Incidence, predictors, and outcome of significant atrioventricular block in acute coronary syndrome − A study from major center in North-Eastern India

Bornali Dutta; Farhin Iqbal; Waseem Farooqui

doi:10.4103/jcpc.jcpc_12_21

ORIGINAL ARTICLE

Year : 2022 | Volume : 11 | Issue : 1 | Page : 15-21

Incidence, predictors, and outcome of significant atrioventricular block in acute coronary syndrome − A study from major center in North-Eastern India

Bornali Dutta, Farhin Iqbal, Waseem Farooqui
Department of Cardiology, Gauhati Medical College, Guwahati, Assam, India

Date of Submission	10-Feb-2021
Date of Decision	04-Aug-2021
Date of Acceptance	14-Oct-2021
Date of Web Publication	21-Apr-2022

Correspondence Address:
DM Cardiology Farhin Iqbal
DM (CARDIO), Department of Cardiology, Gauhati Medical College, Guwahati, Assam
India

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/jcpc.jcpc_12_21

Abstract

Background: Indian studies on significant atrioventricular (AV) block in entire spectrum of acute coronary syndrome (ACS) and its relation with clinical outcome are limited. Aims: The aim of this study is to determine the incidence, clinical predictor, and outcome of significant AV block complicating entire spectrum of ACS. Methods: All patients presenting with ACS from June 2017 to December 2018 were included in the study. The study population was divided into case and control groups based on the presence of significant AV block, either at admission or during hospitalization. The baseline clinical characteristics, mode of presentation, clinical course in the hospital, treatments in hospital, and complications related to the ACS and its treatment were analyzed between case and control groups. The inhospital and 30 day outcome was also analyzed. Results: A total of 1001 patients with ACS were included. One hundred and twenty-five patients of ACS with significant AV block comprised the study population (cases) and the rest 876 patients with ACS without significant AV block comprised the control population. The overall incidence of significant AV block was 12.48%. Patients with significant AV block had higher incidence of diabetes (40% vs. 20.77%, P-0.001), hypertension (36.8% vs. 20.89%, P-0.002), and history of smoking (57.6% vs. 34.2%, P-0.0001). On clinical presentation, patients with significant AV block had lower mean heart rate and higher killip class. Inferior wall myocardial infarction (44.4% vs. 22.8%, P-0.0001) was higher in cases, whereas anterior wall myocardial infarction (25.6% vs. 43.3% P-0.001) and unstable angina (4% vs. 10.2%, P-0.02) were higher in controls. Percentage of patients undergoing temporary pacemaker implantation or percutaneous coronary intervention during hospitalization was higher in cases. At 30 days, mortality was significantly higher among cases (24% vs. 8.1%, P-0.0001). Conclusion: Our data represent the first reported study on significant AV block in entire spectrum of ACS in North-eastern India and has noted the high incidence of significant AV block in our population and is associated with a worse short-term outcome.

Keywords: Acute coronary syndrome, atrioventricular block, North-Eastern India

How to cite this article:
Dutta B, Iqbal F, Farooqui W. Incidence, predictors, and outcome of significant atrioventricular block in acute coronary syndrome − A study from major center in North-Eastern India. J Clin Prev Cardiol 2022;11:15-21

How to cite this URL:
Dutta B, Iqbal F, Farooqui W. Incidence, predictors, and outcome of significant atrioventricular block in acute coronary syndrome − A study from major center in North-Eastern India. J Clin Prev Cardiol [serial online] 2022 [cited 2023 Jun 8];11:15-21. Available from: https://www.jcpconline.org/text.asp?2022/11/1/15/343641

Introduction

Significant atrioventricular (AV) block, defined as the presence of Mobitz type II second-degree or third-degree AV block, complicating acute coronary syndrome (ACS) is often associated with increased morbidity and mortality. Incidence rates of heart blocks vary in different populations and according to the type of ACS. Various studies have reported the incidence of significant AV block in ACS between 3% and 14% with an increased risk of in-hospital death.^{[1],[2],[3],[4],[5],[6],[7]} In the largest global registry on ACS, GRACE incidence of high-grade AV block high grade atrio-ventricular block (HAVB) complicating ACS was found to be 2.9%.^[8]

