Dilated Cardiomyopathy In Children Research Articles

Association between dietary selenium and zinc intake and risk of dilated cardiomyopathy in children: a case-control study

BackgroundDilated cardiomyopathy (DCMP) is characterized by the enlargement and weakening of the heart and is a major cause of heart failure in children. Infection and nutritional deficiencies are culprits for DCMP. Zinc is an important nutrient for human health due to its anti-oxidant effect that protects cell against oxidative damage. This case-control study aimed to investigate the relationship between dietary intake of zinc and selenium and the risk of DCMP in pediatric patients.MethodsA total of 36 DCMP patients and 72 matched controls were recruited, and their dietary intakes were assessed via a validated food frequency questionnaire. We used chi-square and sample T-test for qualitative and quantitative variables, respectively. Logistic regression analysis was applied to assess the relationship between selenium and zinc intake with the risk of DCMP.ResultsAfter fully adjusting for confounding factors, analyses showed that selenium (OR = 0.19, CI = 0.057–0.069, P trend < 0.011) and zinc (OR = 0.12, CI = 0.035–0.046, P trend < 0.002) intake were strongly associated with 81% and 88% lower risk of pediatric DCMP, respectively.ConclusionsThis study highlights the protective role of adequate dietary intake of selenium and zinc in decreasing the risk of DCMP in children. Malnutrition may exacerbate the condition and addressing these micronutrient deficiencies may improve the cardiac function. Further studies are recommended to detect the underlying mechanisms and dietary recommendations for DCMP prevention.

A study of clinical profile and outcome in children with dilated cardiomyopathy

Background: Objective was to analyse the clinical profile of children diagnosed with Dilated cardiomyopathy and to correlate the same with the severity and functional status on 2-D echocardiography. Methods: It was a prospective, retrospective and observational study. A total of 150 subjects were selected from patients visiting the cardiology OPD, admitted in medical wards, paediatric Intensive Care Unit of a tertiary care referral centre. The demographic profile, symptomatology, heart functions and compliance were recorded. The cases were evaluated by detailed history, general and cardiovascular examination and laboratory investigations along with 2D echocardiography. Results: The demographic profile is significant as the age at diagnosis predicts the risk of mortality with older children having the worst outcome. A significant association observed between decreasing ejection fraction and increasing mortality with a p value (p=0.02). Signs of pedal edema and hepatomegaly are associated with unfavourable outcome with a significant p value of (p=0.03). The overall prognosis of children with Dilated cardiomyopathy steadily improved with timely use of appropriate medications. Only 1 patient in this study had undergone orthotopic heart transplant at the age of 15 years (case of chemotherapy induced Dilated cardiomyopathy). Conclusions: Dilated cardiomyopathy is a difficult entity to treat in children as most cases are idiopathic and the therapy remains mostly supportive. Hypovitaminosis-D and hypocalcemia are common treatable causes of dilated cardiomyopathy in children and must be ruled out in all cases of dilated cardiomyopathy. Patients refractory to medical therapy should be considered for ventricular assist devices and orthotopic heart transplantation.

Clinical profile and outcomes of childhood dilated cardiomyopathy - A single-center three-decade experience.

