Publish in this journal
Journal Information
Vol. 73. Issue 7.
Pages 554-560 (July 2020)
Share
Share
Download PDF
More article options
Visits
Not available
Vol. 73. Issue 7.
Pages 554-560 (July 2020)
Original article
DOI: 10.1016/j.rec.2019.09.028
Full text access
Atrioventricular block in patients undergoing treatment with bradycardic drugs. Predictors of pacemaker requirement
Bloqueo auriculoventricular en pacientes en tratamiento con fármacos bradicardizantes. Variables predictoras de la necesidad de implante de marcapasos
Visits
...
Laura Jordán-Martíneza,b,
Corresponding author
laura.jordan.1987@gmail.com

Corresponding author: Avda. de las Fuerzas Armadas 2, 3.o, 18014 Granada, Spain.
, Ricardo Rivera-Lópeza,b, Francisco Bermúdez-Jiméneza,b, Juan Jiménez-Jaimeza,b, Javier Alzuetac, Alberto Barrera-Corderoc, Ricardo Rivera-Fernándezd, Manuel Jiménez-Navarroc, Miguel Álvareza,b, Luis Tercedora,b
a Servicio de Cardiología, Hospital Universitario Virgen de las Nieves, Granada, Spain
b Instituto de Investigación Biosanitaria, ibs.GRANADA, Granada, Spain
c Instituto de Investigación Biomédica de Málaga (IBIMA), UGC Corazón, Hospital Clínico Universitario de Málaga, CIBERCV, Universidad de Málaga (UMA), Málaga, España
d Unidad de Cuidados Intensivos, Complejo Hospitalario de Jaén, Jaén, España
Article information
Abstract
Full Text
Bibliography
Download PDF
Statistics
Figures (2)
Tables (3)
Table 1. Patient characteristics according to persistence (group 1) or not (group 2) of AVB after emergency department attendance
Table 2. Patient characteristics according to need for pacemaker implantation
Table 3. Factors associated with AVB persistence or recurrence at 3 years
Show moreShow less
Abstract
Introduction and objectives

Atrioventricular block (AVB) in the presence of bradycardic drugs (BD) can be reversible, and pacemaker implantation is controversial. Our objective was to analyze the pacemaker implantation rate in the mid-term, after BD suspension, and to identify predictive factors.

Methods

We performed a cohort study that included patients attending the emergency department with high-grade AVB in the context of BD. We studied the persistence of AVB after BD discontinuation, recurrence in patients with AVB resolution, and the predictive variables associated with pacemaker requirement at 3 years.

Results

Of 127 patients included (age, 79 [71-83] years), BAV resolved in 60 (47.2%); among these patients, recurrence occurred during the 24-month median follow-up in 40 (66.6%). Pacemaker implantation was required in 107 patients (84.3%), despite BD discontinuation. On multivariable analysis, the variables associated with pacemaker need at 3 years were heart rate <35 bpm (OR, 8.12; 95%CI, 1.82-36.17), symptoms other than syncope (OR, 4.09; 95%CI, 1.18-14.13), and wide QRS (OR, 5.65; 95%CI, 1.77-18.04). Concomitant antiarrhythmic treatment was associated with AVB resolution (OR, 0.12; 95%CI, 0.02-0.66).

Conclusions

More than 80% of patients with AVB secondary to BD require pacemaker implantation despite drug discontinuation. Predictive variables were wide QRS, heart rate <35 bpm, and clinical presentation other than syncope.

Keywords:
Atrioventricular block
Bradycardic drugs
Antiarrhythmic drugs
Pacemaker
Syncope
Abbreviations:
AVB
BDs
Resumen
Introducción y objetivos

El bloqueo auriculoventricular (BAV) en presencia de fármacos bradicardizantes (FBZ) puede ser reversible, y está en controversia el implante de marcapasos. El objetivo es analizar la necesidad de tratamiento con marcapasos a medio plazo, tras la suspensión de los FBZ, e identificar factores predictores.

Métodos

Se estudió a una cohorte de pacientes que acudieron a urgencias con BAV de alto grado mientras tomaban FBZ. Se estudió la persistencia de BAV tras la interrupción del fármaco, la recurrencia en los pacientes con resolución del BAV y las variables predictoras asociadas con la necesidad de marcapasos a los 3 años de seguimiento.

