Spontaneous Coronary Artery Dissection: Aggressive vs. Conservative Therapy

ABSTRACT: Background. Spontaneous coronary artery dissection (SCAD) is a rare condition that commonly presents as an acute coronary event in the younger population, especially in females of childbearing age. Generally, there is no consensus on the etiology, prognosis, and treatment of SCAD. Methods. The Medline database was searched for “spontaneous coronary artery dissection” between 1931 and 2008. A total of 440 cases of SCAD were identified. Demographic data were analyzed with either the Student’s t-test or the chi-square test for categorical and nominal variables, respectively. Kaplan-Meier outcome analysis was used to assess the outcome of a given treatment for all patients after 1990. Result. SCAD was found more commonly in females with 308 (70%) cases. Pregnancy was associated with SCAD in 80 (26.1%) cases. Among pregnant patients, 67 (83.8%) developed SCAD in the postpartum period and 13 (16.2%) patients in the prepartum period. Analysis of treatment modalities showed that 21.2% of the patients who were conservatively managed after the initial diagnosis eventually required surgical or catheter-based intervention compared to 2.5% of patients who were initially treated with an aggressive strategy. Kaplan-Meier analysis showed that patients with an isolated single lesion in left or right coronary artery had a statistically significant better outcome when treated with an early aggressive strategy, including coronary artery bypass grafting (CABG) or stent placement as compared to a conservative strategy (p = 0.023, p = 0.006, respectively). Conclusion. Early intervention with either CABG or percutaneous coronary intervention following the diagnosis of SCAD leads to a better outcome and less need for further intervention. J INVASIVE CARDIOL 2010;22:222–228 Spontaneous coronary artery dissection (SCAD) is a separation of the coronary artery wall layers by hemorrhage with or without an associated intimal tear.¹ It is a rare condition that mainly presents in the younger female population,^2,3 and typically manifests as an acute coronary event. The first known case was documented in an autopsy performed on a 42-year-old female in 1931. ⁴ Since then, a number of anecdotal references have been made in the literature. Previously, diagnosis was mainly made by postmortem examination until the advent of advanced cardiac imaging. Now, more cases of SCAD are being diagnosed with the widespread use of coronary angiography. SCAD can involve both the left and right coronary arterial system. The treatment modalities consist of conservative medical or aggressive management with percutaneous coronary intervention (PCI) or coronary artery bypass graft surgery (CABG). Currently, there are no outcome studies or treatment guidelines for SCAD. The purpose of this study is to compare the effectiveness of various treatment modalities on the outcome of SCAD.

