Correspondence *Cardiology Department, Princess Alexandra Hospital, Hamstel Road, Harlow CM20 1QX, UK

Email vaezzat@doctors.org.uk

The case

A 44-year-old female was referred to an outpatient department. She had a 10-year history of palpitations and chest pain that occurred predominantly on exertion and were relieved with rest but could also occur with no obvious precipitant. These episodes occurred daily, lasting from only a few minutes to several hours. In addition, the patient reported NYHA class II symptoms of increasing dyspnea on exertion—causing some restriction of her daily activities. Furthermore, in the year before her presentation, she had experienced three syncopal episodes, the exact circumstances of which were unclear. Her medical history included a cholecystectomy, gastric ulcers and a hiatus hernia. She had a 5-year history of hypertension for which she was taking candesartan (4 mg once daily). She had previously been prescribed -blockers, but these had been discontinued several years previously owing to the development of bradycardia. She smoked 20 cigarettes a day and had a strong family history of early ischemic heart disease.

On presentation, the patient's heart rate was 76 beats/min and in sinus rhythm, and her blood pressure was well controlled at 128/79 mmHg. Cardiorespiratory examination was otherwise unremarkable and there were no overt signs of cardiac failure. The results of electrocardiography, echocardiography, cardiac MRI, 24 h Holter monitoring and coronary angiography are summarized in Box 1 and Figure 1. On review of the history, it was felt that the patient's syncopal episodes might not be related to the ventricular arrhythmias, and could represent an epiphenomenon such as neurally mediated hypotension. Subsequent tilt testing confirmed a tendency towards vasovagal syncope.

Box 1 Box 1 List of diagnostic imaging studies performed on the patient at presentation and a summary of the relevant findings.^a

 

Electrocardiography

Sinus rhythm with frequent premature ventricular ectopic beats at rest (Figure 1). These beats had a left-bundle-branch-block morphology and inferior axis consistent with an origin in the right ventricular outflow tract.

Echocardiography^b

Moderate dilatation of the left ventricle (end diastolic dimension 65 mm) and globally reduced systolic function (ejection fraction around 40%). No significant valvular pathology or regional wall motion abnormalities were identified, and the right side of the heart appeared normal.

Cardiac MRI

Findings were consistent with a dilated cardiomyopathy. There was no evidence of arrhythmogenic right ventricular dysplasia/cardiomyopathy, and there was no delayed enhancement when using gadolinium imaging.

24 h Holter monitoring

Over 33,000 ventricular ectopic beats (around 30% of the total number of QRS complexes), 560 episodes of bigeminy and 494 periods of trigeminy (Figure 1).

Coronary angiography

No epicardial stenoses or evidence of any underlying coronary disease.

 

^AThe patient was also scheduled to undergo exercise stress testing but this was cancelled owing to hypertension on the day of investigation. ^bEchocardiography was performed at a different facility and no further details are available regarding the method of calculation of ejection fraction.

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The patient underwent invasive electrophysiological testing around 3 months later, with the aim of mapping and ablating the focus of ventricular ectopy. This testing was performed with the patient in the fasting state and under moderate sedation. Clinical ectopy was present at the start of the procedure. A multielectrode array catheter (EnSite 3000^®, Endocardial Solutions Inc, St Paul, MN) was passed over a wire positioned in the main pulmonary artery and introduced into the right ventricular outflow tract (RVOT) via a 9F sheath placed in the right femoral vein. A 6 mm tip cryoablation catheter (Cryocath Technologies, Montreal, Canada) was used for mapping and ablation. The earliest endocardial activation of the ectopic beat was displayed on an isopotential color map (Figure 2). Initial mapping suggested that endocardial activation began in the posteromedial region of the RVOT before breaking out superiorly.

Figure 2 Invasive electrophysiological testing was performed with the multielectrode array positioned in the right ventricular outflow tract, with the aim of mapping and ablating the focus of the patient's ventricular ectopy.

