Additional diagnostic value of CMR to the European Society of Cardiology (ESC) position statement criteria in a large clinical population of patients with suspected myocarditis.

Aims: To determine the diagnostic yield of tissue characterization by cardiovascular magnetic resonance (CMR) in a large clinical population of patients with suspected acute myocarditis (AM) and to establish its diagnostic value within the 2013 European Society of Cardiology position statement criteria (ESC-PSC) for clinically suspected myocarditis. Methods and results: In this retrospective study, CMR examinations of 303 hospitalized patients referred for work-up of suspected AM in two tertiary referral centres were analysed. CMR was performed at median 7 days (interquartile range 4-20 days) after clinical presentation and included cine imaging, T2-weighted imaging, and late gadolinium enhancement. CMR images were evaluated to assign each patient to a diagnosis. By using non-CMR criteria only, the 2013 ESC-PSC were positive for suspected myocarditis in 151 patients and negative in 30. In the remaining 122 patients, there was insufficient information available for ESC-PSC assessment, mostly due to lack of coronary angiography (CAG) before the CMR examination (n = 116, 95%). There were no in-hospital deaths. CMR provided a diagnosis in 158 patients (52%), including myocarditis in 104 (34%), myocardial infarction in 44 (15%), and other pathology in 10 patients (3%). Non-urgent CAG (>24 h after presentation) was performed before the CMR examination in 85 patients, of which 20 (24%) were done in patients with subsequently confirmed AM, which could potentially have been avoided if CMR was performed first. ESC-PSC was correct in diagnosing AM before the CMR in 50 of the 151 patients (33%) and was correct in ruling out AM in all the 30 patients (100%). However, ESC-PSC provided an incorrect diagnosis of AM in 27 of the 151 patients (18%), which was corrected by CMR through the identification of new cardiac disease that could explain the clinical syndrome. Patients with insufficient ESC-PSC information had a relatively low pre-test probability of coronary artery disease. In this group, CMR confirmed the diagnosis of AM in a relatively high percentage (44%) but still revealed myocardial infarction in 8% of them. Conclusion: Tissue characterization by CMR provided a good diagnostic yield in this large clinical population of patients with suspected AM. CMR provided incremental diagnostic value to the ESC-PSC by ruling out the diagnosis of AM on one hand and by potentially sparing AM patients from CAG on the other.

The influence of microvascular injury on native T1 and T2* relaxation values after acute myocardial infarction: implications for non-contrast-enhanced infarct assessment.

OBJECTIVES: Native T1 mapping and late gadolinium enhancement (LGE) imaging offer detailed characterisation of the myocardium after acute myocardial infarction (AMI). We evaluated the effects of microvascular injury (MVI) and intramyocardial haemorrhage on local T1 and T2* values in patients with a reperfused AMI. METHODS: Forty-three patients after reperfused AMI underwent cardiovascular magnetic resonance imaging (CMR) at 4 [3-5] days, including native MOLLI T1 and T2* mapping, STIR, cine imaging and LGE. T1 and T2* values were determined in LGE-defined regions of interest: the MI core incorporating MVI when present, the core-adjacent MI border zone (without any areas of MVI), and remote myocardium. RESULTS: Average T1 in the MI core was higher than in the MI border zone and remote myocardium. However, in the 20 (47%) patients with MVI, MI core T1 was lower than in patients without MVI (MVI 1048±78ms, no MVI 1111±89ms, p=0.02). MI core T2* was significantly lower in patients with MVI than in those without (MVI 20 [18-23]ms, no MVI 31 [26-39]ms, p<0.001). CONCLUSION: The presence of MVI profoundly affects MOLLI-measured native T1 values. T2* mapping suggested that this may be the result of intramyocardial haemorrhage. These findings have important implications for the interpretation of native T1 values shortly after AMI. KEY POINTS: • Microvascular injury after acute myocardial infarction affects local T1 and T2* values. • Infarct zone T1 values are lower if microvascular injury is present. • T2* mapping suggests that low infarct T1 values are likely haemorrhage. • T1 and T2* values are complimentary for correctly assessing post-infarct myocardium.

