the importance of bundle branch block in the general...

1

The importance of bundle branch block in the general population and in patients with ST-

elevation myocardial infarction

Name: Maaike Yldau van der Ende

Student number: 2096056

E-mail: [email protected] & [email protected]

1st supervisor: Prof. dr. P. van der Harst ([email protected])

2nd

supervisor: Drs. H.T. Hartman ([email protected])

Department: Cardiology, UMCG Groningen

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List of contents

1. Abstract ........................................................................................................................................... 5

2. Introduction ..................................................................................................................................... 7

2.1 Myocardial Infarction ................................................................................................................... 7

2.2 Anatomy of the coronary arteries .................................................................................................. 8

2.3 Bundle Branch block ..................................................................................................................... 8

2.3.1 Left bundle branch block ....................................................................................................... 9

2.3.2 Right bundle branch block ..................................................................................................... 9

2.3.3 Fascicular block ..................................................................................................................... 9

2.4 Bundle branch block in the general population........................................................................... 10

2.5 Bundle branch block in patients with myocardial infarction ...................................................... 10

2.6 Hiatus in knowledge ................................................................................................................... 10

3. Objectives ..................................................................................................................................... 11

4. Hypothesis..................................................................................................................................... 11

5. Methods......................................................................................................................................... 12

5.1 Methods LifeLines database ....................................................................................................... 12

5.1.1 Study population .................................................................................................................. 12

5.1.2 Data collection ..................................................................................................................... 12

5.1.3 Parameters ............................................................................................................................ 12

5.1.4 Statistical analyses ............................................................................................................... 13

5.2 Methods STEMI patients UMCG ............................................................................................... 13

5.2.1 Study population .................................................................................................................. 13

5.2.2 Parameters ............................................................................................................................ 13

5.2.3 Statistical analyses ............................................................................................................... 15

6. Results ........................................................................................................................................... 16

6.1 Results LifeLines database.......................................................................................................... 16

6.1.1 Prevalence of bundle branch block ...................................................................................... 16

6.1.2 Bundle branch block as risk factor for myocardial infarction .............................................. 17

6.1.3 Association between bundle branch block and mortality..................................................... 17

6.2 Results STEMI patients UMCG ................................................................................................. 18


6.2.2 Patient information and baseline characteristics .................................................................. 18

6.2.3 Mortality .............................................................................................................................. 20

6.2.4 Left ventricular ejection fraction .......................................................................................... 21

7. Discussion ..................................................................................................................................... 23

7.1. Discussion LifeLines database ................................................................................................... 23


7.1.2 Bundle branch block as risk factor of mortality and myocardial infarction ......................... 23

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7.2 Discussion STEMI patients UMCG ............................................................................................ 23

7.2.1 Baseline characteristics and treatment ................................................................................. 23

7.2.2 Mortality .............................................................................................................................. 24

7.2.3 Left ventricular ejection fraction .......................................................................................... 24

7.3 Limitations .................................................................................................................................. 25

8. Conclusion .................................................................................................................................... 25

9. Acknowledgements ....................................................................................................................... 25

10. References .................................................................................................................................... 26

11. Appendix ...................................................................................................................................... 31

Table 1. Baseline Characteristics LBBB and RBBB .................................................................... 31

Table 2. Univariate Cox regression: two year mortality ............................................................... 32

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Keywords bundle branch block, myocardial infarction, mortality, left ventricular ejection fraction,

LifeLines

List of abbreviations ACS Acute coronary syndrome

MI Myocardial infarction

STEMI ST elevation myocardial infarction

nSTEMI Non-ST elevation myocardial infarction

CK Creatine kinase

CK-MB Creatine kinase MB

PCI Percutaneous coronary intervention

CABG Coronary artery bypass surgery

ECG Electrocardiogram

TIMI Thrombolysis in myocardial infarction

LCA Left coronary artery

RCA Right coronary artery

LAD Left anterior descending branch

CX Ramus circumflexus

AV-node Atriaventricular node

LBB Left bundle branch

RBB Right bundle branch

LAF Left anterior fasciculus

LPF Left posterior fasciculus

BBB bundle branch block

LBBB Left bundle branch block

RBBB Right bundle branch block

LAFB Left anterior fascicular block

LPFB Left posterior fascicular block

CVD Cardiovascular disease

LVEF Left ventricular ejection fraction

CAG Coronary angiography

CVA Cerebrovascular accident

VF Ventricular fibrillation

PVD Peripheral vascular disease

ACE Angiotensine converting enzyme

hs-TnT High sensitive troponin

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1. Abstract

Background: There is a consensus that presence of bundle branch block (BBB) in the

general population is associated with cardiovascular events. However, the majority of studies

focusing on the prevalence of BBB in the general population date back to the 1990s. Since

then, there have been significant changes in lifestyle. Recent studies only report either the

incidence of a right BBB (RBBB) only or general conduction disorders observed in a

population older than 30 years of age. With respect to patients with acute ST-elevation

myocardial infarction (STEMI) and BBB, higher in-hospital and long-term unadjusted

mortality and lower left ventricular ejection fraction (LVEF) have been reported, irrespective

of whether the observed BBB was left or right. It is important to consider that most of these

findings are based on the outdated recommendation of thrombolysis for treating patients with

STEMI. Nevertheless, since the 1990s, primary angioplasty has become the gold standard,

which has led to a significant improvement in outcome when treating STEMI. In light of the

aforementioned, the aims underlying this study are to determine the prevalence of conduction

disorders and subsequently investigate potential associations between conduction disorders

and cardiovascular events in the contemporary population. Following this, an additional aim

is to investigate the effect of BBB on mortality and LVEF in STEMI patients treated with the

current recommendation of angioplasty.

Methods: The importance of BBB in the general population was investigated in the

LifeLines database, a three generation cohort study and biobank. All 152.180 participants of

LifeLines were included for determining the prevalence of BBB. For further analyses

participants were excluded when no follow-up data was available, or when participants had a

medical history of possible myocardial infarction (MI). Logistic regression was used to study

the relationship between BBB and MI during follow-up. For determining the outcome of

STEMI patients with BBB, a total of 1123 patients with STEMI treated in the University

Medical Center Groningen from January 2011 until May 2013 were included. The follow-up

period was 2 to 4 years. Transthoracic echocardiography was performed to evaluate LVEF

within 6 months after STEMI. Baseline characteristics were compared between patients with

and without a BBB. Relative risk of death and reduced LVEF between groups were

determined using Cox survival analyses and ordered logistic regression.

Results: In the general population, the prevalence of BBB increased significantly with age

and was more common in males. Furthermore, LBBB was associated with MI and mortality

during follow-up. In STEMI patients, a significant difference in two-year mortality was

observed between patients with and without BBB; 25% (n=18) and 9.3% (n=94, p<0.001)

respectively. Mortality observed in patients with LAFB was 15% (n=8). Patients with BBB

more frequently presented a severely reduced LVEF compared to patients without BBB; 19%

(n=8) and 3.6% (n=23, p<0.001) respectively. In addition, patients with BBB less frequently

presented a normal LVEF compared to patients without BBB; 14% (n=6) and 43% (n=287,

p<0.001) respectively. For patients with LAFB, 18% (n=5) had a severely reduced LVEF. In

multivariate analysis, including adjustment for LVEF, BBB or LAFB were not independently

associated with mortality, but presence of BBB was an independent predictor of reduced

LVEF.

Conclusion: In the general population, the prevalence of BBB increased with age and is

higher in males. LBBB was associated with MI and mortality during follow-up. In STEMI

patients, BBB was an independent predictor of reduced LVEF. Conversely, BBB was not an

independent predictor of mortality in the current era of reperfusion therapy.

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Inleiding: De consensus bestaat dat de aanwezigheid van een bundel tak blok (BTB) in de

algemene bevolking wordt geassocieerd met cardiovasculaire events. De meeste studies die

gericht zijn op de prevalentie van BTB in de algemene populatie dateren uit de jaren 90.

Sindsdien zijn er belangrijke veranderingen in lifestyle opgetreden. Recente studies

rapporteren gegevens over alleen de prevalentie van een rechter BTB (RBTB) of hebben

alleen geleidingsstoornissen in een populatie ouder dan 30 jaar waargenomen. Onder

patiënten met een acuut ST-elevatie myocardinfarct (STEMI) en BTB is een hogere

mortaliteit en een lagere linker ventrikel ejectiefractie (LVEF) gerapporteerd, ongeacht of het

BTB links of rechts was. Het is belangrijk om te weten dat de meeste van deze bevindingen

gebaseerd zijn op de verouderde aanbeveling van trombolyse voor de behandeling van

patiënten met STEMI. Sinds de jaren 90 is primaire angioplastiek de gouden standaard, wat

heeft geleid tot verbetering van prognose van STEMI patiënten. De doelstellingen die ten

grondslag liggen aan deze studie zijn het bepalen van de prevalentie van

geleidingsstoornissen en het onderzoeken van mogelijke associaties tussen

geleidingstoornissen en cardiovasculaire events in de hedendaagse bevolking. Een bijkomend

doel is om het effect van een BTB op mortaliteit en LVEF te onderzoeken bij STEMI

patiënten die behandeld worden met angioplastiek.

Methode: Het belang van een BTB in de huidige populatie is onderzocht in de LifeLines

database, een drie generatie cohort studie en biobank. Alle 152.180 deelnemers van de

LifeLines database werden geincludeerd voor het berekenen van de prevalentie van BTB.

Voor verdere analyses werden deelnemers geexcludeerd wanneer geen follow-up data

beschikbaar was of wanneer deelnemers mogelijk een myocard infarct (MI) in het verleden

hadden doorgemaakt. Logistische regressie werd gebruikt voor het bestuderen van de relatie

tussen BTB en MI en mortaliteit in follow-up in de algemene populatie. Voor het bepalen van

de associatie tussen BTB en events in STEMI patiënten, zijn in totaal 1123 STEMI patiënten

geincludeerd, die behandeld zijn in het Universitair Medisch Centrum Groningen (UMCG)

tussen januari 2011 en mei 2013. De follow-up periode was tussen 2 en 4 jaar.

