Class IC antiarrhythmic drugs for suspected premature ventricular contraction–induced cardiomyopathy

      Background

      Class IC antiarrhythmic drugs (IC-AADs) can effectively suppress premature ventricular contractions (PVCs). However, IC-AADs increase mortality in patients with PVCs and left ventricular dysfunction after myocardial infarction. Whether IC-AADs can be safely used to treat premature ventricular contraction–induced cardiomyopathy (PVC-CM) remains to be established.

      Objective

      The purpose of this study was to determine the safety and efficacy of IC-AADs in patients suspected of having PVC-CM.

      Methods

      The electronic medical records at the Hospital of the University of Pennsylvania were screened to identify all patients suspected of having PVC-CM treated with flecainide or propafenone. Clinical, electrocardiographic, and imaging studies were reviewed.

      Results

      Twenty patients suspected of having PVC-CM were treated with IC-AADs. Patients had undergone an average of 1.3 ± 0.2 previous unsuccessful ablations. Six had an implantable or wearable defibrillator. With IC-AAD treatment, mean PVC burden decreased from 36.2% ± 3.5% to 10.0% ± 2.4% (P <.001). Mean left ventricular ejection fraction (LVEF) increased from 37.4% ± 2.0% to 49.0% ± 1.9% (P <.001). Seven patients with myocardial delayed enhancement on cardiac magnetic resonance imaging (all <5% of the total myocardium) experienced similar improvement in LVEF (from 36.8% ± 4.3% before IC-AAD to 51.7% ± 3.7% afterward; P <.01). Over an average 3.8 ± 0.9 treatment-years, no sustained ventricular arrhythmias or sudden cardiac deaths occurred.

      Conclusion

      In patients suspected of having PVC-CM, IC-AADs effectively suppressed PVCs, leading to LVEF recovery in the majority. No adverse events occurred in this small cohort.

