Samuli Rauhalammi

Temporal Evolution of Myocardial Hemorrhage and Edema in Patients After Acute ST‐Segment Elevation Myocardial Infarction: Pathophysiological Insights and Clinical Implications

Background The time course and relationships of myocardial hemorrhage and edema in patients after acute ST‐segment elevation myocardial infarction (STEMI) are uncertain. Methods and Results Patients with ST‐segment elevation myocardial infarction treated by primary percutaneous coronary intervention underwent cardiac magnetic resonance imaging on 4 occasions: at 4 to 12 hours, 3 days, 10 days, and 7 months after reperfusion. Myocardial edema (native T2) and hemorrhage (T2*) were measured in regions of interest in remote and injured myocardium. Myocardial hemorrhage was taken to represent a hypointense infarct core with a T2* value <20 ms. Thirty patients with ST‐segment elevation myocardial infarction (mean age 54 years; 25 [83%] male) gave informed consent. Myocardial hemorrhage occurred in 7 (23%), 13 (43%), 11 (33%), and 4 (13%) patients at 4 to 12 hours, 3 days, 10 days, and 7 months, respectively, consistent with a unimodal pattern. The corresponding median amounts of myocardial hemorrhage (percentage of left ventricular mass) during the first 10 days after myocardial infarction were 2.7% (interquartile range [IQR] 0.0–5.6%), 7.0% (IQR 4.9–7.5%), and 4.1% (IQR 2.6–5.5%; P<0.001). Similar unimodal temporal patterns were observed for myocardial edema (percentage of left ventricular mass) in all patients (P=0.001) and for infarct zone edema (T2, in ms: 62.1 [SD 2.9], 64.4 [SD 4.9], 65.9 [SD 5.3]; P<0.001) in patients without myocardial hemorrhage. Alternatively, in patients with myocardial hemorrhage, infarct zone edema was reduced at day 3 (T2, in ms: 51.8 [SD 4.6]; P<0.001), depicting a bimodal pattern. Left ventricular end‐diastolic volume increased from baseline to 7 months in patients with myocardial hemorrhage (P=0.001) but not in patients without hemorrhage (P=0.377). Conclusions The temporal evolutions of myocardial hemorrhage and edema are unimodal, whereas infarct zone edema (T2 value) has a bimodal pattern. Myocardial hemorrhage is prognostically important and represents a target for therapeutic interventions that are designed to preserve vascular integrity following coronary reperfusion. Clinical Trial Registration URL: https://clinicaltrials.gov/. Unique identifier: NCT02072850.

Myocardial Hemorrhage After Acute Reperfused ST-Segment–Elevation Myocardial Infarction: Relation to Microvascular Obstruction and Prognostic Significance

Background—The success of coronary reperfusion therapy in ST-segment–elevation myocardial infarction (MI) is commonly limited by failure to restore microvascular perfusion. Methods and Results—We performed a prospective cohort study in patients with reperfused ST-segment–elevation MI who underwent cardiac magnetic resonance 2 days (n=286) and 6 months (n=228) post MI. A serial imaging time-course study was also performed (n=30 participants; 4 cardiac magnetic resonance scans): 4 to 12 hours, 2 days, 10 days, and 7 months post reperfusion. Myocardial hemorrhage was taken to represent a hypointense infarct core with a T2* value of <20 ms. Microvascular obstruction was assessed with late gadolinium enhancement. Adverse remodeling was defined as an increase in left ventricular end-diastolic volume ≥20% at 6 months. Cardiovascular death or heart failure events post discharge were assessed during follow-up. Two hundred forty-five patients had evaluable T2* data (mean±age, 58 [11] years; 76% men). Myocardial hemorrhage 2 days post MI was associated with clinical characteristics indicative of MI severity and inflammation. Myocardial hemorrhage was a multivariable associate of adverse remodeling (odds ratio [95% confidence interval]: 2.64 [1.07–6.49]; P=0.035). Ten (4%) patients had a cardiovascular cause of death or experienced a heart failure event post discharge, and myocardial hemorrhage, but not microvascular obstruction, was associated with this composite adverse outcome (hazard ratio, 5.89; 95% confidence interval, 1.25–27.74; P=0.025), including after adjustment for baseline left ventricular end-diastolic volume. In the serial imaging time-course study, myocardial hemorrhage occurred in 7 (23%), 13 (43%), 11 (33%), and 4 (13%) patients 4 to 12 hours, 2 days, 10 days, and 7 months post reperfusion. The amount of hemorrhage (median [interquartile range], 7.0 [4.9–7.5]; % left ventricular mass) peaked on day 2 (P<0.001), whereas microvascular obstruction decreased with time post reperfusion. Conclusions—Myocardial hemorrhage and microvascular obstruction follow distinct time courses post ST-segment–elevation MI. Myocardial hemorrhage was more closely associated with adverse outcomes than microvascular obstruction. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT02072850.

