Sclerostin, which is primarily produced by the osteocytes, inhibits the canonical Wnt pathway and thereby the osteoblasts and stimulates RANKL release by the osteocytes and thereby osteoclast recruitment. Inhibition of sclerostin therefore causes stimulation of bone formation and inhibition of resorption. In clinical trials, romosozumab, an antibody against sclerostin, increases bone mineral density and reduces the risk of fractures compared with placebo and alendronate.The cardiovascular safety of romosozumab was adjudicated in 2 large clinical osteoporosis trials in postmenopausal women. Compared with placebo, the incidence of cardiovascular events was similar in the 2 treatment groups. Compared with alendronate, the incidence of serious cardiovascular events was higher in women treated with romosozumab. The incidence of serious cardiovascular adverse events was low and post hoc analyses should therefore be interpreted with caution; however, the relative risk seemed unaffected by preexisting cardiovascular disease or risk factors.Sclerostin is expressed in the vasculature, predominantly in vascular smooth muscle cells in the media. However, preclinical and genetic studies have not demonstrated any increased cardiovascular risk with continuously low sclerostin levels or inhibition of sclerostin. Furthermore, no potential mechanisms for such an effect have been identified. In conclusion, while there is no preclinical or genetic evidence of a harmful effect of sclerostin inhibition on cardiovascular safety, the evidence from the large clinical trials in postmenopausal women is conflicting. Romosozumab should therefore be used for the treatment of postmenopausal women with osteoporosis at high risk of fracture after careful consideration of the cardiovascular risk and the balance between benefits and risks.

BACKGROUND:Novel cardiac magnetic resonance (CMR) stress T1 mapping can detect ischemia and myocardial blood volume changes without contrast agents and may be a more comprehensive ischemia biomarker than myocardial blood flow. OBJECTIVES:This study describes the performance of the first prospective validation of stress T1 mapping against invasive coronary measurements for detecting obstructive epicardial coronary artery disease (CAD), defined by fractional flow reserve (FFR <0.8), and coronary microvascular dysfunction, defined by FFR ≥0.8 and the index of microcirculatory resistance (IMR ≥25 U), compared with first-pass perfusion imaging. METHODS:Ninety subjects (60 patients with angina; 30 healthy control subjects) underwent CMR (1.5- and 3-T) to assess left ventricular function (cine), ischemia (adenosine stress/rest T1 mapping and perfusion), and infarction (late gadolinium enhancement). FFR and IMR were assessed ≤7 days post-CMR. Stress and rest images were analyzed blinded to other information. RESULTS:Normal myocardial T1 reactivity (ΔT1) was 6.2 ± 0.4% (1.5-T) and 6.2 ± 1.3% (3-T). Ischemic viable myocardium downstream of obstructive CAD showed near-abolished T1 reactivity (ΔT1 = 0.7 ± 0.7%). Myocardium downstream of nonobstructive coronary arteries with microvascular dysfunction showed less-blunted T1 reactivity (ΔT1 = 3.0 ± 0.9%). Stress T1 mapping significantly outperformed gadolinium-based first-pass perfusion, including absolute quantification of myocardial blood flow, for detecting obstructive CAD (area under the receiver-operating characteristic curve: 0.97 ± 0.02 vs. 0.91 ± 0.03, respectively; p < 0.001). A ΔT1 of 1.5% accurately detected obstructive CAD (sensitivity: 93%; specificity: 95%; p < 0.001), whereas a less-blunted ΔT1 of 4.0% accurately detected microvascular dysfunction (area under the receiver-operating characteristic curve: 0.95 ± 0.03; sensitivity: 94%; specificity: 94%: p < 0.001). CONCLUSIONS:CMR stress T1 mapping accurately detected and differentiated between obstructive epicardial CAD and microvascular dysfunction, without contrast agents or radiation.

