The Incidence and Impact of Permanent Right Ventricular Infarction on Left Ventricular Infarct Size in Patients With Inferior ST-Segment Elevation Myocardial Infarction.

Mounting evidence shows that right ventricle (RV) function carries independent prognostic influence in various disease states. This study aimed to investigate the incidence and impact of permanent RV infarction in patients with inferior ST-segment elevation myocardial infarction (STEMI) and culprit lesion in the right coronary artery (RCA). In this substudy of the DANAMI-3 (DANish Study of Optimal Acute Treatment of Patients with ST-segment Elevation Myocardial Infarction) trial, cardiac magnetic resonance was performed in 291 patients at day 1 and follow-up 3 months after primary percutaneous coronary intervention of 674 patients with STEMI with the culprit lesion in the RCA. Final infarct was assessed using late gadolinium enhancement on cardiac magnetic resonance at 3 months. Patients with permanent RV infarction (20%) had lower ventricular function at follow-up; RV ejection fraction (EF) 47% ±6 versus 50% ± 5 (p <0.005) and left ventricular (LV) EF 56% ± 8 versus 60% ± 9 (p <0.006). Furthermore, patients with permanent RV infarction had a higher incidence of microvascular obstruction 39 (67%) versus 81 (39%) (p <0.001), larger final LV infarct size 16% ±8 versus 10% ± 8 (p <0.001) and larger LV area at risk 33% ± 10 versus 29% ± 9 (p <0.001). Permanent RV infarction was an independent predictor of final LV infarct size (p <0.001) but was not associated with LVEF (ß = -0.0; p = 0.13) in multivariable analyses. In conclusion, permanent RV infarction was seen in 20% of patients with inferior STEMI and culprit lesion in RCA and independently predicted final LV infarct size. However, permanent RV infarction did not predict overall LV function. LGE was used to detect infarct location and quantify infarct size.17 LGE in RV free wall on follow-up CMR was considered as permanent infarction. LGE images were obtained 10 minutes after intravenous injection of 0.1-mmol/kg body weight of gadolinium-based contrast (Gadovist; Bayer Schering, Berlin, Germany) using an electrocardiogram (ECG)-triggered inversion-recovery sequence. The inversion time was adjusted to null the signal from the normal myocardium. Short-axis images were acquired from the atrioventricular plane to the apex with adjacent 8-mm slices. The remaining protocol has been described previously.16.

Clinical outcomes of no stenting in patients with ST-segment elevation myocardial infarction undergoing deferred primary percutaneous coronary intervention.

BACKGROUND: ST-segment elevation myocardial infarction (STEMI) is treated with stenting, but the underlying stenosis is often not severe, and stenting may potentially be omitted. AIMS: The aim of the study was to investigate outcomes of patients with STEMI treated with percutaneous coronary intervention (PCI) without stenting. METHODS: Patients were identified through the DANAMI-3-DEFER study. Stenting was omitted in the patients with stable flow after initial PCI and no significant residual stenosis on the deferral procedure, who were randomised to deferred stenting. These patients were compared to patients randomised to conventional PCI treated with immediate stenting. The primary endpoint was a composite of all-cause mortality, recurrent myocardial infarction (MI), and target vessel revascularisation (TVR). RESULTS: Of 603 patients randomised to deferred stenting, 84 were treated without stenting, and in patients randomised to conventional PCI (n=612), 590 were treated with immediate stenting. Patients treated with no stenting had a median stenosis of 40%, median vessel diameter of 2.9 mm, and median lesion length of 11.4 mm. During a median follow-up of 3.4 years, the composite endpoint occurred in 14% and 16% in the no and immediate stenting groups, respectively (unadjusted hazard ratio [HR] 0.87, 95% confidence interval [CI]: 0.48-1.60; p=0.66). The association remained non-significant after adjusting for confounders (adjusted HR 0.53, 95% CI: 0.22-1.24; p=0.14). The rates of TVR and recurrent MI were 2% vs 4% (p=0.70) and 4% vs 6% (p=0.43), respectively. CONCLUSIONS: Patients with STEMI, with no significant residual stenosis and stable flow after initial PCI, treated without stenting, had comparable event rates to patients treated with immediate stenting.

Infarct size following loading with Ticagrelor/Prasugrel versus Clopidogrel in ST-segment elevation myocardial infarction.

