Preventability of unplanned readmissions within 30 days of discharge. A cross-sectional, single-center study.

OBJECTIVES: To identify the preventability, determinants and causes of unplanned hospital readmissions within 30 days of discharge using a multidisciplinary approach and including patients' perspectives. DESIGN: A prospective cross-sectional single-center study. SETTING: Urban teaching hospital in Amsterdam, the Netherlands. PARTICIPANTS: 430 patients were included. Inclusion criteria were: age ≥ 18 years, discharged from one of seven participating clinical departments and an unplanned readmission within 30 days. METHODS: Residents from the participating departments individually assessed whether the readmission was caused by healthcare, the preventability and possible causes of readmissions using a tool. Thereafter, the preventability of the cases was discussed in a multidisciplinary meeting with residents of all participating departments and clinical pharmacists. The primary outcome was the proportion of readmissions that were potentially preventable. Secondary outcomes were the determinants for a readmission, causes for preventable readmissions, the change in the final decision on preventability after the multidisciplinary meeting and the value of patient interviews in assessing preventability. Differences in characteristics of potentially preventable readmissions (PPRs) and non-PPRs were analyzed using multivariable logistic regression. RESULTS: Of 430 readmissions, 56 (13%) were assessed as PPRs. Age was significantly associated with a PPR (adjusted OR: 2.42; 95%, CI 1.23-4.74; p = 0.01). The main causes for PPRs were diagnostic (30%), medication (27%) and management problems (27%). During the multidisciplinary meeting, the final decision on preventability changed in 11% of the cases. When a patient interview was available, it was used as a source of information to assess preventability in 26% of readmissions. In 7% of cases, the patient interview was mentioned as the most important source. CONCLUSION AND IMPLICATIONS: 13% of readmissions were potentially preventable with diagnostic, medication or management problems being main causes. A multidisciplinary review approach and including the patient's perspective could contribute to a better understanding of the complexity of readmissions and possible improvements.

Strain analysis is superior to wall thickening in discriminating between infarcted myocardium with and without microvascular obstruction.

OBJECTIVES: The aim of the present study was to evaluate the diagnostic performances of strain and wall thickening analysis in discriminating among three types of myocardium after acute myocardial infarction: non-infarcted myocardium, infarcted myocardium without microvascular obstruction (MVO) and infarcted myocardium with MVO. METHODS: Seventy-one patients with a successfully treated ST-segment elevation myocardial infarction underwent cardiovascular magnetic resonance imaging at 2-6 days after reperfusion. The imaging protocol included conventional cine imaging, myocardial tissue tagging and late gadolinium enhancement. Regional circumferential and radial strain and associated strain rates were analyzed in a 16-segment model as were the absolute and relative wall thickening. RESULTS: Hyperenhancement was detected in 418 (38%) of 1096 segments and was accompanied by MVO in 145 (35%) of hyperenhanced segments. Wall thickening, circumferential and radial strain were all significantly diminished in segments with hyperenhancement and decreased even further if MVO was also present (all p < 0.001). Peak circumferential strain (CS) surpassed all other strain and wall thickening parameters in its ability to discriminate between hyperenhanced and non-enhanced myocardium (all p < 0.05). Furthermore, CS was superior to both absolute and relative wall thickening in differentiating infarcted segments with MVO from infarcted segments without MVO (p = 0.02 and p = 0.001, respectively). CONCLUSIONS: Strain analysis is superior to wall thickening in differentiating between non-infarcted myocardium, infarcted myocardium without MVO and infarcted myocardium with MVO. Peak circumferential strain is the most accurate marker of regional function. KEY POINTS: • CMR can quantify regional myocardial function by analysis of wall thickening on cine images and strain analysis of tissue tagged images. • Strain analysis is superior to wall thickening in differentiating between different degrees of myocardial injury after acute myocardial infarction. • Peak circumferential strain is the most accurate marker of regional function.

