Arrhythmias in Pregnancy Clinical Trial
Official title:
Sub-project: Use of Small Implantable ECG Recorder in Pregnant Women With Arrhythmia
Study will recruit pregnant or postpartum women presenting to Groote Schuur Hospital with cardiovascular disease in 20 consecutive patients and will insert an implantable ECG monitoring device. The patient will then be followed up over a duration of two year and will be monitored for arrhythmia and mortality.
Background
Worldwide, the numbers of women who have a pre-existing cardiovascular disease or develop
cardiac problems during pregnancy are increasing and, due to the lack of evidenced-based
data, this provides challenges for the treating physician. Cardiovascular disease in
pregnancy is a complex topic as women can present either pre- or postpartum, due to a
pre-existing heart disease such as e.g. operated or unoperated congenital heart disease,
valvular heart disease, and chronic hypertension or familial dilated cardiomyopathy. On the
other hand, there are diseases which are directly associated with pregnancy such as
hypertensive disorders of pregnancy and peripartum cardiomyopathy (PPCM). Women often
present with symptoms and signs of cardiovascular disease such as palpitations and shortness
of breath, or even directly in acute heart failure. There is, in particular, a paucity of
data from developing countries of this unique disease pattern and presentations. Pregnancy
poses a physiological stress test as cardiac output increases by 30-50% close to term.
Further haemodynamic stress occurs during labour and many of the effects of pregnancy on
cardiovascular disease (CVD) persist for several months after delivery.
Awareness of the different cardiovascular diseases that can occur in pregnancy or postpartum
has received limited attention and the main focus has been on hypertension and preeclampsia.
The global impact of elevated blood pressure (BP)/hypertension, in general, is profound, as
it is responsible for more deaths worldwide than any other cardiovascular risk factor,
including tobacco use, obesity and lipid disorders (Vos, Sliwa et al. Lancet 2012; Gersh &
Sliwa, Eur Heart J 2010).
Beyond the higher income countries, 80% of worldwide CVD-related deaths now occur in low-
and middle-income countries (LMICs) (Sliwa, Stewart Circulation 2011; Abergunde, Mathers et
al, Lancet, 2007). In LMICs, morbid and fatal CVD-related events typically occur at a
younger age and affect more women (commonly in pregnancy), thereby exerting a more profound
impact on the family unit and the workforce. The recently published Global Burden of Disease
Study which reports on Years Lived with Disabilities (YLDs) for 1160 sequelae of 289
diseases and injuries does not report on the prevalence of CVD pre- and postpartum as an
entity. However, globally, it is estimated that CVD and, in particular, hypertensive
disorders of pregnancy, complicate 2-8% of pregnancies contributing, to a major extent, to
maternal mortality worldwide (Sliwa, Cardiovascular Research, in press 2014). Chronic
hypertension is now prevalent in 3% of women falling pregnant in the US (Seely and Ecker, N
Engl J Med, 2011) and will also influence the prevalence of acute coronary syndromes (ACS)
in pregnancy.
The recent confidential inquiry into maternal death in South Africa reported that of the
4867 deaths reported over 2 years, 14% were due to hypertensive disorders, with another 8.8%
due to medical and surgical conditions (www.hst.org/za/saving-mothers-2008-2010. This makes
cardiac disease in pregnancy a key focus area, with the aim of reducing morbidity and
mortality, not only by the South African Department of Health but also by the World Health
Organization and World Heart Federation.
We have recently carried out a single-centre prospective study on women presenting with CVD
in pregnancy at Groote Schuur Hospital, University of Cape Town, South Africa (manuscript
submitted). This study investigates an appropriate referral algorithm and reports on disease
presentation (n=226) and outcome of those patients, with significant disease warranting
follow-up at a tertiary care (n=152). Of the 152 women that were asked to come back for
follow-up, the CDMC 122 (80.2%) presented prepartum. The most common diagnoses where
congenital heart disease, valvular heart disease, cardiomyopathy and other diagnoses such as
e.g. Wolf-Parkinson-White, atrial fibrillation, arrhythmogenic right ventricular
cardiomyopathy.
Management of these patients is complex as palpitations in pregnancy are common due to
increased sympathetic tone. It is important to distinguish palpitations secondary to benign
tachycardias, such as sinus tachycardia, from more important arrhythmias, such as
supraventricular or ventricular tachyarrythmias. Supraventricular arrhythmias are known to
increase in pregnancy, presumably because of an increase in sympathetic tone. Ventricular
arrhythmias secondary to some long QT syndrome subtypes are known to increase in the
peripartum period. On the other hand, undiagnosed complex arrhythmia can have serious
consequences for the mother and fetus, including stroke and death. Most CV drugs are
contraindicated in pregnancy or have a FDA class C and D classification - e.g. beta-blockers
(C & D), soltalol (C) and amiodarone (D). The treating physician therefore needs to document
the exact nature of the arrhythmia-causing symptoms, such as palpitations, dizziness and
syncope, prior to making a decision on pharmacological or device management. As 24-hour
holters have a low diagnostic yield, the use of an ECG loop recorder ( REVEAL) could
potentially influence management.
