Mothers with long QT syndrome are at increased risk for fetal death: findings from a multicenter international study.

BACKGROUND: Most fetal deaths are unexplained. Long QT syndrome is a genetic disorder of cardiac ion channels. Affected individuals, including fetuses, are predisposed to sudden death. We sought to determine the risk of fetal death in familial long QT syndrome, in which the mother or father carries the long QT syndrome genotype. In addition, we assessed whether risk differed if the long QT syndrome genotype was inherited from the mother or father. OBJECTIVE: This was a retrospective review of pregnancies in families with the 3 most common heterozygous pathogenic long QT syndrome genotypes in KCNQ1 (LQT1), KCNH2 (LQT2), or SCN5A (LQT3), which occur in approximately 1 in 2000 individuals. The purpose of our study was to compare pregnancy and birth outcomes in familial long QT syndrome with the normal population and between maternal and paternal carriers of the long QT syndrome genotype. We hypothesized that fetal death before (miscarriage) and after (stillbirths) 20 weeks gestation would be increased in familial long QT syndrome compared with the normal population and that the parent of origin would not affect birth outcomes. STUDY DESIGN: Our study was a multicenter observational case series of 148 pregnancies from 103 families (80 mothers, 23 fathers) with familial long QT syndrome (60 with LQT1, 29 with LQT2, 14 with LQT3) who were recruited from 11 international centers with expertise in hereditary heart rhythm diseases, pediatric and/or adult electrophysiology, and high-risk pregnancies. Clinical databases from these sites were reviewed for long QT syndrome that occurred in men or women of childbearing age (18-40 years). Pregnancy outcomes (livebirth, stillbirth, and miscarriage), birthweights, and gestational age at delivery were compared among long QT syndrome genotypes and between maternal vs paternal long QT syndrome-affected status with the use of logistic regression analysis. RESULTS: Most offspring (80%; 118/148) were liveborn at term; 66% of offspring (73/110) had long QT syndrome. Newborn infants of mothers with long QT syndrome were delivered earlier and, when the data were controlled for gestational age, weighed less than newborn infants of long QT syndrome fathers. Fetal arrhythmias were observed rarely, but stillbirths (fetal death at >20 weeks gestation) were 8 times more frequent in long QT syndrome (4% vs approximately 0.5%); miscarriages (fetal death at ≤20 weeks gestation) were 2 times that of the general population (16% vs 8%). The likelihood of fetal death was significantly greater with maternal vs paternal long QT syndrome (24.4% vs 3.4%; P=.036). Only 10% of all fetal deaths underwent postmortem long QT syndrome testing; 2 of 3 cases were positive for the family long QT syndrome genotype. CONCLUSION: This is the first report to demonstrate that mothers with long QT syndrome are at increased risk of fetal death and to uncover a previously unreported cause of stillbirth. Our results suggest that maternal effects of long QT syndrome channelopathy may cause placental or myometrial dysfunction that confers increased susceptibility to fetal death and growth restriction in newborn survivors, regardless of long QT syndrome status.

Blepharoptosis and Cholesterol-Lowering Medications: A Retrospective Study.

PURPOSE: To investigate the prevalence and frequency of patients with blepharoptosis who take anticholesterol therapies. To our knowledge, this is the first large single-center series to evaluate this association. METHODS: A retrospective chart review of adult patients presenting with ptosis on concomitant anticholesterol medications. RESULTS: Two hundred ninety-three adult patients with ptosis taking anticholesterol therapy were identified from October 2011 to October 2016. Forty-seven patients (16.0%) reported muscle weakness. Laboratory markers including creatine kinase (CK) and myoglobin levels were obtained. Of the 47 patients, 13 patients (4.4%) were identified to have ptosis and laboratory confirmed anticholesterol therapy-induced myopathy. Two additional patients with statin-induced myositis and rhabdomyolysis were identified from the period 2008-2011. All patients had measurably elevated CK and/or myoglobin levels. All patients experienced improvement in ptosis or systemic symptoms after discontinuation or changing medications. Nine patients (60%) demonstrated statistically significant improvement in the ptosis. CONCLUSIONS: Many patients with involutional ptosis also have both cardiovascular disease and hyperlipidemia and thus take cholesterol-lowering medication. Our study demonstrates a World Health Organization-defined probable association between ptosis and anticholesterol-induced myopathy. The frequency of anticholesterol-induced myopathy in adult ptosis was 4.4%, which is substantially higher than previously predicted. Anticholesterol-induced myositis can cause a reversible ptosis, and thus, a thorough evaluation of adult patients presenting with involutional ptosis includes inquiry into the use of anticholesterol drugs and associated muscle weakness.Anticholesterol medication may induce or exacerbate myogenic ptosis in some individuals.

