|Year : 2019 | Volume
| Issue : 3 | Page : 87-90
Clinical significance of electrocardiograph abnormalities: Analysis on electrocardiographs of 75 Marfan cases complicated with aortic disease
Yaping He1, Sui-Shane Huang2, Zhenning Nie3
1 Department of Cardiology, Deltahealth Hospital, Shanghai, China
2 Department of Cardiology, Deltahealth Hospital; Department of Cardiology, Zhongshan Hospital, Fudan University; Shanghai Institute of Cardiovascular Diseases, Shanghai, China
3 Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, China
|Date of Submission||01-Jun-2018|
|Date of Acceptance||23-May-2019|
|Date of Web Publication||30-Sep-2019|
Department of Cardiology, Zhongshan Hospital, NO.180, Fenglin Road, Shanghai, 200032
Source of Support: None, Conflict of Interest: None
Purpose: Marfan syndrome (MFS) is one of the most common hereditary connective tissue disorders, with various adverse manifestations ranging from typical ocular, cardiovascular, and musculoskeletal abnormalities to manifestations involving the lungs, skin, and central nervous system. In patients with MFS, the most lethal manifestations are aortic lesion presenting as aortic insufficiency, thoracic and abdominal aortic dilatation, aneurysm, and dissection. Clinically, these patients often present with various types of arrhythmias and abnormal electrocardiographs (EKGs); however, there have been few studies of MFS-associated arrhythmias either in China or abroad. This investigation aims to elucidate the association between Marfan-associated aortic lesions and accompanying arrhythmia characteristics. Methods: From September 2016 to January 2018, 75 consecutive patients diagnosed with MFS and aortic disease manifestation were enrolled in the study (MFS group). During the same time period, 76 consecutive nonMFS patients with aortic disease were enrolled as positive controls (dissection group) and 100 consecutive healthy patients were enrolled during routine health checkups as negative controls (checkup group). EKG characteristics between the three groups were analyzed. Results: Compared to the checkup group, both the MFS group and dissection group showed more EKG abnormalities (P < 0.01). Even though there was no significant difference in the incidence of EKG abnormalities between the MFS group and the dissection group (P > 0.05), the MFS group showed a significantly higher occurrence of sinus bradycardia and first-degree atrioventricular block (P < 0.05) compared to the dissection group. Furthermore, the MFS group showed a significantly higher occurrence of left ventricular high voltage with accompanying ST-T change (P < 0.01) compared to the dissection group. Finally, the MFS group showed a significantly higher occurrence of left atrial abnormality (P < 0.05) compared to the dissection group. Conclusion: Patients with MFS and aortic disease manifestation have unique EKG abnormality characteristics. This may be associated with the connective tissue disease affecting the physiological electric conduction in the heart and long-term volume overload leading to myocardial damage.
Keywords: Aortic disease, electrocardiograph, Marfan syndrome
|How to cite this article:|
He Y, Huang SS, Nie Z. Clinical significance of electrocardiograph abnormalities: Analysis on electrocardiographs of 75 Marfan cases complicated with aortic disease. Cardiol Plus 2019;4:87-90
|How to cite this URL:|
He Y, Huang SS, Nie Z. Clinical significance of electrocardiograph abnormalities: Analysis on electrocardiographs of 75 Marfan cases complicated with aortic disease. Cardiol Plus [serial online] 2019 [cited 2020 May 27];4:87-90. Available from: http://www.cardiologyplus.org/text.asp?2019/4/3/87/268298
| Introduction|| |
Marfan syndrome (MFS) is an inherited autosomal dominant connective-tissue disease, and approximately 80% of patients suffering from MFS have congenital cardiovascular deformities, with aortic disease presenting as the main cause of morbidity and mortality in patients with MFS. The pathological development of MFS aortic disease begins with apoptosis of aortic smooth muscle cells leading to a cyst-like appearance, in conjunction with vessel intimal elastin abnormalities, resulting in a fragile aortic wall structure that is prone to aneurysm and dissection formation., In the clinical setting, the incidences of arrhythmia and electrocardiograph (EKG) abnormalities are often observed in MFS patients with aortic disease manifestation. There are few comprehensive clinical studies on MFS aortic disease-associated arrhythmias, and this investigation aims to elucidate the association between the two. This study is a retrospective study of all the aortic disease patients assessed for surgical intervention at Shanghai Deltahealth Hospital between September 2016 and January 2018. After all aortic disease patients were enrolled into the MFS or dissection groups, EKGs were collected and analyzed.
