Congenital Heart Block

Congenital heart block is a rare disorder, affecting between 1in 15,000 to 1 in 22,000 live-born infants (1,2). The first symptom detected in utero is usually an incidental finding of abnormally low fetal heart rate during prenatal visits. Causes of heart block include autoimmune antibodies and structural heart abnormalities. Transplacental passage of specific antibodies, known as SSA and SSB antibodies, account for 60 to 90 percent of all cases of congenital heart block (3).

Complete atrioventricular (AV) block occurs in 2 percent of offspring who have antibodies to Ro/ SSA and La/ SSB antibodies (4–6). Neonatal lupus is responsible for 80 to 95 percent of all cases of congenital complete heart block in the absence of structural defects diagnosed in utero or in the neonatal period (7, 8). Neonatal lupus is much less common cause of heart block presenting after the neonatal period (7). 

Independent of maternal disease, neonatal lupus is associated with SSA and SSB antibodies (9). Asymptomatic mothers are sometimes diagnosed retrospectively with positive antibodies during work up for a fetus with bradyarrhythmia. The prevalence of SSA antibodies was reported as 0.2 to 0.72 percent in female blood donor (10). The prevalence of SSA antibodies is 40 percent in patients with systemic lupus erythematosys (SLE), and 60 percent in those with Sjogren syndrome (11). 

Congenital heart block results from transplacental passage of maternal SSA and /or SSB antibodies to the fetus (12, 13). Although the precise mechanism of injury is not fully understood, it is proposed that heart block results from one of two theories. In the apoptosis theory, SSA or SSB antibodies bind to fetal cardiac fetal cells that have undergone physiological apoptosis. Normally, these apoptotic cells are phagocytosed and cleared. Binding of SSA or SSB antibodies prevent clearance of these cells. Release and activation of cytokines lead to autoimmune injury and secondary fibrosis of the AV node and its surrounding tissue, resulting in heart block (14). In the calcium channel theory, anti Ro antibodies are thought to inhibit calcium channels by direct interaction. These calcium channels are essential to impulse propagation and conduction in the sinoatrial (SA) and AV nodes. Disruption of intracellular calcium handling leads to apoptosis, inflammation and fibrosis, resulting subsequently in heart block (14).

Heart block may develop as first, second or third degree heart block. Bradycardia is not present in first degree, but is present in second and third degree heart block. Heart block most commonly occurs between 18 and 25 weeks’ gestation (14). When complete heart block occurs, there is no atrioventricular conduction, leading to complete dissociation of atrial and ventricular rates. The atrial rate is usually normal. The ventricular rate is typically between 50 to 80 beats per minute, but can be lower or higher (14). The rate can slow further as the pregnancy progresses.

It is important to monitor for development of heart block as there is significant morbidity and mortality associated with it. More intensive monitoring during pregnancy has been advised for those with SSA and SSB autoantibodies. Detection of heart block at an earlier stage may improve outcomes (15–17). Heart block is most likely to present at 18 to 24 weeks (18). During this period, normal sinus rhythm can progress to complete block in days or less. Heart block is less likely to occur between 26 to 30 weeks of pregnancy and will rarely develop after 30 weeks of pregnancy (19). Most experts advise performing weekly pulsed doppler fetal echocardiogram from 18 to 26 weeks, as this allows for diagnosis of first and second degree block, and provides a window for intervention before progression to complete heart block (19). This can be done through measurement of the mechanical PR interval. 

Mechanical PR interval is the time it takes for the electrical impulse to travel from the SA node to the bundle of His. This represents the onset of the atrial contraction to the onset of the ventricular contraction. It corresponds to the electrical P and QRS waves on an ECG. The normal PR interval is between 120-150 milliseconds (18, 20, 21).

Since both atrial and ventricular contractions need to be assessed, the location for PR interval assessment requires both left ventricular inflow, which corresponds to atrial systolic, and left ventricular outflow, which corresponds to ventricular systole. Pulse wave Doppler of the mitral valve is ideal to assess the PR interval, as the spectral display provides information on both left ventricular inflow and outflow. Time intervals are measured from the onset of the mitral A wave (atrial systole) to the onset of the aortic pulsed Doppler tracing (ventricular systole) (20, 21).

For first degree heart block, which is defined as PR interval greater than 150 ms, treatment with glucocorticoid remains controversial, as there are risks associated with therapy and some cases will revert to normal sinus rhythm spontaneously without treatment. If decision to treat is made, treatment involves fluorinated glucocorticoid, with either dexamethasone or betamethasone. ECHO should be repeated weekly. Medication should be stopped if there is progression to complete block and there is no evidence of extranodal disease (14). 

