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| Annotated Bibliography |
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| VVI/DDD to CRT |
Reference: Sciarra L, Pararella G, Bocchino M, Pastore G, Marras E, Milan D, Moro E, Marcon C, Delise P, Cassin R, Benefits of cardiac resynchronization therapy extends to patients upgraded from right ventricular pacing to biventricular pacing, Europace Supplements 2005; 7: 57 (abstract 110)
This study compared a series of patients fulfilling standard criteria for CRT therapy, but were already being paced for a standard clinical indication, usually AV block such that they were always ventricular paced to a series of patients who had CHF with intact AV nodal conduction, but a wide QRS with a LBBB pattern (n = 49). The paced group (n = 29) with pacing induced (PI) LBBB had a wider QRS (197 ms) than the de-novo group (QRS 178 ms), but this difference was not statistically significant. All patients were able to be either upgraded or have a primary CRT system implanted. Overall, 12 patients (15%) did not respond to CRT therapy – 17% in the PILBBB group and 14% in the LBBB group (not significantly different). The other patients had a comparable level of improvement with a reduction in NYHA functional class by > 1 class, narrowing of the QRS and improvement in Quality of Life. The authors conclude that patients who are paced for a standard indication and who have CHF with mechanical dyssynchrony associated with PILBBB show a similar benefit to those patients with “standard indications” for CRT when upgraded. As such, upgrading to CRT in this group of patients is recommended. |
Reference: De Sisti A, Lavergne T, Toussaint JF, Ollitrault J, Abergel E, Paziaud O, Ait Said M, Le Heusey JY, Sader R, Guize L, In patients with dilated cardiomyopathy and ventricular dyssynchrony, upgrading to cardiac resynchronization is as beneficial as de novo implant, Europace Supplements 2005; 7: 58 (abstract 111)
This study compared a group of 37 patients who were paced for some degree of AV block (2nd degree – 23, 3rd degree – 10, Atrial fib s/p AVN ablation – 4) for standard reasons who developed refractory congestive heart failure to a group of 79 patients who required CRT for the current standard clinical indications. In the upgrade group, the paced QRS duration was > 200 ms, while in the de novo group, the QRS duration had to be greater than 130 ms. At three months, detailed echocardiography and angioscintigraphy was performed. Morbidity and mortality was assessed on a chronic basis. Except for the QRS duration, there was NO difference between these two groups at baseline. Both groups demonstrated a similar degree of improvement with respect to quality of life, a multiplicity of non-invasive measurements, morbidity (HF re-hospitalization) and mortality. This led the investigators to conclude that patients who are conventionally paced from the RV apex who have a very prolonged QRS duration, a dilated ventricle with reduced EF and Class III or IV congestive heart failure despite medical therapy benefit from being upgraded to CRT to a degree that is similar to a primary CRT implant. |
Reference: Michalkiewicz D, Makowski K, Jacewicz K, Olzweski R, Kaminski G, Cholew M, Adamus J, Gnilka A, Biventricular or right ventricular permanent pacing after atrioventricular nodal ablation in patients with advanced heart failure and chronic atrial fibrillation, Europace Supplement 2005; 7: 58 (abstract 112)
This study is similar to the SJM PAVE study; except there was a further requirement that all patients had very compromised LV function. All had chronic atrial fibrillation and were undergoing AV nodal ablation for control of the ventricular rate as this was ineffective with pharmacologic therapy alone. Post-ablation, all would require ventricular pacing. This was also NOT a prospective randomized trial, but started years ago with standard RV pacing following the ablation (n = 28) such that the mean follow-up in this group was a mean of 24 months. Based on PAV and other anecdotal reports, the more recent 25 patients undergoing AV nodal ablation had a BiV pacing system implanted with a mean follow-up of only 14 months.