Long-Term Prognostic Implications of Previous Silent Myocardial Infarction in Patients Presenting With Acute Myocardial Infarction.

OBJECTIVES: This study investigated the prevalence of silent myocardial infarction (MI) in patients presenting with first acute myocardial infarction (AMI), and its relation with mortality and major adverse cardiovascular events (MACE) at long-term follow-up. BACKGROUND: Up to 54% of MI occurs without apparent symptoms. The prevalence and long-term prognostic implications of previous silent MI in patients presenting with seemingly first AMI are unclear. METHODS: A 2-center observational longitudinal study was performed in 392 patients presenting with first AMI between 2003 and 2013, who underwent late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) examination within 14 days post-AMI. Silent MI was assessed on LGE-CMR images by identifying regions of hyperenhancement with an ischemic distribution pattern in other territories than the AMI. Mortality and MACE (all-cause death, reinfarction, coronary artery bypass grafting, and ischemic stroke) were assessed at 6.8 ± 2.9 years follow-up. RESULTS: Thirty-two patients (8.2%) showed silent MI on LGE-CMR. Compared with patients without silent MI, mortality risk was higher in patients with silent MI (hazard ratio: 3.87; 95% confidence interval: 1.21 to 12.38; p = 0.023), as was risk of MACE (hazard ratio: 3.10; 95% confidence interval: 1.22 to 7.86; p = 0.017), both independent from clinical and infarction-related characteristics. CONCLUSIONS: Silent MI occurred in 8.2% of patients presenting with first AMI and was independently related to poorer long-term clinical outcome, with a more than 3-fold risk of mortality and MACE. Silent MI holds prognostic value over important traditional prognosticators in the setting of AMI, indicating that these patients represent a high-risk subgroup warranting clinical awareness.

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

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

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

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

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

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

In vivo assessment of myocardial viability after acute myocardial infarction: A head-to-head comparison of the perfusable tissue index by PET and delayed contrast-enhanced CMR.

BACKGROUND: Early recognition of viable myocardium after acute myocardial infarction (AMI) is of clinical relevance, since affected segments have the potential of functional recovery. Delayed contrast-enhanced magnetic resonance imaging (DCE-CMR) has been validated extensively for the detection of viable myocardium. An alternative parameter for detecting viability is the perfusable tissue index (PTI), derived using [15O]H2O positron emission tomography (PET), which is inversely related to the extent of myocardial scar (non-perfusable tissue). The aim of the present study was to investigate the predictive value of PTI on recovery of LV function as compared to DCE-CMR in patients with AMI, after successful percutaneous coronary intervention (PCI). METHODS: Thirty-eight patients with ST elevation myocardial infarction (STEMI) successfully treated by PCI were prospectively recruited. Subjects were examined 1 week and 3 months (mean follow-up time: 97 ± 10 days) after AMI using [15O]H2O PET and DCE-CMR to assess PTI, regional function and scar. Viability was defined as recovery of systolic wall thickening ≥3.0 mm at follow-up by use of CMR. A total of 588 segments were available for serial analysis. RESULTS: At baseline, 180 segments were dysfunctional and exhibited DCE. Seventy-three (41%) of these dysfunctional segments showed full recovery during follow-up (viable), whereas 107 (59%) segments remained dysfunctional (nonviable). Baseline PTI of viable segments was 0.94 ± 0.09 and was significantly higher compared to nonviable segments (0.80 ± 0.13, P < .001). The optimal cut-off value for PTI was ≥0.85 with a sensitivity of 85% and specificity of 72%, and an area under the curve (AUC) of 0.82. In comparison, a cut-off value of <32% for the extent of DCE resulted in a sensitivity of 72% and a specificity of 69%, and an AUC of 0.75 (AUC PTI vs DCE P = .14). CONCLUSION: Assessment of myocardial viability shortly after reperfused AMI is feasible using PET. PET-derived PTI yields a good predictive value for the recovery of LV function in PCI-treated STEMI patients, in excellent agreement with DCE-CMR.

