Lessons learnt from COVID-19 in adult congenital heart patient in Tehran: a survey-based study of prevention, exposure, susceptibility, and outcomes.

BACKGROUND: COVD-19 pandemic has overwhelmed many healthcare systems worldwide. Underlying cardiovascular disease predisposes to greater disease susceptibility and more complications including mortality. Such data is unverified in adults with congenital heart disease (ACHD). The aim of the study is to report the Tehran experience with respect to preventative self-care measures, disease exposure, susceptibility, and outcomes after COVD-19 infection in ACHD patients. METHODS: A telephone-based survey was conducted in ACHD patients, focusing on new-onset symptoms that might indicate COVID-19 infection, prevention measures, confirmed infection rates, and outcomes. RESULTS: Three-hundred and nine ACHD patients, with a mean age of 29.13 years (range from 14 to 72 years, SD = 10.64), and 170 (55%) women were assessed. The majority (86.7%) had moderate or complex ACHD. Two-thirds (67.3%) of the patients practiced high-level preventative self-care measures. After community exposure, 33.3% developed COVID-19, and after household exposure, 43.7% developed COVID-19. There was only one mortality in a post-operative patient. Thirty-seven patients (12%) reported new symptoms including cough (10%), fatigue (8%), fever (7%), and new dyspnoea (6.5%). Amongst 18 (6%) with confirmed COVID-19, there was only 1 mortality in a post-operative patient. Age (adjusted OR = 1.19, 95% CI: 1.07-1.31, p = 0.001), contact with confirmed COVID-19 cases (adjusted OR = 59.34, 95% CI: 3.68-955.10, p = 0.004) were independently associated with COVID-19 infection. CONCLUSIONS: Mortality risk associated with COVID-19 infection in ACHD patients with moderate or severe disease appears to be relatively low, similar to the general population. Such risk appears to act through conventional risk factors, and in this cohort, we demonstrated age as a significant risk factor in addition to exposure to the development of COVID-19 infection. Preventative self-care measures are a potentially significant and impactful intervention target for intervention and for improving outcomes.

Epidemiology of respiratory syncytial virus infection and its effect on children with heart disease in Hong Kong: a multicentre review.

OBJECTIVES: There is no guideline in Hong Kong regarding respiratory syncytial virus (RSV) immunoprophylaxis for children with heart disease because of a lack of local data on RSV infection. Therefore, this study evaluated the epidemiology and impact of RSV infection on children with heart disease in Hong Kong, with the goal of providing recommendations regarding RSV immunoprophylaxis. METHODS: This multicentre retrospective case-control study on paediatric RSV infection was conducted in four local regional hospitals from 2013 to 2015. The patients' demographic and clinical data were retrieved and analysed. RESULTS: There were 3538 RSV hospitalisations during the study period, and the mortality rate was 0.14%. Some RSV seasonality was present in Hong Kong, primarily in spring and summer. Respiratory syncytial virus infection was positively correlated with relative humidity and negatively correlated with wind speed and atmospheric pressure. Patients with heart disease had a more severe outcome than those without, including longer median hospital stay (4 vs 2 days, P<0.001), higher complication rate (28.6% vs 9.8%, P<0.001), and higher rates of intensive care (11.6% vs 1.4%, P<0.001) and mechanical ventilation (3.6% vs 0.4%, P=0.003). Complications in non-cardiac patients included myocarditis and Kawasaki disease. Predictors of severe RSV infection in patients with heart disease were heart failure, pulmonary hypertension, and severe airway abnormalities associated with congenital heart disease. CONCLUSIONS: Respiratory syncytial virus infection occurs mainly in spring and summer in Hong Kong, and is related to meteorological conditions. Respiratory syncytial virus infection poses a heavy disease burden on children with heart disease. A local guideline on RSV immunoprophylaxis for these children is therefore needed.

Ultrasound Findings Associated With Antepartum Viral Infection.

