Microvascular Obstruction and Intramyocardial Hemorrhage in Reperfused Myocardial Infarctions: Pathophysiology and Clinical Insights From Imaging.

Microvascular injury immediately following reperfusion therapy in acute myocardial infarction (MI) has emerged as a driving force behind major adverse cardiovascular events in the postinfarction period. Although postmortem investigations and animal models have aided in developing early understanding of microvascular injury following reperfusion, imaging, particularly serial noninvasive imaging, has played a central role in cultivating critical knowledge of progressive damage to the myocardium from the onset of microvascular injury to months and years after in acute MI patients. This review summarizes the pathophysiological features of microvascular injury and downstream consequences, and the contributions noninvasive imaging has imparted in the development of this understanding. It also highlights the interventional trials that aim to mitigate the adverse consequences of microvascular injury based on imaging, identifies potential future directions of investigations to enable improved detection of disease, and demonstrates how imaging stands to play a major role in the development of novel therapies for improved management of acute MI patients.

Utilization of Shock Team and Veno-Arterial Extracorporeal Membrane Oxygenation (VA-ECMO) in the Management of Cardiogenic Shock in Northern Ontario.

Background: Despite advancements in critical care and coronary revascularization, cardiogenic shock (CS) outcomes remain poor. Implementing a shock team and use of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) have been associated with improved CS outcomes, but its feasibility in remote and rural areas remains unknown. Methods: This retrospective study included patients with CS who required mechanical circulatory support (MCS) at Health Sciences North, Sudbury, Ontario. The analysis aimed to accomplish 2 objectives: first, to review the outcomes associated with use of Impella (Abiomed, Danvers, MA) and, second, to assess the feasibility of establishing a shock team to facilitate the local implementation of VA-ECMO. The primary endpoint was in-hospital mortality. Results: The outcomes of 15 patients with CS who received Impella between 2015 and 2021 were reviewed. Their average age was 65 years (standard deviation [SD]: 13), and 8 patients (53%) were female. CS was ischemic in 12 patients (80%). Transfemoral Impella CP (cardiac power) was the most frequently used (93%). Thirteen patients (87%) died during the index hospital stay post-Impella because of progressive circulatory failure. The shock team was established following consultations with several Canadian MCS centres, leading to the development of a protocol to guide use of MCS. There have been 4 cases in which percutaneous VA-ECMO using Cardiohelp (Getinge/Maquet, Wayne, NJ) has been used; 3 (75%) survived beyond the index hospitalization. Conclusions: This analysis demonstrated the feasibility of implementing a shock team in remote Northern Ontario, enabling the use of VA-ECMO with success in a centre with a sizeable rural catchment area. This initiative helps address the gap in cardiac care outcomes between rural and urban areas in Ontario.

Introduction: En dépit des avancées des soins aux patients en phase critique et de la revascularisation coronarienne, les résultats du choc cardiogénique (CC) semblent mauvais. La mise en place d'une équipe de choc et l'utilisation de l'oxygénation extracorporelle (ECMO, de l'anglais extracorporeal membrane oxygenation) par voie veino-artérielle (VA) (VA-ECMO) ont été associées à de meilleurs résultats du CC, mais on ignore sa faisabilité dans les régions éloignées et rurales. Méthodes: La présente étude rétrospective portait sur des patients en CC qui ont eu besoin d'une assistance circulatoire mécanique (ACM) à Horizon Santé-Nord, à Sudbury, en Ontario. L'analyse visait 2 objectifs : le premier objectif était de passer en revue les résultats associés à l'utilisation de Impella (Abiomed, Danvers, MA) et, le deuxième était d'évaluer la faisabilité de la mise en place d'une équipe de choc pour faciliter la mise en œuvre locale de la VA-ECMO. Le principal critère d'évaluation était la mortalité intrahospitalière. Résultats: Nous avons passé en revue les résultats cliniques de 15 patients ayant subi un CC qui avaient reçu une Impella entre 2015 et 2021. L'âge moyen était de 65 ans (écart type [ET] : 13), et 8 patients (53 %) étaient des femmes. Le CC était d'origine ischémique chez 12 patients (80 %). L'Impella CP (cardiac power, soit la pompe cardiaque) par voie transfémorale était la plus fréquemment utilisée (93 %). Treize patients (87 %) sont morts durant le séjour de référence à l'hôpital après l'utilisation de l'Impella en raison d'insuffisance circulatoire progressive. La mise en place de l'équipe de choc à la suite des consultations dans plusieurs centres canadiens d'ACM a mené à l'élaboration d'un protocole d'utilisation de l'ACM. Il y a eu 4 cas chez lesquels la VA-ECMO par voie percutanée à l'aide de Cardiohelp (Getinge/Maquet, Wayne, New Jersey, É.-U.) a été utilisée ; 3 (75 %) ont survécu après l'hospitalisation de référence. Conclusions: Cette analyse a démontré la faisabilité de la mise en place d'une équipe de choc dans les régions éloignées du nord de l'Ontario, qui a permis d'utiliser efficacement la VA-ECMO dans un centre d'une circonscription hospitalière rurale non négligeable. Cette initiative aide à remédier à l'écart des résultats en soins cardiaques entre les régions rurales et urbaines de l'Ontario.

