Microvascular resistance predicts myocardial salvage and infarct characteristics in ST-elevation myocardial infarction

<b>Background:</b> The pathophysiology of myocardial injury and repair in patients with ST‐elevation myocardial infarction is incompletely understood. We investigated the relationships among culprit artery microvascular resistance, myocardial salvage, and ventricular function.<p></p> <b>Methods and Results:</b> The index of microvascular resistance (IMR) was measured by means of a pressure‐ and temperature‐sensitive coronary guidewire in 108 patients with ST‐elevation myocardial infarction (83% male) at the end of primary percutaneous coronary intervention. Paired cardiac MRI (cardiac magnetic resonance) scans were performed early (2 days; n=108) and late (3 months; n=96) after myocardial infarction. T2‐weighted‐ and late gadolinium–enhanced cardiac magnetic resonance delineated the ischemic area at risk and infarct size, respectively. Myocardial salvage was calculated by subtracting infarct size from area at risk. Univariable and multivariable models were constructed to determine the impact of IMR on cardiac magnetic resonance–derived surrogate outcomes. The median (interquartile range) IMR was 28 (17–42) mm Hg/s. The median (interquartile range) area at risk was 32% (24%–41%) of left ventricular mass, and the myocardial salvage index was 21% (11%–43%). IMR was a significant multivariable predictor of early myocardial salvage, with a multiplicative effect of 0.87 (95% confidence interval 0.82 to 0.92) per 20% increase in IMR; P<0.001. In patients with anterior myocardial infarction, IMR was a multivariable predictor of early and late myocardial salvage, with multiplicative effects of 0.82 (95% confidence interval 0.75 to 0.90; P<0.001) and 0.92 (95% confidence interval 0.88 to 0.96; P<0.001), respectively. IMR also predicted the presence and extent of microvascular obstruction and myocardial hemorrhage.<p></p> <b>Conclusion:</b> Microvascular resistance measured during primary percutaneous coronary intervention significantly predicts myocardial salvage, infarct characteristics, and left ventricular ejection fraction in patients with ST‐elevation myocardial infarction.<p></p&gt

A randomized trial of deferred stenting versus immediate stenting to prevent no- or slow-reflow in acute ST-segment elevation myocardial infarction (DEFER-STEMI)

Objectives: The aim of this study was to assess whether deferred stenting might reduce no-reflow and salvage myocardium in primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI). Background: No-reflow is associated with adverse outcomes in STEMI. Methods: This was a prospective, single-center, randomized, controlled, proof-of-concept trial in reperfused STEMI patients with ≥1 risk factors for no-reflow. Randomization was to deferred stenting with an intention-to-stent 4 to 16 h later or conventional treatment with immediate stenting. The primary outcome was the incidence of no-/slow-reflow (Thrombolysis In Myocardial Infarction ≤2). Cardiac magnetic resonance imaging was performed 2 days and 6 months after myocardial infarction. Myocardial salvage was the final infarct size indexed to the initial area at risk. Results: Of 411 STEMI patients (March 11, 2012 to November 21, 2012), 101 patients (mean age, 60 years; 69% male) were randomized (52 to the deferred stenting group, 49 to the immediate stenting). The median (interquartile range [IQR]) time to the second procedure in the deferred stenting group was 9 h (IQR: 6 to 12 h). Fewer patients in the deferred stenting group had no-/slow-reflow (14 [29%] vs. 3 [6%]; p = 0.006), no reflow (7 [14%] vs. 1 [2%]; p = 0.052) and intraprocedural thrombotic events (16 [33%] vs. 5 [10%]; p = 0.010). Thrombolysis In Myocardial Infarction coronary flow grades at the end of PCI were higher in the deferred stenting group (p = 0.018). Recurrent STEMI occurred in 2 patients in the deferred stenting group before the second procedure. Myocardial salvage index at 6 months was greater in the deferred stenting group (68 [IQR: 54% to 82%] vs. 56 [IQR: 31% to 72%]; p = 0.031]. Conclusions: In high-risk STEMI patients, deferred stenting in primary PCI reduced no-reflow and increased myocardial salvage

Improving response rates using a monetary incentive for patient completion of questionnaires: an observational study

