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 Table of Contents  
STATE-OF-THE-ART REVIEW
Year : 2022  |  Volume : 6  |  Issue : 1  |  Page : 32-44

Reperfusion Injury-Related Intramyocardial Hemorrhage: Pivotal Role of Echocardiography and Magnetic Resonance Imaging in Diagnosis and Prognosis


1 Department of Cardiology, Jaipur Golden Hospital, Rohini, Delhi, India
2 Department of Cardiology, Jupiter Hospital, Thane, Mumbai, Maharashtra, India

Date of Submission11-Jan-2022
Date of Acceptance16-Jan-2022
Date of Web Publication29-Apr-2022

Correspondence Address:
Prof. Jagdish Chander Mohan
A51, Hauz Khas, New Delhi - 110 016
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jiae.jiae_3_22

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  Abstract 


Myocardial reperfusion injury is defined as the death of cardiomyocytes as a direct result of one or more events initiated by reperfusion. These events could be inflammation, oxidative stress, calcium overload, neurohumoral activation, cytotoxicity of anaerobic metabolites, etc. Intramyocardial hemorrhage as a consequence of ischemia–reperfusion injury during acute myocardial infarction and subsequently is frequent and portends worse prognosis. Animal studies have demonstrated that intramyocardial hemorrhage does not occur with ST-elevation myocardial infarction unless myocardium is reperfused with blood. Magnetic resonance imaging is the technique of choice for its detection but has limited availability in emergencies and is expensive. Echocardiography can be used for indirect myocardial tissue characterization. Echocardiography coupled with myocardial contrast imaging is increasingly being used for detecting hemorrhage in infarcted segments. In the presence of wall motion abnormality, increased segmental echogenicity, significantly increased wall thickness underlying hypermobile endocardium, and neocavitations within the myocardium are the characteristic features. Occasionally, extensive wall splitting and formation of pseudotumor due to large hematoma are the striking features of intramyocardial hemorrhage. Intramyocardial hemorrhage in acute myocardial infarction can occur during early phase, following reperfusion and during remodeling process. There is no definite echocardiographic imaging method to assess reperfusion hemorrhage in vivo, but signal-void cavity-like or cystic appearance within the myocardium in the setting of myocardial infarction is highly suggestive. Detecting hypointense area of hemorrhage could be complicated by low-intensity echoes emanating from the normal myocardium. Echocardiography should be performed in every patient before and after reperfusion therapy and serially till discharge. There are no studies comparing the diagnostic yield of echocardiography compared to magnetic resonance imaging. Those with obvious myocardial hematoma need special attention with regard to antiremodeling agents, dual antiplatelet therapy, and possibly surgery. A majority of patients with significant intramural hemorrhage end up having reduced left ventricular function, adverse remodeling, true or pseudo-aneurysms, and even heart failure although spontaneous resorption has also been reported.

Keywords: Dissecting myocardial hematoma, hemorrhagic infarction, intramyocardial hemorrhage, reperfusion injury


How to cite this article:
Mohan JC, Shukla M, Burkule N. Reperfusion Injury-Related Intramyocardial Hemorrhage: Pivotal Role of Echocardiography and Magnetic Resonance Imaging in Diagnosis and Prognosis. J Indian Acad Echocardiogr Cardiovasc Imaging 2022;6:32-44

How to cite this URL:
Mohan JC, Shukla M, Burkule N. Reperfusion Injury-Related Intramyocardial Hemorrhage: Pivotal Role of Echocardiography and Magnetic Resonance Imaging in Diagnosis and Prognosis. J Indian Acad Echocardiogr Cardiovasc Imaging [serial online] 2022 [cited 2022 May 23];6:32-44. Available from: https://www.jiaecho.org/text.asp?2022/6/1/32/344311




