Author + information
- Received October 9, 2004
- Revision received December 2, 2004
- Accepted December 6, 2004
- Published online April 19, 2005.
- Masao Takemoto, MD⁎ (, )
- Hitoshi Yoshimura, MD,
- Yurika Ohba, MD,
- Yasuharu Matsumoto, MD,
- Umpei Yamamoto, MD,
- Masahiro Mohri, MD,
- Hideo Yamamoto, MD and
- Hideki Origuchi, MD
- ↵⁎Reprint requests and correspondence:
Dr. Masao Takemoto, Internal Medicine, Kyushu Kosei-Nenkin Hospital, 1-8-1 Kishinoura, Yahatanishi-ku, Kitakyushu 806-8501, Japan.
Objectives The present study evaluated clinical benefits of radiofrequency catheter ablation (RFA) for premature ventricular complexes from right ventricular outflow tract (RVOT-PVC) in patients without structural heart disease.
Background It is unknown whether PVC causes left ventricular (LV) dilation, which is a well-recognized precursor of LV dysfunction and heart failure, and whether eliminating PVC by RFA produces clinical benefits in patients with RVOT-PVC.
Methods Frequency of PVC per total heart beats by 24-h Holter monitoring, left ventricular ejection fraction (LVEF), left ventricular end-diastolic internal dimension (LVDd), mitral regurgitation (MR) by echocardiogram, cardiothoracic ratio (CTR) by chest radiogram, and New York Heart Association (NYHA) functional class of 40 patients with RVOT-PVC without structural heart disease were evaluated before and 6 to 12 months after RFA.
Results Before RFA, a subgroup of patients with frequent (>20%) PVC demonstrated significantly enlarged LVDd and CTR, reduced LVEF, increased MR, and deteriorated NYHA functional class as compared to the subgroup with rare (<20%) PVC (54 ± 1 mm vs. 45 ± 1 mm, 52 ± 2% vs. 46 ± 1%, 66 ± 2% vs. 73 ± 2%, 1.2 ± 0.2 degree vs. 0.4 ± 0.1 degree, and 1.8 ± 0.2 vs. 1.3 ± 0.1, respectively; p < 0.05). Furthermore, ablating RVOT-PVC readily produced the improvement of all these abnormalities (47 ± 1 mm, 41 ± 1%, 72 ± 2%, 0.3 ± 0.1 degree, and 1.0 ± 0.0, respectively; p < 0.05 compared with before RFA).
Conclusions These findings suggest that frequent (>20%) RVOT-PVC may be a possible cause of LV dysfunction and/or heart failure, and RFA produces clinical benefits in these patients.
Isolated premature ventricular complexes (PVC) are the most common arrhythmias observed in patients without structural heart disease (1). It has been recently reported that frequent PVC caused left ventricular (LV) dysfunction that can be reversed by suppression of PVC with antiarrhythmic agents (2,3) or radiofrequency catheter ablation (RFA) (4,5) in patients with dilated cardiomyopathy. It is uncertain, however, whether frequent PVC causes LV dilation and dysfunction even in patients with no evidence of structural heart disease and, if so, whether suppression of PVC improves these changes. In recent years, RFA has proven to be a safe and successful therapy for arrhythmias (6,7). The purpose of this study was two-fold: 1) to examine whether frequent premature ventricular complexes from right ventricular outflow tract (RVOT-PVC) without structural heart disease may cause LV dilation, which is a well-recognized precursor of LV dysfunction and congestive heart failure (8); 2) to evaluate the role of ablating RVOT-PVC per RFA on cardiac function in patients with depressed cardiac function.