The Canadian Cardiovascular Society Classification of Acute Atherothrombotic Myocardial Infarction Based on Stages of Tissue Injury Severity: An Expert Consensus Statement.

Myocardial infarction (MI) remains a leading cause of morbidity and mortality. In atherothrombotic MI (ST-elevation MI and type 1 non-ST-elevation MI), coronary artery occlusion leads to ischemia. Subsequent cardiomyocyte necrosis evolves over time as a wavefront within the territory at risk. The spectrum of ischemia and reperfusion injury is wide: it can be minimal in aborted MI or myocardial necrosis can be large and complicated by microvascular obstruction and reperfusion hemorrhage. Established risk scores and infarct classifications help with patient management but do not consider tissue injury characteristics. This document outlines the Canadian Cardiovascular Society classification of acute MI. It is an expert consensus formed on the basis of decades of data on atherothrombotic MI with reperfusion therapy. Four stages of progressively worsening myocardial tissue injury are identified: (1) aborted MI (no/minimal myocardial necrosis); (2) MI with significant cardiomyocyte necrosis, but without microvascular injury; (3) cardiomyocyte necrosis and microvascular dysfunction leading to microvascular obstruction (ie, "no-reflow"); and (4) cardiomyocyte and microvascular necrosis leading to reperfusion hemorrhage. Each stage reflects progression of tissue pathology of myocardial ischemia and reperfusion injury from the previous stage. Clinical studies have shown worse remodeling and increase in adverse clinical outcomes with progressive injury. Notably, microvascular injury is of particular importance, with the most severe form (hemorrhagic MI) leading to infarct expansion and risk of mechanical complications. This classification has the potential to stratify risk in MI patients and lay the groundwork for development of new, injury stage-specific and tissue pathology-based therapies for MI.

Intramyocardial hemorrhage drives fatty degeneration of infarcted myocardium.

Sudden blockage of arteries supplying the heart muscle contributes to millions of heart attacks (myocardial infarction, MI) around the world. Although re-opening these arteries (reperfusion) saves MI patients from immediate death, approximately 50% of these patients go on to develop chronic heart failure (CHF) and die within a 5-year period; however, why some patients accelerate towards CHF while others do not remains unclear. Here we show, using large animal models of reperfused MI, that intramyocardial hemorrhage - the most damaging form of reperfusion injury (evident in nearly 40% of reperfused ST-elevation MI patients) - drives delayed infarct healing and is centrally responsible for continuous fatty degeneration of the infarcted myocardium contributing to adverse remodeling of the heart. Specifically, we show that the fatty degeneration of the hemorrhagic MI zone stems from iron-induced macrophage activation, lipid peroxidation, foam cell formation, ceroid production, foam cell apoptosis and iron recycling. We also demonstrate that timely reduction of iron within the hemorrhagic MI zone reduces fatty infiltration and directs the heart towards favorable remodeling. Collectively, our findings elucidate why some, but not all, MIs are destined to CHF and help define a potential therapeutic strategy to mitigate post-MI CHF independent of MI size.

Intramyocardial Hemorrhage and the "Wave Front" of Reperfusion Injury Compromising Myocardial Salvage.

