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Abstract

Background:

Pacemakers (PM) and implantable cardioverter defibrillators (ICD) may be indicated for sudden death prevention in myotonic dystrophy type 1 (DM1), however the risk of complications after the placement of these devices is unknown.

Objective:

To compare the rate of device-related complications between PM and ICD implantations in patients with DM1.

Methods:

Among 914 patients with DM1 included in the DM1 Heart Registry between January 2000 and January 2010, we retrospectively selected 23 patients who were implanted with an ICD and matched them to 46 controls with a PM on age, gender, and year of device placement.

Results:

Over a 6 years follow-up period, we observed device-related complications in 9 ICD recipients (inappropriate shocks in 5, lead dysfunction in 5, infection in 2) and in 3 PM recipients (lead dysfunction in 3). Patients with an ICD had, compared to those with a PM, higher rates of complications (39.1% vs. 6.5%, p = 0.0006) and more frequent complications requiring hospitalisation and/or re-intervention (respectively 30.4% and 21.7% vs. 0%).

Conclusion:

Our study shows a higher risk of device-related complications after the implantation of an ICD than for a PM in patients presenting with DM1.

Keywords

Myotonic dystrophy 1 complications implantable cardioverter-defibrillator pacemaker

INTRODUCTION

Myotonic dystrophy type 1 (DM1) is the most frequent inherited muscular dystrophy in adults, with an incidence of 1/8,000 births [1], caused by the expansion of a (CTG)n triplet repeat in the untranslated 3’ region of the DMPK gene [2]. The manifestations of the disease include muscle weakness, myotonia,diabetes, respiratory insufficiency, conduction system disease, supraventricular and ventricular arrhythmias [3, 4].

The prevention of sudden death (SD), affecting up to 1/3 of patients, is central in the management of this disorder [5, 6]. Because the largest proportion of SD is attributed to the progression of conduction system disease to complete atrioventricular (AV) block, the implantation of a permanent pacemaker (PM) is recommended in patients presenting with conduction defects on the surface electrocardiogram (ECG) [7 –9]. Recently, the contribution of ventricular arrhythmias to a proportion of SD in patients with DM1 has raised the issue of a potential primary preventive benefit conferred by implantable cardioverter-defibrillators (ICD) [5 , 8]. In the general population, the rate of complications after ICD implantation is higher than after PM implantation, mostly due to local infection of the device, lead dysfunction, and inappropriate shocks. These complications may be severe, requiring re-interventions to extract the device or even sometimes leading to death [10 –18].

Decisions to implant a PM or an ICD rely on the complex evaluation of the ratio between the benefit conferred by the device and the risk of complications. In DM1, the risk of complications following device implantation is unknown and may be higher than in general population with respect to the multisystemic involvement of the disease. We designed this study to determine the risk of complications in patients presenting with DM1 after PM and ICD implantations.

MATERIALS AND METHODS

The DM1 Heart Registry

The DM1 Heart Registry was designed and organized by the Cardiology Department of Cochin Hospital and the Myology Institute in Pitié-Salpêtrière Hospital. We retrospectively identified and included in this Registry 914 consecutive patients >18 years of age, admitted to our Institutions between January 2000 and January 2010 for the management of genetically identified DM1. We retrospectively reviewed the patients’ medical records and entered in a dedicated database the results of their genetic testing, and of all neurological and cardiac investigations. The vital status of all patients was ascertained by consulting the National Death Registry or by contacting their primary physician. This study, which is in compliance with the ethical principles formulated in the declaration of Helsinki, was approved by our local Ethics Committee, and all patients granted their informed, written consent to participate in the Registry.

Patient selection and study outcomes

Among the 914 patients included in the DM1 Heart Registry, we selected patients who underwent the implantation of an ICD during our study period. We matched patients with an ICD to patients with a PM in a 1:2 ratio on: 1) age at the implantation of the device, 2) sex, and 3) year of the procedure. The patient follow-up routinely included ambulatory examinations by a cardiologist 3 months after the implantation of the device and then at least every 6 months.

We analysed the information relative to the characteristics of device-related complications, including their type, delay after the procedure, severity, and treatments. We classified these complications as early or late if they occurred within or after 4 weeks after the implantation of the device. The severity of complications was stratified on the necessity of hospitalisation and re-intervention.