This article reviews the sonographic manifestations of fetal infection and the role of ultrasound in the evaluation of the fetus at risk for congenital infection. Several ultrasound findings have been associated with in utero fetal infections. For the patient with a known or suspected fetal infection, sonographic identification of characteristic abnormalities can provide useful information for counseling and perinatal management. Demonstration of such findings in the low-risk patient may serve to identify the fetus with a previously unsuspected infection. The clinician should understand the limitations of ultrasound in the prenatal diagnosis of congenital infection and discuss them with the patient.

The use of humanized monoclonal antibodies for the prevention of respiratory syncytial virus infection.

Monoclonal antibodies are widely used both in infants and in adults for several indications. Humanized monoclonal antibodies (palivizumab) have been used for many years for the prevention of respiratory syncytial virus infection in pediatric populations (preterm infants, infants with chronic lung disease or congenital heart disease) at high risk of severe and potentially lethal course of the infection. This drug was reported to be safe, well tolerated and effective to decrease the hospitalization rate and mortality in these groups of infants by several clinical trials. In the present paper we report the development and the current use of monoclonal antibodies for prophylaxis against respiratory syncytial virus.

Coxsackievirus B3 Infection Early in Pregnancy Induces Congenital Heart Defects Through Suppression of Fetal Cardiomyocyte Proliferation.

Background Coxsackievirus B (CVB) is the most common cause of viral myocarditis. It targets cardiomyocytes through coxsackie and adenovirus receptor, which is highly expressed in the fetal heart. We hypothesized CVB3 can precipitate congenital heart defects when fetal infection occurs during critical window of gestation. Methods and Results We infected C57Bl/6 pregnant mice with CVB3 during time points in early gestation (embryonic day [E] 5, E7, E9, and E11). We used different viral titers to examine possible dose-response relationship and assessed viral loads in various fetal organs. Provided viral exposure occurred between E7 and E9, we observed characteristic features of ventricular septal defect (33.6%), abnormal myocardial architecture resembling noncompaction (23.5%), and double-outlet right ventricle (4.4%) among 209 viable fetuses examined. We observed a direct relationship between viral titers and severity of congenital heart defects, with apparent predominance among female fetuses. Infected dams remained healthy; we did not observe any maternal heart or placental injury suggestive of direct viral effects on developing heart as likely cause of congenital heart defects. We examined signaling pathways in CVB3-exposed hearts using RNA sequencing, Kyoto Encyclopedia of Genes and Genomes enrichment analysis, and immunohistochemistry. Signaling proteins of the Hippo, tight junction, transforming growth factor-ß1, and extracellular matrix proteins were the most highly enriched in CVB3-infected fetuses with ventricular septal defects. Moreover, cardiomyocyte proliferation was 50% lower in fetuses with ventricular septal defects compared with uninfected controls. Conclusions We conclude prenatal CVB3 infection induces congenital heart defects. Alterations in myocardial proliferate capacity and consequent changes in cardiac architecture and trabeculation appear to account for most of observed phenotypes.

Impact of palivizumab on RSV hospitalizations for children with hemodynamically significant congenital heart disease.

The objective of this study was to evaluate the impact of palivizumab prophylaxis on respiratory syncytial virus (RSV) hospitalizations among children with hemodynamically significant congenital heart disease (CHD). In 2003, the American Academy of Pediatrics (AAP) revised the bronchiolitis policy statement and recommended the use of palivizumab in children <24 months old with hemodynamically significant CHD (HS-CHD). California statewide hospital discharge data from years 2000-2002 (pre-AAP policy revision) were compared to those from years 2004-2006 (post-AAP policy revision). Hospitalizations due to RSV bronchiolitis for children <2 years of age were identified by IDC-9 CM codes 4661.1, 480.1, and 079.6 as the Principal Diagnosis. Children with CHD and children with HS-CHD were identified by the codiagnoses. The overall RSV hospitalization rate was 71 per 10,000 children <2 years of age. Of all RSV hospitalizations, 3.0% were among children with CHD, and 0.50% among children with HS-CHD. HS-CHD patients accounted for 0.56% of RSV hospitalizations in 2000-2002, compared to 0.46% RSV hospitalizations in 2004-2006. That represents a 19% reduction in RSV hospitalizations among HS-CHD patients after 2003. The 19% decrease in RSV hospitalizations equates to seven fewer hospitalizations (76 hospital days) per year among HS-CHD patients. We conclude that, since the recommendation of palivizumab for children with HS-CHD in 2003, the impact on RSV hospitalizations in California among HS-CHD patients has been limited. Considering the high cost of palivizumab administration, the cost-benefit of RSV prophylaxis with palivizumab warrants further investigation.

