Pleomorphism during Ventricular Tachycardia: A Distinguishing Feature between Cardiac Sarcoidosis and Idiopathic VT SUBHANARAYAN PANDA, M.D., D.M.,* DALJEET KAUR, M.D., D.M.,* KRISHNAMOHAN LALUKOTA, M.B.B.S.,* GOMATHI SUNDAR, P.G., (P.A.),* BEHZAD B. PAVRI, M.D.,† and CALAMBUR NARASIMHAN, M.D., D.M.* *From the CARE Hospital, Division of Cardiac Electrophysiology, Hyderabad, India; and †Thomas Jefferson University Hospital, Philadelphia, Pennsylvania Background: Ventricular tachycardia (VT), a common manifestation of cardiac sarcoidosis (CS), is associated with high morbidity and mortality. It could be mistaken for idiopathic VT (IVT) in the absence of systemic manifestations and overt cardiac structural abnormality. We studied the electrocardiogram (ECG) characteristics of VT in CS that may distinguish from IVT and also explored the relationship of the ECG characteristics with imaging findings in patients with CS. Methods and Results: Twelve-lead ECG characteristics of VT in CS patients (Group I = 37) were compared with IVT (Group II = 49). QRS duration, axis, morphology, VT cycle length, and cycle length variation (CLV) were analyzed. In Group I, 18 (49%) had pleomorphic VT (PLVT) and none in Group II. CLV was seen only in Group I (24%). Mean QRS duration (milliseconds) and cycle length (milliseconds) were greater in Group I (QRSd 152.49 [39.3] vs 140.9 [19.2]) and (332.2 [136.5] vs 312.9 [56.2]), the differences not statistically significant. In Group I, myocardial scar was present in 22 of 25 patients and myocardial inflammation in 28 of 29 patients as assessed by cardiac magnetic resonance imaging (delayed enhancement) and 18-fluorodeoxyglucose positron emission computed tomography, respectively. PLVT was seen more commonly in patients with involvement of >1 myocardial region than focal involvement (58% and 30%, respectively, with myocardial scar and 50% and 40%, respectively, with myocardial inflammation). Conclusion: Pleomorphism and CLV during VT may be distinguishing features between IVT and VTs of CS origin. (PACE 2015; 38:694–699) pleomorphic, ventricular tachycardia, cardiac sarcoidosis, idiopathic, cycle length
Introduction Cardiac sarcoidosis (CS) is a potentially lifethreatening disease with ventricular tachycardia (VT) being an important cause of morbidity and sudden cardiac death.1,2 Reentrant substrates causing VT are not only found in the chronic healed phase of CS but also in the active phase of the disease.3 Early recognition of the disease, especially in the active phase with prompt initiation of steroid therapy, yields better outcome by preventing ventricular scarring and ventricular dysfunction.4 Financial support: none. Conflict of Interest: none to declare. Address for reprints: Calambur Narasimhan, M.D., D.M., Division of Cardiac Electrophysiology, CARE Hospital, Road No. 1, Banjara Hills, Hyderabad 500034, India. Fax: 04030418488; e-mail: [email protected] Received November 8, 2014; revised February 23, 2015; accepted March 1, 2015. doi: 10.1111/pace.12626
In the early stages of the disease, CS can be mistaken as idiopathic VT (IVT) as it can present as sustained monomorphic VT (MMVT) in patients with preserved left ventricular (LV) systolic function.4 It is important to distinguish VT due to CS and IVT, as the prognosis and treatment of these two conditions are different.4–6 In clinical practice, VTs with structurally normal heart are often labeled as idiopathic if coronary artery disease is ruled out, but occult pathology such as CS can be easily missed when patients present without any systemic manifestation. Imaging modalities like delayed enhancement cardiac magnetic resonance imaging (DE-CMR) and 18-fluorodeoxyglucose positron emission tomographic scan of the chest (18-FDG PET-CT) are not performed routinely. Due to this, any underlying pathology may be missed and the tachycardia may be erroneously labeled “idiopathic,” resulting in serious implications. To obtain insights into underlying pathophysiology of many cardiac conditions, physicians have relied on the electrocardiogram (ECG) for more than half a century. Prior publications have
©2015 Wiley Periodicals, Inc. 694
June 2015
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PLEOMORPHIC VT IN CARDIAC SARCOIDOSIS