Indian studies on significant AV block complicating ACS have been limited. Most of the Indian studies on conduction block have been done in ST-elevation myocardial infarction (STEMI), mainly inferior wall myocardial infarction (IWMI) and not in the entire spectrum of ACS. Moreover, the associations between clinical factors including in-hospital therapies received and the risk of death within this group of patients has not been well described.^{[9],[10],[11]}

Our study on ACS from North-eastern India has shown that ACS in the region differs from national registry CREATE with greater percentage of STEMI patients, greater delay in seeking treatment, greater 30 day mortality, and lesser percentage of patients receiving reperfusion therapy.^[12] Moreover, the incidence and clinical spectrum of significant AV block in ACS have not been studied in North-east India. To address the above limitation, we prospectively studied our ACS population to determine the incidence, clinical predictor, and outcome of significant AV block complicating the entire spectrum of ACS.

Methods

All patients presenting with ACS from June 2017 to December 2018 were included in the study. Prior ethical clearance from the Institutional Ethics Committee was taken. Written informed consent was taken from the study participants. Detailed history, physical examination, and necessary investigations were done in all patients. Electrocardiographic (ECG) were recorded on admission and everyday thereafter till hospital discharge.

Inclusion criteria:

Patients must be >18 years of age
Patients must fulfil the diagnostic criteria of ACS as given below: Diagnosis of myocardial infarction (MI) was made if there is: Typical rise and gradual fall (troponin) or more rapid rise and fall (CK-MB) of biochemical markers of myocardial necrosis with at least one of the following.^[13]

Ischemic symptoms
Development of pathologic Q waves on the ECG
ECG changes indicative of ischemia (ST-segment elevation or depression.

Cases of ischemic symptoms with elevation of ST segment in ECG leads/presumed new-onset left bundle branch block in ECG were categorized as STEMI. Cases of ischemic symptoms without ST segment elevation were categorized as NSTEMI if their cardiac biomarkers are positive.

Unstable angina (UA) was defined as angina pectoris (or equivalent type of ischemic discomfort) with at least one of the three features: (1) Occurring at rest (or minimal exertion) and usually lasting >20 min (if not interrupted by nitroglycerin administration); (2) being severe and described as frank pain and of new onset (i.e., within 1 month); and (3) occurring with a crescendo pattern (i.e., more severe, prolonged, or frequent than previously); and (4) patients with above features without elevation in cardiac markers were categorized as UA.^[14]

Exclusion criteria:

Patients who were initially treated elsewhere and referred to the study center only for additional management
Patients with proven noncardiac chest pain and
Patients who were discharged before completion of the treatment for any reasons.

The study population was divided into cases and control based on presence of significant AV block, either at admission or during hospitalization. The baseline clinical characteristics, which were analyzed, were the age, gender, hypertension, diabetes mellitus, smoking status, and dyslipidemia. Mode of presentation, clinical course in the hospital, treatments in hospital, and in-hospital and 30-day outcome were also analyzed.

Patients were considered as hypertensive according to JNC 8 (The Eight Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure) criteria, diabetic as per American Diabetes Association criteria, and dyslipidemia according to National Cholesterol Education Program criteria. In addition use of anti-hypertensive, anti-diabetic or lipid lowering medications were used as criteria for hypertension, diabetes, and dyslipidemia, respectively. Either current or past history of tobacco smoking for 6 months was considered as smoking positive.

Those patients giving consent for angiography were taken up for angiography. Angiographic findings were noted. They were categorized as (1) normal coronaries, (2), insignificant disease (<50% diameter stenosis as per visual estimation), (3) single vessel disease, (4), double-vessel disease, (5), triple-vessel disease, and (6) left main disease. A comparison of clinical parameters, treatment received in hospital and outcome and angiographic profile between cases and control was done.

Statistical methods

Statistical analysis was performed using the online statistical calculator, www.graphpad.com. Categorical variables were compared by the Chi-square test and the continuous variables are presented as mean (standard deviation) and were compared by unpaired t-test. A probability value of <0.05 was considered statistically significant.