Baseline characteristics and method
Initially, 154 consecutive aortic disease patients from the Cardiovascular Surgery Ward, Shanghai Deltahealth Hospital, were admitted to the study. Three were excluded because of insufficient EKG results. A total of 151 patients were enrolled into the study with 102 male and 49 female patients. We followed standard MFS diagnosis criteria, which have been in use since they were first described by Wilner and Finby in 1964 and then later revised by Pyeritz and McKusick in 1979. The criteria included (1) musculoskeletal disease: arachnodactyly being the most typical indicator; (2) ocular disease: ectopia lentis being the most typical indicator; (3) cardiovascular disease: aortic root dilatation being the most typical indicator; and (4) family history of MFS. Satisfying two of the four criteria allows for the diagnosis of MFS. Aortic diseases include acute or chronic aortic dissection, aortic dilatation, aortic aneurysm, and aortic aneurysm with dissection. To serve as a negative control, 100 patients from outpatient routine checkup were enrolled into the “checkup” group. There were no clinical aortic diseases or other clinical information from the checkup group. EKGs between the three groups were compared and analyzed. Baseline characteristics showed the MFS group with an average age of 31.9 ± 10.3 years old, lower than dissection groups and checkup groups (51 ± 14.2 years old and 48 ± 11.6 years old, respectively). There were no statistical differences in average age between the dissection group and checkup group. There were no statistical differences in gender among all the three groups.
| Methods|| |
Resting EKG was collected by the PHILIPS PageWriter TC20 Cardiograph within 24 h following aortic disease patient admission to the cardiovascular surgery ward or at the outpatient clinic for a routine health checkup. EKG diagnosis criteria were according to the Huang Wan Clinical Electrocardiography.
| Definition|| |
- Sinus bradycardia is defined as sinus rhythm <60 bpm
- First-degree AVB is defined as PR interval >200 ms
- Left ventricular high voltage with accompanying ST-T change is defined as EKG showing RV5 + SV1 >4.0 mV (men) and RV5 + SV1 >3.5 mV (women) with ST-T elevation or depression >.05 mV
- Left atrial abnormality is defined as a board, notched, or bifid P wave with a duration time ≥0.12 s, ≥0.04 s between the two peaks, most visible in leads I, II, aVL, and a negative P wave component of >0.04 s and >0.1 mV in leads V1 and V2
- QTc elongation is defined as QTc >460 ms (women) and QTc >450 ms (men).
All values were expressed as the mean ± standard deviation or percentages. Differences between the patient groups were tested by univariate analysis (Chi-square test or two-tailed t-test as appropriate). P < 0.05 was considered statistically significant. All analyses were performed using SPSS statistical software (version 23.0 software, Chicago, IL, USA).