BACKGROUND In patients with angina and nonobstructive coronary artery disease (NOCAD), confirming symptoms due to coronary microvascular dysfunction (CMD) remains challenging. Cardiac magnetic resonance (CMR) assesses myocardial perfusion with high spatial resolution and is widely used for diagnosing obstructive coronary artery disease (CAD).OBJECTIVES The goal of this study was to validate CMR for diagnosing microvascular angina in patients with NOCAD, compared with patients with obstructive CAD and correlated to the index of microcirculatory resistance (IMR) during invasive coronary angiography.METHODS Fifty patients with angina (65 +/- 9 years of age) and 20 age-matched healthy control subjects underwent adenosine stress CMR (1.5- and 3-T) to assess left ventricular function, inducible ischemia (myocardial perfusion reserve index [MPRI]; myocardial blood flow [MBF]), and infarction (late gadolinium enhancement). During subsequent angiography within 7 days, 28 patients had obstructive CAD (fractional flow reserve [FFR] <= 0.8) and 22 patients had NOCAD (FFR >0.8) who underwent 3-vessel IMR measurements.RESULTS In patients with NOCAD, myocardium with IMR <25 U had normal MPRI (1.9 +/- 0.4 vs. controls 2.0 +/- 0.3; p = 0.49); myocardium with IMR >= 25 U had significantly impaired MPRI, similar to ischemic myocardium downstream of obstructive CAD (1.2 +/- 0.3 vs. 1.2 +/- 0.4; p = 0.61). An MPRI of 1.4 accurately detected impaired perfusion related to CMD (IMR >= 25 U; FFR >0.8) (area under the curve: 0.90; specificity: 95%; sensitivity: 89%; p < 0.001). Impaired MPRI in patients with NOCAD was driven by impaired augmentation of MBF during stress, with normal resting MBF. Myocardium with FFR >0.8 and normal IMR (< 25 U) still had blunted stress MBF, suggesting mild CMD, which was distinguishable from control subjects by using a stress MBF threshold of 2.3 ml/min/g with 100% positive predictive value.CONCLUSIONS In angina patients with NOCAD, CMR can objectively and noninvasively assess microvascular angina. A CMR-based combined diagnostic pathway for both epicardial and microvascular CAD deserves further clinical validation. (c) 2018 The Authors. Published by Elsevier on behalf of the AmericanCollege of Cardiology Foundation. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

BACKGROUND:In patients with angina and nonobstructive coronary artery disease (NOCAD), confirming symptoms due to coronary microvascular dysfunction (CMD) remains challenging. Cardiac magnetic resonance (CMR) assesses myocardial perfusion with high spatial resolution and is widely used for diagnosing obstructive coronary artery disease (CAD). OBJECTIVES:The goal of this study was to validate CMR for diagnosing microvascular angina in patients with NOCAD, compared with patients with obstructive CAD and correlated to the index of microcirculatory resistance (IMR) during invasive coronary angiography. METHODS:Fifty patients with angina (65 ± 9 years of age) and 20 age-matched healthy control subjects underwent adenosine stress CMR (1.5- and 3-T) to assess left ventricular function, inducible ischemia (myocardial perfusion reserve index [MPRI]; myocardial blood flow [MBF]), and infarction (late gadolinium enhancement). During subsequent angiography within 7 days, 28 patients had obstructive CAD (fractional flow reserve [FFR] ≤0.8) and 22 patients had NOCAD (FFR >0.8) who underwent 3-vessel IMR measurements. RESULTS:In patients with NOCAD, myocardium with IMR <25 U had normal MPRI (1.9 ± 0.4 vs. controls 2.0 ± 0.3; p = 0.49); myocardium with IMR ≥25 U had significantly impaired MPRI, similar to ischemic myocardium downstream of obstructive CAD (1.2 ± 0.3 vs. 1.2 ± 0.4; p = 0.61). An MPRI of 1.4 accurately detected impaired perfusion related to CMD (IMR ≥25 U; FFR >0.8) (area under the curve: 0.90; specificity: 95%; sensitivity: 89%; p < 0.001). Impaired MPRI in patients with NOCAD was driven by impaired augmentation of MBF during stress, with normal resting MBF. Myocardium with FFR >0.8 and normal IMR (<25 U) still had blunted stress MBF, suggesting mild CMD, which was distinguishable from control subjects by using a stress MBF threshold of 2.3 ml/min/g with 100% positive predictive value. CONCLUSIONS:In angina patients with NOCAD, CMR can objectively and noninvasively assess microvascular angina. A CMR-based combined diagnostic pathway for both epicardial and microvascular CAD deserves further clinical validation.