      Keywords

      Introduction

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      Premature ventricular contractions (PVCs) are common in the general population, with an estimated prevalence of 1% to 4%.
      • Kennedy H.L.
      • Whitlock J.A.
      • Sprague M.K.
      • Kennedy L.J.
      • Buckingham T.A.
      • Goldberg R.J.
      Long-term follow-up of asymptomatic healthy subjects with frequent and complex ventricular ectopy.
      The long-term prognosis of asymptomatic PVCs is generally benign when the arrhythmia burden is low. If the burden of PVCs increases beyond a critical threshold, a premature ventricular contraction–induced cardiomyopathy (PVC-CM) may result.
      • Baman T.S.
      • Lange D.C.
      • Ilg K.J.
      • et al.
      Relationship between burden of premature ventricular complexes and left ventricular function.
      This form of cardiomyopathy can be reversed by eliminating or decreasing the PVCs.
      • Mountantonakis S.E.
      • Frankel D.S.
      • Gerstenfeld E.P.
      • et al.
      Reversal of outflow tract ventricular premature depolarization-induced cardiomyopathy with ablation: effect of residual arrhythmia burden and preexisting cardiomyopathy on outcome.
      • Campos B.
      • Jauregui M.E.
      • Park K.M.
      • et al.
      New unipolar electrogram criteria to identify irreversibility of nonischemic left ventricular cardiomyopathy.
      Catheter ablation can be curative in the majority of patients; however, the proximity of PVCs to coronary arteries and the conduction system prohibit successful ablation in some patients. In patients in whom successful ablation is not possible, pharmacologic suppression is desired. Class III antiarrhythmic drugs (AADs), including amiodarone, sotalol, and dofetilide, can be effective, but their use may be limited by organ toxicities, worsening heart failure, poor renal function, and the need for inpatient initiation. Class IC antiarrhythmic drugs (IC-AADs) can also effectively suppress PVCs.
      • Capucci A.
      • Di Pasquale G.
      • Boriani G.
      • Carini G.
      • Balducelli M.
      • Frabetti L.
      • Carozzi A.
      • Finzi A.
      • Pinelli G.
      • Magnani B.
      A double-blind crossover comparison of flecainide and slow-release mexiletine in the treatment of stable premature ventricular complexes.
      • Zhong L.
      • Lee Y.H.
      • Huang X.M.
      • Asirvatham S.J.
      • Shen W.K.
      • Friedman P.A.
      • Hodge D.O.
      • Slusser J.P.
      • Song Z.Y.
      • Packer D.L.
      • Cha Y.M.
      Relative efficacy of catheter ablation vs antiarrhythmic drugs in treating premature ventricular contractions: a single-center retrospective study.
      Ease of initiation, lack of organ toxicity, and nonrenal clearance increase their appeal. These advantages must be weighed against an increase in mortality observed in patients with myocardial infarction treated with IC-AADs in the Cardiac Arrhythmia Suppression Trial (CAST).
      • Echt D.S.
      • Liebson P.R.
      • Mitchell L.B.
      • et al.
      Mortality and morbidity in patients receiving encainide, flecainide, or placebo. The cardiac arrhythmia suppression trial.
      Cardiac Arrhythmia Suppression Trial II Investigators
      Effect of the antiarrhythmic agent moricizine on survival after myocardial infarction.
      • Epstein A.E.
      • Hallstrom A.P.
      • Rogers W.J.
      • Liebson P.R.
      • Seals A.A.
      • Anderson J.L.
      • Cohen J.D.
      • Capone R.J.
      • Wyse D.G.
      Mortality following ventricular arrhythmia suppression by encainide, flecainide, and moricizine after myocardial infarction. The original design concept of the Cardiac Arrhythmia Suppression Trial (CAST).
      • Ruskin J.N.
      The Cardiac Arrhythmia Suppression Trial (CAST).
      Whether IC-AADs increase mortality in patients with nonischemic cardiomyopathy is not known. In a small cohort of patients with arrhythmogenic right ventricular cardiomyopathy, an implantable cardioverter–defibrillator (ICD), and refractory ventricular tachycardia, flecainide was recently demonstrated to reduce arrhythmia recurrence.
      • Ermakov S.
      • Gerstenfeld E.P.
      • Svetlichnaya Y.
      • Scheinman M.M.
      Use of flecainide in combination antiarrhythmic therapy in patients with arrhythmogenic right ventricular cardiomyopathy.
      Whether IC-AADs may be used safely in PVC-CM remains unclear. This strategy is particularly appealing given the potential for the “structural heart disease” to resolve with effective treatment. With this background in mind, we retrospectively determined the safety and efficacy of IC-AADs in patients suspected of having PVC-CM.

      Methods

      Study population

      Patients were retrospectively identified by systematically screening the Hospital of University of Pennsylvania electronic medical records (Figure 1). The PennSeek (http://www.med.upenn.edu/dac/pennseek.html) natural language search tool was used to query outpatient encounters for the terms “PVC-induced cardiomyopathy,” “premature ventricular contraction–induced cardiomyopathy,” “PVC-mediated cardiomyopathy,” “premature ventricular contraction-mediated cardiomyopathy,” “tachycardia-induced cardiomyopathy,” or “tachycardia-mediated cardiomyopathy.” Similarly, patients were identified with International Classification of Diseases codes (versions 9 and 10) for both cardiomyopathy and PVC. All identified patients were cross-referenced for prescriptions for flecainide or propafenone. A manual chart review was performed on this subset of patients to identify those who were actually prescribed a IC-AAD for treatment of suspected PVC-CM. Patients with spontaneous or inducible sustained ventricular tachycardia before IC-AAD initiation were excluded to avoid misclassifying subsequent ventricular tachycardia as IC-AAD proarrhythmia. The study was approved by the Hospital of the University of Pennsylvania institutional review board.
      Figure thumbnail gr1
      Figure 1Screening method used to identify patients with suspected premature ventricular contraction-induced cardiomyopathy (PVC-CM) who were prescribed Class IC antiarrhythmic drugs (IC-AADs). ICD = International Classification of Disease.