BACKGROUND: Treatment with newer direct-acting anti-platelet drugs (Ticagrelor and Prasugrel) prior to primary percutaneous coronary intervention (PCI) is associated with improved outcome in patients with ST-segment elevation myocardial infarction (STEMI) when compared with Clopidogrel. We compared infarct size following treatment with Ticagrelor/Prasugrel versus Clopidogrel in the DANish trial in Acute Myocardial Infarction (DANAMI-3) population of STEMI patients treated with primary PCI. METHODS AND RESULTS: Patients were loaded with Clopidogrel, Ticagrelor or Prasugrel in the ambulance before primary PCI. Infarct size and myocardial salvage index were calculated using cardiac magnetic resonance (CMR) during index admission and at three-month follow-up. Six-hundred-and-ninety-three patients were included in this analysis. Clopidogrel was given to 351 patients and Ticagrelor/Prasugrel to 342 patients. The groups were generally comparable in terms of baseline and procedural characteristics. Median infarct size at three-month follow-up was 12.9% vs 10.0%, in patients treated with Clopidogrel and Ticagrelor/ Prasugrel respectively (p < 0.001), and myocardial salvage index was 66% vs 71% (p < 0.001). Results remained significant in a multiple regression model (p < 0.001). CONCLUSIONS: Pre-hospital loading with Ticagrelor or Prasugrel compared to Clopidogrel, was associated with smaller infarct size and larger myocardial salvage index at three-month follow-up in patients with STEMI treated with primary PCI.

Electrocardiogram to predict reperfusion success in late presenters with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention.

BACKGROUND: Clinical decision-making in patients with ST-segment elevation myocardial infarction (STEMI) presenting beyond 12 h of symptom onset (late presenters) is challenging. However, the electrocardiogram (ECG) may provide helpful information. We investigated the association between three ECG-scores and myocardial salvage and infarct size in late presenters treated with primary percutaneous coronary intervention (primary PCI). METHODS: Sixty-six patients with STEMI and ongoing symptoms presenting 12-72 h after symptom onset were included. Cardiac magnetic resonance was performed at day 1 (interquartile range [IQR], 1-1) and at follow-up at day 93 (IQR, 90-98). The pre-PCI ECG was analyzed for the presence of pathological QW (early QW) as well as Anderson-Wilkins acuteness score (AW-score), the classic Sclarovsky-Birnbaum Ischemia Grading System (classic SB-IG-score) and a modified SB-IG-score including any T-wave morphologies. RESULTS: Early QW was associated with a larger myocardium at risk (39 ± 12 versus 33 ± 12; p = 0.030) and final infarct size (20 ± 11 versus 14 ± 9; p = 0.021) as well as a numerical lower final myocardial salvage (0.52 ± 0.19 versus 0.61 ± 0.23; p = 0.09). The association with final infarct size disappeared after adjusting for myocardium at risk. An AW-score < 3 showed a trend towards a larger final infarct size (18 ± 11 versus 11 ± 11; p = 0.08) and was not associated with salvage index (0.55 ± 0.20 versus 0.65 ± 0.30; p = 0.23). The classic and modified SB-IG-score were not associated with final infarct size (modified SB-IG-score, 17 ± 10 versus 21 ± 13; p = 0.28) or final myocardial salvage (0.53 ± 0.20 versus 0.53 ± 0.26; p = 0.96). CONCLUSION: Of three well-established ECG-scores only early QW and AW-score < 3 showed association with myocardium at risk and infarct size to some extent, but the association with myocardial salvage was weak. Hence, neither of the three investigated ECG-scores are sufficient to guide clinical decision-making in patients with STEMI and ongoing symptoms presenting beyond 12 h of symptom onset.

Early Q-wave morphology in prediction of reperfusion success in patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention - A cardiac magnetic resonance imaging study.

BACKGROUND: Pathological Q-wave (QW) in the electrocardiogram (ECG) before primary percutaneous coronary intervention (primary PCI) is a strong prognostic marker in patients with ST-segment elevation myocardial infarction (STEMI). However, current binary QW criteria are either not clinically applicable or have a lack of diagnostic performance. Accordingly, we evaluated the association between duration, depth and area of QW and markers of the effect of reperfusion (reperfusion success). METHODS: A total of 516 patients with their first STEMI had obtained an ECG before primary PCI and an acute cardiac magnetic resonance imaging (CMR) at day 1 (interquartile range [IQR], 1-1) and at follow-up at day 92 (IQR, 89-96). The largest measurable QW in ECG was used for analysis of duration, depth and area of QW (QW morphology). The QW morphology was evaluated as a continuous variable in linear regression models and as a variable divided in four equally large groups. RESULTS: The QW morphology as four equally large groups was significantly associated with all CMR endpoints (p ≤ 0.001) and showed a linear relationship (p ≤ 0.001) with final infarct size (for QW duration, ß = 0.47; QW depth, ß = 0.41 and QW area, ß = 0.39), final infarct transmurality (for QW duration, ß = 0.36; QW depth, ß = 0.26 and QW area, ß = 0.23) and final myocardial salvage index (for QW duration, ß = -0.34; QW depth, ß = -0.26 and QW area, ß = -0.24). CONCLUSION: Although modest, the QW morphology in STEMI patients showed significant linear association with markers of reperfusion success. Hence, it is suggested that the term pathological is not used as a dichotomous parameter in patients with STEMI but rather evaluated on the basis of extent.