Objectives In patients with angina and non-obstructive coronary arteries, abnormal index of microcirculatory resistance (IMR ≥23) and coronary flow reserve (CFR ≤2.0) confer adverse clinical outcomes. We hypothesised that these prognostic invasive markers of microcirculatory dysfunction are related to impaired downstream myocardial perfusion reserve (MPR) as assessed by CMR. Methods 60 subjects (20 patients with angina and non-obstructive coronary arteries, 20 patients with obstructive coronary artery disease [CAD] and 20 normal controls) underwent CMR for the assessment of LV function (cines), ischaemia (adenosine stress and rest perfusion) and infarction (LGE). During invasive coronary angiography, patients with non-obstructive coronary arteries had fractional flow reserve (FFR), CFR and IMR measured in all 3 coronary arteries (60 vessels), while patients with obstructive CAD had FFR measured in the obstructive coronary artery only (20 vessels). CMR images were analysed blinded to clinical information and invasive coronary data. MPR was derived as the ratio between stress and rest myocardial perfusion signal intensity upslope gradients, normalised to LV blood signal intensity. Results Myocardium with LGE was excluded. Non-infarcted myocardium downstream obstructive coronary arteries (FFR <0.80) had lower MPR compared to controls (1.3±0.4 vs 1.9±0.3, p<0.001). Downstream of non-obstructive coronary arteries (FFR >0.80), myocardium with normal microcirculatory function (normal IMR and CFR) had similar MPR compared to controls (1.9±0.2 vs 1.9±0.3, p=0.83). Myocardium with prognostic microcirculatory dysfunction (IMR ≥23 and CFR≤2.0) had significantly impaired MPR (1.3±0.3, p<0.001); further, the degree of impairment in MPR was similar to ischaemic myocardium downstream obstructive coronary arteries (MPR 1.3±0.3 vs 1.3±0.4, p=0.73; Figure 1). On ROC analysis, a threshold of MPR=1.4 detected prognostic microvascular dysfunction (IMR ≥23 and CFR≤2.0) in non-obstructive coronary arteries with specificity 97%, sensitivity 81%, and accuracy 89% (AUC 0.95±0.02, Figure 2). Conclusions In patients with angina and non-obstructive coronary arteries, an MPR threshold of 1.4 on perfusion CMR accurately detects prognostic invasive markers of microcirculatory dysfunction. This novel MPR threshold can now be used to objectively diagnose microvascular angina in clinical practice and guide disease management. Abstract 022 Figure 1 Patterns of myocardial perfusion reserve (MPR) in normal controls, and downstream of non-obstructive coronary arteries, and obstructive coronary arteries (CAD). All bars represent mean ± SD, *p<0.05, ns denotes p>0.10. IMR: index of microcirculatory resistance; CFR: coronary flow reserve; FFR: fractional flow reserve. Abnormal IMR/CFR was defined as IMR≥23 and CFR≤2.0. Normal IMR/CFR was defined as IMR<23 and CFR>2.0. Abstract 022 Figure 2 Diagnostic performance of myocardial perfusion reserve (MPR) for diagnosing microcirculatory dysfunction (true positives: abnormal IMR≥23 and CFR≤2.0; true negatives: IMR<23 and CFR>2.0). AUC: area under the curve.

Background Early risk stratification after primary percutaneous coronary intervention (PPCI) for ST‐segment–elevation myocardial infarction is currently challenging. Identification of a low‐risk group may improve triage of patients to alternative clinical pathways and support early hospital discharge. Our aim was to assess whether the index of microcirculatory resistance (IMR) at the time of PPCI can identify patients at low risk of early major cardiac complications and to compare its performance against guideline‐recommended risk scores. Methods and Results IMR was measured using a pressure–temperature sensor wire. Cardiac complications were defined as the composite of cardiac death, cardiogenic shock, pulmonary edema, malignant arrhythmias, cardiac rupture, and presence of left ventricular thrombus either before hospital discharge or within 30‐day follow‐up. In total, 261 patients undergoing PPCI who were eligible for coronary physiology assessment were prospectively enrolled. Twenty‐two major cardiac complications were reported. Receiver operating characteristic curve analysis confirmed the utility of IMR in predicting complications and showed significantly better performance than coronary flow reserve, the Primary Angioplasty in Myocardial Infarction II (PAMI‐II), and Zwolle score (P≤0.006). Low microvascular resistance (IMR ≤40) was measured in 159 patients (61%) of the study population and identified all patients who were free of major cardiac complications (sensitivity: 100%; 95% CI, 80.5–100%). Conclusions IMR immediately at the end of PPCI for ST‐segment–elevation myocardial infarction reliably predicts early major cardiac complications and performed significantly better than recommended risk scores. These novel data have implications for early risk stratification after PPCI.