Predictors of Intramyocardial Hemorrhage After Reperfused ST-Segment Elevation Myocardial Infarction.

BACKGROUND: Findings from recent studies show that microvascular injury consists of microvascular destruction and intramyocardial hemorrhage (IMH). Patients with ST-segment elevation myocardial infarction (STEMI) with IMH show poorer prognoses than patients without IMH. Knowledge on predictors for the occurrence of IMH after STEMI is lacking. The current study aimed to investigate the prevalence and extent of IMH in patients with STEMI and its relation with periprocedural and clinical variables. METHODS AND RESULTS: A multicenter observational cohort study was performed in patients with successfully reperfused STEMI with cardiovascular magnetic resonance examination 5.5±1.8 days after percutaneous coronary intervention. Microvascular injury was visualized using late gadolinium enhancement and T2-weighted cardiovascular magnetic resonance imaging for microvascular obstruction and IMH, respectively. The median was used as the cutoff value to divide the study population with presence of IMH into mild or extensive IMH. Clinical and periprocedural parameters were studied in relation to occurrence of IMH and extensive IMH, respectively. Of the 410 patients, 54% had IMH. The presence of IMH was independently associated with anterior infarction (odds ratio, 2.96; 95% CI, 1.73-5.06 [P<0.001]) and periprocedural glycoprotein IIb/IIIa inhibitor treatment (odds ratio, 2.67; 95% CI, 1.49-4.80 [P<0.001]). Extensive IMH was independently associated with anterior infarction (odds ratio, 3.76; 95% CI, 1.91-7.43 [P<0.001]). Presence and extent of IMH was associated with larger infarct size, greater extent of microvascular obstruction, larger left ventricular dimensions, and lower left ventricular ejection fraction (all P<0.001). CONCLUSIONS: Occurrence of IMH was associated with anterior infarction and glycoprotein IIb/IIIa inhibitor treatment. Extensive IMH was associated with anterior infarction. IMH was associated with more severe infarction and worse short-term left ventricular function in patients with STEMI.

Strain analysis in CRT candidates using the novel segment length in cine (SLICE) post-processing technique on standard CMR cine images.

OBJECTIVES: Although myocardial strain analysis is a potential tool to improve patient selection for cardiac resynchronization therapy (CRT), there is currently no validated clinical approach to derive segmental strains. We evaluated the novel segment length in cine (SLICE) technique to derive segmental strains from standard cardiovascular MR (CMR) cine images in CRT candidates. METHODS: Twenty-seven patients with left bundle branch block underwent CMR examination including cine imaging and myocardial tagging (CMR-TAG). SLICE was performed by measuring segment length between anatomical landmarks throughout all phases on short-axis cines. This measure of frame-to-frame segment length change was compared to CMR-TAG circumferential strain measurements. Subsequently, conventional markers of CRT response were calculated. RESULTS: Segmental strains showed good to excellent agreement between SLICE and CMR-TAG (septum strain, intraclass correlation coefficient (ICC) 0.76; lateral wall strain, ICC 0.66). Conventional markers of CRT response also showed close agreement between both methods (ICC 0.61-0.78). Reproducibility of SLICE was excellent for intra-observer testing (all ICC ≥0.76) and good for interobserver testing (all ICC ≥0.61). CONCLUSIONS: The novel SLICE post-processing technique on standard CMR cine images offers both accurate and robust segmental strain measures compared to the 'gold standard' CMR-TAG technique, and has the advantage of being widely available. KEY POINTS: • Myocardial strain analysis could potentially improve patient selection for CRT. • Currently a well validated clinical approach to derive segmental strains is lacking. • The novel SLICE technique derives segmental strains from standard CMR cine images. • SLICE-derived strain markers of CRT response showed close agreement with CMR-TAG. • Future studies will focus on the prognostic value of SLICE in CRT candidates.