Statistical analysis

Data are presented as median (IQR), mean (SD) and number (percentage) as appropriate. We compared the rates of complications in the 2 groups (PM and ICD) with Mann-Whitney U test, chi-square or Fisher exact test. A P-value<0.05 was considered as significant (STATA 13.0 software, StataCorp LP, College station, Tx, USA).

RESULTS

Study population

Among the 914 patients referred to our institutions and included in our registry between January 2000 and December 2009, we identified 23 patients who were implanted with an ICD during this period. We matched these 23 patients on age, sex, and year of implantation to 46 patients who had a PM implanted. The characteristics of our study population at implantation of the device are summarized in Table 1.

Table 1

Patient characteristics at implantation of the device

	Device		P
	ICD (n = 23)	PM (n = 46)
Male	17 (73.9)	34 (73.9)	–
Age	38.9±11.8	39.5±11.2	0.84
CTG repeats	551±360	675±382	0.39
MDRS score	2.7±0.7	3.1±1.0	0.24
MIRS score	0.26
Grade I	1 (4.3)	3 (6.5)
Grade II	6 (26.1)	7 (15.2)
Grade III	12 (52.2)	23 (50.0)
Grade IV	4 (17.4)	8 (17.4)
Grade V	0 (–)	5 (10.9)
Clinical form of the
disease
Congenital	0 (–)	2 (4.3)
Infantile	1 (4.3)	1 (2.2)
Juvenile	10 (43.5)	22 (47.8)
Adult	10 (43.5)	16 (34.8)
Late-onset	2 (8.7)	5 (10.9)
Diabetes	2 (8.7)	8 (17.4)	0.34
Personal history
Supraventricular	10 (43.5)	6 (13.0)	0.004
arrhythmia
Sustained VT	6 (26.1)	1 (2.2)	<0.0001
Cardiac symptoms
Syncope	1 (4.3)	3 (6.5)	0.71
Heart failure	4 (17.4)	0 (0)	0.003
Lightheadedness	3 (13.0)	9 (19.6)	0.50
Palpitations	5 (21.7)	7 (15.2)	0.50
Electrocardiogram
PR interval, ms	198±53	211±27	0.18
QRS interval, ms	118±26	115±26	0.70
RBBB	7 (30.4)	5 (10.9)	0.04
LBBB	7 (30.4)	11 (23.9)	0.56
Echocardiography
LV ejection fraction	55.8±12.9	62.6±6.8	0.007
LV dysfunction*	8 (34.8)	4 (8.7)	0.02
Medical treatment
Vitamin K antagonist	5 (21.7)	1 (2.2)	0.006
Aspirin	3 (13.0)	8 (17.4)	0.64

Abbreviations: ICD = Implantable cardioverter-defibrillator; MDRS = Muscular Disability Rating Scale; MIRS = Muscular Impairment Rating Scale; LBBB = Left bundle-branch block; LV = Left ventricle; PM = Pacemaker; RBBB = Right bundle-branch block; VT = Ventricular tachycardia. *LV dysfunction was defined as LV ejection fraction <45%.

Indications for ICD implantations were severe left ventricular (LV) dysfunction (LV ejection fraction≤35%) in 4 patients, cardiac arrest due to ventricular fibrillation (VF) in 1, sustained ventricular tachycardia (VT) in 6, and inducible VF or sustained VT by programmed ventricular stimulation during electrophysiological study in 12. Indications for permanent pacing included high-degree conduction defects in 4 patients, and 1st degree AV or fascicular block on the surface ECG and/or a HV interval >70 ms on electrophysiological study in 42.

At implantation of the device, patients with an ICD had, compared to those with a PM, more frequently LV systolic dysfunction (34.8 vs. 8.7%, P = 0.02), lower LV ejection fraction (55.8±12.9 vs. 62.6±6.8%, P = 0.007), and a history of supraventricular arrhythmia (43.5 vs. 13.0%, P = 0.004) or sustained VT (26.1 vs. 2.2%, P < 0.0001).

Incidence and characteristics of ICD and PM-related complications

The incidence and the characteristics of device-related complications are presented in Tables 2 and 3. The mean follow-up duration was 69±34 months. One patient out of 23 in the ICD group received an appropriate treatment allowing the termination of a sustained VT. Patients with an ICD had more frequent device-related complications than patients with a PM (39.1 vs. 6.5%, P = 0.0006) and a higher average number of complications per procedure (1.67 vs. 1). Early and late complications were both more frequent in ICD recipients.

