Myocardial Biopsy Research Articles

Advances in Diagnostic Imaging for Cardiac Sarcoidosis

Sarcoidosis is a systemic granulomatous disease of unknown etiology, and its clinical presentation depends on the affected organ. Cardiac sarcoidosis (CS) is one of the leading causes of death among patients with sarcoidosis. The clinical manifestations of CS are heterogeneous, and range from asymptomatic to life-threatening arrhythmias and progressive heart failure due to the extent and location of granulomatous inflammation in the myocardium. Advances in imaging techniques have played a pivotal role in the evaluation of CS because histological diagnoses obtained by myocardial biopsy tend to have lower sensitivity. The diagnosis of CS is challenging, and several approaches, notably those using positron emission tomography and cardiac magnetic resonance imaging (MRI), have been reported. Delayed-enhanced computed tomography (CT) may also be used for diagnosing CS in patients with MRI-incompatible devices and allows acceptable evaluation of myocardial hyperenhancement in such patients. This article reviews the advances in imaging techniques for the evaluation of CS.

Isolation and phenotyping of cardiac-derived progenitor cells from neonatal mice

Dysfunctions of resident progenitor cells play a significant role in the pathogenesis of decreased myocardial contractility in heart failure, so the most promising approaches for the treatment of heart disease are cardiac-derived stem/progenitor cells (CSCs). Materials and methods. Protocols for progenitor cell cultures from different parts of the heart of newborn FVB/N mice have been developed and their proliferative potential has been characterized. Comparative analysis of the expression of CD31, CD34, CD44, CD45, CD73, CD90, CD105, CD117, CD309 and troponin I by cells from native myocardial biopsies and in the obtained cultures was performed by flow cytometric immunophenotyping. Results. The expression of mesenchymal markers CD44 and CD90 in the absence of the hematopoietic marker CD45 was demonstrated in early passages in mouse myocardial progenitor cell cultures. Relatively high expression of CD34 and CD31 was found. The presence of a minor population of CD44+117+ cells which correspond to the phenotype of cardiac progenitor cells, was detected. Expression of troponin I as one of the key markers of cardiomyocytes as well as the vascular endothelial growth factor receptor has been confirmed in terminally differentiated cultures of cells with contractile activity. Conclusions. It was found that newborn mice in the myocardial tissue contain more cells with the expression of markers of cardiac progenitors than in adult animals. The relative content of such cells is higher in the atria than in the ventricles. Cardiac progenitor cells in neonatal mice derived from the atrial appendages have better proliferative potential than cell cultures isolated from the ventricles.

Cardiomyogenic Differentiation Potential of Human Dilated Myocardium-Derived Mesenchymal Stem/Stromal Cells: The Impact of HDAC Inhibitor SAHA and Biomimetic Matrices.

Dilated cardiomyopathy (DCM) is the most common type of nonischemic cardiomyopathy characterized by left ventricular or biventricular dilation and impaired contraction leading to heart failure and even patients’ death. Therefore, it is important to search for new cardiac tissue regenerating tools. Human mesenchymal stem/stromal cells (hmMSCs) were isolated from post-surgery healthy and DCM myocardial biopsies and their differentiation to the cardiomyogenic direction has been investigated in vitro. Dilated hmMSCs were slightly bigger in size, grew slower, but had almost the same levels of MSC-typical surface markers as healthy hmMSCs. Histone deacetylase (HDAC) activity in dilated hmMSCs was 1.5-fold higher than in healthy ones, which was suppressed by class I and II HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) showing activation of cardiomyogenic differentiation-related genes alpha-cardiac actin (ACTC1) and cardiac troponin T (TNNT2). Both types of hmMSCs cultivated on collagen I hydrogels with hyaluronic acid (HA) or 2-methacryloyloxyethyl phosphorylcholine (MPC) and exposed to SAHA significantly downregulated focal adhesion kinase (PTK2) and activated ACTC1 and TNNT2. Longitudinal cultivation of dilated hmMSC also upregulated alpha-cardiac actin. Thus, HDAC inhibitor SAHA, in combination with collagen I-based hydrogels, can tilt the dilated myocardium hmMSC toward cardiomyogenic direction in vitro with further possible therapeutic application in vivo.

Spectrum of desmosomal gene variations in patients with arrhythmogenic right ventricular cardiomyopathy

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a hereditary myocardial disease with a high risk of sudden cardiac death. The most common genetic forms of the disease are associated with desmosomal gene mutations.Aim. To study the prevalence of desmosomal forms of ARVC and to analyze variations in the PKP2, DSG2, DSP, DSC2 and JUP genes in a sample of Russian patients with ARVC.Material and methods. Included patients with ARVC underwent resting electrocardiography (ECG), 24-hour Holter ECG monitoring, echocardiography, chest x-ray, myocardial biopsy (if indicated), contrast-enhanced cardiac magnetic resonance imaging. All patients underwent medical genetic counseling. Mutations in the PKP2, DSG2, DSP, DSC2, and JUP genes was detected using highthroughput sequencing on the IonTorrent platform, followed by Sanger sequencing of uncovered gene regions. The pathogenicity of identified genetic variations was assessed according to modern guidelines.Results. ARVC was established in 80 Russian unrelated patients. More than half of the probands (57%) in the study sample had definite diagnosis of ARVC, while 30% and 13% — borderline and possible ARVC, respectively. A positive family history of heart disease and/or SCD was noted in 30%. Genetic variants of pathogenicity class IV-V were detected in 15 (18,75%) probands in the PKP2, DSG2, DSP genes. The detection of genetic variants of pathogenicity class IV-V was different in the subgroups of patients with varying degrees of diagnosis reliability: 13 probands (28,3%) in the subgroup with definite ARVC and 2 probands (8,3%) in the subgroup with borderline ARVC. No genotype-positive probands were found in the subgroup with possible ARVC. Variations of unknown clinical significance were found in 13 (16,25%) probands.Conclusion. The diagnostic yield of the desmosomal genes PKP2, DSG2, DSP, DSC2, and JUP was 19% with initial diagnosis of ARVC. The detection of mutations was significantly higher in patients with definite ARVC and severe disease manifestations.