Study population and laboratory analysis
From 1994 to 2004, 45 consecutive patients (10 males and 35 females with mean age of 50 ± 2 years and body surface area of 1.57 ± 0.02 m2) with monomorphic RVOT-PVC and no evidence of underlying structural heart disease underwent RFA at our hospital. All patients had their history recorded, and underwent physical examination, laboratory analysis, chest radiogram, 12-lead electrocardiogram, 24-h Holter monitoring, M-mode, two-dimensional, and Doppler echocardiogram (SONOS 2000, Hewlett-Packard, San Diego, California, and SEQUOIA 512, Siemens, Erlangen, Germany) on admission or within at least 1 month before admission, and 6 to 12 months after RFA (average 8 ± 1 month). The 24-h Holter monitoring and echocardiogram were performed on the same day. All patients also took routine echocardiogram on the next day of RFA to evaluate the possible procedure-related complications. We evaluated the chamber size of LV and right ventricle (RV), and degree of mitral regurgitation at parasternal long-axis or apical four-chamber view, respectively. Left ventricular ejection fraction (LVEF) was calculated by the Teichholz method. All values of echocardiogram were recorded during sinus rhythm, but not at the PVC beat, nor at the post-PVC beat. All patients also underwent the exercise electrocardiogram testing, cardiac catheterization with coronary angiography, and/or 201-thallium scintigraphy. These examinations yielded no evidence of clinically overt structural heart disease, including coronary artery disease, valvular heart disease, congenital heart disease, LV hypertrophy, and RV abnormalities in all patients. Brain natriuretic peptide of five recent patients was evaluated on admission and six months after RFA.
Definition of RVOT-PVC
Right ventricular outflow tract-PVC was defined as a characteristic electrocardiographic appearance of a left bundle branch block (LBBB) contour in V1and an inferior axis in the frontal plane. Ventricular tachycardia was defined with standard electrocardiographic criteria of at least five consecutive PVC at a rate >120 beats/min. Patients with ventricular tachycardia and atrial tachyarrhythmia including atrial fibrillation, atrial flutter, atrial tachycardia, and paroxysmal supraventricular tachycardia were excluded in this study because they may cause tachycardia-induced LV dilation (9,10). The region of the LV outflow tract was not an origin of PVC of all patients in this study.
Mapping and catheter ablation procedure
All procedures were performed after written informed consent was obtained. The patients were studied in the fasting state without sedation. Antiarrhythmic drugs were discontinued for at least six half-lives before the procedure. Under local anesthesia, a 7-F deflectable quadripolar ablation catheter (Boston Scientific EP Technologies, Natick, Massachusetts) with a 4-mm-tip electrode was introduced percutaneously into the RV. Based on the 12-surface-lead electrocardiogram with spontaneous RVOT-PVC, pace mapping was done by using bipolar pacing between the distal pair of the electrodes with a stimulation pulse width of 2 ms. If the culprit PVC were not found during the procedure, isoproterenol administration and/or programmed electrical stimulation with digital stimulator (Cardiac Stimulator, Nihon Kohden Co., Tokyo, Japan) was performed to induce the culprit PVC as previously described (6). An optimal pace map was defined as a match of all 12 surface leads by comparing the R/S ratio and subtle notching in the QRS complex during pacing. An identical match was necessary in at least 11 of 12 leads. The RFA was performed based on an optimal pace map for 60 to 90 s with a preset temperature of 50 to 60°C and a power limit of 50 W. A successful ablation was defined as the no recurrence and non-inducibility of culprit PVC with and without isoproterenol administration at the rate of 0.2 to 0.6 μg/min and/or programmed electrical stimulation during at least 30 min after ablation. All 12 surface electrocardiograms and the bipolar intracardiac electrograms (filtered at 30 to 400 Hz) were recorded and stored by using a 48-channel acquisition system (CardioLabEP, Prucka Engineering Inc., Houston, Texas). During the procedure, intravenous heparin was given as a 100 IU/kg bolus dose followed by boluses of 1,000 IU every hour. All patients received oral antiplatelets for eight weeks after RFA, but no antiarrhythmic drugs. Procedural success was defined as no recurrence of culprit PVC within 72 h after procedure under electrocardiogram monitoring.
Numerical results are expressed in the text as the mean ± standard deviation. Paired data were compared by Student ttests. The differences between the continuous variables before and 1 day or 6 to 12 months after RFA in each group, or between the lower, middle, and upper group in each period, were compared by using a repeated-measures analysis of variance followed by Bonferroni’s test for multiple comparisons. Correlation between the two parameters was determined by simple linear regression analysis. A p < 0.05 was considered to indicate statistical significance.