Resultados

De 127 pacientes (edad, 79 [71-83] años), en 60 (47,2%) se resolvió el BAV; de estos, en 40 (66,6%) el BAV recurrió en los 24 meses de seguimiento medio; 107 pacientes (84,3%) tuvieron indicación de implante de marcapasos pese a suspenderse los FBZ. Las variables asociadas con la necesidad de marcapasos a los 3 años en el multivariable fueron: frecuencia cardiaca<35 lpm (OR=8,12; IC95%, 1,82-36,17); síntomas diferentes del síncope (OR=4,09; IC95%, 1,18-14,13) y QRS ancho (OR=5,65; IC95%, 1,77-18,04). El tratamiento con antiarrítmicos no se asoció con necesidad de marcapasos (OR=0,12; IC95%, 0,02-0,66).

Conclusiones

Más del 80% de los pacientes con BAV secundario a FBZ precisan implante de marcapasos a pesar de suspenderlos; los predictores son el QRS ancho, la frecuencia cardiaca <35 lpm y la presentación clínica distinta del síncope.

Palabras clave:
Bloqueo auriculoventricular
Fármacos bradicardizantes
Fármacos antiarrítmicos
Marcapasos
Síncope
Full Text
INTRODUCTION

Atrioventricular block (AVB) frequently develops in patients taking bradycardic drugs (BDs)1 such as beta-blockers, nondihydropyridine calcium antagonists, and digoxin.

BDs have classically been considered a reversible cause of AVB2–4 but it is difficult to determine if a patient's AVB is connected to these drugs per se or if there is an underlying conduction disorder. Moreover, few studies have analyzed the clinical course and prognosis of patients who develop AVB while taking BDs.1,5–8 According to European clinical practice guidelines,2 patients with reversible AVB, such as that caused by BDs, are not indicated for permanent pacemaker implantation (class III recommendation, level of evidence C). However, the new 2018 guidelines of the American College of Cardiology/American Heart Association (ACC/AHA)3 consider permanent pacemaker implantation to be “reasonable” in selected patients who have symptomatic second- or third-degree AVB and are undergoing medically necessary and stable antiarrhythmic or beta-blocker therapy, without the need for a washout period (class IIa recommendation, level of evidence B). Based on recent work,1,6,7 the guidelines additionally assert in the section on specific related recommendations that, although a BD overdose can cause reversible AVB, the therapeutic doses of these drugs do not generally cause AVB. Thus, controversy surrounds the management of high-grade AVB in patients receiving BD therapy.

The objective of this study was to analyze the need for pacemaker implantation in the short- and mid-term after BD discontinuation in a consecutive series of patients attending either of 2 emergency departments with symptomatic high-grade AVB in the presence of BDs. An additional aim was to identify the variables predicting pacemaker requirement in the short-term due to AVB persistence or during follow-up due to recurrence.

METHODSStudy population

The present retrospective observational cohort study enrolled patients consecutively attending the emergency departments of 2 hospitals between January 2012 and December 2015. The study included all patients who, after their stay in the emergency department, were discharged with any of the following International Classification of Diseases, Ninth Revision, Clinical Modification codes: 426.0 (complete AVB), 426.1 (AVB and unspecified AVB), 426.6 (heart block), 426.9 (unspecified conduction disorder), 427.8 (other specified cardiac dysrhythmias), 427.9 (unspecified cardiac dysrhythmia), and 780.2 (syncope and collapse).9 Among the patients identified (figure 1), those who met the following criteria were selected:

  • Diagnosis of third-degree AVB in sinus rhythm or second-degree Mobitz type II atrial fibrillation or 2:1 block.

  • Of these, we selected patients receiving treatment with any of the following BDs: beta-blockers, nondihydropyridine calcium antagonists, or digoxin. Type Ic antiarrhythmics (according to the Vaughan-Williams classification) and amiodarone were considered concomitant medications and were also discontinued in the patients included in the present analysis.

  • Patients with any of the following comorbidities were excluded: acute coronary syndrome, hyperkalemia ≥ 6.5 mEq/L, digoxinemia> 2 ng/mL, AVB secondary to radiofrequency ablation, and clinical impossibility of drug discontinuation.

Figure 1.

Patient flow diagram. AVB, atrioventricular block; PM, pacemaker.