The role of ADAMTS13 in acute myocardial infarction: cause or consequence?

AIMS: ADAMTS13, a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13, is a metalloprotease that cleaves von Willebrand factor (VWF). There is considerable evidence that VWF levels increase and ADAMTS13 levels decrease in ST-elevation myocardial infarction (STEMI) patients. It is unclear whether this contributes to no reflow, infarct size, and intramyocardial haemorrhage (IMH). We aimed to determine the role of ADAMTS13 in STEMI patients and to investigate the benefits of recombinant ADAMTS13 (rADAMTS13) in a porcine model of myocardial ischaemia-reperfusion. METHODS AND RESULTS: In 49 consecutive percutaneous coronary intervention (PCI)-treated STEMI patients, blood samples were collected directly after through 7 days following PCI. Cardiac magnetic resonance was performed 4-6 days after PCI to determine infarct size and IMH. In 23 Yorkshire swine, the circumflex coronary artery was occluded for 75 min. rADAMTS13 or vehicle was administered intracoronary following reperfusion. Myocardial injury and infarct characteristics were assessed using cardiac enzymes, ECG, and histopathology. In patients with IMH, VWF activity and VWF antigen were significantly elevated directly after PCI and for all subsequent measurements, and ADAMTS13 activity significantly decreased at 4 and 7 days following PCI, in comparison with patients without IMH. VWF activity and ADAMTS13 activity were not related to infarct size. In rADAMTS13-treated animals, no differences in infarct size, IMH, or formation of microthrombi were witnessed compared with controls. CONCLUSIONS: No correlation was found between VWF/ADAMTS13 and infarct size in patients. However, patients suffering from IMH had significantly higher VWF activity and lower ADAMTS13 activity. Intracoronary administration of rADAMTS13 did not decrease infarct size or IMH in a porcine model of myocardial ischaemia-reperfusion. These data dispute the imbalance in ADAMTS13 and VWF as the cause of no reflow.

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

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

Fluoroscopy Assisted Scoring of Myocardial Hypoperfusion (FLASH) ratio as a novel predictor of mortality after primary PCI in STEMI patients.

BACKGROUND: The aim of this study was to investigate whether Fluoroscopy Assisted Scoring of Myocardial Hypoperfusion (FLASH) enabled a more accurate assessment of coronary blood flow and prediction of cardiac mortality after primary PCI (pPCI), than the presently used angiographic scores of reperfusion. METHODS: We included 453 STEMI patients who received pPCI at our hospital. Using the novel FLASH algorithm, based on contrast passage time and quantitative coronary analysis, FLASH flow was measured after pPCI and was used to calculate FLASH ratio of culprit and reference artery. In 28 of the 453 patients, FLASH flow was compared to Doppler-derived-flow. RESULTS: FLASH flow had a good correlation with Doppler derived flow (Pearson's R=0.65, p<0.001) and had a high inter-observer agreement (ICC=0.83). FLASH flow was significantly lower in patients that died of cardiac death within six months (25.9±17.7 ml/min vs. 38.2±18.8 ml/min, p=0.004). FLASH ratio had a high accuracy of predicting cardiac mortality with a significant higher area under the curve as compared with CTFC and QuBe (p=0.041 and p=0.008). FLASH ratio was an independent predictor of mortality at 6 months (HR=0.98 per 1% increase, p=0.014). CONCLUSION: FLASH is a simple non-invasive method to estimate coronary blood flow and predict mortality directly following pPCI in STEMI patients, with a higher accuracy compared to the presently used angiographic scores.

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

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

Coronary vasomotor function in infarcted and remote myocardium after primary percutaneous coronary intervention.