      Clinical, electrocardiographic, and imaging characteristics

      Demographic and clinical characteristics were abstracted from the electronic medical records, with particular attention to previous unsuccessful attempts at PVC suppression, including catheter ablation and AADs. Left ventricular end-diastolic diameter, end-systolic diameter, and left ventricular ejection fraction (LVEF) were measured using standard techniques from the Hospital of the University of Pennsylvania echocardiogram most closely preceding IC-AAD initiation. Similarly, baseline PVC burden was quantified from the Holter recording most closely preceding IC-AAD initiation. Cardiac magnetic resonance imaging (MRI) was performed at the discretion of the treating physician. For MRIs performed at the Hospital of the University of Pennsylvania, ECG-gated images were acquired on a 1.5-T MRI scanner (Siemens Magnetom Avanto, Erlangen, Germany). Twelve minutes after intravenous administration of 0.14 mmol/kg of gadobenate dimeglumine (Multihance, Bracco Diagnostics, Princeton, NJ), 2-dimensional and 3-dimensional late gadolinium enhancement (LGE) images were acquired. Inversion time was optimized to null the normal myocardium. In patients with an ICD, additional wideband LGE sequences were obtained to minimize imaging artifact.
      • Rashid S.
      • Rapacchi S.
      • Vaseghi M.
      • Tung R.
      • Shivkumar K.
      • Finn J.P.
      • Hu P.
      Improved late gadolinium enhancement MR imaging for patients with implanted cardiac devices.
      ICDs were interrogated and reprogrammed as appropriate before and after MRI.

      Clinical follow-up

      Patients were generally evaluated in the outpatient clinic at least every 6 months to assess efficacy as well as complications and drug side effects. Holter recordings and transthoracic echocardiograms were also performed at regular intervals, as determined by the treating physician. The last available PVC burden and LVEF while on treatment with IC-AADs were used for pre–post comparisons.

      Statistical analysis

      Continuous variables are given as mean ± SD, and categorical variables are given as percentage. The paired t test was used to compare normally distributed continuous variables, before and after treatment with IC-AADs. The Mann–Whitney U test was used to compare non-normally distributed continuous variables before and after treatment. Analyses were performed using SPSS software, version 22 (SPSS Inc, Chicago, IL). P ≤.05 was considered significant.