(A) Isopotential color maps recorded before ablation, showing the site of the earliest endocardial activation of the ventricular ectopic beat (BO1). Two different anatomical orientations are provided, each related to the reference torso. The virtual electrogram created at BO1 is shown in the box, inset. (B) Isopotential color maps following the application of 11 cryothermal lesions (dark circles). The breakout region (the area where electrical activation begins to spread throughout the rest of myocardium) at the site of the final lesion before cessation of ventricular ectopy is shown (BO5), along with an accompanying electrogram. The orientations of the projections differ slightly from those shown above in order to illustrate the focus of the ablations more clearly. Abbreviation: EA, earliest activation.

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Cryothermal lesions (up to - 80 °C for 3 min) were delivered at the site of earliest activation, with the ablation signal 18 ms ahead of the QRS complex (Figure 3). Repeated analyses following each ablation demonstrated that the site of earliest activation was gradually shifting superiorly towards the pulmonic vein region. Ectopic activity was eventually abolished following the application of 11 cryothermal lesions from the inferomedial to the superomedial regions of the RVOT (Figure 2). No further ectopics were observed in the catheter laboratory. Programmed ventricular stimulation was not carried out.

Figure 3 Intracardiac and surface electrocardiograms, recorded at the ablation site during the procedure, showing a sinus beat followed by a premature ventricular complex.

During the complex, the signal at the ablation site (MapD) can be observed 18 ms ahead of the onset of ectopy.

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The patient was seen in the outpatient department 3 months later. Her symptoms had greatly improved, her left ventricular (LV) dimensions were reduced (end diastolic diameter 54 mm), and LV systolic function had returned to within normal limits (ejection fraction [EF] 62%). Recent 24 h Holter monitoring demonstrated a reduction in the number of premature ventricular complexes (PVCs) to 2,022, with 7 episodes of bigeminy and 121 of trigeminy recorded over this period.

Discussion of diagnosis

PVCs, or extrasystoles, are the most common arrhythmia to be observed in the absence of structural heart disease, and 'frequent' PVCs are estimated to occur in 1–4% of the general population.¹ Idiopathic PVCs usually arise from the RVOT and can be identified on electrocardiography by the characteristic appearance of a QRS complex with left-bundle-branch-block-like morphology and inferior axis. Although RVOT ectopy can cause troublesome and sometimes incapacitating palpitations, the condition was, until recently, considered relatively benign, as long term follow-up of affected individuals suggested a good prognosis.² Indeed, the majority of patients with idiopathic RVOT PVCs have minor symptoms that can often be self-limited with lifestyle modification and reassurance. Although there are reports of malignant polymorphic ventricular tachycardia originating from the RVOT, the coupling interval of these PVCs seems to be significantly shorter than the intervals seen in benign RVOT ventricular tachycardia.³

PVCs also occur in patients with intrinsic cardiac disease and in the case described here it was mandatory—in light of the patient's risk factors—to consider this possibility. The presence of underlying coronary disease was excluded with angiography. Echocardiography, however, demonstrated LV dilatation and impairment of systolic function in the absence of any other discernable abnormalities. Cardiac MRI was, therefore, indicated in order to exclude a diagnosis of arrhythmogenic right ventricular dysplasia/cardiomyopathy.⁴ The differential diagnosis in this case was complicated further by the history of syncopal episodes, which suggested the presence of a more-sustained ventricular arrhythmia. Careful review of the patient's history and further investigation with tilt testing, however, led to a diagnosis of vasovagal syncope that was considered to be unrelated to the patient's arrhythmia. Establishing this coincident diagnosis was important in order to avoid unnecessary therapies such as the implantation of an automatic implantable cardioverter-defibrillator.

