Review Herzschr Elektrophys 2015 · 26:32–38 DOI 10.1007/s00399-014-0346-2 Published online: 10 December 2014 © Springer-Verlag Berlin Heidelberg 2014
S. Serge Barold1 · Carsten W. Israel2 1 Florida Heart Rhythm Institute, Tampa, FL, USA 2 Klinik für Innere Medizin—Kardiologie, Diabetologie und Nephrologie,
Evangelisches Krankenhaus Bielefeld, Bielefeld, Germany
The changing landscape of cardiac pacing Right ventricular (RV) pacing has wellknown long-term deleterious effects not only on already compromised, but also on the normal left ventricle (LV). The activation pattern mimics that of left bundle branch block, with delayed activation of the LV free wall, and results in electrical and mechanical dyssynchrony [1–9]. Important trials (MOST, DAVID, MADIT II, and the Danish AAIR/DDDR) have documented the occurrence and significance of pacing-induced cardiomyopathy (. Table 1) [10–14]. As a result, biventricular pacing has emerged for the prevention and treatment of pacemaker-induced LV dysfunction. The availability of this therapy underscores that the routine follow-up of patients with conventional pacemakers should be upgraded to involve periodic evaluation of LV function and its possible progressive deterioration. In this respect, in a regular pacemaker clinic, the prevalence of significant LV dysfunction (LVEF 50 %) LVEF and expected VP ≥ 80 % First-, second-, and third-degree AV block, heart failure, NYHA class I, II and III and LVEF ≤ 50 %.
History of AF in 10 % of each group
RV apical (n = 58) or BiV pacing (n = 50)
AF in 51.6 % of the BiV group and 54.1 % of the RV group. VP > 97 %.
RV (n = 342) or BiV pacing (n = 349)
37 months mean
AF in 100 %
RV (n = 81) or BiV pacing (n = 81)
6 months
AF 100 %
RV (n = 89) or BiV pacing (n = 89)
20 months median
Persistent AF with AV node ablation (third-degree AV block) Persistent AF with AV nodal ablation (third-degree AV block)
Follow-up duration 2 years for 92 % of each group and 18–24 months for the rest 12 months
Endpoints
Results
LVEF and LVESV
LVEF decreased in the RV group, but remained unchanged in the BiV pacing group. Significant difference of 9.9 percentage points at 2 years (p 95 %). The causes of unsuccessful LV pacing included inability to cannulate the coronary sinus ostium, lead displacement, and unacceptably high threshold.After implantation, LV lead-related complications occurred in 6.4 % of the patients. Such complica-
tions are similar to those reported in the literature. However, the wider use of CRT for new indications will be limited by the greater complications of LV pacing, unfamiliarity with implantation techniques (more complex than simple RV pacing), and cost. Further trials would be helpful especially with regard to the technical aspects of LV lead implantation and more reliable access sites.
Limitations of the BLOCK HF trial The limitations consist mostly of a high crossover rate and a substantial amount of missing echocardiographic data that were censored for use. In 54 patients the primary endpoint was excluded from analysis (26 in the BiV group and 28 in the RV arm). About 97 patients crossed over (13 BiV to RV or 4.6 % and 84 RV to BiV or 24.6 %), but the majority did so after a primary endpoint event (BiV 3 of 13, RV 50 of 84). Ten BiV patients and 34 RV pacing patients crossed over to the other therapy without having already met the primary endpoint. The primary endpoints of the study were death, acute heart failure, and an increase of 15 % or more in LVESVI. The methodology of mixing clinical events with echocardiographic variables seems strange and may show that this combination is inappropriate. In the cohort that received only a pacemaker, one of the first two endpoints above occurred in 52 of 243 patients in the group receiving BiV pacing and 48 of 241 patients in the group receiving RV pacing. Participants who met the endpoint for LVESVI first and subsequently went on to have heart failure or to die were counted only in the endpoint for LVESVI for the primary endpoint analysis. There is a need to explore the shortcomings and pitfalls of LVESVI measurements in greater detail.