BACKGROUND: Reperfusion therapy for acute myocardial infarction (MI) is lifesaving. However, the benefit of reperfusion therapy can be paradoxically diminished by reperfusion injury, which can increase MI size. OBJECTIVES: Hemorrhage is known to occur in reperfused MIs, but whether hemorrhage plays a role in reperfusion-mediated MI expansion is not known. METHODS: We studied cardiac troponin kinetics (cTn) of ST-segment elevation MI patients (n = 70) classified by cardiovascular magnetic resonance to be hemorrhagic (70%) or nonhemorrhagic following primary percutaneous coronary intervention. To isolate the effects of hemorrhage from ischemic burden, we performed controlled canine studies (n = 25), and serially followed both cTn and MI size with time-lapse imaging. RESULTS: CTn was not different before reperfusion; however, an increase in cTn following primary percutaneous coronary intervention peaked earlier (12 hours vs 24 hours; P < 0.05) and was significantly higher in patients with hemorrhage (P < 0.01). In hemorrhagic animals, reperfusion led to rapid expansion of myocardial necrosis culminating in epicardial involvement, which was not present in nonhemorrhagic cases (P < 0.001). MI size and salvage were not different at 1 hour postreperfusion in animals with and without hemorrhage (P = 0.65). However, within 72 hours of reperfusion, a 4-fold greater loss in salvageable myocardium was evident in hemorrhagic MIs (P < 0.001). This paralleled observations in patients with larger MIs occurring in hemorrhagic cases (P < 0.01). CONCLUSIONS: Myocardial hemorrhage is a determinant of MI size. It drives MI expansion after reperfusion and compromises myocardial salvage. This introduces a clinical role of hemorrhage in acute care management, risk assessment, and future therapeutics.

Rare case of iatrogenic aortic valve leaflet tear following a diagnostic coronary angiogram.

We report a rare case of a 44-year-old male who underwent a diagnostic coronary angiogram following a non-ST elevation myocardial infarction complicated by an aortic valve leaflet tear requiring surgical intervention. Routine transthoracic echocardiogram demonstrated a mobile echogenic structure prolapsing into the left ventricular outflow tract. An intraoperative transesophageal echocardiogram confirmed that the structure originated from the ventricular side of left coronary cusp, causing malcoaptation between left and right coronary cusps, and subsequent moderate to severe aortic regurgitation.

An Unusual Case of Cardiac Tamponade Secondary to an Elevated Right Hemidiaphragm.

Diaphragmatic eventration in old age is a rare phenomenon. Typically, it is thought to originate as a result of failure of development of the muscles of the diaphragm. Less commonly, it can occur secondary to acquired conditions resulting from spinal cord or phrenic nerve injury and is only detected incidentally when the patient presents with dyspnea, chest infection, or cardiac compression symptoms. Herein, we report a case of right diaphragmatic paralysis in a 58-year-old man with a presentation of marked elevation of the right hemidiaphragm and ascites causing a picture compatible with cardiac tamponade.

Recent Advances in Cardiovascular Magnetic Resonance: Techniques and Applications.

Cardiovascular magnetic resonance imaging has become the gold standard for evaluating myocardial function, volumes, and scarring. Additionally, cardiovascular magnetic resonance imaging is unique in its comprehensive tissue characterization, including assessment of myocardial edema, myocardial siderosis, myocardial perfusion, and diffuse myocardial fibrosis. Cardiovascular magnetic resonance imaging has become an indispensable tool in the evaluation of congenital heart disease, heart failure, cardiac masses, pericardial disease, and coronary artery disease. This review will highlight some recent novel cardiovascular magnetic resonance imaging techniques, concepts, and applications.

Persistent Microvascular Obstruction After Myocardial Infarction Culminates in the Confluence of Ferric Iron Oxide Crystals, Proinflammatory Burden, and Adverse Remodeling.

BACKGROUND: Emerging evidence indicates that persistent microvascular obstruction (PMO) is more predictive of major adverse cardiovascular events than myocardial infarct (MI) size. But it remains unclear how PMO, a phenomenon limited to the acute/subacute period of MI, drives adverse remodeling in chronic MI setting. We hypothesized that PMO resolves into chronic iron crystals within MI territories, which in turn are proinflammatory and favor adverse remodeling post-MI. METHODS AND RESULTS: Canines (n=40) were studied with cardiac magnetic resonance imaging to characterize the spatiotemporal relationships among PMO, iron deposition, infarct resorption, and left ventricular remodeling between day 7 (acute) and week 8 (chronic) post-MI. Histology was used to assess iron deposition and to examine relationships between iron content with macrophage infiltration, proinflammatory cytokine synthesis, and matrix metalloproteinase activation. Atomic resolution transmission electron microscopy was used to determine iron crystallinity, and energy-dispersive X-ray spectroscopy was used to identify the chemical composition of the iron composite. PMO with or without reperfusion hemorrhage led to chronic iron deposition, and the extent of this deposition was strongly related to PMO volume (r>0.8). Iron deposits were found within macrophages as aggregates of nanocrystals (≈2.5 nm diameter) in the ferric state. Extent of iron deposits was strongly correlated with proinflammatory burden, collagen-degrading enzyme activity, infarct resorption, and adverse structural remodeling (r>0.5). CONCLUSIONS: Crystallized iron deposition from PMO is directly related to proinflammatory burden, infarct resorption, and adverse left ventricular remodeling in the chronic phase of MI in canines. Therapeutic strategies to combat adverse remodeling could potentially benefit from taking into account the chronic iron-driven inflammatory process.