Transthoracale echocardiografie was uitgevoerd om LVEF te bepalen binnen een tijdsbestek

van 6 maanden na STEMI. Baseline karakteristieken werden vergeleken tussen patiënten met

en zonder een BTB. Het relatieve risico op overlijden en abnomale LVEF van deze groepen

werd bepaald en vergeleken met behulp van logistische en Cox regressie.

Resultaten: In de algemene populatie nam de prevalentie van een BTB toe met de leeftijd, en

was de prevalentie was hoger in het mannelijke geslacht. Daarnaast was een LBTB

geassocieerd met MI en mortaliteit in follow-up. De twee jaar mortaliteit van STEMI

patiënten was significant verschillend tussen patiënten met en zonder een BBB,

respectievelijk 25% (n=18) en 9.3% (n=94, p<0.001). De mortaliteit in patiënten met LAHB

was 15% (n=8). Patiënten met een BTB hadden vaker een ernstig afwijkende LVEF; 19%

(n=8) en 3.6% (n=23, p<0.001) en minder vaak een normale LVEF; 14% (n=6) en 43%

(n=287, p<0.001). Van de patiënten met LAFB had 18% (n=5) een ernstig afwijkende LVEF.

In multivariate analyse, was de aanwezigheid van een BTB of LAHB echter geen

onafhankelijke voorspeller van mortaliteit, maar de aanwezigheid van een BTB was een

onafhankelijke voorspeller van verminderde

LVEF na STEMI.

Conclusie: In de huidige populatie neemt de prevalentie van een BTB toe met de leeftijd en

is de prevalentie van een BTB hoger in de mannelijke populatie. Een LBTB is geassocieerd

met een myocard infarct en mortaliteit in follow-up. Een BTB is een onafhankelijke

voorspeller voor een verminderde LVEF, maar niet van mortaliteit in STEMI patiënten in het

huidige tijdperk van primaire angioplastiek.

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2. Introduction

2.1 Myocardial Infarction Acute coronary syndrome (ACS) is the term applied to patients with suspicion of myocardial

infarction (MI). ACS can be divided in three types: ST-elevation MI (STEMI), non-ST

elevation MI (nSTEMI), and unstable angina. The Global Registry of Acute Coronary Events

(GRACE) shows the frequency of these conditions in patients admitted with ACS: 38% had

a final diagnosis of unstable angina, 30% of STEMI and 25% of nSTEMI1. In the

Netherlands, each year 33,000 new patients are diagnosed with an MI2.

A MI is an event caused by prolonged ischemia whereby myocardial necrosis occurs. For

diagnosing a MI there must be a typical rise of biochemical markers at the same time with

one of the following criteria: ischemic symptoms, pathologic Q-waves, ST-elevation or

depression, or coronary artery intervention.

The biochemical markers elevate during or after a MI are troponin, creatine kinase (CK) and

creatine kinase MB (CK-MB). For diagnosing a MI, the value of troponin and CK-MB

should reach the 99th

percentile of the normal range of these enzymes3.

Troponins are proteins that control the interaction of actin and myosin, thus generating the

contraction of the heart muscle/cardiomyocyte4. Two or three hours after the onset of MI,

troponin concentrations usually start to rise and the peak level of troponin is a predictor of

mortality, in which a higher level of troponin result in a higher mortality5,6

. CK is distributed

in many tissues, but the CK-MB fraction is more specific for the heart7. There is a

relationship between the level of CK-MB and infarct size, and the level of CK-MB is also a

predictor of the outcome8. CK-MB starts to rise four to six hours after the onset of infarction,

and peaks around twelve hours9,10

. Because of the delay in biomarker elevations, the

treatment of patients with suspected STEMI should not await of these results11

. Post-mortem,

MI can also be diagnosed by pathologic findings, where myocardial necrosis can be found 6

hours after MI3.

A MI can be divided in the following group according to the assumed cause of myocardial

ischemia12

:

Type 1: MI caused by a pathologic process in the wall of the coronary artery, resulting

in intraluminal thrombus.

Type 2: MI caused by increased oxygen demand or decreased supply. For example

anemia, hypertension, hypotension or coronary artery spasm.

Type 3: MI resulting in sudden unexpected death.

Type 4a (MI related to percutaneous coronary intervention (PCI)): MI defined by the

elevation of biomarker values in patients with normal troponin values or a rise of

values >20% if the baseline values are elevated but stable or falling.

Type 4b (MI related to stent thrombosis): Stent thrombosis associated with MI when

detected by coronary angiography or autopsy in the setting of myocardial ischemia

and with a rise and/or fall of cardiac biomarkers.

Type 5 (MI related to coronary artery bypass surgery (CABG)): MI defined by the

elevation of biomarker values, in patients with normal baseline troponin values.

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Another clinical diagnostic classification is based on electrocardiographic findings, and

includes STEMI and nSTEMI The electrocardiogram (ECG) of a nSTEMI shows ST

depression or T wave inversions, but no ST-elevation. Patients with a nSTEMI are treated

with anti-ischemic, analgesic and antithrombotic therapy13

.

In patients with STEMI, the ECG shows a typical ST-elevation in the specific leads of the

location of the MI. Nowadays, if STEMI is suspected, most patients directly undergo a

diagnostic coronary angiography and, if necessary, treatment by percutaneous coronary

intervention. In the nineties standard therapy was thrombolysis and around 15-20% of

patients died within 1 month of hospitalization as a result of MI, whereas this currently is

estimated at 5-8%2.

Successful reperfusion is also an important prognostic factor. The degree of perfusion in the

infarct-related artery is described by the TIMI flow; where a TIMI flow of zero refers to the

absence of a flow beyond a coronary occlusion; a TIMI flow of one refers to a small

antegrade flow, but the filling of the distal coronary bed is incomplete; a TIMI flow of two is

a delayed antegrade flow, but the distal filling is complete and a TIMI flow of three is a

normal flow14

. A thrombolysis in MI (TIMI) flow grade of 3 after PCI is associated with

lower mortality in

STEMI patients15-17

.

2.2 Anatomy of the coronary arteries The heart is supplied of blood by two coronary

arteries: the left coronary artery (LCA) and right

coronary artery (RCA), which both arise from the

aorta. After the main stem, the LCA splits in the

left anterior descending branch (LAD) and the

ramus circumflexus (CX). The LAD supplies

mainly the left ventricle and the interventricular

septum of the heart, whereas the RCA supplies

the right ventricle18,19

. Figure 1 shows the

coronary arteries.

Figure 1. Coronary arteries

2.3 Bundle Branch block The depolarization of the heart starts in the sinus node,

and reaches, via the atria the atriaventricular node

(AV-node). After the AV-node the depolarization is

conveyed by the bundle of His, that splits in the left

bundle branch (LBB) and right bundle branch (RBB).

The LBB divides again in the anterior and posterior

fasciculus (LAF and LPF)20

. Figure 2.

A bundle branch block (BBB) is an intraventricular

conduction disorder in one of the bundle branches.

This can be subdivided into a left bundle branch block

(LBBB), a right bundle branch block (RBBB), a left

anterior fascicular block (LAFB) or a left posterior

fascicular block (LPFB). In some cases the block is

incomplete, which means that the depolarization is

conveyed delayed instead of totally blocked20

. Figure 2. Bundle branches

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2.3.1 Left bundle branch block

A LBBB is a complete block in the LBB, which is usually located in the mean stem. In

patients with a LBBB the excitation starts in the right ventricle: the reason why the septal

depolarization is directed from right to left. Therefore, the ECG characteristics of a LBBB

are: QRS – complex ≥ 120 ms; a broad notched or slurred R wave in lead 1, aVL, V5, and V6

and a RS pattern in V5 and V6 attributed to displaced transition of QRS complex; absent q

waves in leads I, V5 and V6; R peak time greater than 60 ms in leads V5 and V6 but normal in

leads V1, V2 and V3, when small initial r waves can be discerned in the above leads. Figure 3.

The findings of an incomplete LBBB are the same as the findings of a LBBB, the only

difference is the QRS duration, which lasts between 110 and 120ms in an incomplete bundle

branch block21

. The LAD provides the main blood supply for the LBB, an occlusion of this

artery can result in a LBBB19

.

2.3.2 Right bundle branch block

Patients with a RBBB have a complete block of their RBB, which means that when the

excitation in the left ventricle is almost completed, the excitation starts in the right ventricle.

The following ECG characteristics will be found: a QRS – complex ≥ 120; Rsr’, rsR’, or

rSR’ in leads V1 or V2; normal R peak time in leads V5 and V6 but greater than 50 ms in lead

V1. Figure 3. An incomplete RBBB has a QRS duration between 110 and 120 ms21

. The LAD

also provides the main blood supply for the RBB, therefore an occlusion of the LAD can

result in a RBBB 22,23

.

\

Figure 3. Electrocardiographic characteristics of LBBB and RBBB

2.3.3 Fascicular block

A fascicular block is a complete block in the anterior (LAFB) or posterior (LPFB) fascicle of

the LBB. When a fascicular block is present, there is heart axis deviation. A LAFB has

frontal plane axis between -45⁰ and - 90⁰ and the following ECG characteristics: a qR pattern

in lead aVL, a R peak time in lead aVL of 45 ms or more, a QRS duration less than 120 ms.

LPFB has a frontal plane axis between 90⁰ and 180⁰, a rS pattern in leads I and aVL, a qR

pattern in leads III and aVF and a QRS duration less than 120 ms21

.

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2.4 Bundle branch block in the general population The prevalence of a BBB depends on age and gender. A recent Danish study reported that

4.7% of men and 2.3% of women had an incomplete RBBB and 1.4% of men and 0.5% of

women had a RBBB. The prevalence of RBBB increased with age, whereas the prevalence of

incomplete RBBB was the highest in the youngest and oldest patient groups24

. Another study,

performed in Sweden, showed that the prevalence of BBB in the male population increases

from 1% at age 50 years to 17% at age 80 years. This study suggested that an asymptomatic

BBB a marker was of a slowly progression of degenerative disease that affected the

myocardium25

.

Another study of Fahy et al reported no difference in total survival between individuals with

LBBB and their controls, but the patients with LBBB had an increased prevalence of

cardiovascular disease (CVD) at follow-up (21 vs 11%)26

. Similar findings were shown in the

Framingham study; 48% of individuals with LBBB developed coronary artery disease or

congestive heart failure27

. More recent studies suggested as well that there is an association

between BBB and CVD24,28,29

.

