Ventricular resynchronization through biventricular cardiac pacing for the treatment of refractory heart failure in dilated cardiomyopathy

Original Article

Ventricular Resynchronization Through Biventricular Cardiac Pacing for the Treatment of Refractory Heart Failure in Dilated Cardiomyopathy

Silas S. Galvão Fº, Cecília M. B. Barcellos, J. Tarcísio M. Vasconcelos, Jaime G. M. Arnez, Kátia N. Couceiro, Leudo Campos, Evandro Sbaraini, Maurício G. Lyra, Fernando S. O. Souza

São Paulo, SP - Brazil

OBJECTIVE: The biventricular pacing (BVP) approach has good results in the treatment of congestive heart failure (CHF) in patients (pts) with disorders of intraventricular conduction.

METHODS: We have applied BVP to 28 pts, with left ventricular pacing using minitoracotomy in 3 pts and the transvenous aproach via coronary sinus in 25 pts. The mean duration of the QRS complexes was 187 ms, in the presence of the left branch block in 22 pts, and right branch block + divisional hemiblock in 6 pts. All pts had been considerated candidates to cardiac transplantation, and were under optimized drug therapy. Sixteen pts were in Functional Class (NYHA) IV, and 12 in class III. The ejection fraction varied from 22 to 46% (average = 34%). The pacing mode employed was biventricular triple-chamber in 22 pts, and bi-ventricular dual-chamber in 6 pts (one with ICD).

RESULTS: The pts were followed up for a period that ranged from 10 days to 14 months (mean 5 months). All pts presented clinical improvement after implant, chaging the NYHA Functional Class at the end of follow-up to Class I (9pts), Class II (10 pts) and Class III (6 pts). The initial mean ejection fraction have-raised to 37%. Two pts died suddenly. One patient died due to a pulmonary fungal infection.

CONCLUSION: Ventricular resynchronization through BVP, improved significantly the Functional Class and, therefore, the quality of life. Assessments of myocardial function acutely performed do not reflect the clinical improvement observed.

Key words: biventricular pacing, ventricular resynchronization, heart failure

Heart failure is currently considered a public health problem. In 1997, it accounted for 3.58% of all admissions in the Brazilian public health system, corresponding to 36.95% of the hospitalizations due to cardiocirculatory problems, with mortality of 6.39%, and a cost to the Brazilian government of 3 billion reais ¹. In the USA, from 1970 to 1994, the rate of hospitalizations due to heart failure tripled in patients aged 45 to 65 years, and increased 4 times in those over the age of 65 years ². Despite the great progress in the medicamentous treatment of heart failure, many patients have dilated cardiomyopathy refractory to this type of therapy, with a poor prognosis and a very poor quality of life. Of the nonpharmacological procedures indicated for this type of patient, cardiac transplantation, despite its limitations, remains the gold standard, because other options, such as cardiomyoplasty and Batista's surgery, have results that are somewhat controversial. At the beginning of the '90s, Hochleitner et al ³ proposed for the first time artificial cardiac pacing (dual-chamber pacemaker with a short atrioventricular interval) as a treatment for refractory heart failure, with encouraging acute results; these results, however, proved catastrophic within a short period of follow-up ^4,5. At the beginning of the '90s, Xiao et al ^6,7 studied the effects of intraventricular conduction disorders of the myocardial function in patients with dilated cardiomyopathies and showed that the larger the QRS, the longer the time required for contraction and relaxation of the fibers, impairing myocardial function. Bakker et al ⁸ were the first to report ventricular resynchronization through permanent biventricular pacing using DDD pacemakers with a bifurcated lead in the ventricular exit; the right ventricle was stimulated by anodic current through a conventional endocardial electrode, and the left ventricle by cathodic current through an epimyocardial electrode. In the first half of the '90s, Cazeau et al ⁹ in the classical study with a 4-chamber pacemaker started the era of left ventricular pacing through the coronary sinus. Since then, ventricular resynchronization through biventricular pacing has shown its great value as adjuvant in the treatment of congestive heart failure refractory to medicamentous treatment in patients with dilated cardiomyopathy and intraventricular conduction disorders ^10-12. In this article, we report our experience with this technique in patients with dilated cardiomyopathy and decompensated congestive heart failure who were referred to our hospital for assessment of the possibility of cardiac transplantation.

