with acute dyspnoea. His electrocardiogram showed atrial flutter with 2:1 block and a rate of 150 bpm. Initial investigations revealed a D-dimer level of 6.01 mg/dl. Based on the patient’s complaints and the high D-dimer level, computed tomography pulmonary angiography was immediately performed. This showed no evidence of pulmonary embolism, but there were pneumatic changes in the right upper lung lobe. Antibiotics treatment was started with pipracillin/tazobactam, after which the patient’s condition improved. However, on the third day after admission he developed acute dyspnoea, diaphoresis and cardiopulmonary instability immediately after defecation. To promptly confirm our clinical suspicion of pulmonary embolism, a transthoracic echocardiography was carried out. This demonstrated a worm-like, mobile mass in the right heart. The right ventricle was enlarged, and paradoxical septal motion was present, indicating right ventricular pressure overload. The systolic tricuspid valvular gradient was 56 mmHg. The patient was treated with thrombolysis. His condition was greatly clinically improved after 3 hours. After 10 days of hospitalization, the patient was discharged.

Homozygosity for the E526V Mutation in Fibrinogen A Alpha-Chain Amyloidosis: The First Report

Systemic hereditary amyloidoses are autosomal dominant diseases associated with mutations in genes encoding ten different proteins. The clinical phenotype has implications on therapeutic approach, but it is commonly variable and largely dependent on the type of mutation. Except for rare cases involving gelsolin or transthyretin, patients are heterozygous for the amyloidogenic variants. Here we describe the first patient identified worldwide as homozygous for a nephropathic amyloidosis, involving the fibrinogen variant associated with the fibrinogen alpha-chain E526V (p.Glu545Val) mutation. In 1989, a 44-year-old woman presented with hypertension, hepatosplenomegaly, nephrotic syndrome, and renal failure. She started hemodialysis in 1990 and 6 years later underwent isolated kidney transplantation from a deceased donor. Graft function and clinical status were unremarkable for 16 years, despite progressively increased left ventricular mass on echocardiography. In 2012, 4 months before death, she deteriorated rapidly with severe heart failure, precipitated by Clostridium difficile colitis and urosepsis. Affected family members developed nephropathy, on average, nearly three decades later, which may be explained by the gene dosage effects on the phenotype of E526V (p.Glu545Val) fibrinogen A alpha-chain amyloidosis.

Left Ventricle Non-Compaction Myocardium and Thrombophilia in a Pregnant Woman

Non-compaction of the ventricular myocardium (NCM) is a genetic cardiomyopathy usually due to mutationof the G4.5 gene located in the Xq28 chromosomal region. This congenital disorder is characterized by pronounced trabeculations and intertrabecular recesses resulting from abnormal embryogenesis between the fifth and eighth fetal weeks. The reported prevalence in the general population is between 0.014% and 1.3%. The classic triad of complications includes heart failure, ventricular arrhythmias and systemic embolic events, although some patients have an asymptomatic form. NCM is commonly diagnosed by echocardiography, but contrast ventriculography, CT and MRI can also be used. Here we present a case of left ventricle NCM, manifested after respiratory infection, in a pregnant patient with congenital thrombophilia and a history of myocardial infarction.

Prevalence, types and factors associated with echocardiographic abnormalities among newly diagnosed diabetic patients at Mulago Hospital.