Observation and Results

From June 2017 to December 2018, a total of 1001 patients with ACS with and without significant AV block who were admitted in Cardiology Department of Gauhati Medical College and Hospital, Guwahati, were enrolled in the study after an informed consent. In our study, significant AV block was present in 12.48%, 95 (76%) complicating STEMI and 30 (24%) complicating NSTEMI/UA. The incidence of significant AV block with STEMI, NSTEMI, and UA was 13.4%, 12.6%, and 5.2%, respectively, in our study. Significant AV block occurred at the time of presentation in 44.8% of patients, whereas 55.2% developed this complication during the index hospitalization. Of the total population, 125 patients of ACS with significant AV block comprised the study population (cases) and the rest 876 patients of ACS without significant AV block comprised the control population [Table 1].

Table 1: Comparison of baseline characteristics between cases and control

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Mean age of study population was 57.53 ± 10.32. Mean age of control population was 57.48 ± 10.96. Mean age between cases and controls did not differ significantly. Among cases and controls the majority of cases were males as compared to females [Table 1].

While comparing the baseline characteristic between cases and control, we observed that patients with significant AV block had higher incidence of diabetes, hypertension and history of smoking. On clinical presentation, patients with significant AV block had lower mean heart rate and higher killip class [Table 1].

On analyzing the type of ACS between cases and control, IWMI (44.4% vs. 22.8%, P-0.0001) were higher in cases whereas anterior wall myocardial infarction (AWMI) (25.6% vs. 43.3% P-0.001) and UA (4% vs. 10.2%, P-0.02) were higher in controls. On analyzing the treatment pattern, there were no significant difference in treatment pattern between cases and controls with high percentage of patients in both groups receiving standard medical therapy. However among cases, greater percentage of patients underwent temporary pacemaker implantation (TPI) and went for percutaneous coronary intervention (PCI) during hospitalization. In our study, in patients with significant AV block TPI was done in 40% and permanent pacemaker implantation (PPI) was done in 1.6% during index hospitalization. However overall requirement of PPI was observed in 5.6% of ACS patient with significant AV block. There were two patients that refused PPI in AWMI. In IWMI with significant AV block, none of the patient underwent PPI during index hospitalization, however one patient who refused PPI during index hospitalization later underwent PPI. In our study, out of 5 patients of UA with significant AV block, 2 (40%) of them underwent PPI following Coronary artery bypass surgery (CABG) in other centre, and hence not included in the analysis.

Overall, 68.93% of patients underwent coronary angiography (72% in cases and 68.4% in control P-0.17).We did not observe any difference in the number of vessels involved between cases and control. However disease in right coronary artery (RCA) was significantly higher among cases [Table 1].

On analyzing the outcome at 30 days, we observed significantly higher mortality among cases. Moreover in hospital complication (congestive heart failure, cardiogenic shock and cardiac arrest) were also significantly higher among cases [Table 1].

The mortality rate in ACS patients with significant AV block was 46.82% in AWMI, 18.12% in IWMI and 16.6% in NSTEMI/UA. Of the 32 patients of significant AV block in Anterior wall MI, 15 (46.82%) patients died whereas in case of inferior wall MI only 10 (18.12%) died out of 55 patients. Of the remaining 17 patients of significant AV block in Anterior wall MI, two underwent PPI, whereas it resolved in 13 (40%) patients following revascularization. There were two patients that refused PPI.

Patients with significant AV block who died during hospitalization or at 30 days were analyzed of their clinical parameters during hospitalization. We observed that patients with significant AV block who died were older, had higher incidence of diabetes and history of smoking, higher incidence of AWMI, were in higher killip class at presentation, higher involvement of left anterior descending artery and experienced more in hospital complication including congestive heart failure, cardiogenic shock and cardiac arrest [Table 2].

Table 2: Comparasion of clinical characteristic of significant AV block patients among survivors and those who died

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Discussion

In the first ever study on incidence, predictor and outcome of significant AV block in ACS in North eastern India, we observed high incidence of significant AV block in our population and is associated with worse short term outcome.