|
RV / BiV |
Measurement |
Initial |
12 months |
24 months |
| RV |
NYHA |
2.8 |
2.6 |
2.8 |
| BiV |
3.1 |
2.5 |
|
| RV |
LVEF (%) |
34 |
41 |
37 |
| BiV |
35 |
40 |
|
| RV |
Exercise Duration |
2.1 |
4.4 |
4.3 |
| BiV |
2.1 |
4.4 |
|
| RV |
NT-Pro BNP |
1486 |
705 |
|
| BiV |
1138 |
1013 |
1100 |
There were no deaths in the BiV group and 2 deaths in the RV group, one at 10 months and one at 18 months. In the RV group, there patients underwent upgrade to a CRT system. The investigators concluded that there was improvement following AV nodal ablation in patients with poor ventricular function who were undergoing AV nodal ablation in both groups but there was an overall better result in the BiV group at 12 months and some apparent deterioration in the RV group at 24 months. Longer follow-up was need in the BiV group. It was also noted that in the RV paced group, further improvement could be demonstrated after upgrading to CRT (only 3 patients). |
Reference: Bortnik M, Magnani A, Francalacci G, Devecchi P, Ochetta E, Upgrading from right conventional ventricular pacing to biventricular pacing: hemodynamic benefits and technical issues, Europace Supplement 2005; 7: 58-59 (abstract 113)
At this center, 74 CRT systems have been implanted between 1999 and 2005. Forty-six were de novo implants. 28 patients had had standard pacing or ICD systems anywhere from 1 to 20 years and were attempted to be upgraded to CRT because of refractory CHF. The mean QRS duration with conventional RV apical pacing was 196 ms. Of the 28 patients, upgrade was successful in 20 patients. The reasons for an inability to upgrade them included failure to access the CS in 3, coronary sinus dissection in 3 and 2 patients went into Cardiogenic shock during the upgrade procedure and the attempt was terminated. Of the group that was successfully upgraded, 35% had a standard pacemaker and 65% had had a standard ICD. In 15 of the 20 patients, an entirely new system was implanted on the side of the original implant. Three patients had their chronic leads tunneled to a new pocket on the other side of the chest with placement of the CS lead from that new side. In 2 patients, the original system was totally removed and an entirely new system implanted from the opposite side of the chest. As such, there were significant technical challenges associated with the upgrade procedure. Of those who were successfully upgraded, 4 died in the first year of follow-up. The results in the remaining 16 patients at 1 year of follow-up included:
| |
NYHA Class |
LVEF |
Mitral Regurg |
| Baseline |
3.3 |
28 & |
2.3 |
| 1 year |
2.4 |
35 % |
1.5 |
The authors concluded that while there were challenges with respect to the upgrade procedure, if this was able to be accomplished, the results were similar to a de novo implant for the “standard” CRT indications. |
Reference: Vincenti A, Gasparini M, Lunati M, Santini M, Perego GB, Boriani G, Sassara M, Guzzi D, Upgrade to biventricular pacing device of pacemaker holders for antibradycardia indications, the Insync/Insync ICD Italian registries, Europace Supplement 2005: 7: 59 (abstract 114)
This is a large registry study based in Italy involving multiple centers. In all, there were a total of 1232 patients of whom 20% (243) were upgraded from standard RV pacing, either single or dual-chamber to a CRT system and 80% (989) were de novo implants of a CRT system for standard indications. This study did involve patients with Class II congestive heart failure. The upgrade procedure was performed for either severe CHF despite pharmacologic therapy or at the time of pulse generator replacement for battery depletion with some ventricular dysfunction. Both groups had a similar number of hospitalizations during the year prior to the implant or upgrade procedure (2.1 hospitalizations, mean duration of hospitalization 21 days) and a similar percent of responders following CRT. 71% of the patients who were upgraded demonstrated a beneficial response compared to 67% of the de novo implants. Patients who were NYHA functional class II at the time of the procedure, both de novo implant and upgrade, demonstrated a similar degree of improvement compared to the sicker patients.
