Severe Myocardial Hypertrophy Research Articles

Severe myocardial hypertrophy and fibrosis in a patient with acromegaly: is the prevention of sudden cardiac death needed?

Severe myocardial hypertrophy and fibrosis in a patient with acromegaly: is the prevention of sudden cardiac death needed?

Autopsy findings in a fetus with monosomy 20 mosaicism

Introduction. Mosaic monosomy 20 is a rare chromosomal aberration, without characteristic clinical features. We present a case of a fetus with monosomy 20 mosaicism revealed after prenatal ultrasound detection of anhydramnios and multiple anomalies. Case outline. The second pregnancy of a 33-year-old woman, was terminated at 23rd gestational week, because of the multiple fetal anomalies and anhydramnios, detected by ultrasound. The autopsy of a female fetus revealed multiple congenital anomalies: ventriculomegaly, bilateral choroid plexus cysts, perivascular gliosis in periventricular region of cerebri, hydropericardium, severe cardiomegaly, severe myocardial hypertrophy, hydrothorax, glandular/canalicular stage of fetal lung development, bilateral renal and ureter agenesis (Potter syndrome), bladder aplasia, agenesis of the uterus, fallopian tubes and proximal vagina and valgus deformity of left foot (pes valgus). Fetal growth was adequate for gestational age with no craniofacial dysmorphia or radiographically visible anomalies of the skeleton, without signs of infection. The umbilical cord was too long for gestational age ? 48 cm. Analysis of fetal karyotype from fetal blood sampling revealed monosomy of chromosome 20 in 10% of analyzed cells in metaphase. Conclusion. Revealing the genetic basis of fetal anomalies is at outmost importance not only for further evaluation of pregnancy, but also for proper genetic informing of patients.

Trim65 attenuates isoproterenol-induced cardiac hypertrophy by promoting autophagy and ameliorating mitochondrial dysfunction via the Jak1/Stat1 signaling pathway

Pathological cardiac hypertrophy is a major cause of heart failure, and there is no effective approach for its prevention or treatment. The Trim family is a recently identified family of E3 ubiquitin ligases that regulate cardiac hypertrophy. Trim65, which is a member of the Trim family, previous studies have not determined whether Trim65 affects cardiac hypertrophy. In this study, the effects of Trim65 on isoproterenol (ISO)-induced cardiac hypertrophy and the underlying mechanisms were investigated. In contrast to C57BL/6 mice, Trim65-knockout (Trim65-KO) mice developed more severe myocardial hypertrophy, fibrosis and cardiac dysfunction after being intraperitoneally injected with ISO for 2 weeks. Transmission electron microscopy (TEM) revealed that the autophagic flux was inhibited, mitochondria were swollen, and mitochondrial cristae were lost or decreased in the myocardium of Trim65-KO mice. In vitro studies demonstrated that overexpression of Trim65 inhibited ISO-induced cardiomyocyte hypertrophy by increasing mitochondrial density and membrane potential, and the Stat1 inhibitor fludarabine attenuated the effect of Trim65 knockdown on ISO-induced cardiomyocyte hypertrophy by reducing Reactive oxygen species (ROS) production and increasing the mitochondrial density and membrane potential. Our findings provide the first link between Trim65 and mitochondria, and we found for the first time that Trim65 inhibits mitochondria-dependent apoptosis and autophagy via the Jak1/Stat1 signalling pathway, ultimately attenuating ISO-induced cardiac hypertrophy; this effect of Trim65 might be mediated via the regulation of Jak1 ubiquitination. Taking these findings together, we suggest that genes that are related to mitochondria-dependent apoptosis and that are associated with Trim65 could be promising therapeutic targets for cardiac hypertrophy.

GPR30 Alleviates Pressure Overload-Induced Myocardial Hypertrophy in Ovariectomized Mice by Regulating Autophagy.