  Introduction Top


Acute myocardial infarction remains a major public health challenge both because of its immediate consequences and its long-term impact on health. A significant proportion of patients remain unrecognized till they present with heart failure. Efficacious reperfusion strategy has gained ground in the last 40 years. Initially, reperfusion was via thrombolysis; however, soon, primary percutaneous coronary intervention became the dominant effective strategy. Spontaneous reperfusion in the first 24 h also occurs to a variable extent. Early reperfusion within the first 48 h of onset of symptoms results in salvage of ischemic myocardium, depending upon at what speed ischemic wavefront progresses from subendocardial to subepicardial region[1] [Figure 1]. Earlier is the reperfusion, greater is the benefit [Figure 2]. However, reperfusion is a doubled-edged sword. A part of affected myocardium may be given the kiss of death by what is called “reperfusion injury”[2] [Figure 3] and [Figure 4]a, [Figure 4]b. Cardiomyocytes and capillary endothelial cells, which are destined to survive initial ischemic injury, may be killed by the process of reperfusion[2] [Figure 5]. At tissue level, no-reflow due to microvascular obstruction occurs in about 50% of patients following successful epicardial reperfusion.[3] Microvascular obstruction due to platelet–neutrophil plugs, microthrombi, atheroembolic material, vasospasm, and capillary endothelial swelling leads to severe tissue ischemia and more myocyte death.[5] Quite often, microvascular endothelial cells burst open compromising integrity of the myocardial vasculature with resultant hemorrhage [Figure 6]. Myocardial hemorrhage is frequent and has been reported to occur in 30%–45% of patients.[5] It could also be a manifestation of relative hyperperfusion. Reperfusion injury is relatively time independent unlike ischemic injury [Figure 7]. Reperfusion injury was rare before the era of thrombolysis but is frequently seen following the advent of reperfusion therapy. There are multiple ways reperfusion can occur [Figure 8]. Those who have evidence of reperfusion injury despite occluded affected coronary artery present an interesting challenge. It is possible that these patients undergo the phenomenon of occlusion–ischemia–reperfusion–occlusion.
Figure 1: Theoretical reconstruct of wavefront hypothesis of myocardial necrosis over time following coronary artery occlusion

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Figure 2: Proposed myocardial salvage by timely reperfusion

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Figure 3: Simplified version of reperfusion injury

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Figure 4: (a) Reperfusion injury contributes to the final infarct size to a variable extent following reperfusion. (b) The impact of reperfusion and reperfusion injury on cell death

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Figure 5: Mechanisms of cardiomyocyte loss during AMI. AMI: Acute myocardial infarction

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Figure 6: Mechanism of myocardial hemorrhage. Hypoxia-induced disruption in the endothelial barrier and loss of capillary integrity. Reperfusion-induced rise in intravascular pressure (barotrauma) damages the ischemic swollen endothelial cells causing their rupture. RBCs: Red blood cells

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Figure 7: Relative time-independent phenomenon of reperfusion injury. There can be large reperfusion injury despite very early reperfusion

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Figure 8: Multiple ways of reperfusion-related injury. AMI: Acute myocardial infarction, MVO: Microvascular obstruction, PCI: Percutaneous coronary intervention

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  Manifestations of Reperfusion Injury and Role of Echocardiography Top


[Table 1] shows the components of reperfusion injury wherein echocardiography can be helpful in detection.
Table 1: Techniques for detection of reperfusion injury and myocardial hemorrhage

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  Wall Thickening due to Myocardial Edema Top


Ischemia results in decreased wall thickness due to reduced myocardial blood volume, necrosis, and lack of contraction.[6] Transient segmental wall thickening following reperfusion is frequent and is considered secondary to cellular and interstitial edema caused by osmotically active anaerobic metabolites in the cells, capillary leakage, as well as loss of cell membrane integrity[7] [Figure 9], [Video 1] and [Video 2]. Myocardial edema may contribute to cell death by its physical properties.
Figure 9: (a) Segmental myocardial wall thickening without neo-cavitation, (b) Natural course of reperfusion-induced wall thickening over time LV: Left ventricle

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Video 1: Reperfusion injury manifesting as increased echogenicity and diastolic wall thickening of the basal inferior wall after right coronary intervention.

[Additional file 1]

Video 2: Reperfusion injury presenting as marked diastolic wall thickening and increased echogenicity of basal inferior and inferolateral segments immediately after balloon dilatation of the occluded left circumflex artery. The patient developed acute heart failure and severe mitral regurgitation.

[Additional file 2]

Occasionally, there is marked segmental thickening both in systole and diastole which persists for several weeks following reperfusion or even without apparent reperfusion [Figure 10]. This thickening possibly is a combination of edema, inflammation, and interstitial hemorrhage. Without neocavitation, it becomes difficult to decide on echocardiography if there is associated hemorrhage. Cardiac magnetic resonance (CMR) imaging may be needed to identify the etiology of the wall thickening of the reperfused myocardium. Prolonged T2 time and shortened T2* values are the characteristics of tissues having edema and heme content, respectively. T2 values >2 standard deviation (edema) or <2 standard deviation compared to that of remote myocardium (intramural hemorrhage) are the easiest methods to differentiate the two. However, in emergency settings, it is usually replaced by bedside echocardiography. Based upon previous observations, it is our understanding that increased echogenicity of the affected segment is usually due to factors other than pure edema.[8],[9] Quite often, these patients have some pericardial effusion [Figure 10]a and [Figure 10]b. In our experience, segmental thickening >150% compared to adjacent nonaffected segment is associated with higher morbidity, longer hospital stay, and complications such as heart failure and acute mitral regurgitation. Neocavitations may occur subsequently in some of these cases.
Figure 10: (a) Images of a 53-year old lawyer after primary angioplasty of dominant right coronary artery for acute myocardial infarction. Arrows point to localized thickening with altered echogenicity of basal and mid inferior wall segments and mild pericardial effusion. (b) A 63-year-old male in acute heart failure after percutaneous stent implantation in circumflex artery. Arrows point to marked thickening and altered echogenicity of basal and mid segments of inferior and inferolateral wall. Note mild pericardial effusion. LA: Left atrium, LV: Left ventricle

