Case report of Barth syndrome: a forgotten cause of cardiomyopathy

Background Barth syndrome (BTHS) is a rare X-linked recessive disorder characterized by clinical features including cardiomyopathy, skeletal myopathy, neutropenia, growth delay, and exercise intolerance. It is often considered to be a paediatric disease, owing to most cases being diagnosed during childhood and mortality being the highest during the first few years of life. Case summary We report a case of dilated cardiomyopathy due to BTHS in a 27-year-old adult male patient, who initially presented with lightheadedness, dyspnoea, orthopnoea, and bilateral lower extremity oedema. Key findings from investigations included leukopenia, prolonged QTc interval, reduced left ventricular ejection fraction (LVEF), global enlargement of all heart chambers, patent coronary arteries, and mild pulmonary hypertension. The patient was diuresed to euvolemia and discharged with a LifeVest. Guideline-directed medical therapy was initiated and uptitrated as an outpatient. A repeat echocardiogram 2 years after initial presentation showed marked improvement in LVEF. Discussion It is possible that there are adult patients with idiopathic cardiomyopathy, which may be attributable to BTHS. In the absence of an obvious underlying cause, with the appropriate historical information, clinical exam, laboratory investigations, and imaging findings, BTHS should be considered as a likely cause of non-ischaemic cardiomyopathy.

Prognostic impact of subcutaneous implantable cardioverter-defibrillator appropriate and inappropriate shocks

Funding Acknowledgements Type of funding sources: None. Background Previous studies have shown an adverse prognosis for patients with transvenous implantable cardioverter-defibrillators (ICD) who receive both appropriate and inappropriate shocks. There is a paucity of data regarding the prognosis of inappropriate shocks in patients with a subcutaneous ICD (S-ICD). Purpose To assess and characterize S-ICD appropriate (AS) and inappropriate shocks (IAS) and their impact on mortality. Methods Single center observational registry of 162 consecutive patients who underwent S-ICD implantation for primary and secondary prevention between November 2009 and September 2020. Only follow-up data of at least 6 months was analysed to identify predictors of both IAS and AS and their mortality impact. Results A total of 144 patients were included in the analysis. Mean age was 42.2 ± 16.6 years and 75% of the patients were male. One hundred and four patients (72.2%) implanted the S-ICD in primary prevention. The most common etiology was ischemic cardiomyopathy (22.9%) followed by hypertrophic cardiomyopathy (18.8%) and dilated idiopathic cardiomyopathy (14.6%). During a mean follow-up of 42.3 ± 29.9 months a total of 48 patients (33.3%) experienced at least one S-ICD shock. Twenty-nine (20.1%) patients received AS due to VT/VF and 31 patients (21.5%) received IAS. Eighteen (58.1%) of the IAS were due to oversensing/noise/discrimination errors and the remaining due to supraventricular tachycardia. Overall, patients with AS (HR 4.93, 95% CI 1.58-15.36, p = 0.006) and higher number of total AS (HR 1.10, 95% CI 1.00-1.20, p = 0.044) were associated with higher mortality during follow-up. S-ICD IAS therapy did not affect overall mortality (HR 1.71, 95% CI 0.21-14.0, p = 0.616). Conclusions: In patients with S-ICD, those who receive AS, in contrast to IAS, seem to have a worse prognosis. Large scale studies are needed to confirm this hypothesis and to explain this findings. Abstract Figure. Survival curves for AS and IAS

Genetic Causes of Cardiomyopathy in Children: First Results From the Pediatric Cardiomyopathy Genes Study