Usefulness of cardiac resonance imaging in Churg-Strauss syndrome.

: Churg-Strauss syndrome (CSS) is a rare entity that is characterized by widespread vasculitis, which affects both small and medium-sized blood vessels of nearly all organs. More than 50% of these cases have cardiac involvement, which is the major cause of morbidity and mortality. We describe a case of a patient with cardiac biopsy proven CSS, and we discuss the usefulness of cardiovascular MRI for its diagnosis.

Cardiac magnetic resonance in clinical cardiology.

Over the last decades, cardiac magnetic resonance (CMR) has transformed from a research tool to a widely used diagnostic method in clinical cardiology. This method can now make useful, unique contributions to the work-up of patients with ischemic and non-ischemic heart disease. Advantages of CMR, compared to other imaging methods, include very high resolution imaging with a spatial resolution up to 0.5 mm × 0.5 mm in plane, a large array of different imaging sequences to provide in vivo tissue characterization, and radiation-free imaging. The present manuscript highlights the relevance of CMR in the current clinical practice and new perspectives in cardiology.

Acute myocarditis triggering coronary spasm and mimicking acute myocardial infarction.

A 24-year-old healthy man consulted to our center because of typical on-and-off chest-pain and an electrocardiogram showing ST-segment elevation in inferior leads. An urgent coronary angiography showed angiographically normal coronary arteries. Cardiovascular magnetic resonance imaging confirmed acute myocarditis. Although acute myocarditis triggering coronary spasm is an uncommon association, it is important to recognize it, particularly for the management for those patients presenting with ST-segment elevation and suspect myocardial infarction and angiographically normal coronary arteries. The present report highlights the role of cardiovascular magnetic resonance imaging to identify acute myocarditis as the underlying cause.

Detection of acute reperfusion myocardial hemorrhage with cardiac MR imaging: T2 versus T2.

PURPOSE: To evaluate T2 and T2* changes in acute reperfused hemorrhagic and nonhemorrhagic myocardial infarctions and to determine which technique is more suitable in the detection of intramyocardial hemorrhage at 1.5 T. MATERIALS AND METHODS: Patient studies were approved by the institutional review board and were HIPAA compliant. Patients (n = 14, three women) with first ST-elevation myocardial infarction underwent cardiac magnetic resonance (MR) imaging 3 days after angioplasty. T2* maps, T2 short inversion time inversion-recovery (STIR) images, and late gadolinium enhancement (LGE) images were acquired. Animal studies were approved by the institutional animal care and use committee. Canines (n = 20) were subjected to ischemia-reperfusion injury, and cardiac MR imaging was performed 5 days after reperfusion. T2* and T2 maps and T2 STIR and LGE images were acquired. Repeated-measures analysis of variance or the Friedman test was used to compare T2 and T2* changes in patients with hemorrhagic infarctions and those with nonhemorrhagic infarctions. RESULTS: Relative to remote myocardium, mean T2* of hemorrhagic infarctions was 54% ± 13 (standard deviation) lower in patients (15.9 msec ± 4.5 vs 35.2 msec ± 2.1, P < .001) and 40% ± 10 lower in canines (23.0 msec ± 4.0 vs 39.3 msec ± 2.5, P < .001). Mean T2* of nonhemorrhagic infarctions was marginally elevated by 6% ± 2.5 (37.8 msec ± 2.5, P = .021) in patients and by 8% ± 5 (44.6 msec ± 4.8, P = .012) in canines. In contrast, mean T2 STIR signal intensity (SI) of both hemorrhagic infarctions and nonhemorrhagic infarctions was higher than that in remote myocardium both in patients (hemorrhagic: 37% ± 19, P < .001; nonhemorrhagic: 78% ± 27, P < .001) and in canines (hemorrhagic: 42% ± 22, P < .001; nonhemorrhagic: 65% ± 22, P < .001). Consistent with STIR SI findings, mean T2 of both hemorrhagic (62.0 msec ± 4.9) and nonhemorrhagic (71.7 msec ± 7.3) infarctions in canines was elevated relative to mean T2 of remote myocardium (52.1 msec ± 4.8) by 18% ± 9 and 38% ± 13, respectively (P < .001 for both). CONCLUSION: T2* cardiac MR imaging is more suitable than T2 cardiac MR imaging in the detection and characterization of acute reperfusion myocardial hemorrhage. SUPPLEMENTAL MATERIAL: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.13122397/-/DC1.