The concept that frequent PVCs might themselves be responsible for the development of a cardiomyopathy was originally suggested following the observation that pharmacological suppression of PVCs in patients with presumed idiopathic dilated cardiomyopathy resulted in an improvement of symptomatic LV dysfunction.⁵ Since that time, a number of reports have emerged documenting a reversal of LV dilatation and impairment by both chemical and radiofrequency ablation treatments, supporting the hypothesis that frequent PVCs (including, in one case, those of LV origin) might have a causative role.⁶ The definition of frequent varies substantially in the literature. A pivotal report, published in 2005, divided a series of 40 patients into three arbitrary subgroups on the basis of the proportion of ectopic beats. This retrospective analysis showed that patients with frequent PVCs (>20%) had significantly larger left ventricles, poorer EFs and NYHA functional class, and a greater degree of mitral regurgitation than those with intermediate (10–20%) or rare (<10%) PVCs.¹² In addition, patients with frequent ectopic beats benefited from radiofrequency ablation, whereas those in the other two groups showed no significant change in LV parameters following this treatment.

The patient presented in this report had a very high ectopic burden (around 30%) and—in the absence of any other identifiable cause—it was postulated that this might be responsible for her LV impairment, and that elimination of PVCs would, therefore, lead to an improvement in LV function. It should also be noted, however, that we have previously reported an improvement in PVC-associated LV dysfunction in a patient who had similar clinical characteristics but whose ectopic burden on Holter monitoring was only 4%.⁶ Of further note is a prospective study comprising individuals with normal LV systolic function and frequent PVCs (>10,000 per day) who were undergoing radiofrequency catheter ablation for severe, drug-refractory symptoms.¹⁰ Significant reductions in LV dimensions and levels of serum brain natriuretic peptide were observed in those individuals in whom ablation was successful (PVCs reduced to <1,000 per day), whereas no such changes were seen in the group refractory to ablation. These results suggest that ablation could be beneficial even for patients with a normal EF.

Treatment and management

As the long-term prognosis of frequent PVCs is generally considered to be benign, the preferred treatment is usually reassurance and counseling of the patient and, if necessary, prescription of a -blocker or a non-dihydropyridine calcium-channel-blocker. Catheter ablation of the ectopic focus, particularly if it emanates from the RVOT, has been shown to successfully eliminate monomorphic ventricular ectopic activity and can be considered a reasonable alternative for patients who are severely symptomatic and refractory to drug treatment.¹³

The suppression of PVCs by antiarrhythmic pharmacological agents or catheter ablation is an established treatment for PVC-induced LV dysfunction associated with dilated cardiomyopathy. Considering that PVCs are postulated to be the cause of LV dilatation, eradication of the PVCs might be expected to effectively resynchronize the left ventricle and reduce tachycardia, leading to an improvement in the status of the left ventricle. A number of studies have reported improvements in LV dimensions and function following catheter ablation in patients with frequent isolated ectopics. The most recent and largest study, published by Bogun et al.,¹⁴ also found improvements in LV dysfunction following ablation, and, notably, demonstrated a significant inverse correlation between EF and PVC burden before ablation, and a significant postprocedural improvement in EF in 82% of patients who had abnormal systolic function before ablation. Furthermore, patients who did not undergo ablation experienced no change in, or a worsening of, heart failure status.

The patient presented here reported symptoms that were caused by the arrhythmia itself, as well as symptoms caused by the associated LV impairment. The intended benefit of ablative therapy was, therefore, to alleviate her palpitations and chest pain but, more importantly, to improve her LV dimensions and systolic function with the aim of ameliorating her progressive dyspnea. The safety and efficacy of cryoablation has been shown to be comparable with radiofrequency ablation, and cryoablation was the preferred technique because it offers improved catheter stability during lesion delivery and is virtually pain-free for the patient.¹⁵ Although repeat Holter monitoring following ablation did demonstrate some residual PVCs with the same morphology as those observed earlier, the patient's symptoms and cardiac function were vastly improved and the procedure was deemed a success.

As with any invasive intervention, it is imperative to balance the risks (including potentially life-threatening complications) that can occur with endocardial ablation against any potential symptomatic benefits. It must be stressed that whilst ablation should be considered in a number of individuals with a cardiomyopathy secondary to frequent PVCs, it is not an appropriate treatment for the vast majority of patients with frequent benign PVCs.