Defining myocardial tissue abnormalities in end-stage renal failure with cardiac magnetic resonance imaging using native T1 mapping

Noninvasive quantification of myocardial fibrosis in end-stage renal disease is challenging. Gadolinium contrast agents previously used for cardiac magnetic resonance imaging (MRI) are contraindicated because of an association with nephrogenic systemic fibrosis. In other populations, increased myocardial native T1 times on cardiac MRI have been shown to be a surrogate marker of myocardial fibrosis. We applied this method to 33 incident hemodialysis patients and 28 age- and sex-matched healthy volunteers who underwent MRI at 3.0T. Native T1 relaxation times and feature tracking–derived global longitudinal strain as potential markers of fibrosis were compared and associated with cardiac biomarkers. Left ventricular mass indices were higher in the hemodialysis than the control group. Global, Septal and midseptal T1 times were all significantly higher in the hemodialysis group (global T1 hemodialysis 1171 ± 27 ms vs. 1154 ± 32 ms; septal T1 hemodialysis 1184 ± 29 ms vs. 1163 ± 30 ms; and midseptal T1 hemodialysis 1184 ± 34 ms vs. 1161 ± 29 ms). In the hemodialysis group, T1 times correlated with left ventricular mass indices. Septal T1 times correlated with troponin and electrocardiogram-corrected QT interval. The peak global longitudinal strain was significantly reduced in the hemodialysis group (hemodialysis -17.7±5.3% vs. -21.8±6.2%). For hemodialysis patients, the peak global longitudinal strain significantly correlated with left ventricular mass indices (R = 0.426), and a trend was seen for correlation with galectin-3, a biomarker of cardiac fibrosis. Thus, cardiac tissue properties of hemodialysis patients consistent with myocardial fibrosis can be determined noninvasively and associated with multiple structural and functional abnormalities.

Remote Zone Extracellular Volume and Left Ventricular Remodeling in Survivors of ST-Elevation Myocardial Infarction

The natural history and pathophysiological significance of tissue remodeling in the myocardial remote zone after acute ST-elevation myocardial infarction (STEMI) is incompletely understood. Extracellular volume (ECV) in myocardial regions of interest can now be measured with cardiac magnetic resonance imaging. Patients who sustained an acute STEMI were enrolled in a cohort study (BHF MR-MI [British Heart Foundation Magnetic Resonance Imaging in Acute ST-Segment Elevation Myocardial Infarction study]). Cardiac magnetic resonance was performed at 1.5 Tesla at 2 days and 6 months post STEMI. T1 modified Look-Locker inversion recovery mapping was performed before and 15 minutes after contrast (0.15 mmol/kg gadoterate meglumine) in 140 patients at 2 days post STEMI (mean age: 59 years, 76% male) and in 131 patients at 6 months post STEMI. Remote zone ECV was lower than infarct zone ECV (25.6±2.8% versus 51.4±8.9%; P<0.001). In multivariable regression, left ventricular ejection fraction was inversely associated with remote zone ECV (P<0.001), and diabetes mellitus was positively associated with remote zone ECV (P=0.010). No ST-segment resolution (P=0.034) and extent of ischemic area at risk (P<0.001) were multivariable associates of the change in remote zone ECV at 6 months (&Dgr;ECV). &Dgr;ECV was a multivariable associate of the change in left ventricular end-diastolic volume at 6 months (regression coefficient [95% confidence interval]: 1.43 (0.10–2.76); P=0.036). &Dgr;ECV is implicated in the pathophysiology of left ventricular remodeling post STEMI, but because the effect size is small, &Dgr;ECV has limited use as a clinical biomarker of remodeling. Clinical Trial Registration—URL: https://www.clinicaltrials.gov. Unique identifier: NCT02072850.