For second degree heart block, most will progress to complete heart block. Second degree blocks can revert without treatment, and not all cases will respond to treatment.  The goal of treatment with glucocorticoid is twofold, to decrease inflammation, and to prevent irreversible third degree block (22).

For third degree heart block, treatment with glucocorticoid is not advised, as it does not reverse once diagnosis has been made (23). 

After birth, fetal bradycardia can be controlled by drugs alone, or in combination with transcutaneous pacing and /or temporary cardiac pacing (24). As congenital heart block is irreversible, a permanent pacemaker is necessary in most cases and has been shown to improve long term survival and reduce symptoms (24). The type of pacemaker used will be determined by the patient’s body size and ventricular function.

Prognosis in fetus diagnosed with congenital heart block is depending on the severity of the heart block. Third degree heart block is associated with fetal demise in 5 to 20 percent of cases. Recurrence of congenital heart block occurs in approximately 18 percent in those with a history of congenital heart block in a previous fetus (14). 

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10.      Fritzler MJ, Pauls JD, Kinsella TD, Bowen TJ. Antinuclear, anticytoplasmic, and anti-Sjogren’s syndrome antigen A (SS-A/Ro) antibodies in female blood donors. Clin Immunol Immunopathol. 1985 Jul;36(1):120–8.

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12.      Izmirly PM, Saxena A, Kim MY, Wang D, Sahl SK, Llanos C, et al. Maternal and fetal factors associated with mortality and morbidity in a multi-racial/ethnic registry of anti-SSA/Ro-associated cardiac neonatal lupus. Circulation. 2011 Nov 1;124(18):1927–35.

13.      Izmirly PM, Saxena A, Sahl SK, Shah U, Friedman DM, Kim MY, et al. Assessment of fluorinated steroids to avert progression and mortality in anti-SSA/Ro-associated cardiac injury limited to the fetal conduction system. Ann Rheum Dis. 2016 Jun;75(6):1161–5.

14.      Popescu MR, Dudu A, Jurcut C, Ciobanu AM, Zagrean AM, Panaitescu AM. A Broader Perspective on Anti-Ro Antibodies and Their Fetal Consequences—A Case Report and Literature Review. Diagnostics. 2020 Jul 14;10(7):478.

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17.      Cuneo BF, Buyon JP. Keeping upbeat to prevent the heartbreak of anti-Ro/SSA pregnancy. Ultrasound Obstet Gynecol. 2019 Jul;54(1):7–9.

18.      Friedman DM, Kim MY, Copel JA, Davis C, Phoon CKL, Glickstein JS, et al. Utility of cardiac monitoring in fetuses at risk for congenital heart block: the PR Interval and Dexamethasone Evaluation (PRIDE) prospective study. Circulation. 2008 Jan 29;117(4):485–93.

19.      Brito-Zerón P, Izmirly PM, Ramos-Casals M, Buyon JP, Khamashta MA. The clinical spectrum of autoimmune congenital heart block. Nat Rev Rheumatol. 2015 May;11(5):301–12.

20.      Glickstein JS, Buyon J, Friedman D. Pulsed Doppler echocardiographic assessment of the fetal PR interval. Am J Cardiol. 2000 Jul;86(2):236–9.

21.      Glickstein J, Buyon J, Kim M, Friedman D. The Fetal Doppler Mechanical PR Interval: A Validation Study. Fetal Diagn Ther. 2004;19(1):31–4.

22.      Ciardulli A, D’Antonio F, Magro-Malosso ER, Manzoli L, Anisman P, Saccone G, et al. Maternal steroid therapy for fetuses with second-degree immune-mediated congenital atrioventricular block: a systematic review and meta-analysis. Acta Obstet Gynecol Scand. 2018 Jul;97(7):787–94.

23.      Friedman DM, Kim MY, Copel JA, Llanos C, Davis C, Buyon JP. Prospective Evaluation of Fetuses With Autoimmune-Associated Congenital Heart Block Followed in the PR Interval and Dexamethasone Evaluation (PRIDE) Study. Am J Cardiol. 2009 Apr;103(8):1102–6.

24.      Melim C, Pimenta J, Areias JC. Congenital atrioventricular heart block: From diagnosis to treatment. Revista Portuguesa de Cardiologia. 2022 Mar;41(3):231–40.

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