      Results

      Twenty patients were identified with suspected PVC-CM treated with IC-AAD. Mean cohort age was 48.0 ± 3.7 years (Table 1). Medical comorbidities were uncommon. No patients had a history of coronary artery disease, and 95% had undergone normal stress testing or coronary angiography before IC-AAD initiation. The majority of patients were treated with beta-blockers (90%) and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (75%). Four patients (20%) had an ICD, and 2 patients (10%) were prescribed a wearable cardioverter–defibrillator during treatment with IC-AAD.
      Table 1Baseline clinical, electrocardiographic, and imaging characteristics of patients with suspected premature ventricular contraction–induced cardiomyopathy treated with Class IC antiarrhythmic drugs (n = 20)
      Clinical characteristics
       Male11 (55.0)
       Age (yrs)48.0 ± 3.7
       Body mass index (kg/m2)30.6 ± 1.2
       Atrial fibrillation4 (20.0)
       Diabetes5 (25.0)
       Hypertension8 (40.0)
       Hyperlipidemia8 (40.0)
       Obstructive sleep apnea4 (20.0)
       Chronic obstructive pulmonary disease or asthma2 (10.0)
       Malignancy3 (15.0)
       Serum creatinine (mg/dL)0.9 ± 0.1
       Coronary artery disease0 (0)
       Beta-blocker18 (90.0)
       Calcium channel blocker3 (15.0)
       ACE-I/ARB15 (75.0)
      Electrocardiographic characteristics
       Left bundle PVC morphology7
      Two patients did not have ECG recording of the clinical PVC, only Holter recordings.
      (38.9)
       PVC burden (%)36.2 ± 3.5
       No. of failed previous ablations1.3 ± 0.2
       No. of failed Class III AADs0.8 ± 0.2
       Implantable cardioverter–defibrillator4 (20.0)
       Wearable defibrillator2 (10.0)
      Imaging characteristics
       Left ventricular ejection fraction (%)37.4 ± 2.0
       ≥Moderate mitral regurgitation5 (25)
       Septal thickness (mm)1.1 ± 0.2
       Left ventricular end-diastolic dimension (cm)5.6 ± 0.7
       Regional wall-motion abnormality3 (15.0)
       Cardiac MRI performed17 (85.0)
       Myocardial delayed enhancement7 (41.2)
      Values are given as n (%) or mean ± SD.
      AAD = antiarrhythmic drug; ACE-I = angiotensin-converting enzyme inhibitor; ARB = angiotensin receptor blocker; MRI = magnetic resonance imaging; PVC = premature ventricular contraction.
      Two patients did not have ECG recording of the clinical PVC, only Holter recordings.
      Mean baseline PVC burden was 36.2% ± 3.5%. Patients failed an average of 1.3 ± 0.2 catheter ablations (due to multifocal nature or proximity of the PVC site of origin to coronary arteries or the His bundle) and 0.8 ± 0.2 Class III AADs before IC-AAD initiation. Mean baseline LVEF was 37.4% ± 2.0% with minimal valvular disease. Seventeen patients (85%) underwent cardiac MRI, of whom 7 had LGE. Scar volume was <5% of the total ventricular myocardium in each of these 7 patients.
      Flecainide was used in 13 patients (mean dose 88.5 ± 11.3 mg twice daily) and propafenone in 7 patients (6 with mean dose of sustained release 291.7 ± 19.5 mg twice daily, 1 short-acting 150 mg three times daily). Average duration of treatment was 3.8 ± 0.9 years, with 2 patients (10%) experiencing side effects of blurry vision, dizziness, or fatigue. After IC-AAD treatment, mean PVC burden decreased from 36.2% ± 3.5% to 10.0% ± 2.4% (P <.001) (Figure 2A). Mean LVEF improved from 37.4% ± 2.0% to 49.0% ± 1.9% (P <.001) (Figure 2B). Patients with baseline left ventricular dilation, defined as diastolic dimension >5.8 cm in males and >5.2 cm in females,
      • Lang R.M.
      • Badano L.P.
      • Mor-Avi V.
      • et al.
      Recommendations for cardiac chamber quantification by echocardiography in adults: An update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging.
      experienced similar improvement in LVEF (34.2% ± 4.3% to 48.2% ± 3.0%) as those without baseline left ventricular dilation (41.6% ± 1.4% to 51.5% ± 3.5%; P = NS for interaction). There was no significant difference in the degree of PVC suppression or LVEF improvement between those treated with flecainide (24.5% ± 5.8% reduction in PVC burden, 12.2% ± 2.3% improvement in LVEF) vs those treated with propafenone (29.4% ± 6.3% reduction in PVC burden, 11.2% ± 5.4% improvement in LVEF; P = NS for interaction). LVEF improved continuously over the entire follow-up period (Figure 3). Eight patients (4 propafenone, 4 flecainide) discontinued IC-AAD during the study period (6 due to ineffectiveness, 1 due to side effects, and 1 due to loss of insurance). Among these 8 patients, catheter ablation was performed in 2 and amiodarone initiated in 2.
      Figure thumbnail gr2
      Figure 2Premature ventricular contraction (PVC) burden and left ventricular ejection fraction (LVEF) before and after Class IC antiarrhythmic drug (IC-AAD) treatment. A: PVC burden before and after treatment with IC-AAD among the entire study cohort. B: LVEF before and after treatment with IC-AAD among the entire study cohort. C: PVC burden before and after treatment with IC-AAD among the 7 patients with myocardial delayed enhancement on cardiac magnetic resonance imaging (MRI). D: LVEF before and after treatment with IC-AAD among the 7 patients with myocardial delayed enhancement on cardiac MRI.
      Figure thumbnail gr3
      Figure 3Time course of improvement in left ventricular ejection fraction (LVEF) after Class IC antiarrhythmic drug initiation. Mean LVEF for the entire study cohort is displayed at each time point.
      The 7 patients with myocardial delayed enhancement on cardiac MRI (all <5% of total myocardium) derived similar benefit in terms of PVC suppression (38.8% ± 5.5% to 3.6% ± 3.2%; P <.01) and LVEF improvement (36.8% ± 4.3% to 51.7% ± 3.7%; P <.01) (Figures 2C and 2D, respectively). No serious adverse events occurred in patients while on IC-AAD, including death or sustained ventricular arrhythmias.