An RFA procedure for RVOT-PVC was performed in 45 patients. Because five patients (11%) were lost to follow-up, they were excluded from the statistical analysis. Procedural success was achieved in 37 (93%) of the patients. One patient (3%) suffered from a procedure-related complication with femoral arteriovenous fistula. During follow-up, recurrence of culprit RVOT-PVC was observed in one patient (3%), who underwent repeated RFA with successful result. Relationships between the left ventricular end-diastolic internal dimension (LVDd) and the frequency of PVC (%PVC) by 24-h Holter monitoring of 40 patients before RFA were examined (Fig. 1).The %PVC was calculated as: 100·[number of PVC/number of total heart beats per 24 h] . A significant correlation was found between the LVDd and %PVC (y = 45.8 + 0.254x, r = 0.56, p < 0.01), indicating that frequent PVC might cause LV dilation. Patients (n = 40) were divided into three groups (the lower [<10%; n = 14] , middle [10% to 20%; n = 12] , and upper [>20%; n = 14] group) according to the tertiles of %PVC. Baseline characteristics of the patients are shown in Table 1.There was no statistical difference in body surface area, hemodynamic variables including systolic and diastolic blood pressure and resting heart rate, or the prevalence of diabetes (7%, 8%, and 7%, respectively) or hypertension (21%, 16%, and 21%, respectively) between the three groups. The mean patients’ age was slightly older in the middle and upper groups than the lower group, but the differences were not significant between the three groups. Symptom duration was significantly shorter in the middle and upper groups compared with the lower group (p < 0.05 and 0.05, respectively). No patients had chronic obstructive pulmonary disease, renal dysfunction (serum creatinine more than 1.5 mg/dl), liver disease (liver enzyme values in excess of 2 × normal), or underlying malignant disease.
24-h Holter monitoring
Table 2summarizes analysis of 24-h Holter monitoring. The number of total heart beats was not statistically different before or after RFA between the three groups. However, RFA produced a significant decrease in the number of total heart beats in the upper group (p < 0.05), but not in the lower or middle groups. Radiofrequency ablation significantly reduced the number of total PVC (p < 0.01 for all conditions) and %PVC (p < 0.01 for all conditions) with no evidence of the recurrence of culprit PVC in all three groups. There was no statistical difference of the number of total PVC and %PVC after RFA between the three groups. There was no statistical difference in the frequency of premature atrial complexes before and after RFA between the three groups (data not shown).
Echocardiogram and chest radiography
Figure 2summarizes the results of the analysis of echocardiograms (Figs. 2A to 2E) and chest radiograms (Fig. 2F). Before RFA, a subgroup of patients in the upper group demonstrated significantly reduced LVEF, enlarged LVDd, and left ventricular end-systolic internal dimension (LVDs), and increased degree of mitral regurgitation and cardiothoracic ratio compared with the lower or middle groups (p < 0.05 and 0.05, respectively) (Figs. 2A to 2D and 2F). There was no statistical difference in these parameters between the lower and middle groups. The examination by echocardiogram one day after RFA revealed the same results as those before RFA. However, at the examination 6 to 12 months after RFA, all of these abnormalities seen in the upper group before RFA were completely reversed (Figs. 2A to 2D and 2F), and there was no statistical difference in these parameters between the three groups. There was no statistical difference in these parameters during follow-up in the lower or middle groups. There was no evidence of RV abnormalities in all patients (Fig. 2E), indicating that arrhythmogenic RV cardiomyopathy was unlikely. There was no statistical difference in any of the analyzed parameters between the groups before and after RFA.