Material and Methods

We searched the Medline database using the key words “spontaneous coronary dissection,” and “primary and idiopathic coronary dissection” between 1931 and 2008. A total of 381 articles with a total of 485 published case reports, 7 review articles^5–10,12 and a registry on SCAD11 were found. Forty-five cases, which were reported to be iatrogenic, were excluded. Forty-eight articles in languages other than English were found; however, 34 articles or abstracts contained sufficient data to be included in this analysis. A total of 440 cases with an acceptable pool of information were analyzed in this review. Statistical analysis. All the data were summarized according to the cases observed in the literature. Demographic data were analyzed using either the Student’s t-test or the chi-square test for categorical and nominal variables, respectively. All statistical values were significant at a p-value Results Baseline characteristics. We found a total of 440 patients with SCAD in the literature. We categorized the data based on gender and found that SCAD was more common in females, with 307 (70%) reported cases versus 133 (30.2%) for males. The mean age of the study population was 42.6 years (males: 45.4 ± 14.4 years, females: 41 ± 10.6 years), with a range of 17–82 years. Among female patients, 18 (5.8%) cases were associated with oral contraceptive (OCP) use and 12 (3.9%) cases occurred during activities which involved heavy exertion. Pregnancy was associated with coronary dissection in 80 (26%) cases. Among them, 67 (83.8%) events occurred in the postpartum period and 13 (16.2%) events before delivery (p = 0.001). Among postpartum patients, 47 (70.1%) cases occurred within 2 weeks following delivery. SCAD was more frequently encountered in males during activities which involved heavy exertion (n = 20 [15.3%]) (Table 1). Presentation and anatomy of lesions. Out of the 440 cases of SCAD, 95 (21.5%) were diagnosed during postmortem examination. The diagnosis of SCAD in the remaining 345 (78.5%) cases was made mainly by coronary angiograms, less frequently by cardiac computed tomography (CCT) and rarely by cardiac magnetic resonance imaging. On reviewing histological examination of the postmortem cases, eosinophilic infiltration was the most frequent abnormality found in 23 (21.7%) cases (Figure 1). Analysis of the 95 autopsy cases revealed that eosinophilic infiltration was present in 31.8% of pregnant patients (n = 7/22), whereas, in the absence of pregnancy it was seen in 32.6 % (n = 24/73) of cases (p = 0.537). Further, analysis of the autopsy cases showed, that cystic medial necrosis (CMN) was present in 31.8% (n = 7/22) of pregnant patients, whereas, in the absence of pregnancy, it was detected in 30.13% (n = 22/73) of cases (p = 0.440). Among the 440 patients presenting with SCAD, chest pain was the most frequent symptom and occurred in 339 (77%) patients (Figure 2). Only 322 patients had electrocardiographic examination at the time of diagnosis. Among them, ST-segment elevation was present in 209 (64.9%). Overall, 602 lesions were reported in 440 patients. Dissection was found most frequently in the left anterior descending artery (LAD) (48%) (Figure 3). The coronary artery lesions were classified based on the number and anatomical location. Isolated single-vessel dissection was 2.8 times more common than multivessel dissection (324 [73.6%] patients vs. 116 [26.4%] patients; p = 0.001). Isolated single lesions were found more often among males than among females (108 [81.2%] vs. 216 [70.4%]; p = 0.017). Isolated single lesions were found more often among males than among females (108 [81.2%] vs. 216 [70.4%]; p = 0.017). Isolated LAD, right coronary artery (RCA), left main coronary (LMC) artery and left circumflex artery (LCX) dissections were found in 178 (40.5%), 96 (21.9%), 27 (6.1%) and 23 (5.2%) patients, respectively. Dissection involving 2 coronary vessels was reported in 71 (16.1%) cases of the entire study population (54 females and 17 males). Dissection involving more than 2 coronary vessels was found in 45 (10.2%) cases among all study patients, and was more common in females (38 [12.3%] vs. 7 [5.3%]; p = 0.026) (Table 2, Figure 4). Dissection involving 3 coronary vessels was found in 44 (10%) cases among all study patients, and was more common in females (37 [12.1%] vs. 7 [5.3%]; p = 0.029) (Table 2, Figure 4). Five patients developed new dissection in the coronary arteries which did not show dissection in the initial angiography, of which all 5 patients were conservatively treated. ^13–17 Of the 345 patients with SCAD who were initially diagnosed by coronary angiography or cardiac CT, 121 (35.1%) underwent a subsequent procedure. Indications for a subsequent procedure included chest pain in 37 (30.6%) subjects, cardiogenic shock in 5 (4.1%) and coronary angiography was performed as an elective follow up in the absence of any symptoms in 79 (65.3%) patients. SCAD lesions persisted or worsened in 67.5% of the patients who were treated conservatively and underwent repeat coronary angiography, compared to 25.9% patients who were initially treated with CABG or stenting (p = 0.001). Management strategy. Our analysis showed that common treatment modalities used to manage SCAD were conservative management and catheter-based or surgical intervention. All of the above treatment modalities were not commonly available in the years prior to 1990. Out of 344 cases of SCAD diagnosed after 1990, 30 (8.7%) patients died prior to hospitalization. Of the remaining 314 patients, aggressive management was the first treatment modality in 158 (CABG #91, PCI #67), and conservative management was applied to 156 patients. Among the 314 patients, 110 (35.5%) underwent subsequent coronary angiography. Eighty-three (75.5%) of these patients, were initially managed conservatively compared to 12 (10.9%) subjects who underwent CABG and 15 (13.6%) who were treated with catheter-based intervention. Out of the 83 conservatively managed patients, 33 required further intervention (CABG #19, PCI #14). Among the 12 patients with prior CABG, only 1 required re-do CABG. Among the 15 patients treated with coronary stent placement, 2 required a CABG procedure and 1 needed a second PCI. Overall, 21.2% of the patients who were treated conservatively following the diagnosis of SCAD underwent a surgical or catheter-based intervention, compared to 2.5% who received an early intervention after the diagnosis of SCAD (p = 0.001) (Figure 5). Kaplan-Meier analysis showed that patients with an isolated single SCAD lesions in the left or right coronary artery had a statistically significant better outcome when treated with an early aggressive strategy, including CABG or stent placement as compared to conservative strategy (p = 0.023, p = 0.006, respectively). The analysis of combined left and right coronary arteries with single SCAD was also statistically significant in favor of aggressive strategy (p = 0.001) (Figure 6). In our review, we found that 87 patients (19.8%) received thrombolytic therapy before SCAD was diagnosed. Of these 87 patients, the clinical condition of 52 (59.7 %) patients worsened, while 35 patients remained clinically stable. However, out of 35 stable patients after thrombolytic administration; 59% required further intervention later. Intravascular ultrasound (IVUS) was used in 10.2% (n = 32) vs. 19.1% (n = 21) of patients during the first and second angiographic examinations, respectively.