Fractional flow reserve-guided PCI in patients with and without left ventricular hypertrophy: a DANAMI-3-PRIMULTI substudy.

AIMS: The aim of this substudy was to investigate the correlation between fractional flow reserve (FFR) and diameter stenosis in patients with STEMI with and without left ventricular hypertrophy (LVH), and the influence of LVH on complete FFR-guided revascularisation versus culprit only, in terms of risk of clinical outcome. METHODS AND RESULTS: In this DANAMI-3-PRIMULTI substudy, 279 patients with STEMI had cardiac magnetic resonance (CMR) imaging for assessment of left ventricular mass index. Ninety-six patients had FFR evaluation of a non-culprit lesion. Diameter stenosis of the non-culprit lesion was determined with two-dimensional quantitative coronary analysis. The diameter stenosis (56.9% vs 54.3%, p=0.38) and FFR value (0.83 vs 0.85, p=0.34) were significantly correlated in both groups (Spearman's ρ=-0.40 and -0.41 without LVH and with LVH, respectively; p<0.001) but were not different between patients without and with LVH (p for interaction=0.87). FFR-guided complete revascularisation was associated with reduced risk of death, myocardial infarction or ischaemia-driven revascularisation both for patients without LVH (HR 0.42, 95% CI: 0.20-0.85) and for patients with LVH (HR 0.50, 95% CI: 0.17-1.47), with no interaction between the FFR-guided complete revascularisation and LVH (p for interaction=0.82). CONCLUSIONS: LVH did not interact with the correlation between diameter stenosis and FFR and did not modify the impact of complete revascularisation on the occurrence of subsequent clinical events.

Sub-acute cardiac magnetic resonance to predict irreversible reduction in left ventricular ejection fraction after ST-segment elevation myocardial infarction: A DANAMI-3 sub-study.

AIMS: To predict irreversible reduction in left ventricular ejection fraction (LVEF) during admission for ST-segment elevation myocardial infarction (STEMI) using cardiac magnetic resonance (CMR) in addition to classical clinical parameters. Irreversible reduction in LVEF is an important prognostic factor after STEMI which necessitates medical therapy and implantation of prophylactic implantable cardioverter defibrillator (ICD). METHODS AND RESULTS: A post-hoc analysis of DANAMI-3 trial program (Third DANish Study of Optimal Acute Treatment of Patients With ST-elevation Myocardial Infarction) which recruited 649 patients who had CMR performed during index hospitalization and after 3 months. Patients were divided into two groups according to CMR-LVEF at 3 months: Group 1 with LVEF≤35% and Group 2 with LVEF>35%. Group 1 included 15 patients (2.3%) while Group 2 included 634 patients (97.7%). A multivariate analysis showed that: Killip class >1 (OR 7.39; CI:1.47-36.21, P = 0.01), symptom onset-to-wire ≥6 h (OR 7.19; CI 1.07-50.91, P = 0.04), LVEF≤35% using index echocardiography (OR 7.11; CI: 1.27-47.43, P = 0.03), and infarct size ≥40% of LV on index CMR (OR 42.62; CI:7.83-328.29, P < 0.001) independently correlated with a final LVEF≤35%. Clinical models consisted of these parameters could identify 7 out of 15 patients in Group 1 with 100% positive predictive value. CONCLUSION: Together with other clinical measurements, the assessment of infarct size using late Gadolinium enhancement by CMR during hospitalization is a strong predictor of irreversible reduction in CMR_LVEF ≤35. That could potentially, after validation with future research, aids the selection and treatment of high-risk patients after STEMI, including implantation of prophylactic ICD during index hospitalization.

Complete Revascularization Versus Culprit Lesion Only in Patients With ST-Segment Elevation Myocardial Infarction and Multivessel Disease: A DANAMI-3-PRIMULTI Cardiac Magnetic Resonance Substudy.