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Transient myocardial wall thickening may occur in myocardial infarction due to ischemia–reperfusion injury, Takotsubo syndrome, myocarditis, sepsis, following trauma, cardiopulmonary resuscitation, after cardiopulmonary bypass, or following heart transplantation.[8] Rapid development and then regression of ventricular wall thickening are not due to muscular hypertrophy but due to reversible causes such as myocardial edema or inflammation. Wall thickening with or without subsequent cavitation is also a characteristic of hemorrhage. Thickening of end diastolic wall >120% compared to adjacent normal myocardium is usually considered abnormal. Excessive wall thickening usually has associated extravasation of erythrocytes. Marked segmental wall thickening is associated with worse prognosis[10].


  Reperfusion Is Coupled with Microvascular Obstruction Top


Slow flow or no-reflow following primary angioplasty of acute myocardial infarction has been reported since long and has prognostic significance.[3] No-reflow after angioplasty at tissue level or microvascular obstruction is one of the constant associations of reperfusion injury.[4] It is related to plaque emboli, endothelial swelling, inflammation, extravascular edema, and microvascular spasm.[11] Contrast echocardiography, contrast-enhanced magnetic resonance (MR) imaging, and contrast-enhanced computed tomographic imaging have been used to detect microvascular obstruction. These techniques show microvascular obstruction as a hypoenhanced (signal-void) zone within the acutely reperfused infarct zone [Figure 11]. This hypodense signal disappears after about 10 days. Myocardial hemorrhage is considered a severe form of microvascular obstruction and follows its development in the core of the infarct. The delineation is attributed to inadequate contrast media delivery due to no blood flow. Associated wall thickening or tumor-like appearance on echocardiography is usually due to intramural hematoma (IMH) [Figure 12] and [Figure 13], [Video 3]A and [Video 3]B. It is not certain which factors determine why IMH occurs in some patients with microvascular injury. Myonecrosis-induced inflammation cascade may also have a role. IMH only occurs in the area of microvascular obstruction [Figure 12].
Figure 11: Yellow arrow showing area of microvascular obstruction following primary angioplasty of the right coronary artery using myocardial contrast echocardiography in modified two-chamber view. IVS: Interventricular septum, LV: Left ventricle

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Figure 12: A 67-year-old physician 3 days after primary angioplasty of left anterior artery. Noncontrast echocardiographic view (left panel) shows a cystic mass. Contrast echocardiographic four-chamber view showing a mass with no flow (arrows, hypoechoic mass). Also see Video 3a. LV: Left ventricle

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Figure 13: Neocavitation in the thickened and akinetic segment is a mural hematoma that also shows hypodense appearance on contrast echocardiography. Magnetic resonance detects it reliably by shortened T2* values

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Video 3: (a) A 67-year-old physician presenting with heart failure 3 days after coronary intervention. Contrast echocardiogram in four-chamber view shows a large apicoseptal mass with no contrast entering the space.

[Additional file 3]

(b) Lateral wall intramyocardial hematoma with no contrast entering in the mass.

[Additional file 4]


  Intramyocardial Hemorrhage with or without Hematoma Top


Hemorrhagic transformation of ischemic infarcts has been known for quite some time.[12] It is an under-diagnosed and under-appreciated entity although echocardiography has the potential to show significant IMH [Video 4] and [Video 5]. Tumor or cyst-like appearance within the myocardium with or without protrusion toward cavity is labeled IMH [Video 6]. Myocardial hemorrhage is the final consequence of severe vascular injury and a progressive and prognostically important early complication following infarction. It is a valid but elusive therapeutic target to limit reperfusion injury as it affects healing process, local physiology, and fibrosis. IMH as a complication of reperfusion injury occurs more often in ST elevation myocardial infarction (STEMI) but has also been shown to occur in non-ST elevation infraction.[13] Its presence precedes substantial myocardial and microvascular damage. In the early phase, interstitial blood accumulation creates an external compressive mass on the capillaries. In the chronic phase, it triggers macrophage influx, generation of reactive oxygen species, inflammation, and fibrosis. In selected studies, frequency of patients showing IMH or the amount of IMH is controversially related to time interval between reperfusion and imaging.[14] Temporal evolution of IMH is incompletely understood. There remains a controversy with regard to unimodal versus bimodal pattern of IMH; however, hematoma can be detected even up to 7 months following reperfusion in some cases[5] [Figure 14]. It has been proposed that there are an acute primary phase [<12 h, [Figure 15]] and a subacute secondary phase of IMH[5] [Figure 16].
Figure 14: A middle-aged male presenting with heart failure 2 months after myocardial infarction. Note apical hematoma (arrows). LV: Left ventricle