Background: Poor response rates to postal questionnaires can introduce bias and reduce the statistical power of a study. To improve response rates in our trial in primary care we tested the effect of introducing an unconditional direct payment of 5 pound for the completion of postal questionnaires. Methods: We recruited patients in general practice with knee problems from sites across the United Kingdom. An evidence-based strategy was used to follow-up patients at twelve months with postal questionnaires. This included an unconditional direct payment of 5 pound to patients for the completion and return of questionnaires. The first 105 patients did not receive the 5 pound incentive, but the subsequent 442 patients did. We used logistic regression to analyse the effect of introducing a monetary incentive to increase the response to postal questionnaires. Results: The response rate following reminders for the historical controls was 78.1% ( 82 of 105) compared with 88.0% ( 389 of 442) for those patients who received the 5 pound payment (diff = 9.9%, 95% CI 2.3% to 19.1%). Direct payments significantly increased the odds of response ( adjusted odds ratio = 2.2, 95% CI 1.2 to 4.0, P = 0.009) with only 12 of 442 patients declining the payment. The incentive did not save costs to the trial - the extra cost per additional respondent was almost 50 pound. Conclusion: The direct payment of 5 pound significantly increased the completion of postal questionnaires at negligible increase in cost for an adequately powered study

Sex-based associations with microvascular injury and outcomes after ST-segment elevation myocardial infarction

Objectives: We aimed to assess for sex differences in invasive parameters of acute microvascular reperfusion injury and infarct characteristics on cardiac MRI after ST-segment elevation myocardial infarction (STEMI). Methods: Patients with STEMI undergoing emergency percutaneous coronary intervention (PCI) were prospectively enrolled. Index of microcirculatory resistance (IMR) and coronary flow reserve (CFR) were measured in the culprit artery post-PCI. Contrast-enhanced MRI was used to assess infarct characteristics, microvascular obstruction and myocardial haemorrhage, 2 days and 6 months post-STEMI. Prespecified outcomes were as follows: (i) all-cause death/first heart failure hospitalisation and (ii) cardiac death/non-fatal myocardial infarction/urgent coronary revascularisation (major adverse cardiovascular event, MACE) during 5- year median follow-up. Results: In 324 patients with STEMI (87 women, mean age: 61 ± 12.19 years; 237 men, mean age: 59 ± 11.17 years), women had anterior STEMI less often, fewer prescriptions of beta-blockers at discharge and higher baseline N-terminal pro-B-type natriuretic peptide levels (all p < 0.05). Following emergency PCI, fewer women than men had Thrombolysis in Myocardial Infarction (TIMI) myocardial perfusion grades ≤ 1 (20% vs 32%, p = 0.027) and women had lower corrected TIMI frame counts (12.94 vs 17.65, p = 0.003). However, IMR, CFR, microvascular obstruction, myocardial haemorrhage, infarct size, myocardial salvage index, left ventricular remodelling and ejection fraction did not differ significantly between sexes. Female sex was not associated with MACE or all-cause death/first heart failure hospitalisation. Conclusion: There were no sex differences in microvascular pathology in patients with acute STEMI. Women had less anterior infarcts than men, and beta-blocker therapy at discharge was prescribed less often in women

Comparative Prognostic Utility of Indexes of Microvascular Function Alone or in Combination in Patients with an Acute ST-Segment-Elevation Myocardial Infarction

Background—Primary percutaneous coronary intervention (PCI) is frequently successful at restoring coronary artery blood flow in patients with acute ST-segment elevation myocardial infarction, however, failed myocardial reperfusion commonly passes undetected in up to half of these patients. The index of microvascular resistance (IMR) is a novel invasive measure of coronary microvascular function. We aimed to investigate the pathological and prognostic significance of an index of microvascular resistance (IMR>40), alone or in combination with a coronary flow reserve (CFR≤2.0), in the culprit artery after emergency PCI for acute STEMI. Methods—Patients with acute STEMI were prospectively enrolled during emergency PCI, and categorized according to IMR (≤40 or >40) and CFR (≤2.0 or >2.0). Cardiac MRI was acquired 2 days and 6 months post-MI. All-cause death or first heart failure hospitalization was a pre-specified outcome (median follow-up duration 845 days). Results—IMR and CFR were measured in the culprit artery at the end of PCI in 283 STEMI patients (mean age 60 (12) years, 73% male). The median [interquartile range] IMR and CFR were 25 [15-48] and 1.6 [1.1-2.1], respectively. An IMR>40 was a multivariable associate of myocardial hemorrhage (odds ratio (OR) (95% confidence interval (CI)) 2.10 (1.03, 4.27); p=0.042. An IMR>40 was closely associated with microvascular obstruction. Symptom to reperfusion time, TIMI blush grade, and no (≤30%) ST segment resolution, were not associated with these pathologies. An IMR>40 was a multivariable associate of the changes in LV ejection fraction (coefficient (95% CI) (-2.12 (-4.02, -0.23); p=0.028) and LV end-diastolic volume (7.85 (0.41, 15.29); p=0.039) at 6 months, independent of infarct size. An IMR>40 (odds ratio 4.36 (95% CI 2.10, 9.06); p<0.001) was a multivariable associate of all-cause death or heart failure. Compared with an IMR>40, the combination of IMR>40 with CFR≤2.0 did not have incremental prognostic value. Conclusions—An IMR>40 is a multivariable associate of LV and clinical outcomes post-STEMI, independent of the size of infarction. Compared with standard clinical measures of the efficacy of myocardial reperfusion, including the ischemic time, ST-segment elevation, the angiographic blush grade and CFR, IMR has superior clinical value for risk stratification and may be considered as a reference test for failed myocardial reperfusion