Abstract 10988: Prevalence and Outcomes of Cardiac Amyloidosis in All-Comer Referrals for Bone Scintigraphy

Introduction: The prevalence of cardiac amyloidosis (CA) in the general population as well as prognostic implications remain poorly understood. Hypothesis: We aimed to identify CA prevalence and outcomes in bone scintigraphy referrals. Methods: Between 2010 and 2020, consecutive all-comers undergoing 99mtechnetium-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) bone scintigraphy were included retrospectively. CA was defined as positive cardiac tracer uptake (Perugini grade-1: subclinical CA; grade-2/3: clinical CA). All-cause mortality, cardiovascular (CV) death and hospitalization for heart failure (HHF) served as endpoints. Results: 17387 scans from 11527 subjects (61±16 y/o, 63.0% female, 73.6% cancer) were analyzed. Prevalence of CA was 3.3% (n=376/11527; grade-1: 1.8%, grade-2/3: 1.5%), and was higher among cardiac vs. non-cardiac referrals (18.2% vs. 1.7%). In 4 individuals with >1 scan, progression from subclinical to clinical CA was observed. Cardiac biopsy revealed underlying transthyretin CA in 3 grade-1 patients. After a median of 6 years, clinical event rates were: 29.4% mortality, 2.6% CV death, and 1.5% HHF, all independently predicted by CA. Overall, adverse outcomes were driven by clinical CA (clinical vs. no CA, mortality: adjusted hazard ratio [AHR] 1.46 [95% confidence interval 1.12-1.90]; CV death: AHR 2.34 [1.49-3.68]; HHF: AHR 2.25 [1.51-3.37]). In non-cancer patients, subclinical CA had equally increased mortality to clinical CA (log-rank, p >0.05), presumably due to longer observation/life expectancy. Conclusions: CA was identified in a substantial number of consecutive DPD referrals and associated with adverse outcomes. Subclinical (grade-1) progressed to clinical (grade-2/3) CA at follow-up and both had similarly increased mortality among non-cancer patients. Thus, in grade-1, clarification of the underlying pathology using myocardial biopsy is indicated to enable timely targeted therapy.

Abstract 12357: Discordant Mechanisms in Hypertrophy and Heart Failure

Introduction: Patients with heart failure and a preserved ejection fraction (HFpEF) present heart function abnormalities that remain poorly understood. Defining proteomic signature of HF that is independent of left ventricular hypertrophy (LVH) should allow for stratification of its subtypes and potential mechanism that contributes to the disease. Hypothesis: We hypothesized that HFpEF proteomic signature would be comprised of the hypertrophy and contractile protein phenotype. Methods: Intraoperative left ventricular (LV) myocardial biopsies were obtained from patients (n=21) recruited to undergo coronary artery bypass grafting (CABG). Patients were categorized to: control non-hypertensive (n=9), LVH (n=5), and HFpEF (n=7). Myocardial tissue was subfractionated: cytoplasmic- (neutral pH), myofilament- (acidic pH), and membrane-enriched extract (SDS-soluble). Samples were assessed for protein quantity and Lys/Arg modifications using liquid chromatography mass spectrometry (LC-MS). Results: In HFpEF, 13% of the cardiac LV proteome changed compared to control heart, with a substantial proportion (77%) decreasing in quantity across all three cardiac fractions, while with LVH, 61% of the proteomic LV changes were increased. Although glycolysis and gluconeogenesis increased in both cardiopathies with respect to control, in HFpEF more subtly than in LVH. Modified proteome of the HFpEF was dominated by decreases in protein succinylation (e.g. ATP5L, THIM, IDHP, APOB, GSH1, KNTC1) and to a lesser degree in methylation (ROA3, HSP7C) or acetylation compared to control group. This general trend of down-regulation of succinylation can be attributed to depletion in the levels of succinyl-CoA, the cofactor of enzymatic Lys succinylation. Importantly, there was a striking discordant activation/inhibition of cell death and proliferation pathways between the HFpEF and LVH. Two major upstream regulator clusters linked the proteome changes in cell growth and proliferation to RICTOR and Myc that showed completely opposite trends in LVH and HFpEF groups. Conclusions: HFpEF has a unique proteome signature compared to LV hypertrophy profile which does not arise from sub-proteome involved in contraction but rather is involved in overall cell death.