Changes in remote myocardial tissue after acute myocardial infarction and its relation to cardiac remodeling: A CMR T1 mapping study.

OBJECTIVES: To characterize the temporal alterations in native T1 and extracellular volume (ECV) of remote myocardium after acute myocardial infarction (AMI), and to explore their relation to left ventricular (LV) remodeling. METHODS: Forty-two patients with AMI successfully treated with primary PCI underwent cardiovascular magnetic resonance after 4-6 days and 3 months. Cine imaging, late gadolinium enhancement, and T1-mapping (MOLLI) was performed at 1.5T. T1 values were measured in the myocardial tissue opposite of the infarct area. Myocardial ECV was calculated from native- and post-contrast T1 values in 35 patients, using a correction for synthetic hematocrit. RESULTS: Native T1 of remote myocardium significantly decreased between baseline and follow-up (1002 ± 39 to 985 ± 30ms, p<0.01). High remote native T1 at baseline was independently associated with a high C-reactive protein level (standardized Beta 0.32, p = 0.04) and the presence of microvascular injury (standardized Beta 0.34, p = 0.03). ECV of remote myocardium significantly decreased over time in patients with no LV dilatation (29 ± 3.8 to 27 ± 2.3%, p<0.01). In patients with LV dilatation, remote ECV remained similar over time, and was significantly higher at follow-up compared to patients without LV dilatation (30 ± 2.0 versus 27 ± 2.3%, p = 0.03). CONCLUSIONS: In reperfused first-time AMI patients, native T1 of remote myocardium decreased from baseline to follow-up. ECV of remote myocardium decreased over time in patients with no LV dilatation, but remained elevated at follow-up in those who developed LV dilatation. Findings from this study may add to an increased understanding of the pathophysiological mechanisms of cardiac remodeling after AMI.

Changes in Coronary Blood Flow After Acute Myocardial Infarction: Insights From a Patient Study and an Experimental Porcine Model.

OBJECTIVES: The aim of this study was to determine the effects of an acute myocardial infarction (AMI) on baseline and hyperemic flow in both culprit and nonculprit arteries. BACKGROUND: An impaired coronary flow reserve (CFR) after AMI is related to worse outcomes. The individual contribution of resting and hyperemic flow to the reduction of CFR is unknown. Furthermore, it is unclear whether currently used experimental models of AMI resemble the clinical situation with respect to coronary flow parameters. METHODS: Intracoronary Doppler flow velocity measurements were obtained in culprit and nonculprit arteries immediately after successfully revascularized ST-segment elevation myocardial infarction (n = 40). Stable patients without obstructive coronary artery disease served as control subjects and were selected by propensity-score matching (n = 40). Similar measurements in an AMI porcine model were taken both before and immediately after 75-min balloon occlusion of the left circumflex artery (n = 11). RESULTS: In the culprit artery, CFR was 36% lower than in matched control subjects (Δ = -0.9; 1.8 ± 0.9 vs. 2.8 ± 0.7; p < 0.001) with consistent observations in swine (Δ = -0.9; 1.5 ± 0.4 vs. 2.4 ± 0.9 for after and before AMI, respectively; p = 0.04). An increased baseline and a decreased hyperemic flow contributed to the reduction in CFR in both patients (baseline flow: Δ = +5 and hyperemic flow: Δ = -7 cm/s) and swine (baseline flow: Δ = +8 and hyperemic flow: Δ = -6 cm/s). Similar changes were observed in nonculprit arteries (CFR: 2.8 ± 0.7 vs. 2.0 ± 0.7 for STEMI patients and control subjects; p < 0.001). CFR significantly correlated with infarct size as a percentage of the left ventricle in both patients (r = -0.48; p = 0.001) and swine (r = -0.61; p = 0.047). CONCLUSIONS: CFR in both culprit and nonculprit coronary arteries decreases after AMI with contributions from both an increased baseline flow and a decreased hyperemic flow. The decreased CFR after AMI in culprit and nonculprit vessels is not a result of pre-existing microvascular dysfunction, but represents a combination of post-occlusive hyperemia, myocardial necrosis, hemorrhagic microvascular injury, compensatory hyperkinesis, and neurohumoral vasoconstriction.