Persistence of Infarct Zone T2 Hyperintensity at 6 Months after Acute ST-Segment-Elevation Myocardial Infarction:Incidence, Pathophysiology, and Prognostic Implications

Background—The incidence and clinical significance of persistent T2 hyperintensity after acute ST-segment–elevation myocardial infarction (STEMI) is uncertain. Methods and Results—Patients who sustained an acute STEMI were enrolled in a cohort study (BHF MR-MI: NCT02072850). Two hundred eighty-three STEMI patients (mean age, 59±12 years; 75% male) had cardiac magnetic resonance with T2 mapping performed at 2 days and 6 months post-STEMI. Persisting T2 hyperintensity was defined as infarct T2 >2 SDs from remote T2 at 6 months. Infarct zone T2 was higher than remote zone T2 at 2 days (66.3±6.1 versus 49.7±2.1 ms; P<0.001) and 6 months (56.8±4.5 versus 49.7±2.3 ms; P<0.001). Remote zone T2 did not change over time (mean change, 0.0±2.7 ms; P=0.837), whereas infarct zone T2 decreased (−9.5±6.4 ms; P<0.001). At 6 months, T2 hyperintensity persisted in 189 (67%) patients, who were more likely to have Thrombus in Myocardial Infarction flow 0 or 1 in the culprit artery (P=0.020), incomplete ST-segment resolution (P=0.037), and higher troponin (P=0.024). Persistent T2 hyperintensity was associated with NT-proBNP (N-terminal pro-B-type natriuretic peptide) concentration (0.57 on a log scale [0.42–0.72]; P=0.004) and the likelihood of adverse left ventricular remodeling (>20% change in left ventricular end-diastolic volume; 21.91 [2.75–174.29]; P=0.004). Persistent T2 hyperintensity was associated with all-cause death and heart failure, but the result was not significant (P=0.051). ΔT2 was associated with all-cause death and heart failure (P=0.004) and major adverse cardiac events (P=0.013). Conclusions—Persistent T2 hyperintensity occurs in two thirds of STEMI patients. Persistent T2 hyperintensity was associated with the initial STEMI severity, adverse remodeling, and long-term health outcome. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT02072850

Coronary thermodilution waveforms after acute reperfused stsegment-elevation myocardial infarction:Relation to microvascular obstruction and prognosis

Background: Invasive measures of microvascular resistance in the culprit coronary artery have potential for risk stratification in acute ST‐segment–elevation myocardial infarction. We aimed to investigate the pathological and prognostic significance of coronary thermodilution waveforms using a diagnostic guidewire. Methods and Results: Coronary thermodilution was measured at the end of percutaneous coronary intervention, (PCI) and contrast‐enhanced cardiac magnetic resonance imaging (MRI) was intended on day 2 and 6 months later to assess left ventricular (LV) function and pathology. All‐cause death or first heart failure hospitalization was a pre‐specified outcome (median follow‐up duration 1469 days). Thermodilution recordings underwent core laboratory assessment. A total of 278 patients with acute ST‐segment elevation myocardial infarction EMI (72% male, 59±11 years) had coronary thermodilution measurements classified as narrow unimodal (n=143 [51%]), wide unimodal (n=100 [36%]), or bimodal (n=35 [13%]). Microvascular obstruction and myocardial hemorrhage were associated with the thermodilution waveform pattern (P=0.007 and 0.011, respectively), and both pathologies were more prevalent in patients with a bimodal morphology. On multivariate analysis with baseline characteristics, thermodilution waveform status was a multivariable associate of microvascular obstruction (odds ratio [95% confidence interval]=5.29 [1.73, 16.22];, P=0.004) and myocardial hemorrhage (3.45 [1.16, 10.26]; P=0.026), but the relationship was not significant when index of microvascular resistance (IMR) >40 or change in index of microvascular resistance (5 per unit) was included. However, a bimodal thermodilution waveform was independently associated with all‐cause death and hospitalization for heart failure (odds ratio [95% confidence interval]=2.70 [1.10, 6.63]; P=0.031), independent of index of microvascular resistance>40, ST‐segment resolution, and TIMI (Thrombolysis in Myocardial Infarction) Myocardial Perfusion Grade. Conclusions: The thermodilution waveform in the culprit coronary artery is a biomarker of prognosis and may be useful for risk stratification immediately after reperfusion therapy