      Discussion

      In this cohort of 20 patients with suspected PVC-CM, flecainide and propafenone significantly reduced PVC burden. These patients subsequently experienced a significant increase in LVEF. Of note, no sustained ventricular arrhythmias or deaths occurred over mean follow-up of nearly 4 years.
      The IC-AADs are known to effectively suppress ventricular ectopy with good tolerance and low risk of organ toxicity.
      • Zhong L.
      • Lee Y.H.
      • Huang X.M.
      • Asirvatham S.J.
      • Shen W.K.
      • Friedman P.A.
      • Hodge D.O.
      • Slusser J.P.
      • Song Z.Y.
      • Packer D.L.
      • Cha Y.M.
      Relative efficacy of catheter ablation vs antiarrhythmic drugs in treating premature ventricular contractions: a single-center retrospective study.
      • Prystowsky E.N.
      • Padanilam B.J.
      • Fogel R.I.
      Treatment of atrial fibrillation.
      In patients without structural heart disease, more than 90% of those treated with flecainide or propafenone have a significant (>70%) reduction in PVC burden.
      • Capucci A.
      • Di Pasquale G.
      • Boriani G.
      • Carini G.
      • Balducelli M.
      • Frabetti L.
      • Carozzi A.
      • Finzi A.
      • Pinelli G.
      • Magnani B.
      A double-blind crossover comparison of flecainide and slow-release mexiletine in the treatment of stable premature ventricular complexes.
      • Zhong L.
      • Lee Y.H.
      • Huang X.M.
      • Asirvatham S.J.
      • Shen W.K.
      • Friedman P.A.
      • Hodge D.O.
      • Slusser J.P.
      • Song Z.Y.
      • Packer D.L.
      • Cha Y.M.
      Relative efficacy of catheter ablation vs antiarrhythmic drugs in treating premature ventricular contractions: a single-center retrospective study.
      We found a similarly potent suppressive effect of IC-AADs. Of note, the effectiveness of IC-AADs has been described to wane in some patients over time, which occurred in 3 of the patients in our study.
      • Ling Z.
      • Liu Z.
      • Su L.
      • et al.
      Radiofrequency ablation versus antiarrhythmic medication for treatment of ventricular premature beats from the right ventricular outflow tract: prospective randomized study.
      These three patients experienced initial PVC suppression with IC-AAD (2 flecainide, 1 propafenone), with increased burden 9 to 12 months later, requiring a change in treatment.
      After publication of the CAST study, guidelines have discouraged use of IC-AADs, not only in patients with ischemic cardiomyopathy but also among those with nonischemic cardiomyopathy.
      • January C.T.
      • Wann L.S.
      • Alpert J.S.
      • et al.
      2014 AHA/AC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society.
      Whether IC-AADs increase arrhythmia events and mortality in nonischemic cardiomyopathy remains unclear.
      • Mueller K.A.L.
      • Heinzmann D.
      • Klingel K.
      • et al.
      Histopathological and immunological characteristics of tachycardia-induced cardiomyopathy.
      In fact, sustained ventricular arrhythmias decreased, rather than increased, in patients with arrhythmogenic right ventricular cardiomyopathy treated with flecainide.
      • Ermakov S.
      • Gerstenfeld E.P.
      • Svetlichnaya Y.
      • Scheinman M.M.
      Use of flecainide in combination antiarrhythmic therapy in patients with arrhythmogenic right ventricular cardiomyopathy.
      The increased mortality observed among patients postmyocardial infarction in CAST may be related to the interaction of IC-AAD with residual ischemia. Faber et al
      • Faber T.S.
      • Zehender M.
      • Krahnefeld O.
      • Daisenberger K.
      • Meinertz T.
      • Just H.
      Propafenone during acute myocardial ischemia in patients: a double-blind, randomized, placebo-controlled study.
      reported a randomized, double-blind study of 98 patients undergoing percutaneous coronary intervention who were pretreated with propafenone or placebo. During ischemia, particularly occlusion of the left anterior descending coronary artery, propafenone led to a significant increase in QT dispersion, which the investigators attributed to inhomogeneous ventricular repolarization and a clinically important interaction between myocardial ischemia, repolarization, and propafenone.
      • Faber T.S.
      • Zehender M.
      • Krahnefeld O.
      • Daisenberger K.