2.5 Bundle branch block in patients with myocardial infarction Studies from the pre-thrombolytic

30-32 and thrombolysis era

33-40 have reported that patients

who had a BBB, regardless of whether this was a LBBB or RBBB, following MI, had higher

in-hospital and long-term unadjusted mortality. In patients with reduced left ventricular

systolic function, RBBB predicted mortality and was related to increased risk of sudden

cardiac arrest. LBBB was a marker of increased mortality in patients with preserved left

ventricular systolic function and was associated with increased risk for all-cause death,

cardiovascular death and sudden cardiac arrest40,41

. Besides this, the presence of BBB in

general was an independent predictor of lower left ventricular ejection fraction (LVEF)

before discharge40,42-44

. It was suggested that RBBB plus LAFB is associated with the highest

mortality39

, but having an isolated LAFB seemed not to be an independent predictor for

worse outcome45

.

2.6 Hiatus in knowledge The majority of studies focusing on the prevalence of BBB in the general population date

back to the 1990s25,26

. Since then, there have been significant changes in lifestyle such as a

reduced prevalence of heavy smokers and drinkers and an increased prevalence of obesity46

.

Recent studies only reported either the incidence of RBBB24

only or general conduction

disorders observed in a population older than 30 years of age29

.

Because of the change in lifestyle in this time period, we want to determine the prevalence of

all types of BBB in the contemporary population and subsequently investigate potential

associations between BBB and MI and mortality in follow-up. This will be investigated in the

LifeLines cohort, whereby we can investigate BBB in a great study population with the age

of 18 years and older.

Most of the data regarding the influence of BBB on outcome in STEMI patients is outdated.

Data is provided by studies that included patients hospitalized between 1990 till

200036,37,41,42

. The recommended treatment for patients with a MI in that period was

thrombolysis. At the end of the 90s, primary angioplasty appeared to be superior to

thrombolytic therapy for treatment of patients with MI and is considered standard therapy

nowadays47,48

. The change in treatment of MI has improved outcome enormously. In the

more recent studies, significantly fewer patients with a BBB underwent coronary

angiography (CAG) after a MI compared with patients without a BBB, and whether a BBB is

11

a risk factor for worse outcome after MI is still unknown41,43,44,49,50

. Therefore we aim to

study the impact of a BBB on mortality and LVEF in patients presenting with STEMI.

Furthermore, a second aim of this study is to determine if there is a difference in mortality

and LVEF between patients with a LBBB versus a RBBB.

3. Objectives

The overall aim of my scientific clerkship “The importance of bundle branch block in the

healthy population and in patients with ST-elevation myocardial infarction” was to

investigate the importance of BBB in the general population and specifically in patients

presenting with STEMI. We wanted to achieve the following objectives:

- Determine the prevalence of a BBB in the general population

- Determine the association between BBB and cardiovascular events.

- Investigate the impact of the presence of a BBB on mortality and LVEF in STEMI

patients. Effect of possible confounders on outcome in multivariate analysis were

studied.

- Study the differences in mortality and LVEF between STEMI patients with a LBBB

or a RBBB.

4. Hypothesis

We hypothesized that in the LifeLines population, the prevalence of BBB increased with age

and was higher in the males. Besides that we hypothesized that participants with BBB were at

higher risk of MI and mortality. We hypothesize that STEMI patients with a BBB, treated

with the current therapy, had the same mortality and LVEF as patients without a BBB. It was

also expected that STEMI patients with RBBB had the same mortality and LVEF as patients

with LBBB.

12

5. Methods

5.1 Methods LifeLines database

5.1.1 Study population

In 2006, LifeLines started with collecting data of the population of the north of The

Netherlands. For this research participants will be followed for a minimum of 30 years51

. In

January 2015 baseline data of 152,180 participants of LifeLines was available. This data was

used for calculating the prevalence of BBB. For further analyses, participants were excluded

when no follow-up data was available or when participants had a possible medical history of

MI.

5.1.2 Data collection

The study design of LifeLines has been described in detail elsewhere52

. All participants were

invited to visit a LifeLines research site, where physical examination was performed.

Nowadays, the first visit has been completed, the second visit ongoing and the third being

currently planned. Between the visits, participants received follow-up questionnaires. By

questionnaire information about demographics, health status, lifestyle and psychosocial

aspects was collected.

5.1.3 Parameters

Age and sex of the participants were collected by questionnaire. In the LifeLines population a

possible medical history of MI was defined as follows: an affirmative answer in the baseline

questionnaire in combination with the use of platelet aggregation inhibitors. Prescribed

medication was obtained from questionnaire as well and was represented in the LifeLines

database with ATC code53

. ATC codes of platelet aggregation inhibitors were collected and a

new variable was created for the use of platelet aggregation inhibitors, in which a zero was

represented when participants were not treated with platelet aggregation inhibitors, and an

one when participants were treated with platelet aggregation inhibitors. The following

flowchart shows the procedure of defining a possible history of MI.

Figure 4. Definition MI at baseline.

Have you ever had a heart

attack?

Medication related to MI MI unlikely

Possible medical history of MI

no

no

yes

yes

n = 1.650

n = 1.436

n = 214

MI unlikely

n = 150.530

Baseline electrocardiogram (ECG) was available of all 152.180 participants. In 20.85% of

cases (31,724 out of 152,180) automatic evaluation of the ECG was classified as abnormal

after which ECG was reviewed manually by a cardiologist. Based on these analyses we

13

divided patients in the following groups: LBBB, RBBB, LAFB, LPFB and control group (no

BBB).

The outcome variables were self reported MI and mortality. Self reported MI was defined by

an affirmative answer on the question: “Have you had a heart attack and/or balloon

angioplasty and/or bypass surgery since the last time you filled out this questionnaire?”.

Mortality was obtained from the municipal personal records database and represented as

death year when a death had occurred. A new binary variable was created, in which a zero

was represented when no death had occurred and an one when a death had occurred.

5.1.4 Statistical analyses

Prevalence of BBB was presented as percentages with related number of observations. The

Chi-square test was used to compare the prevalence of BBB in male and female. ANOVA

was used to compare the prevalence of BBB in different age groups. Logistic regression was

used to study the relation between BBB and MI and mortality in follow-up. Univariate

variables with p-value ≤0.10 were included in the multivariate ordered logistic regression.

For all analyses a p-value ≤0.05 was considered as significant and all statistical analysis were

performed by using StataIC 11.

5.2 Methods STEMI patients UMCG

5.2.1 Study population

Inclusion criteria

- Patients with STEMI in the period of the 1st of January 2011 till the 31

st of May 2013,

treated in the UMCG

- All patients with STEMI underwent diagnostic coronary angiography (CAG) and PCI.

- Patients with the age of eighteen years and older.

Exclusion criteria

- Patients were excluded when no PCI was performed.

- Patients were excluded when no significant coronary artery disease was found.

Power

According to the literature, the expected difference in mortality between patients with and

without a BBB was ten percent37,40-43

. For this research we used a power of 95% and a

significance level of 0,05. In multivariate regression we wanted to include approximately 20

predictors. With the above values we calculated a sample size of 325 patients per group. Due

to the fact that we wanted to compare three patient groups, we included a minimum of 975

patients.

5.2.2 Parameters

Baseline characteristics

Baseline characteristics were collected for all STEMI patients. Gender and age were obtained

from the medical files of the patients. CVD risk factors at presentation were classified in (1)

body mass index (BMI) calculated as the ratio of weight and height squared (kg/m2) (2)

hypertension defined as a systolic blood pressure above 140 mmHG, a diastolic blood

pressure above 90 mmHg or the use of antihypertensive medication (3) diabetes (type 1 and

2) defined as a fasting glucose level of ≥7.0 mmol/L, a non-fasting glucose level of ≥11.1

mmol/L or the use of anti-diabetic drugs (4) hypercholesterolemia defined as a total serum

cholesterol >6.5 mmol/L or the use of lipid-lowering medication (5) smoking and (6) family

14

history. Medical history and information about medication use were obtained from the

medical files and included MI, PCI, CABG, cerebrovascular accident (CVA), ventricular

fibrillation (VF), malignancy, peripheral vascular disease (PVD), beta blocker, angiotensine

converting enzyme inhibitor (ACE-inhibitor), angiotensin II receptor blockers, diuretics, anti-

arrythmica, insulin, metformine. Measurement of CK, CK-MB and hs-TnT was performed

according to local hospital standards on standard laboratory assays as part of standard care.

Enzyme release of CK, CK-MB and hs-TnT was routinely measured during the stay at the

coronary care unit after primary PCI. Peak values were calculated over the first 36 hours

post-PCI. At clinical presentation heart frequency, systolic and diastolic blood pressure were

measured and collected. Infarct location was obtained by the location of the culprit: culprit 1,

2, 3, 4 and 16 were categorized as RCA, culprit 5 as LMCA, culprit 11, 12, 13, 14 and 15 as

CX and culprit 6, 7, 8, 9 and 10 as LAD). Successful PCI was defined as a TIMI-flow grade

3 after CAG15-17

. Finally, discharge mediation (beta blocker, ACE-inhibitor, apirine, statin,

clopidogrel/ticagrelor) was obtained from medical files.

Myocardial Infarction

The criteria for STEMI was 12-lead ECG changes suggestive of infarction: new ST elevation

at the J point in two contiguous leads with the cut-points: ≥0,1 mV in all leads other than

leads V2-V3 where the following cut points apply: ≥0,2 mV in men ≥40 years; ≥0,25 mV in

men <40 years, or ≥0,15 mV in women12

.

Bundle Branch Block

For this research, patients were divided in 3 groups: no BBB, BBB (LBBB or RBBB) and

LAFB. Separate groups for patients with LBBB and RBBB were made as well. An aberrant

ECG at presentation was the criteria for the presence of a block.