Dilated cardiomyopathy (DCM) is an important cause of heart failure (HF) among children. Research on pediatric DCM remains surprisingly scarce. The primary objective of the study was to evaluate the clinical profile and outcomes of pediatric DCM and the secondary objective was to study the predictors of outcome. We enrolled all patients with cardiomyopathy who presented to us between 1990 and 2020 and were younger than 18 years. During the 30-year study period, we identified 233 cases of pediatric cardiomyopathy. One hundred and nineteen (51%) cases had DCM. This retrospective cohort was analyzed to study their outcome and the possible predictors of outcome. Nearly, 8% presented in the neonatal period, and 37% in infancy. The most common mode of presentation was dyspnea on exertion (71%). Ninety-three patients presented in heart failure (78%). The median left ventricular dimension z-score in diastole was 4.3 (range 2.5-9.06). The median left ventricle (LV) ejection fraction was 31%. Seventy-two percent of this cohort were on angiotensin-converting-enzyme inhibitors, 40% on aldosterone antagonists, and 47% on beta-blockers. One-third had syndromic, metabolic, genetic, or any secondary cause identified. Twenty-seven patients satisfied the three-tiered clinical classification for the diagnosis of probable acute myocarditis. Over a mean follow-up of 3.29 years, 27% were lost to follow-up. Among the remaining patients who were on follow-up (n = 86), 39 (45%) died, 31 (36%) recovered, and 16 (18%) had persistent LV dysfunction. Heart Failure was the most common cause of death. Eight patients in this cohort (4.2%) had thromboembolic phenomena. Nine had sustained ventricular arrhythmias and six had atrial/junctional arrhythmias. Among the various risk factors studied, only infantile onset had a significant relationship with death or ventricular arrhythmias (P value- 0.05). The 5-year survival rate of DCM patients was 59%. A reasonably good percentage of our population showed recovery of the left ventricular function (36%). Only infantile onset had a significant relationship with death or ventricular arrhythmias. The outcome in our DCM cohort is similar to other population cohorts.

Exploring the Possible Impact of Echocardiographic Diastolic Function Parameters on Outcome in Paediatric Dilated Cardiomyopathy.

Diastolic dysfunction is an important determinant for prognosis and survival in several paediatric heart diseases. We aimed to explore its possible impact on outcome in children with dilated cardiomyopathy. From 2006 to 2016, children less than 18 years old with dilated cardiomyopathy were retrospectively enrolled. Echocardiographic diastolic function parameters and child outcomes were analysed. Of 43 children aged 0.2 to 16.1 years old referred with dilated cardiomyopathy, 8 patients required cardiac transplant or mechanical assist devices (18%), 24 had persistently abnormal left ventricular function and/or dilatation (56%) and 11 patients recovered (26%). There was no significant difference in mitral velocities on Tissue Doppler Imaging, mitral valve inflow velocities, isovolumic relaxation time, left atrial area z-score and mitral lateral E/e’ ratios between patients with recovery and patients with disease progression or persistently abnormal ventricular function and/or dilation. This is the first study on childhood dilated cardiomyopathy to address individual echocardiographic diastolic function parameters and their association to recovery. In this study, echocardiographic parameters for diastolic function did not predict recovery.

MiR-454-3p and miR-194-5p targeting cardiac sarcolemma ion exchange transcripts are potential noninvasive diagnostic biomarkers for childhood dilated cardiomyopathy in Egyptian patients

BackgroundChildhood dilated cardiomyopathy (CDCM) is the most common cardiomyopathy in children and it is risk factor to heart failure and sudden death. Most of the different etiologic factors which have been postulated to DCM are idiopathic, and its pathogenesis remains uncertain. So it was worth investigating the potential DCM pathogenicity models to establish early noninvasive diagnosis parameters especially in CDCM patients. Beside that miRNAs in the circulatory blood are genetically considered the best option for noninvasive diagnosis; also, implementation of miRNAs as early diagnostic markers for children with DCM is urgent because those children have high risk to sudden heart death. We aimed to identify discriminator diagnostic circulatory miRNA expression levels in CDCM patients.ResultsThe expression levels of miR-454-3p and miR-194-5p were found significant upregulated (p value = 0.001 and 0.018; CI 95%, respectively), while miR-875-3p was found significant downregulated (p value = 0.040; CI 95%). A receiver operating characteristic (ROC) curve analysis showed significant AUC = 1.000 and 0.798 for miR-454-3p and miR-194-5p, respectively, and the optimal discriminated diagnostic cut-points were computed by index of union (IU) method. Enrichment analysis for the potential targeted mature mRNAs by miR-454-3p and miR-194-5p pointed that Ca, Na and K ions homeostasis in cardiac sarcolemma consider potential CDCM pathogenicity model.ConclusionsmiR-454-3p and miR-194-5p are highly influencing noninvasive biomarkers for CDCM, and further circulatory miRNAs-implicated studies are highly recommended.

A multi-site survey of providers on the management of heart failure with dilated cardiomyopathy in children.