The incidence of heart failure mainly resulting from cardiac hypertrophy and fibrosis increases sharply in post-menopausal women compared with men at the same age, which indicates a cardioprotective role of estrogen. Previous studies in our group have shown that the novel estrogen receptor G Protein Coupled Receptor 30 (GPR30) could attenuate myocardial fibrosis caused by ischemic heart disease. However, the role of GPR30 in myocardial hypertrophy in ovariectomized mice has not been investigated yet. In this study, female mice with bilateral ovariectomy or sham surgery underwent transverse aortic constriction (TAC) surgery. After 8 weeks, mice in the OVX + TAC group exhibited more severe myocardial hypertrophy and fibrosis than mice in the TAC group. G1, the specific agonist of GPR30, could attenuate myocardial hypertrophy and fibrosis of mice in the OVX + TAC group. Furthermore, the expression of LC3II was significantly higher in the OVX + TAC group than in the OVX + TAC + G1 group, which indicates that autophagy might play an important role in this process. An in vitro study showed that G1 alleviated AngiotensionII (AngII)-induced hypertrophy and reduced the autophagy level of H9c2 cells, as revealed by LC3II expression and tandem mRFP-GFP-LC3 fluorescence analysis. Additionally, Western blot results showed that the AKT/mTOR pathway was inhibited in the AngII group, whereas it was restored in the AngII + G1 group. To further verify the mechanism, PI3K inhibitor LY294002 or autophagy activator rapamycin was added in the AngII + G1 group, and the antihypertrophy effect of G1 on H9c2 cells was blocked by LY294002 or rapamycin. In summary, our results demonstrate that G1 can attenuate cardiac hypertrophy and fibrosis and improve the cardiac function of mice in the OVX + TAC group through AKT/mTOR mediated inhibition of autophagy. Thus, this study demonstrates a potential option for the drug treatment of pressure overload-induced cardiac hypertrophy in postmenopausal women.

Del Nido cardioplegia in patients with severe myocardial hypertrophy

Del Nido cardioplegia in patients with severe myocardial hypertrophy

1029 FABRY DISEASE: A RARE CAUSE TO REMEMBER WHEN FACING ACUTE KIDNEY INJURY IN YOUNG

Abstract Introduction Anderson-Fabry disease (FD) is a rare X-linked hereditary disease caused by mutations in the alpha-galactosidase A (GLA) gene, a lysosomal hydrolase that catabolizes lipids. GLA deficency leads to a progressive accumulation of undegraded glycosphingolipids, mainly Globotriaosylceramide (GB3), within lysosomes of cells (epithelial and endothelial cells, neurons, cardiomyocytes and renal cells), leading to cellular dysfunction. The incidence of FD is 1:117.000 but in patients with end stage renal disease (ESRD), incidence is higher, ranging from 0.04% up to 1.16% in male dialysis patients. Classical form of the disease shows renal, cardiac and cerebrovascular involvements usually. Cardiac involvement includes hypertrophic cardiomyopathy, arrhythmias such as complete heart block, valve dysfunction and myocardial infarction. Renal manifestations include proteinuria, progressive loss of renal function with chronic kidney disease (CKD) that leads to ESRD. The diagnosis of FD can be very difficult and often is delayed due to subtle clinical manifestations, but an early diagnosis is crucial to start enzyme replacement therapy (ERT), based on recombinant human GLA, as soon as possible. Clinical Case we describe the case of a 36-years-old male admitted to the Emergency Room of our hospital due to asthenia, nausea, dysphagia, anuria and loss of weight. At physical examination, apical systolic murmur and a bilateral ankle edema. Blood pressure was 195/100 mmHg, heart rate 125 beats per minute, peripheral oxygen saturation 100%. Blood test showed Hemoglobin 8 g/dL, Blood Urea 422 mg/dL, Creatinine 20 mg/dL, Na+ 135 mEq/L, K+ 4 mEq/L, Phosphorus 9 mg/dL. Arterial blood gas analysis showed metabolic and lactic acidosis. The diagnosis of acute kidney injury (AKI) was made, and a dialytic treatment was scheduled. During dialytic session, the patient had a syncope. EKG showed a complete left bundle branch block (LBBB) with advanced atrio-ventricular block (2:1, complete). An echocardiogram highlighted a severe myocardial hypertrophy (septal wall 25 mm) involving also the right ventricle with “ground glass” aspect of the posterolateral, posterior and inferior septum, with minimal pericardial effusion. Heart MRI scan confirmed LV myocardial hypertrophy with circumferential aspect (interventricular septum 26.6 mm), mild decrease in left ventricular ejection fraction (47%) and myocardial hypointensity area in the FSE sequences. Renal ultrasound showed bilateral cortical hyperecogenity, small cortico-medullary border, initial reduction of kidney volume and diffuse perirenal edema. In consideration of the high probability of a storage disease, we performed genetic testing for FD and Gaucher disease, peri-umbilical fat biopsy for Amyloid Disease and a renal biopsy. The genetic test resulted positive for typical mutation of FD and renal biopsy documented ESRD secondary to glycosphingolipid storage disease ceramid type from FD. Conclusion Differential diagnosis of AKI in a young male should include FD, as suggested by the clinical case reported, and nephrologist should screen young patients for α-GLA enzyme deficiency (diagnostic for FD) possibly coupled with renal biopsy in uncertain cases.