Pacemaker-induced cardiomyopathy Khurshid et al. [33] recently evaluated 277 pacemaker patients for pacemaker-induced cardiomyopathy: preimplantation LVEF ≥ 50 % and a drop in LVEF ≥ 10 %. Of these 277 patients, 207 remained with preserved LVEF through the end of fol-
Herzschrittmachertherapie + Elektrophysiologie 1 · 2015
| 35
Review low-up (mean: 3.3 years, range: 0.08–9.4). Of the 70 patients who developed cardiomyopathy, 20 were excluded for an alternative potential explanation, leaving 50 patients with pacemaker-induced cardiomyopathy (incidence 19.5 %). In the patients with pacing-induced cardiomyopathy, the mean baseline LVEF was 62.1 %, and at follow-up (3.3 years) the mean LVEF was 36.2 %. Among those with ventricular pacing percentages of 20– 39, 40–59, 60–79, and 80–100, the incidence of pacemaker-induced cardiomyopathy was 13.0, 16.7, 26.1, and 19.8 %, respectively (p = 0.7 for comparison across groups). The shortest time to development of pacemaker-induced cardiomyopathy was 1 month and the longest time was 8.4 years. Pacemaker-induced cardiomyopathy was more likely to occur in men, with a wide native QRS complex, and a lower pre-implant LVEF. Native QRS duration of > 115 ms (excluding typical bundle branch block) was 90 % specific for development of pacemaker-induced cardiomyopathy. If 13 % of patients who have pacing only 20–40 % of the time develop cardiomyopathy in 3 years, the threshold of 40 % as suggested by the MOST trial may indeed be too high. Interestingly, when the number of premature ventricular contractions reaches about 25 % of all QRS complexes, it is considered to be enough to cause LV remodeling [34, 35].
Upgrading from conventional pacemaker or ICD to biventricular pacing In some registries, upgrading from RV to BiV pacing constitutes close to 30 % of all implanted BiV systems. Patients with pacemaker-induced cardiomyopathy respond favorably (in about two third of cases) to upgrading suggesting that the LV dysfunction is partially reversible [36– 41]. Several studies have shown that patients with RV pacing (and low LVEF) improved after upgrading to BiV pacing with a benefit that was comparable or even better than that observed in heart failure patients with native LV conduction delay who underwent de novo CRT implantation (follow-up: 3–38 months) [42–46]. Upgrading to BiV pacing should be considered in patients requiring fre-
quent RV pacing, if they have symptomatic heart failure and low LVEF (
S. Serge Barold1 · Carsten W. Israel2 1 Florida Heart Rhythm Institute, Tampa, FL, USA 2 Klinik für Innere Medizin—Kardiologie, Diabetologie und Nephrologie,
Evangelisches Krankenhaus Bielefeld, Bielefeld, Germany
The changing landscape of cardiac pacing Right ventricular (RV) pacing has wellknown long-term deleterious effects not only on already compromised, but also on the normal left ventricle (LV). The activation pattern mimics that of left bundle branch block, with delayed activation of the LV free wall, and results in electrical and mechanical dyssynchrony [1–9]. Important trials (MOST, DAVID, MADIT II, and the Danish AAIR/DDDR) have documented the occurrence and significance of pacing-induced cardiomyopathy (. Table 1) [10–14]. As a result, biventricular pacing has emerged for the prevention and treatment of pacemaker-induced LV dysfunction. The availability of this therapy underscores that the routine follow-up of patients with conventional pacemakers should be upgraded to involve periodic evaluation of LV function and its possible progressive deterioration. In this respect, in a regular pacemaker clinic, the prevalence of significant LV dysfunction (LVEF 50 %) LVEF and expected VP ≥ 80 % First-, second-, and third-degree AV block, heart failure, NYHA class I, II and III and LVEF ≤ 50 %.
History of AF in 10 % of each group
RV apical (n = 58) or BiV pacing (n = 50)
AF in 51.6 % of the BiV group and 54.1 % of the RV group. VP > 97 %.