reported either polymorphic7 or MMVT8,9 in patients with CS. We observed pleomorphic VT (PLVT) in some of our patients diagnosed with CS. This prompted us to systematically review the VT ECGs to identify if pleomorphism or any ECG characteristics that may aid in distinguishing IVT from VT due to CS. We also studied the characteristics of VT in CS patients in relation to their imaging findings (DE-CMR and 18-FDG PET-CT). Methods This is a retrospective study approved by the Institutional Ethics Committee. Patient Population From June 2009 until December 2013, consecutive patients who presented with sustained VT and were diagnosed with CS formed the study group (Group I). Diagnosis of sarcoidosis was confirmed by histopathological examination of enlarged intrathoracic lymph nodes elicited by 18FDG PET-CT or DE-CMR. Patients with IVT formed Group II. The VT was labeled idiopathic when cardiac abnormalities were definitively excluded by echocardiogram, coronary angiogram, DE-CMR, and/or 18-FDG PET-CT. VT due to metabolic and electrolyte abnormalities or any other cause were excluded. Imaging Methodology Contrast-enhanced 64-slice computed tomogram (Siemens, Erlangen, Germany) was used to assess ongoing myocardial inflammation. Resting PET study was done after administration of 18-fluorodeoxyglucose in conjunction with the computed tomogram. In order to minimize FDG uptake by normal myocardial tissues, the test was done after a low carbohydrate, high protein, and high fat diet for a day followed by at least 12 hours of fasting. High 18-FDG uptake in the myocardium was interpreted as inflammation; matched perfusion and metabolism defects were interpreted as scar. DE-CMR was done with a 1.5-T scanner (Siemens) in patients without prior implanted devices. ECG Analysis Twelve-lead ECGs of VT (recorded at 25 mm/s paper speed) during the presenting episode were analyzed. The ECGs were digitally scanned and measurements made with the use of digital calipers (Cardio Calipers version 3.3; Iconico Inc., New York, NY, USA). ECGs were analyzed by two independent observers blinded to the diagnosis of the disease and results of imaging studies. Discrepancies in observations were resolved by mutual consensus.
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Figure 1. (A) Monomorphic ventricular tachycardia— QRS morphology is the same from beat to beat (B1), (B2), and (B3). Pleomorphic ventricular tachycardia— examples (C). Polymorphic ventricular tachycardia— beat-to-beat variation in QRS morphology along with axis change. Numbering shows the repeating patterns of QRS complex morphologies in each example.
Definition of ECG Parameters MMVT: VT with a stable, single QRS morphology from beat to beat. PLVT: VT with more than one morphologically distinct QRS complex occurring during the same episode of VT, but the QRS not continuously changing10 (Fig. 1). This is different from polymorphic VT which has a continuously changing QRS configuration from beat to beat. QRS duration (QRSd): Interval measured from beginning of the Q to the end of S wave in the precordial leads. Cycle length: Average of cycle length of 10 consecutive cycles. Cycle length variation (CLV): Difference between longest R-R interval and shortest R-R interval ࣙ50 ms. Statistical Analysis Descriptive statistics for the categorical variables were performed by computing the frequencies (percentages) in each category. For the quantitative variables, approximate normality of the distribution was assessed. Variables with parametric distribution are presented as mean and standard deviation (SD), whereas those without parametric distribution as median (interquartile range [IQR]). Mean values of continuous variables with normal distribution were compared using unpaired two-tailed t-test. Categorical variables were compared using Fisher’s exact test. A P value of 1 myocardial region
N=10/29 (34%)
N=18/29 (62%)
MMVT (N=49/49)
No scar
Scar in 1 Scar in >1 myocardial region myocardial region
N=3**/25 (12%) N=10/25 (40%)
N=12/25 (48%)
PLVT
PLVT
PLVT
PLVT
PLVT
PLVT
0/1
4/10 (40%)
9/18 (50%)
1/3 (33%)
3/10 (30%)
7/12 (58%)
Figure 2. Figure shows the study flow, imaging results, and corresponding VT QRS configuration. CS = cardiac sarcoidosis; DE-CMR = delayed enhanced cardiac magnetic resonance imaging; 18-FDG PET-scan = 18fluorodeoxyglucose positron emission tomography; IVT = idiopathic ventricular tachycardia; MMVT = monomorphic ventricular tachycardia; PLVT = pleomorphic ventricular tachycardia; VT = ventricular tachycardia. *Myocardial scar present. **Myocardial inflammation present.