Microvascular resistance of the culprit coronary artery in acute ST-elevation myocardial infarction

BACKGROUND. Failed myocardial reperfusion is common and prognostically important after acute ST-elevation myocardial infarction (STEMI). The purpose of this study was to investigate coronary flow reserve (CFR), a measure of vasodilator capacity, and the index of microvascular resistance (IMR; mmHg × s) in the culprit artery of STEMI survivors. METHODS. IMR (n = 288) and CFR (n = 283; mean age [SD], 60 [12] years) were measured acutely using guide wire–based thermodilution. Cardiac MRI disclosed left ventricular pathology, function, and volumes at 2 days (n = 281) and 6 months after STEMI (n = 264). All-cause death or first heart failure hospitalization was independently adjudicated (median follow-up 845 days). RESULTS. Myocardial hemorrhage and microvascular obstruction occurred in 89 (42%) and 114 (54%) patients with evaluable T2*-MRI maps. IMR and CFR were associated with microvascular pathology (none vs. microvascular obstruction only vs. microvascular obstruction and myocardial hemorrhage) (median [interquartile range], IMR: 17 [12.0–33.0] vs. 17 [13.0–39.0] vs. 37 [21.0–63.0], P < 0.001; CFR: 1.7 [1.4–2.5] vs. 1.5 [1.1–1.8] vs. 1.4 [1.0–1.8], P < 0.001), whereas thrombolysis in myocardial infarction blush grade was not. IMR was a multivariable associate of changes in left ventricular end-diastolic volume (regression coefficient [95% CI] 0.13 [0.01, 0.24]; P = 0.036), whereas CFR was not (P = 0.160). IMR (5 units) was a multivariable associate of all-cause death or heart failure hospitalization (n = 30 events; hazard ratio [95% CI], 1.09 [1.04, 1.14]; P < 0.001), whereas CFR (P = 0.124) and thrombolysis in myocardial infarction blush grade (P = 0.613) were not. IMR had similar prognostic value for these outcomes as <50% ST-segment resolution on the ECG. CONCLUSIONS. IMR is more closely associated with microvascular pathology, left ventricular remodeling, and health outcomes than the angiogram or CFR. TRIAL REGISTRATION. NCT02072850. FUNDING. A British Heart Foundation Project Grant (PG/11/2/28474), the National Health Service, the Chief Scientist Office, a Scottish Funding Council Senior Fellowship, a British Heart Foundation Intermediate Fellowship (FS/12/62/29889), and a nonfinancial research agreement with Siemens Healthcare.

Assessment of Fractional Flow Reserve in Patients With Recent Non–ST-Segment–Elevation Myocardial Infarction Comparative Study With 3-T Stress Perfusion Cardiac Magnetic Resonance Imaging

Background—The use of fractional flow reserve (FFR) in acute coronary syndromes is controversial. The British Heart Foundation Fractional Flow Reserve Versus Angiography in Guiding Management to Optimize Outcomes in Non-ST-Elevation Myocardial Infarction (FAMOUS-NSTEMI) study (NCT01764334) has recently demonstrated the safety and feasibility of FFR measurement in patients with non–ST-segment–elevation myocardial infarction. We report the findings of the cardiac magnetic resonance (CMR) substudy to assess the diagnostic accuracy of FFR compared with 3.0-T stress CMR perfusion. Methods and Results—One hundred six patients with non–ST-segment–elevation myocardial infarction who had been referred for early invasive management were included from 2 centers. FFR was measured in all major patent epicardial coronary arteries with a visual stenosis estimated at ≥30%, and if percutaneous coronary intervention was performed, an FFR assessment was repeated. Myocardial perfusion was assessed with stress perfusion CMR at 3 T. The mean age was 56.7±9.8 years; 82.6% were men. Mean time from FFR evaluation to CMR was 6.1±3.1 days. The mean±SD left ventricular ejection fraction was 58.2±9.1%. Mean infarct size was 5.4±7.1%, and mean troponin concentration was 5.2±9.2 &mgr;g/L. There were 34 fixed and 160 inducible perfusion defects. There was a negative correlation between the number of segments with a perfusion abnormality and FFR (r=−0.77; P<0.0001). The overall sensitivity, specificity, positive predictive value, and negative predictive value for an FFR of ⩽0.8 were 91.4%, 92.2%, 76%, and 97%, respectively. Diagnostic accuracy was 92%. The positive and negative predictive values of FFR for flow-limiting coronary artery disease (FFR⩽0.8) in patients with non–ST-segment–elevation myocardial infarction (n=21) who underwent perfusion CMR before invasive angiography were 92% and 93%, respectively. Receiver operating characteristic analysis indicated that the optimal cutoff value of FFR for demonstrating reversible ischemia on CMR was ⩽0.805 (area under the receiver operating characteristic curve, 0.94 [0.9–0.99]; P<0.0001). Conclusions—FFR in patients with recent non–ST-segment–elevation myocardial infarction showed high concordance with myocardial perfusion in matched territories as revealed by 3.0-T stress perfusion CMR. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT02073422.