(0.18MB).

The protocol was approved by the relevant ethics committee.

Patient flow

The sample was divided into 2 groups (figure 1) based on whether the bradyarrhythmia resolved after a 48-hour BD washout period. This length of time was chosen because it is similar to that used in other studies1 and because it exceeds the average half-lives of the BDs analyzed. Group 1 comprised patients with persistent AVB who underwent pacemaker implantation, whereas group 2 comprised patients with AVB resolution who were discharged from the emergency department without a pacemaker. In the latter group, analysis was performed of the rate of symptomatic AVB recurrence motivating a repeat visit to the emergency department after BD discontinuation during a 3-year follow-up; these patients were divided into group 2 A, who had recurrence and required pacemaker implantation, and group 2 B, who did not have recurrence.

Variables analyzed

Demographic variables were recorded, as well as cardiovascular risk factors, the symptoms motivating emergency department attendance, previous heart diseases, electrolytes, renal function measured by serum creatinine, heart rate, the presence of wide QRS, and the use of BDs and antiarrhythmic drugs. For more practical assessment and treatment, the variable heart rate at admission was divided into ranges to identify the cutoff point providing the best discriminatory power.

Also recorded were pacemaker therapy during the first admission or after discharge and events during follow-up: 3-year mortality and emergency department attendance due to symptomatic bradyarrhythmia, syncope, and trauma as secondary endpoints.

Finally, as primary endpoint, the need for pacemaker implantation was studied at 3 years of follow-up. AVB electrocardiographically recorded in patients was considered to be recurrence (the secondary endpoint mortality was considered absence of recurrence, except when ECG-documented AVB was recorded as the cause of death).

Follow-up

Follow-up was performed by 2 cardiologists using the same protocol for all patients in both centers. The data examined to establish if the patients had experienced any recurrence or event during follow-up were collected from the hospital medical records and health center and via centralized telephone calls. Although the follow-up was completed in all patients, a 3-year follow-up cutoff was applied in the univariable and multivariable analyses performed to identify the variables associated with pacemaker indication at 3 years and to homogenize follow-up durations. To analyze trauma during follow-up and mortality, another cutoff was established at 3 years: this cutoff point was chosen because it is the longest follow-up possible for the most recently enrolled patients (those from 2015).

Statistical analysis

The chi-square test was used for qualitative variables; continuous variables were analyzed with the Mann-Whitney U test and are expressed as median [25th and 75th percentiles]. P <.05 was considered statistically significant. A multivariable logistic regression analysis was performed to predict pacemaker requirement at 3 years. In this analysis, we included the variables associated with P <.20 with AVB persistence and recurrence in the univariable analysis, applying stepwise selection and removing from the model those variables with P> .05.

Next, the area under the receiver operating characteristic (ROC) curve of the logistic regression model was analyzed to predict pacemaker requirement at 3 years using only those variables significantly associated with pacemaker requirement at 3 years in the multivariable analysis. The sensitivity and specificity values of this model were determined by analyzing the different cutoff points and selecting the one offering the best results.

Data were analyzed using the R statistical package.

RESULTS

The patient flow diagram of the study can be seen in figure 1. Of the 152 patients who attended the emergency department with high-grade AVB while taking BDs, we studied 127 patients meeting the inclusion criteria. Thus, 25 patients were excluded (due to acute coronary syndrome [n=12], clinical impossibility of drug discontinuation [n=7], digoxinemia> 2 ng/mL [n=4], and hyperkalemia ≥ 6.5 mEq/L [n=2]).

Of the 127 patients finally included (age, 79 [71-83] years; 50.4% men), 52.8% (n=67) still had AVB after BD discontinuation (group 1); the remainder (n=60) recovered atrioventricular conduction and were discharged without pacemaker implantation (group 2). The mean follow-up duration was 24 months and 2 patients (1.5%) were lost to follow-up. During this period, 40 patients in group 2 (66.6%) had AVB recurrence and underwent pacemaker implantation; in 37 of these, the block recurred in the 3 years after emergency department discharge (group 2 A).

In the overall sample, 107 patients (84.36%) required acute pacemaker implantation or implantation during follow-up despite drug discontinuation; 104 required the pacemaker implantation at the 3-year follow-up (groups 1 and 2 A), whereas the AVB resolved and did not recur after drug discontinuation in only 23 (18.1%; group 2 B) (figure 1). The median time to AVB recurrence was 65 [12-201] days.

