郑刚教授：一文了解，室性早搏诱发的心肌病|缺血性|心律失常

虽然20世纪初首次在心房纤颤（AF）患者中描述了心律失常引起的心肌病（T-CM），但直到90年后的1998年才发现室性早搏诱发的心肌病（PVC-CM）[1-2]。在分别于1962年和2011年开发的动物实验模型[3-4]证明这些持续的心律失常可能导致结构正常心脏的左心室功能障碍之前，人们对心律失常和心肌病之间的病因关系仍持怀疑态度。PVC-CM被《2016年美国心脏协会扩张型心肌病科学声明》[1]认定为一种独特的临床实体。PVC-CM被定义为由频繁的PVC引起的左心室功能障碍。叠加的PVC-CM可被定义为因既往已知心肌病患者的频发PVC而使左室射血分数（LVEF）恶化至少10%。频发PVC通常被认为是＞5%的PVC负荷，PVC负荷≥10%则通常被认为是高且显著的，会引发PVC-CM。作者：郑刚 泰达国际心血管病医院本文为作者授权医脉通发布，未经授权请勿转载。PART01PVC和PVC-CM的流行病学在没有心脏病的患者中，12导联心电图在10s内PVC的发病率估计在1%~4%之间[5-6]。在动态心电图记录期间，PVC的患病率明显更高（在24h和48h动态心电图监测中，PVC的患病率分别为40%和75%）[6]。这可以通过PVC频率随时间的显著变化来解释[7]。此外，PVC患病率还与年龄有关，11岁以下儿童的患病率<1%，75岁及以上受试者的患病率接近70%[5-6]。PVC更常见于心梗后、冠心病以及扩张型心肌病和心衰患者中[5,8]。几乎一半的II级和III级心衰患者有频发PVC（>1000个PVC/d）[8]。临床研究发现，即使在校正年龄和其他心电图异常后，高PVC负荷也与左心室功能障碍、收缩性心衰（HR=1.48-1.8）和死亡率（HR= 1.31）[9-15]增加有关[5]。令人惊讶的是，据报道，在没有其他心血管风险因素的情况下，<65岁的PVC受试者发生收缩性心衰的风险增加了6倍（HR=6.5）[16]，而心率>100 bpm的受试者死亡率更高[5]。对ARIC研究的二次分析显示，PVC高负荷患者发生卒中的风险显著增加（HR=1.71），且或可归因于房室重构[17]。在PVC负荷＞10%的患者中，PVC-CM的患病率为7%[18]。然而，PVC-CM的患病率可能被低估[6]。临床研究报告，在转诊进行射频消融（RFA）的PVC患者中，有9%~30%的患者被诊断为PVC-CM[9,12,19-21]。对CHF-STAT研究的二次分析[22]（>10 PVCs/h，LVEF<40%）同样显示，所有心肌病患者的PVC-CM发生率约为40%，非缺血性心肌病患者的PVC-CM发生率则高达66%[23]。这些数据提示，频发PVC是收缩性心衰和死亡率增加的一个重要且可改变的风险因素。PART02PVC的急性影响及PVC-CM的潜在诱因PVC具有先天性的急性内在影响，包括心律不规则、早搏后强化作用（post-extrasystolic potentiation）、左心室不同步、房室不同步和心率增快[14,24-28]。目前，尚未明确这些因素是否可以通过改变血液动力学和自主神经系统（ANS）的触发因素来助力PVC-CM的发展，也不清楚其是如何导致PVC-CM发展的[29-30]。早搏后强化作用、心律不规则、左心室不同步、房室分离和ANS改变可能是PVC-CM的潜在诱因。PVC-CM和T-CM之间细胞和电重构的差异提示，心动过速不可能是PVC-CM的唯一诱因。早搏后强化和心律不规则的作用可以通过评估缺乏左心室不同步的频繁起搏的慢性影响来解决。尽管Pacchia等[31]证明心肌病可由房早二联律诱发，但在临床和其他动物模型中尚未观察到这一点[32-34]。这些发现表明，心律不规则和早搏后强化作用在PVC-CM的病理生理学中起着有限的作用（如果有的话）。Gerstenfeld等[33]在二元PVC动物模型中证明，左心室功能障碍在来自左心室外膜的PVC中更为明显，因为与心内膜右心室（RV）游离壁相比，它们表现出更高程度的不同步性[33]。这也与临床研究一致，其中心外膜PVC和QRS>150ms是PVC-CM的预测因素[35-36]。PART03PVC-CM的潜在机制与T-CM相比，PVC-CM细胞机制尚未得到广泛研究。然而，很明显，与包括T-CM在内的其他模型相比，组织病理学和细胞特征存在明显差异[3-4,33,37-38]。PVC-CM收缩功能障碍的主要原因似乎是钙诱导的钙释放机制本身的紊乱，L型钙通道和Ryanodine受体功能改变也被认为是一种潜在的机制。与其他心肌病相似，该PVC-CM模型揭示了电生理重塑。组织病理学异常是明显的，没有炎症或细胞凋亡增加的证据，也没有纤维化。线粒体研究表明氧化磷酸化没有变化[3]。在临床实践中，PVC-CM患者的心脏核磁显像（MRI）显示无瘢痕，也支持了上述结果[12]。这些发现进一步证实了原发性功能异常是这种可逆心肌病的主要机制[3,12,33,37-38]。然而，是否所有的细胞和分子变化都是对心肌病的反应，而不是心肌病的原因尚不清楚。PART04PVC-CM的预测因子PVC负荷已被证明是PVC-CM的主要预测因素（PVC负荷每增加1%，OR=1.25）[9,19,36-40]。两项主要研究表明，＞16%和24%的PVC负荷最能识别诊断为PVC-CM的患者（敏感性和特异性分别为79%~100%和78%~87%）[9,18]。虽然多项研究显示，诱导PVC-CM需要至少10%的PVC负荷[9,18,41-43]，但也有研究对此提出了质疑，这些研究显示PVC负荷低至6%~8%时左心室功能才能得到改善[22,25,39,44-46]。此外，动态心电图监测的时长具有重要意义，将持续时间从24h增加到7d可以使达到10%阈值的患者数量增加一倍[47]。值得一提的是，一些患者即使在PVC负荷很高的情况下也不会出现心肌病，提示其他患者特征和/或PVC特征也可能在PVC-CM的病理生理学中发挥作用。一些其他PVC特征已被发现是PVC-CM的独立预测因素，如男性[48]、无症状（调整OR=13.1）或心悸持续时间>30个月、PVC耦合间隔的变异性（OR=1.04）[13]、PVC的QRS持续时间>150ms和心外膜起源[11,18-19,35-36,40,48-49]。其他不太常见的独立预测因子是体重指数（BMI）>30kg/m2（OR=3.03）[13]、昼夜节律PVC分布的变异性较小（OR=16.3）[50]和逆行P波的存在（OR=2.79）[40]。此外，PVC期间的房室不同步可能是一个潜在的预测因素，但仍有待研究[27,40]。除了PVC负荷外，大多数预测因素的相关报道并不统一，反映了不同人群的异质性。尽管还需要进一步验证，但已经开发了PVC-CM指数，包括PVC负荷、PVC-QRS宽度和心外膜起源，试图识别出患有PVC-CM的高概率患者[36]。