Discussion

This is the first analysis that was performed to determine in detail the natural history of coronary artery dissection, the lesion characteristics, therapeutic modalities, and the short-term outcome of various management strategies. Our study was the first to identify that coronary intervention had statistically significant superior outcomes to conservative, watchful medical management in SCAD. This was observed for both right and left coronary artery lesions. Our analysis uncovered a significant gender disparity regarding the incidence of SCAD, lesion characteristics and risk-factor profile. We found that pregnancy and labor were associated with an increased risk of coronary artery dissection, comprising nearly 18% of our total patient population, and over one-fourth of the female population. Interestingly, we found that more than 50% of coronary dissections in pregnant patients occurred within the first week of delivery. This analysis suggests that acute blood pressure elevation may be an important contributing factor to SCAD, especially during the extreme exertion of labor and rigorous exercise. This is also the first study to analyze the common histological characteristics underlying the dissected coronary lesions. Eosinophilic infiltration and cystic medial necrosis were important associated findings in one-third of all autopsy reports. Pathogenesis. There is growing evidence that suggests lytic action of proteases released from eosinophils is responsible for collagenolysis and weakening of the coronary arterial wall. Borczuk et al, based on animal models, postulated that eosinophils infiltrate the cervix and coronary arterial wall at the time of parturition and during the postpartum period. Furthermore, they concluded that inappropriate eosinophilic degranulation leads to release of collagenase within the coronary artery wall and a predisposition to SCAD. ¹⁸ Our analysis of eosinophilic infiltration in pregnant and nonpregnant patients with SCAD showed no statistically significant difference between the two groups. This was contrary to the hypothesis suggesting a likely association between SCAD and eosinophilic infiltration during pregnancy. ^19,28 However, higher rates of eosinophilic infiltration (32.6%) were found in one-third of all postmortem examinations. A number of authors have suggested that female hormonal changes in pregnancy may alter and weaken the ground substance and connective tissue within the coronary arterial wall. ^20,21 This subsequently leads to disruption of the elastic fibers and formation of cystic medial necrosis in the coronary arterial wall. ²² Some authors have favored the role of a hyperestrogenic state during pregnancy²³ or OCP use²⁴ as a predisposing factor in SCAD. In contrast, Slight et al hypothesized that a hypoestrogenic state during postpartum and menstrual periods predisposes females to SCAD based on the suppressive effects of female sex hormones, in particular estrogen, on vascular smooth muscle cell activity. ^25,26 We did not find any statistically significant difference when cystic medial necrosis lesions were compared in pregnant and non-pregnant patients. However, like eosinophilic infiltration, cystic medial necrosis was found in one-third of all autopsy reports of the study population, which points to a common etiology and calls for more investigation. Females, despite being younger, healthier and with a lower risk-factor profile for atherosclerotic coronary artery disease, not only expressed a higher incidence of dissection, but also showed the more severe type of multivessel SCAD. Some studies suggest that hemodynamic factors such as an acute increase in blood pressure due to heavy exertion amplify the shear forces on the arterial wall which may lead to coronary artery dissection even in healthy trained athletes. ^27,28 Moreover, the higher incidence of SCAD during the peripartum period and labor, as suggested by some authors, was thought to be secondary to high cardiocirculatory stresses and increased shear forces⁸ on the coronary arterial wall, especially with drastic increases in blood volume and basal cardiac output up to 80% during vaginal delivery. ^29–32 Our study showed that more than 50% of SCAD cases related to pregnancy and labor occurred within the first week, and 70% within second week of the postpartum period when the female vascular system is still subjected to high cardiocirculatory stresses. This may suggest that increased shear forces and blood pressure may contribute to an intimal tear with progression of subsequent dissection in some patients. However, some coronary dissections occur days after delivery when blood pressure is normalized, this may be explained by an initial asymptomatic dissection leading to a symptomatic event later. ^20,33–35 Although labor is associated with high blood pressure and cardiocirculatory stress on maternal vasculature, coronary dissection is a rare condition. There may be other unknown contributing factors which predispose women to coronary dissection around the time of labor. Diagnosis. The diagnosis of SCAD should be suspected in the setting of anginal chest pain, MI and fluctuating ST-segment elevation^36,37 following heavy exertion in patients with low risk factors for CAD or during labor in females. Fluctuating ST segments with transient sequential elevation and normalization of ST segments in different leads over a short period of time was observed in a number of reports of multivessel coronary dissection. Cardiac CT has been used in the diagnosis of coronary artery dissection, ^38,41 especially when diagnostic coronary angiography is inconclusive when dissection creates an enclosed hematoma within the coronary wall without communication to the true lumen. However, the accuracy of diagnostic CCT for SCAD is unknown. ⁴² Based on our study, the combination of coronary angiography and intravascular ultrasound (IVUS) is a superior diagnostic strategy to the other methods since it can be utilized as a therapeutic modality at the time of diagnosis. Treatment. Our analysis showed that one-fifth of the patients who were conservatively managed after the initial diagnosis of SCAD eventually required surgical or catheter-based intervention compared to the small percentage of patients (2.5%) who were initially treated with an aggressive strategy. Our analysis revealed that when surgical or catheter-based intervention was not the initial treatment in patients who underwent repeat coronary angiography, 60% of SCAD lesions remained the same or progressed. Furthermore, Kaplan-Meier outcome analysis showed that patients who underwent aggressive treatment with CABG or stent placement at the time of diagnosis had a statistically significant longer symptom-free period and lower mortality rates compared to those who were managed with a conservative medical strategy (Figure 6). Based on the above information, we believe that early coronary artery intervention with CABG or catheter-based intervention for SCAD is superior to conservative, watchful waiting, especially in isolated single lesions. Some patients in the study received thrombolytic therapy prior to the diagnosis of SCAD. Our analysis showed that the clinical condition of nearly 60% of the patients with SCAD who received thrombolytic agents deteriorated, necessitating rescue PCI or CABG. There is a difference of opinion as to whether thrombolytic agents should be used or avoided for patients in whom SCAD is suspected. Some authors favor using thrombolytic agents^24,43 in SCAD, postulating that it may lyse the thrombus in the false lumen, allowing the true lumen to expand and thus restoring coronary blood flow. By contrast, some authors advocate against using thrombolytic therapy, ^{44, 45} speculating that it might extend the dissection. It is difficult to determine, whether the progression of dissection is solely due to the nature of the disease or the usage of thrombolytic agents. Based on our observations in this study, we believe that patients with SCAD may benefit from coronary angiography, with or without IVUS, for the accurate diagnosis and probable treatment of SCAD at the time of presentation more than they would benefit from other therapeutic methods. If the coronary angiography cannot emergently be carried out, then it is prudent to perform CCT within the window of time recommended in the STEMI treatment guidelines. If SCAD is diagnosed by CCT, thrombolytics should be postponed and the patients should proceed with coronary angiography as a first measure for diagnosis and possible therapeutic intervention, even if it requires transfer to a PCI-capable institution. We also believe that patients with SCAD might benefit from lower blood pressure achieved by beta-blocker agents which are known to reduce the shear forces on the arterial wall. Since the majority of SCAD lesions will persist following conservative management, follow-up coronary angiography or CCT is warranted to reevaluate the lesion, regardless of the patient’s clinical symptoms.