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Figure 15: A 57-year-old male presenting with acute chest pain and re-elevation of ST segments 30 min after primary angioplasty of the left anterior artery. Patent stent on check angiogram with large intramural hematoma projecting in the cavity like a tumor (arrows). LV: Left ventricle

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Figure 16: Routine echocardiography at discharge on day 4 after primary angioplasty of the left anterior artery following anterior myocardial infarction. Note midseptal hematoma (arrow) in four-chamber and tilted long-axis views. LA: Left atrium, LV: Left ventricle

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Video 4: Apicoseptal hematoma after percutaneous intervention in a 45-year-old male performed within 30 min of onset of chest pain.

[Additional file 5]

Video 5: Large apical hematoma with mobile overlying endocardium seen 2 months after acute myocardial infarction. LA: Left atrium, LV: Left ventricle, RA: Right atrium, RV: Right ventricle.

[Additional file 6]

Video 6: Parasternal long-axis view showing dissection of anterior interventricular septum in a 67-year-old woman who had presented with acute ST-elevation myocardial infarction with recanalized left anterior artery. LA: Left atrium, LV: left ventricle.

[Additional file 7]

Factors that affect occurrence of IMH include collateral flow, ischemic preconditioning, amount of necrosis, distal microembolization, delayed reperfusion, and risk factors such as diabetes and smoking.[15] It is also possible that occasionally, blood from the cavity may be trapped within the myocardium due to a crack in the subendocardium which gets sealed or becomes invisible.

Occasionally, IMH has been reported in old myocardial infarction as a result of remodeling process[16] [Figure 17]. Rise in mural pressure due to IMH leads to increased filling pressures resulting in acute heart failure in many.
Figure 17: (a) Delayed intramural hematoma (arrows) development in a 45-year-old patient who suffered from anterior myocardial infarction 1 year before and was enrolled in a randomized trial for stem cell therapy. (b) No contrast enters the affected myocardium due to microvascular obstruction. LA: Left atrium, LV: Left ventricle, RV: Right ventricle

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In a recent large multicenter observational study of 410 patients, 54% of acute myocardial infarction patients exhibited intramural hemorrhage. Intramural hemorrhage was present in 65% of patients scanned a week after reperfusion therapy and in 30% of patients scanned a day after therapy. The independent predictors were anterior location and use of glycoprotein IIb/IIIa receptor antagonists.[17] However, another study of consecutive acute myocardial infarction patients detected intramural hemorrhage in 10% of cases only.[18] IMH is associated with larger infarcts, lower left ventricular function, adverse remodeling, sudden death, and shortened life span[19],[20],[21] [Figure 18] and [Figure 19].
Figure 18: Formation of the apical aneurysm 6 months after acute myocardial infarction. Note left ventricular apical hematoma (yellow arrow) in (a). LA: Left atrium, LV: Left ventricle

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Figure 19: Apical hematoma (a) evolving into a large true aneurysm (b) with spontaneous echo contrast. The left ventricular ejection fraction fell to 20%. LV: Left ventricle

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  Dissecting Myocardial Hematoma: A Distinct Entity? Top


An IMH is a form of contained myocardial rupture, consisting of massive infiltration of blood into and through the myocardial wall. The endocardium and epicardium are intact, and the hematoma is contained entirely within the myocardium. Dissecting myocardial hematoma (DMH) is a term applied to a myocardial appearance by any imaging technique in which spiral fibers are separated by extravasation of large quantities of blood [Figure 20], [Figure 21], [Figure 22], [Video 7]. Occasionally, the apex shows a three-layered structure [Figure 20], [Figure 21], [Figure 22], [Video 8]. Thus, DMH is an unusual form of subacute cardiac rupture that tends to develop along naturally occurring dissection planes between the spiral muscles of the ventricle. The diagnosis is commonly made at surgery, at postmortem examination, or by echocardiography. Variable acoustic densities of the progressive clotting of the IMH, its extension through the hemorrhagic dissection, as well as its independency in relation to ventricular cavities and extracardiac space confirming intact epicardial and endocardial layers are important features.
Figure 20: Elderly gentleman presenting with worsening heart failure 2 months after acute chest pain. Both panels show a dissecting myocardial hematoma separating the spiral apical fibers (arrows) with lakes of hypoechoeic areas. Right panel in diastole. Also see Video 7. IVS: Interventricular septum, LV: Left ventricle, RV: Right ventricle