Abstract 11656: Chagas Disease Reactivation After Heart Transplant in an Endemic Country

Introduction: Chagas disease (CD) is a common cause of advanced heart failure in Colombia and the third cause of heart transplant in our center. For transplanted patients the immunomodulatory therapy is crucial, but it makes them susceptible to CD reactivation. Fiorelli et al showed a frequency of reactivation of 40% based in histological diagnosis; also, Gray et al reported a frequency of 61% using quantitative PCR. The estimation of this phenomenon in our population is essential to improve its management. Methods: We performed a retrospective cohort study of patients with heart transplant due to chagasic cardiomyopathy. The primary outcome was the prevalence of CD reactivation. Secondary outcomes included the description of clinical manifestations, immunomodulatory therapies used and the time elapsed since the transplant until the reactivation. Reactivation was defined as a positive RT-PCR for T.cruzi after heart transplant or a compatible endomyocardial biopsy. The RT-PCR test was performed if clinical deterioration, ventricular disfunction, or either randomly according to physician criteria. Results: Fifteen patients were included in the analysis. The age at the moment of the transplant was 54 YO (IQR 43-56), 67% were men. CD reactivation was diagnosed in the 67% of patients (Figure 1a). The median of the time to CD reactivation after the transplant is 12 months (95%-CI:3,16-20,8) (Figure 1b). The mortality during follow-up was 0% and the longest follow-up time was 11 years.The most frequently used drugs in patients with reactivation were cyclosporine, tacrolimus and corticosteroids. All of the patients with reactivation received benznidazole. Conclusions: There is a high prevalence of CD reactivation in heart transplanted patients due to Chagasic cardiomyopathy, especially during the first year. Protocols for screening these condition are necessary for an adequate care of these patients. Cualitative RT-PCR test and myocardial biopsy should be considered.

Abstract 14247: Myocardial Histopathology In Atrial Cardiomyopathy

Background: Atrial cardiomyopathy (ACM) is characterized by multiple histopathological features but the entity lacks systematic validation. Objectives: We sought to correlate atrial histopathology with clinical characteristics of patients with ACM and AF and outcomes following cardiac surgery. Methods: The pathological findings of the atrial myocardial biopsies from 178 patients who underwent any cardiac surgery between 2016-2018. Atrial cell nuclear structure and morphology, myocyte hypertrophy and interstitial fibrosis were graded and analyzed quantitatively. Study population was divided in three groups based on preoperative ECG: 1) patients in sinus rhythm with no signs of ACM (P wave duration <120ms)(SRn); 2) patients in sinus rhythm and ACM (P>=120 or biphasic waves in inferior leads)(SRa); and 3) atrial fibrillation (AF). Results: SRa patients had decreased number of nuclei/area and smaller total cardiomyocyte area compared to SRn patients (p=0.04 forboth). Patients with AF had bigger, less solid and circular nuclei compared to SRn patients (p<0.01 for all). AF patients had increased area of interstitial fibrosis (p<0.01) compared to SRn patients. Conclusions: Histopathological characteristics of ACM include changes in nuclear chromatin structure.

Comparative analysis of phasic left atrial strain and left ventricular posterolateral strain to discriminate Fabry cardiomyopathy from other forms of left ventricular hypertrophy

Abstract Background “Classic” echocardiographic signs of Fabry cardiomyopathy (FC), such as left ventricular hypertrophy (LVH) and posterolateral strain deficiency (PLSD) have a low diagnostic accuracy in clinical practice. Purpose Our aim was to evaluate the diagnostic accuracy of phasic left atrial strain impairment compared to PLSD to discriminate FC from other forms of LVH. Methods 40 patients with LVH due to bioptically and genetically confirmed FC or with LVH due to other causes, defined by exclusion of storage diseases, such as Amyloidosis or FC, by myocardial biopsy, were retrospectively analysed. Standard echocardiographic views (Vivid E9, GE, Vingmed, Horton) were used to analyse left atrial (LA) reservoir, conduit, and contraction strain using 2D speckle tracking echocardiography (2DSTE; EchoPAC software, GE) as well as the PLSD, obtained by the mean of deformation values in basal posterior and lateral segments in a 17-segment model. Receiver operating characteristic (ROC) curve analysis and a logistic regression model were performed to assess the diagnostic accuracy of LA and LV strain impairment. Results FC was confirmed in 20 patients by genetic testing and myocardial biopsy. In the LVH group, 12 patients were classified to have hypertrophic cardiomyopathy, two had hypertensive heart disease, and six expressed the pattern of LV hypertrophy combined with borderline myocarditis. LV septum thickness (15.8mm±3.4 in FC; 17.9mm±4.3 in LVH) and left atrial volume index (LAVI) (36.7ml/m2±11.3 in FC; 45.7ml/m2±16.3 in LVH) as well as LVEF (54.2%± 9.8 in FC; 52.5%±7.7 in LVH,) were not statistically different between groups. LV filling parameters such as E/A (1.2±0.5 in FC; 1.2±0.7 in LVH) and E/e' (11.0±4.9 in FC; 13.2±5.3 in LVH) showed a slightly more advanced impairment in the LVH group. Global and regional LV function was not different between groups (LVGLS −13.8±3.7% in FC and −12.8±3.7% in LVH; PLSD −10.7±5.2% in FC and −8.85±3.9% in LVH; p-value?). LA reservoir strain (LASr) and LA conduit strain (LAScd) were significantly impaired in FC compared to the LVH group (LASr 14,6±2.5% in FC and 26.3±8.5% in LVH, p<0.01; LAScd −5.9±2.6% in FC and −15.8±4.7% in LVH, p<0.01). In ROC analysis, LASr, with an area under the curve (AUC) of 0.81 (95% CI 0.64–0.97) and LAScd with an AUC of 0.85 (95% CI 0.71–0.99), respectively, showed the highest diagnostic accuracy to discriminate FC. PLSD, in contrast, held a low diagnostic accuracy with an AUC of only 0.47 (95% CI 0.27–0.68). Conclusion A substantially higher diagnostic accuracy could be shown for LASr and LAScd impairment in discriminating FD and other forms of LVH compared to PLSD. The echocardiographic assessment of phasic LA strain may help to identify FC in patients with unclear LVH. Funding Acknowledgement Type of funding sources: None. ROC analysisRepresentative examples