Table 2

Comparison of the characteristics of the device-related complications

	Device		P
	ICD (n = 23)	PM (n = 46)
Patients with≥1 complication	9 (39.1)	3 (6.5)	0.0006
Average number of complications per patient	1.67	1.0	–
Delay after device implantation
Within 1 month	3 (7.8)	1 (2.2)	0.04
Beyond 1 month	12 (31.3)	2 (4.3)	0.001
Complications severity
Hospitalisation	7 (30.4)	0 (0)	–
Re-intervention	5 (21.7)	0 (0)	–
Type of complication
Infections	2 (8.6)	0 (0)	–
Lead dysfunction	5 (21.7)	3 (6.5)	–
Inappropriate shocks	5 (21.7)	–	–
Device pocket migration	1 (4.3)	0	–
Device premature wear	1 (4.3)	0	–
Innominate vein thrombosis	1 (4.3)	0	–

Abbreviations: ICD = Implantable cardioverter-defibrillator; PM = Pacemaker.

Table 3

Individual characteristics of the 12 patients with device-related complications

No	Sex	CTG	MDRS	Device	Complication
					Delay (months)	Type	Treatments	Hospitalisation/
								Re-intervention
1	M	433	2	ICD	Late (30)	Lead rupture	Lead replacement	Yes/Yes
					Late (66)	Device pocket migration	Device replacement, device pocket refection	Yes/Yes
2	M	300	3	ICD	Late (60)	Pocket infection, lead rupture, inappropriate shock	Antibiotics, device replacement, pocket refection	Yes/Yes
							Lead replacement
3	M	830	3	ICD	Late (5)	Inappropriate shock	–	Yes/No
					Late (36)	Device premature wear	Device replacement	Yes/Yes
4	M	1100	4	ICD	Early (0,1)	Atrial undersensing	–	No/No
					Late (11)	Pocket infection, lead endocarditis	Antibiotics, device and lead replacement, device pocket refection	Yes/Yes
5	M	1000	3	ICD	Early (1)	Atrial undersensing	Lead repositioning	Yes/Yes
					Late (13)	Inappropriate shock	–	Yes/No
6	M	360	3	ICD	Late (5)	Innominate vein thrombosis	–	No/No
7	M	70	1	ICD	Early (0,1)	Ventricular undersensing	–	No/No
8	M	1000	3	ICD	Late (9)	Inappropriate shock	–	Yes/No
9	M	260	2	ICD	Late (60)	Inappropriate shock	–	Yes/No
10	M	300	3	PM	Late (110)	Atrial undersensing	–	No/No
11	F	333	2	PM	Early (0,5)	Atrial undersensing	–	No/No
12	M	1200	2	PM	Late (36)	Atrial undersensing	–	No/No

Abbreviations: ICD = Implantable Cardioverter Defibrillator; MDRS = Muscular Disability Rating Scale; PM = Pacemaker.

After ICD placement, complications included lead dysfunction in 5 patients (21.7%), infections in 2 (8.6%), inappropriate shocks in 5 (21.7%), and miscellaneous other events in 3 (13.0%). These complications specifically required a hospitalisation for management in 7 patients (30.4%) and/or re-intervention in 5 (21.7%). After PM placement, complications were exclusively atrial lead dysfunction and were managed in an outpatient setting.

Case studies of two patients with severe complications after ICD placement

We selected the observations of two patients who had complications following the implantation of their ICD to illustrate the possible severity of these events and the complexity of their management.

Case 1 – A 43 year-old patient with DM1 (#4) presented in our department with asymptomatic conduction defects on the ECG and non-sustained VT on 24-hours ambulatory ECG. Electrophysiological study showed a prolongation of HV interval >70 ms and the triggering of VF by programmed ventricular stimulation. A dual chamber ICD was thereafter implanted under local anaesthesia in the left retropectoral area. At hospital discharge, the ICD review displayed minor atrial undersensing. Eleven months after the implantation, he was diagnosed with an endocarditis revealed by prolonged fever with vegetations on the ventricular lead. He was treated with antibiotics for several months and the device and the probes were removed. An ICD was placed in the right retropectoral area 3 months after the completion of antibiotics.