We conducted a scientific survey of paediatric practitioners who manage heart failure with dilated cardiomyopathy in children. The survey covered management from diagnosis to treatment to monitoring, totalling 63 questions. There were 54 respondents from 40 institutions and 3 countries. There were diverse selections of management options by the respondents in general, but also unanimity in some management options. Variation in practice is likely due to the relative paucity of scientific data in this field and lack of strong evidence-based recommendations from guidelines, which presents an opportunity for future research and quality improvement efforts as the evidence base continues to grow.

Changes of serum uric acid and its clinical correlation in children with dilated cardiomyopathy.

BackgroundDilated cardiomyopathy (DCM) is the most common type of childhood cardiomyopathy and uric acid (UA) is considered closely associated with cardiovascular disease. There are few reports about the relationship between serum UA level and DCM in children, and the present study aimed to analyze the changes and clinical correlation of the two.MethodsThe clinical data of 49 children under 16 years old and who were hospitalized with DCM, and 44 healthy children who underwent physical examination in the same period at Tianjin Children’s Hospital from June 2015 to November 2019 were analyzed retrospectively.ResultsThe 49 children in the case group included 17 males and 32 females, aged from 2 to 172 months. The case group were divided into New York Heart Association (NYHA) functional class I (n=2), class II (n=17), class III (n=11), and class IV (n=19). The 44 healthy children selected as the control group included 20 males and 24 females aged from 2 to 161 months. The serum UA level was detected, and an ultrasonic cardiogram was conducted in each child. The serum UA level, left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), and left atrial diameter (LAD) of the case group were higher than that of the control group, while the left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) were lower than that of the control group, and significant statistical differences were seen between the two groups (P<0.01). The serum UA level, LVEDD, LVESD, and LAD of NYHAIII–IV class patients were higher than that of the NYHAI–II class, but LVEF and LVFS were lower than that of the NYHA I–II class, and there were significant statistical differences between the two groups (P<0.01). Statistical correlations were seen between the serum UA level and NYHA functional class, LVEDD, LVESD, LAD, LVEF, and LVFS (rs=0.599, 0.567, 0.579, 0.475, −0.333, −0.341, respectively, P<0.05).ConclusionsElevated serum UA levels exist in children with DCM and correlate with NYHA functional class and ultrasonic values. Change in serum UA levels may be used as a biomarker reflecting the severity of DCM in children.

Do not accept diagnosis of “Idiopathic dilated cardiomyopathy” in pediatric age group: Before comprehensive

Idiopathic dilated cardiomyopathy in children is a hopeless disease; most of the time, patients are destine to die or ultimately become transplant candidate. In our case series, on meticulous re-examination, treatable conditions such as obstructive disease (aortic stenosis, coarctation of aorta) or coronary artery abnormality (anomalous origin of the left coronary artery from the pulmonary artery and coronary artery occlusion by thrombus) or rhythm abnormality (supraventricular tachycardia) were diagnosed, and all patients were improved after successful correction of underlying cardiac disease.

Longitudinal Prediction of Transplant-Free Survival by Echocardiography in Pediatric Dilated Cardiomyopathy

BackgroundThe prognostic significance of serial echocardiography and its rate of change in children with dilated cardiomyopathy (DCM) is incompletely defined. MethodsWe retrospectively analysed up to 4 serial echocardiograms. Associations between mortality/transplant and echocardiographic parameters over time and between outcomes and the rate of change of echocardiographic parameters were analysed. Estimation of patient-specific intercepts and slopes was done using linear regression models. ResultsFifty-seven DCM children were studied (50% male; median age, 0.6 year; average follow-up, 2.1 ± 2.4 years). The median time to transplant or death was 2.0 years. Increased left ventricular (LV) diastolic (LVEDD) and systolic (LVESD) dimensions and myocardial performance index (MPI) were associated with increased mortality and transplant risk. Increased LV ejection fraction, mitral E-deceleration time, right ventricular (RV) fractional area change, and tricuspid annular plane systolic excursion were associated with reduced mortality and transplant risk. Transplant/mortality likelihood increased by 41.6% and 19.8% for each unit increase in LVEDD and LVESD z scores, respectively (LVEDD: hazard ratio [HR], 1.416; 95% confidence interval [CI], 1.285-1.560; P < 0.001; LVESD: HR, 1.198; 95% CI, 1.147-1.251; P < 0.001). A higher monthly change in LVESD z score increased transplant/mortality likelihood by 85.6% (HR, 1.856; 95% CI, 1.572-2.191; P = 0.015). Greater changes in mitral E/eʹ (HR, 0.707; 95% CI, 0.636-0.786; P < 0.001) and RV MPI (HR, 0.412; 95% CI, 0.277-0.613; P < 0.001) were associated with reduced mortality and transplant risk. ConclusionsLV and RV systolic and diastolic dimensions and function over time and their rate of change are associated with risk for transplant and mortality in childhood DCM. Serial changes in these parameters may be useful to predict clinical outcomes.