Challenges in a unique presentation of congenital dengue with congenital heart disease.

Vertical transmission of dengue has been documented and is associated with diverse presentations in newborns. Care of such babies requires meticulous support to maintain homeostasis until the baby recovers. We present a neonate diagnosed with congenital dengue, born to a mother diagnosed with dengue on the second day after delivery. Baby was diagnosed by serological tests, underwent appropriate management in neonatal intensive care but was noted to have had coexistent persistent ductus arteriosus and pulmonary hypertension complicating pneumonia and seizures. Management of the baby was complicated by persistent haematological derangements caused by dengue and haemodynamic alterations caused by the heart disease.

Maternal Viral Infection and Risk of Fetal Congenital Heart Diseases: A Meta-Analysis of Observational Studies.

Background At present, the association between maternal viral infection and risk of congenital heart diseases ( CHD ) in offspring is uncertain; additionally, a complete overview is missing. A meta-analysis of observational studies was performed to address the question of whether women who had a history of viral infection in early pregnancy were at an increased risk of CHD in offspring, compared with mothers without viral infection. Methods and Results Unrestricted searches were conducted, with an end date parameter of July 15, 2018, of PubMed, Embase, Google Scholar, Cochrane Libraries, and Chinese databases, to identify studies that met prestated inclusion criteria. Seventeen case-control studies involving 67 233 women were included for analysis. Both fixed-effects models (odds ratio [OR], 1.83; 95% CI , 1.58-2.12; P<0.0001) and random-effects models ( OR , 2.28; 95% CI , 1.54-3.36; P<0.0001) suggested that mothers who had a history of viral infection in early pregnancy experienced a significantly increased risk of developing CHD in offspring. For specific viral infections, the risk of developing CHD in offspring was significantly increased among mothers with rubella virus (OR, 3.49, 95% CI, 2.39-5.11 in fixed-effects models; and OR, 3.54; 95% CI, 1.75-7.15 in random-effects models) and cytomegalovirus (OR, 3.95; 95% CI, 1.87-8.36 in fixed-effects models) in early pregnancy; however, other maternal viral infections in early pregnancy were not significantly associated with risk of CHD in offspring. Sensitivity analysis yielded consistent results. No evidence of publication bias was observed. Conclusions Although the role of potential bias and evidence of heterogeneity should be carefully evaluated, the present study suggests that maternal viral infection is significantly associated with risk of CHD in offspring.

Nationwide survey of palivizumab for respiratory syncytial virus prevention in Japanese children with congenital heart disease.

A questionnaire study was performed to determine the current status of palivizumab prophylaxis against respiratory syncytial virus infection in Japanese children with congenital heart disease <2 years of age. Palivizumab prophylaxis decreased the respiratory syncytial virus hospitalization rate by 42.8%.

Respiratory virus prophylaxis in congenital heart disease.

Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infections and causes up to 200,000 infant deaths a year worldwide. The average rate of hospitalization for severe RSV infection is 5 per 1000 children, and the rate is three-times higher in those with congenital heart disease (CHD). Palivizumab, a monoclonal antibody, reduces hospitalization rates and intensive care admissions. It is used prophylactically and is administered as monthly doses during the RSV season. Hemodynamically unstable CHD is the most susceptible CHD to a severe episode of RSV infection. This review explores current evidence surrounding therapies, patterns of infection and identifies groups which may still be vulnerable to severe RSV infection.

Respiratory syncytial virus hospitalization risk in the second year of life by specific congenital heart disease diagnoses.

