Abstract
Spontaneous coronary intramural hematoma (SCIH) was one type of spontaneous coronary artery dissection without obvious intimal tear, which is easy to misdiagnose. We aimed to study the characteristics, management, and prognosis of SCIH in our center. All the SCIH patients (n = 30) diagnosed by coronary angiography from January 1, 2012 to December 31, 2018 were enrolled. The demographic characteristics, history, therapy, and follow-up were collected. The mean age of the patients was 51.8 ± 9.5 years. Most of the patients were females (66.7%) with hypertension. Patients with diffuse lesion, focal lesion, and multiple vessels were 70%, 13.3%, and 16.7%, respectively. Conservative treatment was the first choice (76.7%). The mean follow-up time was 29.3 ± 13.5 months. None of the patients had unplanned readmission due to worsening symptoms. Nine patients underwent coronary artery computed tomography reexamination after 10.3 ± 7.5 months, which showed complete recovery of SCIH. Eight patients were hospitalized for coronary angiography 6.4 ± 4.7 months later, which did not show any sign of SCIH. Spontaneous coronary intramural hematoma was most common in post-menopausal women with hypertension. Possibly, antiplatelet drugs should be avoided in SCIH. Waiting for the hematoma to heal was preferable and had a good prognosis.
Keywords
Introduction
Spontaneous coronary intramural hematoma (SCIH) refers to spontaneous hematoma formation between the intima and media of a coronary artery. The mechanism of SCIH involves rupture of the coronary vasorum with an intact inner membrane or breakage of the intima with a small or no outlet, which causes the blood to enter the mid-membrane cavity, the inner membrane to shift inward, and the outer membrane to shift outward to form a hematoma.1,2 SCIH is currently considered a type of spontaneous coronary artery dissection (SCAD) according to the published expert consensus of the American Heart Association (AHA) 3 and European Society of Cardiology (ESC), 4 but, because of the unintelligible rupture intima, SCIH is easily misdiagnosed as atherosclerotic plaque stenosis. 2 In this study, we investigated the management and prognosis of SCIH in our center.
Methods
Study Population
We retrospectively analyzed patients with SCIH from January 1, 2012 to December 31, 2018 at Zhongshan Hospital, Fudan University. According to the literature, SCIH was defined as SCAD without obvious intima tear on coronary angiography, that is, non-classical SCAD (type 1 SCAD).3,4 The study was approved by the institutional review board, and all patients signed a general informed consent form.
Definition
All the clinical baseline data, examinations, treatment, and coronary angiography findings, including whether percutaneous coronary intervention (PCI) was performed, were collected. The SCIH was classified as type 1, 2, and 3 in this study based on the angiography findings (Figure 1). Type 1 refers to diffuse stenosis (length greater than 20 mm) and can be subclassified as type 1A based on long diffuse arterial narrowing in the middle coronary artery and or type 1B based on diffuse narrowing that extends to the distal tip of the artery, including occlusion of the distal coronary artery. Type 2 is characterized by focal nonatherosclerotic smooth stenosis, which is usually diagnosed by intracoronary imaging. The involvement of multiple vessels (different coronary arteries rather than one main branch with side branches) was classified as type 3 SCIH. The angiographic classification of SCIH. (a to c) type 1: diffuse stenosis (a) type 1a: long diffuse arterial narrowing in the middle coronary artery (b) type 1B: diffuse narrowing extending to the distal tip of the artery (c) type 1a and 1b: diffuse stenosis from middle to end of coronary artery (d) type 2: focal nonatherosclerotic smooth stenosis (e and f) type 3: multiple vessels (left circumflex branch and right coronary artery from a patient). Arrows indicate the sites of SCIH. SCIH, spontaneous coronary intramural hematoma.
Data Collection
All the patients were followed up by telephone, office visit, or hospitalization reexamination. The patients experienced the following main adverse cardiovascular events: angina pectoris, myocardial infarction, malignant arrhythmia, heart failure, cardiac death, and PCI.
Statistical Analysis
Results are expressed as mean ± standard deviation, and the categorical variables are expressed as the rate or constituent ratio. All the data were processed using SPSS 24.0 statistics software (IBM, Armonk, New York, USA).
Results
Clinical Data
Clinical Characteristics of Spontaneous Coronary Intramural Hematoma Patients.
Data presented as n or n(%).