Dilated cardiomyopathy in children

Pediatric cardiomyopathies are infrequent diseases of the cardiac muscle, with an annual inciden ce of 1.1 to 1.2 per 100,000 children. Dilated cardiomyopathy (DCM) is the predominant form, characterized by ventricular dilatation and systolic dysfunction. Etiologies are multiple, with at least 50%-70% of cases being idiopathic. When assessing a child with DCM, secondary potentially reversible causes must be ruled out. The main diagnostic tool is the echocardiogram which allows the identification of cardiac phenotype, to establish the degree of functional compromise, and res ponse to medical therapy. Prognosis is limited but more favorable in infants younger than 1 year at the onset, post myocarditis, or with a lesser degree of ventricular dysfunction. At least 20% of patients may recover ventricular function in the first 2 years after the onset and 40%-50% may die or need heart transplant in the first 5 years. Medical therapy is mainly based on adult experience with limited scientific evidence in children. Heart transplant is the therapy of choice in patients with end-stage disease, with excellent short- and medium-term survival. A significant proportion of patients may require stabilization on the waiting list, including the use of mechanical circulatory support as a bridge to transplantation. The purpose of this revision is to update the available infor mation on etiology, physiopathological mechanisms, prognostic factors, and management of DCM in children.

Biallelic variants in PPP1R13L cause paediatric dilated cardiomyopathy.

Childhood dilated cardiomyopathy (DCM) is a leading cause of heart failure requiring cardiac transplantation and approximately 5% of cases result in sudden death. Knowledge of the underlying genetic cause can aid prognostication and clinical management and enables accurate recurrence risk counselling for the family. Here we used genomic sequencing to identify the causative genetic variant(s) in families with children affected by severe DCM. In an international collaborative effort facilitated by GeneMatcher, biallelic variants in PPP1R13L were identified in seven children with severe DCM from five unrelated families following exome or genome sequencing and inheritance-based variant filtering. PPP1R13L encodes inhibitor of apoptosis-stimulating protein of p53 protein (iASPP). In addition to roles in apoptosis, iASPP acts as a regulator of desmosomes and has been implicated in inflammatory pathways. DCM presented early (mean: 2 years 10 months; range: 3 months-9 years) and was progressive, resulting in death (n = 3) or transplant (n = 3), with one child currently awaiting transplant. Genomic sequencing technologies are valuable for the identification of novel and emerging candidate genes. Biallelic variants in PPP1R13L were previously reported in a single consanguineous family with paediatric DCM. The identification here of a further five families now provides sufficient evidence to support a robust gene-disease association between PPP1R13L and severe paediatric DCM. The PPP1R13L gene should be included in panel-based genetic testing for paediatric DCM.

Clinical evaluation of the course of dilated cardiomyopathy in children depending on the debut of the diseases

Clinical evaluation of the course of dilated cardiomyopathy in children depending on the debut of the diseases

Detection of parvovirus B19 and human herpesvirus 6 in pediatric dilated cardiomyopathy: Impact after heart transplantation.