OBJECTIVES: The aim of this study was to evaluate the effect of fractional flow reserve (FFR)-guided revascularization compared with culprit-only percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI) on infarct size, left ventricular (LV), function, LV remodeling, and the presence of nonculprit infarctions. BACKGROUND: Patients with STEMI with multivessel disease might have improved clinical outcomes after complete revascularization compared with PCI of the infarct-related artery only, but the impact on infarct size, LV function, and remodeling as well as the risk for periprocedural infarction are unknown. METHODS: In this substudy of the DANAMI-3 (Third Danish Trial in Acute Myocardial Infarction)-PRIMULTI (Primary PCI in Patients With ST-Elevation Myocardial Infarction and Multivessel Disease: Treatment of Culprit Lesion Only or Complete Revascularization) randomized trial, patients with STEMI with multivessel disease were randomized to receive either complete FFR-guided revascularization or PCI of the culprit vessel only. The patients underwent cardiac magnetic resonance imaging during index admission and at 3-month follow-up. RESULTS: A total of 280 patients (136 patients with infarct-related and 144 with complete FFR-guided revascularization) were included. There were no differences in final infarct size (median 12% [interquartile range: 5% to 19%] vs. 11% [interquartile range: 4% to 18%]; p = 0.62), myocardial salvage index (median 0.71 [interquartile range: 0.54 to 0.89] vs. 0.66 [interquartile range: 0.55 to 0.87]; p = 0.49), LV ejection fraction (mean 58 ± 9% vs. 59 ± 9%; p = 0.39), and LV end-systolic volume remodeling (mean 7 ± 22 ml vs. 7 ± 19 ml; p = 0.63). New nonculprit infarction occurring after the nonculprit intervention was numerically more frequent among patients treated with complete revascularization (6 [4.5%] vs. 1 [0.8%]; p = 0.12). CONCLUSIONS: Complete FFR-guided revascularization in patients with STEMI and multivessel disease did not affect final infarct size, LV function, or remodeling compared with culprit-only PCI.

Assessment of the myocardial area at risk: comparing T2-weighted cardiovascular magnetic resonance imaging with contrast-enhanced cine (CE-SSFP) imaging-a DANAMI3 substudy.

AIMS: Myocardial salvage following treatment for ST-segment elevation myocardial infarction is prognostic for morbidity and mortality. Studies with myocardial salvage as endpoint rely on valid assessment of the myocardial area at risk (AAR). T2-weighted cardiovascular magnetic resonance (CMR) imaging is the preferred method to assess the AAR. However, T2-weighted imaging can be of poor image quality and uninterpretable. Contrast-enhanced (CE) cine imaging can also show AAR and our aim was to investigate if CE-cine can replace T2-weighted imaging. Cine imaging is part of a standard CMR-protocol and implementing CE-cine imaging for assessment of the AAR would mean shorter investigation time. METHODS AND RESULTS: As a DANAMI-3 substudy, we performed successful dual imaging of the AAR in 166 participants using both T2-weighted short tau inversion recovery (T2-STIR) and CE-cine imaging. T2-STIR imaging was non-diagnostic in nine and CE-cine in one scan during the period. CE-cine measured 4.7% of left ventricle (LV) [95% confidence interval 3.2-6.2%] smaller AAR compared with T2-STIR images (P < 0.001). Visual analysis of a plot of infarct size vs. AAR showed an overestimation of the AAR when measured with T2-STIR images. There was no difference in AAR with CE-cine in an interobserver analysis of 46 scans [1.2 g (standard deviation 9.5), P = 0.42]. CONCLUSIONS: CE-cine imaging shows good internal consistency in assessment of the AAR. A visual inspection reveals possible overestimation of AAR with T2-STIR images. There is good interobserver agreement in the analysis of CE-cine imaging. CE-cine can replace T2-STIR imaging resulting in a more valid assessment of the myocardial AAR.

Subacute cardiac rubidium-82 positron emission tomography (82Rb-PET) to assess myocardial area at risk, final infarct size, and myocardial salvage after STEMI.