Conclusion

In summary, our study found that in patients with SCAD, early intervention following diagnosis produces a better outcome and less need for further intervention compared to a conservative, watchful waiting approach. Study limitations. We believe that our study will shed some light on this important and rare clinical condition. This study is a retrospective analysis of a reported pool of cases with different baseline demographic and clinical characteristics. There is also a paucity of periprocedural information and subsequent follow up, especially after second angiograms. We analyzed only those studies that had a second catheterization, which accounts for about 60% of the cases. The analysis was performed for reported cases found in the medical literature. There might be some cases that could have been diagnosed, but went unreported. In patients treated conservatively, the worse outcome does not necessarily convey an inferior method of treatment, since patient-related factors might have affected the physician’s choice of treatment modality at the time of presentation. This information was not reliably available to us through the case reports in the literature. The data regarding other comorbidities in conservative versus aggressively treated patients was not consistently available in the literature. Hence, it was not included in our analysis. A prospective study is a better way to analyze such data, however, because of the rarity of such cases, it may be difficult to conduct such a study. There are some promising prospective studies like the DISCOVERY registry, ¹¹ that might shed more light on SCAD in the future.

References

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__________________________________________________________ From the Department of Internal Medicine, Division of Cardiovascular Diseases, Howard University Hospital, Washington, D.C. and the *University of Maryland, School of Pharmacy, Baltimore, Maryland. The authors report no conflicts of interest regarding the content herein. Manuscript submitted October 22, 2009, provisional acceptance given November 30, 2009, final version accepted December 16, 2009. Address for correspondence: Behrooz K. Shamloo, MD, 4058 Norbeck Sq. Drive, Rockville, MD 20853. E-mail: bzshamloo@gmail.com