Abbreviations: MI, myocardial infarction; PCI, percutaneous coronary intervention; CABG, coronary artery bypass grafting; SCIH, spontaneous coronary intramural hematoma; ACEI/ARB, angiotensin converting enzyme inhibitor/angiotensin receptor blocker; CCB, calcium channel blocker; DHP, dihydropyridine.
When admitted, 93.3% (28/30) of the patients had an acute myocardial infarction (AMI) and 6 patients (6/30) exhibited ST-segment elevation AMI (STEMI). The other 2 patients were diagnosed with unstable angina. Six patients demonstrated regional wall motion abnormalities of the left ventricle in echocardiograms. The left ventricular ejection fraction (LVEF) was 62.8 ± 5.4%.
Coronary Angiography and PCI
Although most of the patients had ACS, only 3 patients underwent emergency PCI. The mean time from symptom onset to coronary angiography was 7.0 ± 5.4 days, and the median time was 6 days. The reasons for delayed examinations are delay in visiting a doctor, patient transfer, low risk of patients, willingness to agree to undergo coronary angiography, and the medical insurance protocols.
Thirty-five coronary arteries had SCIH. The most affected vessel was the left anterior descending branch (LAD), and which was detected in 20 patients (66.7%). The left circumflex branch (LCX) and right coronary artery were affected in 7 (23.3%) and 8 (26.7%) of the patients, respectively. Four patients exhibited both the LAD and LCX, and both the LCX and RCA were affected in 1 patient. According to the classification of SCIH in this study, 70%, 13.3%, and 16.7% of the patients were classified as type 1, 2, and 3, respectively. Among the 21 patients with type 1 SCIH, 7 (33.3%) patients were classified as subtypes 1A, 1B, 1A, and 1B, respectively.
The diagnosis of 20 patients was confirmed by intravascular ultrasound (IVUS), which depended on the interventional cardiologists, and intimal tears were only found in 4 patients. Seven patients had a PCI, and 2 patients were subjected to balloon dilation, including a cutting balloon (1 patient). Five patients underwent both balloon dilation and drug eluting stent implantation.
Medication
Conservative treatment was the first choice for the SCAD patients included in this study. Dual antiplatelet therapy (aspirin combined with clopidogrel or ticagrelor) was administered to 19 patients (63.3%). In contrast, 7 patients were administered aspirin alone (23.3%), 1 patient was administered clopidogrel alone (3.3%), and 3 patients (10%) did not receive any antiplatelet drugs. Twenty patients (66.7%) were using beta-blockers, and 23 cases (76.7%) were administered angiotensin converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB) drugs. Nine patients (30%) were administered nitrate drugs, and 25 patients (83.3%) were administered statins. For the treatment of coronary spasms, 4 patients (13.3%) were administered diltiazem, 5 patients (16.7%) were administered benidipine, and 1 patient was administered both diltiazem and benidipine.
Follow-up
The mean follow-up time was 29.3 ± 13.5 months, and 2 patients were lost to follow-up. None of the patients were readmitted due to worsening symptoms, and 5 patients complained of occasional agnogenic discomfort. The LVEF at follow-up was 65.8 ± 4.6% after 6.6 ± 3.1 months. Four patients with stent implantation continued dual antiplatelet therapy for 1 year and then changed to aspirin. Eight patients who were initially administered dual antiplatelet therapy were changed to single antiplatelet therapy after 2.9 ± 1.5 months, and 5 patients stopped antiplatelet treatment based on their doctors’ advice 2.2 ± 1.1 months. Eight patients continued aspirin treatment, and 1 patient continued clopidogrel treatment. Twelve patients continued to use beta-blockers. With normal left ventricular ejection fraction and no hypertension, 12 patients stopped ACEI/ARB treatment. Twelve patients discontinued statin treatment because they had optimal low density lipoprotein cholesterol with low atherosclerotic cardiovascular disease risk and no hyperlipemia. Only 1 patient continued to use diltiazem.
Nine patients underwent coronary artery computed tomography (CT) reexamination after 10.3 ± 7.5 months, which showed recovery of SCIH. Eight patients were hospitalized for coronary angiography 6.4 ± 4.7 months later and did not show any sign of SCIH, as was confirmed by IVUS for 1 patient. One patient showed restenosis of the stent and was subsequently subjected to drug-coated balloon intervention.