Methods

From April 1999 to August 2000, we implanted pacemakers with biventricular pacing in 28 patients (23 males and 5 females) with dilated cardiomyopathy, important intraventricular conduction disorders (QRS >140ms), and uncontrollable congestive heart failure despite the optimized medicamentous treatment. Their ages ranged from 36 to 84 years (mean = 58.5). They were referred to our hospital by cardiologists who, not being able to control their congestive heart failure, asked for assessment aiming at cardiac transplantation. All patients had intraventricular conduction disorders as follows: 6 had complete right bundle-branch block with the axis shifted to the left, 16 had left bundle-branch block, and 6 had interventricular conduction disorders (an electrocardiographic pattern of left bundle-branch block) consequent to exclusive left ventricular pacing (single-site pacing of the right ventricle). QRS width ranged from 140 to 220 (mean = 187) milliseconds. In regard to NYHA functional class, the patients were classified as follows: 12 were functional class III, 16 were functional class IV, and 6 were not discharged from the intensive care unit because of vasoactive-drug dependence. The sole indication for the procedure was the need for ventricular resynchronization, and no primary indication for reestablishing cardiac rhythm or atrioventricular synchronism, or both, existed. Right ventricular pacing was performed with a conventional endocardial electrode in all patients, and left ventricular pacing was performed with an epimyocardial electrode in the first 3 patients, and through the coronary sinus in 26 patients (1 patient with an epimyocardial electrode had elevation of the pacing threshold and required implantation of a new electrode through the coronary sinus) (fig. 1). The electrodes used for left ventricular pacing through the coronary sinus were the Biotronic Corox CX LV-75 in 10 patients and the Medtronic 2187 - 75cm in 16 patients. For biventricular pacing, we used the following: 1 single-chamber pacemaker with a bifurcated lead in the exit; 22 dual-chamber pacemakers, 18 of which had a duplicator in the ventricular exit (for those without a duplicator in the ventricular exit, the atrial chamber was connected to the first ventricle to be activated during the patient's own rhythm, right ventricle in the case of left bundle-branch block, and the ventricular chamber was connected to the other ventricle, the atrioventricular interval being programmed at 0 milliseconds); and 4 special triple-chamber pacemakers (single atrial exit and double ventricular exit). One patient with permanent atrial fibrillation, severe ventricular arrhythmia, and adequate ventricular response underwent placement of an implantable cardioverter-defibrillator with biventricular antibradycardia function (fig. 2). All patients were informed that they were undergoing a new procedure that was still being investigated. The etiologies of dilated cardiomyopathies were as follows: ischemic in 13 patients, chagasic in 5, alcoholic in 2, hypertensive in 1, valvular in 2, and idiopathic in 5. The patients underwent clinical assessment and complementary tests in the preoperative period, on the 10^th postoperative day, and every 3 months after the procedure. All patients were able to perform the 6-minute walking test after the procedure, but only 13 could undergo this test prior to the procedure. The other 15 patients did not undergo this test preoperatively for the following reasons: 8 were not able because of poor condition, and 6 due to a flaw in the protocol. Ejection fraction was assessed preoperatively on Doppler echocardiography in all patients, and ranged from 22% to 46% (mean = 34±0.57%). It is worth noting that all patients with ejection fraction above 40% had undergone treatment with vasoactive drugs in the intensive care unit a few days before the test; this value was, therefore, overestimated. Myocardial scintigraphy was performed prior to the procedure in 18 patients and ranged from 8% to 39% (mean = 20±7.4%).

Results

Table I shows QRS width, the ejection fraction measured on Doppler echocardiography and on gated cardiac scanning, and the pre- and postoperative NYHA functional class.

All patients improved their functional classes. In the preoperative period, most of them (16/28) were in functional class IV; after biventricular pacing, the great majority (19/28) were functional class I or II. Of the patients who were functional class IV before the procedure, 3 underwent cardiac transplantation in the 4^th, 5^th, and 6^th postoperative month. Three patients died, 2 suddenly on the 3^rd and 10^th days after the procedure, and 1 due to pulmonary fungal infection on the 5^th day after the procedure. One patient had dislocation of the electrode from the coronary sinus, which was solved with implantation of a second-generation electrode in the coronary sinus with a passive-fixation mechanism. One patient had infection at the site of pacemaker implantation requiring removal of the triple-chamber pacing system, treatment with antibiotics, and later reimplantation of a new system on the other side. The ejection fraction determined on Doppler echocardiography passed from the preoperative mean of 33% to 37% 10 days after the procedure. In 17 patients who were followed up for 3 months, the ejection fraction passed from 34% in the preoperative period to a mean of 43% 90 days after the procedure. In regard to the ejection fraction determined on myocardial scintigraphy, a 1^st evaluation performed 10 days after the procedure involving 18 patients showed that the initial preoperative mean passed from 20.8% to 21.2%, and a 2^nd evaluation carried out 90 days after the procedure in 10 patients from the 1^st sample showed that the preoperative mean passed from 22.9% to 23.4%.