Objectives:The aim of this study is to evaluate HHV-6 and PVB19 infection using polymerase chain reaction (PCR) and immunofluorescent assay (IFA) in the myocardium of pediatric patients with dilated cardiomyopathy (DCM) and the impact of viral persistence in the cardiac allograft after heart transplantation (HT).Methods:Multiplex droplet digital PCR was used to analyze the prevalence of viral sequences in myocardial samples from 48 pediatric DCM patients and 10 control subjects. Of the 48 DCM patients, 44 underwent HT. After HT, consecutive endomyocardial biopsy (EMB) samples were analyzed for the presence of PVB19 and HHV-6 antigens using IFA and the patients were evaluated for rejections, coronary vasculopathy, and graft loss.Results:Of the 48 DCM patients, 14 had positive viral PCR results in explanted/autopsy hearts. Among them, PVB19 was found in 8/48, HHV6 in 4/48, both PVB19 and HHV6 in 1/48, and enterovirus in one, but no adenovirus was found. The EMB samples obtained after HT were positive for PVB19 and HHV-6 in 7/44 and 3/44 cases, respectively. Viral presence in both the explanted heart and the cardiac allograft was demonstrated in 4 patients, 3 of whom were positive for PVB19, and one of whom was positive for HHV-6 pretransplant. Coronary vasculopathy and graft loss were more common in patients with PVB19-positive myocardial tissues versus those who were PVB19-negative.Conclusions:There is an association between PVB19 and HHV-6 infection and DCM in children. The study suggests the persistence of PVB19 and HHV-6 in the host can lead to subsequent viral reactivation in the transplanted heart, even in those recipients who do not have active myocarditis. PVB19 in the cardiac allograft tended toward higher adverse post-HT events.

Evaluation of Drug-Related Receptors in Children With Dilated Cardiomyopathy.

Background: Effective treatments for pediatric dilated cardiomyopathy (DCM) are limited. Currently, pediatric DCM therapy mainly includes supportive heart failure (HF) treatment. While the treatment for child DCM patients is generally the same as that for adult DCM patients, few randomized prospective studies on the clinical efficacy of treatments for pediatric DCM have been published. We explored the appropriate treatments for child patients.Methods: The ultrastructure of pediatric DCM and control hearts was analyzed by electron microscopy and HE staining. Left ventricular tissues from children in the DCM and control groups were subjected to quantitative RT-PCR (qRT-PCR) to study the mRNA expression of receptors related to various treatments, including drugs targeting the renin-angiotensin-aldosterone system (RAAS) system, digoxin, milrinone, and β-receptor blockers, in child patients in the clinic. Furthermore, the differences in drug receptors in heart tissues between children and adults with DCM were analyzed.Results: Compared with the control children, the children in the DCM group showed marked abnormalities in structure and organelles. The mRNA levels of angiotensin-converting enzyme (ACE), REN, prorenin receptor (PRR), NEP, ATP1A1, and phosphodiesterase3 (PDE3A) were higher in the pediatric DCM group than the control group. Interestingly, the mRNA expression of these treatment-related receptors was much higher in children than in adults.Conclusion: ACE inhibitors, PRR or REN receptor inhibitors, PDE3 inhibitors and LCZ696 may be effective in children with DCM. However, β-receptor blockers are not valid treatments for pediatric DCM. Moreover, high receptor expression was observed in children. These data will improve the selection of drugs for DCM patients, enhance treatment, and increase the survival rate.

Effects of pulmonary artery banding in doxorubicin-induced left ventricular cardiomyopathy