Children with hemodynamically significant congenital heart disease (CHD) are at elevated risk of morbidity and mortality due to respiratory syncytial virus (RSV) disease compared to their healthy peers. Previous studies have demonstrated lower RSV hospitalization risk among all children with CHD at 12-23 months of age versus 0-11 months of age. However, RSV hospitalization risk at 12-23 months of age by specific CHD diagnosis has not been characterized. Both case-control and cohort studies were conducted using data from the US National Inpatient Sample from 1997 to 2013 to characterize relative risk of RSV hospitalization among children 12-23 months of age with CHD. Related CHD diagnoses were combined for analysis. Hospitalizations for RSV and unspecified bronchiolitis were described by length of stay, mechanical ventilation use, mortality, and total charges. Over the 17-year period, 1,168,886 live birth hospitalizations with CHD were identified. Multiple specific CHD conditions had an elevated odds ratio or relative risk of RSV hospitalization. Mean total RSV hospitalization charges were significantly higher among children with CHD relative to those without CHD ($19,650 vs $7,939 in 2015 dollars) for this period. Compared to children without CHD, children with Ebstein's anomaly, transposition of the great arteries, aortic stenosis, heterotaxia, and aortic arch anomalies had 367-, 344-, 203-, 117- and 47-fold increased risk of inpatient RSV mortality, respectively. Unspecified bronchiolitis hospitalization odds and relative risk across CHD diagnoses were similar to those observed with RSV hospitalization; however, unspecified bronchiolitis hospitalizations were associated with shorter mean days of stay and less frequently associated with mechanical ventilation or mortality. Among children with more severe CHD diagnoses, RSV disease remains an important health risk through the second year of life. These data can help inform decisions regarding interventions to protect children with CHD from severe RSV disease during their second year of life.

Secondary congenital aphakia.

UNLABELLED: Abstract PURPOSE: We present the clinical, paraclinical and therapeutic features in a patient with secondary congenital aphakia. METHODS: A 2-year-old patient, diagnosed with congenital rubella syndrome including sensorineural deafness, congenital heart disease, intellectual disability, microcephaly, microphthalmia, and congenital cataract, presented to our clinic for the surgical treatment of cataract. RESULTS: During the surgery, the absence of the lens' cortex was observed, hence, the final diagnose was of secondary congenital aphakia. Surgery was then continued with a posterior capsulorhexis and an anterior vitrectomy, deciding to postpone the implantation of the posterior chamber intraocular lens.

The detection of viral genomes by polymerase chain reaction in the myocardium of pediatric patients with advanced HIV disease.

OBJECTIVES: The aim of this study was to investigate the frequency of viral nucleic acid detection in the myocardium of human immunodeficiency virus (HIV)-infected children to determine whether an association exists with the development of heart disease. BACKGROUND: As improved medical interventions increase the life expectancy of HIV-infected patients, increased incidences of myocarditis and dilated cardiomyopathy (DCM) are becoming more apparent, even in patients without clinical symptoms. METHODS: Myocardial samples were obtained from the postmortem hearts of 32 HIV-infected children and from 32 age-matched controls consisting of patients with structural congenital heart disease and no myocardial inflammation and no cardiac or systemic viral infection. The hearts were examined histologically and analyzed for the presence of viral sequences by polymerase chain reaction (PCR) or reverse transcription-PCR. RESULTS: Myocarditis was detected histologically in 11 of the 32 HIV-infected patients, and borderline myocarditis was diagnosed in another 13 cases. Infiltrates were confined to the epicardium in two additional hearts. Virus sequences were detected by PCR in 11 of these 26 cases (42.3%); adenovirus in 6, CMV in 3 and both adenovirus and CMV in 2. Two cases without infiltrates were also positive for adenovirus: one had congestive heart failure (CHF) and the other adenoviral pneumonia. No other viruses were detected by PCR, including HIV proviral DNA. All control samples were negative for all viruses tested. CONCLUSIONS: These data suggest that the presence of viral nucleic acid in the myocardium is common in HIV-infected children, and may relate to the development of myocarditis, DCM or CHF and may contribute to the rapid progression of HIV disease.

Incidence of the involvement of the cardiovascular system in HIV infection.