Post-COVID myocarditis diagnosed by endomyocardial biopsy and/or magnetic resonance imaging 2–9 months after acute COVID-19

Abstract Purpose To study clinical features of myocarditis and its possible mechanisms (including persistence of SARS-Cov-2 in the myocardium) in the long-term period after acute COVID-19. Methods Fifteen patients (8 male and 7 female, mean age 47.8±13.4, 24–65 years) diagnosed with postcovid myocarditis were included in the study. The diagnosis of COVID-19 was confirmed by positive PCR results in 40%, and seroconversion in all patients. The average time of admission after COVID-19 was 4 [3; 7] months, from 2 to 9 months. The diagnosis of myocarditis was confirmed by cardiac MRI in 10 patients and by right ventricular endomyocardial biopsy (EMB) in 6 patients. The PCR for cardiotropic viruses and PCR with immunohistochemical study for SARS-Cov2 detection were used. All patients had study for anti-heart antibodies (AHA), EchoCG, and Holter ECG. Coronary atherosclerosis was excluded in all patients over 40 years (7 coronary angiography, 4 cardiac CT). Results A clear association of the cardiac symptoms with a previous new coronavirus infection was noted in all patients. The symptoms started 1–5 months following COVID-19. MRI showed subepicardial and intramyocardial LGE, signs of hyperemia, increased T1 relaxation time, edema. AHA levels were increased 3–4-fold in 73%. Two variants of postcovid myocarditis were observed. 1. Arrhythmic variant (n=6) – newly developed frequent supraventricular or ventricular extrasystole, recurrent atrial fibrillation in the absence of systolic dysfunction. 2. Decompensated variant with biventricular heart failure (n=9): the mean LV EF was 34.1±7.8% (23 to 46%), LV EDD 5.8±0.7 cm, EDV 153.8±46.1 ml, pulmonary artery systolic pressure 40.7±11.2 mmHg. In one case, myocarditis was accompanied by IgG4- and ANCA-negative aortitis. SARS-Cov-2 RNA was detected in 4 of 5 myocardial biopsies (in one case the material in the study). The longest period of virus persistence after COVID-19 was 9 months. By using spike and nucleocapsid antibodies, coronavirus was detected in cardiomycytes and macrophages. Data of patients with morphologically proved myocarditis are presented in Table 1. Lymphocytic myocarditis was diagnosed and confirmed immunohistochemically (n=5); giant cell myocarditis with atrial standstill was detected in one more case (Fig. 1). Three patients had also signs of endocarditis, in two cases with parietal thrombosis. Conclusions COVID-19 can lead to the subacute and chronic myocarditis of varying severity. Post-COVID myocarditis manifests itself in two main clinical forms - isolated arrhythmias and systolic dysfunction with heart failure. Post-COVID myocarditis is characterized by prolonged persistence of coronavirus (up to 9 months in this study, in most patients with decompensated variant) in combination with high immune activity (high titers of AHA), which should be considered as the main mechanisms of its long-term course. Treatment approaches for such myocarditis require investigation. Funding Acknowledgement Type of funding sources: None. Table 1. Patients with EMB proved myocarditisFigure 1. The EMB in postcovide myocarditis