尽管短的PVC偶联间隔与特发性室颤有关[51]，但大多数研究尚未发现PVC偶联间隔和心肌病之间的明确关系[11]。一些研究提示interpolated PVC或耦合间期<450ms或为PVC-CM的预测因素[41,52]；有些研究还显示，PVC偶联间期变异性（离散度）不仅与更高的PVC-CM风险相关，而且与心血管死亡率相关[13,53-54]。除心外膜起源外，其他PVC起源位置可能不是PVC-CM的预测因素[19,41]。大型系列研究发现，对于PVC-CM患者，分别有24%、21%、28%、7%、5%和4%的PVC起源于冠状窦（心外膜）、右心室（RV）流出道，左心室（RV）流出道、二尖瓣环（心内膜）RV/LV隔膜和RV/LV心尖。遗传易感性也可以解释为什么一些患者倾向于发展为PVC- CM，而另一些患者即使有类似的PVC负担却没有发展为PVC-CM，如钠通道Nav1.5亚基的R222Q错义变体，导致更大和更早的钠电流，被归因于浦肯野的速率依赖性异位，并与胺碘酮或氟卡尼治疗后可逆的心肌病相关[55]。PART05PVC-CM的临床表现PVC-CM发展的时间进程尚不清楚，估计在数月至数年内[36,40,49]。动物实验显示，持续高PVC负荷（33%~50%）的动物可在4周内发展为心肌病[3,24]，但在人类研究并不一致。PVC-CM患者的临床表现各异，从无症状或模糊症状到心衰甚至晕厥。目前尚未明确患者有无症状的机制，但PVC偶联间隔比<0.5（PVC偶联间隔/窦偶联间隔比）被认为是出现临床症状的重要标志[56]。PVC-CM患者可能出现轻至中度左心室收缩功能障碍、左心室扩张、轻度MR和左心房扩大，可在消除PVC后2~12周内消失[3,15,24]。PART06诊断和影像学特征PVC-CM是一种排除性诊断，在PVC负荷＞10%，尤其是非缺血性CM患者中应该被怀疑。在疑似患者中，超声心动图和PVC特征有助于识别这些患者[1]。心电图，尤其是长程动态心电图对提高PVC负荷诊断率同样至关重要。心脏成像是识别左心室功能障碍和高PVC负荷（≥10%）患者的关键。晚期钆增强的心脏MR具有识别瘢痕和量化瘢痕负荷的优势，这反过来又可预测对PVC抑制的反应[59]。此外，详细的病史询问和相关检测，有助于排除心肌病的其他病因。除不规则的心音和轻微的心衰迹象外，患者的体格检查结果通常正常。PART07PVC-CM的治疗目前，RFA或抗心律失常药物（AADs）的PVC抑制策略是一种广泛接受的干预措施，用于治疗可能由频发PVC引起或加重的心肌病[58]。然而，在没有左心室功能障碍（LVEF≥50%）、症状或特发性室颤的情况下，对频发PVC（负荷≥10%）的治疗尚不明确。RFA和AADs抑制PVC的长期成功率相似，约为70%~80%[19,22,36,41,43,66]。成功的RFA可能局限于起源于乳头肌、心外膜或附近关键结构（如冠状动脉和传导系统）的PVC患者[14,19,41]。因此，大约5%~15%的RFA患者可能需要AADs治疗[41]。PVC抑制策略（RFA或AADs）总体风险较低。据报道，RFA的并发症发生率在5%~8%之间，但AADs的停用率接近10%，这是由于短期和长期副作用[19,41,59,66-67]以及可能随着时间的推移而降低的疗效[68]。RFA反应的独立预测因素包括消融成功（OR=15.7）、心肌瘢痕量<9gm（OR=0.9）和平均PVC负荷减少（OR=1.09）[59,66]；这些均支持使用具有晚期钆增强的心脏MR来评估瘢痕负担，以预测PVC抑制的应答者与非应答者。然而，如果PVC负荷显著减少（>20%），心肌瘢痕的存在似乎与预测反应不太相关[59]。相反，PVC位置似乎不能预测LVEF的改善[67]。最近，通过有创血压监测评估的早搏后强化作用被描述为RFA后左心室功能恢复的预测指标[71]。多项临床试验一致表明，应用AADs抑制PVC后，左心室功能显著增强，范围为10%~13%[22,41]。然而，CAST试验表明，在心梗后PVC频发的患者中，使用IC类AADs会增加死亡率，不鼓励在缺血性和非缺血性心肌病患者中使用，但GESICA、CAMIAT和CHF STAT试验表明，心梗后使用胺碘酮可以降低非缺血性心肌病的发生[22,69]。虽然现有文献支持通过消除PVC来改善左心室功能和症状，但有限的数据表明，PVC抑制会改变包括心衰和死亡在内的心血管事件风险[72-73]。未来尚需进行进一步试验，以了解如何最好地治疗频发PVC和心肌病患者[70,72]。PART08PVC-CM患者随访由缺乏PVC-CM发展潜在风险的数据，因此患者需要每6~12个月进行一次随访，如果出现心衰症状，则需要更密切地随访。在随访时，应重复超声心动图，以确认左心室功能正常，同时应考虑长程动态心电图监测以重新评估PVC负荷。专家简介郑刚 教授•现任泰达国际心血管病医院特聘专家，济兴医院副院长•中国高血压联盟理事，中国心力衰竭学会委员，中国老年医学会高血压分会天津工作组副组长、中国医疗保健国际交流促进会高血压分会委员。天津医学会心血管病专业委员会委员，天津医学会老年病专业委员会常委。天津市医师协会高血压专业委员会常委，天津市医师协会老年病专业委员会委员，天津市医师协会心力衰竭专业委员，天津市医师协会心血管内科医师分会双心专业委员会委员。天津市心脏学会理事、天津市心律学会第一届委员会委员，天津市房颤中心联盟常委。天津市医药学专家协会第一届心血管专业委员会委员，天津市药理学会临床心血管药理专业委员会常委。天津市中西医结合学会心血管疾病专业委员会常委•《中华老年心脑血管病杂志》编委，《中华临床 医师杂志》（电子版）特邀审稿专家，《中华诊断学电子杂志》审稿专家，《华夏医学》杂志副主编，《中国心血管杂志》常务编委，《中国心血管病研究》杂志第四届编委，《世界临床药物》杂志编委、《医学综述》杂志会编委、《中国医药导报》杂志编委、《中国现代医生》杂志编委、《心血管外科杂志（电子版）》审稿专家•本人在专业期刊和心血管网发表文章948篇其中第一作者759篇，参加著书11部•获天津市2005年度“五一劳动奖章和奖状” 和 “天津市卫生行业第二届人民满意的好医生”称号参考文献1. Duffee DF, Shen WK, Smith HC. Suppression of frequent premature ventricular contractions and improvement of left ventricular function in patients with presumed idiopathic dilated cardiomyopathy. Mayo Clin Proc 1998;73:430–3.2. Chugh SS, Shen