The presence of LBBB was based on 12-lead ECG criteria used in other studies and defined

as followed21

; a QRS – complex ≥ 120 ms; a broad notched or slurred R wave in lead I, aVL,

V5, and V6 and a RS pattern in V5 and V6 attributed to displaced transition of QRS complex;

absent q waves in leads I, V5 and V6. Figure 2. A RBBB had the following

electrocardiographic characteristics: a QRS – complex ≥ 120; Rsr’, rsR’, or rSR’ in leads V1

or V2; normal R peak time in leads V5 and V6 but greater than 50 ms in lead V1. Figure 2. A

LAFB had frontal plane axis between -45⁰ and - 90⁰, and besides that the following

electrocardiographic characteristics: a qR pattern in lead aVL, a R peak time in lead aVL of

45 ms or more, a QRS duration less than 120 ms. A LPFB had a frontal plane axis between

90⁰ and 180⁰, a rS pattern in leads I and aVL, a qR pattern in leads III and aVF and a QRS

duration less than 120 ms.

Mortality and left ventricular ejection fraction

The outcome variables were two-year mortality and LVEF. Mortality data was obtained via

the municipal personal records database and available for all 1123 patients. Groups of LVEF

were based on the recommendations for cardiac chamber quantification by Echocardiography

in adults: in males the normal range was 52-72%, the mildly reduced range was 41-51%, the

moderately reduced range was 30-40% and the severely reduced range was <30%. In females

the normal range was 54-74%, the mildly reduced range is 41-53, the moderately reduced

range was 30-40% and the severely reduced range is <30%54

. LVEF was measured by

eyeballing or biplane simpson method and due to the echo quality, some values had a range.

Table 1 shows the ranges and the associated group. Statistical analyses were performed on

patients with information about their LVEF.

15

Table 1. Division of ranges of LVEF and associated LVEF groups.

5.2.3 Statistical analyses

This research was performed with the help of a retrospective cohort. For all analyses a p-

value ≤0,05 was considered as significant and all statistical analysis were performed by using

StataIC 11. The database was made anonymous by removing individual patient data, after

which statistical analyses was performed.

Descriptive statistics

Dichotomous variables were presented as percentages, and continuous variables as mean and

standard deviation (SD). Continuous variables, not normally distributed, were presented as

medians with their interquartile ranges (IQRs). The Chi-square test was used to compare

frequencies of events in patients with and without a BBB, patients with LAFB and without

BBB and in patients with LBBB and RBBB. Continuous variables were ascertained by t-test.

Fisher’s exact test was used to compare patients with and without BBB and LVEF groups.

Survival analysis

Uni- and multivariate Cox regression analyses were performed to determine correlates of

BBB and two year mortality and baseline variables. These variables included cardiovascular

risk factors, medical history, medication use, lab values, physical examination, infarct

location, successful PCI, discharge medication and LVEF. Univariate regression analysis was

reported with p-value and when significant, concomitant hazard ratio and confidence interval.

Univariate variables with p-value ≤0.10 were included in the multivariate Cox regression.

Downwards-stepwise multivariate Cox regression analyses were performed to determine

independent predictors of two year mortality (cutoff for entry 0.10; and removal 0.05). To

validate the models, forward stepwise multivariate Cox regression was performed as well

(cutoff for entry and removal set at a significance level of 0.05).

Ordered logistic regression

For LVEF as independent variable, ordered logistic regression was used. Univariate ordered

regression analysis was reported with p-value and when significant, concomitant odds ratio

and confidence interval. Univariate variables with p-value ≤0.10 were included in the

downwards-stepwise multivariate ordered logistic regression and was validated with forward

stepwise multivariate ordered logistic regression.

Range LVEF Group Range LVEF Group

25-30 4 35-50 2

25-35 3 40-50 2

25-40 3 45-50 2

30-35 3 45-55 2

30-40 3 45-60 Female 2, Male 1

30-45 3 50-60 1

30-50 2 50-55 Female 2, Male 1

35-40 3 55-60 1

35-45 2

16

6. Results

6.1 Results LifeLines database

6.1.1 Prevalence of bundle branch block

In the LifeLines database eleven out of 1000 participants (1.13%, n = 1717) had BBB, of

which 0.34% (n = 523) had LBBB and 0.78 (n = 1194) had RBBB. Besides that, of the

participants 1.88% (n = 2853) had LAFB and 0.08% (n = 119) had LPFB. Tables 2 and 3 and

figures 5 and 6 show the prevalence of RBBB, LBBB, LAFB and LPFB in different age

groups and gender. The prevalence of BBB increases significantly with age, and the

prevalence of RBBB, LAFB and LPFB is higher in the males.

Table 2. Prevalence of BBB in different age groups

Age in years

≥18 & <40

n = 52.162

Age in years

≥40 & <65

n = 87.406

Age in years

≥65 & <75

n = 10.424

Age in years

≥75 & <85

n = 2.035

Age in years

≥ 85

n = 153

P value

LBBB % (n) 0.06 (30) 0.33 (287) 1.47 (153) 2.26 (46) 4.61 (7) <0.001

RBBB % (n) 0.33 (171) 0.71 (621) 2.69 (280) 5.46 (111) 7.24 (11) <0.001

LAFB % (n) 0.42 (218) 2.00 (1746) 6.55 (682) 9.2 (187) 13.16 (20) <0.001

LPFB % (n) 0.06 (30) 0.08 (72) 0.12 (13) 0.20 (4) 0 (0) 0.004

Table 3. Prevalence of BBB by sex.

Male

n = 63.130

Female

n = 89.050

P value

LBBB % (n) 0.33 (209) 0.35 (314) 0.479

RBBB % (n) 1.29 (817) 0.42 (377) <0.001

LAFB % (n) 2.95 (1860) 1.12 (993) <0.001

LPFB % (n) 0.14 (86) 0.04 (33) <0.001

Figures 5 & 6: Prevalence of BBB in different age groups and sex

05

15

10

Pre

vale

nce c

on

du

ction

dis

ord

ers

(%

)

18-39 40-64 65-74 75-84 85+Age group (years)

LBBB RBBB

LAFB LPFB

01

32

Pre

vale

nce c

on

du

ction

dis

ord

ers

(%

)

Male Female

LBBB RBBB

LAFB LPFB

17

6.1.2 Bundle branch block as risk factor for myocardial infarction

To determine the association between BBB and MI, 29,312 participants were excluded

because of lacking follow-up data and another 1,436 participants were excluded because of a

possible medical history of MI. In the remaining study population (n=121,432), 284

participants (0.23%) developed MI. The follow-up period was between eleven and 92

months. Respectively, six, four, sixteen and zero participants with LBBB, RBBB, LAFB and

LPFB developed MI. Univariate logistic regression showed that LBBB and LAFB were

associated with increased risk of developing MI. In multivariate logistic regression, adjusting

for age and gender, only LBBB seemed to be an independent predictor of MI.

Table 4. Univariate and multivariate logistic regression: Self-reported MI during follow-up

Univariate logistic regression

P value Odds ratio 95% CI

Multivariate logistic regression


Age (per year) <0.001 1.081 1.071 – 1.091 <0.001 1.078 1.068 – 1.088

Female <0.001 0.334 0.260 – 0.427 <0.001 0.370 0.288 – 0.474

LBBB 0.004 6.768 2.996 – 15.290 0.012 2.907 1.267 – 6.666

RBTB 0.232 1.950 0.725 – 5.242

LAFB <0.001 3.241 1.954 – 5.376

6.1.3 Association between bundle branch block and mortality

Mortality data was available for all 152,180 participants. Between 2007 and 2014, 645

participants died. Seventeen participants with LBBB, fifteen participants with RBBB, 23

participants with LAFB and one participant with LPFB died. In univariate logistic regression,

all types of BBB were associated with death. In multivariate logistic regression, adjusted for

age and gender, LBBB was an independent predictor of death.

Table 5. Univariate and multivariate logistic regression: mortality

Univariate logistic regression


Multivariate logistic regression


Age (per year) <0.001 1.084 1.078 – 1.091 <0.001 1.083 1.076 – 1.089

Female <0.001 0.456 0.389 – 0.534 <0.001 0.495 0.422 – 0.581

LBBB <0.001 8.090 4.958 – 13.120 <0.001 2.912 1.761 – 4.815

RBTB <0.001 3.040 1.816 – 5.089

LAFB 0.005 1.945 1.281 – 2.954

LPFB <0.001 1,995 0.278 – 14.302

18

6.2 Results STEMI patients UMCG

6.2.1 Prevalence of bundle branch block

23 (2.0%) Patients presented with LBBB, 49 (4.4%) patients with RBBB and 52 (4.6%) with

LAFB. Because of the small amount of patients with LPFB, no separate group was made for

these patients.

Figure 7. Prevalence of BBB in the STEMI database

6.2.2 Patient information and baseline characteristics

Baseline characteristics of patients with and without a BBB are presented in table 6. Patients

with BBB were older compared to patients without BBB (mean ± SD, 70.2 ±12.6 vs 61.8

±12.6). Cardiac biomarkers were significantly higher in patients with BBB. Also, patients

with BBB more often had hypertension, diabetes, a history of MI, CABG or cancer, but were

less often smokers or had less often a family history of CVD. At presentation, patients with

BBB used more often medication (ACE-inhibitors, anti-arrythmic, or metformine). Peak

laboratory values of CK, CK-MB and hs-TnT were higher in patients with BBB as well as

the heart rate. Patients with BBB had less often an occlusion of the RCA and were less likely

to have a successful PCI compared to patients without BBB. At discharge patients with BBB

less often used beta-blockers.

A comparison was made between patients with LAFB and patients without BBB, and is

presented in table 6. Patients with LAFB were older, were more likely to have previous MI

or PVD, to use insulin, had higher laboratory peak values of CK-MB or hs-TnT and had more

often an occlusion of the LAD, but less often of the RCA. On discharge, patients with LAFB

were less likely to receive aspirine or statine.

At baseline patients, with LBBB and RBBB were slightly different: patients with LBBB were

less often male, had more often a history of ventricular fibrillation and used more often a

calcium channel blocker compared to patients with RBBB. Appendix, table 1.