Baseline characteristics and univariable analysis: variables related to the need for acute pacemaker implantation

Atrioventricular conduction recovery was more frequent in patients taking 2 negative chronotropic drugs (particularly digoxin) or with narrow QRS, a higher heart rate, or atrial fibrillation (table 1). Notably, all patients receiving treatment with 2 drugs had atrial fibrillation.

Table 1.

Patient characteristics according to persistence (group 1) or not (group 2) of AVB after emergency department attendance

  Total (n=127)  AVB persistence (n=67)  No AVB persistence (n=60)  P 
Men  64 (50.4)  36 (53.7)  28 (46.7)  .427 
Age, y  79 [71-83]  79 [70-83]  78 [71-83]  .179 
Mode of presentation        .302 
Syncope  45 (35.4)  24 (35.8)  21 (35.0)   
Presyncope  37 (29.1)  18 (26.9)  19 (31.7)   
Asthenia  16 (12.6)  6 (8.9)  10 (16.7)   
Heart failure  29 (22.8)  19 (28.4)  10 (16.7)   
Heart rate during the AVB, bpm  35 [30-40]  35 [30-40]  36 [32-40]  .100 
Creatinine  1.1 [0.8-1.6]  1.1 [0.8-1.4]  1.1 [0.9-1.6]  .434 
QRS interval  120 [110-140]  130 [110-140]  115 [100-140]  .110 
PR interval  210 [180-240]  220 [180-240]  200 [160-240]  .523 
Wide QRS  70 (55.1)  42 (62.7)  28 (46.7)  .070 
Heart disease  58 (45.7)  29 (43.3)  29 (48.3)  .568 
Ischemic heart disease  36 (28.3)  21 (31.3)  15 (25.0)   
Other  26 (20.5)  11 (16.4)  15 (25.0)   
Atrial fibrillation  41 (32.3)  16 (23.9)  25 (41.7)  .032 
Hypertension  108 (85.0)  58 (86.6)  50 (83.3)  .610 
Diabetes mellitus  70 (55.1)  40 (59.7)  30.0 (50.0)  .272 
Beta-blockers  99 (78.0)  52 (77.6)  47 (78.3)  .922 
Calcium antagonists  23 (18.1)  13 (19.4)  10 (16.7)  .689 
Digoxin  15 (11.8)  4 (6.0)  11 (18.3)  .051 
Flecainide  5 (3.9)  2 (3.0)  3 (5.0)  .666 
Amiodarone  6 (4.8)  2 (3.0)  4 (6.7)  .420 
Antiarrhythmic agents  11(8.6)  4 (6.0)  7 (11.7)  .347 
2 drugsa  22 (17.3)  6 (9.0)  16 (26.7)  .008 
Mortalityb  25 (19.6)  15 (22.3)  10 (16.6)  .412 

AVB, atrioventricular block.

Data are expressed as No. (%) or as median [interquartile range]

a

Patients with 2 drugs were treated with digoxin or antiarrhythmic agents + beta-blockers or calcium antagonists.

b

Mortality at 3 years of follow-up.

Mortality and events during follow-up

There were no significant differences in 3-year mortality between groups 1 and 2 (table 1).

Of the 40 patients with AVB recurrence, 16 (40%) had syncope, 8 (20%) had presyncope, and 16 (40%) had asthenia and effort intolerance.

There was a tendency for a higher incidence of trauma requiring emergency department treatment at 3 years of follow-up in group 2 than in group 1 (13.3% [n=8] vs 4.4% [n=3]; P=.11). During the complete follow-up, group 1 patients had 2 traumatic brain injuries and 1 had hip fracture. Group 2 patients had 7 traumatic brain injuries and 2 had rib fractures.

Comparison of groups 1 and 2 A with group 2 B. Variables associated with the mid-term need for pacemaker implantation

The 23 patients whose AVB had not recurred 3 years after BD discontinuation (table 2) had a higher heart rate in the emergency department, as well as a higher prevalence of narrow QRS, clinical presentation as syncope or presyncope (vs asthenia or heart failure), and concomitant antiarrhythmic treatment. Although few patients were receiving treatment with digoxin, the need for pacemaker implantation was particularly high in this group.