MicroRNA expression profiles in familial hypertrophic cardiomyopathy with myosin-binding protein C3 (MYBPC3) gene mutations

Familial hypertrophic cardiomyopathy (FHCM) is an autosomal dominant inherited disease caused by mutations in genes encoding cardiac sarcomere proteins. MicroRNAs (miRNAs) play an important role in the pathogenesis of FHCM. In the present study, we aimed to determine the miRNA profile in FHCM patients with myosin-binding protein C3 (MYBPC3) gene mutations. We recruited three FHCM patients and age- and sex-matched controls. The three probands all had hypertrophic obstructive cardiomyopathy with severe myocardial hypertrophy, and two of the three had a history of sudden cardiac death, representing a “malignant” phenotype. We then compared the miRNA expression profiles of three FHCM patients carrying MYBPC3 gene mutations with those of the normal control group using miRNA sequencing technology. Differentially expressed miRNAs were verified using real-time polymerase chain reaction (qPCR). Target genes and signaling pathways of the identified differentially expressed miRNAs were predicted using bioinformatics analysis. A total of 33 significantly differentially expressed miRNAs were detected in the peripheral blood of the three probands, of which 28 were upregulated, including miR-208b-3p, and 5 were downregulated. Real-time PCR confirmed the upregulated expression of miR-208b-3p in FHCM patients (P < 0.05). Bioinformatics analysis showed that miR-208b-3p was mainly enriched in 79 target genes including UBE2V2, MED13, YBX1, CNKSR2, GATA4, andSOX5/6, et al. Gene ontology (GO) analysis of target genes showed that miR-208b was mainly involved in the processes of negative regulation of transcription from RNA polymerase II promoter, and regulation of transcription, DNA templated. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that the target genes regulated by miR-208b-3p were mainly involved in the Wnt signaling pathway. These findings suggest that FHCM patients with MYBPC3 gene mutations have a specific miRNA expression profile, and that miR-208b-3p is significantly upregulated in cardiac hypertrophy. Our results also indicate that miRNA-208b-3p activates the Wnt signaling pathway through its target gene to promote cardiac hypertrophy.

Myocardial biopsy of Liwen procedure: representability and etiological diagnostic value of cardiac samples obtained by a novel technique in patients with hypertrophic cardiomyopathy

Objective: To investigate the representability and etiological diagnostic value of myocardium samples obtained from patients with hypertrophic cardiomyopathy (HCM) by transthoracic echocardiography-guided percutaneous intramyocardial septal biopsy (myocardial biopsy of Liwen procedure). Methods: This study was a retrospective case-series analysis. Patients with HCM, who underwent myocardial biopsy of Liwen procedure and radiofrequency ablation in Xijing Hospital, Air Force Military Medical University from July to December 2019, were included. Demographic data (age, sex), echocardiographic data and complications were collected through electronic medical record system. The histological and echocardiographic features, pathological characteristics of the biopsied myocardium of the patients were analyzed. Results: A total of 21 patients (aged (51.2±14.5) years and 13 males (61.9%)) were enrolled. The thickness of ventricular septum was (23.3±4.5)mm and the left ventricular outflow tract gradient was (78.8±42.6)mmHg (1 mmHg=0.133 kPa). Eight patients (38.1%) were complicated with hypertension, 1 patient (4.8%) had diabetes, and 2 patients (9.5%) had atrial fibrillation. Hematoxylin-eosin staining of myocardial samples of HCM patients before radiofrequency ablation evidenced myocytes hypertrophy, myocytes disarray, nuclear hyperchromatism, hypertrophy, atypia, coronary microvessel abnormalities, adipocyte infiltration, inflammatory cell infiltration, cytoplasmic vacuoles, lipofuscin deposition. Interstitial fibrosis and replacement fibrosis were detected in Masson stained biopsy samples. Hematoxylin-eosin staining of myocardial samples of HCM patients after radiofrequency ablation showed significantly reduced myocytes, cracked nuclear in myocytes, coagulative necrosis, border disappearance and nuclear fragmentation. Quantitative analysis of myocardial specimens of HCM patients before radiofrequency ablation showed that there were 9 cases (42.9%) with mild myocardial hypertrophy and 12 cases (57.1%) with severe myocardial hypertrophy. Mild, moderate and severe fibrosis were 5 (23.8%), 9 (42.9%) and 7 (33.3%), respectively. Six cases (28.6%) had myocytes disarray. There were 11 cases (52.4%) of coronary microvessel abnormalities, 4 cases (19.0%) of adipocyte infiltration, 2 cases (9.5%) of inflammatory cell infiltration,6 cases (28.5%) of cytoplasmic vacuole, 16 cases (76.2%) of lipofuscin deposition. The diameter of cardiac myocytes was (25.2±2.8)μm, and the percentage of collagen fiber area was 5.2%(3.0%, 14.6%). One patient had severe replacement fibrosis in the myocardium, with a fibrotic area of 67.0%. The rest of the patients had interstitial fibrosis. The myocardial specimens of 13 patients were examined by transmission electron microscopy. All showed increased myofibrils, and 9 cases had disorder of myofibrils. All patients had irregular shape of myocardial nucleus, partial depression, mild mitochondrial swelling, fracture and reduction of mitochondrial crest, and local aggregation of myofibrillary interfascicles. One patient had hypertrophy of cardiomyocytes, but the arrangement of muscle fibers was roughly normal. There were vacuoles in the cytoplasm, and Periodic acid-Schiff staining was positive. Transmission electron microscopy showed large range of glycogen deposition in the cytoplasm, with occasional double membrane surround, which was highly indicative of glycogen storage disease. No deposition of glycolipid substance in lysozyme was observed under transmission electron microscope in all myocardial specimens, which could basically eliminate Fabry disease. No apple green substance was found under polarized light after Congo red staining, which could basically exclude cardiac amyloidosis. Conclusion: Myocardium biopsied samples obtained by Liwen procedure of HCM patients are representative and helpful for the etiological diagnosis of HCM.