ObjectiveCentral pulmonary banding has been proposed as a novel alternative for the treatment of left ventricular dilated cardiomyopathy in children. We sought to investigate the effects of central pulmonary banding in an experimental model of doxorubicin-induced left ventricular dilated cardiomyopathy. MethodsFour-month-old sheep (n = 28) were treated with intermittent intracoronary injections of doxorubicin (0.75 mg/kg/dose) into the left main coronary artery. A total dose of up to 2.15 mg/kg of doxorubicin was administered until signs of left ventricular dilation with functional impairment occurred by transthoracic echocardiography evaluation. Animals that survived were treated with surgical central pulmonary banding through a left anterior thoracotomy or sham surgery. Transthoracic echocardiography and pressure-volume loop measurements were used to compare left ventricular function preoperatively and 3 months later. Macroscopic and microscopic histologic examinations followed after hearts were harvested. ResultsNine animals from the central pulmonary banding group and 8 animals from the sham group survived and were included in the final analysis. Both groups showed similar inflammation and fibrosis upon histologic examination consistent with the toxic myocardial effects of doxorubicin. There were no differences in the echocardiographic measurements before central pulmonary banding or sham operation. Baseline measurements before the central pulmonary banding/sham operation were considered as 100%. The central pulmonary banding group had better left ventricular ejection fraction (102.5% ± 21.6% vs 76.7% ± 11.7%, P = .01), with a tendency for smaller left ventricular end-diastolic (101.2% ± 7.4% vs 120.4% ± 10.8%, P = .18) and significantly smaller end-systolic (100.3% ± 12.9% vs 116.5 ± 9.6%, P = .02) diameter of the left ventricle in comparison with the sham animals at 3 months. The end-systolic volume (101.4% ± 31.6% vs 143.4% ± 28.6%, P = .02) was significantly lower in the central pulmonary banding group 3 months postoperatively. Fractional shortening in the long axis (118.5% ± 21.5% vs 85.2% ± 22.8%, P = .016) and short axis (122.5% ± 18% vs 80.9% ± 13.6%, P = .0005) revealed significantly higher values in the central pulmonary banding group. In the conductance catheter measurements, no significant differences were seen between the groups for the parameters of systolic and diastolic function. ConclusionsCentral pulmonary artery banding in the setting of experimental toxic left ventricular dilated cardiomyopathy improved left ventricular echocardiographic function and dimensions.

Clinical course of dilated cardiomyopathy in children

Background: Dilated cardiomyopathy (DCM) in children is a serious disorder. Here authors study the risk factors for predicting prognosis of dilated cardiomyopathy in children.Methods: An observational case series study done in Institute of child health and research centre, Government Rajaji hospital, Madurai during September 2012 to August 2014. The diagnosis of DCM was based on clinical examination and echocardiographic evidence. Patients were followed up and grouped according to the outcome as improved or cured (group I), no change in clinical status (group II) and worsened or dead (group III).Results: 31 children less than 12 years of age were diagnosed as DCM. 13 children came under group I with a mean age of 2.15±2.5 and the mean cardiothoracic diameter ratio in chest X-ray was 59.8±3.3. The mean left ventricular ejection fraction at the time of admission was 38.7±3.04 and was 52.1±2.7 on last follow up. 11 children came under Group III with a mean age of 5.35±4.4 and the mean cardiothoracic diameter ratio was 65.3±2.7. The mean left ventricular ejection fraction was 35.8±3.7 at admission and 32.6±2.9 on last follow up. Only two children came under Group II and hence their comparison is negligible.Conclusions: Children with higher age at the time of diagnosis, higher cardiothoracic diameter ratio in chest X-ray and a low left ventricular ejection fraction on serial echocardiogram were associated with a poor outcome.

Digenic Inheritance of LAMA4 and MYH7 Mutations in Patient with Infantile Dilated Cardiomyopathy.

Background and objectives: Dilated cardiomyopathy (DCM) is a rare cardiac disease characterised by left ventricular enlargement, reduced left ventricular contractility, and impaired systolic function. Childhood DCM is clinically and genetically heterogenous and associated with mutations in over 100 genes. The aim of this study was to identify novel variations associated with infantile DCM. Materials and Methods: Targeted next generation sequencing (NGS) of 181 cardiomyopathy-related genes was performed in three unrelated consanguineous families from Saudi Arabia. Variants were confirmed and their frequency established in 50 known DCM cases and 80 clinically annotated healthy controls. Results: The three index cases presented between 7 and 10 months of age with severe DCM. In Family A, there was digenic inheritance of two heterozygous variants: a novel variant in LAMA4 (c.3925G > A, p.Asp1309Asn) and a known DCM mutation in MYH7 (c.2770G > A; p.Glu924Lys). The LAMA4 p.Asp1309Asn variant was predicted to be likely pathogenic according to international guidelines. The other two families had no identifiable potentially deleterious variants. Conclusions: Inheritance of two genetic variants may have a synergistic or dose effect to cause severe DCM. We report of a novel p.Asp1309Asn variation associated with DCM. Targeted NGS is useful in the molecular diagnosis of DCM and to guide whole-family management and counselling.