Background Pediatric cardiomyopathy is a genetically heterogeneous disease with substantial morbidity and mortality. Current guidelines recommend genetic testing in children with hypertrophic, dilated, or restrictive cardiomyopathy, but practice variations exist. Robust data on clinical testing practices and diagnostic yield in children are lacking. This study aimed to identify the genetic causes of cardiomyopathy in children and to investigate clinical genetic testing practices. Methods and Results Children with familial or idiopathic cardiomyopathy were enrolled from 14 institutions in North America. Probands underwent exome sequencing. Rare sequence variants in 37 known cardiomyopathy genes were assessed for pathogenicity using consensus clinical interpretation guidelines. Of the 152 enrolled probands, 41% had a family history of cardiomyopathy. Of 81 (53%) who had undergone clinical genetic testing for cardiomyopathy before enrollment, 39 (48%) had a positive result. Genetic testing rates varied from 0% to 97% between sites. A positive family history and hypertrophic cardiomyopathy subtype were associated with increased likelihood of genetic testing ( P =0.005 and P =0.03, respectively). A molecular cause was identified in an additional 21% of the 63 children who did not undergo clinical testing, with positive results identified in both familial and idiopathic cases and across all phenotypic subtypes. Conclusions A definitive molecular genetic diagnosis can be made in a substantial proportion of children for whom the cause and heritable nature of their cardiomyopathy was previously unknown. Practice variations in genetic testing are great and should be reduced. Improvements can be made in comprehensive cardiac screening and predictive genetic testing in first‐degree relatives. Overall, our results support use of routine genetic testing in cases of both familial and idiopathic cardiomyopathy. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01873963.

Association of ADRB1 gene polymorphism with dilated cardiomyopathy

Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Prof. V.F. Voino-Yasenetsky Krasnoyarsk State Medical University Aim. To evaluate the Association of rs1801252 polymorphism of the ADRB1 gene with dilated idiopathic cardiomyopathy (DCMP) and myocardial dilation of ischemic origin (DMI). Subjects and methods. The study included patients with ICMP and MD IG in the number of 221 people. The average age of the subjects was in the range of 55.30 ± 9.69 years. We divided the patients into 2 groups: the first – patients diagnosed with idiopathic dilatation cardiomyopathy and the second-patients with myocardial dilatation of ichemic origin. The number of patients in the first group was 111, including 99 men (89.2%) and 12 women (10.8%). The average age of patients in this group is 51.73 ± 9.74 years, in men 51.00 ± 8.96 years, in women 57.75 ± 3.71 years. The second group included patients with myocardial dilatation of ischemic origin. Their number is 110 people, including 100 men (91.5%) and 10 women (8.5%). The average age of respondents is 58.68 ± 8.38 years, for men 58.29 ± 8.46 years, for women 62.90 ± 6.29 years. The control group included patients who had no manifestations of cardiovascular diseases. Their number is 121 people (average age 53.6 ± 4.8 years). The patients underwent laboratory and instrumental studies, as well as molecular and genetic studies of the A145G polymorphism of the ADRB1 gene (rs1801252 ). All patients underwent coronary angiography. Based on the anamnesis data and instrumental studies, those patients who could be said to have no risk factors for the development of dilatation of the heart cavities were identified in the first group. And those patients who were reliably diagnosed with CHD were in the second group, that is, dilatation of the heart cavities is due to a previous myocardial infarction, existing angina pectoris. Results. In the group with DCMP 70.3% of patients were carriers of the common homozygous A145A genotype, the heterozygous A145G genotype-27.0%, and the rare homozygous G145G genotype-2.7%. In the control group 71.9% of patients were identified as carriers of a homozygous genotype by a common allele, and 25.3% were carriers heterozygous genotype, and homozygous genotype for a rare allele – 2.7%. Statistical analysis showed no achievement of statistical significance level across any of the genotypes. In the group with DM IG, there was no association with the rs1801252 polymorphism of the ADRB1 gene. Conclusion. A statistically significant association of rs1801252 of the ADRB1 gene with DCMP was not found. The association of DM IG c rs1801252 could not be confirmed.