Background: The prevalence of Diabetes mellitus (DM) is on a rise in sub-Saharan Africa and will more than double by 2025. Cardiovascular disease (CVD) accounts for up to 2/3 of all deaths in the diabetic population. Of all the CVD deaths in DM, 3/4 occur in sub Saharan Africa (SSA). Non invasive identification of cardiac abnormalities, such as Left Ventricular Hypertrophy (LVH), diastolic and systolic dysfunction, is not part of diabetes complications surveillance programs in Uganda and there is limited data on this problem. This study sought to determine the prevalence, types and factors associated with echocardiographic abnormalities among newly diagnosed diabetic patients at Mulago National referral hospital in Uganda. Methods: In this cross sectional study conducted between June 2014 and December 2014, we recruited 202 newly diagnosed adult diabetic patients. Information on patients\' socio-demographics, bio-physical profile, biochemical testing and echocardiographic findings was obtained for all the participants using a pre-tested questionnaire. An abnormal echocardiogram in this study was defined as the presence of LVH, diastolic and/or systolic dysfunction and wall motion abnormality. Bivariate and multivariate logistic regression analyses were used to investigate the association of several parameters with echocardiographic abnormalities. Results: Of the 202 patients recruited, males were 102(50.5%) and the mean age was 46±15 years. Majority of patients had type 2 DM, 156(77.2%) and type 1 DM, 41(20.3%) with mean HbA1C of 13.9±5.3%. Mean duration of diabetes was 2 months. The prevalence of an abnormal echocardiogram was 67.8 % (95% CI 60%-74%). Diastolic dysfunction, systolic dysfunction, LVH and wall motion abnormalities were present in 55.0%, 21.8%, 19.3% and 4.0% of all the participants respectively. In bivariate logistic regression analysis, the factors associated with an abnormal echocardiogram were age (OR 1.09 [95% CI 1.06–1.12], P <0.0001), type 2 DM (OR 5.8[95% CI 2.77-12.07], P<0.0001), hypertension (OR 2.64[95% CI 1.44-4.85], P=0.002), obesity (OR 3.51[955 CI 1.25-9.84], P=0.017 and increased waist circumference (OR 1.02[95% CI 1.00-1.04], P=0.024. On Multiple logistic regression analysis, age was the only factor associated with an abnormal echocardiogram (OR 1.09[95%CI 1.05-1.15], P<0.0001). Conclusion: Echocardiographic abnormalities were common among newly diagnosed adults with DM. Traditional CVD risk factors were associated with an abnormal echocardiogram in this patient population. Due to a high prevalence of echocardiographic abnormalities among newly diagnosed diabetics, we recommend screening for cardiac disease especially in patients who present with traditional CVD risk factors. This will facilitate early diagnosis, management and hence better patient outcomes.

A home-based treadmill training reduced epicardial and abdominal fat in postmenopausal women with metabolic syndrome

Introduction: The current study was designed to determine the effect of home-based treadmill training on epicardial and abdominal adipose tissue in postmenopausal women with metabolic syndrome (MS). A secondary objective was to identify significant correlations between imaging and conventional anthropometric parameters. Material and methods: Sixty postmenopausal women with MS volunteered for the current trial. Thirty were randomly assigned to perform a supervised home-based 16-week treadmill training program, 3 sessions/week, consisting of a warm-up, 30-40 min treadmill exercise (increasing 5-minutes each 4-weeks) at a work intensity of 60-75% of peak heart rate (increasing 5% each 4-weeks) and cooling-down. Epicardial fat thickness (EFT) was assessed by echocardiography. Abdominal fat mass in the lumbar regions L1-L4 and L4-L5 was determined by dual X-ray absorptiometry. Results: Epicardial fat thickness and abdominal fat percentages were significantly improved after the completion of the training program. Another striking feature of the current study was the moderate correlation that was found between EFT and waist circumference (WC). Conclusion: Home-based treadmill training reduced epicardial and abdominal fat in postmenopausal women with MS. A secondary finding was that a moderate correlation was found between EFT and WC. While current investigations are promising, future studies are still required to consolidate this approach in clinical application.

Associação entre a apresentação fenotípica e os indicadores de prognóstico em gatos com cardiomiopatia hipertrófica

Dissertação de Mestrado Integrado em Medicina Veterinária

Implantation of mouse embryonic stem cell-derived cardiac progenitor cells preserves function of infarcted murine hearts.