1282 Patients

1012 without BBB 111 with BBB

38 LAFB23 LBBB 33 RBBB 14 RBBB & LAFB 2 RBBB & LPFB

159 no PCI or no significant coronary artery

disease

excluded

1 LPFB

19

Table 6. Baseline Characteristics no BBB, BBB and LAFB

Table 6. no BBB

n = 1012

BBB

n = 72

p-value LAFB

n = 52

p-value

Male (%) 71.8 77.8 0.277 81.3 0.088

Age (yrs) 61.8 (21.6) 70.2 (12.6) <0.001 68.9 (12) <0.001

Risk factors

BMI (kg/m2) 27.0 (4.1) 26.4 (4.0) 0.277 26.2 (3.1) 0.163

Hypertension (%) 36.5 44.4 0.027 32.7 0.859

Diabetes (%) 16.9 29.6 0.007 25.0 0.133

Hypercholesterolemia (%) 32.9 30.6 0.362 28.9 0.564

Current smoker (%) 47.3 27.8 0.002 38.5 0.373

Family history (%) 41.3 27.8 0.020 40.4 0.232

Medical history

MI (%) 11.8 23.6 0.011 28.9 0.001

PCI (%) 9.9 11.1 0.060 15.4 0.171

CABG (%) 2.5 6.9 0.002 1.9 0.283

CVA (%) 3.9 8.3 0.161 5.8 0.713

VF (%) 7.8 12.5 0.315 3.9 0.501

Malignancy (%) 7.5 16.7 0.020 5.8 0.784

PVD (%) 13.8 22.9 0.330 31.0 0.040

Medication

Beta-Blocker (%) 20.5 31.9 0.059 25.0 0.722

ACE-inhibitors (%) 11.3 26.4 <0.001 19.2 0.212

Angiotensin II receptor antagonist (%) 8.1 9.7 0.851 1.9 0.268

Diuretics (%) 11.9 12.5 0.958 11.5 0.997

Calcium Channel Blockers (%) 8.4 13.9 0.263 9.6 0.953

Anti-arrythmic (%) 0.6 5.6 <0.001 1.9 0.506

Insulin (%) 4.8 9.7 0.166 15.4 0.004

Metformine (%) 7.0 20.8 <0.001 13.5 0.197

Lab-values

Peak CK in hospital (U/L) 1175 (462 - 2702) 1968 (817 - 4328) <0.001 1448 (622 - 4025) 0.084

Peak Ck-MB in hospital (U/L) 149 (63 - 295) 269 (109 - 493) <0.001 172 (93 - 477) 0.008

Peak hs-TnT in hospital (µg/L) 2308 (833 - 5524) 5279 (2327 - 9756) <0.001 3986 (1316 - 8040) 0.01

Physical examination

Heart rate (beats/min) 77.7 (18.0) 84.1 (20.7) 0.004 78.4 (17.7) 0.800

Systolic blood pressure (mmHg) 136.4 (26.1) 133.8 (30.8) 0.465 133.6 (26.2) 0.466

Diastolic blood pressure (mmHg) 85 (14.8) 84.9 (17) 0.945 84.6 (15.8) 0.870

Infarct location

RCA (%) 40.9 27.8 0.028 21.2 0.005

LMCA (%) 1.0 2.8 0.161 1.7 0.516

CX (%) 18.5 16.7 0.701 17.3 0.832

LAD (%) 38.4 45.8 0.214 59.6 0.002

Successful PCI (%) 88.7 77.5 0.033 90.9 0.693

Discharge medication

Beta-Blocker (%) 90.5 84.4 0.012 87.2 0.547

ACE-inhibitors (%) 66.5 65.6 0.344 55.3 0.226

Aspirine (%) 91.1 87.5 0.067 78.7 0.003

Statine (%) 92.4 90.6 0.102 85.1 0.045

Clopidogrel/ticagrelor (%) 90.1 83.3 0.068 84.6 0.200

20

6.2.3 Mortality

In patients with BBB, the mortality was higher. In the group with BBB, 18 (25.0%) patients

died within two years compared to 94 (9.3%) patients the group without BBB. Univariate cox

analysis showed that a BBB was associated with increased mortality (Appendix, table 2).

Figure 8 displays the Kaplan-Meier estimates for two year mortality in the two groups of

patients. In a Cox regression model adjusting for significant baseline characteristics the

difference in mortality between the two groups did not remain significant. Peak value of hs-

TnT was dropped because of collinearity with peak value of CK-MB. Table 7 shows the

independent predictors of two-year mortality after STEMI.

Eight patients out of 52 (15.4%) with LAFB, seven out of 23 patients (30.4%) with LBBB

and eleven out of 49 patients (22.4%) with RBBB died within two years. No significant

difference in mortality was found between patients without BBB and LAFB and between

patients with LBBB and RBBB (Appendix table 2).

Figure 8. Kaplan-Meier survival curve in patients with and without BBB

Table 7. Multivariate Cox regression model: two year mortality

Table 7. p value Haz. Ratio 95% CI

Age (per year) 0.002 1.069 1.025 – 1.114

Medication at presentation

Calcium Channel Blockers 0.008 1.188 1.046 – 1.348

Heart rate (per 10 beats/min) 0.001 1.370 1.136 – 1.653

Systolic blood pressure (per 1 mmHg) 0.011 0.978 0.962 – 0.995


Clopidogrel/ticagrelor <0.001 0.112 0.043 – 0.290

LVEF group (reference: normal LVEF)

Moderately reduced LVEF 0.032 4.312 1.134 – 16.391

Severely reduced LVEF 0.002 10.398 2.364 – 45.734

21

6.2.4 Left ventricular ejection fraction LVEF data was available for 741 patients. 42, 28 And 671 patients with BBB, LAFB and

without BBB had information about their LVEF within half a year after STEMI. Patients with

BBB less frequently had a normal LVEF (n=6, 14.3%), compared with patients without a

BBB (n=287, 42.8%, p<0.001). Patients with BBB had more often a severely reduced LVEF

after STEMI (n=8, 19.0%) compared with patients without BBB (n=23, 3.6%, p<0.001).

Between mildly and moderate LVEF no difference was found between patients with and

without BBB (n=18, 42.9% and n=10, 23.8% vs n=269, 40.1% and n=92, 13.7%, figure 9).

Table 8 presents univariate and multivariate ordered logistic regression and shows that BBB

is an independent predictor of lower LVEF.

Patients with LAFB were more likely to have a severely reduced LVEF after STEMI

compared with patients without BBB (n=5, 17.9%, p=0.012). In univariate logistic regression

there was an association between LAFB and reduced LVEF, but in multivariate logistic

regression, LAFB was not an independent predictor of reduced LVEF (table 8).

No difference was found between LBBB and RBBB and LVEF group in ordered logistic

regression (table 8).

Figure 9. categorization on LVEF in patients with and without BBB

p < 0.001

p = 0.420

p = 0.107

p < 0.001

01

03

02

05

06

04

0

Pa

tien

ts p

er

LV

EF

gro

up

(%

)

no BBB BBB

Normal LVEF Mildly reduced LVEF

Moderately reduced LVEF Severely reduced LVEF

22

Table 8. Univariate and multivariate ordered logistic regression: LVEF group

Table 8. Univariate ordered logistic regression

p-value Coef 95% CI R² Multivariate ordered logistic regression

p-value Coef 95% CI

BBB <0.001 1.447 0.859 - 2.034 0.014 0.002 1.152 0.456 – 2.049

LAFB 0.005 0.903 0.272 - 0.1533 0.005

LBBB vs RBBB 0.950

Male 0.500

Age (per year) <0.001 0.021 0.010 - 0.033 0.008 0.005 0.021 0.006 - 0.036

Risk factors

BMI (per 1 kg/m2) 0.222

Hypertension 0.090 0.063 -0.010 - 0.136 0.002

Diabetes 0.11

Hypercholesterolemia 0.073 0.051 -0.005 - 0.106 0.002

Current smoker 0.113

Family history 0.008 0.087 0.023 - 0.151 0.004

Medical history

MI 0.009 0.473 0.029 - 0.917 0.004

PCI 0.059 0.224 -0.009 - 0.456 0.002

CABG 0.153

CVA 0.015 1.072 0.211 - 1.933 0.004

VF 0.834

Malignancy 0.789

PVD 0.152

Medication

Beta-Blocker 0.600

ACE-inhibitors 0.586

Angiotensin II receptor antagonist 0.729

Diuretics 0.803

Calcium Channel Blockers 0.747

Anti-arrythmic 0.767

Insulin 0.793

Metformine 0.344

Lab-values

Peak CK in hospital (per 100 U/L) <0.001 0.037 0.030 - 0.044 0.080 <0.001 0.038 0.029 - 0.047

Peak Ck-MB in hospital (per 100 U/L) <0.001 0.015 0.012 - 0.018 0.086

Peak troponin in hospital (per 100 U/L) <0.001 0.015 0.012 - 0.018 0.086


Heart rate (per 10 beats/min) <0.001 0.015 0.007 - 0.023 0.009

Systolic blood pressure (per 1 mmHg) 0.051 0.006 -0.011 - 0.00 0.002

Diastolic blood pressure (per 1 mmHg) 0.335

Infarct location

RCA <0.001 0.749 -1.032 - -0.466 0.016

LMCA 0.049 1.300 0.052 - 2.548 0.002

CX <0.001 0.594 -0.938 - -0.250 0.007 0.004 -0.711 -1.200 - -0.221

LAD <0.001 1.078 0.795 - 1.362 0.034 <0.001 0.695 0.324 - 1.065

Culprit <0.001

Successful PCI <0.001 1.020 -1.506 - -0.533 0.013 0.003 -0.800 -1.320 - -0.281


Beta-Blocker 0.448


Aspirine 0.062 0.215 -0.469 - 0.039 0.002

Statine 0.297

Clopidogrel/ticagrelor 0.726

23

7. Discussion

7.1. Discussion LifeLines database 7.1.1 Prevalence of bundle branch block The prevalence of LBBB was 0.34% and the prevalence of RBBB was 0.78% in the

LifeLines population. 1.88% Of the participants had a LAFB and 0.08% a LPFB. The study

of Haataja et al showed a prevalence of 0.9% of LBBB in men and women and prevalences

of 1.5% and 0.7% of RBBB, 1.2% and 0.9% of LAFB and 0.2% and 0.1% of LPFB in men

and woman29

. This study only included individuals 30 years or older. The prevalence of a

BBB increases with age and 13.9% (n= 21.165) of the individuals included in our study were

30 years of younger, which can explain the lower prevalence. Another study, including

18.974 individuals older than 20 years of age found RBBB prevalence of 1.4% and 0.5%

respectively for men and women24

, but no other types of BBB were observed. These

prevalences are similar to results found in our study (1.29% in male, and 0.42% in female).