Ventricular-vascular coupling is predictive of adverse clinical outcome in paediatric pulmonary arterial hypertension.

AIMS: Ventricular-vascular coupling, the ratio between the right ventricle's contractile state (Ees) and its afterload (Ea), may be a useful metric in the management of paediatric pulmonary arterial hypertension (PAH). In this study we assess the prognostic capacity of the ventricular-vascular coupling ratio (Ees/Ea) derived using right ventricular (RV) pressure alone in children with PAH. METHODS: One hundred and thirty paediatric patients who were diagnosed with PAH via right heart catheterisation were retrospectively reviewed over a 10-year period. Maximum RV isovolumic pressure and end-systolic pressure were estimated using two single-beat methods from Takeuchi et al (Ees/Ea_(Takeuchi)) and from Kind et al (Ees/Ea_(Kind)) and used with an estimate of end-systolic pressure to compute ventricular-vascular coupling from pressure alone. Patients were identified as either idiopathic/hereditary PAH or associated PAH (IPAH/HPAH and APAH, respectively). Haemodynamic data, clinical functional class and clinical worsening outcomes-separated into soft (mild) and hard (severe) event categories-were assessed. Adverse soft events included functional class worsening, syncopal event, hospitalisation due to a proportional hazard-related event and haemoptysis. Hard events included death, transplantation, initiation of prostanoid therapy and hospitalisation for atrial septostomy and Pott's shunt. Cox proportional hazard modelling was used to assess whether Ees/Ea was predictive of time-to-event. RESULTS: In patients with IPAH/HPAH, Ees/Ea_(Kind) and Ees/Ea_(Takeuchi) were both independently associated with time to hard event (p=0.003 and p=0.001, respectively) and when adjusted for indexed pulmonary vascular resistance (p=0.032 and p=0.013, respectively). Neither Ees/Ea_(Kind) nor Ees/Ea_(Takeuchi) were associated with time to soft event. In patients with APAH, neither Ees/Ea_(Kind) nor Ees/Ea_(Takeuchi) were associated with time to hard event or soft event. CONCLUSIONS: Ees/Ea derived from pressure alone is a strong independent predictor of adverse outcome and could be a potential powerful prognostic tool for paediatric PAH.

Home Monitoring for Fetal Heart Rhythm During Anti-Ro Pregnancies.

BACKGROUND: Fetal atrioventricular block (AVB) occurs in 2% to 4% of anti-Ro antibody-positive pregnancies and can develop in <24 h. Only rarely has standard fetal heart rate surveillance detected AVB in time for effective treatment. OBJECTIVES: Outcome of anti-Ro pregnancies was surveilled with twice-daily home fetal heart rate and rhythm monitoring (FHRM) and surveillance echocardiography. METHODS: Anti-Ro pregnant women were recruited from 16 international centers in a prospective observational study. Between 18 and 26 weeks' gestation, mothers checked FHRM twice daily with a commercially available Doppler monitor and underwent weekly or biweekly surveillance fetal echocardiograms. If FHRM was abnormal, a diagnostic echocardiogram was performed. Cardiac cycle length and atrioventricular interval were measured, and cardiac function was assessed on all echocardiograms. After 26 weeks, home FHRM and echocardiograms were discontinued, and mothers were monitored during routine obstetrical visits. Postnatal electrocardiograms were performed. RESULTS: Most mothers (273 of 315, 87%) completed the monitoring protocol, generating 1,752 fetal echocardiograms. Abnormal FHRM was detected in 21 mothers (6.7%) who sought medical attention >12 h (n = 7), 3 to 12 h (n = 9), or <3 h (n = 5) after abnormal FHRM. Eighteen fetuses had benign rhythms, and 3 had second- or third-degree AVB. Treatment of second-degree AVB <12 h after abnormal FHRM restored sinus rhythm. Four fetuses had first-degree AVB diagnosed by echocardiography; none progressed to second-degree AVB. No AVB was missed by home FHRM or developed after FHRM. CONCLUSIONS: Home FHRM confirms the rapid progression of normal rhythm to AVB and can define a window of time for successful therapy. (Prospective Maternal Surveillance of SSA [Sjögren Syndrome A] Positive Pregnancies Using a Hand-held Fetal Heart Rate Monitor; NCT02920346).