WK, Luria DM, Smith HC. First evidence of premature ventricular complex-induced cardiomyopathy: a potentially reversible cause of heart failure. J Cardiovasc Electrophysiol 2000; 11: 328–9.3. Huizar JF, Kaszala K, Potfay J et al. Left ventricular systolic dysfunction induced by ventricular ectopy: a novel model for premature ventricular contraction-induced cardiomyopathy. Circ Arrhythm Electrophysiol 2011;4:543–9.4. Shinbane JS, Wood MA, Jensen DN, Ellenbogen KA, Fitzpatrick AP, Scheinman MM. Tachycardia-induced cardiomyopathy: a review of animal models and clinical studies. J Am Coll Cardiol 1997;29:709–15.5. Engel G, Cho S, Ghayoumi A et al. Prognostic significance of PVCs and resting heart rate. Ann Noninvasive Electrocardiol 2007;12:121–9.6. Lee GK, Klarich KW, Grogan M, Cha YM. Premature ventricular contraction-induced cardiomyopathy: a treatable condition. Circ Arrhythm Electrophysiol 2012;5:229–36.7. Schmidt G, Ulm K, Barthel P, Goedel-Meinen L, Jahns G, Baedeker W. Spontaneous variability of simple and complex ventricular premature contractions during long time intervals in patients with severe organic heart disease. Circulation 1988;78:296–301.8. Chen T, Koene R, Benditt DG, Lu F. Ventricular ectopy in patients with left ventricular dysfunction: should it be treated? J Card Fail 2013;19:40–9.9. Baman TS, Lange DC, Ilg KJ et al. Relationship between burden of premature ventricular complexes and left ventricular function. Heart Rhythm 2010;7:865–9.10. Bogun F, Crawford T, Reich S et al. Radiofrequency ablation of frequent, idiopathic premature ventricular complexes: comparison with a control group without intervention. Heart Rhythm 2007;4:863–7.11. Del Carpio Munoz F, Syed FF, Noheria A et al. Characteristics of premature ventricular complexes as correlates of reduced left ventricular systolic function: study of the burden, duration, coupling interval, morphology and site of origin of PVCs. J Cardiovasc Electrophysiol 2011;22:791–8.12. Hasdemir C, Yuksel A, Camli D et al. Late gadolinium enhancement CMR in patients with tachycardia-induced cardiomyopathy caused by idiopathic ventricular arrhythmias. Pacing Clin Electrophysiol 2012;35:465–70.13. Kawamura M, Badhwar N, Vedantham V et al. Coupling interval dispersion and body mass index are independent predictors of idiopathic premature ventricular complex-induced cardiomyopathy. J Cardiovasc Electrophysiol 2014;25:756–62.14. Maeda S, Chik WW, Liang JJ et al. Recovery of renal dysfunction after catheter ablation of outflow tract ventricular arrhythmias in patients with ventricular premature depolarization-mediated cardiomyopathy. J Interv Card Electrophysiol 2017;48:43–50.15. Takemoto M, Yoshimura H, Ohba Y et al. 