Association of CTLA4 gene polymorphism with dilated cardiomyopathy

Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Prof. V.F. Voino-Yasenetsky Krasnoyarsk State Medical University Aim. To evaluate the Association of rs231775 polymorphism of the CTLA4 gene with dilated idiopathic cardiomyopathy (DCMP) and myocardial dilation of ischemic origin (DMI). Subjects and methods. The study included patients with ICMP and DMI in the number of 221 people. The average age of the subjects was in the range of 55.30 ± 9.69 years. We divided the patients into 2 groups: the first – patients diagnosed with idiopathic dilatation cardiomyopathy and the second-patients with myocardial dilatation of ichemic origin. The number of patients in the first group was 111, including 99 men (89.2%) and 12 women (10.8%). The average age of patients in this group is 51.73 ± 9.74 years, in men 51.00 ± 8.96 years, in women 57.75 ± 3.71 years. The second group included patients with myocardial dilatation of ischemic origin. Their number is 110 people, including 100 men (91.5%) and 10 women (8.5%). The average age of respondents is 58.68 ± 8.38 years, for men 58.29 ± 8.46 years, for women 62.90 ± 6.29 years. The control group included patients who had no manifestations of cardiovascular diseases. Their number is 121 people (average age 53.6 ± 4.8 years). The patients underwent laboratory and instrumental studies, as well as molecular and genetic studies of the 49A/G polymorphism of the CTLA4 gene (rs231775). All patients underwent coronary angiography. Based on the anamnesis data and instrumental studies, those patients who could be said to have no risk factors for the development of dilatation of the heart cavities were identified in the first group. And those patients who were reliably diagnosed with CHD were in the second group, that is, dilatation of the heart cavities is due to a previous myocardial infarction, existing angina pectoris. Results. In the group with DCMP 34.2% of patients were carriers of the common homozygous 49AA genotype, the heterozygous 49AG genotype-48.6%, and the rare homozygous 49GG genotype-17.1%. In the control group 33.5% of patients were identified as carriers of a homozygous genotype by a common allele, and 49.3% were carriers heterozygous genotype, and homozygous genotype for a rare allele – 17.2%. The analysis revealed a statistically non significant increase in the frequency of carrying the homozygous AA genotype in patients with DCMP compared to the control group of the rs231775 polymorphism of the CTLA4 gene. In the group with DMI, there was no association with the rs231775 polymorphism of the CTLA4 gene. Conclusion. A statistically significant association of rs231775 of the CTLA4 gene with DCMP was not found. The association of DMI c rs231775 could not be confirmed.

Association of ADRB2 gene polymorphism with dilated cardiomyopathy

Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Prof. V.F. Voino-Yasenetsky Krasnoyarsk State Medical University Aim. To evaluate the Association of rs1042713 polymorphism of the ADRB2 gene with dilated idiopathic cardiomyopathy (DCMP) and myocardial dilation of ischemic origin (DMI). Subjects and methods. The study included patients with ICMP and DMI in the number of 221 people. The average age of the subjects was in the range of 55.30 ± 9.69 years. We divided the patients into 2 groups: the first – patients diagnosed with idiopathic dilatation cardiomyopathy and the second-patients with myocardial dilatation of ichemic origin. The number of patients in the first group was 111, including 99 men (89.2%) and 12 women (10.8%). The average age of patients in this group is 51.73 ± 9.74 years, in men 51.00 ± 8.96 years, in women 57.75 ± 3.71 years. The second group included patients with myocardial dilatation of ischemic origin. Their number is 110 people, including 100 men (91.5%) and 10 women (8.5%). The average age of respondents is 58.68 ± 8.38 years, for men 58.29 ± 8.46 years, for women 62.90 ± 6.29 years. The control group included patients who had no manifestations of cardiovascular diseases. Their number is 121 people (average age 53.6 ± 4.8 years). The patients underwent laboratory and instrumental studies, as well as molecular and genetic studies of the 16 AG polymorphism of the ADRB2 gene (rs1042713). All patients underwent coronary angiography. Based on the anamnesis data and instrumental studies, those patients who could be said to have no risk factors for the development of dilatation of the heart cavities were identified in the first group. And those patients who were reliably diagnosed with CHD were in the second group, that is, dilatation of the heart cavities is due to a previous myocardial infarction, existing angina pectoris. Results. In the group with DCMP 10.8% of patients were carriers of the common homozygous 16AA genotype, the heterozygous 16AG genotype-48.6%, and the rare homozygous 16GG genotype-40.5%. In the control group 11.8% of patients were identified as carriers of a homozygous genotype by a common allele, and 47.5% were carriers heterozygous genotype, and homozygous genotype for a rare allele – 40.7%. The analysis non revealed a statistically significant decrease in the frequency of carrying the homozygous 16GG genotype in patients with DCMP compared to the control group of the rs1042713 polymorphism of the ADRB2 gene. In the group with DM IG, there was no association with the rs1042713 polymorphism of the ADRB2 gene. Conclusion. A statistically significant association of rs1042713 of the ADRB2 gene with DCMP was not found. The association of DMI c rs1042713 could not be confirmed.