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Figure 21: (a) Separation of spiral fibers following acute myocardial infarction in (green arrow) and (b) subsequent development of a true aneurysm 3 months later in a 53-year-old policeman. The same patient is also depicted in Videos 8 and 12. A: Aneurysm, LA: Left atrium, LV: Left ventricle

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Figure 22: Separation of two layers of anterior interventricular septum (left panel, arrows) seen in a 68-year-old female patient a day after coronary stenting. Also see Video 11. LA: Left atrium, LV: Left ventricle

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Video 7: Classic dissecting intramyocardial hematoma at left ventricular apex showing separation of spiral fibers and neocavitations. IVS: Interventricular septum, LV: Left ventricle, RV: Right ventricle.

[Additional file 8]

Video 8: Apical dissecting hematoma in a 53-year-old policeman.

[Additional file 9]

The entire myocardium is two-layered structure and hence late separation with DMH is possible [Video 9] and [Video 10], As the interventricular septum is a also two-layered structure, IMH in this region has been often termed DMH [Figure 22], [Video 11].

Video 9: Large apicolateral hematoma in a 47-year-old male who suffered from anterior wall myocardial infarction 1 year before. LA: Left atrium, LV: Left ventricle.

[Additional file 10]

Video 10: The same patient as shown in Video 11. A typical dissecting hematoma is seen in three-dimensional echocardiography.

[Additional file 11]

Video 11: Immediate splitting of anterior septum following left anterior descending artery stent implantation.

[Additional file 12]

There are many reports in the literature wherein neocavitation within the myocardium with thick mobile subendocardial curtain and/or papilla-like projections in the cavity have been labeled DMH [Figure 23], [Figure 24], [Figure 25]. Differentiation between IMH and DMH is essentially semantic. All intramyocardial space-occupying cavitating lesions following myocardial infarction can be termed DMH.
Figure 23: Apical dissecting myocardial hematoma in four-chamber view (arrows) in a 37-year-old male with cardiogenic shock who underwent delayed percutaneous coronary intervention. Note the thick subendocardial curtain with fronds in the cavity Persistent heart failure and death occurred 7 weeks after discharge. LV: Left ventricle

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Figure 24: A 42-year-old male presenting with worsening heart failure of short duration with electrocardiographic evidence of ST-elevation myocardial infarction. Note large left ventricle apical hematoma (arrows) in four-chamber view (left panel) and in short-axis view (right panel) with thick mobile subendocardial curtain. LA: Left atrium, LV: Left ventricle

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Figure 25: A middle-aged man with old anteroseptum myocardial infarction and heart failure presenting with sudden worsening. Echocardiographic parasternal long-axis view (left panel) shows dissecting hematoma. Three-dimensional short-axis view (right panel) shows an interesting echo appearance of dissection. Ao: Aorta, LA: Left atrium, LV: Left ventricle

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Following echocardiographic features of DMH have been described in the literature: [20],[22],[23]

  1. Formation of neocavity with the echo-lucent center
  2. The inner border should be mobile and endomyocardial
  3. The outer side of neocavity should be lined by the myocardium
  4. Changing echogenicity of a cavity with time, suggestive of blood in the cavity
  5. Partial or complete absorption of a cavity
  6. Continuity between dissecting hematoma and the ventricular cavity may occur
  7. Doppler demonstration of color flow in the cavity may be possible [Figure 26].
Figure 26: Color flow velocity profile in an apical DMH. The fluid shows passive motion in phases of cardiac cycle. DMH: Dissecting myocardial hematoma, LV: Left ventricle

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It is proposed that at least three of the above seven echocardiographic characteristics should be present to diagnose DMH. IMH or DMH usually leaves behind sequelae during healing process [Video 12]; however, spontaneous resolution with minimal remodeling has been reported.[24]

Video 12: Formation of apical aneurysm 3 months after acute infarction in the same policeman as shown in Video 8. A: Aneurysm, LA: Left atrium, LV: Left ventricle.