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 2005;45:1259–65.16. Agarwal V, Vittinghoff E, Whitman IR, Dewland TA, Dukes JW, Marcus GM. Relation Between Ventricular Premature Complexes and Incident Heart Failure. Am J Cardiol 2017;119:1238–1242.17. Agarwal SK, Heiss G, Rautaharju PM, Shahar E, Massing MW, Simpson RJ Jr. Premature ventricular complexes and the risk of incident stroke: the Atherosclerosis Risk In Communities (ARIC) Study. Stroke 2010;41:588–93.18. Hasdemir C, Ulucan C, Yavuzgil O et al. Tachycardia-induced cardiomyopathy in patients with idiopathic ventricular arrhythmias: the incidence, clinical and electrophysiologic characteristics,and the predictors. J Cardiovasc Electrophysiol 2011;22:663–8.19. Latchamsetty R, Yokokawa M, Morady F et al. Multicenter Outcomes for Catheter Ablation of Idiopathic Premature Ventricular Complexes. JACC Clin Electrophysiol 2015;1:116–123.20. Lu F, Benditt DG, Yu J, Graf B. Effects of catheter ablation of “asymptomatic” frequent ventricular premature complexes in patients with reduced (<48%) left ventricular ejection fraction. Am J Cardiol 2012;110:852–6.21. Yokokawa M, Good E, Crawford T et al. Recovery from left ventricular dysfunction after ablation of frequent premature ventricular complexes. Heart Rhythm 2013;10:172–5.22. Singh SN, Fletcher RD, Fisher SG et al. Amiodarone in patients with congestive heart failure and asymptomatic ventricular arrhythmia. Survival Trial of Antiarrhythmic Therapy in Congestive Heart Failure. N Engl J Med 1995;333:77–82.23. Huizar JF, Fisher SG, Kaszala K et al. Amiodarone is an Effective Treatment of PVC-Cardiomyopathy in the Veteran Population (Abstract 14667). Circulation 2017;136.24. Tan AY, Hu YL, Potfay J et al. Impact of ventricular ectopic burden in a premature ventricular contraction-induced cardiomyopathy animal model. Heart Rhythm 2016;13:755–61.25. Sadron Blaye-Felice M, Hamon D, Sacher F et al. Reversal of left ventricular dysfunction after ablation of premature ventricular contractions related parameters, paradoxes and exceptions to the rule. Int J Cardiol 2016;222:31–6.26. Potfay J, Kaszala K, Tan AY et al. Abnormal Left Ventricular Mechanics of Ventricular Ectopic Beats: Insights Into Origin and Coupling Interval in Premature Ventricular Contraction-Induced Cardiomyopathy. Circ Arrhythm Electrophysiol 2015;8:1194–200.27. Kuroki K, Tada H, Seo Y et al. Prediction and mechanism of frequent ventricular premature contractions related to haemodynamic deterioration. Eur J Heart Fail 2012;14:1112–20.28. Cooper MW. Postextrasystolic potentiation. Do we really know what it means and how to use it? Circulation 1993;88:2962–71.29. Hamon D, Rajendran PS, Chui RW et al. Premature Ventricular Contraction Coupling Interval Variability Destabilizes Cardiac Neuronal and Electrophysiological Control: Insights From imultaneous Cardioneural Mapping. Circ Arrhythm Electrophysiol 2017;10.30. Smith ML, Hamdan MH, Wasmund SL, Kneip CF, Joglar JA, Page RL. High-frequency ventricular ectopy can increase sympathetic