Pediatric cardiomyopathies harbour significant phenotypic and genetic heterogeneity. Genetic testing is essential for the initial evaluation and the ongoing care of child and family, although ...challenges remain regarding its appropriate clinical implementation in minors. We here discuss the key role of genetic diagnosis in the clinical management of two patients.
•Genetics can help to make the diagnosis in hidden Cardiomyopathies and to identify the risk stratification in relatives.•Genetics results can influence the clinical treatment, the life style decisions and the prenatal counselling.•Genetics can be valuable to optimize chemotherapy and cardioprotective therapy in oncological patients at high risk for DCM.
Due to their rare prevalence and marked heterogeneity, pediatric cardiomyopathies (CMPs) are little known and scarcely reported. We report the etiology, clinical profile and outcome of a consecutive ...cohort of children diagnosed with CMP and followed at Meyer Children's Hospital over a decade.
We retrospectively reviewed patients consecutively referred from May 2008 to May 2019 for pediatric onset CMP (<18 years). Heart disease caused by arrhythmic disorders, toxic agents, rheumatic conditions and maternal disease were excluded.
We enrolled 110 patients (65 males), diagnosed at a median age of 27 4-134 months; 35% had an infant onset (<1 year of age). A positive family history was more often associated with childhood-onset (38.8%). Hypertrophic cardiomyopathy (HCM; 48 patients) was the most frequent phenotype, followed by dilated cardiomyopathy (DCM; 35 patients). While metabolic and idiopathic etiologies were preponderant in infants, metabolic and sarcomeric diseases were most frequent in the childhood-onset group. Major adverse cardiac events (MACE) occurred in 31.8% of patients, including hospitalization for acute heart failure in 25.5% of patients, most commonly due to DCM. Overall, the most severe outcomes were documented in patients with metabolic diseases.
In a consecutive cohort of pediatric patients with CMP, those with infantile onset and with a metabolic etiology had the worst prognosis. Overall, MACE occurred in 41% of the entire population, most commonly associated with DCM, inborn errors of metabolism and genetic syndromes. Systematic NGS genetic testing was critical for etiological diagnosis and management.
Despite the recent advances, the clinical approach to persistent pulmonary hypertension of the newborn (PPHN) still represents an important challenge for neonatologists. The care of newborns with ...PPHN requires meticulous therapeutic and ventilation strategies including, besides the stabilization of the newborn, the use of nitric oxide and high-frequency ventilation. However, not all the neonates with PPHH are responsive to this clinical approach. Recent studies have proposed the use of sildenafil, a phosphodiesterase 5 inhibitor, in refractory forms of PPHN. The aim of this study is to review the cases and the clinical approach of PPHN in the Neonatal Intensive Care Unit of Meyer Children Hospital in the year 2009 and to discuss the possible role of sildenafil in the management of PPHN.
Abstract
Introduction
Pediatric cardiomyopathies (CMP) are disorders of the morphology and function of the heart, with a greater heterogeneity concerning etiology and clinical presentation than adult ...CMP. The assessment of etiology and genetic status is of paramount importance for prognosis, family screening, and therapeutic choices.
Purpose
To report clinical presentation, etiology, and outcome of a cohort of children diagnosed with CMP followed at tertiary care pediatric referral centre.
Methods
We retrospectively reviewed clinical, laboratory and imaging data of all patients referred to our cardiomyopathy centre from May 2008 to May 2019 for pediatric CMP (<18 years). CMP due to arrhythmic disorders, toxic agents' exposure, rheumatic conditions and maternal disease (i.e. maternal diabetes) were excluded. Primary endpoint was a composite of major adverse cardiovascular events (MACE: cardiovascular death, heart failure HF hospitalization, arrhythmic events, need for surgery or heart transplant referral).
Results
We enrolled 110 patients (65 males, age at diagnosis 67±71 months). Hypertrophic cardiomyopathy (HCM, N=48, 44%) was most frequent, followed by dilated cardiomyopathy (DCM, N=35 32%) and left ventricular non-compaction phenotype (LVNC, N=12, 11%). Mixed phenotype (N=7, 6%) and restrictive cardiomyopathy (RCM, N=3, 3%) were less common. No cases of arrhythmogenic right ventricular cardiomyopathy (ARVC) were detected. Five genotype-positive patients presented with negative clinical phenotype. A diagnosis was confirmed in all patients; the most common was sarcomere disease (30%, N=33) followed by metabolic (28%,N=31) disease, genetic syndromes (11%, N=12), neuromuscular (7,3%, N=8) diseases, and post-myocarditis cases (4,5%,N=5). Twenty-one patients (19%) were identified as idiopathic. At referral, 4,5% of children presented with NYHA class III/IV.
At 35 14–72 months, 4 (3.7%) patients required ICD implantation, 8 (7.4%) underwent cardiac surgery, and 1 (1%) underwent heart transplant. Furthermore, 28 (26%) patients required hospitalization due to acute HF, with DCM patients being at higher risk (p<0.01), 7 (6.8%) experienced arrhythmic events and 4 (3.9%) had syncope. Overall, 13 (12%) died (7 with metabolic disorders, 3 with genetic syndromes, 1 with a sarcomeric mutation, 1 post myocarditis, and 1 idiopathic).