RV (n = 342) or BiV pacing (n = 349)
37 months mean
AF in 100 %
RV (n = 81) or BiV pacing (n = 81)
6 months
AF 100 %
RV (n = 89) or BiV pacing (n = 89)
20 months median
Persistent AF with AV node ablation (third-degree AV block) Persistent AF with AV nodal ablation (third-degree AV block)
Follow-up duration 2 years for 92 % of each group and 18–24 months for the rest 12 months
Endpoints
Results
LVEF and LVESV
LVEF decreased in the RV group, but remained unchanged in the BiV pacing group. Significant difference of 9.9 percentage points at 2 years (p 95 %). The causes of unsuccessful LV pacing included inability to cannulate the coronary sinus ostium, lead displacement, and unacceptably high threshold.After implantation, LV lead-related complications occurred in 6.4 % of the patients. Such complica-
tions are similar to those reported in the literature. However, the wider use of CRT for new indications will be limited by the greater complications of LV pacing, unfamiliarity with implantation techniques (more complex than simple RV pacing), and cost. Further trials would be helpful especially with regard to the technical aspects of LV lead implantation and more reliable access sites.
Limitations of the BLOCK HF trial The limitations consist mostly of a high crossover rate and a substantial amount of missing echocardiographic data that were censored for use. In 54 patients the primary endpoint was excluded from analysis (26 in the BiV group and 28 in the RV arm). About 97 patients crossed over (13 BiV to RV or 4.6 % and 84 RV to BiV or 24.6 %), but the majority did so after a primary endpoint event (BiV 3 of 13, RV 50 of 84). Ten BiV patients and 34 RV pacing patients crossed over to the other therapy without having already met the primary endpoint. The primary endpoints of the study were death, acute heart failure, and an increase of 15 % or more in LVESVI. The methodology of mixing clinical events with echocardiographic variables seems strange and may show that this combination is inappropriate. In the cohort that received only a pacemaker, one of the first two endpoints above occurred in 52 of 243 patients in the group receiving BiV pacing and 48 of 241 patients in the group receiving RV pacing. Participants who met the endpoint for LVESVI first and subsequently went on to have heart failure or to die were counted only in the endpoint for LVESVI for the primary endpoint analysis. There is a need to explore the shortcomings and pitfalls of LVESVI measurements in greater detail.
Pacemaker-induced cardiomyopathy Khurshid et al. [33] recently evaluated 277 pacemaker patients for pacemaker-induced cardiomyopathy: preimplantation LVEF ≥ 50 % and a drop in LVEF ≥ 10 %. Of these 277 patients, 207 remained with preserved LVEF through the end of fol-
Herzschrittmachertherapie + Elektrophysiologie 1 · 2015
| 35
Review low-up (mean: 3.3 years, range: 0.08–9.4). Of the 70 patients who developed cardiomyopathy, 20 were excluded for an alternative potential explanation, leaving 50 patients with pacemaker-induced cardiomyopathy (incidence 19.5 %). In the patients with pacing-induced cardiomyopathy, the mean baseline LVEF was 62.1 %, and at follow-up (3.3 years) the mean LVEF was 36.2 %. Among those with ventricular pacing percentages of 20– 39, 40–59, 60–79, and 80–100, the incidence of pacemaker-induced cardiomyopathy was 13.0, 16.7, 26.1, and 19.8 %, respectively (p = 0.7 for comparison across groups). The shortest time to development of pacemaker-induced cardiomyopathy was 1 month and the longest time was 8.4 years. Pacemaker-induced cardiomyopathy was more likely to occur in men, with a wide native QRS complex, and a lower pre-implant LVEF. Native QRS duration of > 115 ms (excluding typical bundle branch block) was 90 % specific for development of pacemaker-induced cardiomyopathy. If 13 % of patients who have pacing only 20–40 % of the time develop cardiomyopathy in 3 years, the threshold of 40 % as suggested by the MOST trial may indeed be too high. Interestingly, when the number of premature ventricular contractions reaches about 25 % of all QRS complexes, it is considered to be enough to cause LV remodeling [34, 35].
Upgrading from conventional pacemaker or ICD to biventricular pacing In some registries, upgrading from RV to BiV pacing constitutes close to 30 % of all implanted BiV systems. Patients with pacemaker-induced cardiomyopathy respond favorably (in about two third of cases) to upgrading suggesting that the LV dysfunction is partially reversible [36– 41]. Several studies have shown that patients with RV pacing (and low LVEF) improved after upgrading to BiV pacing with a benefit that was comparable or even better than that observed in heart failure patients with native LV conduction delay who underwent de novo CRT implantation (follow-up: 3–38 months) [42–46]. Upgrading to BiV pacing should be considered in patients requiring fre-
quent RV pacing, if they have symptomatic heart failure and low LVEF (