To the best of our knowledge, we calculated the prevalence of different types of BBB in the

largest group of subjects so far.

7.1.2 Bundle branch block as risk factor of mortality and myocardial infarction

LBBB was associated with MI and death during follow-up. Similar result have been

published by a study of Erikkson et al and reported an increased risk of developing MI in

men with LBBB, but not in men with RBBB28

. This study observed 10.000 men and followed

them over a period of 28 years. An association between RBBB and MI in 15-year follow-up

was found in the study of Bussink et al24

. The appearance of LBBB was associated with

increased risk of CVD mortality in the Framingham study, with a follow-up of 18 years27

.

Follow-up time in our study was between eleven and 92 months after baseline. When more

follow-up data is available in the LifeLines database, analyses can be repeated to study the

effect of BBB during long-term follow-up.

As aforementioned, STEMI patients with BBB had more comorbidities compared to STEMI

patients without BBB. In logistic regression we did not adjust for risk factors of CVD. A

study that excluded participants with risk factors, reported an association of LBBB and

mortality in follow-up, but in multivariate Cox regression LBBB was not an independent

predictor of mortality26

. This study found a higher incidence of CVD in participants with

LBBB, but not in participants with RBBB compared to participants without BBB. In further

research risk factors of CVD will be taken into account.

7.2 Discussion STEMI patients UMCG The major findings of this study, regarding STEMI patients and BBB, were: (1) differences at

baseline between patients with and without a BBB; (2) no higher mortality in the BBB group

when adjusting for significant baseline characteristics and (3) an increased risk of reduced

LVEF in patients with BBB.

7.2.1 Baseline characteristics and treatment

STEMI patients with BBB had more co-morbidities compared to patients without BBB.

Patients with BBB were older, more often had diabetes or hypertension and were more likely

to have a history of MI, CABG or cancer. These findings and the lower frequency of smokers

among BBB patients are conforming other studies35-37,40-44

and suggest a higher clinical risk

profile in patients with BBB, which contributes to the poor outcome of STEMI patients with

BBB.

24

7.2.2 Mortality Mortality was higher in STEMI patients with BBB treated with the current reperfusion

therapy, compared to patients without BBB. In multivariate analyses BBB did not remain an

independent predictor of mortality. This is in contrast with most studies reporting BBB as an

independent predictor of in-hospital, and future mortality34-36,39,43,44,49

. In previous studies,

patients with BBB did not undergo, or underwent less frequently PCI42,49

. This difference in

treatment could be an explanation of higher mortality rates in earlier studies. In this study,

BBB patients were less likely to receive beta-blockers after STEMI, because of

contraindications with the already existing conduction delay, but otherwise they received

similar medicinal treatment compared with patients without BBB. Because medicinal

treatment was almost equal and all patients underwent PCI, this study suggests that patients

with BBB may have a better outcome when treated with reperfusion therapy compared to

thrombolytic therapy. In a similar study on patients undergoing PCI, a higher mortality was

reported in patients with LBBB compared to patients with RBBB43

. By reason of the low

prevalence of LBBB and RBBB among STEMI patients, we did not make a distinction

between LBBB and RBBB. Further research has to be performed to see if there is a

difference between these two groups. The higher mortality among BBB patients in this study

seemed to be determined by the bigger infarct size and lower LVEF in this patient group,

together with the higher age and the higher number of co-morbidities. Therefore, ischemic

time in STEMI patients with BBB should be kept as low as possible to limit the infarct

size17,55

and recommendations for these patients should be focused on the therapy of heart

failure.

To our knowledge, very few data is published so far investigating the outcome of STEMI

patients with LAFB. In one previous study, LAFB was not an independent predictor of

mortality45

. A similar study showed that the likelihood to die is the highest in the patient

group with RBBB and LAFB39

. In this study, eleven patients had RBBB with LAFB; due to

this small amount, we did not perform additional analyses.

7.2.3 Left ventricular ejection fraction BBB is an independent predictor of lower LVEF. There is a paucity of data concerning the

influence of BBB on LVEF in patients with MI and BBB. In a study of Stenestrand et al, it is

suggested that patients with BBB are at higher risk of developing clinical signs of heart

failure40,42

. Due to a lack of pre-STEMI data we could not make a distinction between new

onset and pre-existent BBB. A BBB can be a manifestation of an underlying heart disease

and appears to associated with low LVEF56-58

. Whether the lower LVEF in BBB patients is a

result of STEMI or pre-existing heart disease is unknown. On top of that, patient with BBB

have higher lab values (peak CK (U/L), peak Ck-MB (U/L) and peak hs-TnT (µg/L). These

data indicate that BBB in STEMI patients is associated with larger infarct size. In general,

larger infarct size is associated with lower LVEF8. Performing PCI provides information

about the TIMI flow after the procedure, which is an important prognostic factor of outcome

after STEMI. In this study, patients with BBB had less often a successful PCI (TIMI flow of

three after PCI) compared with patients with BBB, which is suggestive for a worse outcome

as well.

Patients with a LAFB more often had an anterior infarction. An anterior infarction is an

important predictor of lower LVEF59

. The major part of the bundle branches are supplied

with blood by the LAD coronary artery, this can explain the higher incidence of a LAFB and

anterior infarction60

. In univariate ordered logistic regression, patients with LAFB were more

25

likely to have a moderately or severely reduced LVEF after MI but in multivariate logistic

regression LAFB seems not to be an independent predictor.

7.3 Limitations The LifeLines database consisted of voluntary participation and a lot of data was based on

self-administered questionnaire, therefore the following biases may have occurred: (1) a

selection bias, assuming that more healthy people participated in this research and therefore a

lower frequency of patients with BBB or MI may have been found (2) participants may have

forgotten to fill in questions or may have given the wrong answers. (3) No influence could be

exerted on the questions or measurements and therefore medication use was not available in

follow-up data, the reason we could not validate the self-reported MI. The follow-up time

was a limitation of the LifeLines database as well, whereby only a few participants with BBB

developed MI during follow-up. By repeating these analyses in future more events will have

occurred and analyses will be more reliable. The sample size in the STEMI database was the

main limitation of this study and denied us the possibility of analyzing differences between

LBBB and RBBB and between transient and persistent BBB. Due to a lack of pre-STEMI

ECG data we could not make a distinction between a new onset and pre-existent BBB and

between transient and persistent BBB. Previous studies suggests that the likelihood for death

higher is in patients with persistent BBB than in those with transient BBB and that new BBB

result in higher mortality than known BBB34,37,61

. In our study, LVEF is often determined

with a range because of the echo quality. Some ranges have an overlap with two LVEF

groups, whereby a bias can occur. By consequently placing the same ranges in the same

groups, the bias is kept as small as possible. In future research we want to take these

limitations into account.

8. Conclusion In the general population, the prevalence of BBB increases with age and is more common in

males. LBBB, but no other types of BBB, is associated with MI and mortality in follow-up.

In STEMI patients, BBB is an independent predictor of an reduced LVEF, but not an

independent predictor of mortality in the current era of reperfusion therapy.

9. Acknowledgements I would like to thank Pim van der Harst and Minke Hartman for their supervision of my

scientific internship. I would like to thank Rik van der Werf, Erik Lipsic and Tom Hendriks

for their feedback on the paper I wrote about this study. And finally, I would like to thank

Renier Snieders for his help with regard to the LifeLines database.

26

10. References

(1) Fox KA, Goodman SG, Klein W, Brieger D, Steg PG, Dabbous O, et al. Management of acute

coronary syndromes. Variations in practice and outcome; findings from the Global Registry of Acute

Coronary Events (GRACE). Eur Heart J 2002 Aug;23(15):1177-1189.

(2) Koopman C, van Dis I, Visseren FLJ, Vaartjes I, Bots ML. Cijfers over risicofactoren, ziekte en

sterfte, Hart- en vaatziekten in Nederland 2012. 2012; Available at:

http://www.act020.nl/uploads/111/Cijfers%20HVZ%202012_compleet.pdf, 2012.

(3) Alpert J S JS. Myocardial infarction redefined--a consensus document of The Joint European

Society of Cardiology/American College of Cardiology Committee for the redefinition of myocardial

infarction. J Am Coll Cardiol 2000-9;36(3):959-69.

(4) Adams JE,3rd, Abendschein DR, Jaffe AS. Biochemical markers of myocardial injury. Is MB

creatine kinase the choice for the 1990s? Circulation 1993 Aug;88(2):750-763.

(5) Macrae AR, Kavsak PA, Lustig V, Bhargava R, Vandersluis R, Palomaki GE, et al. Assessing the

requirement for the 6-hour interval between specimens in the American Heart Association

Classification of Myocardial Infarction in Epidemiology and Clinical Research Studies. Clin Chem

2006 May;52(5):812-818.

(6) James SK, Armstrong P, Barnathan E, Califf R, Lindahl B, Siegbahn A, et al. Troponin and C-

reactive protein have different relations to subsequent mortality and myocardial infarction after acute

coronary syndrome: a GUSTO-IV substudy. J Am Coll Cardiol 2003 Mar 19;41(6):916-924.

(7) Roberts R, Gowda KS, Ludbrook PA, Sobel BE. Specificity of elevated serum MB creatine

phosphokinase activity in the diagnosis of acute myocardial infarction. Am J Cardiol 1975 Oct

6;36(4):433-437.

(8) Vatner SF, Baig H, Manders WT, Maroko PR. Effects of coronary artery reperfusion on

myocardial infarct size calculated from creatine kinase. J Clin Invest 1978 Apr;61(4):1048-1056.

(9) Puleo PR, Guadagno PA, Roberts R, Scheel MV, Marian AJ, Churchill D, et al. Early diagnosis of

acute myocardial infarction based on assay for subforms of creatine kinase-MB. Circulation 1990

Sep;82(3):759-764.