Perfusion cardiovascular magnetic resonance (CMR) performed with inadequate adenosine stress leads to false-negative results and suboptimal clinical management. The recently proposed marker of adequate stress, the “splenic switch-off” sign, detects splenic blood flow attenuation during stress perfusion (spleen appears dark), but can only be assessed after gadolinium first-pass, when it is too late to optimize the stress response. Reduction in splenic blood volume during adenosine stress is expected to shorten native splenic T1, which may predict splenic switch-off without the need for gadolinium.

Objectives The index of microcirculatory resistance (IMR) provides a reproducible assessment of the status of coronary microvasculature in patients with ST-elevation myocardial infarction (STEMI). Frequency-domain optical coherence tomography (FD-OCT) enables detailed assessment of the morphology of coronary plaque. We sought to determine the influence of the initial culprit coronary plaque anatomy within the infarct-related artery on IMR after stenting in STEMI. Patients and methods In 25 STEMI patients IMR was measured immediately before and after stent implantation. FD-OCT imaging was performed at the same time points and atherothrombotic volume (ATV) before stenting, prolapsed+floating ATV after stenting and ΔATV was measured using three different strategies. Results There were no relationships between preprocedural IMR and FD-OCT parameters. Prestenting IMR was related only to pain to wire time (P: 0.02). Irrespective of the method adopted, the final IMR was related to prestenting ATV (ρ: 0.44, P: 0.03 for method I, ρ: 0.48, P: 0.02 for method II and ρ: 0.30, P: 0.06 for method III) and ΔATV (ρ: 0.41, P: 0.04 for method II and ρ: 0.44, P: 0.03 for method III). Conclusion IMR measured before stenting is independent of the appearances of the culprit coronary plaque within the infarct-related artery. IMR after stenting, and more importantly, the change in IMR after stenting, reflect the degree of distal embolization during stent implantation.

Background In over 50% of patients with angina, the underlying ischaemia is related to microvascular dysfunction (MVD), rather than epicardial coronary artery disease (CAD). Clinically, MVD remains a major diagnostic challenge, which hinders targeted therapy and confers impaired clinical outcomes. Myocardial perfusion reserve (MPR), as assessed by cardiovascular magnetic resonance (CMR), is impaired in those with microvascular angina. We sought to objectively diagnose microvascular ischaemia using CMR by defining an MPR cut-off, validated against invasive coronary microvascular physiology (Index of Microvascular Resistance, IMR). Methods 75 subjects (50 patients with angina and suspected CAD; 25 healthy controls) underwent CMR to assess LV function, MPR (adenosine stress/rest first-pass perfusion imaging) and viability (late gadolinium enhancement). All patients underwent invasive coronary angiography with pressure-wire assessment of IMR and fractional flow reserve (FFR). A total of 120 coronary arteries were assessed. CMR images were analysed by observers blinded to clinical and angiographic data. MPR was defined as the ratio of stress/rest myocardial signal intensity upslope gradients during gadolinium first-pass perfusion imaging, normalised to LV blood pool enhancement. Infarcted myocardium was identified using LGE and excluded from analysis. Results For reference, myocardium downstream of significant epicardial stenosis (FFR<0.8) had lower MPR than healthy controls (1.3±0.4 vs 1.9±0.4, p<0.001, figure 1). Downstream of unobstructed epicardial coronary arteries (FFR>0.8), non-infarcted myocardium had intermediate MPR: (unobstructed-CAD 1.6±0.4, obstructed-CAD 1.3±0.4; controls: 1.9±0.4, p<0.001 by ANOVA). When further stratified by IMR, myocardium with IMR<20 had comparable MPR to normal controls (1.9±0.5 vs 1.9±0.4, p=0.98); as IMR increased, there was progressive reduction in MPR (IMR<20: 1.9±0.5, IMR20-40: 1.5±0.4, IMR>40: 1.3±0.4; all p<0.01 by ANOVA). Myocardium with high IMR>40 but unobstructed epicardial coronary arteries had equivalent MPR to ischaemic myocardium supplied by significant epicardial stenosis (1.3±0.4 vs 1.3±0.4, p=0.48, figure 1). Downstream of unobstructed epicardial coronary arteries of CAD patients, MPR 1.5 detected microvascular ischaemia (defined by IMR>40) with a sensitivity of 82%, specificity of 83%, and accuracy of 83% on ROC analysis (AUC 0.87±0.06, figure 2). Conclusions Microvascular ischaemia can be objectively diagnosed using CMR perfusion imaging. Reduced MPR is related to increased microvascular resistance, as validated by invasive IMR. The novel MPR criterion of 1.5, to detect high IMR>40, can confirm the clinical diagnosis of microvascular ischaemia, enabling targeted therapy and disease monitoring.