Table 2.

Patient characteristics according to need for pacemaker implantation

  PM need (n=104)  No PM need (n=23)  P 
Sex, male  53 (51.0)  11 (47.8)  .785 
Age, y  79 [71-83]  74 [68-82]  .519 
Syncope as presentation  63 (60.6)  19 (82.6)  .054 
Heart rate during the AVB, bpm  35 [30-40]  40 [35-43]  .014 
Creatinine  1.2 [0.9-1.6]  1 [0.8-1.3]  .902 
Wide QRS  63 (60.6)  7 (30.4)  .011 
Heart disease  47 (45.2)  11 (47.8)  .819 
Atrial fibrillation  32 (30.8)  9 (39.1)  .432 
Hypertension  88 (84.6)  20 (87.0)  .776 
Diabetes mellitus  60 (57.7)  10 (43.5)  .204 
Beta-blockers  80 (76.9)  19 (82.6)  .552 
Calcium antagonists  18 (17.3)  5 (21.7)  .617 
Digoxin  15 (14.4)  .071 
Flecainide  3 (2.9)  2 (8.7)  .222 
Amiodarone  4 (3.8)  2 (8.7)  .297 
Antiarrhythmic agents  7 (6.7)  4 (17.4)  .113 
2 drugs*  16 (15.4)  6 (26.1)  .231 
Heart rate <35 bpm  43 (41.3)  3 (13.0)  .017 

AVB, atrioventricular block; PM, pacemaker.

Data are expressed as No. (%) or median [interquartile range].

*

Patients with 2 drugs were treated with digoxin or antiarrhythmic agents + beta-blockers or calcium antagonists.

Acute or 3-year need for pacemaker implantation

Multivariable analysis with multiple logistic regression (table 3) showed that pacemaker need due to irreversible AVB or AVB recurrence at the 3-year follow-up was significantly associated with the following: heart rate <35 bpm (odds ratio [OR]=8.12; 95% confidence interval [95%CI], 1.82-36.17; P=.006), wide QRS on ECG (OR=5.65; 95%CI, 1.77-18.04; P=.003), and a clinical presentation other than syncope or presyncope (OR=4.09; 95%CI, 1.18-14.13; P=.026). Concomitant antiarrhythmic treatment was a protective factor (OR=0.12; 95%CI, 0.02-0.66; P=.014). This model had an area under the ROC curve discrimination of 0.82 (0.71-0.94) (figure 2) to identify patients requiring a pacemaker at 3 years of follow-up despite BD discontinuation. A probability value of 0.85 with 75% sensitivity and 87% sensitivity was chosen because it provided the best discriminatory power.

Table 3.

Factors associated with AVB persistence or recurrence at 3 years

Variable  Crude OR  P  Adjusted OR  P 
Heart rate <35 bpm  4.69 [1.31-16.81]  .017  8.12 [1.82-36.17]  .006 
Wide QRS  3.51 [1.33-9.28]  .011  5.65 [1.77-18.04]  .003 
Without syncope*  3.09 [0.98-9.74]  .054  4.09 [1.18-14.13]  .026 
Antiarrhythmic agents  0.34 [0.11-1.29]  .113  0.12 [0.02-0.66]  .014 
Diabetes mellitus  1.77 [0.71-4.41]  .204    .246 
Digoxin  77.91 [0.01-5.13 × 105.071    .998 

AVB, atrioventricular block; OR, odds ratio.

*

Mode of presentation other than syncope or presyncope.

Figure 2.

Area under the receiver operating characteristic (ROC) curve of the logistic regression model for the need for pacemaker implantation at 3 years of follow-up.

(0.05MB).
DISCUSSION

Our results show that almost 85% of patients who attend an emergency department with AVB while taking BDs ultimately require permanent pacemaker implantation. These data are in line with those published previously,1,5–8 but our work involves a series of patients from 2 centers and a larger sample size, enabling more robust analysis. In addition, 4 independent variables were identified that could help to predict patients who will eventually require a permanent pacemaker or, in contrast, to identify patients, fewer than 20%, who will not require a pacemaker in the mid-term.