BACKGROUND: Determining infarct size and myocardial salvage in patients with ST-segment elevation myocardial infarction (STEMI) is important when assessing the efficacy of new reperfusion strategies. We investigated whether rest 82Rb-PET myocardial perfusion imaging can estimate area at risk, final infarct size, and myocardial salvage index when compared to cardiac SPECT and magnetic resonance (CMR). METHODS: Twelve STEMI patients were injected with 99mTc-Sestamibi intravenously immediate prior to reperfusion. SPECT, 82Rb-PET, and CMR imaging were performed post-reperfusion and at a 3-month follow-up. An automated algorithm determined area at risk, final infarct size, and hence myocardial salvage index. RESULTS: SPECT, CMR, and PET were performed 2.2 ± 0.5, 34 ± 8.5, and 32 ± 24.4 h after reperfusion, respectively. Mean (± SD) area at risk were 35.2 ± 16.6%, 34.7 ± 11.3%, and 28.1 ± 16.1% of the left ventricle (LV) in SPECT, CMR, and PET, respectively, P = 0.04 for difference. Mean final infarct size estimates were 12.3 ± 15.4%, 13.7 ± 10.4%, and 11.9 ± 14.6% of the LV in SPECT, CMR, and PET imaging, respectively, P = .72. Myocardial salvage indices were 0.64 ± 0.33 (SPECT), 0.65 ± 0.20 (CMR), and 0.63 ± 0.28 (PET), (P = .78). CONCLUSIONS: 82Rb-PET underestimates area at risk in patients with STEMI when compared to SPECT and CMR. However, our findings suggest that PET imaging seems feasible when assessing the clinical important parameters of final infarct size and myocardial salvage index, although with great variability, in a selected STEMI population with large infarcts. These findings should be confirmed in a larger population.

Impact of diagnostic ECG-to-wire delay in STEMI patients treated with primary PCI: a DANAMI-3 substudy.

AIMS: We aimed to evaluate the impact of delay from diagnostic pre-hospital electrocardiogram (ECG) to wiring of the infarct-related vessel (ECG-to-wire) >120 minutes on cardiovascular magnetic resonance (CMR) markers of reperfusion success and clinical outcome in patients with ST-segment elevation myocardial infarction (STEMI). METHODS AND RESULTS: We included 1,492 patients in the analyses of clinical outcome. CMR was performed in 748 patients to evaluate infarct size and myocardial salvage. In total, 304 patients (20%) had ECG-to-wire >120 minutes, which was associated with larger acute infarct size (18% [interquartile range (IQR), 10-28] vs. 15% [8-24]; p=0.022) and smaller myocardial salvage (0.42 [IQR 0.28-0.57] vs. 0.50 [IQR 0.34-0.70]; p=0.002). However, 33% of the patients with ECG-to-wire >120 minutes still had a substantial myocardial salvage ≥0.50. In a multivariable analysis, ECG-to-wire >120 minutes was associated with an increased risk of all-cause mortality and heart failure (hazard ratio 1.61, 95% confidence interval [CI] 1.14-2.26, p=0.007). CONCLUSIONS: ECG-to-wire >120 minutes was associated with larger infarct size, smaller myocardial salvage and a poorer clinical outcome in STEMI patients transferred for primary percutaneous coronary intervention. However, myocardial salvage was still substantial in one third of patients treated beyond 120 minutes of delay.

Myocardial Damage in Patients With Deferred Stenting After STEMI: A DANAMI-3-DEFER Substudy.

BACKGROUND: Although some studies found improved coronary flow and myocardial salvage when stent implantation was deferred, the DANAMI-3-DEFER (Third DANish Study of Optimal Acute Treatment of Patients With ST-elevation Myocardial Infarction) did not show any improvement in clinical outcome in patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI) and deferred stenting. OBJECTIVES: This study sought to evaluate the effect of deferred stent implantation on infarct size, myocardial salvage, and microvascular obstruction (MVO) in patients with STEMI. METHODS: In the present DANAMI-3 substudy, a total of 510 patients with STEMI were randomized to PCI with deferred versus immediate stent implantation. The patients underwent a cardiac magnetic resonance examination before discharge after the index procedure and again 3 months later. The primary endpoint was final infarct size. RESULTS: Deferred stenting did not reduce final infarct size (9% left ventricle [LV]; interquartile range [IQR]: 3% to 18% vs. 10% LV; IQR: 3% to 18%; p = 0.67). Similarly, deferred stenting was not associated with myocardial salvage index (66%; IQR: 50% to 89% vs. 67%; IQR: 49% to 88%; p = 0.80) or presence of MVO (43% vs. 42%; p = 0.78). In a post hoc analysis, stent length was the only subgroup of 7 that had an effect on outcome. In patients with a stent length ≥24 mm, deferred stenting reduced the final infarct size (6% LV; IQR: 2% to 18% vs. 13% LV; IQR: 7% to 23%; p = 0.006; and p for interaction = 0.005). CONCLUSIONS: In the DANAMI-3-DEFER cardiac magnetic resonance substudy, routine deferred stenting did not reduce infarct size or MVO and did not increase myocardial salvage. These results do not support the use of routine deferred stenting in STEMI patients treated with primary PCI. (DANish Study of Optimal Acute Treatment of Patients With ST-elevation Myocardial Infarction [DANAMI-3]; NCT01435408).