AIMS:Restoration of effective myocardial reperfusion by primary percutaneous coronary intervention (PPCI) in patients with ST-elevation myocardial infarction is difficult to predict. A method to assess the likelihood of a suboptimal response to conventional pharmacomechanical therapies could be beneficial. We aimed to derive and validate a scoring system that can be used acutely at the time of coronary reopening to predict the likelihood of downstream microvascular impairment in patients with STEMI. METHODS AND RESULTS:A score estimating the risk of post-procedural microvascular injury defined by an index of microcirculatory resistance (IMR) >40 was initially derived in a cohort of 85 STEMI patients (derivation cohort). This score was then tested and validated in three further cohorts of patients (retrospective [30 patients], prospective [42 patients] and external [29 patients]). The ATI score (age [>50=1]; pre-stenting IMR [>40 and <100=1; ≥100=2]; thrombus score [4=1; 5=3]) was highly predictive of a post-stenting IMR >40 in all four cohorts (AUC: 0.87; p<0.001-derivation cohort, 0.84; p=0.002-retrospective cohort, 0.92; p<0.001-prospective cohort and 0.81; p=0.006-external cohort). In the whole population, an ATI score ≥4 presented a 95.1% risk of final IMR >40, while no cases of final IMR >40 occurred in the presence of an ATI score <2. CONCLUSIONS:The ATI score appears to be a promising tool capable of identifying patients during PPCI who are at the highest risk of coronary microvascular impairment following revascularisation. This procedural risk stratification has a number of potential research and clinical applications and warrants further investigation.

Aim Restoration of effective myocardial reperfusion by primary percutaneous coronary intervention (PPCI) in patients with STEMI is not predictable. A method to assess the likelihood of a suboptimal response to conventional pharmaco-mechanical therapies could be beneficial. We aimed to derive and validate a scoring system that can be used acutely at the time of coronary reopening to predict the likelihood of downstream microvascular impairment in patients with STEMI. Methods and Results A score estimating the risk of post-procedural microvascular injury defined by an index of microcirculatory resistance (IMR) > 40, was initially derived in a cohort of 85 STEMI patients (Derivation cohort). This score was then tested and validated in three further cohorts of patients (Retrospective (30 patients), Prospective (42 patients) and External (29 patients). The ATI score [Age ( > 50 = 1); pre-stenting IMR (> 40 and < 100 = 1; ≥ 100 = 2); Thrombus score (4=1; 5=3)] was highly predictive of a post-stenting IMR > 40 in all the four cohorts (AUC:0.87; p < 0.001-Derivation cohort, 0.84; p: 0.002-Retrospective cohort, 0.92; p < 0.001-Prospective cohort and 0.81; p: 0.006-External cohort). In the whole population an ATI score ≥ 4 presented a 95.1% risk of final IMR >40, while no cases of final IMR >40 occurred in the presence of an ATI score < 2. Conclusions The ATI score appears to be a promising tool capable of identifying patients during PPCI that are at the highest risk of an adverse outcome following revascularisation.