[Additional file 13]

There are instances wherein myocardial dissection may be seen either spontaneously or following myocardial infarction without central echo-lucency [Figure 27], [Figure 28], [Figure 29]. This could be DMH with minimal blood extravasation or could be isolated myocardial dissection.
Figure 27: An 80-year-old female with anterior myocardial infarction with spontaneous dissection of the basal anterior septum. No intervention was performed. Persistent heart failure and pericardial effusion. IVS: Interventricular septum, LV: Left ventricle, MV: Mitral valve

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Figure 28: Spontaneous dissection of anterior septum in a 54-year-old female presenting with acute heart failure, typical ST-elevation myocardial infarction on electrocardiogram and normal coronary angiogram. The patient died after 3 weeks of presentation. Ao: Aorta, LA: Left atrium, LV: Left ventricle

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Figure 29: A 60-year-old female presenting with constant dull ache in the chest. Note layered separation of the anterior interventricular septum (arrow) in long- and short-axis views (a and b). LA: Left atrium, LV: Left ventricle, PM: Papillary muscle

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DMH is sinister. In a review of literature involving 42 patients with DMH, in-hospital mortality was 23% and 38% of patients underwent surgery. Those presenting with DMH late (>24 h) had 50% in-hospital mortality.[25] Nearly 66% of cases had anterior location. DMH is a complication not only following acute myocardial infarction but has also been described to occur spontaneously, following trauma, cardiopulmonary resuscitation, and cardioplegic arrest. It can also occur in the right ventricle.[26],[27] The authors reported a first series of six cases from India with three-dimensional echocardiographic features in 2011.[28] DMH without reperfusion has been seen in authors' experience.

The most important differential diagnosis of DMH is pseudoaneurysm, prominent trabeculations and intracavitary thrombosis [Figure 30] and [Figure 31]. A completely irregular shape of the ventricular wall with flow within it is the hallmark of prominent trabeculations. Unlike pseudoaneurysm, DMH is entirely encompassed within the myocardium. Transthoracic echocardiography and/or transesophageal echocardiography are usually enough to differentiate these entities, but sometimes, the diagnosis is confirmed only at the time of surgery or by CMR imaging.
Figure 30: A 43-year-old male seen a week after percutaneous coronary intervention. Two-dimensional echocardiographic view shows an apical thrombus-like structure (a). Computed tomography (b) shows apical thickening with no contrast going around and similar to myocardial appearance indicating intramural hematoma which is supported by Houndsfield unit of 40 (similar to that of myocardium). LV: Left ventricle, PE: Pericardial effusion

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Figure 31: Dissecting myocardial hematoma at apex of the left ventricle. In reality, it is a pseudoaneurysm with to-and-fro flow (right panel). LA: Left atrium, LV: Left ventricle

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Septal dissection or DMH may be complicated by ventricular septal rupture and left-to-right shunt.[29] In a recent review of literature, Hajsadeghi et al. reported a total of 37 cases who had DMH involving septum that resulted in ventricular septal defect.[30] Several such cases have been seen by authors [Figure 32].
Figure 32: A 65-year-old female presenting with acute anterior myocardial infarction. H indicates myocardial hematoma and arrow points to rupture. H appears like a thrombus. Ao: Aorta, LA: Left atrium, LV: Left ventricle, RA: Right atrium, RVOT: Right ventricular outflow tract

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  Role of Cardiac Magnetic Resonance Imaging in Differentiating Apical Thrombus Versus Apical Hematoma Top


DMH is nothing but an incomplete ventricular rupture or hemorrhagic dissection. When the tear through the myocardium is limited within the myocardial tissues, a mass of blood can form, leading to an IMH. Echocardiographic features which support the diagnosis of an IMH rather than an apical thrombus include variable acoustic densities, a well-visualized myocardial dissecting curtain, leading into a neocavity filled with low contrast blood and an independent mobile endocardial layer seen above the hematoma. Sometimes, a definite plane of separation from unaffected myocardium in the form of a creek may be visible. A pulsatile mass with systolic expansion when present is diagnostic of IMH or DMH. Serial echocardiographic examinations can also resolve the issue. CMR imaging has a much higher sensitivity and accuracy in detecting subtle myocardial hemorrhage within the infarct zone. However, there is usually limited utility of CMR imaging to differentiate IMH and DMH from thrombus or trabeculations in nonapical regions. Differentiating a layered apical clot from apical hematoma is important from diagnostic, therapeutic, and prognostic viewpoints and herein comes the role of MR imaging. Integrity of thickened endocardium separates clot from dissection. In layered clot, endocardium may not be differentiable from the thrombus mass. Occasionally, both can co-exist.