Stem cell transplantation holds great promise for the treatment of myocardial infarction injury. We recently described the embryonic stem cell-derived cardiac progenitor cells (CPCs) capable of differentiating into cardiomyocytes, vascular endothelium, and smooth muscle. In this study, we hypothesized that transplanted CPCs will preserve function of the infarcted heart by participating in both muscle replacement and neovascularization. Differentiated CPCs formed functional electromechanical junctions with cardiomyocytes in vitro and conducted action potentials over cm-scale distances. When transplanted into infarcted mouse hearts, CPCs engrafted long-term in the infarct zone and surrounding myocardium without causing teratomas or arrhythmias. The grafted cells differentiated into cross-striated cardiomyocytes forming gap junctions with the host cells, while also contributing to neovascularization. Serial echocardiography and pressure-volume catheterization demonstrated attenuated ventricular dilatation and preserved left ventricular fractional shortening, systolic and diastolic function. Our results demonstrate that CPCs can engraft, differentiate, and preserve the functional output of the infarcted heart.

Efficacy and Safety of Using Amplatzer Ductal Occluder for Transcatheter Closure of Perimembranous Ventricular Septal Defect in Pediatrics

Background: Perimembranous Ventricular Septal Defect (PMVSD) is the most common subtype of ventricular septal defects. Transcatheter closure of PMVSD is a challenging procedure in management of moderate or large defects. Objectives: The purpose of this study was to show that transcatheter closure of perimembranous ventricular septal defect with Amplatzer Ductal Occluder (ADO) is an effective and safe method. Patients and Methods: Between April 2012 and April 2013, 28 patients underwent percutaneous closure of PMVSD using ADO. After obtaining the size of VSD from the ventriculogram a device at least 2 mm larger than the narrowest diameter of VSD at right ventricular side was chosen. The device deployed after confirmation of its good position by echocardiography and left ventriculography. Follow up evaluations were done 1 month, 6 months, 12 months and yearly after discharge with transthoracic echocardiography and 12 lead electrocardiography. Results: The mean age of patients at procedure was 4.7 ± 6.3 (range 2 to 14) years, mean weight 14.7 ± 10.5 (range 10 to 40) kg. The mean defect size of the right ventricular side was 4.5 ± 1.6 mm. The average device size used was 7.3 ± 3.2mm (range 4 to 12 mm). The ADOs were successfully implanted in all patients. The VSD occlusion rate was 65.7% at completion of the procedure, rising up to 79.5% at discharge and 96.4% during follow-up. Small residual shunts were seen at completion of the procedure, but they disappeared during follow-up in all but one patient. The mean follow-up period was 8.3 ± 3.6 months (range 1 to 18 months). Complete atrioventricular block (CAVB), major complication or death was not observed in our study. Conclusions: Transcatheter closure of PMVSD with ADO in children is a safe and effective treatment associated with excellent success and closure rates, but long-term follow-up in a large number of patients would be warranted.

Cayler Cardio-Facial Syndrome: An Uncommon Condition in Newborns

Introduction: Cayler cardio-facial syndrome is a rare syndrome associated with asymmetric crying faces with congenital heart disease. We report a newborn that was diagnosed as case of Cayler Cardio-facial syndrome based on clinical features and was confirmed with FISH analysis. Case Presentation: A term male baby, born to non-consanguineous couple through normal vaginal delivery was diagnosed to have asymmetric crying faces with deviation of angle of mouth to left side at the time of birth. The baby had normal faces while sleeping or silent. Mother was known case of hypothyroidism and was on treatment. Baby was diagnosed as case of Cayler Cardio-facial Syndrome and was investigated with echocardiogram, brain ultrasound, total body X-ray examination, X-ray of cervico-thoracic vertebral column and fundus examination. Echocardiogram showed muscular VSD, brain ultrasound was normal and fundus examination showed tortuous retinal vessels. Whole body X-ray and lateral X-ray of cervico-thoracic vertebral column were not suggestive of any skeletal abnormalities. The other associated malformation was right ear microtia. Baby FISH karyotype analysis showed deletion of 22q11.2 deletion. Baby was discharged and now on follow-up. Conclusions: Cayler syndrome is a rare syndrome which must be suspected if a baby has asymmetrical cry pattern and normal facies when baby sleeps. Patient must be evaluated with echocardiography to find out associated cardiac malformations. These infants should undergo FISH analysis for 22q11.2 deletion syndrome.