Intraoperative myocardial protection in patients with severe myocardial hypertrophy

<h3>ЦЕЛЬ ИССЛЕДОВАНИЯ</h3> Сравнение двух методик защиты миокарда у пациентов с выраженной гипертрофией миокарда, причиной которой явился аортальный стеноз или гипертрофическая кардиомиопатия. <h3>МАТЕРИАЛ И МЕТОДЫ</h3> С января по декабрь 2022 г. прооперированы 17 больных с выраженной гипертрофией миокарда левого желудочка вследствие аортального стеноза или гипертрофической кардиомиопатии. Пациенты рандомизированы на две группы в зависимости от методики кардиоплегии (Дель Нидо и Кустодиол). <h3>РЕЗУЛЬТАТЫ</h3> Получены сопоставимые результаты хирургического лечения в обеих группах относительно частоты осложнений, выживаемости, интраоперационных и ранних послеоперационных показателей. Тяжесть периоперационного ишемического повреждения миокарда по данным морфологических исследований не имела значимых межгрупповых различий. <h3>ВЫВОД</h3> Методика защиты миокарда по Дель Нидо может успешно применяться во взрослой кардиохирургической практике, в т. ч. у больных с тяжелой гипертрофией миокарда.

Cпектр мутаций в генах саркомерных белков и их фенотипическое проявление у белорусских пациентов с гипертрофической кардиомиопатией