95 days) and for PET-CT, median 10 days (IQR: 25, range –7 to 133 days). Imaging findings are shown in Figure 2. Discussion We found VT ECG to be useful in distinguishing IVT from VT due to CS. In the absence of overt systemic involvement as in our group of patients, CS might be easily missed by an unsuspecting physician. VT with normal LV ejection fraction and absence of coronary artery disease is assumed to be idiopathic, but occult heart disease (sarcoidosis, right ventricular cardiomyopathy, etc.) must be excluded. CS often presents with sustained VT and preserved LV function.4 The characteristics of VT associated with CS have not been fully characterized. The observation of PLVT only in CS patients in our study is supported by a similar observation in a previous study by Suzuki.11 In that study,
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none of the IVTs had pleomorphism as opposed to 19 of 42 of PLVT observed in patients with various underlying cardiac conditions, viz., myocardial infarction, hypertrophic cardiomyopathy, dilated cardiomyopathy, alcoholic cardiomyopathy, right ventricular dysplasia, postoperative tetralogy of Fallot. Although PLVT is not pathognomonic of any single condition, the presence of this feature in a structurally normal heart and in the absence of coronary artery disease could provide an important clue to alerting the treating physician for additional diagnostic work up. Since the original description of pleomorphism during VT in 1979,12 several mechanisms have been proposed. Josephson originally proposed that the mechanism of pleomorphism was a reentry circuit with different exit sites, that is, variable conduction out of one isthmus. Subsequently, it was shown that PLVTs could also arise from different but adjacent circuits in proximity with regions of shared conduction,
June 2015
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PANDA, ET AL.
that is, variable fusion.13 VTs that originate from anatomically distinct regions have also shown to cause pleomorphism.14,15 It has been hypothesized that pleomorphism, in the setting of functional barriers that are not fixed, can arise during ischemia which generally does not play a role in MMVT. A similar mechanism could be postulated for CS also. During the acute phase of the disease, inflammation and sarcoid granulomas in different regions of the myocardium may act as functional barriers in VT leading to different circuit length, exit sites, and variable VT morphology. In patients with CS, more than one of the above-mentioned mechanisms could be involved. Our results indicate that PLVT was observed more in comparison to MMVT among patients with more than one area of myocardial involvement. This shows that pleomorphic morphology may be due to multiple regions of myocardial involvement. Pleomorphism could also be indicative of early phase of the disease. Although in our study, the time from index VT to the imaging studies was short, PLVT was observed in nearly half of the patients. The LV function of these patients was also preserved. In addition, PLVT was observed in one patient who had only myocardial inflammation but no scar. Our findings are in contrast to the observation made in a substudy of the DATAS trial16 where it was reported that PLVT could be a consequence of deterioration in the clinical condition and ventricular function. On the other hand, we believe that irreversible heart failure could be the result of late recognition of CS when scarring on multiple regions of the myocardium sets in. In a study done by Naruse
et al.,17 myocardial scar was an independent predictor for recurrent VT in spite of corticosteroid therapy. Milman et al.18 described four cases of CS who underwent cardiac transplantation. In these patients, the diagnosis of sarcoid was established late. The explanted hearts showed diffuse fibrosis of the myocardium. We believe that early recognition and disease-specific treatment could have possibly limited the inflammation and scar formation. Limitations of the Study The retrospective nature of our study has its inherent limitations. The findings observed are not exclusive to CS and may be seen in other inflammatory/infiltrative myocardial disease. It would have been ideal for patients in the IVT group to have undergone both 18-FDG PET-CT scan and DE-CMR to rule out latent disease. In some patients this was not possible due to economical constraints and the decision to choose from the two imaging modalities were clinically driven. Therefore, we could not completely rule out the possibility of latent inflammation/scar in these patients. Finally, we have noted that some but not all CS patients had resolution of VT with steroids, but we do not have systematic follow-up on all patients and hence cannot report precisely on how CS patients responded to steroid therapy. Conclusion Pleomorphism and CLV in VT could be a distinguishing feature between CS and VTs of idiopathic origin, though the absence of this finding does not rule out the disease.