Neutrophil-to-lymphocyte ratio used as prognostic factor marker for dilated cardiomyopathy in childhood and adolescence.

Objective:The objective of this study is to evaluate the neutrophil-to-lymphocyte ratio (NLR) and platelet–lymphocyte ratio, from the hemograms obtained from children and adolescents with dilated cardiomyopathy (DCM), and to correlate them with the levels of B-type natriuretic peptide (BNP) and with the clinical evolution of these patients in the long term.Materials and Methods:Follow-up of 57 patients with DCM was made retrospectively, with hemogram and BNP level determination being performed after optimized therapy for heart failure. We compared the findings of the patients' examinations that progressed with stability in relation to the occurrence of transplant listing, cardiac transplantation, or evolution to death.Results:The average age was 48 months, and the follow-up was 64 months. The average of the levels of neutrophils was greater in poor evolution group (7026 vs. 3903; P = 0.011) as well as the average of NLR (5.5 vs. 1.9; P = 0.034). The averages of hemoglobin, total leukocytes, lymphocytes, and platelets were similar in the groups. The area under the receiver operating characteristic curve for NLR in relation to the poor evolution was of 72.9%, being the best cutoff point of NLR ≥5.2 (sensitivity: 93.8% and specificity: 87.8%). Kaplan–Meier curves demonstrate that patients with NLR ≤5.2 (P = 0.001) and BNP <1000 pg/dl (P < 0.0001) presented greater survival.Conclusions:NLR (≥5.2) and lymphopenia (≤1000 lymphocyte/μL) were associated with a poor prognosis and a higher chance of evolution to death or cardiac transplant, similar to the findings for BNP.

Genetic Basis of Severe Childhood-Onset Cardiomyopathies

BackgroundChildhood cardiomyopathies are progressive and often lethal disorders, forming the most common cause of heart failure in children. Despite severe outcomes, their genetic background is still poorly characterized. ObjectivesThe purpose of this study was to characterize the genetics of severe childhood cardiomyopathies in a countrywide cohort. MethodsThe authors collected a countrywide cohort, KidCMP, of 66 severe childhood cardiomyopathies from the sole center in Finland performing cardiac transplantation. For genetic diagnosis, next-generation sequencing and subsequent validation using genetic, cell biology, and computational approaches were used. ResultsThe KidCMP cohort presents remarkable early-onset and severe disorders: the median age of diagnosis was 0.33 years, and 17 patients underwent cardiac transplantation. The authors identified the pathogenic variants in 39% of patients: 46% de novo, 34% recessive, and 20% dominantly-inherited. The authors report NRAP underlying childhood dilated cardiomyopathy, as well as novel phenotypes for known heart disease genes. Some genetic diagnoses have immediate implications for treatment: CALM1 with life-threatening arrhythmias, and TAZ with good cardiac prognosis. The disease genes converge on metabolic causes (PRKAG2, MRPL44, AARS2, HADHB, DNAJC19, PPA2, TAZ, BAG3), MAPK pathways (HRAS, PTPN11, RAF1, TAB2), development (NEK8 and TBX20), calcium signaling (JPH2, CALM1, CACNA1C), and the sarcomeric contraction cycle (TNNC1, TNNI3, ACTC1, MYH7, NRAP). ConclusionsChildhood cardiomyopathies are typically caused by rare, family-specific mutations, most commonly de novo, indicating that next-generation sequencing of trios is the approach of choice in their diagnosis. Genetic diagnoses may suggest intervention strategies and predict prognosis, offering valuable tools for prioritization of patients for transplantation versus conservative treatment.

Problems of modern diagnostics and treatment of dilated cardiomyopathy in children

Data on the etiology of dilated cardiomyopathy in children (post myocarditis, metabolic, associated with neuromuscular pathology, idiopathic) are presented. Genetic aspects of the disease are covered, a wide spectrum of mutationsin genes encoding proteins of various structures of the cardiomyocyte (sarcomeric complex, cytoskeleton, Z-disks, mitochondria), different variants of inheritance are described. The need for early diagnosis of metabolic cardiomyopathiesis underlined. Criteria for unfavorable prognosis are presented. Modern approaches to medical and surgical treatment of dilated cardiomyopathy are covered.