      • Meinertz T.
      • Just H.
      Propafenone during acute myocardial ischemia in patients: a double-blind, randomized, placebo-controlled study.
      In a CAST substudy, the presence of non–Q-wave infarction was associated with death, suggesting that a drug–ischemia interaction rather than a drug–scar interaction mediates the risk for death.
      • Akiyama T.
      • Pawitan Y.
      • Greenberg H.
      • Kuo C.S.
      • Reynolds-Haertle R.A.
      Increased risk of death and cardiac arrest from encainide and flecainide in patients after non-q-wave acute myocardial infarction in the cardiac arrhythmia suppression trial. Cast investigators.
      This was confirmed in a larger analysis of the CAST population, which showed that both non–Q-wave myocardial infarction and angina were associated with subsequent death, further supporting a link between ischemia and electrical instability.
      • Anderson J.L.
      • Platia E.V.
      • Hallstrom A.
      • Henthorn R.W.
      • Buckingham T.A.
      • Carlson M.D.
      • Carson P.E.
      Interaction of baseline characteristics with the hazard of encainide, flecainide, and moricizine therapy in patients with myocardial infarction. A possible explanation for increased mortality in the Cardiac Arrhythmia Suppression Trial (CAST).
      Finally, in the European Rythmol/Rytmonorm Atrial Fibrillation Trial (ERAFT), patients with previous myocardial infarction were included, and no increased mortality or proarrhythmia was observed in the propafenone arm.
      • Meinertz T.
      • Lip G.Y.
      • Lombardi F.
      • Sadowski Z.P.
      • Kalsch B.
      • Camez A.
      • Hewkin A.
      • Eberle S.
      Efficacy and safety of propafenone sustained release in the prophylaxis of symptomatic paroxysmal atrial fibrillation (the European Rythmol/Rytmonorm Atrial Fibrillation Trial [ERAFT] study).
      Thus, available evidence suggests that ischemia and not the presence of structural heart disease per se increases the risk of using IC-AADs in patients with structural heart disease. This makes considering the use of these drugs more rational in patients with nonischemic cardiomyopathy.
      PVC-CM is a unique form of nonischemic cardiomyopathy in that it can be reversed with PVC suppression.
      • Penela D.
      • Van Huls Van Taxis C.
      • Aguinaga L.
      • et al.
      Neurohormonal, structural, and functional recovery pattern after premature ventricular complex ablation is independent of structural heart disease status in patients with depressed left ventricular ejection fraction: a prospective multicenter study.
      Thus, even if IC-AADs increase the risk of sudden cardiac death while LVEF is depressed, this period of risk may be transient only until LVEF recovers. Furthermore, the risk during this transition period could be mitigated through the use of wearable defibrillators. For example, when patients with suspected PVC-CM fail catheter ablation, a IC-AAD and a wearable defibrillator can be prescribed. If LVEF normalizes, the wearable defibrillator can then be discontinued. If LVEF remains depressed, then the IC-AAD could be discontinued and alternative treatment pursued, such as repeat ablation, Class III AAD, and/or an ICD.
      Seven of our patients had myocardial delayed enhancement on MRI, yet LVEF in 6 of these patients improved after IC-AAD initiation. Others have reported that scar on MRI is useful for identifying the ventricular arrhythmia site of origin but not for predicting recovery of LVEF.
      • El Kadri M.
      • Yokokawa M.
      • Labounty T.
      • et al.
      Effect of ablation of frequent premature ventricular complexes on left ventricular function in patients with nonischemic cardiomyopathy.
      On the other hand, the extent of myocardial delayed enhancement has been correlated to risk of sudden cardiac death in other populations.
      • Halliday B.P.
      • Gulati A.
      • Ali A.
      • et al.
      Association between midwall late gadolinium enhancement and sudden cardiac death in patients with dilated cardiomyopathy and mild and moderate left ventricular systolic dysfunction.
      In the present cohort, it is important to note that the burden of scar was <5% in each patient. Thus, conclusions should be limited regarding the impact of more extensive myocardial delayed enhancement on reversibility of PVC-CM and safety of IC-AADs.