Association Between Early Q Waves and Reperfusion Success in Patients With ST-Segment-Elevation Myocardial Infarction Treated With Primary Percutaneous Coronary Intervention: A Cardiac Magnetic Resonance Imaging Study.

BACKGROUND: Pathological early Q waves (QW) are associated with adverse outcomes in patients with ST-segment-elevation myocardial infarction (STEMI). Primary percutaneous coronary intervention (PCI) may therefore be less beneficial in patients with QW than in patients without QW. Myocardial salvage index and microvascular obstruction (MVO) are markers for reperfusion success. Thus, to clarify the benefit from primary PCI in STEMI patients with QW, we examined the association between baseline QW and myocardial salvage index and MVO in STEMI patients treated with primary PCI. METHODS AND RESULTS: The ECG was assessed before primary PCI for the presence of QW (early) in 515 STEMI patients. The patients underwent a cardiac magnetic resonance imaging scan at day 1 (interquartile range [IQR], 1-1) and again at day 92 (IQR, 89-96). Early QW was observed in 108 (21%) patients and was related to smaller final myocardial salvage index (0.59 [IQR, 0.39-0.69] versus 0.65 [IQR, 0.46-0.84]; P<0.001) and larger MVO (1.4 [IQR, 0.0-5.4] versus 0.0 [IQR, 0.0-2.4]; P<0.001) compared with non-QW. QW remained associated with both final myocardial salvage index (ß=-0.12; P=0.03) and MVO (ß=0.18; P=0.001) after adjusting for potential confounders. CONCLUSIONS: Patients presenting with their first STEMI and early QW in the ECG had smaller myocardial salvage index and more extensive MVO than non-QW despite treatment within 12 hours after symptom onset. However, final myocardial salvage index in patients with QW was substantial, and patients with QW still benefit from primary PCI. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01435408.

Left Ventricular Hypertrophy Is Associated With Increased Infarct Size and Decreased Myocardial Salvage in Patients With ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention.

BACKGROUND: Approximately one third of patients with ST-segment elevation myocardial infarction (STEMI) have left ventricular hypertrophy (LVH), which is associated with impaired outcome. However, the causal association between LVH and outcome in STEMI is unknown. We evaluated the association between LVH and: myocardial infarct size, area at risk, myocardial salvage, microvascular obstruction, left ventricular (LV) function (all determined by cardiac magnetic resonance [CMR]), and all-cause mortality and readmission for heart failure in STEMI patients treated with primary percutaneous coronary intervention. METHODS AND RESULTS: In this substudy of the DANAMI-3 trial, 764 patients underwent CMR. LVH was defined by CMR and considered present if LV mass exceeded 77 (men) and 67 g/m2 (women). One hundred seventy-eight patients (24%) had LVH. LVH was associated with a larger final infarct size (15% [interquartile range {IQR}, 10-21] vs 9% [IQR, 3-17]; P<0.001) and smaller final myocardial salvage index (0.6 [IQR, 0.5-0.7] vs 0.7 [IQR, 0.5-0.9]; P<0.001). The LVH group had a higher incidence of microvascular obstruction (66% vs 45%; P<0.001) and lower final LV ejection fraction (LVEF; 53% [IQR, 47-60] vs 61% [IQR, 55-65]; P<0.001). In a Cox regression analysis, LVH was associated with a higher risk of all-cause mortality and readmission for heart failure (hazard ratio 2.59 [95% CI, 1.38-4.90], P=0.003). The results remained statistically significant in multivariable models. CONCLUSIONS: LVH is independently associated with larger infarct size, less myocardial salvage, higher incidence of microvascular obstruction, lower LVEF, and a higher risk of all-cause mortality and incidence of heart failure in STEMI patients treated with primary percutaneous coronary intervention. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01435408.

Predictors and prognostic value of left atrial remodelling after acute myocardial infarction.