Введение. Гипертрофическая кардиомиопатия (ГКМП) относится к наследственной патологии, основной причиной которой являются мутации в генах, кодирующих белковые компоненты миофибрильного аппарата кардиомиоцитов, при этом спектр этих генетических изменений имеет популяционные особенности. Целью данного исследования являлось определение спектра мутаций в генах, кодирующих саркомерные белки, у пациентов с ГКМП из Беларуси, а также изучение взаимосвязей между генотипом и фенотипическими проявлениями заболевания. Материалы и методы. В исследование были включены 340 неродственных пациентов с ГКМП, проживающих в Беларуси. Обнаружение мутаций в кодирующих последовательностях генов ACTC1, MYBPC3, MYH7, MYL2, MYL3, TNNI3, TNNT2, TNNС1 и TPM1 у 89 пациентов проводили методом высокопроизводительного секвенирования (NGS). Направленный поиск выявленных методом NGS генетических дефектов осуществлялся методом автоматического секвенирования по Сэнгеру, а также с использованием ПЦР-ПДРФ анализа. Результаты. У 51,7% пациентов методом NGS обнаружены мутации в генах: MYBPC3 (20,2%), MYH7 (16,9%), TPM1 (3,4%), ACTC1 (2,3%), MYL2 (1,1%) и TNNC1 (1,1%). У 6,7% индивидуумов встречались две (5,6%) или три (1,1%) замены. Обнаружены новые мутации p.Ala49Asn, p.Val1407Phe в гене MYH7; р.Tyr501Ser, р.Trp1007fs, р.Tyr1043*, р.Pro1066Arg, p.Arg1138fs, р.Pro1181Gln, р.Cys1202Arg в гене MYBPC3. Установлены часто встречающиеся мутации: р.Gln1233*, р.Ser871Alafs, комбинация р.Glu1265Val+р.Cys1266Arg, р.Gln401* и р.Trp1214Arg в гене MYBPC3, p.Arg403Trp, p.Arg663Cys, p.Arg663His, p.Ala729Pro, p.Glu924Lys и p.Glu1356Lys в гене MYH7. По данным ЭхоКГ-исследования носители мутаций в генах белков саркомера, особенно обладатели миссенс-мутаций в гене MYBPC3, имели более выраженную гипертрофию миокарда и раннюю манифестацию заболевания по сравнению с пациентами без мутаций в этих генах. Для носителей наиболее распространенной среди белорусских пациентов мутации р.Gln1233* характерны позднее начало заболевания, умеренная гипертрофия миокарда левого желудочка, частое развитие фибрилляции предсердий. Выводы. Распределение встречаемости мутаций в генах, кодирующих саркомерные белки, у пациентов с ГКМП из Беларуси не отличалось от других европейских популяций. 84,9% обнаруженных мутаций локализовано в генах MYBPC3 и MYH7. Background. Hypertrophic cardiomyopathy (HCM) is a hereditary pathology, the main cause of which is mutations in the genes encoding the protein components of the myofibril apparatus of cardiomyocytes, and the spectrum of these genetic changes has population features. The aim of the study was to determine the spectrum of mutations in the genes encoding sarcomeric proteins in patients with HCM from Belarus, as well as to study the association between the genotype and the phenotypic manifestations of the disease. Materials and methods. The study included 340 unrelated patients with HCM from Belarus. Mutation detection in the coding sequences of ACTC1, MYBPC3, MYH7, MYL2, MYL3, TNNI3, TNNT2, TNNС1 и TPM1 genes was performed by next generation sequencing (NGS) in 89 patients. The directed search for genetic defects detected by the NGS method was carried out by the automatic sequencing method using Sanger and PCR-RFLP analysis. Results. The NGS method allowed to detect mutations in the genes of 51,7% of patients: MYBPC3 (20,2%), MYH7 (16,9%), TPM1 (3,4%), ACTC1 (2,3%), MYL2 (1,1 %) and TNNC1 (1,1%). In 6,7% of individuals two (5,6%) or three (1,1%) substitutions were observed. New mutations were found: p.Ala49Asn, p.Val1407Phe in the MYH7 gene; p.Tyr501Ser, p.Trp1007fs, p.Tyr1043*, p.Pro1066Arg, p.Arg1138fs, p.Pro1181Gln, р.Cys1202Arg in the MYBPC3 gene. The most frequently occurring mutations were identified: p.Gln1233*, p.Ser871Alafs, the combination of the р.Glu1265Val + p.Cys1266Arg, R.Gln401*, and Trp1214Arg in the MYBPC3 gene, p.Glu924Lys and p.Glu1356Lys in the MYH7 gene. According to the ECG study, carriers of mutations in sarcomere protein genes, especially with missense mutations in the MYBPC3 gene, had more severe myocardial hypertrophy and early disease manifestation then patients without mutations in those genes. The p.Gln1233* mutation was the most common among Belarusian patients and characterized by late onset of the disease, mild left ventricular myocardial hypertrophy and the more frequent development of atrial fibrillation. Conclusions. In general, the distribution of mutations in the genes encoding sarcomeric proteins in patients with HCM from Belarus didn’t differ from other European populations. 84,9% of the detected mutations were localized in MYBPC3 and MYH7 genes.

Comparison of effect of antegrade with combined antegrade/retrograde cardioplegia on inflammatory response and left ventricular systolic function in coronary bypass surgery: a prospective randomized study

Aim: Nonhomogeneous distribution of antegrade cardioplegia especially in cases with severe myocardial hypertrophy or proximal stenosis of coronary arteries may be a serious problem. This prospective randomized study was designed to determine whether combined antegrade–retrograde cardioplegia provides improved myocardial protection in the early period and is associated with better laboratory results compared with antegrade technique alone.Material and Methods: A total of 60 patients who underwent coronary artery bypass grafting surgery, 45 (75%) males and 15 (25%) females, were included in the study as 2 groups: In Group 1, 30 patients were given the combined cardioplegia solution antegrade via the aortic root and retrograde via the coronary sinus, in Group 2, 30 patients were given only antegrade cardioplegia solution via the aortic root. The CK-MB, TpI, TNF- α, IL-1, IMA, ICAM-1, and BNP parameters were studied in the blood samples which were taken preoperatively, intraoperatively and postoperative sixth day. The patients were evaluated preoperatively and on the sixth postoperative day using transthoracic echocardiography.Results: The postoperative mean EF decrease was significantly lower in Group 1 compared to Group 2 (4.13 ± 9.09 vs 8.90 ± 10.76 in Group 1 vs. Group 2, respectively, p=0.046). When the change in TNF-α levels were compared between groups 1 and 2, the magnitude of increase in TNF-α was significantly higher in Group 2 (p=0.047). Conclusion: We concluded that co-administration of antegrade and retrograde cardioplegia may provide improved myocardial protection compared to antegrade cardioplegia method alone in the early postoperative period.