| |
|
NYHA |
LVEF |
QRS |
MR |
LVEDD |
Upgrade
N = 243 |
Baseline |
3.1 |
27 % |
173 ms |
2.2 |
68 |
| Follow-up |
2.2 |
35 % |
137 ms |
1.8 |
66 |
| De novo N = 989 |
Baseline |
2.9 |
27 % |
168 ms |
2.1 |
69 |
| Follow-up |
2.2 |
35 % |
133 ms |
1.8 |
66 |
The authors concluded that CRT was able to have a positive impact in improvement in cardiac function in patients who were paced previously for standard indication and then upgraded due to symptoms of refractory CHF or evidence of ventricular dysfunction even if they had only mild CHF symptoms (NYHA functional class II). Hence, CRT was also demonstrated to beneficial in a “healthier” subgroup of patients. |
Reference: Maria I, Gurevitz O, Gurevitz O, Carasso S, Luria D, Bar-Lev D, Feinberg M, Eldar M, Glikson M, Patients with right ventricular apical pacing and drug refractory heart failure benefit significantly from cardiac resynchronization therapy, Europace Supplement 2005; 7: 59 (abstract 115)
This was a comparative study between a group of patients who were undergoing CRT for standard reasons (n = 73) and those who were already paced for standard pacing indications and had developed congestive symptoms (n = 25). The standard indications included some degree of AV block in 19 (5 having chronic AF as well), sick sinus syndrome with first degree AV block such that they were always ventricular paced in 5 and 1 with carotid sinus syndrome. The previously implanted pacing systems were VVIR in 4, VDD in 1 and DDD/DDDR in 20. Baseline characteristics and echocardiographic measurements were similar in both groups except for QRS duration (paced 203 ms vs de novo 163 ms, p < 0.001), and 6 minute walk test (paced 222 meters vs de novo 362 meters, p < 0.005). Following either CRT implant or upgrade, the paced group showed an improved NYHA functional class of 3.2 at baseline decreasing to 2.5 at 3 months of follow-up, while the de novo CRT group went from a baseline of 3.1 to 2.9. At three months, there had not been a significant change in echo-derived measurements, but the 6 minute walk test increased in the previously paced group from 222 meters to 315 meters and in the de novo group from 362 meters to 398 meters. While the within group improvement was statistically significant, the relative degree of improvement was not statistically different between the two groups. In the upgrade group, 76% of the patients demonstrated an improvement while only 42% of the patients in the primary implant group showed a clinical improvement. This last number is low with respect to the generally reported experience concerning CRT therapy and no explanation was provided. |
Reference: Kutarski A, Rucinski P, Sodolski T, Trojnar M, Widomska-Czekjaska T, Which factors influence hemodynamic improvement after right ventricular pacing to biventricular pacing system upgrade?, Europace Supplement 2005; 7: 88 (abstract 406)
This was an acute comparison of RV pacing, LV pacing and BiV pacing in a group of 69 patients who had chronic RV pacing, symptomatic CHF and were upgraded to a CRT system. Hemodynamic measurements were assessed using the CardioDynamics BioZ impedance cardiography (ICG) system as well as standard echocardiographic measurements. These investigators found that multiple acute echocardiographic measurements were ineffective in demonstrating which patients would show an improvement with BiV pacing. The best measurement was cardiac index (CI) using the ICG system with a higher CI in BiV than in either RV or LV pacing. Further, the improvement when going from RV pacing to BiV pacing correlated with the best results and this correlated with the difference between RV pacing CI and LV pacing CI. This study was only a poster and presented the conclusions without the detailed measurements. Also, it was not absolutely clear if these were upgraded patients who had been chronic RV pacing and were upgraded to BiV or had devices capable of independent RV and LV programming allowing these acute measurements to be obtained despite the title that implied a system upgrade. |
Reference: Baker CM, Christopher TJ, Smith PF, Langberg JJ, DeLurgio DB, Leon AR, Addition of a left ventricular lead to convention pacing systems in patients with congestive heart failure: feasibility, safety and early results in 60 consecutive patients, PACE 2002; 25: 1166-1171
Until the Italian Insync/Insync ICD registry, this was the largest single center published series with respect to upgrading patients from RV apical pacing to biventricular pacing. All patients selected for an upgrade had severe symptomatic CHF (NYHA functional class III or IV) despite optimal pharmacologic therapy for CHF, had dilated ventricles, an EF below 35% and a very wide QRS associated with RV pacing. Of this group of 60 patients, an upgrade procedure was successful in 54 (90%) involving 15 single chamber and 39 dual chamber pacing systems. The reason that the procedure failed in 6 patients was an inability to cannulate the CS in 1 patients and an inability to find an adequate LV pacing site in the other 5. Procedure complications included 1 lead dislodgment, 1 pocket hematoma, 2 superficial infections