Beta‐blockers are the only anti‐arrhythmic drugs that improve mortality post myocardial infarction (MI), but a significant risk of ventricular arrhythmia remains. We have shown that ventricular fibrillation threshold is reduced following high‐level sympathetic stimulation even in the presence of a beta‐blocker due to release of the sympathetic co‐transmitter neuropeptide‐Y (NPY). We hypothesized that exogenous NPY would increase the prevalence of ventricular arrhythmias following ischemia reperfusion in the isolated rat heart. Moreover, we hypothesized that plasma NPY levels would correlate with ventricular arrhythmias following primary percutaneous intervention (PPCI) in patients being treated for ST‐elevation MI (STEMI). In the isolated Langendorff perfused (10ml/min) rat heart NPY (250nM, n=10) significantly increased the prevalence of ventricular arrhythmias (90% v's 20%, p<0.01) following 7 minutes of no flow ischemia compared to control (n=10), and also their severity as measured by arrhythmia scoring (2.0±0.4 v's 0.3±0.2, mean±SEM, p<0.01). In 55 patients presenting with left coronary artery STEMI for PPCI, those with venous plasma NPY levels taken immediately post PPCI above the median (>19 pg/ml) were significantly older (68.0±2.2 v's 58.2±2.5 year old, p<0.01) but had similar cardiovascular risk factors, peak troponin rise and beta‐blocker usage. There was no difference in ejection fraction measured on cardiac MRI after 24 hours (45.3±2.1 v's 46.3±1.9%, n=39) and 6 months (51.8±2.6 v's 55.0±2.9%, n=34) post STEMI between the two groups, and no difference in infarct size (20.4±2.8 v's 17.2±2.6% late Gd enhancement at 6 months). However, over the course of the coronary care unit admission following PPCI, those with NPY levels above the median had a higher prevalence (53.6% v's 25.9%, p=0.03) and a higher severity of ventricular arrhythmias (score: 0.96±0.23 v's 0.33±0.12, p=0.02). NPY may be a novel arrhythmic trigger during ischemia reperfusion and drugs inhibiting NPY or NPY receptors may offer a potential therapeutic opportunity.Support or Funding InformationSupported by the British Heart Foundation and NIHR Oxford Biomedical Research Centre

Atrial septal defect device closure in the elderly, symptomatic benefits except for arrhythmia

Aims Primary percutaneous coronary intervention (PPCI) is the optimal treatment for patients presenting with ST-elevation myocardial infarction (STEMI). An elevated index of microcirculatory resistance (IMR) reflects microvascular function and when measured after PPCI, it can predict an adverse clinical outcome. We measured coronary microvascular function in STEMI patients and compared sequential changes before and after stent implantation. Methods and results In 85 STEMI patients, fractional flow reserve, coronary flow reserve, and IMR were measured using a pressure wire (Certus, St Jude Medical, St Paul, MN, USA) immediately before and after stent implantation. Stenting significantly improved all of the measured parameters of coronary physiology including IMR from 67.7 [interquartile range (IQR): 56.2–95.8] to 36.7 (IQR: 22.7–59.5), P < 0.001. However, after stenting, IMR remained elevated (>40) in 28 (32.9%) patients. In 15 of these patients (17.6% of the cohort), only a partial reduction in IMR occurred and these patients were more likely to be late presenters (pain to wire time >6 h). The extent of jeopardized myocardium [standardized beta: −0.26 (IMR unit/Bypass Angioplasty Revascularization Investigation score unit), P: 0.009] and pre-stenting IMR [standardized beta: −0.34 (IMR unit), P: 0.001] predicted a reduction in IMR after stenting (ΔIMR = post-stenting IMR − pre-stenting IMR), whereas thrombotic burden [standardized beta: 0.24 (IMR unit/thrombus score unit), P: 0.01] and deployed stent volume [standardized beta: 0.26 (IMR unit/mm3 of stent), P: 0.01] were associated with a potentially deleterious increase in IMR. Conclusion Improved perfusion of the myocardium by stent deployment during PPCI is not universal. The causes of impaired microvascular function at the completion of PPCI treatment are heterogeneous, but can reflect a later clinical presentation and/or the location and extent of the thrombotic burden.