Post-COVID morphologically proved endocarditis: infective and nonbacterial forms

PurposeTo study clinical features of endocarditis and its possible mechanisms (infective and nonbacterial) in the long-term period after acute COVID-19.MethodsThree patients (two male and one female, age 64, 39 and 46 years) diagnosed with postcovid endocarditis were included in the study. One patient had severe bilateral coronavirus pneumonia; the other two had only fever and weakness. The diagnosis of COVID-19 was confirmed by seroconversion. The time of admission after COVID-19 was from 4 to 7 months. All patients had study for anti-heart antibodies (AHA), EchoCG, Holter ECG, and endomyocardial biopsy (EMB) with PCR for SARS-Cov2 and cardiotropic viruses. The indication for EMB was suspected myocarditis. Blood cultures and procalcitonin levels were tested in one patient due to a prolonged febrile fever.ResultsTwo variants of postcovid endocarditis have been diagnosed. The first variant was detected in two patients by EMB only. This patients had severe lymphocytic and giant cell myocarditis. In addition, EMB showed signs of lymphocytic endocarditis with infiltrates, marked thickening and fibrosis of the endocardium (Fig. 1). Some biopsy specimen were represented by fresh thrombotic masses, infiltrated with neutrophilic leukocytes. No intraventricular thrombus was detected on EchoCG and MRI. The second variant of postcovid endocarditis developed in a patient with bicuspid aortic valve and met the criteria of infectious endocarditis 2015: mobile vegetations on the valve with aortic regurgitation II, splenomegaly, irregular fever up to 39°C for six months, marked increase of CRP, procalcitonin and ferritin, hypochromic anemia, LV EF 25%. Blood culture was negative. After intravenous therapy with antibiotics and immunoglobulin, EMB confirmed the active lymphocytic myocarditis and only slight fibrosis of right ventricular endocardium. The bacteriological study of endocardium was negative. SARS-Cov-2 RNA was detected by PCR in myocardial biopsy specimens of two patients; the biopsy of one patient is in the study now. All patients had significantly elevated antibody titers to various cardiac antigens, but the level of antibodies to endothelial antigens remained completely normal. It is possible to suggest an active deposition of immune complexes in the endothelium. Two surviving patients receive steroid therapy (in case of IE with antibiotics).ConclusionsSARS-Cov-2 infection induces the prolonged non-bacterial thromboendocarditis or infective endocarditis. In both cases, autoimmune mechanisms play a significant role, as evidenced by the simultaneous lymphocytic/giant cell myocarditis and high titers of AHA. Long-term persistence of coronavirus in the myocardium can also be considered as an etiological factor of endocarditis. In favor of this hypothesis is the parietal thrombosis in the absence of bacterial infection. Corticosteroids and anticoagulants should be considered for the treatment of postcovid endocarditis.Funding AcknowledgementType of funding sources: None. Figure 1. The EMB in in postcovid endocarditis

IS THERE ANY INFLUENCE OF THE ANTIRHEUMATIC THERAPY ON HEART DAMAGE IN SYSTEMIC LUPUS ERYTHEMATOSUS?

TOPIC: Cardiovascular Disease TYPE: Original Investigations PURPOSE: Cardiovascular involvement in systemic lupus erythematosus (SLE) patients can be associated with disease severity, activity and treatment-related factors. The goal is to determine possible differences in the structure and frequency of heart damage in SLE patients, with and without antirheumatic therapy. METHODS: This is a prospective cross-sectional study including 87pts (91% females, aged 32[28-41]years (median[interquartile range 25%-75%]) with SLE(SLICC 2012 criteria). All patients were divided into 2 groups: the 1st group was composed of “untreated” patients and the 2nd – of patients receiving antirheumatic therapy. The 1st group included 42pts(93% females) aged 31[27–40]years who were not receiving steroids, immunosuppressants and biological agents, 4(10%) of them were on hydroxychloroquine (HCQ) therapy 200 mg/day. The 2nd group is represented by 45pts(89% females) aged 34[28-45]years. Out of them 44(98%) patients were on prednisone therapy at 10[8-15]mg/day, 9(21%)- on cyclophosphamide, 6(13%)-azathioprine, 4(8%)-mycophenolate mofetil, 4(8%)-methotrexate, 32(71%)–HCQ, and 9(19%)–on biologic (rituximab, belimumab). Patients receiving antirheumatic therapy (group 2) had longer disease duration (96 vs 18 months, p<0,00001), lower disease activity (SLEDAI-2K 4 vs 12 scores,p<0,001), higher SLICC/DI (1 vs 0 score,p<0,001); lower percentage of them had skin lesions (11 vs 57%,p<0,0001), arthritis (22 vs 52%,p<0,05) and hematological disorders (24 vs 74%,p<0,0001) than “untreated” patients from the 1st group.Serum levels of NT-proBNP were measured using electrochemiluminescence method Elecsys proBNP II(Roche Diagnostics, Switzerland). Normal NT-proBNP levels should vary within ≤125pg/ml. RESULTS: No differences in terms of pericarditis (43% and 47%) (both exudative and adhesive), endocarditis (26% and 33%), arrhythmias (19% and 18%) and cardiac conduction defect (2% each), coronary artery disease (2% and 9%), myocardial infarction (0 and 4%), and heart failure (7% and 15%) frequencies were found between the “treatment-na?v” SLE patients and patients receiving antirheumatic therapy (p>0,05 for all cases). NT-proBNP concentrations were higher in “treatment-na?v”patients (150,7 vs 32,6 pg/ml,p<0,01), exceeding normal values (>125,0pg/ml).Myocarditis diagnosed by based on clinical, laboratory and instrumental findings (without myocardial biopsy) were documented in “treatment-na?v” patients only, but difference did not reach statistical significance (10% vs 0,p=0,050).Hypertension was more common in patients from the 2ndgroup (62% and 29%,p<0,01), but no differences were found in the frequency of other traditional risk factors, although total cholesterol levels and body mass index (BMI) were higher than in 1stgroup: 5,7 vs 4,5 mmol/L,p<0,05; 22,66 and 22,10 kg/m2,p<0,01, respectively. CONCLUSIONS: Antirheumatic therapy does not seemingly aggravate the heart damage in SLE patients, yielding no statistical difference in both - variety or frequency of most common CV pathologies. But the therapy (mostly steroids) and longer disease duration is associated with hypertension, high cholesterol level and BMI. Higher disease activity (in “treatment-na?v” patients) is associated with the increased NT-proBNP level, and possibly, higher frequency of myocarditis. CLINICAL IMPLICATIONS: Antirheumatic therapy does not aggravate the heart damage in SLE DISCLOSURES: No relevant relationships by Elena Gerasimova, source=Web Response No relevant relationships by Yulia Gorbunova, source=Web Response No relevant relationships by Liubov Kondrateva, source=Web Response No relevant relationships by Tatiana Panafidina, source=Web Response No relevant relationships by Tatiana Popkova, source=Web Response

Role of Cardiac Magnetic Resonance Imaging in Hypocalcemia-Induced Dilated Cardiomyopathy in Pediatric Population.