requiring antibiotics and one pocket infection requiring removal of the entire system. A total of 10 patients died during follow-up. Two of the patients who were not able to be upgraded died. Two of the patients who were successfully upgraded experienced sudden death and 5 had progressive congestive heart failure. One died as a complication of a motor vehicle accident. One patient deteriorated post-upgrade and had a cardiac transplant. At the three month follow-up evaluation, QOL scores improved 31 points (p < 0.0001) compared to baseline, NYHA functional class improved from 3.5 to 2.4 (p < 0.0001) and the LV ejection fraction increased from 0.23 to 0.29 (p < 0.0003). The authors concluded that modification of RV pacing to a biventricular system was able to be performed effectively and safely using commercially available leads, adapters and other equipment. They also demonstrated that these patients experienced a significant clinical improvement similar to that demonstrated with an initial implant of a CRT system for standard clinical indications. |
Reference: Leon AR, Greenberg JM, Kanuru N, Baker CM, Mera FV, Smith AL, Langberg JJ, DeLurgio DB, Cardiac resynchronization in patients with congestive heart failure and chronic atrial fibrillation, effect of upgrading to biventricular pacing after chronic right ventricular pacing, J Amer Coll Cardiol 2002; 39: 1258-1263
This study involved a series of 20 patients with chronic atrial fibrillation who had undergone AV nodal ablation (standard ablate and pace) followed by implantation of a VVIR pacing system with a RV apical lead. The other requirements included that RV pacing be at least 6 months in duration, persistent symptoms of CHF (Functional Class III or IV) despite optimal pharmacologic therapy, EF less than 35% and very wide QRS associated with RV pacing. The upgrade procedure was limited to the addition of a LV lead and use of a CRT-P system. Of these initial 20 patients, 17 were still alive as of a mean follow-up of 17 months post-upgrade. Of the three deaths, one was due to an infection complicating chronic peritoneal dialysis and the two other patients died of progressive congestive heart failure. One patient developed symptomatic VT and was further upgraded to a biventricular ICD.
| |
Pre-Upgrade |
Post-Upgrade |
P value |
| NYHA Class |
3.4 ± 0.5 |
2.4 ± 0.6 |
< 0.001 |
| # Hospitalizations |
1.9 ± 0.8
1 year prior |
0.4 ± 0.6
1 year following |
< 0.001 |
| MLWHF –QOL |
78 ± 24 |
52 ± 23 |
< 0.01 |
| QRS duration (ms) |
213 ± 40 |
172 ± 31 |
< 0.0001 |
| LVEF (%) |
21.5 ± 6.9 |
30.9 ± 11.5 |
< 0.001 |
| LVEDD (mm) |
67.9 ± 8.3 |
63.5 ± 7.7 |
< 0.003 |
| LVESD (mm) |
56.3 ± 9.8 |
51.5 ± 10.9 |
< 0.01 |
Based on this experience, the authors felt that it was appropriate to upgrade patients with chronic VVI pacing for atrial fibrillation and high grade AV block when they experienced persistent congestive heart failure. This was an incremental improvement over simple rate control for the chronic atrial fibrillation as that had been performed a sufficient time previously, often more than a year although the minimal requirement was 6 months. Despite the rate control and optimal pharmacologic therapy, these patients continued to be highly symptomatic. |
Leclercq C, Cazeau S, Fossati LF, Anselme F, Davy LM, Sadoul N, Klug D, Mollo L, Daubert JC, Upgrading from RV pacing to biventricular pacing in previously paced patients with severe heart failure and left ventricular systolic dysfunction, the RD-CHF controlled study, PACE 2003; 26: 983 (abstract 219)
This was a single-blind randomized cross over study to assess the clinical efficacy of upgrading from RV pacing to BiV pacing in a series of 54 patients with chronic RV pacing for standard indications, persistent severe CHF (NYHA functional class III or IV), EF < 35%, a very wide QRS associated with RV apical pacing and mechanical dyssynchrony as confirmed on echocardiography. Patients were randomized to either RV followed by BiV or BiV followed by RV pacing for three months each. During follow-up, 6 patients died. Two from progressive CHF, 2 from sudden death and 2 from non-cardiac causes. From the time of randomization to the end of follow-up, there were 25 hospitalizations. 81% of the hospitalizations occurred during RV pacing compared to only 19% in the BiV group.
| |
Baseline |
RV pacing |
BiV pacing |
P value |
| QRS (ms) |
210 |
207 |
157 |
0.002 |
| NHYA class |
3.2 |
2.65 |
2.15 |
0.02 |
| 6 min walk (m) |
300 |
325 |
390 |
0.009 |
| QOL |
54 |
45 |
34 |
0.005 |
| HF as cause of hospitalization |
|
8 |
1 |
0.004 |
These authors conclude that in patients requiring RV pacing for standard clinical indications, but then have persistent HF despite optimal pharmacologic therapy, upgrading to a BiV system results in an improvement in symptoms, improvement in QOL, improvement in exercise tolerance and a reduction in the number of hospitalizations for HF. |
Reference: Horwich T, Foster E, De Marco T, Tseng Z, Saxon L, Effects of resynchronization therapy on cardiac function in pacemaker patients „upgraded“ to biventricular devices, J Cardiovasc Electrophysiology 2004; 15: 1284-1289.