References 1. Roberts WC, McAllister HA Jr., Ferrans VJ. Sarcoidosis of the heart. A clinicopathologic study of 35 necropsy patients (group 1) and review of 78 previously described necropsy patients (group 11). Am J Med 1977;63:86–108. 2. Fleming H. Cardiac sarcoidosis. Semin Respir Med 1986;8:65–71. 3. Furushima H, Chinushi M, Sugiura H, Kasai H, Washizuka T, Aizawa Y. Ventricular tachyarrhythmia associated with cardiac sarcoidosis: Its mechanisms and outcome. Clin Cardiol 2004;27:217– 222. 4. Thachil A, Christopher J, Sastry BS, Reddy KN, Tourani VK, Hassan A, Raju BS, et al. Monomorphic ventricular tachycardia and mediastinaladenopathy due to granulomatous infiltration in patients with preserved ventricular function. J Am Coll Cardiol 2011;58:48–55. 5. Uusimaa P, Ylitalo K, Anttonen O, Kerola T, Virtanen V, P¨aa¨ kko¨ E, Raatikainen P. Ventricular tachyarrhythmiaas as a primary presentation of sarcoidosis. Europace 2008;10:760–766. 6. Mezaki T, Chinushi M, Washizuka T, Furushima H, Chinushi Y, Ebe K, Okumura H, et al. Discrepancy between inducibility of ventricular tachycardia and activity of cardiac sarcoidosis. Requirement of defibrillator implantation for the inactive stage of cardiac sarcoidosis. Intern Med 2001;40:731–735. 7. Okamoto M, Hashimoto M, Sueda T, Munemori M, Yamada T. Polymorphic ventricular tachycardia with cardiac sarcoidosis:
698
8.
9.
10.
11.
June 2015
Treatment with low-dose metoprolol and cibenzoline. Intern Med 1994;33:296–299. Koplan BA, Soejima K, Baughman K, Epstein LM, Stevenson WG. Refractory ventricular tachycardia secondary to cardiac sarcoid: Electrophysiologic characteristics, mapping, and ablation. Heart Rhythm 2006;3:924–929. Winters SL, Cohen M, Greenberg S, Stein B, Curwin J, Pe E, Gomes JA. Sustained ventricular tachycardia associated with sarcoidosis: Assessment of the underlying cardiac anatomy and the prospective utility of programmed ventricular stimulation, drug therapy and an implantable antitachycardia device. J Am Coll Cardiol 1991;18:937– 943. Aliot EM, Stevenson WG, Almendral-Garrote JM, Bogun F, Calkins CH, Delacretaz E, Della Bella P, et al. EHRA/HRS Expert Consensus on Catheter Ablation of Ventricular Arrhythmias. Developed in a partnership with the European Heart Rhythm Association (EHRA), a Registered Branch of the European Society of Cardiology (ESC), and the Heart Rhythm Society (HRS); in collaboration with the American College of Cardiology (ACC) and the American Heart Association (AHA). Heart Rhythm 2009;6: 886–933. Suzuki K. Clinical features of sustained ventricular tachycardia among various underlying heart diseases. Tohoku J Exp Med 1990;162:15–26.