CARDIOMYOPATHY IN THE FRIEDREICH ATAXIA: CLINICAL PRESENTATION AND DIAGNOSTICS OF COMPLICATIONS

Friedreich’s ataxia (FA) is one of the most prevalent variants of the inherited ataxias. The disease is characterized by complicated phenotype that includes neurological signs (ataxia, sensory polyneuropathy, dysarthria, disorders of deep sensitivity, areflexia, pyramid symptoms with lower extremities involvement, vegetative disorders, sometimes — psychopathological symptoms), cardiological disorders (cardiomyopathy, heart failure, arrhythmias), and disorders of carbohydrate metabolism, and skeletal deformities. If neurological disorders lead to significant decrease of life quality and disability, cardiovascular complications are the main cause of fatal outcome in FA. It is worthy to mention that involvement of the heart into pathological process might long remain undiagnosed. Recently, most of abroad and local publications on FA are related to neurological presentation. Cardiovascular side of the problem in the scientific society remains underestimated, regardless the risk of sudden death and of heart failure (due to symmetric myocardial hypertrophy with the areas of intramyocardial fibrosis) being high. We present clinical and genetic observation of a 27-year old patient with FA, moderate neurological disorders and severe myocardial hypertrophy. The article is focused on the contemporary clinical and diagnostic aspects of FA associated cardiomyopathy.

Limited Ventricular Preload is the Main Reason for Reduced Stress Reserve After Atrial Baffle Repair.

The atrial baffle repair (ABR) significantly improved the fate of patients with transposition of the great arteries (TGA). However, these patients show impaired exercise tolerance and some present severe decline of systemic ventricular function. Intrinsic myocardial weakness, low heart rate response to exercise and diastolic filling impairment are discussed to be causative. Forty-nine long-term survivors with TGA (median age 23.7year) after ABR were catheterized with measured oxygen consumption in four conditions (baseline, volume, atrial pacing, dobutamine) and the results were compared to 10 normal controls. Median cardiac output was significantly lower in the ABR group (2.2 vs. 2.6l/min/m2; p=0.015), and systemic resistance was significantly elevated (28.9 vs. 22.2 Um2; p=0.04) in comparison with normals. While stroke volume rose by 27% in the control group, it dropped by 7% in patients after ABR at atrial pacing (80/min). Stroke volume increase after dobutamine was significantly lower after ABR in comparison with normal controls (34 vs. 106%; p=0.001). Higher NYHA class (p=0.043), degree of tricuspid regurgitation (p=0.009) and ventricular function (p=0.028) were associated with lower stroke volume increase. Limited exercise capability of patients after ABR for TGA is primarily due to limited diastolic filling of the ventricles due to stiff non-compliant atrial pathways. Elevated systemic resistance may lead to severe myocardial hypertrophy with possible ischemia and contribute to the multifactorial decline of ventricular function in some patients.

The CarboMedics supra-annular Top Hat valve improves long-term left ventricular mass regression

The present study aimed to identify potential differences in hemodynamic performance between the supra-annular CarboMedics Top Hat valve and the intra-annular CarboMedics standard valve in terms of the long-term left ventricular mass reduction and transvalvular gradients. We retrospectively reviewed a series of 186 consecutive patients who had undergone aortic valve replacement with a small size mechanical prosthesis at our institution from 2003 to 2013, receiving either a CarboMedics Top Hat valve (53 patients, valve size, 21 mm in 52.8% and 23 mm in 47.2%) or a CarboMedics standard prosthesis (133 patients, valve size, 19 mm in 14.3% and 21 mm in 85.7%). The in-hospital mortality was 9.4% and 11.3% in the Top Hat and standard groups, respectively (P = .71). The mean percentage of left ventricular mass reduction was greater in the Top Hat group (33% ± 15.8% vs 20.1% ± 16.6%, P < .001). The mean postoperative peak aortic gradient was lower in the Top Hat group (19.9 ± 8.9 vs 29.6 ± 8.6 mm Hg; P < .001). Spearman analysis showed a positive correlation between the indexed effective orifice area and the percentage of left ventricular mass reduction (Rho = +0.65, P = .02). The survival in the Top Hat group was 79.7% and 71.7% at 5 and 10 years, respectively. In the standard group, survival was 66.8% and 61.5% at 5 and 10 years, respectively (log-rank test, 0.19). Cox regression demonstrated severe myocardial hypertrophy (hazard ratio, 2.559; 95% confidence interval, 1.095-5.981) as one of the independent predictors of survival. The Top Hat valve surpasses hemodynamically the intra-annular valve. We suggest the supra-annular Top Hat prosthesis can be especially recommended for patients with a small aortic root and severe myocardial hypertrophy.

Post-Mortem Cardiac 3-T Magnetic Resonance Imaging: Visualization of Sudden Cardiac Death?