neural activity in humans. Heart Rhythm 2010;7:497–503.31. Pacchia CF, Akoum NW, Wasmund S, Hamdan MH. Atrial bigeminy results in decreased left ventricular function: an insight into the mechanism of PVC-induced cardiomyopathy. Pacing Clin Electrophysiol 2012;35:1232–5.32. Kowgli NG, Jovin D, O’Quinn M et al. Neither Irregularity nor Tachycardia are Triggers of PVC-cardiomyopathy: Comparing Persistent Atrial and Ventricular Ectopy in an Animal Model. Heart Rhythm 2018;15:S594.33. Walters TE, Rahmutula D, Szilagyi J et al. Left Ventricular Dyssynchrony Predicts the Cardiomyopathy Associated with Premature Ventricular Contractions (In Press). J Am Coll Cardiol 201834. Akyeampong D, Tan AY, kaszala K, Ellenbogen KA, Huizar JF. Premature Atrial Contractions Are Not associated With Left Ventricular Dysfunction (Abstract 14896). Circulation 2016;134.35. Yokokawa M, Kim HM, Good E et al. Impact of QRS duration of frequent premature ventricular complexes on the development of cardiomyopathy. Heart Rhythm 2012;9:1460–4.36. Hamon D, Blaye-Felice MS, Bradfield JS et al. A New Combined Parameter to Predict Premature Ventricular Complexes Induced Cardiomyopathy: Impact and Recognition of Epicardial Origin. J Cardiovasc Electrophysiol 2016;27:709–17.37. Wang Y, Eltit JM, Kaszala K et al. Cellular Mechanism of Premature Ventricular Contraction-Induced Cardiomyopathy. Heart Rhythm 2014.38. Jiang M, Zhang M, Howren M et al. JPH-2 interacts with Cai-handling proteins and ion channels in dyads: Contribution to premature ventricular contraction-induced cardiomyopathy. Heart Rhythm 2016;13:743–52.39. Lee A, Denman R, Haqqani HM. Ventricular Ectopy in the Context of Left Ventricular Systolic Dysfunction: Risk Factors and Outcomes Following Catheter Ablation. Heart Lung Circ 2018.40. Ban JE, Park HC, Park JS et al. Electrocardiographic and electrophysiological characteristics of premature ventricular complexes associated with left ventricular dysfunction in patients without structural heart disease. Europace 2013;15:735–41.41. Zhong L, Lee YH, Huang XM et al. Relative efficacy of catheter ablation vs antiarrhythmic drugs in treating premature ventricular contractions: a single-center retrospective study. Heart Rhythm 2014;11:187–93.42. Penela D, Van Huls Van Taxis C, Van Huls Vans Taxis C 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. J Am Coll Cardiol 2013;62:1195–202.43. Penela D, Acosta J, Aguinaga L et al. Ablation of frequent PVC in patients meeting criteria for primary prevention ICD implant: Safety of withholding the implant. Heart Rhythm 2015;12:2434–42.44. Yarlagadda RK, Iwai S, Stein KM et al. Reversal of cardiomyopathy in patients with repetitive monomorphic ventricular ectopy originating from the right ventricular outflow tract. Circulation 2005;112:1092–7.45. Shanmugam N, Chua TP, Ward D. ‘Frequent’ ventricular bigeminy--a