PURPOSE: Left atrial (LA) volume is a strong prognostic predictor in patients following ST-segment elevation myocardial infarction (STEMI). However, the change in LA volume over time (LA remodelling) following STEMI has been scarcely studied. We sought to identify predictors for LA remodelling and to evaluate the prognostic importance of LA remodelling. METHODS: This is a subgroup analysis from a randomised clinical trial that evaluated the cardioprotective effect of exenatide treatment. A total of 160 patients with STEMI underwent a cardiovascular MR (CMR) 2 days after primary angioplasty and a second scan 3 months later. LA remodelling was defined as changes in LA volume or function from baseline to 3 months follow-up. Major adverse cardiac events were registered after a median of 5.2 years. RESULTS: Adverse LA minimum volume (LAmin) remodelling was correlated to the presence of hypertension, larger infarct size by CMR, higher peak troponin T, larger area at risk and adverse left ventricular (LV) remodelling. LA maximum volume (LAmax) remodelling was correlated to larger infarct size by CMR, higher peak troponin T, larger area at risk, larger LV mass, impaired LV function and adverse LV remodelling. Kaplan-Meier and Log Rank analyses showed that patients in the highest tertiles of LAmin or LAmax remodelling are at higher risk (0.030 and p=0.018). CONCLUSIONS: After a myocardial infarction, LA remodelling reflects a parallel ventricular-atrial remodelling. Infarct size is a major determinant of LA remodelling following STEMI and adverse LA remodelling is associated with an unfavourable prognosis.

Basal hyperaemia is the primary abnormality of perfusion in Takotsubo cardiomyopathy: a quantitative cardiac perfusion positron emission tomography study.

AIMS: Takotsubo cardiomyopathy (TTC) is characterized by acute completely reversible regional left ventricle (LV) akinesia and decreased tracer uptake in the akinetic region on semi-quantitative perfusion imaging. The latter may be due to normoperfusion of the akinetic mid/apical area and basal hyperperfusion. Our aim was to examine abnormalities of perfusion in TTC, and we hypothesized that basal hyperperfusion is the primary perfusion abnormality in the acute state. METHOD AND RESULTS: Twenty-five patients were diagnosed with TTC due to (i) acute onset of symptoms, (ii) typical apical ballooning, (iii) absence of significant coronary disease, and (iv) complete remission on 4-month follow-up. The patients underwent coronary angiography (CAG), echocardiography, cardiac magnetic resonance imaging (CMR), and (13)NH3/(82)Rb positron emission tomography (PET) in the acute state and-except CAG-on follow-up. Patients initially had severe heart failure, mid/apical oedema but no infarction, and a rise in cardiac biomarkers. On initial perfusion PET imaging, eight patients appeared to have normal, whereas 17 patients had impaired LV perfusion. In the latter, flow in the basal region was increased in the acute state (1.5 ± 0.1 vs. 1.2 ± 0.1 mL/g/minRPP-corrected, P < 0.01), whereas midventricular (1.7 ± 0.1 vs. 1.6 ± 0.1 mL/g/minRPP-corrected, P = 0.21) and apical (1.4 ± 0.1 vs. 1.5 ± 0.1 mL/g/minRPP-corrected, P = 0.36) flow was unchanged between acute and follow-up, and within normal range. CONCLUSION: Our results suggest an abnormal LV perfusion distribution in the acute state of TTC with basal hyperperfusion and a normoperfused akinetic region. The proportion of patients without visualized perfusion abnormalities in the acute state may represent a subgroup with fast remission.

Myocardial fibrosis in patients with myotonic dystrophy type 1: a cardiovascular magnetic resonance study.

BACKGROUND: Myotonic dystrophy type 1 (DM1) is associated with increased cardiac morbidity and mortality. Therefore, assessment of cardiac involvement and risk stratification for sudden cardiac death is crucial. Nevertheless, optimal screening-procedures are not clearly defined. ECG, echocardiography and Holter-monitoring are useful but insufficient. Cardiovascular magnetic resonance (CMR) can provide additional information of which myocardial fibrosis may be relevant. The purpose of this study was to describe the prevalence of myocardial fibrosis in patients with DM1 assessed by CMR, and the association between myocardial fibrosis and abnormal findings on ECG, Holter-monitoring and echocardiography. METHODS: We selected 30 unrelated patients with DM1: 18 patients (10 men, mean age 51 years) with, and 12 patients (7 men, mean age 41 years) without abnormal findings on ECG and Holter-monitoring. Patients were evaluated with medical history, physical examination, ECG, Holter-monitoring, echocardiography and CMR. RESULTS: Myocardial fibrosis was found in 12/30 (40%, 9 men). The presence of myocardial fibrosis was associated with the following CMR-parameters: increased left ventricular mass (median (range) 55 g/m² (43-83) vs. 46 g/m² (36-64), p = 0.02), increased left atrial volume (median (range) 52 ml/m² (36-87) vs. 46 ml/m² (35-69), p = 0.04) and a trend toward lower LVEF (median (range) 63% (38-71) vs. 66% (60-80), p = 0.06). Overall, we found no association between the presence of myocardial fibrosis and abnormal findings on: ECG (p = 0.71), Holter-monitoring (p = 0.27) or echocardiographic measurements of left ventricular volumes, ejection fraction or global longitudinal strain (p = 0.18). CONCLUSION: Patients with DM1 had a high prevalence of myocardial fibrosis which was not predicted by ECG, Holter-monitoring or echocardiography. CMR add additional information to current standard cardiac assessment and may prove to be a clinically valuable tool for risk stratification in DM1.