Non-invasive imaging to identify susceptibility for ventricular arrhythmias in ischaemic left ventricular dysfunction.

OBJECTIVE: Non-invasive imaging of myocardial perfusion, sympathetic denervation and scar size contribute to enhanced risk prediction of ventricular arrhythmias (VA). Some of these imaging parameters, however, may be intertwined as they are based on similar pathophysiology. The aim of this study was to assess the predictive role of myocardial perfusion, sympathetic denervation and scar size on the inducibility of VA in patients with ischaemic cardiomyopathy in a head-to-head fashion. METHODS: 52 patients with ischaemic heart disease and left ventricular ejection fraction (LVEF) ≤35%, referred for primary prevention implantable cardioverter-defibrillator (ICD) implantation, were included. Late gadolinium-enhanced cardiovascular MRI was performed to assess LV volumes, function and scar size. Using [(15)O]H2O and [(11)C]hydroxyephedrine positron emission tomography, both resting and hyperaemic myocardial blood flow (MBF), and sympathetic innervation were assessed. After ICD implantation, an electrophysiological study (EPS) was performed and was considered positive in case of sustained VA. RESULTS: Patients with a positive EPS (n=25) showed more severely impaired global hyperaemic MBF (p=0.003), larger sympathetic denervation size (p=0.048) and tended to have larger scar size (p=0.07) and perfusion defect size (p=0.06) compared with EPS-negative patients (n=27). No differences were observed in LV volumes, LVEF and innervation-perfusion mismatch size. Multivariable analysis revealed that impaired hyperaemic MBF was the single best independent predictor for VA inducibility (OR 0.78, 95% CI 0.65 to 0.94, p=0.007). A combination of risk markers did not yield incremental predictive value over hyperaemic MBF alone. CONCLUSIONS: Of all previously validated approaches to evaluate the arrhythmic substrate, global impaired hyperaemic MBF was the only independent predictor of VA inducibility. Moreover, a combined approach of different imaging variables did not have incremental value.

Kinetics of coagulation in ST-elevation myocardial infarction following successful primary percutaneous coronary intervention.

INTRODUCTION: ST-elevated myocardial infarction (STEMI) is most frequently caused by coronary occlusion due to formation of an intracoronary thrombus in reaction to rupture of atherosclerotic plaques. Little is known about kinetics of coagulation markers after STEMI in patients treated according to current guidelines. We aimed to investigate kinetics of important coagulation markers in percutaneous coronary intervention (PCI)-treated STEMI patients. MATERIALS AND METHODS: 60 consecutive PCI-treated STEMI patients were prospectively included. Blood samples were collected immediately after as well as 1, 4 and 7 days following PCI. Samples collected 90 days after PCI served as baseline values. ADAMTS13 activity, VWF (von Willebrand factor) activity, VWF antigen, VWF propeptide, fibrinogen antigen, D-dimer, alpha2-antiplasmin (α2AP), plasmin-alpha2-antiplasmin complex (PAP), prothrombin fragment F1+2 (F1+2), prothrombin time (PT), activated partial thromboplastin time (aPTT), and anti-factor Xa (anti-Xa) were measured. Cardiac magnetic resonance (CMR) was performed at 4-6 and 90 days after PCI in 49 patients and left ventricular ejection fraction (LVEF), infarct size and microvascular injury (MVI) were determined. RESULTS: Immediately after PCI, ADAMTS13 activity, fibrinogen antigen and α2AP levels were significantly decreased and VWF activity, VWF antigen and VWF propeptide levels were significantly elevated, compared to baseline. Individual coagulation markers and different combinations thereof were not related to LVEF or infarct size at 90 days, or the occurrence of MVI at 4-6 days after PCI. CONCLUSION: Coagulation parameters show a very dynamic profile in the early days after STEMI. However, individual coagulation parameters or combinations thereof do not predict CMR-defined LVEF, infarct size or MVI.

