Severe Maternal Morbidity and Neonatal Mortality After COVID-19 Infection: Case Report.

BACKGROUND: Maternal coagulopathy and adverse fetal effects are both possible results of COVID-19 infection during pregnancy. This case demonstrates the potentially fatal outcomes when both occur simultaneously. CASE PRESENTATION: A 39-year-old multiparous woman at 31 weeks gestation presented with mild COVID-19 symptoms and decreased fetal movement. Evaluation included a biophysical profile with 2/8 scoring and fetal heart rate tracing that developed a terminal bradycardia. She underwent an emergent cesarean delivery that was complicated by disseminated intravascular coagulation (fibrinogen < 60mg/dL, platelets 34, international normalized ratio [INR] 2.1) and maternal hemorrhage requiring massive transfusion. The neonate ultimately required prolonged resuscitation with Apgar scores of 0/0/0 at 1, 5, and 10 minutes and passed away on day 6 of life. CONCLUSIONS: Even in the absence of severe symptoms, maternal COVID-19 infection during pregnancy can cause a maternal systemic and placental reaction that can lead to serious maternal morbidity, as well as fetal or neonatal morbidity and mortality.

Genomic Context Differs Between Human Dilated Cardiomyopathy and Hypertrophic Cardiomyopathy.

Background Inherited cardiomyopathies display variable penetrance and expression, and a component of phenotypic variation is genetically determined. To evaluate the genetic contribution to this variable expression, we compared protein coding variation in the genomes of those with hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM). Methods and Results Nonsynonymous single-nucleotide variants (nsSNVs) were ascertained using whole genome sequencing from familial cases of HCM (n=56) or DCM (n=70) and correlated with echocardiographic information. Focusing on nsSNVs in 102 genes linked to inherited cardiomyopathies, we correlated the number of nsSNVs per person with left ventricular measurements. Principal component analysis and generalized linear models were applied to identify the probability of cardiomyopathy type as it related to the number of nsSNVs in cardiomyopathy genes. The probability of having DCM significantly increased as the number of cardiomyopathy gene nsSNVs per person increased. The increase in nsSNVs in cardiomyopathy genes significantly associated with reduced left ventricular ejection fraction and increased left ventricular diameter for individuals carrying a DCM diagnosis, but not for those with HCM. Resampling was used to identify genes with aberrant cumulative allele frequencies, identifying potential modifier genes for cardiomyopathy. Conclusions Participants with DCM had more nsSNVs per person in cardiomyopathy genes than participants with HCM. The nsSNV burden in cardiomyopathy genes did not correlate with the probability or manifestation of left ventricular measures in HCM. These findings support the concept that increased variation in cardiomyopathy genes creates a genetic background that predisposes to DCM and increased disease severity.

Prevalence of Abnormal Heart Weight After Sudden Death in People Younger than 40 Years of Age.

Background After sudden cardiac death in people aged <40 years, heart weight is a surrogate for cardiomegaly and a marker for cardiomyopathy. However, thresholds for cardiomegaly based on heart weight have not been validated in a cohort of cases of sudden cardiac death in young people. Methods and Results We surveyed medical examiner offices to determine which tools were used to assess heart weight norms. The survey determined that there was no gold standard for cardiomegaly (52 centers reported 22 different methods). We used a collection of heart weight data from sudden deaths in the Northwestern Sudden Death Collaboration (NSDC) to test the 22 methods. We found that the methods reported in our survey had little consistency: they classified between 18% and 81% of NSDC hearts with cardiomegaly. Therefore, we obtained biometric and postmortem data from a reference population of 3398 decedents aged <40 years. The reference population was ethnically diverse and had no known cardiac pathology on autopsy or histology. We derived and validated a multivariable regression model to predict normal heart weights and a threshold for cardiomegaly (upper 95% CI limit) in the young reference population (the Chicago model). Using the new model, the prevalence of cardiomegaly in hearts from the NSDC was 19%. Conclusions Medical examiner offices use a variety of tools to classify cardiomegaly. These approaches produce inconsistent results, and many overinterpret cardiomegaly. We recommend the model proposed to classify postmortem cardiomegaly in cases of sudden cardiac death in young people.

Cardiac Evaluation of Children With a Family History of Sudden Death.

BACKGROUND: After sudden death occurs in the young, first-degree family members should undergo clinical screening for occult cardiac disease, but the diagnostic yield from screening is not well-defined in the United States. OBJECTIVES: The purpose of this study was to determine the clinical predictors of cardiac diagnosis in children referred for evaluation following a sudden death in the family. METHODS: Patients referred for a family history of sudden death were evaluated in a retrospective review from a tertiary pediatric referral center. RESULTS: Among 419 pediatric relatives of 256 decedents, 27% of patients were diagnosed with a disease or had a clinical finding of uncertain significance. Patients were diagnosed with heritable cardiac disease in 39 cases (9.3%). Nonheritable cardiac disease was diagnosed in another 5.5% of patients. Clinical findings of uncertain significance were present in 52 patients (12.4%), including abnormal electrophysiological test results (41 of 52) or imaging test results (11 of 52). Among patients diagnosed with a heritable cardiac disease, the nearest affected relative was almost always a first-degree relative (37 of 39, 95%). The strongest predictors for a successful diagnosis in the patient were an abnormal electrocardiogram and a first-degree relationship to the nearest affected relative (odds ratios: 24.2 and 18.8, respectively). CONCLUSIONS: Children referred for a family history of sudden death receive cardiac disease diagnoses (14%), but clinical findings of uncertain significance increase the challenge of clinical management. The importance of a diagnosis in first-degree affected relatives supports the clinical practice of testing intervening family members first when patients are second- or higher-degree relatives to the decedent.

Treatment of calmodulinopathy with verapamil.

Pathological variants in genes encoding calmodulin are associated with severe clinical presentations, including recurrent ventricular fibrillation and sudden death. Beta-receptor antagonists (beta-blockers) and sodium-channel antagonists have been reported as pharmacotherapies in these disorders; however, recent data have demonstrated the importance of derangements in calcium channel inactivation. We report a sustained attempt to use calcium-channel antagonists to treat calmodulinopathy and review the treatment strategies reported in the literature to date.