This study aimed to investigate post-mortem magnetic resonance imaging (pmMRI) for the assessment of myocardial infarction and hypointensities on post-mortem T2-weighted images as a possible method for visualizing the myocardial origin of arrhythmic sudden cardiac death. Sudden cardiac death has challenged clinical and forensic pathologists for decades because verification on post-mortem autopsy is not possible. pmMRI as an autopsy-supporting examination technique has been shown tovisualize different stages of myocardial infarction. In 136 human forensic corpses, a post-mortem cardiac MR examination was carried out prior to forensic autopsy. Short-axis and horizontal long-axis images were acquired in situ on a 3-T system. In 76 cases, myocardial findings could be documented and correlated to the autopsy findings. Within these 76 study cases, a total of 124 myocardial lesions were detected on pmMRI (chronic: 25; subacute: 16; acute: 30; and peracute: 53). Chronic, subacute, and acute infarction cases correlated excellently to the myocardial findings on autopsy. Peracute infarctions (age range: minutes to approximately 1 h) were not visible on macroscopic autopsy or histological examination. Peracute infarction areas detected on pmMRI could be verified in targeted histological investigations in 62.3% of cases and could be related to a matching coronary finding in 84.9%. A total of 15.1% of peracute lesions on pmMRI lacked a matching coronary finding but presented with severe myocardial hypertrophy or cocaine intoxication facilitating a cardiac death without verifiable coronary stenosis. 3-T pmMRI visualizes chronic, subacute, and acute myocardial infarction in situ. In peracute infarction as a possible cause of sudden cardiac death, it demonstrates affected myocardial areas not visible on autopsy. pmMRI should be considered as a feasible post-mortem investigation technique for the deceased patient if no consent for a clinical autopsy is obtained.

Danon disease presenting as severe myocardial hypertrophy

A 15-year-old boy presented with abnormal electrocardiogram on regular examination, which showed left ventricular hypertrophy and a Wolff–Parkinson–White pre-excitation pattern. Clinical examination displayed mild limb muscle weakness and atrophy and slight mental retardation. Laboratory testing revealed increased plasma creatine kinase …

Neurosciences on Everest

This study aimed to investigate post-mortem magnetic resonance imaging (pmMRI) for the assessment of myocardial infarction and hypointensities on post-mortem T2-weighted images as a possible method for visualizing the myocardial origin of arrhythmic sudden cardiac death.Sudden cardiac death has challenged clinical and forensic pathologists for decades because verification on post-mortem autopsy is not possible. pmMRI as an autopsy-supporting examination technique has been shown to visualize different stages of myocardial infarction.In 136 human forensic corpses, a post-mortem cardiac MR examination was carried out prior to forensic autopsy. Short-axis and horizontal long-axis images were acquired in situ on a 3-T system.In 76 cases, myocardial findings could be documented and correlated to the autopsy findings. Within these 76 study cases, a total of 124 myocardial lesions were detected on pmMRI (chronic: 25; subacute: 16; acute: 30; and peracute: 53). Chronic, subacute, and acute infarction cases correlated excellently to the myocardial findings on autopsy. Peracute infarctions (age range: minutes to approximately 1 h) were not visible on macroscopic autopsy or histological examination. Peracute infarction areas detected on pmMRI could be verified in targeted histological investigations in 62.3% of cases and could be related to a matching coronary finding in 84.9%. A total of 15.1% of peracute lesions on pmMRI lacked a matching coronary finding but presented with severe myocardial hypertrophy or cocaine intoxication facilitating a cardiac death without verifiable coronary stenosis.3-T pmMRI visualizes chronic, subacute, and acute myocardial infarction in situ. In peracute infarction as a possible cause of sudden cardiac death, it demonstrates affected myocardial areas not visible on autopsy. pmMRI should be considered as a feasible post-mortem investigation technique for the deceased patient if no consent for a clinical autopsy is obtained.