Myocardial strain in healthy adults across a broad age range as revealed by cardiac magnetic resonance imaging at 1.5 and 3.0T: Associations of myocardial strain with myocardial region, age, and sex

To assess myocardial strain using cine displacement encoding with stimulated echoes (DENSE) using 1.5T and 3.0T MRI in healthy adults.

Diagnostic accuracy of 3.0-T magnetic resonance T1 and T2 mapping and T2-weighted dark-blood imaging for the infarct-related coronary artery in Non-ST-segment elevation myocardial infarction

Background Patients with recent non–ST‐segment elevation myocardial infarction commonly have heterogeneous characteristics that may be challenging to assess clinically. Methods and Results We prospectively studied the diagnostic accuracy of 2 novel (T1, T2 mapping) and 1 established (T2‐weighted short tau inversion recovery [T2W‐STIR]) magnetic resonance imaging methods for imaging the ischemic area at risk and myocardial salvage in 73 patients with non–ST‐segment elevation myocardial infarction (mean age 57±10 years, 78% male) at 3.0‐T magnetic resonance imaging within 6.5±3.5 days of invasive management. The infarct‐related territory was identified independently using a combination of angiographic, ECG, and clinical findings. The presence and extent of infarction was assessed with late gadolinium enhancement imaging (gadobutrol, 0.1 mmol/kg). The extent of acutely injured myocardium was independently assessed with native T1, T2, and T2W‐STIR methods. The mean infarct size was 5.9±8.0% of left ventricular mass. The infarct zone T1 and T2 times were 1323±68 and 57±5 ms, respectively. The diagnostic accuracies of T1 and T2 mapping for identification of the infarct‐related artery were similar (P=0.125), and both were superior to T2W‐STIR (P<0.001). The extent of myocardial injury (percentage of left ventricular volume) estimated with T1 (15.8±10.6%) and T2 maps (16.0±11.8%) was similar (P=0.838) and moderately well correlated (r=0.82, P<0.001). Mean extent of acute injury estimated with T2W‐STIR (7.8±11.6%) was lower than that estimated with T1 (P<0.001) or T2 maps (P<0.001). Conclusions In patients with non–ST‐segment elevation myocardial infarction, T1 and T2 magnetic resonance imaging mapping have higher diagnostic performance than T2W‐STIR for identifying the infarct‐related artery. Compared with conventional STIR, T1 and T2 maps have superior value to inform diagnosis and revascularization planning in non–ST‐segment elevation myocardial infarction. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT02073422.

Myocardial hemorrhage after acute reperfused ST-segment-elevation myocardial infarction