Takotsubo cardiomyopathy, a two-stage recovery of left ventricular systolic and diastolic function as determined by cardiac magnetic resonance imaging.

AIMS: Takotsubo cardiomyopathy (TTC) is an entity mimicking acute myocardial infarction, characterized by transient severe systolic heart failure. Echocardiographic studies suggest that diastolic dysfunction is present in TTC at presentation; however, no reports exist regarding the time course of left ventricular (LV) recovery. This study describes the recovery of LV systolic and diastolic function in TTC. We hypothesized that, in TTC, there is diastolic dysfunction at admission, and that recovery is delayed compared with systolic function. METHODS AND RESULTS: We enrolled (consecutively 2010-12) 16 patients (mean age 66, range 39-84 years) diagnosed with TTC and 20 healthy matched controls. We performed cardiac magnetic resonance imaging (CMR) at admission, pre-discharge, and 3-month follow-up. Diastolic function was assessed by LV peak filling rate (LVPFR) and left atrial (LA) emptying volumes. At admission, LV ejection fraction was low, increased at pre-discharge (37 ± 6 vs. 58 ± 6%, P < 0.001), and normalized at follow-up (to 65 ± 5%, P = 0.01). LVPFR did not increase during hospitalization (80 ± 3 vs. 89 ± 4 mL/s/m(2), P = 0.21), but was normalized at follow-up (to 206 ± 19, P < 0.001; controls, 214 ± 13, P = 0.23). During hospitalization, LA passive emptying volume remained low (6 ± 2 vs. 8 ± 3 mL/m(2), P = 0.05) and LA active emptying volume remained high (17 ± 3 vs. 16 ± 3 mL/m(2), P = 0.71), whereas LA conduit volume increased (7 ± 3 vs. 23 ± 4 mL/m(2), P < 0.001). T2-weighted imaging demonstrated non-coronary distributed apical oedema without contrast enhancement. CONCLUSION: Patients with TTC undergo fast systolic recovery. However, at discharge, profound diastolic dysfunction is demonstrated by CMR. At follow-up, both LV systolic and diastolic function is normalized in patients with recovered TTC.

The decrease of cardiac chamber volumes and output during positive-pressure ventilation.

Positive-pressure ventilation (PPV) is widely used for treatment of acute cardiorespiratory failure, occasionally at the expense of compromised cardiac function and arterial blood pressure. The explanation why has largely rested on interpretation of intracardiac pressure changes. We evaluated the effect of PPV on the central circulation by studying cardiac chamber volumes with cardiac magnetic resonance imaging (CMR). We hypothesized that PPV lowers cardiac output (CO) mainly via the Frank-Starling relationship. In 18 healthy volunteers, cardiac chamber volumes and flow in aorta and the pulmonary artery were measured by CMR during PPV levels of 0, 10, and 20 cmH2O applied via a respirator and a face mask. All cardiac chamber volumes decreased in proportion to the level of PPV. Following 20-cmH2O PPV, the total diastolic and systolic cardiac volumes (±SE) decreased from 605 (±29) ml to 446 (±29) ml (P < 0.001) and from 265 (±17) ml to 212 (±16) ml (P < 0.001). Left ventricular stroke volume decreased by 27 (±4) ml/beat; heart rate increased by 7 (±2) beats/min; and CO decreased by 1.0 (±0.4) l/min (P < 0.001). From 0 to 20 cmH2O, right and left ventricular peak filling rates decreased by -146 (±32) and -187 (±64) ml/s (P < 0.05) but maximal emptying rates were unchanged. Cardiac filling and output decrease with increasing PPV in healthy volunteers. The decrease is seen even at low levels of PPV and should be taken into account when submitting patients to mechanical ventilation with positive pressures. The decrease in CO is fully explained by the Frank-Starling mechanism.