Chronic manifestation of postreperfusion intramyocardial hemorrhage as regional iron deposition: a cardiovascular magnetic resonance study with ex vivo validation.

BACKGROUND: Intramyocardial hemorrhage frequently accompanies large reperfused myocardial infarctions. However, its influence on the makeup and the ensuing effect on the infarcted tissue during the chronic phase remain unexplored. METHODS AND RESULTS: Patients (n=15; 3 women), recruited after successful percutaneous coronary intervention for first segment-elevation myocardial infarction, underwent cardiovascular magnetic resonance imaging on day 3 and month 6 after percutaneous coronary intervention. Patients with hemorrhagic (Hemo+) infarctions, as determined by T2* cardiovascular magnetic resonance on day 3 (n=11), showed persistent T2* losses colocalized with scar tissue on the follow-up scans, suggesting chronic iron deposition. T2* values of Hemo+ territories were significantly higher than nonhemorrhagic (Hemo-) and remote territories (P<0.001); however, T2* values of nonhemorrhagic (Hemo-) and remote territories were not different (P=0.51). Canines (n=20) subjected to ischemia-reperfusion injury (n=14) underwent cardiovascular magnetic resonance on days 3 and 56 after ischemia-reperfusion injury. Similarly, sham-operated animals (Shams; n=3) were imaged using cardiovascular magnetic resonance at similar time points. Subsequently, hearts were explanted and imaged ex vivo, and samples of Hemo+, Hemo-, remote, and Sham myocardium were isolated and stained. The extent of iron deposition ([Fe]) within each sample was measured using mass spectrometry. Hemo+ infarcts showed significant T2* losses compared with the other (control) groups (P<0.001), and Perls stain confirmed localized iron deposition. Mean [Fe] of Hemo+ was nearly an order of magnitude greater than that of the control groups (P<0.001), but no significant differences were observed among the control groups. A strong linear relationship was observed between log(T2*) and -log([Fe]); R(2)=0.7 and P<0.001. The monoclonal antibody Mac387 stains, along with Perls stains, showed preferential localization of newly recruited macrophages at the site of chronic iron deposition. CONCLUSIONS: Hemorrhagic myocardial infarction can lead to iron depositions within the infarct zones, which can be a source of prolonged inflammatory burden in the chronic phase of myocardial infarction.

Late gadolinium enhancement in cardiac transplant patients is associated with adverse ventricular functional parameters and clinical outcomes.

BACKGROUND: Heart transplant recipients (HTRs) experience multiple cardiac complications, many of which might produce myocardial fibrosis. Cardiovascular magnetic resonance imaging (CMR) can image myocardial fibrosis using late gadolinium enhancement (LGE) imaging. We hypothesized that the presence and volume of LGE in heart transplant recipients correlates with left ventricular (LV) functional parameters and clinical outcomes. METHODS: Thirty-eight stable HTRs underwent a CMR study and clinical follow-up. RESULTS: In 38 stable HTRs, LGE was seen in 19 patients (50%), of which 15 (79%) had a nonischemic pattern and 4 (21%) had an ischemic pattern. LGE volume was associated with reduced LV ejection fraction (EF) (R(2) = 0.57; P = 0.001) and increased LV end-diastolic volume (R(2) = 0.59; P = 0.001). The presence of LGE was associated with cardiovascular death or hospitalization within the next year (P = 0.04), and patients who died or were hospitalized had more LGE than those that were not hospitalized (15 g vs 7 g; P = 0.03). CONCLUSIONS: LGE is common in HTR and is associated with adverse ventricular remodelling and adverse clinical outcomes. LGE might be a useful noninvasive approach to monitor graft disease in asymptomatic patients after heart transplant.

Sudden cardiac arrest due to subtotal absence of left-sided pericardium--case report and review of the literature.

Congenital absence of the pericardium is a very rare cardiac malformation, usually diagnosed fortuitously on autopsy or surgery. Symptoms related to these abnormalities are usually benign, and fatalities reported in the literature are almost exclusively secondary to herniation of the heart through a partial defect. We present the unusual case of a 44-year-old woman admitted for sudden cardiac arrest. Initial evaluation suggested acute anterior myocardial infarction, but further investigation ruled out coronary heart disease. No arrhythmia could be initiated on electrophysiological study, and absence of most of the left pericardium was confirmed by cardiac magnetic resonance imaging. After the exclusion of common etiologies such as idiopathic ventricular fibrillation, transient great vessel torsion due to hypermobility of the heart with secondary malignant arrhythmia was considered to be the most likely mechanism for the sudden cardiac arrest. A review of the available literature on clinical presentation, diagnostic tools, and therapeutic options is also presented.