OBJECTIVE: In patients with acute myocardial infarction (AMI), coronary vasomotor function is impaired in the myocardial territory supplied by the culprit artery and in remote myocardium supplied by angiographically normal vessels. The aim was to investigate the temporal evolution of coronary vasodilatory reserve in patients with AMI by use of [(15)O]H2O positron emission tomography, after successful percutaneous coronary intervention. METHODS: 44 patients with AMI and successful revascularisation by percutaneous coronary intervention were included. Subjects were examined 1 week and 3 months after AMI with [(15)O]H2O positron emission tomography to assess the coronary flow reserve (CFR). CFR was defined as the ratio of myocardial blood flow (MBF) during hyperaemia and rest. Additionally, 45 age-matched and sex-matched subjects underwent similar scanning procedures and served as controls. RESULTS: At baseline, CFR averaged 1.81±0.66 in infarcted myocardium versus 2.51±0.81 in remote myocardium (p<0.01). In comparison, CFR in the control group averaged 4.16±1.45 (p=0.001 vs both). During follow-up, the CFR increased to 2.74±0.85 in infarcted myocardium (p<0.01), and to 2.85±0.70 in remote myocardium (p<0.01). This was predominantly due to an increase in hyperaemic MBF, from 1.62±0.54 mL/min/g to 2.19±0.68 mL/min/g in infarcted myocardium (p<0.001), and 2.17±0.54 mL/min/g to 2.60±0.65 mL/min/g in remote myocardium (p<0.001). CONCLUSIONS: CFR in infarcted and remote myocardium is impaired 1 week after AMI. After 3 months vasomotor function partially recovers. However, as compared with control patients, MBF remains impaired in culprit and reference territories in patients with AMI. CLINICAL TRIAL REGISTRATION: NTR3164.

MAb therapy against the IFN-α/ß receptor subunit 1 stimulates arteriogenesis in a murine hindlimb ischaemia model without enhancing atherosclerotic burden.

AIMS: IFN-beta (IFNß) signalling is increased in patients with insufficient coronary collateral growth (i.e. arteriogenesis) and IFNß hampers arteriogenesis in mice. A downside of most pro-arteriogenic agents investigated in the past has been their pro-atherosclerotic properties, rendering them unsuitable for therapeutic application. Interestingly, type I IFNs have also been identified as pro-atherosclerotic cytokines and IFNß treatment increases plaque formation and accumulation of macrophages. We therefore hypothesized that mAb therapy to inhibit IFNß signalling would stimulate arteriogenesis and simultaneously attenuate-rather than aggravate-atherosclerosis. METHODS AND RESULTS: In a murine hindlimb ischaemia model, atherosclerotic low-density lipoprotein receptor knockout (LDLR(-/-)) mice were treated during a 4-week period with blocking MAbs specific for mouse IFN-α/ß receptor subunit 1 (IFNAR1) or murine IgG isotype as a control. The arteriogenic response was quantified using laser Doppler perfusion imaging (LDPI) as well as immunohistochemistry. Effects on atherosclerosis were determined by quantification of plaque area and analysis of plaque composition. Downstream targets of IFNß were assessed by real-time PCR (RT-PCR) in the aortic arch. Hindlimb perfusion restoration after femoral artery ligation was improved in mice treated with anti-IFNAR1 compared with controls as assessed by LDPI. This was accompanied by a decrease in CXCL10 expression in the IFNAR1 MAb-treated group. Anti-IFNAR1 treatment reduced plaque apoptosis without affecting total plaque area or other general plaque composition parameters. Results were confirmed in a short-term model and in apolipoprotein E knockout (APOE)(-/-) mice. CONCLUSION: Monoclonal anti-IFNAR1 therapy during a 4-week treatment period stimulates collateral artery growth in mice and did not enhance atherosclerotic burden. This is the first reported successful strategy using MAbs to stimulate arteriogenesis.

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

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

Invasive measurement of coronary microvascular resistance in patients with acute myocardial infarction treated by primary PCI.