      Study limitations

      Our cohort is single center and modestly sized. Given limited power, conclusions regarding the safety of IC-AADs in PVC-CM are limited, particularly with regard to rare events such as sudden cardiac death. Significantly larger studies are needed to confidently establish safety. It also should be noted that our clinical practice is to perform screening stress tests for patients before initiating IC-AADs and at regular intervals, to exclude coronary ischemia. Additionally, given our retrospective, observational design, there is potential for selection bias, wherein the 20 patients treated with IC-AADs differ in other significant ways from the larger population with PVC-CM.

      Conclusion

      In a modest-size cohort of patients suspected of having PVC-CM, IC-AADs effectively suppressed PVCs, leading to substantial LVEF recovery, without any significant adverse events. Larger studies are needed to confidently establish the safety of this approach.

      Appendix. Supplementary Data

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      Linked Article

      • To the Editor— Flecainide and propafenone: Good twins for premature ventricular contractions’ killing but not exactly superimposable
        Heart RhythmVol. 15Issue 9
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          We have read with great interest the article by Hyman et al1 dealing with successful use of class IC antiarrhythmic drugs (IC-AADs) in patients with premature ventricular contraction (PVC)–induced cardiomyopathy. Their results are of great practical interest despite the small population studied. Even though the long-term efficacy of IC-AADs as PVC killer is well known since 1980s,2 their use in people with left ventricular dysfunction is not established at all. We have 2 comments for the sake of practical use.
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      • Class IC antiarrhythmic agents in structural heart disease: Is nothing CAST in stone?
        Heart RhythmVol. 15Issue 2
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          The development or worsening of cardiomyopathy due to frequent premature ventricular contractions (PVCs) is a well-recognized clinical entity.1 Suppression of PVCs with radiofrequency ablation or drug therapy can improve or even normalize ventricular dysfunction in patients with this form of cardiomyopathy.2–5 Suppression of PVCs with pharmacologic therapy becomes the logical therapeutic option in patients initially taking a noninvasive approach. Because drug selection is principally guided by safety concerns, a trial of beta-blockers is a logical and commonly used treatment strategy.
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