The ramifications of these results are substantial because they indicate the need to consider a change to the clinical practice. First, according to our findings and those of other studies,1,5–8 AVB is rarely attributable to BDs alone. Rather, the results seem to indicate that these drugs reveal a latent conduction disorder. In addition, the delay to pacemaker implantation, imposed to determine whether the block resolves with drug discontinuation, can have deleterious consequences for patients due to reduced cardiac output or the need for a temporary pacemaker, with the associated comorbidities,6 as well as for the health care system due to a prolonged hospital stay, particularly that in the emergency department or coronary care unit.

In the mid-term, the clinical recurrence of AVB can have severe repercussions for patients, such as syncope, trauma, and fractures. These are particularly impactful in vulnerable elderly patients,10 who are more susceptible to developing bradycardia secondary to BD therapy.11

Although BD use is a relatively frequent finding in the presence of symptomatic AVB, few studies have analyzed its clinical course.1,6 Those results, similar to those published by other authors, such as Zeltser et al.,1 indicate a recurrence rate close to 50%. In an interesting study, Knudsen et al.6 analyzed patients under treatment with BDs who required temporary pacemaker implantation due to AVB: about 90% ultimately required a permanent pacemaker, with a nonnegligible complication rate. In this context, some authors have proposed pacemaker implantation independently of BD use.12 Notable considerations include the waste of resources due to the need for patient monitoring while the BD is eliminated, as well as the risk of a clinical deterioration in these patients while they await definitive treatment. In addition, the risk of syncope or sudden cardiac death is negligible in patients who have been discharged after restoration of atrioventricular conduction. In contrast, it should not be forgotten that pacemaker implantation is still an invasive procedure, one that is not complication-free. Accordingly, it is essential to identify those patients who will benefit from the device. A specially designed comparative study is required to investigate the prognosis of early pacemaker implantation in patients who recover from pharmacological AVB vs a conservative strategy.

The innovative aspect of the present work is that it identifies variables that help to predict those patients attending an emergency department with BD-associated AVB who will eventually require a definitive pacemaker. These variables, which can be obtained in the first bedside evaluation, predict the clinical course and reduce possible complications due to a delay to the permanent treatment. They also indicate patient groups with different behaviors who should be the focus of future studies for further knowledge advances. Notably, although the need for pacemaker implantation (acute or during follow-up) was high in all groups, a pacemaker was ultimately required by 90% of patients with wide QRS and a very low heart rate (< 35 bpm) or with a clinical presentation other than syncope. In addition, patients under treatment with groups Ic and II antiarrhythmic agents13 (flecainide, propafenone, and amiodarone) in combination with BDs appear to have fewer intrinsic conduction disorders and to recover normal conduction without the need for pacemakers. This could be explained by the effect of these drugs on the His-Purkinje system and on cell refractoriness.14–17 For their part, beta-blockers, nondihydropyridine calcium antagonists, and digoxin are characterized by their stronger negative chronotropic effects due to their direct action on the sinoatrial and atrioventricular nodes and lack of action on intra-Hisian and infra-Hisian conduction.18–22 This finding reinforces the belief that His-Purkinje involvement and its correct identification are crucial for clinical decision making. Indeed, the electrocardiographic variables independently associated with the eventual need for pacemaker implantation (wide QRS and heart rate <35 bpm) indicate an infra-Hisian location of the AVB. This location should not be affected by beta-blockers, calcium antagonists, or digoxin, which would reinforce the hypothesis of an underlying conduction disorder with a high risk of recurrence even without BDs. Although few patients were being treated with digoxin (n=15), their recurrence rate was very high, which is why it should be taken into account, despite not being included in the logistic regression model.

Another interesting finding is that patients with more latent symptoms, such as asthenia and heart failure, seem to more frequently have a more permanent conduction system disorder than those who initially have syncope or presyncope, whose bradyarrhythmia is more likely to resolve without recurrence. A possible explanation for this finding could be that, while a sudden clinical presentation such as syncope may be related to paroxysmal AVB, heart failure or asthenia could be related to persistent AVB that has become established during a sufficiently prolonged period to lead to more durable symptoms. Regarding the literature, our data fail to confirm the findings of Osmonov et al.,7 which indicated that a history of heart failure could protect against pacemaker need.

Limitations

The present article has some limitations. First, because the data were retrospectively collected, the variables analyzed were those described in the medical records. Thus, there may be other variables that more accurately predict recurrence. However, this characteristic does not invalidate the findings reported in the present work, which also offer excellent predictive capacity. Moreover, our prospective analysis of the diagnostic classification of the enrolled patients minimized the possibility of missing patients who should have been included in the study.