OBJECTIVES The aim of this study was to define which measure of microvascular best predicts the extent of left ventricular (LV) infarction.BACKGROUND Microvascular injury after ST-segment elevation myocardial infarction (STEMI) is an important determinant of outcome. Several invasive measures of the microcirculation at primary percutaneous coronary intervention (PPCI) have been described. One such measure is zero-flow pressure (Pzf), the calculated pressure at which coronary flow would cease.METHODS In 34 STEMI patients, Pzf, hyperemic microvascular resistance (hMR), and index of microcirculatory resistance (IMR) were derived using thermodilution flow/pressure and Doppler flow/pressure wire assessment of the infarct-related artery following PPCI. The extent of infarction was determined by blinded late gadolinium enhancement on cardiac magnetic resonance at 6 months post-PPCI. Infarction of >= 24% total LV mass was used as a categorical cutoff in receiver-operating characteristic curve analysis.RESULTS Pzf was superior to both hMR and IMR for predicting >= 24% infarction area under the curve: 0.94 for Pzf versus 0.74 for hMR (p = 0.04) and 0.54 for IMR (p = 0.003). Pzf >= 42 mm Hg was the optimal cutoff value, offering 100% sensitivity and 73% specificity. Patients with Pzf >= 42 mm Hg also had a lower salvage index (61.3 +/- 8.1 vs. 44.4 +/- 16.8, p = 0.006) and 6-month ejection fraction (62.4 +/- 3.6 vs. 49.9 +/- 9.6, p = 0.002). In addition, there were significant direct relationships between Pzf and troponin area under the curve (rho = 0.55, p = 0.002), final infarct mass (rho = 0.75, p < 0.0001), percentage of LV infarction and percent transmurality of infarction (rho = 0.77 and 0.74, respectively, p < 0.0001), and inverse relationships with myocardial salvage index (rho = - 0.53, p = 0.01) and 6-month ejection fraction (rho = - 0.73, p = 0.0001).CONCLUSIONS Pzf measured at the time of PPCI is a better predictor of the extent of myocardial infarction than hMR or IMR. Pzf may provide important prognostic information at the time of PPCI and merits further investigation in clinical studies with relevant outcome measures. (C) 2015 by the American College of Cardiology Foundation.

BACKGROUND Invasive assessment of coronary physiology (IACP) offers important prognostic insights in ST-segment elevation myocardial infarction (STEMI) but the dynamics of coronary recovery are poorly understood.OBJECTIVES This study sought to examine the evolution of coronary flow reserve (CFR), index of microcirculatory resistance (IMR), ratio of distal coronary pressure (Pd) to mean aortic pressure (Pa), and fractional flow reserve (FFR) in patients undergoing primary percutaneous coronary intervention (PPCI).METHODS 82 patients with STEMI underwent IACP at PPCI. Repeat IACP was performed in 61 patients (74%) at day 1 and in 46 patients (56%) at 6 months. Contrast-enhanced cardiac magnetic resonance imaging (CMR) was performed in 45 patients (55%) at day 1 and in 41 patients (50%) at 6 months. Changes in IACP were compared between patients with and without microvascular obstruction (MVO) on CMR.RESULTS MVO was present in 21 of 45 patients (47%). Patients with MVO had lower CFR at PPCI and day 1 (p < 0.05) and a trend toward higher IMR values (p = 0.07). At 6 months, CFR and IMR were not significantly different between the groups. Baseline flow and Pd/Pa remained stable over time but FFR reduced significantly between PPCI and 6 months (p = 0.008); this reduction was mainly observed in patients with MVO (p = 0.006) but not in those without MVO (p = 0.21).CONCLUSIONS In PPCI-treated patients with STEMI, coronary microcirculation begins to recover within 24 h and recovery progresses further by 6 months. FFR significantly reduces from baseline to 6 months. The presence of MVO indicates a highly dysfunctional microcirculation. (C) 2014 by the American College of Cardiology Foundation.