Background Hypocalcemia is a rare reversible cause of dilated cardiomyopathy in pediatric population. Myocarditis is another more frequent cause of cardiomyopathy with overlapping presenting features. Cardiac magnetic resonance imaging (CMRI) is a vital modality capable of tissue characterization for the evaluation of cardiomyopathy. The present study is the first attempt to determine if any specific characteristics on CMR exist in patients with hypocalcemic dilated cardiomyopathy. Methods A retrospective analysis of 10 cases of hypocalcemic dilated cardiomyopathy (August 2012–August 2019), among which CMRI of nine patients were analyzed. Patients were categorized in to three categories; category 1 defined as absence of edema and late gadolinium enhancement (LGE), category 2 having edema only, and category 3 with presence of both edema and LGE. A diagnosis of myocarditis was considered if both edema and LGE were present. Results The mean age of the cohort was 5.5 ± 3.3 months. The mean ejection fraction of the cohort was 20.5 ± 6.85% that improved significantly to 35.22 ± 9.3% at the time of discharge. Five of nine patients had no edema or LGE (category 1), whereas two patients each were categorized into category 2 and 3. All cases in category 1 had normalized ventricular function on follow-up. One patient in category 2 had normal ejection fraction and one was lost to follow-up. Out of the two patients in category 3, there was one mortality and another was lost to follow-up. Of the six patients at follow-up (19 ± 11.0 months), the mean left ventricle ejection fraction improved to 56.5 ± 6.1%. Conclusion Hypocalcemic dilated cardiomyopathy has a favorable outcome on rapid initiation of treatment. CMR can be utilized for further prognostication of these patients. Absence of edema and LGE predicts a good outcome, whereas presence of LGE and/or edema either indicates a worse prognosis or an underlying coexistent myocarditis warranting an early myocardial biopsy.

СASE STUDY OF HEPATO-RENAL FAILURE IN A PATIENT AFTER ORTHOTOPIC HEART TRANSPLANTATION

Introduction. Heart transplantation remains the only radical treatment for end-stage heart failure (HF). Liver and / or renal dysfunction is common in patients with HF, which is also exacerbated by the use of artificial circulation and immunosuppressive therapy, and leads to postoperative complications and mortality. Case description. Patient P., 49 years old, after orthotopic heart transplantation was admitted to the intensive care unit (ICU) with signs of multiple organ failure. Graft rejection syndrome was suspected, but was not confirmed after the detailed clinical and laboratory examinations and according to the myocardial biopsy. Because of severe renal and hepatic insufficiency, patient at the ICU started to receive hemodiaultrafiltration with a flow of 190 ml/min; ultrafiltration – 100 ml/h. The condition, that developed was due to the direct effect of tacrolimus as the patient had a critically high plasma concentration of this drug (&gt; 30 ng / ml) after the standard recommended postoperative dose (0.2 mg / kg per day). According to the literature, the elimination of the tacrolimus is provided by the liver, with microsomal cytochrome P450 3A4. Thus, the patient most likely had a failure of hepatic metabolism. Conclusion: Because of the systemic toxicity of tacrolimus, it is important to monitor its concentration after the first dose. Diagnosis of metabolic disorders at an early stage will prevent further systemic toxicity of tacrolimus. Efferent methods at ICU are the important tools for the correction of hepatic and renal insufficiency throughout toxic effects of tacrolimus.

Endovascular therapy for severely calcified plaque at the superficial femoral artery using myocardial biopsy forceps

BackgroundCurrently, the success rate of EVT for treating CTO of the SFA is high; however, EVT is still found to be insufficient in treating CTOs with severely calcified lesions. Even if the guidewire crosses the lesion, the calcifications may still cause difficulties during stent expansion.Main textA 78-year-old male had been reported to have intermittent claudication with chronic total occlusion (CTO) of the right superficial femoral artery (SFA). Angiography revealed severely calcified plaque (Angiographic calcium score: Group4a [1]) at the ostium of the SFA. Stenting posed a risk of underexpansion, causing the plaque to shift to the deep femoral artery. we decided to remove the calcified plaque using biopsy forceps. After removing the extended calcified plaque, the guidewire could cross easily, and the self-expandable stent was well dilated without causing the plaque to shift to the DFA.ConclusionsBiopsy forceps may be used in some endovascular cases to remove severely calcified lesions.To ensure the safety of the patient, the physician must be adept at performing this technique before attempting it.

The association of left ventricular histologically verified myocardial fibrosis with pulmonary hypertension in severe aortic stenosis.