Cine steady-state free-precession sequence provides excellent visualization of the left ventricle, apical thrombus, and dissecting endocardial flap, the typical anatomical structure of DMH [Figure 33], [Figure 34], [Figure 35]. The T1 and T2 sequences are sensitive to blood products and often help in the diagnosis. IMH can be visualized by T2-weighted CMR sequences, because breakdown products of hemoglobin are paramagnetic and can influence magnetic properties of the infarcted myocardium like the MR relaxation times (T1, T2, and T2*). CMR is the only imaging modality able to exactly detect in vivo IMH.
Figure 33: Apical thrombus (red arrow) attached to the thin akinetic segment (yellow arrow) protruding in the cavity on steady-state free precession imaging in two-chamber view (Panel 4). Gray-color map shows that the clot is isointense compared to the myocardium. Panel 1 shows avascular mass on first-pass perfusion study using gadolinium (yellow arrow). Panel 2 and 5 show late gadolinium enhancement sequences in three-chamber and two-chamber views showing bright apical infarct (yellow arrow). Green arrow points to an old scar. Panel 3 exhibits native parametric T1 map in four-chamber view showing higher T1 values of fresh thrombus compared to normal myocardium. Panel 6 is postgadolinium T1 map showing lower values of postcontrast T1 of fresh thrombus rich in plasma (white). Blue color of cavity and infarcted myocardium (higher postcontrast T1) is due to retained gadolinium. (b) Parametric (color coded) T2 map of left ventricular four-chamber view shows large apical clot (black arrow) with higher T2 values than the myocardium (white arrow). See the corresponding color coding on the right-sided color spectrum bar (higher values green to red shades and lower values blue to black shades). Fresh clot is rich in water (trapped plasma) content and hence shows higher T2 values than the myocardium

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Figure 34: Cine-magnetic resonance imaging (steady-state free-precession) in left ventricular four-, three-, and two-chamber views showing apical mass (red arrow), protruding in left ventricular cavity and invaginating into the akinetic and partially thinned left ventricular apical infarct segments (yellow arrow). The grayscale of the clot is hypointense compared to myocardium due to the haem (iron) content of the extravasated blood pool in the intramyocardial dissecting hematoma

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Figure 35: Late gadolinium enhancement sequence (infrared-gradient echo) in left ventricular four-, three-, and two-chamber views showing apical mass (red arrow), without late gadolinium enhancement, with irregular margins and invaginating into left ventricular apical infarct segments (yellow arrow) which are showing transmural late gadolinium enhancement. The nonenhanced mass is extravasated blood pool in the intramyocardial dissecting hematoma and the enhanced surrounding is the infarcted myocardium and tissue tags

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T1-weighted image typically shows hyperintense lesion in the affected region corresponding to blood products due to subacute hemorrhage. The T2-weighted image shows hyperintense foci due to edema or inflammation in infarcted segment but hypointense zone of IMH [Figure 36]. T2 values are higher in a fresh thrombus due to its plasma content but lower in IMH. The delayed enhancement images show the intramural hematoma surrounded with a bright rim of hyperintense infarcted myocardium and dissecting endocardial flap along with hypointense core.[31],[32],[33],[34] Color-coded parametric imaging provides valuable insights in detecting IMH and also its differentiation from a fresh thrombus [Figure 37], [Figure 38], [Figure 39], [Figure 40]. Fresh clot is rich in water (trapped plasma) content and hence shows higher T2 values than the myocardium, while the zone of hemorrhage shows lower T2 values.
Figure 36: Schematic diagram showing utility of parametric magnetic resonance imaging in detecting IMH. IMH: Intramyocardial hemorrhage

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Figure 37: Parametric (color coded) T2 map of left ventricular four-chamber view shows apical mass (black arrow) with very low T2 values than the myocardium (white arrow) while the apical infarcted myocardium (blue arrow) shows higher T2 values. See the corresponding color coding on the right-side color spectrum bar (higher values orange to white shades and lower values red to dark blue shades). The extravasated blood pool in the intramyocardial hematoma is rich in heme (iron) content and hence shows very low T2 values than the myocardium

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Figure 38: Parametric (color-coded) T2 map of left ventricular four-chamber view with T2* values at various regions of interest. The region of interest 1 (red graph line) is situated on the septum (salvaged edematous myocardium, mean T2* = 49.4 ms). The region of interest 2 (blue graph line) is situated in the apical mass (high heme iron content of the extravasated blood pool in the intramyocardial dissecting hematoma, mean T2* = 22 ms). The region of interest 3 (green graph line) is situated on the remote myocardium at basal lateral wall (normal myocardium, mean T2* = 35.4 ms)