reversible cause of dilated cardiomyopathy. How frequent is ‘frequent’? Eur J Heart Fail 2006;8:869–73.46. Sarrazin JF, Labounty T, Kuhne M et al. Impact of radiofrequency ablation of frequent post-infarction premature ventricular complexes on left ventricular ejection fraction. Heart Rhythm 2009;6:1543–9.47. Loring Z, Hanna P, Pellegrini CN. Longer Ambulatory ECG Monitoring Increases Identification of Clinically Significant Ectopy. Pacing Clin Electrophysiol 2016;39:592–7.48. Yokokawa M, Kim HM, Good E et al. Relation of symptoms and symptom duration to premature ventricular complex-induced cardiomyopathy. Heart Rhythm 2012;9:92–5.49. Carballeira Pol L, Deyell MW, Frankel DS et al. Ventricular premature depolarization QRS duration as a new marker of risk for the development of ventricular premature depolarization-induced cardiomyopathy. Heart Rhythm 2014; 11:299–306.50. Bas HD, Baser K, Hoyt J et al. Effect of circadian variability in frequency of premature ventricular complexes on left ventricular function. Heart Rhythm 2016;13:98–102.51. Knecht S, Sacher F, Wright M et al. Long-term follow-up of idiopathic ventricular fibrillation ablation: a multicenter study. J Am Coll Cardiol 2009;54:522–8.52. Olgun H, Yokokawa M, Baman T et al. The role of interpolation in PVC-induced cardiomyopathy.Heart Rhythm 2011;8:1046–9.53. Lee CH, Park KH, Nam JH et al. Increased variability of the coupling interval of premature ventricular contractions as a predictor of cardiac mortality in patients with left ventricular dysfunction. Circ J 2015;79:2360–6.54. Bradfield JS, Homsi M, Shivkumar K, Miller JM. Coupling interval variability differentiates ventricular ectopic complexes arising in the aortic sinus of valsalva and great cardiac vein from other sources: mechanistic and arrhythmic risk implications. J Am Coll Cardiol 2014;63:2151–2158.55. Mann SA, Castro ML, Ohanian M et al. R222Q SCN5A mutation is associated with reversible ventricular ectopy and dilated cardiomyopathy. J Am Coll Cardiol 2012;60:1566–73.56. Hwang JK, Park SJ, On YK, Kim JS, Park KM. Clinical Characteristics and Features of Frequent Idiopathic Ventricular Premature Complexes in the Korean Population. Korean Circ J 2015;45:391–7.57. 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. Heart Rhythm 2015;12:706–13.58. Bozkurt B, Colvin M, Cook J et al. Current Diagnostic and Treatment Strategies for Specific Dilated Cardiomyopathies: A Scientific Statement From the American Heart Association. Circulation 2016;134:e579–e646.59. Penela D, Martinez M, Fernandez-Armenta J et al. Influence of myocardial scar on the response to frequent premature ventricular complex ablation. Heart 2018.60. Topaloglu S, Aras D, Cagli K et al. Evaluation of left ventricular diastolic functions in patients with frequent premature ventricular contractions from right ventricular outflow tract. Heart Vessels 