To evaluate the association between histologically verified left ventricular (LV) myocardial fibrosis (MF) and its bio- and functional markers with pulmonary hypertension (PH) in severe aortic stenosis (AS). About 34 patients with isolated severe AS underwent 2D echocardiography, cardiac magnetic resonance (CMR) imaging, and plasma NT-proBNP evaluation before aortic valve replacement (AVR). LV measurements were analyzed by CMR and LV strain using feature tracking software (Medis Suite QStrain 2.0). Myocardial biopsy sampled at the time of AVR was assessed by a histomorphometric analysis. PH was defined as pulmonary artery systolic pressure (PASP) ⩾ 45 mm Hg. Patients with severe AS and PH (mean PASP 53 ± 3.7 mm Hg) had higher extent of diffuse MF versus patients without PH (12 (10.4-12.7)% vs 6.6 (4.6-8.2)% (p = 0.00)). The extent of diffuse MF correlated with LV dilatation (r = 0.7, p = 0.02), indices of LV dysfunction (lower ejection fraction (r = -0.6, p < 0.001), global longitudinal (r = -0.5, p = 0.02) and circumferential strain (r = -0.5, p = 0.05), elevated NT-proBNP (r = 0.5, p = 0.005) and elevated PASP (r = 0.6, p < 0.001)). Histological MF > 10% (AUC 94.9%), LV global longitudinal strain > -15.5% (AUC 86.3%), and NT-proBNP > 2090 ng/l (AUC 85.1%) were independent predictors of PH in severe AS. The extent of diffuse myocardial fibrosis in combination with reduced longitudinal left ventricular strain and increased plasma levels of NT-proBNP relates to pulmonary hypertension in severe aortic stenosis.

A Novel Diagnostic Score Integrating Atrial Dimensions to Differentiate between the Athlete’s Heart and Arrhythmogenic Right Ventricular Cardiomyopathy

Objective: The 2010 Task Force Criteria (TFC) have not been tested to differentiate ARVC from the athlete’s heart. Moreover, some criteria are not available (myocardial biopsy, genetic testing, morphology of ventricular tachycardia) or subject to interobserver variability (right ventricular regional wall motion abnormalities) in clinical practice. We hypothesized that atrial dimensions are useful and robust to differentiate between both entities and proposed a new diagnostic score based upon readily available parameters including echocardiographic atrial dimensions. Methods: In this observational study, 21 patients with definite ARVC were matched for age, gender and body mass index to 42 athletes. Based on ROC analysis, the following parameters were included in the score: indexed right/left atrial volumes ratio (RAVI/LAVI ratio), NT-proBNP, RVOT measurements (PLAX and PSAX BSA-corrected), tricuspid annular motion (TAM), precordial TWI and depolarization abnormalities according to TFC. Results: ARVC patients had a higher RAVI/LAVI ratio (1.76 ± 1.5 vs. 0.87 ± 0.2, p < 0.001), lower right ventricular function (fac: 29 ± 10.1 vs. 42.2 ± 5%, p < 0.001; TAM: 19.8 ± 5.4 vs. 23.8 ± 3.8 mm, p = 0.001) and higher serum NT-proBNP levels (345 ± 612 vs. 48 ± 57 ng/L, p < 0.001). Our score showed a good performance, which is comparable to the 2010 TFC using those parameters, which are available in routine clinical practice (AUC93%, p < 0.001 (95%CI 0.874–0.995) vs. AUC97%, p < 0.001 (95%CI 0.93–1.00). A score of 6/12 points yielded a specificity of 91% and an improved sensitivity of 67% for ARVC diagnosis as compared to a sensitivity of 41% for the abovementioned readily available 2010 TFC. Conclusions: ARVC patients present with significantly larger RA compared to athletes, resulting in a greater RAVI/LAVI ratio. Our novel diagnostic score includes readily available clinical parameters and has a high diagnostic accuracy to differentiate between ARVC and the athlete’s heart.

Специфічність діабетичної кардіоміопатії за наявності коморбідних серцево-судинних захворювань: клініко-ультраструктурні дослідження

Актуальність. Концепція про діабетичну кардіоміопатію вперше була запропонована С. Рублер та співавт. понад 100 років тому, але цей діагноз рідко використовується клініцистами через існування, переважно в пацієнтів із цукровим діабетом (ЦД), таких коморбідних захворювань, як ішемічна хвороба серця (ІХС) і гіпертонічна хвороба. Різноманітні механізми спричинюють патогенез діабетичної кардіоміопатії, але її специфічні ознаки досі остаточно не встановлені. Мета дослідження — з’ясувати ультраструктурні особливості ремоделювання кардіоміоцитів, характерні для діабетичної кардіоміопатії, за наявності коморбідної ІХС та артеріальної гіпертензії (АГ). Матеріали і методи. Були порівняні результати клінічного обстеження та ультраструктурного дослідження експрес-некропсій та періопераційних біопсій міокарда в 25 пацієнтів із ЦД 2-го типу за наявності супутньої АГ та ІХС. Результати. Виявлені ультраструктурні особливості гібернації кардіоміоцитів, характерні для ЦД 2-го типу, відмінні від їх гібернації за наявності ІХС та АГ. З’ясовано, що гібернація кардіоміоцитів за ЦД виникає вже на ранніх стадіях захворювання, ще до розвитку АГ та ІХС, тобто за відсутності гіпертрофії кардіоміоцитів та їх оглушеності, характерних для серцево-судинних захворювань. Висновки. Діабетична кардіоміопатія виникає в результаті дисметаболічних і мікроциркуляційних розладів, що призводить до гібернації кардіоміоцитів. Тригерами розвитку діабетичної кардіоміопатії є декомпенсація ЦД і серцево-судинні захворювання. Гіберновані кардіоміоцити гинуть шляхом апоптозу або вторинного некрозу, що обумовлює трансформацію діастолічної дисфункції лівого шлуночка в систолічну.