This study did not exclude patients taking group I and III antiarrhythmic agents, as done in similar studies, although we only included patients taking beta-blockers, nondihydropyridine calcium antagonists, or digoxin. These drugs have a more marked effect on the His-Purkinje system and may have a clearer relationship with AVB development, as shown by our results.

Finally, the small number of patients with antiarrhythmic therapy in the present study limited our ability to draw definitive conclusions, although the results nonetheless show that these drugs may have different implications and should be analyzed in future studies with larger sample sizes. Other drugs such as ivabradine were not included in the analysis because their main effect is on the sinoatrial node; some authors23,24 have already published an effect, albeit minor, of ivabradine on the atrioventricular node.

CONCLUSIONS

In most patients with AVB taking BDs, the bradyarrhythmia persists or recurs after drug discontinuation, indicating the presence of an intrinsic conduction disorder. In the mid-term, more than 80% of such patients require pacemaker implantation. Predictive variables can help to identify patients who will require a pacemaker, without the need to wait for new recurrences and avoiding the associated complications.

FUNDING

No funding has been received to support this study.

CONFLICTS OF INTEREST

None to declare.

WHAT IS KNOWN ABOUT THE TOPIC?

  • AVB in patients taking BDs is a frequent clinical challenge with controversial management.

  • Few studies have analyzed the clinical course and prognosis of these patients but the current literature indicates a high rate of AVB recurrence, despite drug discontinuation.

WHAT DOES THIS STUDY ADD?

  • The present study provides data on the largest patient sample to date with the longest follow-up period.

  • A high rate of pacemaker implantation was found, both acute and during follow-up, and several predictive variables were identified.

  • Also analyzed were the rates of syncope and injuries associated with AVB recurrence, which are elevated, particularly considering their clinical impact in elderly patients.

  • The high discriminatory power of the predictive model, based on clinical and electrocardiographic characteristics, facilitates the early identification of patients with AVB taking BDs who will ultimately require a permanent pacemaker.