(10) Puleo PR, Meyer D, Wathen C, Tawa CB, Wheeler S, Hamburg RJ, et al. Use of a rapid assay of

subforms of creatine kinase-MB to diagnose or rule out acute myocardial infarction. N Engl J Med

1994 Sep 1;331(9):561-566.

(11) Antman EM, Anbe DT, Armstrong PW, Bates ER, Green LA, Hand M, et al. ACC/AHA

guidelines for the management of patients with ST-elevation myocardial infarction; A report of the

American College of Cardiology/American Heart Association Task Force on Practice Guidelines

(Committee to Revise the 1999 Guidelines for the Management of patients with acute myocardial

infarction). J Am Coll Cardiol 2004 Aug 4;44(3):E1-E211.

(12) Thygesen K, Alpert JS, Jaffe AS, Simoons ML, Chaitman BR, White HD, et al. Third universal

definition of myocardial infarction. Circulation 2012 Oct 16;126(16):2020-2035.

http://www.act020.nl/uploads/111/Cijfers%20HVZ%202012_compleet.pdf

27

(13) Simons MS, Aroesty M, J.M. Trials of conservative versus early invasive therapy in unstable

angina and non-ST elevation myocardial infarction . 2014; Available at:

http://www.uptodate.com/contents/trials-of-conservative-versus-early-invasive-therapy-in-unstable-

angina-and-non-st-elevation-myocardial-

infarction?source=search_result&search=treatment+nSTEMI&selectedTitle=4%7E141. Accessed

03/25.

(14) Gibson CM, Cannon CP, Murphy SA, Ryan KA, Mesley R, Marble SJ, et al. Relationship of

TIMI myocardial perfusion grade to mortality after administration of thrombolytic drugs. Circulation

2000 Jan 18;101(2):125-130.

(15) Mehta RH, Ou FS, Peterson ED, Shaw RE, Hillegass WB,Jr, Rumsfeld JS, et al. Clinical

significance of post-procedural TIMI flow in patients with cardiogenic shock undergoing primary

percutaneous coronary intervention. JACC Cardiovasc Interv 2009 Jan;2(1):56-64.

(16) Smit JJ, Ottervanger JP, Slingerland RJ, Suryapranata H, Hoorntje JC, Dambrink JH, et al.

Successful reperfusion for acute ST elevation myocardial infarction is associated with a decrease in

WBC count. J Lab Clin Med 2006 Jun;147(6):321-326.

(17) De Luca G, Ernst N, Zijlstra F, van 't Hof AW, Hoorntje JC, Dambrink JH, et al. Preprocedural

TIMI flow and mortality in patients with acute myocardial infarction treated by primary angioplasty. J

Am Coll Cardiol 2004 Apr 21;43(8):1363-1367.

(18) Levick JR. Coronary circulation. An introduction to Cardiovascular Physiology. 5th ed.: Hodder

Arnold; 2010. p. 279-278.

(19) prof. dr. E.E. van der Wall, prof. dr. F. van de Werf, prof. dr. F. Zijlstra. Coronaire anatomie.

Cardiologie. 2e ed.: Bohn Stafleu van Loghum; 2002. p. 161-162, 163.

(20) Arntzenius dAC, Meurs dAAH. Praktische elektrocardiografie. 3rd ed. Houten/Diegem: Bohn

Stafleu Van Loghum; 1989.

(21) Kligfield Paul P. Recommendations for the standardization and interpretation of the

electrocardiogram: part I: The electrocardiogram and its technology: a scientific statement from the

American Heart Association Electrocardiography and Arrhythmias Committee, Council on Clinical

Cardiology; the American College of Cardiology Foundation; and the Heart Rhythm Society:

endorsed by the International Society for Computerized Electrocardiology. Circulation 2007-3-

13;115(10):1306-24.

(22) Strauss DG, Loring Z, Selvester RH, Gerstenblith G, Tomaselli G, Weiss RG, et al. Right, but

not left, bundle branch block is associated with large anteroseptal scar. J Am Coll Cardiol 2013 Sep

10;62(11):959-967.

(23) Arslan U, Balcioglu S, Tavil Y, Ozdemir M, Cengel A. Clinical and angiographic importance of

right bundle branch block in the setting of acute anterior myocardial infarction. Anadolu Kardiyol

Derg 2008 Apr;8(2):123-127.

(24) Bussink BE, Holst AG, Jespersen L, Deckers JW, Jensen GB, Prescott E. Right bundle branch

block: prevalence, risk factors, and outcome in the general population: results from the Copenhagen

City Heart Study. Eur Heart J 2013 Jan;34(2):138-146.

(25) Eriksson P, Hansson PO, Eriksson H, Dellborg M. Bundle-branch block in a general male

population: the study of men born 1913. Circulation 1998 Dec 1;98(22):2494-2500.

http://www.uptodate.com/contents/trials-of-conservative-versus-early-invasive-therapy-in-unstable-angina-and-non-st-elevation-myocardial-infarction?source=search_result&search=treatment+nSTEMI&selectedTitle=4%7E141



28

(26) Fahy GJ, Pinski SL, Miller DP, McCabe N, Pye C, Walsh MJ, et al. Natural history of isolated

bundle branch block. Am J Cardiol 1996 Jun 1;77(14):1185-1190.

(27) Schneider JF, Thomas HE,Jr, Kreger BE, McNamara PM, Kannel WB. Newly acquired left

bundle-branch block: the Framingham study. Ann Intern Med 1979 Mar;90(3):303-310.

(28) Eriksson P, Wilhelmsen L, Rosengren A. Bundle-branch block in middle-aged men: risk of

complications and death over 28 years. The Primary Prevention Study in Goteborg, Sweden. Eur

Heart J 2005 Nov;26(21):2300-2306.

(29) Haataja P, Nikus K, Kahonen M, Huhtala H, Nieminen T, Jula A, et al. Prevalence of ventricular

conduction blocks in the resting electrocardiogram in a general population: the Health 2000 Survey.

Int J Cardiol 2013 Sep 1;167(5):1953-1960.

(30) Dubois C, Pierard LA, Smeets JP, Foidart G, Legrand V, Kulbertus HE. Short- and long-term

prognostic importance of complete bundle-branch block complicating acute myocardial infarction.

Clin Cardiol 1988 May;11(5):292-296.

(31) Bauer GE, Julian DG, Valentine PA. Bundle-branch block in acute myocardial infarction. Br

Heart J 1965 Sep;27(5):724-730.

(32) Roos JC, Dunning AJ. Right bundle-branch block and left axis deviation in acute myocardial

infarction. Br Heart J 1970 Nov;32(6):847-851.

(33) Wong CK, Stewart RA, Gao W, French JK, Raffel C, White HD. Prognostic differences between

different types of bundle branch block during the early phase of acute myocardial infarction: insights

from the Hirulog and Early Reperfusion or Occlusion (HERO)-2 trial. Eur Heart J 2006 Jan;27(1):21-

28.

(34) Ricou F, Nicod P, Gilpin E, Henning H, Ross J,Jr. Influence of right bundle branch block on

short- and long-term survival after acute anterior myocardial infarction. J Am Coll Cardiol 1991 Mar

15;17(4):858-863.

(35) Melgarejo-Moreno A, Galcera-Tomas J, Garcia-Alberola A, Valdes-Chavarri M, Castillo-Soria

FJ, Mira-Sanchez E, et al. Incidence, clinical characteristics, and prognostic significance of right

bundle-branch block in acute myocardial infarction: a study in the thrombolytic era. Circulation 1997

Aug 19;96(4):1139-1144.

(36) Go AS, Barron HV, Rundle AC, Ornato JP, Avins AL. Bundle-branch block and in-hospital

mortality in acute myocardial infarction. National Registry of Myocardial Infarction 2 Investigators.

Ann Intern Med 1998 Nov 1;129(9):690-697.

(37) Brilakis E S ES. Bundle branch block as a predictor of long-term survival after acute myocardial

infarction. American Journal of Cardiology, The 2001-8-1;88(3):205-9.

(38) Newby KH, Pisano E, Krucoff MW, Green C, Natale A. Incidence and clinical relevance of the

occurrence of bundle-branch block in patients treated with thrombolytic therapy. Circulation 1996

Nov 15;94(10):2424-2428.

29

(39) Sgarbossa EB, Pinski SL, Topol EJ, Califf RM, Barbagelata A, Goodman SG, et al. Acute

myocardial infarction and complete bundle branch block at hospital admission: clinical characteristics

and outcome in the thrombolytic era. GUSTO-I Investigators. Global Utilization of Streptokinase and

t-PA [tissue-type plasminogen activator] for Occluded Coronary Arteries. J Am Coll Cardiol 1998

Jan;31(1):105-110.

(40) Lewinter Christian C. Right and left bundle branch block as predictors of long-term mortality

following myocardial infarction. European Journal of Heart Failure 2011-12;13(12):1349-54.

(41) Bogale Nigussie N. Usefulness of either or both left and right bundle branch block at baseline or

during follow-up for predicting death in patients following acute myocardial infarction. American

Journal of Cardiology, The 2007-3-1;99(5):647-50.

(42) Stenestrand Ulf U. Comorbidity and myocardial dysfunction are the main explanations for the

higher 1-year mortality in acute myocardial infarction with left bundle-branch block. Circulation

2004-10-5;110(14):1896-902.

(43) Guerrero Mayra M. Comparison of the prognostic effect of left versus right versus no bundle

branch block on presenting electrocardiogram in acute myocardial infarction patients treated with

primary angioplasty in the primary angioplasty in myocardial infarction trials. American Journal of

Cardiology, The 2005-8-15;96(4):482-8.

(44) Yeo KK, Li S, Amsterdam EA, Wang TY, Bhatt DL, Saucedo JF, et al. Comparison of clinical

characteristics, treatments and outcomes of patients with ST-elevation acute myocardial infarction

with versus without new or presumed new left bundle branch block (from NCDR(R)). Am J Cardiol

2012 Feb 15;109(4):497-501.

(45) Zhang H, Goodman SG, Steg GP, Budaj A, Lopez-Sendon J, Dorian P, et al. Clinical

characteristics and outcomes of acute coronary syndrome patients with left anterior hemiblock. Heart

2014 Sep 15;100(18):1456-1461.

(46) StatLine C. Health, lifestyle, health care use and supply, causes of death; from 1900. 2015;

Available at:

http://statline.cbs.nl/Statweb/publication/?VW=T&DM=SLEN&PA=37852eng&D1=a&D2=0,10,20,

30,40,50,60,70,80,90,100,(l-1)-l&HD=150630-1104&LA=EN&HDR=G1&STB=T. Accessed 06/30,

2015.

