Abstract
Background: High degree atrioventricular block (HDAVB) is an uncommon complication of non-ST-segment elevation myocardial infarction (NSTEMI) that frequently necessitates pacemaker implantation. This contemporary analysis compares need for pacemaker implantation based on the timing of intervention in acute NSTEMI complicated by HDAVB.
Methods: We used 2016-2017 National Inpatient Sample database to identify admissions with NSTEMI and HDAVB. Time to coronary intervention from initial admission was used to segregate the admissions into two groups: early invasive strategy (EIS) (<24 hours) and delayed invasive strategy (DIS) (>24 hours). Multivariable linear and logistic regression analysis was performed to compare in-hospital outcomes among the two groups.
Results: Out of 949,984 NSTEMI related admissions, coexistent HDAVB was present in 0.7% (n=6725) patients. Amongst those, 55.61% (n=3740) hospitalizations included invasive intervention (EIS=1320, DIS=2420). Patients treated with EIS were younger (69.95 years vs. 72.38 years, P<0.05) and had concomitant cardiogenic shock. Contrarily, prevalence of chronic kidney disease, heart failure, and pulmonary hypertension was higher in DIS group. EIS was associated with lower length of stay and total hospitalization cost. In-hospital mortality and pacemaker implantation rates were not significantly different between patients in the EIS and DIS groups.
Conclusion: HDAVB is a rare complication of NSTEMI and often associated with right coronary artery disease. The timing of revascularization does not appear to influence the rate of pacemaker placement in NSTEMI complicated by HDAVB. Further studies are needed to assess if early invasive strategy can benefit all patients with NSTEMI and HDAVB.
- HDAVB
- High degree atrioventricular block
- Non-ST segment elevation myocardial infarction
- NSTEMI
- Pacemaker implantation
Approximately, 1.5 million patients suffer from acute coronary syndrome (ACS) in the United States annually, and an increasing proportion of these patients are presenting with non-ST-segment elevation myocardial infarction (NSTEMI). In a previously published study by Rogers et al,1 prevalence of NSTEMI in patients with ACS increased from 14.1% to 59.1% from 1990 to 2006. Although traditionally ST-segment elevation myocardial infarction (STEMI) has been considered to have worse outcomes, at 6 months post NSTEMI, mortality rates may equal or exceed those of STEMI.2 This is due to significant complications associated with NSTEMI, which include cardiogenic shock, electrophysiologic abnormalities, and sudden cardiac death. A small portion of these patients present with high-degree atrioventricular block (HDAVB), which is characterized by two or more consecutive non-conducted p waves on the electrocardiogram (EKG). It is a transient or permanent conduction abnormality where the atrial and ventricular contractions become almost completely dissociated and often lead to hemodynamic instability requiring pacemaker implantation. Though HDAVB is rare, it is often life-threatening because of association with the greater extent of myocardial injury and involvement of the conduction system. NSTEMI can be treated with an ischemia-guided strategy or an invasive strategy based on symptoms and risk stratification.3 Invasive therapy can be further classified into immediate, early invasive strategy (EIS), within 24 hours of admission, and delayed invasive strategy (DIS), within 24 to 72 hours of admission. Current guidelines recommend prophylactic placement of temporary pacemaker in patients with NSTEMI and HDAVB and EIS only in patients with complications such as cardiogenic shock.3 It is, however, not known if an early invasive approach improves outcomes in patients with NSTEMI and HDAVB. Therefore, we carried out this study using the publicly available Nationwide Inpatient Sample (NIS) database to determine if EIS in patients with NSTEMI and HDAVB is associated with decreased mortality and need for permanent pacemaker placement.