| Results|| |
Clinical characteristic comparison between the three groups
Clinical characteristics of the three groups are summarized in [Table 1]. Checkup group comprised 100 randomly selected health routine checkup patients from the outpatient clinic. There were no clinical aortic diseases or other clinical information from the checkup group. The dissection group has a higher incidence of hypertension than that of the MFS group (32.9% vs. 4.0%, P < 0.01). There were no significant differences in perioperative cardiac insufficiency, which was defined by brain natriuretic peptide (BNP >400 pg/ml) within 2 weeks of surgical intervention, between the dissection group and MFS group (19.8% vs. 14.7%). Compared to dissection group, the MFS group had a higher rate of reoperation (48% vs. 18.4%, P < 0.01), higher rate of combined thoracic and abdominal aortic disease (26.7% vs. 9.2%, P < 0.01), lower rate of ascending aortic disease (40% vs. 64.5%, P < 0.01), and a lower rate of emergency admission (5.3% vs. 53.9%, P < 0.01). Echocardiogram analysis showed that the MFS group had a higher left ventricular end-diastolic diameter than that of the dissection group (53.2 ± 9.95 mm vs. 47.8 ± 5.65 mm, P < 0.01); however, there were no significant differences in left ventricular diameter (LVD), left ventricular ejection fraction, and left ventricular wall thickness (36.3 ± 9.8 mm vs. 34.2 ± 6.6 mm, 60.4 ± 12.15% vs. 62.0 ± 7.75%, and 10.3 ± 1.7 mm vs. 11.5 ± 1.4 mm, respectively) between the two groups.
Electrocardiograph characteristic comparison between the three groups
EKG characteristics of the three groups are summarized in [Table 2]. There were only 4 cases of sinus bradycardia, 1 case of first-degree atrioventricular block (1° AVB), 1 case of left ventricular high voltage, and the rest were normal EKGs. Between the dissection group and MFS group, there were only 17 and 16 cases with normal EKGs, respectively, and the rest of the remaining cases had EKG abnormalities. By tallying each count of EKG abnormalities, including sinus bradycardia, 1° AVB, left ventricular high voltage, ST-T change, QT prolongation, left atrial abnormality, bundle branch block, premature atrial contraction, premature ventricular contraction, and atrial fibrillation, the MFS group showed higher combined EKG abnormalities than that of the dissection group (1.7 vs. 1.2, P < 0.05). The data showed that aortic disease often had accompanying EKG abnormalities, including sinus bradycardia, 1° AVB, left ventricular high voltage, ST-T change, and QT prolongation, with left ventricular high voltage, ST-T change, and QT prolongation having the highest prevalence. The MFS group showed a higher prevalence of EKG abnormalities compared to the dissection group in sinus bradycardia (10.7% vs. 1.3%, P < 0.05), 1° AVB (13.3% vs. 3.9%, P < 0.05), and left ventricular high voltage with accompanying ST-T change (20.0% vs. 2.6%, P < 0.01).
| Discussion|| |
This study showed that only 21.9% of aortic disease patients have normal EKGs, and the rest displayed various degrees of EKG abnormality, such as conduction delay, QT prolongation, and atrial and ventricular arrhythmias. The results indicated that aortic diseases with accompanying EKG abnormality are a common phenomenon. Acute aortic dissection may cause aortic regurgitation, insufficient coronary artery perfusion, and cardiac tamponade, which may all lead to EKG abnormalities. Chronic aortic dissections, aortic root dilatation, aortic aneurysm, or aortic aneurysm with dissection may cause chronic cardiac preload increase and chronic myocardial damage, which can lead to EKG abnormalities. Researchers have shown that nonMFS aortic disease patients have a higher rate of accompanying hypertension and atherosclerosis, and these systemic diseases may affect the cardiac microcirculation causing widespread myocardial damage, manifesting in various types of EKG abnormalities.,
Compared to regular aortic disease patients, the results indicated that a surprising amount of MFS patients have multiple combined EKG abnormalities. From the clinical baseline statistics, the results showed that MFS group are younger in age, have less prevalence of hypertension, and have less incidence of emergency room admission, but have a higher rate of combined thoracic and abdominal aortic surgery and a higher rate of reoperation. However, from our previous understanding of major vessel disease risk factors related to arrhythmia, young age, nonemergency setting, no accompanying chronic diseases, and combined thoracic and abdominal aortic disease rather than ascending aortic disease all seem to be negatively correlated factors.,, Although EKG studies on MFS patients are few, the results implied that MFS itself may be the cause of various combined EKG abnormalities. Further in-depth studies are required to justify the cause and effect of MFS-related EKG abnormalities.