(47) Aversano Thomas T. Thrombolytic therapy vs primary percutaneous coronary intervention for

myocardial infarction in patients presenting to hospitals without on-site cardiac surgery: a randomized

controlled trial. JAMA 2002-4-17;287(15):1943-51.

(48) Le May M R MR. Stenting versus thrombolysis in acute myocardial infarction trial (STAT). J

Am Coll Cardiol 2001-3-15;37(4):985-91.

(49) Sorensen JT, Stengaard C, Sorensen CA, Thygesen K, Botker HE, Thuesen L, et al. Diagnosis

and outcome in a prehospital cohort of patients with bundle branch block and suspected acute

myocardial infarction. Eur Heart J Acute Cardiovasc Care 2013 Jun;2(2):176-181.

(50) Farre N, Merce J, Camprubi M, Mohandes M, Guarinos J, Fernandez F, et al. Prevalence and

outcome of patients with left bundle branch block and suspected acute myocardial infarction. Int J

Cardiol 2014 Dec 30;182C:164-165.

http://statline.cbs.nl/Statweb/publication/?VW=T&DM=SLEN&PA=37852eng&D1=a&D2=0,10,20,30,40,50,60,70,80,90,100,(l-1)-l&HD=150630-1104&LA=EN&HDR=G1&STB=T

http://statline.cbs.nl/Statweb/publication/?VW=T&DM=SLEN&PA=37852eng&D1=a&D2=0,10,20,30,40,50,60,70,80,90,100,(l-1)-l&HD=150630-1104&LA=EN&HDR=G1&STB=T

30

(51) Doel en uitgangspunten LifeLines. Available at: https://www.lifelines.nl/organisatie/doel-en-

uitgangspunten.

(52) Scholtens S, Smidt N, Swertz MA, Bakker SJ, Dotinga A, Vonk JM, et al. Cohort Profile:

LifeLines, a three-generation cohort study and biobank. Int J Epidemiol 2014 Dec 14.

(53) WHO Collaborating Centre for Drug Statistics Methodology. ATC/DDD index 2015. 2015;

Available at: http://www.whocc.no/atcddd/. Accessed 06/30, 2015.

(54) Lang RM, Badano LP, Mor-Avi V, Afilalo J, Armstrong A, Ernande L, et al. Recommendations

for cardiac chamber quantification by echocardiography in adults: an update from the american

society of echocardiography and the European association of cardiovascular imaging. Eur Heart J

Cardiovasc Imaging 2015 Mar;16(3):233-271.

(55) Fokkema ML, Wieringa WG, van der Horst IC, Boersma E, Zijlstra F, de Smet BJ. Quantitative

analysis of the impact of total ischemic time on myocardial perfusion and clinical outcome in patients

with ST-elevation myocardial infarction. Am J Cardiol 2011 Dec 1;108(11):1536-1541.

(56) Harimoto K, Kawasaki T, Honda S, Miki S, Kamitani T. Right bundle branch block and

ventricular septal fibrosis in patients with hypertrophic cardiomyopathy. J Electrocardiol 2014 Sep-

Oct;47(5):636-641.

(57) Unverferth DV, Magorien RD, Moeschberger ML, Baker PB, Fetters JK, Leier CV. Factors

influencing the one-year mortality of dilated cardiomyopathy. Am J Cardiol 1984 Jul 1;54(1):147-

152.

(58) Xiao HB, Roy C, Fujimoto S, Gibson DG. Natural history of abnormal conduction and its

relation to prognosis in patients with dilated cardiomyopathy. Int J Cardiol 1996 Feb;53(2):163-170.

(59) Stone PH, Raabe DS, Jaffe AS, Gustafson N, Muller JE, Turi ZG, et al. Prognostic significance

of location and type of myocardial infarction: independent adverse outcome associated with anterior

location. J Am Coll Cardiol 1988 Mar;11(3):453-463.

(60) James TN, Burch GE. Blood supply of the human interventricular septum. Circulation 1958

Mar;17(3):391-396.

(61) Hod H, Goldbourt U, Behar S. Bundle branch block in acute Q wave inferior wall myocardial

infarction. A high risk subgroup of inferior myocardial infarction patients. The SPRINT Study Group.

Secondary Prevention Reinfarction Israeli Nifedipine Trial. Eur Heart J 1995 Apr;16(4):471-477.

https://www.lifelines.nl/organisatie/doel-en-uitgangspunten

https://www.lifelines.nl/organisatie/doel-en-uitgangspunten

http://www.whocc.no/atcddd/

31

11. Appendix

Table 1. Baseline Characteristics LBBB and RBBB

LBBB

n = 23

RBBB

n = 49

p-value

Male (%) 60.9 85.7 0.018

Age (yrs) 70.6 (2.9) 70.0 (1.7) 0.852

Risk factors

BMI (kg/m2) 26.6 (1.1) 26.3 (0.5) 0.782

Hypertension (%) 39.1 46.9 0.782

Diabetes (%) 26.1 31.3 0.656

Hypercholesterolemia (%) 13.0 38.8 0.084

Current smoker (%) 13.0 34.7 0.160

Family history (%) 13.0 34.7 0.128

Medical history

MI (%) 17.4 26.5 0.395

PCI (%) 4.4 14.3 0.261

CABG (%) 8.7 6.1 0.579

CVA (%) 4.4 10.2 0.402

VF (%) 26.1 6.1 0.017

Malignancy (%) 26.1 12.2 0.142

PVD (%) 8.3 30.4 0.139

Medication

Beta-Blocker (%) 26.1 34.7 0.153

ACE-inhibitors (%) 17.4 30.6 0.113

Angiotensin II receptor antagonist (%) 17.4 6.1 0.038

Diuretics (%) 17.4 10.2 0.090

Calcium Channel Blockers (%) 26.1 8.2 0.012

Anti-arrythmic (%) 4.4 6.1 0.161

Insulin (%) 8.7 10.2 0.336

Metformine (%) 17.4 22.5 0.622

Lab-values

Peak CK in hospital (U/L) 1515 (567 - 5836) 2411 (846 - 4049) 0.491

Peak Ck-MB in hospital (U/L) 179 (79 - 509) 304 (135 - 477) 0.723

Peak hs-TnT in hospital (µg/L) 4142 (1550 - 9747) 6226 (3006 - 11961) 0.284


Heart rate (beats/min) 84.9 (4.7) 83.8 (2.9) 0.829

Systolic blood pressure (mmHg) 132.3 (7.6) 134.9 (4.8) 0.689

Diastolic blood pressure (mmHg) 82.2 (3.1) 85.9 (2.9) 0.454

Infarct location

RCA (%) 17.4 32.7 0.178

LMCA (%) 4.4 2.0 0.579

CX (%) 26.1 12.2 0.142

LAD (%) 43.5 46.9 0.076

Culprit 0.680

Successful PCI (%) 80.0 76.0 0.769


Beta-Blocker (%) 77.3 88.1 0.257

ACE-inhibitors (%) 63.6 66.7 0.808

Aspirine (%) 86.4 88.1 0.842

Statine (%) 86.4 92.9 0.397

Clopidogrel/ticagrelor (%) 87.0 81.6 0.572

32

Table 2. Univariate Cox regression: two year mortality

Factor Univariate cox regression

p-value Haz. ratio 95% CI

P –value Odds ratio 95% CI

R²

BBB <0.001 3.425 2.054 – 5.708

LAFB 0.085

0 2.018 0.976 – 4.172

LBBB vs RBBB 0.564

Male 0.218

Age (per year) <0.001 1.051 1.034 – 1.067

Risk factors

BMI (per 1 kg/m2) 0.339

Hypertension <0.001 1.265 1.208 – 1.324

Diabetes 0.1013

Hypercholesterolemia <0.001 1.257 1.201 – 1.316

Current smoker <0.001 1.275 1.215 – 1.338

Family history <0.001 1.290 1.231 – 1.350

Medical history

MI 0.253

PCI 0.738

CABG 0.989

CVA 0.471

VF 0.002 1.270 1.130 – 1.427

Malignancy 0.608

PVD 0.149

Medication at presentation

Beta-Blocker <0.001 1.154 1.092 – 1.219

ACE-inhibitors <0.001 1.147 1.086 – 1.212

Angiotensin II receptor antagonist <0.001 1.151 1.090 – 1.215

Diuretics <0.001 1.166 1.106 – 1.228

Calcium Channel Blockers <0.001 1.161 1.101 – 1.224

Anti-arrythmic <0.001 1.148 1.088 – 1.211

Insulin 0.111

Metformine 0.324

Lab-values

Peak CK in hospital (per 100 U/L) <0.001 1.014 1.011 – 1.017

Peak Ck-MB in hospital (per 100 U/L) <0.001 1.002 1.001 – 1.002

Peak troponin in hospital (per 100 U/L) <0.001 1.002 1.001 – 1.002


Heart rate (per 10 beats/min) <0.001 1.250 1.133 – 1.379

Systolic blood pressure (per 1 mmHg) <0.001 0.978 0.969 – 0.987

Diastolic blood pressure (per 1 mmHg) <0.001 0.961 0.945 – 0.977

Infarct location

RCA 0.187

LMCA 0.054 3.958 1.254 – 12.485

CX 0.198

LAD 0.383

Culprit 0.095

Successful PCI 0.113


Beta-Blocker 0.901


Asprine 0.409

Statine 0.754

Clopidogrel/ticagrelor 0.189

LVEF group

Normal LVEF (reference) <0.001

Mildly abnomal LVEF 0.463 1.710 0.409 – 7.154

Moderately reduced LVEF <0.001 10.017 2.757 – 36.401

Severely reduced LVEF <0.001 24.221 6.262 – 93.683

the importance of bundle branch block in the general...

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