In our study, incidence of significant AV block was 12.48%. Previous studies have reported varying incidence rates of significant AV block complicating MI with more recent studies reporting lower incidence rates. The thrombolysis and angioplasty in MI study group reported that the incidence of congenital heart block (CHB) in 373 patients with inferior STEMI who received thrombolytic therapy was 13%.^[2] Data from a study in Israel that examined the incidence rates of CHB in patients hospitalized with AMI in the prethrombolytic era (1981–1983) compared with those hospitalized in the thrombolytic era (1992–1996) showed a decline in incidence rates of CHB from 5.3% to 3.7%.^[3] Recent global studies, in the cotemporary PCI era has however found a lower incidence.^{[4],[5],[6],[7]} In the global registry GRACE, the overall incidence of HAVB in entire spectrum of ACS was found to be 2.9%.^[8]

However, similar to our study, the incidence of AV block in MI, was found to be similar, or lower to various studies from our country.^{[9],[10],[11]} Kumar et al., in their study on 573 patients with IWMI observed 39.3% had conduction blocks.^[9] The increased incidence of significant AV block in our study population, can be multi factorial. Compared to western data we had higher percentage of STEMI (70.7% in our study, compared to 37% in global registry, GRACE and studies has consistently shown that significant AV block is mainly observed in STEMI. Moreover in our study, lesser percentage of patient underwent primary PCI or thrombolysis mainly due to delayed presentation which may also contribute to higher incidence of significant AV block.

In our study, most of the patients were males, both cases and controls. This finding is similar to various studies, where males were predominant. Hreybe and Saba, studied 21,807 AMI from 1996 to 2003, where 63.4% patients were males.^[15] In the study by Kumar et al., 81.2% were males.^[9] In the global registry GRACE, males were predominant both in cases and controls.^[8]

In our study, we observed that that patient with significant AV block had higher incidence of diabetes, hypertension and history of smoking. Similar findings were observed by most other studies. Hreybe and Saba, studied 21,807 patients with a primary diagnosis of AMI. The prevalence of hypertension and of diabetes mellitus was 22.3% and 20.2%, respectively.^[15] Meine et al., had combined data on patients from 4 similar studies of STEMI and in their study, significant independent predictors of AV block included inferior MI, older age, worse Killip class at presentation, female sex, current smoking, hypertension, and diabetes.^[4]

Studies on the use of temporary or permanent pacing for significant AV block in the setting of ACS are limited. In our study, in patient with significant AV block, TPI was done in 40% and PPI was done in 1.6%. However, overall requirement of PPI was observed in 5.6% of ACS patient with significant AV block in our study. In the study by Meine et al., TPI was used in 53.6% and PPI in 10.1% of the patients with CHB and acute MI.^[4] In the GRACE study, TPI was done in 35% and PPI in 5.9% of the patients with HAVB in ACS.^[8] In the study by Harikrishnan et al., TPI was used in 31.8% and PPI in 13.4% of the STEMI patients with CHB.^[7] Compared to above studies, there was the similar use of temporary pacing but less frequent use of permanent pacing during index hospitalization in our study. Temporary pacing, is indicated in this population but was not associated with a reduction in in-hospital death as in our study, as we observed higher use of temporary pacemaker in significant AV block patients who died in hospital (63.3% vs. 32.6%, P-0.004).

Multiple mechanisms for significant AV block have been proposed in the setting of ACS. Vagally mediated mechanism is well documented in patients with myocardial ischemia or injury. Ischemic-mediated mechanical stretch and chemical substances stimulate parasympathetic afferent nerves in the inferior–posterior wall of the left ventricle. Activation of parasympathetic afferent nerves may result in reflex bradycardia and AV block (Bezold–Jarisch reflex). AV conduction defects may also occur as a direct result of ischemia. While the AV nodal artery typically arises from the RCA, collateral blood supply to the AV node is provided by the septal perforators of the left anterior descending artery with variable dual supply provided by either the RCA or left circumflex artery. The conduction system being relatively resistant to ischemia, can recover function faster than the adjacent myocardium once the ischemia is reversed. However, prolonged ischemia with extensive myocardial necrosis may result in irreversible injury to conduction system. Extensive MI involving the septum, in the setting of an AWMI, may result in extensive bilateral bundle branch infarction. Whereas AV block due to necrosis of the conduction system would invariably be irreversible and lead to PPI, the alternative reversible mechanism can also occur in AWMI. Wilber et al. described two patients who showed resolution of complete AV block within minutes of late reperfusion (>40 h) by angioplasty in anterior infarction, suggesting reversible ischemia as the mechanism of heart block.^[16] Transient complete AV block has also been reported as being caused by occlusion of the first septal perforator branch during PCI of left anterior descending coronary artery.^[17] As observed in our study, among cases overall mortality and need of permanent pacing was much higher in AWMI compared to IWMI, however 40% of patient had their AV block reversed following revascularization in AWMI with significant AV block, which is suggestive of significant benefit of revascularization in this high risk group. Similar observation has also been made in other studies.^[8],[7]