References
[1]
D. Zeltser, D. Justo, A. Halkin, et al.
Drug-induced atrioventricular block: prognosis after discontinuation of the culprit drug.
J Am Coll Cardiol., 44 (2004), pp. 105-108
[2]
M. Brignole, A. Auricchio, G. Baron-Esquivias, European Society of Cardiology (ESC), European Heart Rhythm Association (EHRA), 2013 ESC Guidelines on cardiac pacing and cardiac resynchronization therapy: The Task Force on cardiac pacing and resynchronization therapy of the European Society of Cardiology (ESC). Developed in collaboration with the European Heart Rhythm Association (EHRA), et al.
Europace, 15 (2013), pp. 1070-1118
[3]
F.M. Kusumoto, M.H. Schoenfeld, C. Barrett, et al.
2018 ACC/AHA/HRS Guideline on the Evaluation and Management of Patients With Bradycardia and Cardiac Conduction Delay: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines, and the Heart Rhythm Society.
J Am Coll Cardiol., 74 (2019), pp. 932-987
[4]
J.M. Mangrum, J.P. DiMarco.
The evaluation and management of bradycardia.
N Engl J Med., 342 (2000), pp. 703-709
[5]
R. Shohat-Zabarski, Z. Iakobishvili, J. Kusniec, A. Mazur, B. Strasberg.
Paroxysmal atrioventricular block: clinical experience with 20 patients.
Int J Cardiol., 97 (2004), pp. 399-405
[6]
M.B. Knudsen, A.M. Thøgersen, S.P. Hjortshøj, S. Riahi.
The impact of drug discontinuation in patients treated with temporary pacemaker due to atrioventricular block.
J Cardiovasc Electrophysiol., 24 (2013), pp. 1255-1258
[7]
D. Osmonov, I. Erdinler, K.S. Ozcan, et al.
Management of patients with drug-induced atrioventricular block.
Pacing Clin Electrophysiol., 35 (2012), pp. 804-810
[8]
J.H. Lee, H.M. Ryu, M.H. Bae, et al.
Prognosis and natural history of drug-related bradycardia.
Korean Circ J., 39 (2009), pp. 367-371
[9]
Ministerio de Sanidad, Consumo y Bienester Social. Gobierno de España. Clasificación Internacional de Enfermedades, Novena Revisión, Modificación Clínica. Available at: https://eciemaps.mscbs.gob.es/ecieMaps/browser/index_9_mc.html#search=&flags=111100&flagsLT=11111111&searchId=1568049011002∈diceAlfabetico=&listaTabular=426&expand=0&clasification=cie9mc&version=2014. Accessed 9 Sep 2019.
[10]
I.G. Matthews, I.A. Tresham, S.W. Parry.
Syncope in the older person.
Cardiol Clin., 33 (2015), pp. 411-421
[11]
H.T. Lu, J. Kam, R.B. Nordin, et al.
Beta-blocker use and risk of symptomatic bradyarrhythmias: A hospital-based case-control study.
J Geriatr Cardiol., 13 (2016), pp. 749-759
[12]
M.O. Sweney.
Not So Temporary Pacing.
J Cardiovasc Electrophysiol., 24 (2013), pp. 1259
[13]
E.M. Vaughan Williams.
A classification of antiarrhythmic actions reassessed after a decade of new drugs.
J Clin Pharmacol., 24 (1984), pp. 129-147
[14]
K.J. Hellestrand, R.S. Bexton, A.W. Nathan, R.A. Spurrell, A.J. Camm.
Acute electrophysiological effects of flecainide acetate on cardiac conduction and refractoriness in man.
Br Heart J., 48 (1982), pp. 140-148
[15]
D.P. Zipes, E.N. Prystowsky, J.J. Heger.
Amiodarone: electrophysiologic actions, pharmacokinetics and clinical effects.
J Am Coll Cardiol., 3 (1984), pp. 1059-1071
[16]
M. Shenasa, S. Kenker, R. Mahmud, M. Lehmann, A. Estrada, M. Akhtar.
Effect of amiodarone on conduction and refractoriness of the His-Purkinje system in the human heart.
J Am Coll Cardiol., 4 (1984), pp. 105-110
[17]
B.N. Singh.
Mechanism of action of antiarrhythmic agents: focus on propafenone.
J Electrophysiol., 1 (1987), pp. 503-516
[18]
S.F. Seides, M.E. Josephson, W.P. Batsford, G.M. Weisfogel, S.H. Lau, A.N. Dameto.
The electrophysiology of propranolol in man.
Am Heart J., 88 (1974), pp. 733-741
[19]
P. Rizzon, M. Di Biase, A. Chiddo, D. Mastrangelo, L. Sorgente.
Electrophysiological properties of intravenous metoprolol in man.
Br Heart J., 40 (1978), pp. 650-655
[20]
H. Dargie, E. Rowland, D. Krikler.
Role of calcium antagonists in cardiovascular therapy.
Br Heart J., 46 (1981), pp. 8-16
[21]
G.J. Klein, S. Gulamhusein, E.N. Prystowsky, S.G. Carruthers, A.P. Donner, P.T. Ko.
Comparison of the electrophysiologic effects of intravenous and oral verapamil in patients with paroxysmal supraventricular tachycardia.
Am J Cardiol., 49 (1982), pp. 117-124
[22]
P. Alboni, N. Shantha, L. Filippi, et al.
Clinical effects of digoxinon sinus node and atrioventricular node function after pharmacologic autonomic blockade.
Am Heart J., 108 (1984), pp. 1255-1261
[23]
A. Fontenla, L. Villagraz, J. De Juan, Á. Lozano, S. Giacoman, M. López-Gil.
Ivabradine as an alternative to AV node ablation in a patient with permanent atrial fibrillation.
Rev Esp Cardiol., 70 (2017), pp. 1019-1020
[24]
R.L. Verrier, R. Bonatti, A.F. Silva, et al.
Inhibition in the atrioventricular node by ivabradine causes rate-dependent slowing of conduction and reduces ventricular rate during atrial fibrillation.
Heart Rhythm., 11 (2014), pp. 2288-2296
Copyright © 2019. Sociedad Española de Cardiología
Idiomas
Revista Española de Cardiología (English Edition)

Subscribe to our newsletter

Article options
Tools
es en

¿Es usted profesional sanitario apto para prescribir o dispensar medicamentos?

Are you a health professional able to prescribe or dispense drugs?