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PLEOMORPHIC VT IN CARDIAC SARCOIDOSIS 12. Josephson ME, Horowitz LN, Farshidi A, Spielman SR, Michelson EL, Greenspan AM. Recurrent sustained ventricular tachycardia. 4. Pleomorphism. Circulation 1979;59:459– 468. 13. Fitzgerald DM, Friday KJ, Yeung-Lai-Wah JA. Myocardial regions of slow conduction participating in the reentrant circuit of multiple ventricular tachycardias: Report on ten patients. J Cardiovasc Electrophysiol 1991;2:193–206. 14. Josephson ME, Horowitz LN, Spielman SR, Greenspan AM, VandePol C, Harken AH. Comparison of endocardial catheter mapping with intraoperative mapping of ventricular tachycardia. Circulation 1980;61:395–404. 15. Miller JM, Kienzle MG, Harken AH, Josephson ME. Morphologically distinct sustained ventricular tachycardias in coronary artery
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disease: Significance and surgical results. J Am Coll Cardiol 1984;4:1073–1079. 16. Hadid C, Almendral J, Ortiz M, Schwab JO, Janko S, Mischke K, Arribas F, et al. Incidence, determinants, and prognostic implications of true pleomorphism of ventricular tachycardia in patients with implantable cardioverter-defibrillators: A substudy of the DATAS Trial. Circ Arrhythm Electrophysiol 2011; 4:33–42. 17. Naruse Y, Sekiguchi Y, Nogami A, Okada H, Yamauchi Y, Machino T, Kuroki K, et al. A systematic treatment approach to ventricular tachycardia in cardiac sarcoidosis. Circ Arrhythm Electrophysiol 2014;7:407–413. 18. Milman N, Andersen CB, Mortensen SA, Sander K. Cardiac sarcoidosis and heart transplantation: A report of four consecutive patients. Sarcoidosis Vasc Diffuse Lung Dis 2008;25:51–59.
June 2015
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Introduction Cardiac sarcoidosis (CS) is a potentially lifethreatening disease with ventricular tachycardia (VT) being an important cause of morbidity and sudden cardiac death.1,2 Reentrant substrates causing VT are not only found in the chronic healed phase of CS but also in the active phase of the disease.3 Early recognition of the disease, especially in the active phase with prompt initiation of steroid therapy, yields better outcome by preventing ventricular scarring and ventricular dysfunction.4 Financial support: none. Conflict of Interest: none to declare. Address for reprints: Calambur Narasimhan, M.D., D.M., Division of Cardiac Electrophysiology, CARE Hospital, Road No. 1, Banjara Hills, Hyderabad 500034, India. Fax: 04030418488; e-mail: [email protected] Received November 8, 2014; revised February 23, 2015; accepted March 1, 2015. doi: 10.1111/pace.12626
In the early stages of the disease, CS can be mistaken as idiopathic VT (IVT) as it can present as sustained monomorphic VT (MMVT) in patients with preserved left ventricular (LV) systolic function.4 It is important to distinguish VT due to CS and IVT, as the prognosis and treatment of these two conditions are different.4–6 In clinical practice, VTs with structurally normal heart are often labeled as idiopathic if coronary artery disease is ruled out, but occult pathology such as CS can be easily missed when patients present without any systemic manifestation. Imaging modalities like delayed enhancement cardiac magnetic resonance imaging (DE-CMR) and 18-fluorodeoxyglucose positron emission tomographic scan of the chest (18-FDG PET-CT) are not performed routinely. Due to this, any underlying pathology may be missed and the tachycardia may be erroneously labeled “idiopathic,” resulting in serious implications. To obtain insights into underlying pathophysiology of many cardiac conditions, physicians have relied on the electrocardiogram (ECG) for more than half a century. Prior publications have
©2015 Wiley Periodicals, Inc. 694
June 2015
PACE, Vol. 38
PLEOMORPHIC VT IN CARDIAC SARCOIDOSIS
reported either polymorphic7 or MMVT8,9 in patients with CS. We observed pleomorphic VT (PLVT) in some of our patients diagnosed with CS. This prompted us to systematically review the VT ECGs to identify if pleomorphism or any ECG characteristics that may aid in distinguishing IVT from VT due to CS. We also studied the characteristics of VT in CS patients in relation to their imaging findings (DE-CMR and 18-FDG PET-CT). Methods This is a retrospective study approved by the Institutional Ethics Committee. Patient Population From June 2009 until December 2013, consecutive patients who presented with sustained VT and were diagnosed with CS formed the study group (Group I). Diagnosis of sarcoidosis was confirmed by histopathological examination of enlarged intrathoracic lymph nodes elicited by 18FDG PET-CT or DE-CMR. Patients with IVT formed Group II. The VT was labeled idiopathic when cardiac abnormalities were definitively excluded by echocardiogram, coronary angiogram, DE-CMR, and/or 18-FDG PET-CT. VT due to metabolic and electrolyte abnormalities or any other cause were excluded. Imaging Methodology Contrast-enhanced 64-slice computed tomogram (Siemens, Erlangen, Germany) was used to assess ongoing myocardial inflammation. Resting PET study was done after administration of 18-fluorodeoxyglucose in conjunction with the computed tomogram. In order to minimize FDG uptake by normal myocardial tissues, the test was done after a low carbohydrate, high protein, and high fat diet for a day followed by at least 12 hours of fasting. High 18-FDG uptake in the myocardium was interpreted as inflammation; matched perfusion and metabolism defects were interpreted as scar. DE-CMR was done with a 1.5-T scanner (Siemens) in patients without prior implanted devices. ECG Analysis Twelve-lead ECGs of VT (recorded at 25 mm/s paper speed) during the presenting episode were analyzed. The ECGs were digitally scanned and measurements made with the use of digital calipers (Cardio Calipers version 3.3; Iconico Inc., New York, NY, USA). ECGs were analyzed by two independent observers blinded to the diagnosis of the disease and results of imaging studies. Discrepancies in observations were resolved by mutual consensus.