Methods
Data were obtained from NIS, Healthcare Cost and Utilization Project, and Agency for Healthcare Research and Quality. The NIS is a de-identified data with the protection of patient’s health information, so we were not required to obtain institutional review board permission for our study. NIS from 2016-2017 was queried to identify all unweighted admissions of patients aged >18 years with discharge diagnosis of NSTEMI. Sampling weights were applied to derive national estimates, which minimizes the margin of error, representing over 96% of the US population. Admissions with primary discharge diagnosis of NSTEMI (ICD-10-CM code I21.4) were selected for study. Patients with existing pacemaker (ICD-10-CM code Z95.0) or implantable cardioverter-defibrillator implantation (ICD-10-CM code Z95.810) were excluded to improve cohort characteristics and specificity. Patients with HDAVB were identified by using ICD-10-CM code I44.1 and I44.2 consisting of Mobitz-type II second-degree AV block or complete AV block, respectively. Pacemaker insertion was identified by ICD-10-PCS codes 02H and 0JH. We then used procedural day variable available in NIS to identify time to coronary intervention, since initial admission and divided admissions into two groups: early intervention strategy or EIS (<24 hours) and delayed intervention strategy or DIS (>24 hours) (Figure 1). ICD-10 CM and ICD-10 PCS codes were used to identify baseline demographics, clinically relevant comorbidities, secondary diagnoses, and procedures.
Flowchart of patients who developed HDAVB after presenting with NSTEMI.
Primary and Secondary Outcomes
The primary outcome of analysis was to study impact of timing of intervention on rate of permanent pacemaker placement. Secondary outcomes included all-cause in-hospital mortality, hospital length of stay, and the cost of hospitalization.
Statistical Analysis
Differences between categorical variables were tested using Pearson chi-square test, and between continuous variables using t-test. Categorical data are described as frequencies in percentages, and continuous data are expressed as mean ± standard deviation. A value of P < 0.05 was considered significant. Multivariable or logistic regression models were utilized for dependent variables such as mortality, pacemaker implantation, and length of stay. All statistical analyses were performed with STATA version 16.1 (STATA Corp, College Station, Texas).
Results
We identified 949,984 weighted admissions with discharge diagnosis of NSTEMI, out of which 6725 (0.7%) had HDAVB. Of these, 3740 (EIS=1320, DIS=2420) patients were treated with invasive strategy; 410 patients were excluded as per previously defined exclusion criteria (presence of pacemaker=355, presence of defibrillator=55) (Figure 1). Majority patients were males (65.15 vs. 63.45%) and of Caucasian ethnicity (78.78% and 76.05%) in both the cohorts. Patients in EIS group were younger (69.95 vs 72.38, P≤0.05), more likely to have cardiogenic shock (24.24% vs. 14.86%, P<0.05) and a history of smoking (25.38% vs. 18.27%, P<0.05). Patients in DIS group were more likely to have congestive heart failure (CHF) (10.61% vs. 16.12%, P<0.05), chronic kidney disease (CKD) (21.59% vs. 29.75%, P<0.05), and pulmonary hypertension (4.55% vs. 9.92%, P<0.05). Most hospitalizations were in large (59.09% vs 58.47%), urban (95.45% vs 95.66%), and teaching hospitals (73.86% vs 73.38%). There was no statistical difference between two groups in terms of gender, race, income, and other comorbidities such as hypertension, hyperlipidemia, diabetes mellitus (DM). Baseline characteristics of the groups are presented in Table 1.
Baseline characteristics of patients with NSTEMI and HDAVB treated with early invasive strategy vs delayed invasive strategy
Overall, 26.47% (990) admissions with NSTEMI complicated by HDAVB required pacemaker implantation during the index hospitalization. 24.24% (330) patients in EIS group required pacemaker placement as compared to 27.07% (660) in DIS group (Table 2, Figure 2A). After multivariable analysis, EIS was not associated with a statistically significant decrease in the risk of permanent pacemaker implantation (OR 0.98, CI 0.67-1.43, P=0.91). CKD (OR 0.50, CI 0.30-0.83, P≤0.05) was associated with decreased risk of pacemaker implantation, whereas older age (OR 1.03, CI 1.01-1.05, P≤0.05) was associated with an increased risk of pacemaker implantation. Overall mortality rate of 8.02% was noted in patients with in patients with NSTEMI and HDAVB; a trend towards higher mortality was noted in the EIS group (10.61% vs 6.61%, P=0.06) (Figure 2A). After multivariate analysis, cardiogenic shock (OR10.36, CI 5.49-19.57, P≤0.05), cardiac arrest (OR3.98, CI 1.82-8.67, P≤0.05), and acute kidney injury (OR3.03, CI 1.09-3.75, P≤0.05) were associated with higher mortality. Odds of death in the EIS group were not found to be significantly different compared to the DIS group (OR1.21, CI 0.62-2.32, P=0.58).The mean length of stay was 6.47 days for the entire study cohort. The mean length of stay (5.20 days vs. 7.29 days, P≤0.05) and the cost of hospitalization ($153,698 vs. $176,187, P≤0.05) were higher in patients in the DIS group (Table 2, Figure 2B).