Interestingly, we have used the REVEAL XT in 2 pregnant women with newly diagnosed
arrrythmogenic right ventricular cardiomyopathy and a strong family history of sudden
cardiac death. Sinus tachycardia was present and correlated with the symptoms of
palpitations. As only supraventricular tachycardia was detected, patients could be managed
conservatively and had good maternal and fetal outcome. On the other hand, 2 other women
presenting with palpitations and dizziness in pregnancy were subsequently diagnosed with
cardiac sarcoidosis, a serious condition associated with sudden cardiac death.
1. Objectives:
1.1. To investigate the use of a small ECG loop recorder (REVEAL devices) in pregnant
women, with or without structural heart disease, in whom supra/ventricular
tachyarrhythmias and bradyarrythmias are suspected.
2.1. To investigate if the REVEAL device will change management compared to a single 24
hour holter done at presentation.
Our research question is based on preliminary information, having used the REVEAL XT in
2 pregnant women with newly diagnosed arrhythmogenic right ventricular cardiomyopathy
and a strong family history of sudden cardiac death. As only supraventricular sinus
tachycardia was detected, patients could be managed conservatively and had good
maternal and fetal outcome. On the other hand, 2 other women presenting with
palpitations and dizziness in pregnancy were subsequently diagnosed with cardiac
sarcoidosis, a serious condition associated with sudden cardiac death. A REVEAL device
should have been used to guide the physician in management.
2. Patient population
The patients will be recruited via a single-centre, prospective study of women with
cardiovascular disease presenting pre- or postpartum, attending Groote Schuur Hospital.
Since 1 July 2010, these patients have been seen at a weekly clinic, jointly run by
cardiologists and obstetricians, under the leadership of Prof. Karen Sliwa and Prof
John Anthony. We see about 100 new patients presenting with cardiovascular disease in
pregnancy per annum. About 200 newly diagnosed pregnant women with documented or
suspected cardiovascular disease will be screened for the indication to insert a REVEAL
device. Those patients will be part of an ongoing registry entitled: Registry of newly
diagnosed cases with cardiac disease in maternity-Phase II ( CDM-2).
Device:
The REVEAL device has the size of a larger USB stick and can be inserted under local
anaesthetic under sterile conditions as e.g. a minor procedure room. It is inserted
under the skin and there are no wires connecting it e.g. to the cardiac chambers or any
vessels. The device can record the cardiac rhythm for the period to up to one year. The
REVEAL is routinely ised in South Africa for more than 10 years.
3. Study design and treatment groups
A single-centre, observational outcome study investigating peripartum women presenting
with symptoms and signs of arrhythmia.
We aim to recruit 20 consecutive women with an indication for the REVEAL, from a
population of about 200 pregnant women with documented or suspected cardiovascular
disease as part of the ongoing cardiovascular disease in pregnancy registry.
Human Ethics Committee approval has been obtained for the overall prospective outcome
study on cardiovascular disease in pregnancy (HEC REF: 173/2010)
Estimate study duration: 2 years Estimate study start date: June 2014 Estimate study
end date: May 2016
4. Endpoints
Our prospective study will answer the questions whether REVEAL devices:
4.1. Are acceptable as a diagnostic tool in pregnant women. This will be assessed by
documentation of a number of women presenting with an indication to have the REVEAL
inserted (based on standard criteria) and a number of women accepting to have the
device. We see about 100 new patients presenting with cardiovascular disease in
pregnancy per annum.
4.2. Detect arrhythmias in pregnancy and can guide the cardiologist and obstetrician in
appropriate management, ranging from assurance, to medical therapy, to device therapy
or termination of pregnancy.
4.3. Change the management of the condition compared to a single ECG performed at the
day of offering insertion of the REVEAL device.
5. Measurable outputs and Publication Plan
Presentation of data In the past decade I have been invited annually to present my research
in the form of invited lectures at the following meetings: Congress of the Heart Failure
Association of the ESC; European Cardiac Society of Cardiology, World Congress of
Cardiology, South African Heart Failure Society, Pan African Cardiac Society. The data
obtained from the study will be presented at those meetings.
Publication of Original Data The data will be published as part of the overall cardiac
disease in pregnancy registry and as a separate paper.
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Time Perspective: Prospective