All differences observed between data prior to and after the procedure underwent a statistical test of significance, comparing the value of Student's t calculated with n-1 degrees of freedom with the corresponding critical value obtained from statistical tables (tab. II). This comparison allowed the following conclusion: 1) in regard to QRS width, a significant reduction in this value is statistically evident, even considering the 0.5% level of significance; 2) in regard to the ejection fraction measured on Doppler echocardiography, the improvement obtained over 3 months is statistically evident at the same level of significance; however, over the first 10 days, this evidence only manifested at the 5% significance level; 3) in regard to the ejection fraction measured on gated cardiac scanning, no statistical evidence of improvement was observed by the end of the 3^rd month after the procedure, not even at the 10% significance level, which may be due to the reduced size of the sample (10 patients); over the first 10 days, however, a trend towards statistical improvement was observed at the latter significance level.

In regard to the implantations of pacemaker leads in the left ventricle through the coronary sinus, we obtained the following positions: anterior wall in 9 patients, lateral wall in 15, and posterior wall in 2. Left ventricular endocavitary potential and intraoperative and postoperative biventricular potential, and left ventricular command threshold and intraoperative and postoperative biventricular command threshold are shown in table II. In 1 patient, phrenic stimulation with consequent diaphragmatic stimulation through the electrode in the coronary sinus made left ventricular pacing through this via impossible. Two increases in left ventricular pacing threshold occurred, both in epimyocardial pacemaker leads, 1 immediately before cardiac transplantation, and the other repaired with implantation of a 2^nd pacemaker electrode in the left ventricle through the coronary sinus (fig. 1).

Discussion

Artificial cardiac pacing seems to be approaching a new era in which the objective of the procedure is not only to reestablish the usual cardiac rhythm, but also to contribute to hemodynamics by resynchronizing the cardiac chambers. Ventricular resynchronization through biventricular pacing has demonstrated good results in the treatment of refractory congestive heart failure of dilated cardiomyopathy in patients with intraventricular conduction disorders.

Because our hospital is a referral center for cardiac transplantations, most of our patients are candidates for cardiac transplantation with no possibility of waiting due to complete myocardial failure (patients in the intensive care unit, depending on parenteral vasoactive drugs), or are extremely limited patients with very poor quality of life, who await the procedure.

In our experience, reproducing other similar studies in the literature ^13,14, we observed a significant acute clinical improvement in all patients, whose functional classes changed favorably after the procedure. This evident clinical improvement, however, was not accompanied by a proportional increment in the indices of ejection fraction measured on Doppler echocardiography and myocardial scintigraphy performed acutely (10^th postoperative day). These indices showed mild improvements, consisting of only statistical evidence on Doppler echocardiography performed on the 3^rd month after the procedure.

Implantation of an epicardial pacemaker lead in the left ventricle, which previously required thoracotomy, has been very simplified with the adoption of the endocavitary access, being performed with local anesthesia. We believe that the development of new pacemaker leads with special guides for catheterization of the coronary sinus will make this method even simpler.

Recently, dual-site right ventricular pacing was proposed as an option to biventricular pacing in ventricular resynchronization ¹⁵. This procedure was attempted for the first time in 1997 when Depuis et al ¹⁶ were not able to show the benefits of right ventricular dual-site pacing in relation to the isolated pacing of the right ventricular outflow tract. These results were also reproduced by LeHelloco et al ¹⁷. In our opinion, right ventricular dual-site pacing may bring some benefits to ventricular resynchronization; these benefits, however, cannot be compared with those of complete ventricular resynchronization provided by biventricular pacing.

It is worth noting that even though the benefit provided by ventricular resynchronization may be great, patients with cardiomyopathies persist with a severe myocardial disease, and they may experience decompensation with intraventricular conduction disorders. Therefore, this procedure may be a very good nonpharmacological option, mainly due to its minimally invasive feature.

Based on this initial experience, we conclude that ventricular resynchronization through biventricular pacing is an excellent nonpharmacological option for the treatment of congestive heart failure refractory to medicamentous treatment in patients with dilated cardiomyopathy with intraventricular conduction disorders.

Further in-depth studies may show the extension and duration of the benefits provided by this technique, and also identify the patients who will benefit the most from it.

Real e Benemérita Beneficência Portuguesa de São Paulo

Mailing address: Silas S. Galvão Fº - Rua Maestro Cardim, 1041 – 01323-001 São Paulo, SP, Brazil - E-mail: [e-mail] English version by Stela Maris C. e Gandour

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Publication Dates

• Publication in this collection
  19 Feb 2002
• Date of issue
  Jan 2002