Outcomes of patients with NSTEMI and HDAVB treated with early invasive strategy vs delayed invasive strategy.
Outcomes of patients with NSTEMI and HDAVB treated with early invasive strategy vs delayed invasive strategy (Panels A and B).
Discussion
Our study is the first to report data on in-hospital outcomes of patients with NSTEMI and HDAVB treated with invasive strategy and their outcomes based on timing of coronary intervention. A few notable findings were as follows: (1) Slightly decreased rate of pacemaker implantation was seen in patients with HDAVB, and NSTEMI treated with early intervention (24.24%) as compared to delayed intervention (27.07%). The difference, however, was not statistically significant; (2) NSTEMI presenting with cardiogenic shock lead to early intervention but was associated with significantly higher mortality in our study cohort; (3) In patients with NSTEMI and HDAVB, delayed intervention was associated with increased length of hospital stay and cost of hospitalization.
Our analysis showed NSTEMI is complicated by development of HDAVB in 0.7% of the patients, which is similar to what has been reported in previous studies using NIS and randomized control trial data.4,5 It is also important to note that a majority of patients were treated with delayed (64.71%) than early (35.29%) invasive strategy in our cohort. Patients who were younger and those who presented with cardiogenic shock were much more likely to receive catheterization within 24 hours (EIS), which indicates that severity of presentation was a determinant of how the patients were treated.
In patients with NSTEMI, two possible mechanisms have been hypothesized to account for conduction abnormalities. According to vagal theory, the infarcted area causes stretch and distension of myocardium and release of chemical substances (prostaglandins, serotonin, free radicals) which activate efferent vagal fibers. This leads to hypotension and bradyarrhythmia. This phenomenon is also known as Bezold-Jarisch reflex.6 According to ischemia theory, AV nodal conduction defects are directly related to ischemia due to right coronary artery occlusion, and such abnormalities tend to resolve with revascularization.7 The 2008 ACC/AHA/HRS Guidelines for Device-Based Therapy acknowledge that, in cases of third-degree AV block complicating inferior wall myocardial infarction, permanent pacing should be reserved for patients in whom the block does not resolve with revascularization.8 Our study attempts to fulfill the gap in data on the timing of the revascularization and its association with reversibility of HDAVB in patients with NSTEMI.
Limitations
Our study had several limitations. Like any other study using administrative database, our study was a retrospective analysis. The incidence of HDAVB in our analysis is based on the coded diagnoses of each hospitalization and is prone to errors. The nature of the database and limitation of data did not allow us to analyze exact timeframe of procedures, and hence, we relied on the day of the procedure. We did not have information regarding specific types of NSTEMI, results from the left heart catheterization (culprit lesion, etc.), lab results, and medications that can affect sinus node or AV node function, which may affect outcomes.
Conclusions
Although HDAVB is an infrequent complication of NSTEMI, it is associated with substantial short-term mortality. Approximately, one out of four patients with NSTEMI and HDAVB received pacemaker implant in our study, and the timing of revascularization did not affect the rate of pacemaker placement in these patients.
Footnotes
Disclosures: The authors have not reported any financial support or conflicts of interest related to this work.
- Received March 7, 2022.
- Revision received August 1, 2022.
- Accepted September 26, 2022.
References
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