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Figure 1. (A) Monomorphic ventricular tachycardia— QRS morphology is the same from beat to beat (B1), (B2), and (B3). Pleomorphic ventricular tachycardia— examples (C). Polymorphic ventricular tachycardia— beat-to-beat variation in QRS morphology along with axis change. Numbering shows the repeating patterns of QRS complex morphologies in each example.
Definition of ECG Parameters MMVT: VT with a stable, single QRS morphology from beat to beat. PLVT: VT with more than one morphologically distinct QRS complex occurring during the same episode of VT, but the QRS not continuously changing10 (Fig. 1). This is different from polymorphic VT which has a continuously changing QRS configuration from beat to beat. QRS duration (QRSd): Interval measured from beginning of the Q to the end of S wave in the precordial leads. Cycle length: Average of cycle length of 10 consecutive cycles. Cycle length variation (CLV): Difference between longest R-R interval and shortest R-R interval ࣙ50 ms. Statistical Analysis Descriptive statistics for the categorical variables were performed by computing the frequencies (percentages) in each category. For the quantitative variables, approximate normality of the distribution was assessed. Variables with parametric distribution are presented as mean and standard deviation (SD), whereas those without parametric distribution as median (interquartile range [IQR]). Mean values of continuous variables with normal distribution were compared using unpaired two-tailed t-test. Categorical variables were compared using Fisher’s exact test. A P value of 1 myocardial region
N=10/29 (34%)
N=18/29 (62%)
MMVT (N=49/49)
No scar
Scar in 1 Scar in >1 myocardial region myocardial region
N=3**/25 (12%) N=10/25 (40%)
N=12/25 (48%)
PLVT
PLVT
PLVT
PLVT
PLVT
PLVT
0/1
4/10 (40%)
9/18 (50%)
1/3 (33%)
3/10 (30%)
7/12 (58%)
Figure 2. Figure shows the study flow, imaging results, and corresponding VT QRS configuration. CS = cardiac sarcoidosis; DE-CMR = delayed enhanced cardiac magnetic resonance imaging; 18-FDG PET-scan = 18fluorodeoxyglucose positron emission tomography; IVT = idiopathic ventricular tachycardia; MMVT = monomorphic ventricular tachycardia; PLVT = pleomorphic ventricular tachycardia; VT = ventricular tachycardia. *Myocardial scar present. **Myocardial inflammation present.