Case 2 – A 32 year-old patient with DM1 (#2) was referred to our department for the management of 1st degree atrioventricular blocks on his ECG and asymptomatic sinus bradycardia. Electrophysiological study showed mild prolongation of conduction time intervals (HV between 55 and 70 ms), but sustained VT was triggered by ventricular stimulation for which the patient was put on beta-blocker. Two years after, the patient presented with three episodes of syncope without progression of conduction defects on his ECG. An electrophysiological study was performed and triggered VF that was terminated with external electric shocks. An ICD was implanted in the left retropectoral area without any early complications. At five years, the patient was reviewed in our clinic for left retropectoral pain and an inappropriate shock in relation with a device-pocket infection and lead fracture with ventricular oversensing. The ICD had to be explanted and prolonged intravenous antibiotic treatment was started.

DISCUSSION

In this study, we identified in DM1 patients implanted with an ICD a higher risk of device-related complications than in those with a PM (39.1 and 6.5%, respectively, over a mean 6-year follow-up duration). Complications were more severe in ICD recipients with respect to the need for hospitalisation or re-intervention for their management.

In the general population, higher rates of complications after ICD versus PM placements have also been previously reported, ranging from 7.4% to 11.5% [10–12 , 20] and from 1.9% to 8.4% [10 , 22] respectively. While the 6.5% incidence of PM-related complications in our study population was close to that reported in the general population, the incidence of ICD-related complications was much higher. The higher morbidity with ICDs is generally explained by the more complex and more prolonged procedures to insert the device, its larger size requiring a longer cutaneous incision, and the fact that only ICDs expose patients to inappropriate shocks [10 , 23]. It should also be noted that the risk for ICD complications in our patients was close to that reported in patients presenting with other inherited heart disease such as hypertrophic cardiomyopathy (30% to 39%) [24 –26] or Brugada syndrome (34.6%) [27] who are also implanted at a younger age than in the general population.

It is noteworthy that the two most frequent complications observed in our patients with ICDs - infections and inappropriate shocks - have both been associated with high morbidity and mortality in the general population [10, 19]. Infections indeed require in almost all cases the extraction of the material, sometimes surgically, and expose patients to sudden death due to complete atrioventricular block or ventricular tachyarrhythmias during the period of weeks to months until another device can be placed. Inappropriate shocks have also been associated, aside from their frequent devastating psychological effects, with an increased risk of all-cause mortality [28].

Our observation of a high rate of complication following ICD implantations in DM1 patients has implications with regards to patient management, especially for the choice of the most appropriate device to prevent sudden death. Current guidelines recommend a PM in DM1 patients when AV or fascicular block, with or without symptoms, are present on the ECG and an ICD in the presence of a personal history of sustained VT or when left ventricular ejection fraction is below 35% [29]. In our study, of the 23 patients implanted with an ICD, only one received an appropriate therapy by the device, which was remarkably low compared to the 16 to 23% proportion of patients with other inherited cardiac conditions such as Brugada syndrome or hypertrophic cardiomyopathy who have been reported to receive appropriate shocks [24 , 27]. Our observation and current recommendations have been recently strengthened by the results of a study showing that sustained ventricular tachyarrhythmias are by far less frequent than high-degree conduction defects in DM1 patients and can be independently predicted by a personal history of non-sustained VT [30]. A global strategy of sudden death prevention based on 1) prophylactic PM in a majority of patients and 2) individualised, targeted indications for prophylactic ICD is also supported by our results. The high morbidity associated with ICD placement observed in our study provides a new insight into the difficult estimation of the ratio between benefits and risks conferred by the placement of these two devices.

Our study has several limitations. First, we analysed retrospectively our data, however the influence of our retrospective design may have been limited by the absence of patients lost to follow-up. Second, the number of patients with ICDs was relatively small, which may have biased the estimation of the risk for complications.

In conclusion, in our study, among patients presenting with DM1, device-related complications were significantly more frequent and more severe after the implantation of an ICD than for a PM.

ACKNOWLEDGMENTS INCLUDING SOURCES OF SUPPORT

This study was funded by grants from AFM-Téléthon.

CONFLICTS OF INTEREST

The authors have no conflict of interest to report.

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