Feasibility and outcome of the implementation of a screening program for panic disorder in noncardiac chest pain patients in cardiac emergency department routine care.

OBJECTIVE: This study assesses the feasibility and outcome of the implementation of a screening program for classifying panic disorder (PD) in patients presenting with noncardiac chest pain (NCCP(1)), when integrated in routine cardiac emergency department (CED(2)) care. METHODS: Barrier analyses were made during the pilot phase and implementation period. NCCP patients aged 18-70 years presenting at the CED (n=252) were eligible for screening with the Hospital Anxiety and Depression Scale (HADS). Those scoring above cutoff on the HADS were referred to the psychiatric department and received the Composite International Diagnostic Interview. RESULTS: Screening was initiated in 60 patients (23.8%), of whom nine refused participation. Staff adherence remained low despite implementing several improvements in the screening procedure. In total, 39 patients completed the program; 8 were diagnosed with a psychiatric disorder, including 2 patients with PD. CONCLUSION: Feasibility of implementation of this screening program for PD in NCCP patients in routine CED care was limited because offering screening frequently conflicted with provision of acute care and because patients showed relatively high refusal rates. Contrasting our assumption, various other psychiatric disorders besides PD were classified.

Clinical Impact of Cardiac Magnetic Resonance Imaging Versus Echocardiography-Guided Patient Selection for Primary Prevention Implantable Cardioverter Defibrillator Therapy.

The main eligibility criterion for primary prevention implantable cardioverter defibrillator (ICD) therapy, that is, left ventricular ejection fraction (LVEF), is based on large clinical trials using primarily 2-dimensional echocardiography (2DE). Presently, cardiac magnetic resonance imaging (MRI) is considered the gold standard for LVEF assessment. It has been demonstrated that cardiac MRI assessment results in lower LVEFs compared with 2DE. Consequently, cardiac MRI-LVEF assessment may lead to more patients eligible for ICD implantation with potential clinical consequences. The aim of this study was to evaluate the clinical impact of cardiac MRI-LVEF versus 2DE-LVEF assessment for ICD eligibility. A total of 149 patients with cardiac MRI-LVEF ≤35% referred for primary prevention ICD implantation who underwent both 2DE and cardiac MRI-LVEF assessment were retrospectively included. 2DE-LVEF was computed by Simpson's biplane method. Cardiac MRI-LVEF was computed after outlining the endocardial contours in short-axis cine images. Appropriate device therapy (ADT) and all-cause mortality were evaluated during 2.9 ± 1.7 years of follow-up. The present study found that cardiac MRI-LVEF was significantly lower compared with 2DE-LVEF (23 ± 8% vs 30 ± 8%, respectively, p <0.001), resulting in 29 (19%) more patients eligible for ICD implantation according to the current guidelines (LVEF ≤35%). Patients with 2DE-LVEF >35% but cardiac MRI-LVEF ≤35% experienced a lower ADT rate compared with patients having 2DE-LVEF ≤35% (2.1% vs 10.4% per year, respectively, p = 0.02). Application of cardiac MRI-LVEF cutoff of 30% resulted in 119 eligible patients experiencing 9.9% per year ADT, comparable with 2DE-LVEF cut-off value of 35%. In conclusion, cardiac MRI-LVEF assessment resulted in more patients eligible for ICD implantation compared with 2DE who showed a relatively low event rate during follow-up. The event rate in patients with cardiac MRI-LVEF ≤30% was comparable with patients having a 2DE-LVEF ≤35%. This study suggests the need for re-evaluation of cardiac MRI-based LVEF cut-off values for ICD eligibility.