Background—The success of coronary reperfusion therapy in ST-segment–elevation myocardial infarction (MI) is commonly limited by failure to restore microvascular perfusion. Methods and Results—We performed a prospective cohort study in patients with reperfused ST-segment–elevation MI who underwent cardiac magnetic resonance 2 days (n=286) and 6 months (n=228) post MI. A serial imaging time-course study was also performed (n=30 participants; 4 cardiac magnetic resonance scans): 4 to 12 hours, 2 days, 10 days, and 7 months post reperfusion. Myocardial hemorrhage was taken to represent a hypointense infarct core with a T2* value of <20 ms. Microvascular obstruction was assessed with late gadolinium enhancement. Adverse remodeling was defined as an increase in left ventricular end-diastolic volume ≥20% at 6 months. Cardiovascular death or heart failure events post discharge were assessed during follow-up. Two hundred forty-five patients had evaluable T2* data (mean±age, 58 [11] years; 76% men). Myocardial hemorrhage 2 days post MI was associated with clinical characteristics indicative of MI severity and inflammation. Myocardial hemorrhage was a multivariable associate of adverse remodeling (odds ratio [95% confidence interval]: 2.64 [1.07–6.49]; P=0.035). Ten (4%) patients had a cardiovascular cause of death or experienced a heart failure event post discharge, and myocardial hemorrhage, but not microvascular obstruction, was associated with this composite adverse outcome (hazard ratio, 5.89; 95% confidence interval, 1.25–27.74; P=0.025), including after adjustment for baseline left ventricular end-diastolic volume. In the serial imaging time-course study, myocardial hemorrhage occurred in 7 (23%), 13 (43%), 11 (33%), and 4 (13%) patients 4 to 12 hours, 2 days, 10 days, and 7 months post reperfusion. The amount of hemorrhage (median [interquartile range], 7.0 [4.9–7.5]; % left ventricular mass) peaked on day 2 (P<0.001), whereas microvascular obstruction decreased with time post reperfusion. Conclusions—Myocardial hemorrhage and microvascular obstruction follow distinct time courses post ST-segment–elevation MI. Myocardial hemorrhage was more closely associated with adverse outcomes than microvascular obstruction. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT02072850.

79 Diagnostic Accuracy of Myocardial Fractional Flow Reserve for Reversible Perfusion Abnormalities in Patients with Recent Non-ST Elevation Myocardial Infarction

Background Myocardial fractional flow reserve (FFR) has uncertain validity in patients with recent myocardial infarction and the use of FFR in this setting is controversial. We performed a prospective study to assess the diagnostic accuracy of FFR in patients with a recent non-ST segment myocardial infarction (NSTEMI). Methods NSTEMI patients who had been referred for early invasive management were included. FFR was measured in all major patent epicardial coronary arteries with a visual stenosis estimated at ≥30% severity. Where clinically appropriate, an FFR assessment following PCI was also performed. Patients were scheduled for a stress perfusion 3T MRI following discharge from hospital.In a subsetof patients MRI was performed prior to coronary angiography/PCI. Baseline stress (I.V. adenosine 140 µg/kg/min) and rest perfusion MRI images were analysed side-by-side using dedicated software (Argus Dynamic Signal, Siemens, Erlangen, Germany). The stress and rest perfusion scans were viewed simultaneously, areas of hypoperfusion were assigned to coronary territories using the American Heart Association coronary arterial segment model. The analyses were performed independently by two observers who were blinded to the FFR results. In each patient, the coronary artery territories with abnormal perfusion were recorded. In cases of disagreement between observers, a third blinded observer adjudicated. Results 106 NSTEMI patients (mean age 56.7 ± 9.8 years, 82.6% male) were included. The mean time between the FFR evaluation and MRI was 5.8 ± 3.1 days. The mean ± SD left ventricular ejection fraction was 58.2 ± 9.1%. Mean infarct size was 5.4 ± 7.1% and mean troponin was 5.2 ± 9.2 g/L. A total of 1696 segments were available for analysis. 34 segments were excluded from the analysis due to problematic image quality so 1664 segments were finally included.Of these, 824 segments were available for comparison with FFR. 156 coronary arteries were assessed 92 in the infarct-related arteries and 64 in the non-infarct-related arteries. Of these, 28(17.1%) and 33(21.1%) arteries had an FFR ≤ 0.75 and ≤0.80, respectively. There was a negative correlation between the number of ischaemic segments and FFR (r = -0.79, 0 < 0.0001).The sensitivity, specificity, PPV and NPV for FFR ≤ 0.8 was 91.17%, 95.7%, 91.2% and 95.7% respectively. ROC analysis defined the optimal FFR cut off value for identification of reversible ischaemia on MRI to be ≤0.8 (AUC 0.94 (0.89–0.99), p < 0.0001). An FFR ≤ 0.8 was associated with a sensitivity of 88.6% and a specificity of 94%. Conclusion FFR measured in patients with recent NSTEMI has a high level of accuracy for inducible perfusion abnormalities revealed by 3T stress MRI, a non-invasive reference method.