Гострий тромбоз стента при інфаркті міокарда, ускладненому кардіогенним шоком, за наявності цукрового діабету 2-го типу

Актуальність. Гострий тромбоз стента (ТС) є нечастим, але грізним ускладненням при стентуванні вінцевих артерій. Він виникає під час черезшкірних коронарних втручань або впродовж 24 годин після цієї процедури. Мета дослідження: з’ясувати причини та проаналізувати фактори, що призвели до гострого ТС при гострому коронарному синдромі і цукровому діабеті (ЦД) 2-го типу, для уникнення подібних ускладнень. Матеріали та методи. Обстежено 119 пацієнтів із гострим інфарктом міокарда з елевацією сегмента ST, які лікувалися в інфарктному відділенні комунального некомерційного підприємства «Клінічна лікарня швидкої медичної допомоги м. Львова». Усім пацієнтам проводили коронарографію та стентування вінцевих артерій, ультраструктурні дослідження тромбоцитів венозної крові за допомогою електронної мікроскопії. Результати. Пацієнти із ЦД 2-го типу мають вищий кардіоваскулярний ризик розвитку серцево-судинних ускладнень, що пов’язано з ендотеліальною дисфункцією, схильністю до гіперкоагуляції і, як наслідок, тенденцією до вазоконстрикції, запальних реакцій та порушень гемостазу. У цієї категорії пацієнтів спостерігається підвищена адгезивність тромбоцитів і збільшена концентрація тканинного активатора плазміногену. В експрес-некроптатах і періопераційних біоптатах міокарда пацієнтів із ЦД нами виявлено домінування процесів гіперкоагуляції в мікросудинах міокарда в результаті активності системи згортання крові за відсутності безпосередньої участі тромбоцитів, оскільки частина з них була кальцифікована (осміофільні) і мала знижену функціональну здатність, в результаті чого відмічається резистентність до аспірину. В осіб із ЦД 2-го типу виникає зазвичай тяжкий і більш генералізований коронаросклероз, що призводить до погіршення перебігу гострого коронарного синдрому і частішого виникнення ТС, що робить доцільним додаткове призначення ривароксабану цій категорії пацієнтів. Висновки. Враховуючи виявлені нами ознаки зниженої реактивності тромбоцитів і домінування активації системи згортання крові у хворих на ЦД і з підвищеним ризиком коронаротромбозу, вважаємо, що застосування нових пероральних антикоагулянтів є актуальним і заслуговує подальших досліджень.

The relationship between myocardial fibrosis and left ventricular remodeling following aortic valve replacement

Aim. Aortic valve diseases are associated with myocardial fibrosis. The relationship between severity of myocardial fibrosis and left ventricular mass reduction (LVMR) after aortic valve replacement (AVR) still needs to be elucidated. Methods. In a single-center, retrospective trial, 130 patients underwent AVR with/without concomitant surgery. The study population was divided by etiology into aortic stenosis (AS) and aortic regurgitation (AR) groups. LV end-diastolic diameter, LV septal and posterior thicknesses, LV mass, and aortic annulus were obtained in all study patients. Left ventricular mass regression index (iLVMR) was found by the difference between preoperative iLVM and follow-up iLVM. iLVMR in months was calculated by divided iLVMR on the number of months before follow-up visit. Myocardial tissue was embedded in paraffin, and sectioned into 4 µm slices for histological staining (picrosirius red) and scanning. The fraction of myocardial volume occupied by collagen tissue was determined. Results. The left ventricular remodeling of AS and AR patients is presented in Table 3. There was significant LV mass reduction in both aortic valve disease groups in the follow-up period (AS group, p < 0.001; AR group, p < 0.05). The number of LVH cases decreased in both groups in the follow-up period (AS group, p < 0.001; AR group, p < 0.05). In Post-AVR period the ejection fraction of LV did not improve in the AS group, compare to AR group (p<0.05). In both groups number of patients with impaired LV EF was increased in Post-AVR period, but not significantly. Moreover, the LV septal thickness, and iLVEDD significantly decreased in the AS group (p<0.001 and p<0.001), compared to the AR group (p=NS, p<0.05). We did not found correlations between MF and LVM in preoperative, and follow-up periods for AS and AR groups. Moreover, MF did not correlate significantly to iLVMR and iLVMR in months. A significant correlation exists in AS patients between MF and preoperative iLVEDD (r = 0.21, p = 0.04). Conclusion. The LVM reduction was observed in both AS and AR groups. LVM of AS group recovered more quickly than that of AR group. In our study MF does not affect LVM regression. Large cohort of patients with myocardial biopsies and long-term follow-up are needed to access the impact of the MF on the LVMR.