Diagnosis of myocarditis: Current state and future perspectives.

Myocarditis, i.e. inflammation of the myocardium, is one of the leading causes of sudden cardiac death (SCD) and dilated cardiomyopathy (DCM) in young adults, and is an important cause of symptoms such as chest pain, dyspnea and palpitations. The pathophysiological process of disease progression leading to DCM involves an ongoing inflammation as a result of a viral-induced auto-immune response or a persisting viral infection. It is therefore crucial to detect the disease early in its course and prevent persisting inflammation that may lead to DCM and end-stage heart failure. Because of the highly variable clinical presentation, ranging from mild symptoms to severe heart failure, and the limited available diagnostic tools, the evaluation of patients with suspected myocarditis represents an important clinical dilemma in cardiology. New approaches for the diagnosis of myocarditis are needed in order to improve recognition, to help unravel its pathophysiology, and to develop new therapeutic strategies to treat the disease. In this review, we give a comprehensive overview of the current diagnostic strategies for patients with suspected myocarditis, and demonstrate several new techniques that may help to improve the diagnostic work-up.

Doppler-derived intracoronary physiology indices predict the occurrence of microvascular injury and microvascular perfusion deficits after angiographically successful primary percutaneous coronary intervention.

BACKGROUND: A total of 40% to 50% of patients with ST-segment-elevation myocardial infarction develop microvascular injury (MVI) despite angiographically successful primary percutaneous coronary intervention (PCI). We investigated whether hyperemic microvascular resistance (HMR) immediately after angiographically successful PCI predicts MVI at cardiovascular magnetic resonance and reduced myocardial blood flow at positron emission tomography (PET). METHODS AND RESULTS: Sixty patients with ST-segment-elevation myocardial infarction were included in this prospective study. Immediately after successful PCI, intracoronary pressure-flow measurements were performed and analyzed off-line to calculate HMR and indices derived from the pressure-velocity loops, including pressure at zero flow. Cardiovascular magnetic resonance and H2 (15)O PET imaging were performed 4 to 6 days after PCI. Using cardiovascular magnetic resonance, MVI was defined as a subendocardial recess of myocardium with low signal intensity within a gadolinium-enhanced area. Myocardial perfusion was quantified using H2 (15)O PET. Reference HMR values were obtained in 16 stable patients undergoing coronary angiography. Complete data sets were available in 48 patients of which 24 developed MVI. Adequate pressure-velocity loops were obtained in 29 patients. HMR in the culprit artery in patients with MVI was significantly higher than in patients without MVI (MVI, 3.33±1.50 mm Hg/cm per second versus no MVI, 2.41±1.26 mm Hg/cm per second; P=0.03). MVI was associated with higher pressure at zero flow (45.68±13.16 versus 32.01±14.98 mm Hg; P=0.015). Multivariable analysis showed HMR to independently predict MVI (P=0.04). The optimal cutoff value for HMR was 2.5 mm Hg/cm per second. High HMR was associated with decreased myocardial blood flow on PET (myocardial perfusion reserve <2.0, 3.18±1.42 mm Hg/cm per second versus myocardial perfusion reserve ≥2.0, 2.24±1.19 mm Hg/cm per second; P=0.04). CONCLUSIONS: Doppler-flow-derived physiological indices of coronary resistance (HMR) and extravascular compression (pressure at zero flow) obtained immediately after successful primary PCI predict MVI and decreased PET myocardial blood flow. CLINICAL TRIAL REGISTRATION URL: http://www.trialregister.nl. Unique identifier: NTR3164.

Sympathetic denervation is associated with microvascular dysfunction in non-infarcted myocardium in patients with cardiomyopathy.