New York Heart Association (NYHA) functional class and serum brain natriuretic peptide concentration
The NYHA functional class was evaluated in all patients on admission and 6 to 12 months after RFA. Before ablation, NYHA functional class was demonstrated to be significantly worse in accordance with %PVC (p < 0.05) (Fig. 3).Radiofrequency ablation significantly improved NYHA functional class in each group compared with before intervention. The serum brain natriuretic peptide concentration of five recent patients was evaluated; one in the lower group, one in the middle group, and three in the upper group, respectively. The serum brain natriuretic peptide level in the upper group was elevated to 56 ± 3 pg/dl before RFA. However, it significantly decreased to 3.7 ± 0.3 pg/dl six months after RFA (p < 0.01). The value of two patients in the lower and middle groups did not elevate before and after RFA (data not shown).
Patients symptoms and medications
On admission, all patients had PVC-associated symptoms (Table 3).Of 40 patients, 26 patients (65%) had been taking antiarrhythmic agents before admission, such as beta-blocker, bepridil, class Ia, Ib, and/or Ic agents of Vaughan Williams classification (Table 3). However, these agents were not sufficiently effective to eliminate PVC-associated symptoms. No patients had been on amiodarone or sotalol. All of the patients with successful procedure reported the absence of PVC-associated symptoms and could discontinue antiarrhythmic agents after RFA. The antihypertensive or antidiabetic agents, such as beta-blockers, calcium-channel blockers, angiotensin-converting enzyme inhibitors, or sulfonylurea, were continued in patients with hypertension or diabetes before and after RFA.
Outcome of patients with unsuccessful RFA
Of 40 patients, three patients were procedurally unsuccessful in this study; one in the upper group, and two in the middle group. Table 4summarizes the results of the analysis of echocardiograms, chest radiograms, and NYHA functional class of these patients. All three patients took medications, which seemed to be partially effective in the patient in the upper group. All of these factors in two patients of the middle group did not further deteriorate during follow-up. Interestingly, the LVDd, LVDs, LVEF, degree of mitral regurgitation by echocardiogram, and cardiothoracic ratio by chest radiogram of the patient with unsuccessful RFA in the upper group still deteriorated during follow-up.
Isolated PVC are the most common arrhythmia that physicians often see during patient examination (1). The presence of PVC has been found to be an independent risk factor for sudden death (11), especially in patients after myocardial infarction (12,13). Many patients with PVC often experience disabling symptoms and sometimes need long-term antiarrhythmic medications. However, the latter are often ineffective and may have adverse effects, such as the increasing mortality, probably due to their proarrhythmic effects, even though markedly suppressing the occurrence of PVC (14–16). It has been reported that RFA produces clinical benefits to the patients with ventricular tachycardia (6,7,17), and some case reports have shown that the dilated cardiomyopathy patients with PVC-depressed cardiac function and successful RFA of these arrhythmias improved LV function (4,5). However, these phenomena have never been documented in the large series of patients with PVC without underlying heart disease.
An RFA procedure for RVOT-PVC was performed in 45 patients, mostly females in this study. The reasons for a much higher prevalence of women may be that the study population was limited to the patients with disabling PVC-associated symptoms. This retrospective study provides evidence in support of the concept that some of the patients with frequent RVOT-PVC, more than 20% per total heart beats, without overt underlying structural heart disease were associated with LV dilation (Figs. 1, 2B, 2C, and 2F), which was known to be a risk factor for LV dysfunction and congestive heart failure (8). Before RFA, LVEF, degree of mitral regurgitation, and NYHA functional class in these patients were worse as compared to the patients with rare RVOT-PVC, <20% per total heart beats (Figs. 2A, 2D, and 3). These abnormalities were still present one day after successful RFA. Furthermore, these parameters of the patient with unsuccessful RFA with frequent PVC, but not with rare PVC, still deteriorated during follow-up. These findings may indicate that the frequent RVOT-PVC, more than 20% per total heart beats, may be an important and independent risk factor on progressing LV dysfunction and heart failure. The findings of elevated serum brain natriuretic peptide level and total heart rate (Table 2) before RFA in the upper group may also support the possibility of heart failure progression. When the patients were divided into three groups according to the tertiles of the absolute number of PVC before RFA, the number of PVC more than 20,000 beats per day was shown to be at risk (data not shown). More importantly, ablating RVOT-PVC readily produced the improvement of these abnormalities without adverse effects. Attenuation of progressive LV dilation has proven to reduce the risk of cardiovascular events (8,10), and RFA is known to be safe and effective for the treatment of arrhythmias as compared with medical therapy (7,14). Thus, RFA may be considered as the first choice of therapy for patients with frequent RVOT-PVC with LV dilation.