Discussion
The current research and guidelines regarding SCIH as a type of SCAD, and classical SCAD, that is, type 1 SCAD, differs from SCIH.2-4 SCIH has been separately investigated in very few studies; thus, the characteristics and prognosis of SCIH are unclear. In this retrospective study, the patients with SCIH were mainly middle-aged and elderly, and men were slightly older than women, which is similar to previous studies.5,6 In addition to high blood pressure, the proportion of risk factors for coronary heart disease was deficient. More than 50% of the patients had a history of hypertension, and the ratio of hypertension in SCAD patients in previous studies was up to 50%. Intimal injury in patients with hypertension might be a potential mechanism for SCIH. In contrast to the previous studies,7,8 no other pathogenesis, such as connective tissue disease or fibromuscular dysplasia, was found in any of the patients except for 1 female patient with SLE; this might be related to insufficient detection; thus, the correlation between SCIH and other diseases was not supported by the findings of the present study.
In contrast to classical SCAD, SCIH demonstrates no intimal flap on coronary angiography. Based on published studies and guidelines, we divided SCAD into 3 classifications: diffuse lesion (type 1), focal lesion (type 2), and multivessel disease (type 3). Type 1 was the most common, whereas type 2 was the least common, which was consistent with the results of previous studies.2,9,10 Some patients were misdiagnosed in previous studies due to the difficulty in distinguishing SCIH from focal atherosclerosis lesions without intracoronary imaging. The present study proposes the existence of type 3 SCIH, which indicates that at least 2 coronary arteries were affected. Similar cases involving multiple coronary arteries were ignored by previous studies.3,11 2 patients with type 3 SCIH suffered from STEMI. Whether the different coronary arteries were affected simultaneously or individually is unclear. Until now, the mechanism of SCIH was unclear, and the existence of type 3 SCIH implies that the pathogenesis of SCIH differs from that of classical coronary artery dissection. The pathogenesis of classical coronary artery dissection involves coronary artery intima tear or rupture. In the absence of atherosclerosis, the intima of 2 different vessels is very unlikely to have broken simultaneously or separately.
Although dual antiplatelet therapy should be administered to MI patients, antiplatelet therapies are controversial in classical SCAD. 12 Evidence from clinical trials is lacking. The expert consensus and guideline at present recommend that dual antiplatelet therapy may be considered during the acute phase of SCAD.3,4 But because quality data are missing, the kind and duration of antiplatelet therapy should be determined for each patient, especially for SCIH patients. The hematoma of SCIH is squeezed, and the coronary artery cavity becomes small, which causes flow obstruction and increases the risk of thrombosis. So, the use of antiplatelet therapy is reasonable. But antiplatelet drugs might also not benefit SCIH. The intima is complete or slightly broken without plaques, and the probability of thrombosis event occurrence is very low. In addition, antiplatelet drugs might cause hematoma progression or absorption delay; thus, antiplatelet drugs for SCIH may be more harmful than beneficial, even though 19 patients in this study were administered dual antiplatelet therapy. Like antiplatelet drugs, statin therapy is generally not helpful for SCIH unless the patients also have hyperlipidemia. More than half of the patients had hypertension, and beta-blockers and ACEI/ARBs are beneficial for controlling blood pressure, particularly in patients with reduced LVEF. Given the possibility of coronary spasm, some patients might experience symptom improvement by using antispasmodic medications. 13
Conservative treatment was the most selected therapy of most interventional physicians, consistent with previous studies.12,14,15 Because the hematoma can be naturally absorbed weeks later, it is reasonable to wait for healing. In addition, coronary stent implantation might cause iatrogenic extension of the hematoma. If coronary flow is poor, balloon dilation of the coronary artery to restore blood flow is the method that had to be adopted. Patients with unstable hemodynamic conditions and coronary progression may require early coronary revascularization. However, the identification of high-risk and progressive patients is challenging. A previous study showed that patients with SCIH, multiple coronary arteries affected, and long lesions are prone to early progression. 16 Waterbury et al. found that 6 days after the onset of SCAD was the high-risk period for early SCAD extension; the median time was 3 days. 16 Gad et al. found that the worsening of SCAD most likely occurs during the first 7 days, which most commonly occurs during the first 2 days. 11 However, all the patients in this study did not exhibit any symptom aggravation during the follow-up period. Follow-up coronary angiography or CT showed recovery of the coronary artery. Based on this study, SCIH is not a high-risk factor for easy progression. Conservative treatment and waiting for recovery are the best treatment for these patients.