Up to 40% of patients with acute myocardial infarction develop microvascular obstruction (MVO) despite successful treatment with primary percutaneous coronary intervention (PCI). The presence of MVO is linked to negative remodelling and left ventricular dysfunction, leading to decreased long-term survival, increased morbidity and reduced quality of life. The acute obstruction and dysfunction of the microvasculature can potentially be reversed by pharmacological treatment in addition to the standard PCI treatment. Identifying patients with post-PCI occurrence of MVO is essential in assessing which patients could benefit from additional treatment. However, at present there is no validated method to identify these patients. Angiographic parameters like myocardial blush grade or corrected Thrombolysis In Myocardial Infarction (TIMI) flow do not accurately predict the occurrence of MVO as visualised by MRI in the days after the acute event. Theoretically, acute MVO can be detected by intracoronary measurements of flow and resistance directly following the PCI procedure. In MVO the microvasculature is obstructed or destructed and will therefore display a higher coronary microvascular resistance (CMVR). The methods for intracoronary assessment of CMVR are based on either thermodilution or Doppler-flow measurements. The aim of this review is to present an overview of the currently available methods and parameters for assessing CMVR, with special attention given to their use in clinical practice and information provided by clinical studies performed in patients with acute myocardial infarction.

Magnetic resonance imaging-defined areas of microvascular obstruction after acute myocardial infarction represent microvascular destruction and haemorrhage.

AIMS: Lack of gadolinium-contrast wash-in on first-pass perfusion imaging, early gadolinium-enhanced imaging, or late gadolinium-enhanced (LGE) cardiovascular magnetic resonance (CMR) imaging after revascularized ST-elevation myocardial infarction (STEMI) is commonly referred to as microvascular obstruction (MVO). Additionally, T2-weighted imaging allows for the visualization of infarct-related oedema and intramyocardial haemorrhage (IMH) within the infarction. However, the exact histopathological correlate of the contrast-devoid core and its relation to IMH is unknown. METHODS AND RESULTS: In eight Yorkshire swine, the circumflex coronary artery was occluded for 75 min by a balloon catheter. After 7 days, CMR with cine imaging, T2-weighted turbospinecho, and LGE was performed. Cardiovascular magnetic resonance images were compared with histological findings after phosphotungstic acid-haematoxylin and anti-CD31/haematoxylin staining. These findings were compared with CMR findings in 27 consecutive PCI-treated STEMI patients, using the same scanning protocol. In the porcine model, the infarct core contained extensive necrosis and erythrocyte extravasation, without intact vasculature and hence, no MVO. The surrounding-gadolinium-enhanced-area contained granulation tissue, leucocyte infiltration, and necrosis with morphological intact microvessels containing microthrombi, without erythrocyte extravasation. Areas with IMH (median size 1.92 [0.36-5.25] cm(3)) and MVO (median size 2.19 [0.40-4.58] cm(3)) showed close anatomic correlation [intraclass correlation coefficient (ICC) 0.85, r = 0.85, P = 0.03]. Of the 27 STEMI patients, 15 had IMH (median size 6.60 [2.49-9.79] cm(3)) and 16 had MVO (median size 4.31 [1.05-7.57] cm(3)). Again, IMH and MVO showed close anatomic correlation (ICC 0.87, r = 0.93, P < 0.001). CONCLUSION: The contrast-devoid core of revascularized STEMI contains extensive erythrocyte extravasation with microvascular damage. Attenuating the reperfusion-induced haemorrhage may be a novel target in future adjunctive STEMI treatment.

The coronary collateral circulation: genetic and environmental determinants in experimental models and humans.

Obstruction of coronary arteries leads to an arteriogenic response. Pre-existent collateral networks enlarge, forming large conductance arteries with the capability to compensate for the loss of perfusion due to the occlusion. Interestingly, significant differences exist between patients regarding the capacity to develop such a collateral circulation. This heterogeneity in arteriogenic response is also found between and even within animal species and it strongly suggests that next to environmental factors, innate genetic factors play a key role. The present review focuses on this heterogeneity of genetic as well as non-genetic determinants of the coronary collateral circulation. This article is part of a Special Issue entitled "Coronary Blood Flow".