Conclusions

We report the case of a woman with a dilated cardiomyopathy secondary to multiple PVCs and no other evidence of cardiac disease. Ablation of the ectopic foci resulted in an improvement in both her symptoms and LV function. Although traditionally considered to be benign, multiple PVCs can be responsible for significant LV dysfunction, and definitive treatment with electrophysiological mapping and catheter ablation should be considered in these circumstances.

References

1. Kostis JB et al. (1981) Premature ventricular complexes in the absence of identifiable heart disease. Circulation 63: 1351–1356 | PubMed | ChemPort |
2. Gaita F et al. (2001) Long-term follow-up of right ventricular monomorphic extrasystoles. J Am Coll Cardiol 38: 364–370 | Article | PubMed | ChemPort |
3. Noda T et al. (2005) Malignant entity of idiopathic ventricular fibrillation and polymorphic ventricular tachycardia initiated by premature extrasystoles originating from the right ventricular outflow tract. J Am Coll Cardiol 46: 1288–1294 | Article | PubMed |
4. Corrado D et al. (1997) Spectrum of clinicopathologic manifestations of arrhythmogenic right ventricular cardiomyopathy/dysplasia: a multicenter study. J Am Coll Cardiol 30: 1512–1520 | Article | PubMed | ISI | ChemPort |
5. Duffee DF et al. (1998) Suppression of frequent premature ventricular contractions and improvement of left ventricular function in patients with presumed idiopathic dilated cardiomyopathy. Mayo Clin Proc 73: 430–433 | PubMed | ChemPort |
6. Shanmugam N et al. (2006) 'Frequent' ventricular bigeminy—a reversible cause of dilated cardiomyopathy. How frequent is 'frequent'. Eur J Heart Fail 8: 869–873 | Article | PubMed | ChemPort |
7. Shiraishi H et al. (2002) A case of cardiomyopathy induced by premature ventricular complexes. Circ J 66: 1065–1067 | Article | PubMed |
8. Chugh SS et al. (2000) First evidence of premature ventricular complex-induced cardiomyopathy: a potentially reversible cause of heart failure. J Cardiovasc Electrophysiol 11: 328–329 | Article | PubMed | ChemPort |
9. Satish OS et al. (2005) Premature ventricular contraction-induced concealed mechanical bradycardia and dilated cardiomyopathy. J Cardiovasc Electrophysiol 16: 88–91 | Article | PubMed |
10. Sekiguchi Y et al. (2005) Chronic hemodynamic effects after radiofrequency catheter ablation of frequent monomorphic ventricular premature beats. J Cardiovasc Electrophysiol 16: 1057–1063 | Article | PubMed |
11. Yarlagadda RK et al. (2005) Reversal of cardiomyopathy in patients with repetitive monomorphic ventricular ectopy originating from the right ventricular outflow tract. Circulation 112: 1092–1097 | Article | PubMed |
12. Takemoto M et al. (2005) Radiofrequency catheter ablation of premature ventricular complexes from right ventricular outflow tract improves left ventricular dilation and clinical status in patients without structural heart disease. J Am Coll Cardiol 45: 1259–1265 | Article | PubMed |
13. Zhu DW et al. (1995) Radiofrequency catheter ablation for management of symptomatic ventricular ectopic activity. J Am Coll Cardiol 26: 843–849 | Article | PubMed | ChemPort |
14. Bogun F et al. (2007) Radiofrequency ablation of frequent, idiopathic premature ventricular complexes: comparison with a control group without intervention. Heart Rhythm 4: 863–867 | Article | PubMed |
15. Kurzidim K et al. (2005) Cryocatheter ablation of right ventricular outflow tract tachycardia. J Cardiovasc Electrophysiol 16: 366–369 | PubMed |

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Subject areas under which this article appears: Arrhythmias | Cardiomyopathy and heart failure