Association of SCN5A gene polymorphism with dilated cardiomyopathy

Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Prof. V.F. Voino-Yasenetsky Krasnoyarsk State Medical University Aim. To evaluate the Association of rs1805124 polymorphism of the SCN5A gene with dilated idiopathic cardiomyopathy (DCMP) and myocardial dilation of ischemic origin (DMI). Subjects and methods. The study included patients with ICMP and MD IG in the number of 221 people. The average age of the subjects was in the range of 55.30 ± 9.69 years. We divided the patients into 2 groups: the first – patients diagnosed with idiopathic dilatation cardiomyopathy and the second-patients with myocardial dilatation of ichemic origin. The number of patients in the first group was 111, including 99 men (89.2%) and 12 women (10.8%). The average age of patients in this group is 51.73 ± 9.74 years, in men 51.00 ± 8.96 years, in women 57.75 ± 3.71 years. The second group included patients with myocardial dilatation of ischemic origin. Their number is 110 people, including 100 men (91.5%) and 10 women (8.5%). The average age of respondents is 58.68 ± 8.38 years, for men 58.29 ± 8.46 years, for women 62.90 ± 6.29 years. The control group included patients who had no manifestations of cardiovascular diseases. Their number is 121 people (average age 53.6 ± 4.8 years). The patients underwent laboratory and instrumental studies, as well as molecular and genetic studies of the A/G polymorphism of the SCN5A gene (rs 1805124). All patients underwent coronary angiography. Based on the anamnesis data and instrumental studies, those patients who could be said to have no risk factors for the development of dilatation of the heart cavities were identified in the first group. And those patients who were reliably diagnosed with CHD were in the second group, that is, dilatation of the heart cavities is due to a previous myocardial infarction, existing angina pectoris. Results. In the group with DCMP 51.4% of patients were carriers of the common homozygous AA genotype, the heterozygous AG genotype-40.5%, and the rare homozygous GG genotype-8.1%. In the control group 63.3% of patients were identified as carriers of a homozygous genotype by a common allele, and 33.5% were carriers heterozygous genotype, and homozygous genotype for a rare allele – 3.2%. The analysis revealed a statistically significant decrease in the frequency of carrying the homozygous AA genotype in patients with DCMP compared to the control group of the rs1805124 polymorphism of the SCN5A gene. In the group with DM IG, there was no association with the rs1805124 polymorphism of the SCN5A gene. Conclusion. A statistically significant Association of rs1805124 of the SCN5A gene with DCMP was found. The Association of DM IG c rs1805124 could not be confirmed.