The epidemiology of cardiac complications related to HIV, including cardiomyopathy, increased left ventricular mass, myocarditis, pericardial effusion, endocarditis, and malignancy, are discussed. An increased number of HIV-infected individuals may present with cardiac complications in the next decade as chronic viral infection, co-infections, drug therapy, and immunosuppression affect the heart. Understanding the nature and course of cardiac illness related to HIV infection may allow appropriate monitoring, early intervention and therapy, and will provide a baseline to evaluate the effects of new therapeutic regimens such as highly active antiretroviral therapy on the cardiovascular system.

Prevalence of human parvovirus B19 DNA in cardiac tissues of patients with congenital heart diseases indicated by nested PCR and in situ hybridization.

BACKGROUND: Infection with parvovirus B19 (B19) was reported to be correlated with myocarditis, cardiomyopathy, and kawasaki disease. But no information is available about the relationship between inutero B19 infection and congenital heart disease (CHD). OBJECTIVE: To explore whether there is relationship between B19 infection and CHD. STUDY DESIGN: Retrospective investigation of biopsy samples from CHD patients from January 1996 to December 1998. METHODS: Parvovirus B19 was detected in biopsy samples from 42 cases of CHD patients and 38 cases of biopsy or autopsy samples from patients with other diseases (controls) by nested polymerase chain reaction (PCR) and in situ hybridization (ISH) technique. HE staining was also performed to observe the morphology of these cardiac tissue samples. RESULTS: Nested PCR assay indicated that seven of 42 (16.7%) CHD cardiac tissue were B19 DNA positive, while all the 38 controls were B19 DNA negative, the difference is significant (P = 0.012). ISH assay indicated that five of 42 (11.7%) CHD cardiac tissues were positive for B19 DNA and none of the control cardiac tissue were positive, all B19 DNA positive signals were located in the nucleuses of cardiac cells. HE staining showed that there was no inflammatory change in B19 DNA positive cardiac tissue. CONCLUSIONS: Parvovirus B19 DNA was presented in part of CHD cardiac tissues and located in nucleus, which suggested that inutero B19 infection might be correlated with CHD.

Cardiotropic viruses in the myocardium of children with end-stage heart disease.

BACKGROUND: Transplantation has become a lifesaving procedure for children with end-stage heart failure. The long-term outcome for children who undergo transplantation has been of considerable interest, but the causes of graft failure and death are largely unknown, and the role of pre-transplant viral infection is unclear. METHODS: Myocardial samples from 80 explanted hearts from children with end-stage heart disease caused by congenital heart disease (CHD), cardiomyopathy, or chronic rejection were analyzed using polymerase chain reaction and reverse-transcriptase polymerase chain reaction for cardiotropic viruses using virus-specific primers. We used immunohistochemical analysis of cytoskeletal proteins to evaluate myocyte architecture. RESULTS: We identified parvoviral genomes in 6 patients (3 with CHD and 3 with cardiomyopathy). We detected no other viruses. Immunohistochemistry showed normal staining for key components of the cytoskeleton/sarcolemma, sarcomere, and nuclear membrane in the 6 virus-positive samples. The clinical outcome of these children was worse (4 long-term survivors, but 2 deaths) than for individuals without the genome. CONCLUSIONS: Detecting viruses within the myocardium at the point of end-stage heart failure is not common, regardless of the primary pathology. However, the presence of viruses may result in poor outcome for the patient.

Echocardiography on HIV patients admitted to the ICU.

A prospective echocardiographic study was conducted in 68 patients with the human immunodeficiency virus (HIV) admitted to the intensive care unit (ICU) (C3 stage 78%, i.v. drug abuse 71%) in order, firstly to, assess the prevalence of cardiac abnormalities, and, secondly, to make an early therapeutic decision. Only five patients presented clinical evidence of cardiac disease. Echocardiographic abnormalities were identified in 35 patients (51%): pericardial effusion: 20 cases (29%), with tamponade in 2 cases that led to an immediate pericardiocentesis. Left ventricular dysfunction: 15 cases (22%) requiring treatment of cardiac failure. Mitral bioprosthesis rupture in 1 patient that led to a surgical procedure. Vegetations of the tricuspid value in 3 drug addicts (4%) requiring early antibiotic treatment. Echocardiography proved to be very helpful in detecting hidden cardiac dysfunctions. It is immensely valuable in ICU management of HIV patients, since prompt initiation of appropriate treatment is essential.