Although the EKG abnormality occurrences between the MFS and dissection groups were similar, the MFS group's EKG abnormalities had unique characteristics, particularly in bradycardia, AVB, and left ventricular high voltage with ST-T change. Since the pathological and pathophysiological factors caused by aortic diseases are considered the same between MFS group and aortic disease-positive control group, it is reasonal to infer that EKG abnormalities in MFS group are unique to Marfan syndrome itself. The echocardiogram analysis between the MFS and dissection groups showed no significant difference in heart structure or function; thus, the EKG abnormalities in the MFS group must be attributed to other factors. Savolainen et al. had conducted a Holter monitor on 45 MFS patients and showed that MFS patients have higher incidence of AV conduction delay and ST-T change compared to a negative control group, which were independent of echocardiogram-measured ascending aortic root diameter, left atrial diameter, LVD, left ventricular wall thickness, and contraction function. These results align with our current findings. The current study raises speculation that MFS itself may be a dominating factor in cardiac electric conduction system abnormalities. We hypothesized that MFS collagen deficiency may cause myocardium interstitial microfibril deficiency, subsequently leading to a delay in cardiac electric conduction. However, this hypothesis needs further in-depth research to provide a significant proof. Jianzhong and Dengwei had reported two cases of sudden death in young MFS patients, demonstrating coronary artery intimal hyperplasia leading to stenosis in the sinoatrial node and atrioventricular node area with decreased sinoatrial node cells and increased fibrosis in the area. This is an indicator that MFS may have significant pathological changes affecting cardiac electric conduction system.
| Conclusion|| |
MFS is a complex disease affecting multiple organ systems. This investigation is a retrospective observatory research on aortic disease accompanying EKG abnormalities and reports unique characteristics in MFS aortic disease accompanying EKG abnormalities for the first time. MFS aortic disease accompanying EKG abnormalities may be associated with connective tissue disease affecting the cardiac electric conduction system and chronic volume overload-related myocardial damage.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Radke RM, Baumgartner H. Diagnosis and treatment of Marfan syndrome: An update. Heart 2014;100:1382-91.
Devereux RB, Roman MJ. Aortic disease in Marfan's syndrome. N Engl J Med 1999;340:1358-9.
Pyeritz RE, McKusick VA. The Marfan syndrome: Diagnosis and management. N Engl J Med 1979;300:772-7.
Wan H. Clinical Electrocardiography. 5th
ed. Beijing: People's Medical Publishing House; 2010. p. 6-46.
Hagan PG, Nienaber CA, Isselbacher EM, Bruckman D, Karavite DJ, Russman PL, et al.
The international registry of acute aortic dissection (IRAD): New insights into an old disease. JAMA 2000;283:897-903.
Johnston KW, Rutherford RB, Tilson MD, Shah DM, Hollier L, Stanley JC, et al.
Suggested standards for reporting on arterial aneurysms. Subcommittee on reporting standards for arterial aneurysms, Ad Hoc Committee on Reporting Standards, Society for Vascular Surgery and North American Chapter, International Society for Cardiovascular Surgery. J Vasc Surg 1991;13:452-8.
Yuan SM, Jing H. Cardiac surgery and hypertension: A dangerous association that must be well known. Rev Bras Cir Cardiovasc 2011;26:273-81.
Yiu KH, Tse HF. Hypertension and cardiac arrhythmias: A review of the epidemiology, pathophysiology and clinical implications. J Hum Hypertens 2008;22:380-8.
Mirza M, Strunets A, Shen WK, Jahangir A. Mechanisms of arrhythmias and conduction disorders in older adults. Clin Geriatr Med 2012;28:555-73.
Savolainen A, Kupari M, Toivonen L, Kaitila I, Viitasalo M. Abnormal ambulatory electrocardiographic findings in patients with the Marfan syndrome. J Intern Med 1997;241:221-6.
Jianzhong Z, Dengwei Z. Pathological changes of cardiac conduction system in Marfan's syndrome: A report of two cases. Acta Acad Med Militaris Ertiae 1985;7:372-5.
[Table 1], [Table 2]