AIMS: Sympathetic denervation typically occurs in the infarcted myocardium and is associated with sudden cardiac death. Impaired innervation was also demonstrated in non-infarcted myocardium in ischaemic and dilated cardiomyopathy (ICMP and DCMP). Factors affecting sympathetic nerve integrity in remote myocardium are unknown. Perfusion abnormalities, even in the absence of epicardial coronary artery disease, may relate to sympathetic dysfunction. This study was aimed to assess the interrelations of myocardial blood flow (MBF), contractile function, and sympathetic innervation in non-infarcted remote myocardium. METHODS AND RESULTS: Seventy patients with ICMP or DCMP and LVEF ≤35% were included. [(15)O]H2O- and [(11)C]hydroxyephedrine (HED) PET was performed to quantify resting MBF, hyperaemic MBF, and sympathetic innervation. Cardiovascular magnetic resonance (CMR) imaging was performed to assess left ventricular function, mass, wall thickening, and scar size. Wall thickening, [(11)C]HED retention index (RI), and MBF were assessed in remote segments without scar, selected on CMR. [(11)C]HED RI was correlated with resting MBF (r = 0.41, P < 0.001) and hyperaemic MBF (r = 0.55, P < 0.001) in remote myocardium in both ICMP and DCMP. In addition, LV volumes (r = -0.40, P = 0.001), LV mass (r = -0.31, P = 0.008), and wall thickening (r = 0.45, P < 0.001) correlated with remote [(11)C]HED RI. Multivariable analysis revealed that hyperaemic MBF (B = 0.79, P < 0.001), wall thickening (B = 0.01, P = 0.03), and LVEDV (B = -0.03, P = 0.02) were independent predictors for remote [(11)C]HED RI. CONCLUSION: Hyperaemic MBF is independently associated with sympathetic innervation in non-infarcted remote myocardium in patients with ICMP and DCMP. This suggests that microvascular dysfunction might be an important factor related to sympathetic nerve integrity. Whether impaired hyperaemic MBF is the primary cause of this relation remains unclear.

Intramyocardial haemorrhage after acute myocardial infarction.

In patients with acute myocardial infarction (AMI), the guideline-recommended treatment is mechanical revascularization by percutaneous coronary intervention (PCI), which is effective at reducing mortality. However, a substantial proportion of patients with AMI develop chronic cardiac failure owing to poor restoration of microvascular function and myocardial perfusion, despite restoration of epicardial vessel patency. This occurrence is called the 'no-reflow' phenomenon. Although pathological and clinical observations initially seemed to support the hypothesis that no-reflow was the result of microvascular obstruction, irreversible microvascular injury and subsequent intramyocardial haemorrhage are now also thought to be important factors in this process. Intramyocardial haemorrhage shares several pathophysiological features with the haemorrhagic transformation that occurs after ischaemic stroke. Understanding of the role of intramyocardial haemorrhage in the no-reflow phenomenon and myocardial injury is crucial to the development of new therapeutic strategies to treat AMI. In this Review, we provide a comprehensive overview of the pathogenesis and clinical relevance of intramyocardial haemorrhage, and discuss diagnostic options and future therapeutic strategies.

Evaluating the optimal timing of revascularisation in patients with transient ST-segment elevation myocardial infarction: rationale and design of the TRANSIENT Trial.

Patients with chest pain and a prehospital ST-segment elevation myocardial infarction (STEMI) are preferably treated with immediate percutaneous coronary intervention (PCI). However, patients with normalization of symptoms and ST-segment elevation upon hospital arrival (transient STEMI) received inconsistent therapy due to logistic reasons and the absence of evidence or explicit guidelines. In this trial, the optimal timing of coronary angiography and subsequent revascularisation is investigated in patients presenting with transient STEMI. In this prospective, multicentre, randomized controlled clinical trial, 142 consecutive patients with initially acute chest pain and STEMI, whose symptoms and ST-segment elevation resolve upon admission, are randomized to immediate intervention or a delayed intervention. Primary outcome is infarct size measured at 4 days determined by cardiovascular magnetic resonance. Secondary outcomes are left ventricular function and volumes, myocardial salvage and microvascular injury at baseline; the change in left ventricular function, volumes and infarct size at 4 months; and major adverse cardiac events at 4 and 12 months. The TRANSIENT Trial evaluates whether a delayed invasive strategy (according to NSTEMI-guidelines) is superior to an immediate invasive strategy (according to STEMI-guidelines) in patients with a transient STEMI.