95 days) and for PET-CT, median 10 days (IQR: 25, range –7 to 133 days). Imaging findings are shown in Figure 2. Discussion We found VT ECG to be useful in distinguishing IVT from VT due to CS. In the absence of overt systemic involvement as in our group of patients, CS might be easily missed by an unsuspecting physician. VT with normal LV ejection fraction and absence of coronary artery disease is assumed to be idiopathic, but occult heart disease (sarcoidosis, right ventricular cardiomyopathy, etc.) must be excluded. CS often presents with sustained VT and preserved LV function.4 The characteristics of VT associated with CS have not been fully characterized. The observation of PLVT only in CS patients in our study is supported by a similar observation in a previous study by Suzuki.11 In that study,
PACE, Vol. 38
none of the IVTs had pleomorphism as opposed to 19 of 42 of PLVT observed in patients with various underlying cardiac conditions, viz., myocardial infarction, hypertrophic cardiomyopathy, dilated cardiomyopathy, alcoholic cardiomyopathy, right ventricular dysplasia, postoperative tetralogy of Fallot. Although PLVT is not pathognomonic of any single condition, the presence of this feature in a structurally normal heart and in the absence of coronary artery disease could provide an important clue to alerting the treating physician for additional diagnostic work up. Since the original description of pleomorphism during VT in 1979,12 several mechanisms have been proposed. Josephson originally proposed that the mechanism of pleomorphism was a reentry circuit with different exit sites, that is, variable conduction out of one isthmus. Subsequently, it was shown that PLVTs could also arise from different but adjacent circuits in proximity with regions of shared conduction,
June 2015
697
PANDA, ET AL.
that is, variable fusion.13 VTs that originate from anatomically distinct regions have also shown to cause pleomorphism.14,15 It has been hypothesized that pleomorphism, in the setting of functional barriers that are not fixed, can arise during ischemia which generally does not play a role in MMVT. A similar mechanism could be postulated for CS also. During the acute phase of the disease, inflammation and sarcoid granulomas in different regions of the myocardium may act as functional barriers in VT leading to different circuit length, exit sites, and variable VT morphology. In patients with CS, more than one of the above-mentioned mechanisms could be involved. Our results indicate that PLVT was observed more in comparison to MMVT among patients with more than one area of myocardial involvement. This shows that pleomorphic morphology may be due to multiple regions of myocardial involvement. Pleomorphism could also be indicative of early phase of the disease. Although in our study, the time from index VT to the imaging studies was short, PLVT was observed in nearly half of the patients. The LV function of these patients was also preserved. In addition, PLVT was observed in one patient who had only myocardial inflammation but no scar. Our findings are in contrast to the observation made in a substudy of the DATAS trial16 where it was reported that PLVT could be a consequence of deterioration in the clinical condition and ventricular function. On the other hand, we believe that irreversible heart failure could be the result of late recognition of CS when scarring on multiple regions of the myocardium sets in. In a study done by Naruse
et al.,17 myocardial scar was an independent predictor for recurrent VT in spite of corticosteroid therapy. Milman et al.18 described four cases of CS who underwent cardiac transplantation. In these patients, the diagnosis of sarcoid was established late. The explanted hearts showed diffuse fibrosis of the myocardium. We believe that early recognition and disease-specific treatment could have possibly limited the inflammation and scar formation. Limitations of the Study The retrospective nature of our study has its inherent limitations. The findings observed are not exclusive to CS and may be seen in other inflammatory/infiltrative myocardial disease. It would have been ideal for patients in the IVT group to have undergone both 18-FDG PET-CT scan and DE-CMR to rule out latent disease. In some patients this was not possible due to economical constraints and the decision to choose from the two imaging modalities were clinically driven. Therefore, we could not completely rule out the possibility of latent inflammation/scar in these patients. Finally, we have noted that some but not all CS patients had resolution of VT with steroids, but we do not have systematic follow-up on all patients and hence cannot report precisely on how CS patients responded to steroid therapy. Conclusion Pleomorphism and CLV in VT could be a distinguishing feature between CS and VTs of idiopathic origin, though the absence of this finding does not rule out the disease.
References 1. Roberts WC, McAllister HA Jr., Ferrans VJ. Sarcoidosis of the heart. A clinicopathologic study of 35 necropsy patients (group 1) and review of 78 previously described necropsy patients (group 11). Am J Med 1977;63:86–108. 2. Fleming H. Cardiac sarcoidosis. Semin Respir Med 1986;8:65–71. 3. Furushima H, Chinushi M, Sugiura H, Kasai H, Washizuka T, Aizawa Y. Ventricular tachyarrhythmia associated with cardiac sarcoidosis: Its mechanisms and outcome. Clin Cardiol 2004;27:217– 222. 4. Thachil A, Christopher J, Sastry BS, Reddy KN, Tourani VK, Hassan A, Raju BS, et al. Monomorphic ventricular tachycardia and mediastinaladenopathy due to granulomatous infiltration in patients with preserved ventricular function. J Am Coll Cardiol 2011;58:48–55. 5. Uusimaa P, Ylitalo K, Anttonen O, Kerola T, Virtanen V, P¨aa¨ kko¨ E, Raatikainen P. Ventricular tachyarrhythmiaas as a primary presentation of sarcoidosis. Europace 2008;10:760–766. 6. Mezaki T, Chinushi M, Washizuka T, Furushima H, Chinushi Y, Ebe K, Okumura H, et al. Discrepancy between inducibility of ventricular tachycardia and activity of cardiac sarcoidosis. Requirement of defibrillator implantation for the inactive stage of cardiac sarcoidosis. Intern Med 2001;40:731–735. 7. Okamoto M, Hashimoto M, Sueda T, Munemori M, Yamada T. Polymorphic ventricular tachycardia with cardiac sarcoidosis:
698
8.