Investigation of parvovirus B19 in cardiac tissue from patients with congenital heart disease.

OBJECTIVE: To explore the correlation between human parvovirus B19 (HPV-B19) and congenital heart (CHD) and to investigate the teratogenic effect of HPV-B19. METHODS: A case control study was conducted to investigate the embedded autopsy cardiac tissues of 29 cases of CHD and 30 controls without CHD with nest polymerase chain reaction (PCR). Other viruses, including herpes simplex virus (HSV). Toxoplasma gondii (TOX), cytomegalovirus (CMV) and rubella virus (RV) were also studied in 10 cases of each group with corresponding PCR kits. RESULTS: Five of 29 (17.2%) CHD cases were positive for HPV-B19, while all the 30 controls were negative for HPV-B19 (P=0.0237). All cases studied were negative for both HSV and TOX. Three cases in each group were positive for CMV, with presence of HPV-B19 DNA in 2 cases in the CHD group. Only two cases in the CHD group showed positive reaction for RV. CONCLUSIONS: As far as we know, it is the first report of the presence of HPV-B19 in cardiac tissues of CHD patients. The detection rate of HPV-B19 DNA is significantly different between the two groups, inferring that HPV-B19 might be correlated with CHD.

[Relationship between human parvovirus B19 infection and spontaneous abortion and congenital heart disease in China].

OBJECTIVE: To explore the status of human parvovirus B19(HPV B19) infection to the fetus in China and the relationship between HPV B19 infection and spontaneous abortion,and congenital heart disease (CHD). METHODS: Nest polymerase chain reaction (PCR) and in situ hybridization (ISH) were used to detect HPV B19-DNA in the tissues of spontaneous abortion and cardiac muscle of CHD, enzyme linked immunosorbent assay (ELISA) to detect HPV B19-IgM. RESULTS: (1) The positive rate of HPV B19-DNA was 25.8%(47/182) in spontaneous abortion, comparing with artificial abortion 5.0%(2/40). (2) The positive rate in cardiac muscle tissues of CHD in autopsy and biopsy were 17.2%(5/29) and 18.9%(7/37), respectively. The total rate was 18.2% (12/66), but the positive case was not found in control group (0/30). The HPV B19 gene were found locating in the nucleus of cardiac cell by ISH. The HPV B19-IgM was negative in the blood in all patients when the HPV B19-DNA positive in the cardiac cell of biopsy. CONCLUSION: (1)There may be a relationship between HPV B19 infection and spontaneous abortion and CHD. (2) Two spontaneous abortion specimens from one person in the different period were both positive. It indicated that, there was a persistent infection. It may be one cause in frequently abortion.

Respiratory syncytial virus-associated intensive care unit admission in children in Southern China.

BACKGROUND: There are incomplete data on the global burden of viral lower respiratory tract infection, in particular the role of Respiratory Syncytial Virus, in children requiring health services. FINDINGS: In this study set in a large urban area of southern China from 1 January 2007 to 31 December 2010, children 1 month to 14 years of age with RSV-associated "severe" or "very severe pneumonia" according to World Health Organization definitions, and meeting local criteria for admission to the pediatric intensive care unit, were followed for the course of their admission. The median age was 3 months and 79% (135/171) of children with RSV were under six months of age. All children needed supplemental oxygen, and 22% required mechanical ventilatory support. The mortality rate was 3.5%. In multivariate analysis, congenital heart disease and Trisomy 21 were associated with death. CONCLUSIONS: Children admitted to an intensive care unit with RSV-associated severe/very pneumonia in a large urban setting in southern China were most commonly ≤ six months old and almost one quarter of these had respiratory failure. The overall mortality rate was 3.5%. RSV vaccine strategies that would protect children from early infancy are urgently needed.