2007;22:328–34.61. Wijnmaalen AP, Delgado V, Schalij MJ et al. Beneficial effects of catheter ablation on left ventricular and right ventricular function in patients with frequent premature ventricular contractions and preserved ejection fraction. Heart 2010;96:1275–80.62. Yao J, Xu J, Yong YH, Cao KJ, Chen SL, Xu D. Evaluation of global and regional left ventricular systolic function in patients with frequent isolated premature ventricular complexes from the right ventricular outflow tract. Chin Med J (Engl) 2012;125:214–20.53. Tung R, Bauer B, Schelbert H et al. Incidence of abnormal positron emission tomography in patients with unexplained cardiomyopathy and ventricular arrhythmias: The potential role of occult inflammation in arrhythmogenesis. Heart Rhythm 2015;12:2488–98.64. Chen Y, Wu S, Li W et al. Higher High-Sensitivity C Reactive Protein is Associated with Future Premature Ventricular Contraction: a Community Based Prospective Cohort Study. Scientific Reports 2018;8:1–7.65. Anastasiou-Nana MI, Menlove RL, Nanas JN, Anderson JL. Changes in spontaneous variability of ventricular ectopic activity as a function of time in patients with chronic arrhythmias. Circulation 1988;78:286–95. [PubMed: 2456167]66. Mountantonakis SE, Frankel DS, Gerstenfeld EP et al. Reversal of outflow tract ventricular premature depolarization-induced cardiomyopathy with ablation: effect of residual arrhythmia burden and preexisting cardiomyopathy on outcome. Heart Rhythm 2011;8:1608–14.67. Zang M, Zhang T, Mao J, Zhou S, He B. Beneficial effects of catheter ablation of frequent premature ventricular complexes on left ventricular function. Heart 2014;100:787–93.68. Hyman MC, Mustin D, Supple G et al. Class IC antiarrhythmic drugs for suspected premature ventricular contraction-induced cardiomyopathy. Heart Rhythm 2018;15:159–163.69. Naccarelli GV, Wolbrette DL, Patel HM, Luck JC. Amiodarone: clinical trials. Curr Opin Cardiol 2000;15:64–72.70. Penela D, Acosta J, Aguinaga L et al. Ablation of frequent PVC in patients meeting criteria for primary prevention ICD implant: Safety of withholding the implant. Heart Rhythm 2015;12:2434–42.71. Krishnan B, Sankar A, Anand I et al. Post-Extrasystolic Potentiation as a Predictor of Recovery of Left Ventricular Dysfunction After Radiofrequency Catheter Ablation. JACC Clin Electrophysiol 2017;3:1283–1291.72. Dukes JW, Dewland TA, Vittinghoff E et al. Ventricular Ectopy as a Predictor of Heart Failure and Death. J Am Coll Cardiol 2015;66:101–9.73. Noda T, Shimizu W, Taguchi A et al. 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 2005;46:1288–94.74. Meinertz T, Hofmann T, Kasper W et al. Significance of ventricular arrhythmias in idiopathic dilated cardiomyopathy. Am J Cardiol 1984;53:902–7.医脉通是专业的在线医生平台，“感知世界医学脉搏，助力中国临床决策”是平台的使命。医脉通旗下拥有「临床指南」「用药参考」「医学文献王」「医知源」「e研通」「e脉播」等系列产品，全面满足医学工作者临床决策、获取新知及提升科研效率等方面的需求。