In our study, number of patients of UA with significant AV block was very small, however out of five patient of UA with significant AV block, one died and three of them underwent CABG for diffuse multivessel disease. Two patients underwent PPI following surgical revascularization in other centre. Although the mechanism of AV block in UA is not firmly established, presence of severe coronary artery disease reflects some irreversible damage to conduction system. Similar observation has been made in few other studies and case reports. In the GRACE study, 1.5% of UA patient had high grade AV block. They observed worse prognosis with UA or non-STEMI compared with STEMI, which may reflect the fact that patients with UA and non-STEMI typically have multi-vessel ischemia with compromised primary and collateral blood flow to the AV node and the septum resulting in more severe conduction impairment.^[8] Narin et al., reported two cases of complete heart block in patients with UA that required CABG. When AV block in one of the patients remained on postoperative day 15, he received a permanent pacemaker, whereas other patient reverted to 1:1 AV conduction immediately after surgical revascularization.^[18]

Previous studies have shown that ACS complicated by significant AV block had higher killip class and increased risk of in hospital complications e.g., cardiogenic shock, intra-ventricular arrhythmias, and increased risk of in hospital mortality.^[6],[7],[8] In our study too, patients with significant AV block presented with higher Killip class and had unfavorable short-term outcome, including death which may be related to the extent of myocardial injury, beyond that attributed to the AV block itself. Besides, being a marker of extensive myocardial injury, the development of significant AV block in ACS is also associated with a higher risk for cardiac death. In our study, the overall 30-day mortality in patients with ACS and significant AV block was 24%, which was almost 3-fold higher than in-ACS patients without significant AV block. Our findings reaffirm that significant AV block remains a severe prognostic marker in patients with ACS.

In our study, the mortality rate in ACS patients with significant AV block was 46.82% in AWMI, 18.12% in IWMI and 16.6% in NSTEMI/UA. Hence, there was significantly high mortality among AWMI patient developing significant AV block in our study. Similar observation has also been made in other studies.^[8],[7] In the study by Harikrishnan et al., CHB was associated with an approximately 4-fold increase in mortality among patients with anterior STEMI, compared to only a 2-fold increase in mortality in patients with inferior STEMI irrespective of the treatment strategy.^[7]

In our study, patients of ACS with significant AV block who died were older, had higher incidence of diabetes and history of smoking, higher incidence of AWMI, and were in higher killip class at presentation and experienced more in hospital complication. Similar observation was made in other studies. In GRACE study, the patients with HAVB who died in hospital were older (74 vs. 69 years, P < 0.001) and experienced more in-hospital complications including myocardial re-infarction (15 vs. 2.7%, P < 0.001), congestive heart failure (53 vs. 24%, P < 0.001), cardiogenic shock (67 vs. 11%, P < 0.001), and ventricular arrhythmias (28 vs. 9.8%, P < 0.001).^[8]

Study limitations

This was a single-center observational study with limited number of patients (n = 1001). Results might vary in multicenter study with larger population. Moreover, only 690 (68.93%) patients underwent coronary angiography due to cost constraints, which may be a confounding factor.

Conclusion

Our data represent the first reported study on significant AV block in the entire spectrum of ACS in North-eastern India and has noted the high incidence of significant AV block in our population and is associated with a worse short-term outcome. In the present study, significant AV block conferred a higher risk of congestive heart failure, cardiogenic shock, cardiac arrest, and death during hospitalization and at 30 days.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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