Spontaneous coronary intramural hematoma is considered one type of SCAD, but the ESC and AHA guidelines only describe the characteristics of SCIH. A previous study suggested that SCIH is the initial stage of SCAD. 16 The hematoma can extend horizontally and vertically, leading to increased pressure and rupture of the inner membrane. 16 The pressure of the middle membrane cavity decreases after breakage of the inner membrane, which is beneficial. However, SCIH and classical SCAD are different. First, their pathogenesis differs. Endothelial rupture, which IVUS can confirm, is the marker of classical SCAD but is not necessary for SCIH. Second, the definition of coronary dissection is based on the tear of the intima, but the term intramural hematoma focuses on the accumulated blood between the intima and media. Third, coronary artery events have different causes. The symptoms of SCAD are partly due to hematoma extrusion and decreased blood flow along the vessel cavity. The broken intima in SCAD could cause the clotting system to activate and induce coronary artery thrombus, which are symptoms that might not be observed in SCIH patients. At present, intracoronary imaging is thought not to be beneficial for the therapy and prognosis of SCAD and worse coronary hematoma and is not routinely recommended for SCAD patients. 4 The broken intima might be temporarily closed due to compression of the hematoma, and thus, it is not easy to accurately distinguish SCIH from classical SCAD. Given the lower spatial resolution of IVUS, OCT is recommended over IVUS to assess SCAD. A larger series of SCAD patients has been reported in OCT studies by Jackson et al. 17 A total of 65 SCAD patients (68 vessels) were included, and type 1 patients were 16, and other types were 49. Twenty-five fenestrated cases were identified on OCT, which implies that 18.37% (9/49) non-classical SCAD patients had intimal tear. In our study, 20% (4/20) SCIH patients who underwent IVUS had an intimal tear. Jackson et al. postulated 2 hypotheses for how SCAD develops. 17 The “inside-out” theory proposes that a primary event within the vessel wall leads to false lumen formation. The “outside-in” mechanism hypothesizes that a spontaneous hemorrhage from the vasa vasorum starts the dissection process. They concluded that the absence of a fenestration leads to increased false lumen and compression of the true lumen, and the “outside-in” hypothesis could be a unified theory for the development of SCAD. Their observations and hypothesis are consistent with ours. We think that SCIH and classical SCAD are different. The abnormal vasa vasorum hemorrhage was the basis of SCIH and “outside-in” theory. The feature of classical SCAD was an intimal tear which was a key feature of the “inside-out” theory. So, SCIH should be separately studied as a unique SCAD.
Study Limitations
This study has limitations. First, the time from symptom onset to coronary angiography was long, and the time at which the hematoma is most serious after the occurrence of SCIH is unknown. Half of the patients underwent coronary angiography 1 week later. The time to diagnosis for SCIH patients in this study might be too long to observe changes in the lesion, and thus, these changes might have been ignored. Second, the number of SCIHs was small, and very few patients underwent follow-up coronary imaging. Third, this study was not a randomized controlled trial aiming to compare SCIH and classical SCAD, and all the differences between SCIH and classical SCAD are not easily recognized. Fourth, possibly because of insufficient detection, only 1 patient had another disease which might influence the occurrence/outcome of SCIH. Fifth, IVUS is not the best method to detect intimal tears and is likely to fail to recognize classical SCAD from SCIH.
Conclusions
This retrospective study showed that SCIH occurs more often in post-menopausal women, and many of these patients also had hypertension. The LAD, which was the most affected artery, displayed diffuse narrowing, and the end segment might be involved, which could lead to insufficient perfusion. Due to differences in opinion among cardiologists, the patients were administered different drugs, but conservative treatment is currently considered the best choice. Based on our findings that SCIH patients had good prognosis with reduced dosage and shorter course of antiplatelet treatment, SCIH patients may not be administered antiplatelet drugs, particularly strong dual antiplatelet drugs. Furthermore, based on the differences between SCIH and classical SCAD, we recommended that the term SCAD might be renamed SCAD/IH.
Footnotes
Author Contributions
All authors contributed to: (1) substantial contributions to conception and design, or acquisition of data, or analysis and interpretation of data, (2) drafting the article or revising it critically for important intellectual content, and, (3) final approval of the version to be published.
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by Project of Shanghai Municipal Health Commission, China (Grant No. 201940152).
