Influence of Pregnancy in Patients With Congenital Long QT Syndrome

Garg, Lohit; Garg, Jalaj; Krishnamoorthy, Parasuram; Ahnert, Amy M.; Shah, Neeraj; Dusaj, Raman; Bozorgnia, Babak

doi:10.1097/crd.0000000000000108

Cited by 13 publications

(13 citation statements)

References 49 publications

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“…This discrepancy may be due to the fact that all of the monkeys in this study were bred in cages, and their exercise load and diet differed from those of humans. It has also been reported that human females have a higher risk of long-QT syndrome due to the increased levels of progesterone during pregnancy [ 7 ]. It is thought that progesterone is one of the factors for heart disease in women.…”

Section: Discussionmentioning

confidence: 99%

Usefulness of cardiac hormones for evaluating valvular disease in cynomolgus monkeys (<i>Macaca fascicularis</i>)

Pai

Nakayama

Ito-Fujishiro

et al. 2021

The Journal of Veterinary Medical Science

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Nonhuman primates are commonly used as experimental animals due to their biological resemblance to humans. In patients with cardiac disease, the levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) tend to increase in response to cardiac damage, and they are thus used as indicators for the diagnosis of human heart failure. However, no reference values for ANP and BNP have been reported for heart disease in nonhuman primates. In this study, we recorded the age, sex, and body weight of 202 cynomolgus monkeys, and performed evaluations to assess the ANP and BNP levels, electrocardiography and echocardiography, and accordingly divided the monkeys into two groups: healthy monkeys and those with spontaneous cardiac disease. Statistical analysis was performed to determine the relationship of ANP and BNP with the factors of age, sex, and body weight. No significant relationship was found between the levels of ANP and BNP and the factors of age, sex, and body weight. However, both the ANP and BNP levels were significantly different between the healthy monkeys and monkeys with valvular disease. Similar to humans, the ANP and BNP levels tended to increase with the progression of cardiac disease in monkeys. Based on these results, we concluded that ANP and BNP are indicators of cardiac disease in nonhuman primates, and that this nonhuman primate cardiac disease model is applicable for cardiology research in humans.

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Section: Discussionmentioning

confidence: 99%

Usefulness of cardiac hormones for evaluating valvular disease in cynomolgus monkeys (<i>Macaca fascicularis</i>)

Pai

Nakayama

Ito-Fujishiro

et al. 2021

The Journal of Veterinary Medical Science

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“…β-receptor blockers are effective in reducing life-threatening CE in iLQTS and therefore should be continued during pregnancy and postpartum as pregnant iLQTS women are at a risk to develop CE [8-10, 17, 45]. β-receptor blockers are not teratogenic, but they are categorized by former FDA category as “C,” whereas atenolol is categorized as “D.” They can cause IUGR commonly and additionally bradycardia, apnea, hypoglycemia, and hyperbilirubinemia have been reported in the newborn infant [17-20].…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, the birth weight for newborns of iLQTS mothers seems to be lower if adjusted for gestational age compared to those of iLQTS fathers [6]. It is important to highlight that pregnant iLQTS women themselves are at an increased risk for cardiac events (CE) postpartum, particularly in case of a LQTS type 2 (LQTS2) [8-11]. The mothers have an alternated sleep pattern, lack of sleep, and an increased physical/emotional stress, which might lead to an increased sympathetic activity, with an increased gene-specific CE risk postpartum [9, 11, 12].…”

Section: Introductionmentioning

confidence: 99%

Intrauterine Growth Retardation in Pregnant Women with Long QT Syndrome Treated with Beta-Receptor Blockers

2021

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Pregnant women with inherited long QT syndrome (iLQTS) are at an increased risk for preterm delivery and intrauterine growth retardation (IUGR) due to their underlying disease. Additionally, they are at a risk of arrhythmogenic events, particularly during the postpartum period because of physiological changes and increased emotional/physical stress. β-receptor blockers can effectively prevent life-threatening Torsades de Pointes ventricular tachycardia and they are the treatment of choice in iLQTS. Use of β-receptor blockers in pregnancy is recommended, although IUGR is commonly reported for prenatally exposed infants. IUGR, particularly in preterm infants, can result in adverse neonatal outcomes. This review was performed to support clinicians in their selection of β-receptor blocker treatment for their pregnant iLQTS women by (i) summarizing the available literature addressing the impact of different β-receptor blockers on IUGR and (ii) reporting additional aspects which might influence the β-receptor blocker selection. In general, experts recommend to use nonselective β-receptor blockers, such as nadolol and propranolol, for iLQTS management as these drugs seem to be superior in effectiveness. However, β-1-selective receptor blockers, such as bisoprolol or metoprolol, seem to affect less likely uterine contraction, peripheral vasodilation, and are associated with lower IUGR rates and fetal hypoglycemia. They are therefore recommended, except atenolol, as first-line therapy for pregnant women. Additionally, maternal factors such as iLQTS genotype, other underlying comorbidities (e.g., diabetes mellitus type 1, asthma bronchiale), and uteroplacental dysfunction or fetal factors have to be taken into account. Therefore, each woman with iLQTS who wants to become pregnant should be well-advised for a personalized β-receptor blocker therapy according to the individual risk-benefit evaluation by a multidisciplinary team of cardiologists, gynecologists, pediatric cardiologists, neonatologists, and clinical pharmacologists. During pregnancy, a close monitoring of IUGR and, after birth, monitoring of bradycardia, hypoglycemia, and respiratory depression in the neonate is mandatory. This review summarizes available data on β-receptor blocker-related risk for IUGR in prenatally exposed infants and illustrates which factors might influence β-receptor blocker selection with the aim to support clinicians in their pharmacological management of their pregnant iLQTS patients.