Comments on imaging and management of hepatic hemangiomas

Sir, I read with interest the case report by van der Meijs and colleagues [1] regarding a neonate with an extensive “hepatic hemangioendothelioma.” I would like to congratulate the authors for their relentless attempts to help this patient and for reporting their experience. While one cannot argue in principle with the diagnosis of liver hemangioma and the major systemic and local burden of this extensive lesion, I would disagree with some of the management measures provided to this child. There are a few key points on which I would like to comment. First, the proper name for these benign liver tumors is simply “liver hemangiomas”. This name was adopted by the International Society for the Study of Vascular Anomalies based on the classification of vascular anomalies by Mulliken and Glowacki in 1982 [2]. “Hemangioendothelioma” of the liver typically refers to the adult-onset hepatic epithelioid hemangioendothelioma, a rare vascular mesenchymal neoplasm with borderline malignant potential [3]. Though still in common use in the published literature, using this term to refer to the commonly encountered infantile lesions can be confusing and is better avoided in favor of “liver hemangioma.” Second, a CT-guided biopsy was performed on this child before an MRI study was obtained. Liver hemangiomas, as the authors demonstrated with the Doppler US study, are very vascular and percutaneous biopsies carry a significant risk of bleeding, especially if the infant is coagulopathic. The MR imaging features, shown in Fig. 2, are classic for liver hemangiomas. Had the MRI study been performed earlier, the biopsy could have been entirely avoided. The deterioration of the clinical status which developed following the liver biopsy still could have been related to bleeding. The authors stated that “the possibility of a bleed as a result of the biopsy was excluded,” without providing any further details. Bleeding can occur within the lesion and cause serious distension and consumptive coagulopathy. Regarding the alpha-fetoprotein (AFP) level in this neonate, it is worth mentioning that the AFP reference range for normal, full-term neonates and infants is 105–22,000 μg/l [4]. The AFP level of 42,683 μg/ l reported in this paper might be within the normal range and does not, based on this number alone, justify performing a biopsy. The authors’ description of the lesions as “partially cystic” is one of the commonly seen inaccuracies with US studies for liver hemangiomas. The “involuting” center of these lesions can be quite hypoechoic and frequently mistaken for cystic changes. As demonstrated by the MR image provided, the lesions were completely solid. In an attempt to achieve a rapid decrease in tumor size, the authors started the neonate on high-dose prednisone. Why not initiate steroid treatment as early as the diagnosis was made? In addition, the patient was simultaneously given vincristine. The patient developed severe side effects to this treatment (pulmonary hypertension and severe myocardial hypertrophy). It is unclear if or when these drugs were discontinued. Four days following the initiation of medical treatment the authors repeated the MRI study, which demonstrated no response. The more commonly followed protocol is to examine the patient for evidence of regression (or stabilization) of the hemangioma 2 weeks after the initiation Pediatr Radiol (2009) 39:637–638 DOI 10.1007/s00247-009-1244-3

Surgical Treatment of Hypertrophic Obstructive Cardiomyopathy in Pediatric Patients With Severe Hypertrophy

We have undertaken a study over a period of 5 years on 35 hypertrophic obstructive cardiomyopathy (HOCM) patients with severe hypertrophy in the age range between 8 and 15 years. The indication for surgery was based on the diagnosis of severe myocardial hypertrophy in association with serious cardiac failure (New York Heart Association class III or IV) or elevated intraventricular pressure gradients refractory to medical therapy. Furthermore, patients were considered for operation if they met a history of sudden death within their families. A new technique of HOCM surgical correction in pediatric patients with severe hypertrophy was proposed. Conceptually, this approach offers a number of advantages: it affords the excision of the asymmetrically hypertrophied area of the ventricular septum without penetration into the left ventricle cavity; it avoids mechanical damage to the heart conduction system and aortic valve; and for the surgeon, it improves visual inspection of the area to be resected. Here, we describe the disease history of 35 patients, their diagnostic evaluations, the surgical procedure, and the postoperational observations as well as the results of follow-up assessments. We state that the surgery was successful in all 35 cases. There were no early or late deaths. Acute postoperative pericarditis developed in three patients early after surgery. The follow-up period was 38 +/- 7 months, and complications were not observed so far.

Adenosine stress first pass perfusion for the detection of coronary artery disease in patients with aortic stenosis: a feasibility study

Detection of coronary artery disease (CAD) with magnetic resonance imaging (MRI) using adenosine stress first pass perfusion in patients with aortic stenosis in comparison with invasive angiography. Twenty-three consecutive patients (15 male, mean age 68 +/- 12 years) with relevant aortic stenosis (aortic valve area 0.90 +/- 0.41 cm(2)) were examined by MRI (1.5 T, Philips Intera CV). Contrast-enhanced first pass perfusion was performed with adenosine stress (140 microg/kg/min) and under rest conditions. The results were compared with invasive coronary angiography with regard to the presence of a relevant coronary artery stenosis (>70%). Three of 23 patients (13%) had contraindications for adenosine administration (one patient with atrioventricular block, two patients with mild claustrophobia). In the remaining 20 patients, adenosine stress perfusion could be performed without any complications. CAD was correctly detected in eight patients and correctly ruled out in 10 of 12 patients. False-positive results were seen in two patients with severe myocardial hypertrophy. Sensitivity, specificity, positive predictive value, and negative predictive value were 100%, 80%, 83%, and 100%, respectively. Adenosine stress perfusion can be performed without complications even in patients with high grade aortic stenosis. MRI is helpful to detect and rule out significant CAD in these patients. Severe myocardial hypertrophy may lead to false-positive results. Our initial results indicate that due to a high negative predictive value pre-operative invasive coronary angiography might probably be waived in patients without perfusion defects in stress MRI.