Kardiomiopati Peripartum: Manajemen Anestesi Terbaru

Kardiomiopati peripartum (KMPP) atau Peripartum cardiomyopathy (PPCM) adalah kelainan jantung idiopatik dengan karakteristik disfungsi sistolik dan simptom gagal jantung pada akhir masa kehamilan atau beberapa bulan setelah kehamilan tanpa sebab lain yang mengancam jiwa maternal dengan risiko morbiditas dan mortalitas postpartum cukup tinggi. Penelitian terbaru dalam pemahaman tentang patofisiologi PPCM menunjukkan proses yang melibatkan faktor endotel dan faktor toksik kardio, seperti sFlt-1 dan 16 kDa prolaktin, sehingga kemampuan jantung beradaptasi terhadap kehamilan normal terlampaui pada ibu yang sudah rentan terhadap serangan jantung. Terapi spesifik PPCM belum dapat ditentukan. Bromokriptin yang bekerja memblok pelepasan prolaktin dari glandula pituitaria, pada beberapa penelitian awal menghasilkan perbaikan fraksi ejeksi ventrikel kiri secara bermakna. Penelitian lebih lanjut dengan jumlah sampel yang lebih besar masih harus dilakukan untuk terapi ini. Prinsip manajemen direkomendasikan sesuai dengan patofisiologi yang terjadi. Optimalisasi atau reduksi preload baik dengan reduksi natrium maupun cairan dan penggunaan diuretika, menurunkan afterload dengan vasodilator, dan memperbaiki kontraktilitas jantung dengan inotropik, dromotropik, atau inodilator adalah strategi utama yang direkomendasikan. Tidak ada perubahan strategi dalam manajemen terapi ini, tetapi pilihan teknik anestesi saat ini lebih berkembang ke analgesi/anestesi regional. Pemahaman penggunaan dosis dan konsentrasi anestetika lokal menjadi penting untuk mencapai target dalam strategi yang direkomendasikan. Peripartum Cardiomyopathy: Update in Anesthesia Management Abstract Peripatum cardiomyopathy (PPCM) is an idiopathic cardiomyopathy presenting with heart failure secondary to left ventricle systolic dysfunction towards the end of pregnancy or in the months following delivery, where no other cause for heart failure is identified, life-threatening, and postpartum high morbidity and mortality risk. Recent studies in the understanding of PPCM pathophysiology indicate that there’s processes involving endothelial and cardio-toxic factors such as e.g. sFlt-1 and 16 kDa prolactin, leading the heart’s capacity to adapt to a normal pregnancy may be exceeded in some women already susceptible to cardiac insult. Spesific therapy for PPCM can not be determined. Bromocriptine that blocks the release of a hormone called prolactine from the pituitary gland in some preliminary studies improved left ventricular ejection fraction significantly. Further research with larger sample size remains to be done for this therapy. Management principles for PPCM are recommended in accordance with the pathophysiology. Depending on the volume status, preload has to be optimized by either fluid administration or sodium restriction and diuretics, decrease afterload using vasodilator, and improve contractility by using inotropic, dromotropic, or inodilator are the main strategies. There is no change in management strategy for PPCM, but regional analgesia/anesthesia preferably for now. Understanding the dose and concentration administration of local anesthethic drugs are important to achieve targets recommendation.

Expression of Interleukin 1, Interleukin 27 and TNF α Genes in Patients with Ischemic Cardiomyopathy Versus Idiopathic Dilated Cardiomyopathy

Objective: Congestive Heart failure (CHF) is a complex multifactorial syndrome due to tissue hypo perfusion that is affected by some factors like inflammatory cytokines. In our study we investigated the exact gene expression of three inflammatory cytokines in ischemic and idiopathic cardiomyopathy patients.Materials and Methods: From 49 studied recipients in ischemic group, 23 (46.9%) were male and from 40 studied recipients in idiopathic dilated cardiomyopathy group, 19 (47.5%) were male. For the quantitative analysis of Interleukin (IL)1, IL-27 and TNF-α mRNAs expression level, the SYBR Green Real-Time PCR method was performed using SYBRPremix Ex TaqTM II (Tli RNaseH Plus) (Takara, Japan) and designed primers specific for each genes in an iQ5 thermocycler (BioRad Laboratories, USA) according to the manufacturer’s instructions.Results: Our results showed that the expression level of IL-1 and TNF-α were significantly higher in the ischemic patients compared to healthy controls (P<0.001, P<0.01, respectively); also we found higher levels of IL-1 and IL-27 gene expressions in idiopathic patients compared to healthy controls (P<0.001, P<0.001, respectively). There were not any significant difference of IL-1, IL-27 and TNF-α expression levels between ischemic patients and idiopathic ones.Conclusion: Although we would introduce IL1, IL-27 and TNF α as effective inflammatory cytokines on myocardial functions in ischemic and idiopathic cardiomyopathy patients; there is not any difference between these two groups in gene expression of three main inflammatory cytokines.