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“…The adrenergic nature of labor and delivery may lead to catecholaminergic polymorphic ventricular tachycardia in these patients. Furthermore, patients with congenital long QT syndrome are also at risk during a nine-month post-partum period 19 . Treatment with beta-blockers are the mainstay of therapy during pregnancy and in the post-partum period 19 .…”

mentioning

confidence: 99%

“…Furthermore, patients with congenital long QT syndrome are also at risk during a nine-month post-partum period 19 . Treatment with beta-blockers are the mainstay of therapy during pregnancy and in the post-partum period 19 . There is a lack of data for therapeutics that may be urgently needed intrapartum that may prolong the QT interval in susceptible patients.…”

mentioning

confidence: 99%

Drug Therapy during Pregnancy

Sun

Hutson

Bournissen

2020

Preprint

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Drug therapy in pregnancy may cause anxiety to both physicians and patients due to uncertainty regarding dosing and safety. Nevertheless, the need for medication is high given that maternal chronic illnesses such as hypertension or diabetes are on the rise 1 . In a national study in the United States over 33 years, the prevalence of prescription medication use by pregnant women in the first trimester increased by 62.5% between the first 2 years of the study and the last 2 years 2 . Furthermore, the average number of medications used anytime in pregnancy has increased two-fold 2 . More recent research from different countries has found that medications are widely used in pregnancy, with the prevalence of using at least one drug ranging from 60 to 90 percent, excluding vitamins and minerals [3][4][5] . Prescription of drugs with potential teratogenicity has also increased in pregnancy, including folate antagonists or angiotensin converting enzyme inhibitors 3,4 . This suggests that many women go into pregnancy with chronic conditions that require medications, including those may pose some degrees of risk to the fetus, since the maternal benefit may outweigh the risk or if the pregnancy is unplanned. Successful treatment of pregnant patients requires a correct diagnosis and providing treatment that not only is effective but also balances risks and benefits, as maternal health is the best defense for fetal health. However, concomitant health conditions, and the intrinsic complex physiological changes associated to pregnancy can make prescribing in this population a particularly challenging balancing act. Very few drugs have specific pregnancy dosing regimens supported by scientific evidence in spite of well-known pharmacokinetics changes during pregnancy affecting a large proportion of medications (Table 1) [6][7][8][9][10] . Data on drug efficacy and safety is sorely lacking for pregnant women, even for drugs that have been available for decades. Pregnant patients are commonly excluded from clinical trials during the drug development process due to ethical and safety concerns, which implies that the majority of drug therapy data in pregnancy have been extrapolated from males and to a much lesser extent, from non-pregnant females 11 . However, using extrapolated data in pregnancy has a number of major drawbacks such as that the extrapolation commonly fails to account for the changes in drug metabolism related to pregnancy 6 . Multiple physiological changes in pregnancy, including those affecting pharmacokinetics, must be considered when prescribing. Furthermore, these changes can also be affected by genetic variability 10 . Some drugs need to be used at higher doses in pregnancy due to increasing metabolic demand. A classic example is thyroid hormone, which requires a 30 to 45 percent higher dose in order to maintain euthyroid state due to limited compensation in pregnant patients with underlying thyroid disease 12 . One of the biggest physiologic changes in pregnancy is the expansion of plasma volume by approximatel...

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Influence of Pregnancy in Patients With Congenital Long QT Syndrome

Cited by 13 publications

References 49 publications

Usefulness of cardiac hormones for evaluating valvular disease in cynomolgus monkeys (<i>Macaca fascicularis</i>)

Usefulness of cardiac hormones for evaluating valvular disease in cynomolgus monkeys (<i>Macaca fascicularis</i>)

Intrauterine Growth Retardation in Pregnant Women with Long QT Syndrome Treated with Beta-Receptor Blockers

Drug Therapy during Pregnancy

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