The Fetal Pacemaker

The Fetal Pacemaker

Yaniv Bar-Cohen

Gerald E. Loeb

Michael J. Silka

Jay D. Pruetz

Ramen H. Chmait


Severe bradycardia, particularly when there is a sustained fetal heart rate (FHR) < 50 beats per minute (bpm), is infrequent but carries a high mortality and is usually associated with hydrops fetalis due to the development of heart failure.1 There are several reasons for the poor outcome of these fetuses. First, functional elements to increase cardiac output are limited in the fetal heart. Cardiac myocytes lack well-developed sarcoplasmic reticulum, sympathetic innervation, and beta-adrenergic receptors.2,3,4 Beyond 19 weeks of gestation, the fetal heart is operating near the top of the Frank-Starling curve5; that is, both ventricles have a diminished capacity to increase stroke volume from increased preload.5,6 With reduced contractility and a limited ability to increase stroke volume, fetal cardiac output is largely FHR dependent. Second, medical therapy with chronotropic agents such as terbutaline may increase FHR for a time, but tachyphylaxis develops, and maternal side effects are often not tolerated.7,8 After birth, several reliable options are available for cardiac pacing in the neonate, child, and adult.9 However, in utero pacing to resolve hydrops and prolong the pregnancy to a mature gestation is a tremendous challenge. Currently, there are no proven methods available for successful fetal pacing.

Etiologies of Bradycardia

There are multiple etiologies for bradycardia, but not all are severe. The bradycardias with a 1:1 atrioventricular (AV) relationship result from sinus node (SAN) abnormalities associated with heterotaxy, usually left atrial isomerism in which the SAN is frequently absent. Although mutations of ion channel coding genes such as SCN510 and HCN411 and genes involved in SAN development12,13,14 have been identified as a cause of bradycardia during postnatal life, these appear to be rare in the fetus. Lastly, the SAN can be damaged by inflammation leading to fibrosis from viruses and maternal anti-Ro/SSA antibodies.15,16 In some cases, the entire atrium can be rendered electrically inert secondary to maternal antibodies.17

The bradycardias without a 1:1 relationship include AV block associated with maternal anti-Ro/SSA antibodies, structural cardiac anomalies, or functional AV block in long QT syndrome (LQTS).18 Regardless of etiology, fetuses with AV block are at high risk for severe bradycardia. It is this population that may benefit most from fetal cardiac pacing.

The development of hydrops fetalis due to congestive heart failure is seen in a quarter of pregnancies complicated by anti-Ro/SSA antibody-mediated AV block.1,19 The risk is higher in those with structural heart anomalies and AV block but unknown in fetuses with LQTS and functional AV block. Once hydrops fetalis occurs, if the fetus cannot be delivered due to prematurity or other clinical concerns, fetal demise is nearly inevitable.1,19 Although the degree of myocardial dysfunction is variable, successful pacing of a fetus with AV block and hydrops fetalis could theoretically allow resolution of hydrops over several weeks and permit and conclude in a term gestation. As a result, the specific group of patients with AV block and hydrops fetalis has historically been a target for fetal pacing despite the untested and invasive procedures. Unfortunately, to date, all attempts at pacing human fetuses have invariably failed with no survivors.

To address the challenge of fetal pacing, investigators at Children’s Hospital Los Angeles and the University of Southern California have developed a novel pacing system specifically designed for minimally invasive implantation in a human fetus. This chapter will discuss the challenges of fetal pacing, describe a number of historical attempts at fetal pacing, and outline the indications for and strategy behind a proposed fetal micropacemaker.


In the setting of a fetus with severe bradycardia, the development of hydrops fetalis carries an extremely poor prognosis. During the past three decades, there have been several reports attempting fetal pacing. Indications in all cases have been severe bradycardia, hydrops fetalis, and AV block. These cases are described below.