Although the mechanism(s) of LV dilation in those with RVOT-PVC is not completely elucidated, several potential mechanisms can be raised. Most of the patients with RVOT-PVC demonstrate LBBB and inferior axis morphology, and wide QRS complex generally >120 ms (1). It has been reported that LBBB causes asynchronous myocardial activation, which progresses into LV diastolic dysfunction and mitral regurgitation leading to decreased LV stroke volume (18,19). Recent clinical trials revealed that permanent RV apical pacing, which demonstrated LBBB promoted heart failure progression (20–23). Furthermore, both permanent RV apical pacing and RVOT pacing could not improve quality of life or give other clinical benefits in patients with permanent pacemaker implantation (24,25). Thus, LBBB-induced asynergic LV wall motion caused by frequent RVOT-PVC might be one of the important factors of progressing LV dilation and reduced LVEF observed in this study. Moreover, it has been reported that LV contraction usually moves from the apical to the basal portion with LV apex rotation in accordance with squeezing effect (4) and torsional deformation (26,27) during sinus rhythm. Because the direction of LV contraction is reversed during RVOT-PVC, these effects may cause disruption and further progression of asynergic LV wall motion. Recent clinical studies reported that cardiac resynchronization resulted in significant clinical improvements in patients who had chronic heart failure and wide QRS interval (28,29). In view of these findings, eliminating RVOT-PVC by RFA may be a subset of resynchronization therapy.
Limitations of the study
Our study is limited by its retrospective design and relatively short follow-up period. Serum brain natriuretic peptide concentration was not evaluated in all patients. Although the differences in LV dilation, LVEF, degree of mitral regurgitation, and NYHA functional class observed in patients with frequent PVC after RFA were statistically significant, they were relatively mild. Whether our results can safely be extrapolated to the patients with much larger LV and reduced LVEF should be determined in further studies. Recent case reports showed that a similar beneficial effect of RFA on LV function was seen in patients with a more severe form of heart failure (4,5), supporting our hypothesis.
A subgroup of patients with frequent (>20%) PVC demonstrated significantly enlarged LVDd, reduced LVEF, increased mitral regurgitation, and deteriorated NYHA functional class as compared to the subgroup with rare (<20%) PVC. Furthermore, the ablation of these arrhythmias was associated with the normalization of these abnormalities without adverse effects. These findings suggest that RVOT-PVC may be a possible cause of LV dysfunction and/or heart failure. Thus, the physicians should be aware of the condition when examining a patient with LV dilation and/or reduced LVEF in the presence of frequent RVOT-PVC because it may be at least one important risk factor on progressing LV dysfunction and heart failure. Radiofrequency catheter ablation may be considered as the first choice of therapy for those patients.
The authors thank Fumiko Hori, Hiroko Ohnagamitsu, Yukimi Takahashi, and Kenji Sakuma for their technical assistance with the electrophysiological study and RFA in the cardiac catheterization laboratory, and Machiko Murata, Kikuko Akimitsu, Tomoyo Okuda, Miya Shimizu, Aki Ogawa, and Keiko Matsumura for their technical assistance with echocardiographic analysis in the echocardiographic laboratory.
- Abbreviations and Acronyms
- left bundle branch block
- left ventricle/ventricular
- left ventricular end-diastolic internal dimension
- left ventricular end-systolic internal dimension
- left ventricular ejection fraction
- New York Heart Association
- premature ventricular complexes
- radiofrequency catheter ablation
- right ventricle/ventricular
- right ventricular outflow tract
- frequency of premature ventricular complexes
- Received October 9, 2004.
- Revision received December 2, 2004.
- Accepted December 6, 2004.
- American College of Cardiology Foundation
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