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Figure 39: Parametric (color-coded) T1 map of left ventricular four-chamber view shows apical mass with lower T1 values (white arrow) than the normal myocardium (red arrows) while the edematous recently infarcted apical segments (black arrows) show high T1 values. See the corresponding color coding on the right-side color spectrum bar (higher values yellow to white shades and lower values green to dark blue shades). The low T1 values inside the mass is due to the heme (iron) content of the extravasated blood pool in the intramyocardial hematoma. The surrounding infarcted myocardium contains trapped water (edema) and hence shows higher T1 values than the myocardium

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Figure 40: Parametric (color-coded) T1 map of left ventricular four-chamber view with T1 values at various regions of interest. The region of interest 1 (red graph line) is situated on the septum. (salvaged edematous myocardium, mean T1 = 1323 ms). The region of interest 2 (blue graph line) is situated in the apical mass. (high heme iron content of the extravasated blood pool in the intramyocardial dissecting hematoma, mean T1 = 1086 ms). The region of interest 3 (green graph line) is situated on the tissue tag in the apical mass (infarcted myocardium, mean T1 = 1412 ms). The region of interest 4 (yellow graph line) is situated on the remote myocardium at basal lateral wall (normal myocardium, mean T1 = 1195 ms).

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Occasionally, DMH invaginates the adjacent myocardium like a wavefront and is hypointense compared to myocardium and provides distinct MR images [Figure 35].

Extravasated blood due to its heme content and paramagnetic properties provides invaluable insights in pathophysiology of reperfusion injury when viewed by parametric MR imaging [Figure 36], [Figure 37], [Figure 38], [Figure 39, [Figure 40].

T2* sequences are more accurate for IMH detection than T2 ones, probably for the signal intensity changes in the earlier stage. T2*-weighted CMR technique is very sensitive to the paramagnetic effects of iron content of heme, but it requires relatively longer echo times that may degrade image quality during cardiac imaging. Combined T2-weighted and T2* sequences provide a better definition of IMH.[33],[34] It is apparent that T2*-weighted imaging is more sensitive and potentially more specific technique for detecting IMH. T2*-weighted imaging can be created as a postexcitation refocused gradient echo sequence with small flip angle.


  Implications Top


The patients reported in this and other series have shown significantly adverse prognostic value of IMH. Development of new therapeutic strategies to limit or obviate IMH will definitely improve prognosis of acute myocardial infarction. Reperfusion injury such as IMH is the frontier yet to be conquered. Occasionally, spontaneous resolution with no or minimal remodeling is possible.[24] Animal studies and proof-of-concept human trials have shown significant benefits of pharmacotherapy and procedures such as hyperbaric oxygen and hypothermia. However, the clinical benefits are yet to be observed. As capillary over-pressurization may play a role in the development of myocardial edema and IMH, mechanical interventions to prevent uncontrolled pressure rise following epicardial reperfusion might be an appropriate strategy to prevent IMH. However, regulated microcirculation reperfusion after stenting is not an easy thing. It is impractical to perform graded balloon dilatation to allow controlled reperfusion. Certainly, delayed intervention may result in more harm and should be performed only in carefully selected patients. Delayed percutaneous coronary intervention may be the reason for increasingly more number of such patients being seen in India. The magic bullet to prevent reperfusion injury is still to be discovered. Still, judicious use of antithrombotic agents during cath laboratory interventions, avoiding opening infarct-related arteries beyond 48 h and intraprocedural precautions to prevent distal embolization may be helpful.


  Conclusion Top


Unlike CMR imaging, echocardiography detects intramural hemorrhage, IMH and other related injuries following reperfusion in a small number of patients. This figure is close to 5%–10% of all ST elevation myocardial infarctions in authors' experience. However, it is important to diagnose this condition before intervention to prevent unnecessary and potentially harmful procedures, and also after intervention to prognosticate these patients and advise suitable pharmacotherapy. Surgery may be required in some cases although experience is limited in this field.

Financial support and sponsorship

Nil.

Conflicts of interest

J C Mohan is an editorial board member of the Journal of The Indian Academy of Echocardiography & Cardiovascular Imaging. The article was subject to the journal's standard procedures, with peer review handled independently of this editor and their research groups.

There are no other conflicts of interest.



 
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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9], [Figure 10], [Figure 11], [Figure 12], [Figure 13], [Figure 14], [Figure 15], [Figure 16], [Figure 17], [Figure 18], [Figure 19], [Figure 20], [Figure 21], [Figure 22], [Figure 23], [Figure 24], [Figure 25], [Figure 26], [Figure 27], [Figure 28], [Figure 29], [Figure 30], [Figure 31], [Figure 32], [Figure 33], [Figure 34], [Figure 35], [Figure 36], [Figure 37], [Figure 38], [Figure 39], [Figure 40]
 
 
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