In 1986, Carpenter et al first reported an attempt at fetal pacing20 in a fetus with maternal anti-Ro/SSA-mediated AV block and an FHR of 44 bpm at 27 1/2 weeks of gestation. A 17-gauge needle was advanced though the uterine cavity and fetal thorax and into the right ventricular cavity. A bipolar pigtail pacing catheter was placed through this needle into the fetal right ventricle, and the needle was subsequently removed. The pacing wire was attached to an external pacing system, and pacing was initiated at 120 bpm. Initially, the capture threshold (the minimum amount of energy required to a cause cardiac contraction) was 1.5 mA, and the heart was paced at 6 mA. After 4 hours and 15 minutes, intermittent heart tones were heard, and the output was increased to 20 mA without improvement. Five minutes later, heart sounds were absent, and an ultrasound confirmed asystole, despite the pacing catheter having remained in the right ventricle with no evidence for hematoma, thrombi, or pericardial effusions. At postmortem examination, a serosanguinous pericardial effusion was present, but the cause of loss of pacing capture was not clear. Although the cause of death was not known, the authors describe the pacing lead as being only moderately flexible with the possibility of dislodgement or injury with vigorous fetal movement.

A second fetal pacing attempt was made on a 24-week fetus of an anti-Ro/SSA-positive pregnancy who also had hydrops and AV block but had not survived.21 The fetal umbilical vein was punctured using a 20-gauge needle, and a Teflon-coated pacing lead (0.009 in) was placed into the inferior vena cava just below the diaphragm and advanced through the right atrium into the right ventricle. Extra loops of wire were positioned in the fetal abdomen and in the amniotic fluid, and the pacing wire was connected to a Legend II pacemaker (Medtronic Inc., Minneapolis, MN) which was
implanted subcutaneously in the maternal abdominal wall. Pacing at 140 bpm was initiated (at 5 V with a 0.5 ms pulse width—capture threshold was 0.5 V), and the heart rate was 140 bpm 8 hours later. Soon thereafter, however, a return to a slow heart rate was seen, which was presumed to be due to lead displacement. Five days later, an attempt at placing a larger pacing wire along the complete length of the umbilical cord was made in an attempt to reduce the risk for dislodgement. The placental cord was directly punctured, and an 18-gauge needle was used. However, just after the umbilical vein was punctured, the heart rate fell further and asystole followed. An autopsy did not show hemorrhage or tamponade of the cord, but a bright yellow spot was visible at the right ventricular apex, the presumed initial site of pacing.

In 1998, the next report of an attempt at fetal pacing for severe bradycardia and immune-mediated AV block was via an open fetal surgery (maternal laparotomy and hysterotomy) and fetal thoracotomy for direct epicardial pacemaker placement. Unfortunately, the fetus did not survive the procedure.22

The first reported pacing attempt in a fetus with complex congenital heart disease and AV block was described by Assad et al in 2003.23 The fetus was at 24-week gestation at the time of the procedure and had complete AV block, severe bradycardia, marked hydrops, and left atrial isomerism with an atrioventricular septal defect. The novel lead was T-shaped and was introduced through an 18-gauge needle directly into the fetal myocardium (FIG. 6.3.1). A second lead was placed in the thoracic wall for bipolar stimulation, and both leads were connected to a pacemaker (Biotronik ERA 300; Berlin, Germany) implanted in the maternal abdominal wall. Pacing at 140 bpm was initiated, but cardiac tamponade was apparent during the procedure and managed with pericardiocentesis. By the first postoperative day, myocardial function had recovered with a mild pericardial effusion present. After 36 hours of pacing, however, asystole was noticed by ultrasound, and the pericardial effusion appeared significant. Fetal autopsy suggested that a moderate bloody effusion in the pericardial sac was the probable cause of death; the leads were in the left ventricle muscle and thoracic wall as expected.

Another attempt at open fetal pacing was described in 2011 by Eghtesady et al24 who reported on a 32-year-old mother with a 29-week gestation with immune-mediated AV block, hydrops fetalis, and heart rates in the mid-40s bpm. Open fetal surgery was
performed to implant the small Microny pacemaker (St. Jude Medical Inc., St. Paul, MN). On the first postoperative day, mild oligohydramnios was present, but cardiac output had appeared to be 150% of the prepacing cardiac output assessment. The next day, an attempt was made to increase the pacing rate due to persistent oligohydramnios; however, communication with the device to alter the pacing parameters was not successful despite repositioning attempts. Fetal demise was seen 5 days after the procedure and was attributed to chronic multiorgan failure based on the autopsy findings.

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Dec 30, 2020 | Posted by in CARDIOLOGY | Comments Off on The Fetal Pacemaker

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