In-vivo T1 cardiovascular magnetic resonance study of diffuse myocardial fibrosis in hypertrophic cardiomyopathy.

BACKGROUND: In hypertrophic cardiomyopathy (HCM), autopsy studies revealed both increased focal and diffuse deposition of collagen fibers. Late gadolinium enhancement imaging (LGE) detects focal fibrosis, but is unable to depict interstitial fibrosis. We hypothesized that with T1 mapping, which is employed to determine the myocardial extracellular volume fraction (ECV), can detect diffuse interstitial fibrosis in HCM patients. METHODS: T1 mapping with a modified Look-Locker Inversion Recovery (MOLLI) pulse sequence was used to calculate ECV in manifest HCM (n = 16) patients and in healthy controls (n = 14). ECV was determined in areas where focal fibrosis was excluded with LGE. RESULTS: The total group of HCM patients showed no significant changes in mean ECV values with respect to controls (0.26 ± 0.03 vs 0.26 ± 0.02, p = 0.83). Besides, ECV in LGE positive HCM patients was comparable with LGE negative HCM patients (0.27 ± 0.03 vs 0.25 ± 0.03, p = 0.12). CONCLUSIONS: This study showed that HCM patients have a similar ECV (e.g. interstitial fibrosis) in myocardium without LGE as healthy controls. Therefore, the additional clinical value of T1 mapping in HCM seems limited, but future larger studies are needed to establish the clinical and prognostic potential of this new technique within HCM.

Cell therapy in reperfused acute myocardial infarction does not improve the recovery of perfusion in the infarcted myocardium: a cardiac MR imaging study.

PURPOSE: To investigate the effects of cell therapy on myocardial perfusion recovery after treatment of acute myocardial infarction (MI) with primary percutaneous coronary intervention (PCI). MATERIALS AND METHODS: In this HEBE trial substudy, which was approved by the institutional review board (trial registry number ISRCTN95796863), the authors assessed the effects of intracoronary infusion with bone marrow-derived mononuclear cells (BMMCs) or peripheral blood-derived mononuclear cells (PBMCs) on myocardial perfusion recovery by using cardiac magnetic resonance (MR) imaging after revascularization. In 152 patients with acute MI treated with PCI, cardiac MR imaging was performed after obtaining informed consent-before randomization to BMMC, PBMC, or standard therapy (control group)-and repeated at 4-month follow-up. Cardiac MR imaging consisted of cine, rest first-pass perfusion, and late gadolinium enhancement imaging. Perfusion was evaluated semiquantitatively with signal intensity-time curves by calculating the relative upslope (percentage signal intensity change). The relative upslope was calculated for the MI core, adjacent border zone, and remote myocardium. Perfusion differences among treatment groups or between baseline and follow-up were assessed with the Wilcoxon signed rank or Mann-Whitney U test. RESULTS: At baseline, myocardial perfusion differed between the MI core (median, 6.0%; interquartile range [IQR], 4.1%-8.0%), border zone (median, 8.4%; IQR, 6.4%-10.2%), and remote myocardium (median, 12.2%; IQR, 10.5%-15.9%) (P < .001 for all), with equal distribution among treatment groups. These interregional differences persisted at follow-up (P < .001 for all). No difference in perfusion recovery was found between the three treatment groups for any region. CONCLUSION: After revascularization of ST-elevation MI, cell therapy does not augment the recovery of resting perfusion in either the MI core or border zone.