9.
10.
11.
June 2015
Treatment with low-dose metoprolol and cibenzoline. Intern Med 1994;33:296–299. Koplan BA, Soejima K, Baughman K, Epstein LM, Stevenson WG. Refractory ventricular tachycardia secondary to cardiac sarcoid: Electrophysiologic characteristics, mapping, and ablation. Heart Rhythm 2006;3:924–929. Winters SL, Cohen M, Greenberg S, Stein B, Curwin J, Pe E, Gomes JA. Sustained ventricular tachycardia associated with sarcoidosis: Assessment of the underlying cardiac anatomy and the prospective utility of programmed ventricular stimulation, drug therapy and an implantable antitachycardia device. J Am Coll Cardiol 1991;18:937– 943. Aliot EM, Stevenson WG, Almendral-Garrote JM, Bogun F, Calkins CH, Delacretaz E, Della Bella P, et al. EHRA/HRS Expert Consensus on Catheter Ablation of Ventricular Arrhythmias. Developed in a partnership with the European Heart Rhythm Association (EHRA), a Registered Branch of the European Society of Cardiology (ESC), and the Heart Rhythm Society (HRS); in collaboration with the American College of Cardiology (ACC) and the American Heart Association (AHA). Heart Rhythm 2009;6: 886–933. Suzuki K. Clinical features of sustained ventricular tachycardia among various underlying heart diseases. Tohoku J Exp Med 1990;162:15–26.
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PLEOMORPHIC VT IN CARDIAC SARCOIDOSIS 12. Josephson ME, Horowitz LN, Farshidi A, Spielman SR, Michelson EL, Greenspan AM. Recurrent sustained ventricular tachycardia. 4. Pleomorphism. Circulation 1979;59:459– 468. 13. Fitzgerald DM, Friday KJ, Yeung-Lai-Wah JA. Myocardial regions of slow conduction participating in the reentrant circuit of multiple ventricular tachycardias: Report on ten patients. J Cardiovasc Electrophysiol 1991;2:193–206. 14. Josephson ME, Horowitz LN, Spielman SR, Greenspan AM, VandePol C, Harken AH. Comparison of endocardial catheter mapping with intraoperative mapping of ventricular tachycardia. Circulation 1980;61:395–404. 15. Miller JM, Kienzle MG, Harken AH, Josephson ME. Morphologically distinct sustained ventricular tachycardias in coronary artery
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disease: Significance and surgical results. J Am Coll Cardiol 1984;4:1073–1079. 16. Hadid C, Almendral J, Ortiz M, Schwab JO, Janko S, Mischke K, Arribas F, et al. Incidence, determinants, and prognostic implications of true pleomorphism of ventricular tachycardia in patients with implantable cardioverter-defibrillators: A substudy of the DATAS Trial. Circ Arrhythm Electrophysiol 2011; 4:33–42. 17. Naruse Y, Sekiguchi Y, Nogami A, Okada H, Yamauchi Y, Machino T, Kuroki K, et al. A systematic treatment approach to ventricular tachycardia in cardiac sarcoidosis. Circ Arrhythm Electrophysiol 2014;7:407–413. 18. Milman N, Andersen CB, Mortensen SA, Sander K. Cardiac sarcoidosis and heart transplantation: A report of four consecutive patients. Sarcoidosis Vasc Diffuse Lung Dis 2008;25:51–59.
June 2015
699