This study is based on 15 patients acquired between three different academic institutions who had persistent severe congestive heart failure and chronic RV pacing for standard pacing indications. All patients were pacemaker dependent and thus paced in the ventricle virtually 100% of the time. Mean duration of RV pacing prior to the upgrade was 5.8 years. They had a mean LVEF of 24 percent (enrollment required an EF < 35%), Class III or IV heart failure and a wide baseline QRS (paced QRS duration was 190 ms). Two patients had chronic atrial fibrillation and AV block, the others all had an intact sinus rhythm in conjunction with AV block. Five patients were upgraded to a CRT-D, while the others were all upgraded to a CRT-P system. The LV lead was placed in the lateral, posterolateral or anterolateral vein.
| |
Baseline |
CRT upgrade |
P vale |
| Paced QRS (ms) |
190 |
167 |
0.005 |
| LVEF (%) |
24 |
31 |
0.02 |
| LVEDV (ml) |
270 |
254 |
0.0001 |
| LV outflow VTI |
14.1 |
14.7 |
ns |
| LV electromechanical delay (ms) |
180 |
161 |
0.03 |
| Myocardial performance index |
0.90 |
0.55 |
0.01 |
One patient had incessant VT following upgrade to CRT. This was managed by RF ablation of the ventricular tachycardia focus. The overall magnitude of improvement in this small series of patients was similar to or exceeded that seen in chronic studies for CRT for native LBBB and refractory congestive heart failure. The authors concluding that upgrading a chronic RV pacing system (either VVI or DDD) would result in symptomatic improvement in the majority of patients with persistent symptomatic heart failure despite optimal pharmacologic therapy. |
Comment:
In 2002, the American College of Cardiology, American Heart Association and Heart Rhythm Society upgraded cardiac resynchronization therapy from a Class III indication to a Class IIa indication in their Pacemaker and ICD Implant Guidelines. In Guidelines for the management of congestive heart failure issued in 2005 developed by the European Society of Cardiology, CRT therapy is now considered a Class I indication for the management of congestive heart failure and hence, is becoming a primary therapeutic modality for patients with severe CHF and LV mechanical dyssynchrony (usually due to electrical dyssynchrony with a LBBB pattern on their ECG) when they have persistent symptoms despite optimal pharmacologic therapy. From multiple studies as the data is retrospectively analyzed (MOST, MADIT II, MIDAS 6) and prospectively analyzed (DAVID), there has been an increased awareness that RV apical pacing may have deleterious effects when it is not needed, but is forced on the patient. MIDAS 6 infers that there may even be a possible adverse effect when ventricular pacing therapy is required. There were 3 published papers and one abstract presented over the last couple of years suggesting that in patients with chronic RV pacing for standard clinical pacing indications, an upgrade to CRT therapy was both feasible and beneficial. There were multiple presentations at Europace 2005 supporting these earlier papers such that there is now a growing body of literature to support upgrading patients who have pacing for standard indications to CRT when they have a very wide QRS (in the range of 200 ms), EF below 35% and dilated ventricles. Based on the Italian Insync/Insync ICD registry involving over 200 patients, who were upgraded, Class II patients also benefit given underlying poor LV function even though symptoms are relatively mild. The degree of improvement in all of these studies was similar in the upgraded patients to those patients who do not have an indication for pacing, but were receiving a CRT system for the primary management of congestive heart failure with refractory symptoms despite maximum tolerated pharmacologic regimen.
Further, in these studies, the mortality was relatively low in the upgraded group although follow-up was usually less than 1 year. In most cases, the patients received a CRT-P rather than CRT-D system. The topic of the role of CRT-D pacing came up frequently in the Q&A sessions following these presentations and in other sessions on CRT therapy with a consensus by the European physicians who presented these studies that CRT-D was NOT required. Their goal in these patients was improvement in quality of life and apropos of the CARE-HF study published in 2005, there appeared to be a reduction in mortality with cardiac resynchronization even without defibrillator back-up. In the studies that have been fully published in peer-reviewed journals (n = 3), the incidence of sudden death, while not zero, was not the predominant cause of death.
Indexing terms:
• Cardiac resynchronization therapy
•
Upgrade from standard pacing
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