Persistent Iron Within the Infarct Core After ST-Segment Elevation Myocardial Infarction:Implications for Left Ventricular Remodeling and Health Outcomes

Objectives: This study sought to determine the incidence and prognostic significance of persistent iron in patients post–ST-segment elevation myocardial infarction (STEMI). Background: The clinical significance of persistent iron within the infarct core after STEMI complicated by acute myocardial hemorrhage is poorly understood. Methods: Patients who sustained an acute STEMI were enrolled in a cohort study (BHF MR-MI [Detection and Significance of Heart Injury in ST Elevation Myocardial Infarction]). Cardiac magnetic resonance imaging including T2* (observed time constant for the decay of transverse magnetization seen with gradient-echo sequences) mapping was performed at 2 days and 6 months post-STEMI. Myocardial hemorrhage or iron was defined as a hypointense infarct core with T2* signal <20 ms. Results: A total of 203 patients (age 57 ± 11 years, n = 158 [78%] male) had evaluable T2* maps at 2 days and 6 months post-STEMI; 74 (36%) patients had myocardial hemorrhage at baseline, and 44 (59%) of these patients had persistent iron at 6 months. Clinical associates of persistent iron included heart rate (p = 0.009), the absence of a history of hypertension (p = 0.017), and infarct size (p = 0.028). The presence of persistent iron was associated with worsening left ventricular (LV) end-diastolic volume (regression coefficient: 21.10; 95% confidence interval [CI]: 10.92 to 31.27; p < 0.001) and worsening LV ejection fraction (regression coefficient: −6.47; 95% CI: −9.22 to −3.72; p < 0.001). Persistent iron was associated with the subsequent occurrence of all-cause death or heart failure (hazard ratio: 3.91; 95% CI: 1.37 to 11.14; p = 0.011) and major adverse cardiac events (hazard ratio: 3.24; 95% CI: 1.09 to 9.64; p = 0.035) (median follow-up duration 1,457 days [range 233 to 1,734 days]). Conclusions: Persistent iron at 6 months post-STEMI is associated with worse LV and longer-term health outcomes. (Detection and Significance of Heart Injury in ST Elevation Myocardial Infarction [BHF MR-MI]; NCT02072850

Prognostic significance of infarct core pathology revealed by quantitative non-contrast in comparison with contrast cardiac magnetic resonance imaging in reperfused ST-elevation myocardial infarction survivors

Aims To assess the prognostic significance of infarct core tissue characteristics using cardiac magnetic resonance (CMR) imaging in survivors of acute ST-elevation myocardial infarction (STEMI). Methods and results We performed an observational prospective single centre cohort study in 300 reperfused STEMI patients (mean ± SD age 59 ± 12 years, 74% male) who underwent CMR 2 days and 6 months post-myocardial infarction (n = 267). Native T1 was measured in myocardial regions of interest (n = 288). Adverse remodelling was defined as an increase in left ventricular (LV) end-diastolic volume ≥20% at 6 months. All-cause death or first heart failure hospitalization was a pre-specified outcome that was assessed during follow-up (median duration 845 days). One hundred and sixty (56%) patients had a hypo-intense infarct core disclosed by native T1. In multivariable regression, infarct core native T1 was inversely associated with adverse remodelling [odds ratio (95% confidence interval (CI)] per 10 ms reduction in native T1: 0.91 (0.82, 0.00); P = 0.061). Thirty (10.4%) of 288 patients died or experienced a heart failure event and 13 of these events occurred post-discharge. Native T1 values (ms) within the hypo-intense infarct core (n = 160 STEMI patients) were inversely associated with the risk of all-cause death or first hospitalization for heart failure post-discharge (for a 10 ms increase in native T1: hazard ratio 0.730, 95% CI 0.617, 0.863; P < 0.001) including after adjustment for left ventricular ejection fraction, infarct core T2 and myocardial haemorrhage. The prognostic results for microvascular obstruction were similar. Conclusion Infarct core native T1 represents a novel non-contrast CMR biomarker with potential for infarct characterization and prognostication in STEMI survivors. Confirmatory studies are warranted

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