Conclusions
In our cohort, HCM was the most common cause of pediatric CMP followed by DCM and non-compaction. MACE were present in 41% of patients. While HCM had a less severe phenotype (characterized by a higher arrhythmic burden), DCM was characterized by a higher prevalence of HF hospitalizations. DCM, inborn errors in metabolism and genetic syndromes had the worst outcome in terms mortality and heart failure long term.
Widespread availability of genetic testing provides several benefits to the clinician, confirming diagnosis in ambiguous cases and defining etiology in order to guide management and identifying relatives at risk.
Figure 1
Funding Acknowledgement
Type of funding source: None
Abstract
Background
Hypertrophic Cardiomyopathy (HCM) is the most common genetic cardiomyopathy. However, few studies have systematically investigated the clinical course of pregnancy in HCM.
Purpose
...To determine whether pregnancy is well tolerated in HCM.
Methods
Women consecutively referred to our Tertiary Clinic for Cardiomyopathies from 1969 to
2019 were retrospectively reviewed. Only women with complete data regarding pregnancy and with a follow up (FU)>1 year were included in the study. Overall, of the 647 women followed at our center, 378 (58%) fulfilled our inclusion criteria. Demographic, clinical and instrumental records were retrieved. The peripartum period was defined as the timeframe from −1 to 6 months after delivery.
Results
There were 433 pregnancies in 239 (63%) women with 132 (62%) having >1 pregnancy. By contrast, 139 (37%) reported no pregnancy or miscarriages: in 6 cases pregnancy was discouraged due to advanced disease stage. Twenty-eight (12%) women had 39 pregnancies after HCM diagnosis and were followed by the obstetrics department: this subset was significantly younger at diagnosis (age at diagnosis: 21 13–29 vs 56 47–66 vs 45 24–62 years, p<0.001, in women with a pregnancy after diagnosis vs women diagnosed after the pregnancy vs women with no pregnancy, respectively). Instrumental characteristics were comparable among women. Thirty percent presented with obstructive physiology at baseline. Among the 39 pregnancies in women who had a pregnancy after the diagnosis, there were 3 reported episodes of paroxysmal atrial fibrillation, one sustained ventricular tachycardia with pulse and three episodes of non-sustained ventricular tachycardia in the peripartum period. In this cohort, prevalence of intra-uterine growth delay and miscarriage was 8%. Only 3 women experienced a worsening clinical profile requiring hospitalization during the peripartum period: 2 were hospitalized for acute heart failure (AHF) and 1 was experienced a resuscitated cardiac arrest. Of note, 2/3 of patients were carriers of a (likely)pathogenic troponin mutation.
Long-term (FU: 5±3 years), nulligravida women were more symptomatic at last evaluation (NYHA III/IV: 25 vs 17, p<0.05), reported a higher incidence of ICD appropriate shocks (26 vs 12%p=0.02) but had similar rates of heart transplant (2.1 vs 0.5%, p=0.143) and episodes of AHF (12 vs 14%, p=0.193). Eighteen patients (8.2%) died: incidence of cardiovascular mortality was 4.8%, with a lower rate in patients who reported a pregnancy (0.8%/year vs 2.8%/year, p=0.01).
Conclusions
Women with HCM tolerate pregnancy well. Rare complications occurred in the peripartum period which were manageable. In the long-term, pregnancy, even when multiple, did not influence the long-term course of the disease nor its outcome. Strategies to support appropriate counselling and antenatal care should be implemented to identify those at greater risk of disease progression.
Funding Acknowledgement
Type of funding sources: None.
STUDY OBJECTIVE To investigate the utility of capture-recapture methods to estimate prevalence of subjects with alcohol related disorders using multiple incomplete lists. DESIGN This was a cross ...sectional study of alcohol related disorders in a large community. SETTING During 1997 identified cases with known alcohol related disorders were independently flagged by four sources (self help volunteering groups; psychiatric ambulatory; public alcohology service; hospital discharges). PATIENTS 381 records were flagged, corresponding to 349 individual cases from a target population resident in a northern Italy area. MAIN RESULTS The two sample capture-recapture estimates were clearly biased because of dependencies among sources. Estimates based on log-linear models showed prevalent counts ranged from 2297 (95% confidence intervals: 1524, 3794) to 2523 (95% confidence intervals: 1623, 4627) after adjustment for dependence among sources only or also for heterogeneity in catchability among age categories (< 50 and ⩾ 50 years), respectively. CONCLUSIONS The study suggests that capture-recapture is an appropriate approach for estimating prevalence of subjects with alcohol related problems who seek or need treatment and assistance when different lists of alcoholics can be obtained from different types of agencies involved with problematic use of alcohol. Critical factors are the complexity in case definition and the analysis of heterogeneity among people. Accurate estimates are needed to plan and evaluate public health interventions.
Survival of neonates with critical pulmonary obstruction depends on cardiac morphology and function but also on proper perinatal management.
Postnatal outcome of five neonates with critical pulmonary ...stenosis or pulmonary atresia detected in utero is reported.
Right ventricular morphology and ratio between tricuspid and mitral annulus at Fetal Echocardiography were the most important prognostic parameters. Increasing severity of obstruction and of right ventricular hypoplasia was documented in two fetuses.
Prenatal diagnosis was useful for planning delivery; we hypothesize that it can be of benefit on postnatal outcome. In selected cases, earlier delivery and relief of obstruction could have beneficial effect on prognosis.
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