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

Safety of guidewire-based measurement of fractional flow reserve and the index of microvascular resistance using intravenous adenosine in patients with acute or recent myocardial infarction

Aims: Coronary guidewire-based diagnostic assessments with hyperemia may cause iatrogenic complications. We assessed the safety of guidewire-based measurement of coronary physiology, using intravenous adenosine, in patients with an acute coronary syndrome. Methods: We prospectively enrolled invasively managed STEMI and NSTEMI patients in two simultaneously conducted studies in 6 centers (NCT01764334; NCT02072850). All of the participants underwent a diagnostic coronary guidewire study using intravenous adenosine (140 μg/kg/min) infusion for 1–2 min. The patients were prospectively assessed for the occurrence of serious adverse events (SAEs) and symptoms and invasively measured hemodynamics were also recorded. Results: 648 patients (n = 298 STEMI patients in 1 hospital; mean time to reperfusion 253 min; n = 350 NSTEMI in 6 hospitals; median time to angiography from index chest pain episode 3 (2, 5) days) were included between March 2011 and May 2013. Two NSTEMI patients (0.03% overall) experienced a coronary dissection related to the guidewire. No guidewire dissections occurred in the STEMI patients. Chest symptoms were reported in the majority (86%) of patient's symptoms during the adenosine infusion. No serious adverse events occurred during infusion of adenosine and all of the symptoms resolved after the infusion ceased. Conclusions: In this multicenter analysis, guidewire-based measurement of FFR and IMR using intravenous adenosine was safe in patients following STEMI or NSTEMI. Self-limiting symptoms were common but not associated with serious adverse events. Finally, coronary dissection in STEMI and NSTEMI patients was noted to be a rare phenomenon

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

Carers' perspectives on the presentation of community-acquired pneumonia and empyema in children: a case series

Objective To describe carers’ perceptions of the development and presentation of community-acquired pneumonia or empyema in their children. Design Case series. Setting Seven hospitals with paediatric inpatient units in South Wales, UK. Participants Carers of 79 children aged 6 months to 16 years assessed in hospital between October 2008 and September 2009 with radiographic, community-acquired pneumonia or empyema. Methods Carers were recruited in hospital and participated in a structured face-to-face or telephone interview about the history and presenting features of their children's illnesses. Responses to open questions were initially coded very finely and then grouped into common themes. Cases were classified into two age groups: 3 or more years and under 3 years. Results The reported median duration of illness from onset until the index hospital presentation was 4 days (IQR 2–9 days). Pain in the torso was reported in 84% of cases aged 3 or more years and was the most common cause for carer concern in this age group. According to carer accounts, clinicians sometimes misjudged the origin of this pain. Almost all carers reported something unusual about the index illness that had particularly concerned them—mostly non-specific physical symptoms and behavioural changes. Conclusions Pain in the torso and carer concerns about unusual symptoms in their child may provide valuable additional information in a clinician's assessment of the risk of pneumonia in primary care. Further research is needed to confirm the diagnostic value of these features

What makes you not a Sikh? : a preliminary mapping of values

This study sets out to establish which Sikh values contrasted with or were shared by non-Sikh adolescents. A survey of attitude toward a variety of Sikh values was fielded in a sample of 364 non-Sikh schoolchildren aged between 13 and 15 in London. Values where attitudes were least positive concerned Sikh duties/code of conduct, festivals, rituals, prayer Gurdwara attendance, listening to scripture recitation, the amrit initiation. Sikh values empathized with by non-Sikhs concerned family pride, charity, easy access to ordination and Gurdwaras, maintaining the five Ks, seeing God in all things, abstaining from meat and alcohol and belief in the stories of Guru Nanak. Further significant differences of attitude toward Sikhism were found in comparisons by sex, age and religious affiliation. Findings are applied to teaching Sikhism to pupils of no faith adherence. The study recommends the extension of values mapping to specifically Sikh populations

Discordance between resting and hyperemic indices of coronary stenosis severity: the VERIFY 2 study (a comparative study of resting coronary pressure gradient, instantaneous wave-free ratio and fractional flow reserve in an unselected population referred for invasive angiography)

Background—Distal coronary to aortic pressure ratio (Pd/Pa) and instantaneous wave-free ratio (iFR) are indices of functional significance of a coronary stenosis measured without hyperemia. It has been suggested that iFR has superior diagnostic accuracy to Pd/Pa when compared with fractional flow reserve (FFR). We hypothesized that in comparison with FFR, revascularization decisions based on either binary cutoff values for iFR and Pd/Pa or hybrid strategies incorporating iFR or Pd/Pa will result in similar levels of disagreement. Methods and Results—This is a prospective study in consecutive patients undergoing FFR for clinical indications using proprietary software to calculate iFR. We measured Pd/Pa, iFR, FFR, and hyperemic iFR. Diagnostic accuracy versus FFR ≤0.80 was calculated using binary cutoff values of ≤0.90 for iFR and ≤0.92 for Pd/Pa, and adenosine zones for iFR of 0.86 to 0.93 and Pd/Pa of 0.87 to 0.94 in the hybrid strategy. One hundred ninety-seven patients with 257 stenoses (mean diameter stenosis 48%) were studied. Using binary cutoffs, diagnostic accuracy was similar for iFR and resting Pd/Pa with misclassification rates of 21% versus 20.2% (P=0.85). In the hybrid analysis, 54% of iFR cases and 53% of Pd/Pa cases were outside the adenosine zone and rates of misclassification were 9.4% versus 11.9% (P=0.55). Conclusions—Binary cutoff values for iFR and Pd/Pa result in misclassification of 1 in 5 lesions. Using a hybrid strategy, approximately half of the patients do not receive adenosine, but 1 in 10 lesions are still misclassified. The use of nonhyperemic indices of stenosis severity cannot be recommended for decision making in the catheterization laboratory. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT02377310

Pathophysiology of myocardial remodeling in survivors of ST-elevation myocardial infarction revealed by native T1 mapping: inflammation, remote myocardium and prognostic significance

Background: The pathophysiology and prognostic significance of remote myocardium in the natural history of STEMI is uncertain. Cardiac magnetic resonance (CMR) provides a non-invasive assessment of myocardial pathology that is spatially and temporally coordinated. Native T1 quantified by CMR (T1 relaxation time, milliseconds) is a fundamental tissue property determined by water content and cellularity. We aimed to investigate the clinical significance of remote myocardium in survivors of acute ST-elevation myocardial infarction (STEMI) using native T1 mapping. Methods: We performed a prospective single center cohort study in reperfused STEMI patients who underwent CMR 2 days and 6 months post-MI and long term follow-up (18 months minimum). Native T1 CMR (MOLLI investigational prototype sequence: 3 (3) 3 (3) 5) was measured in regions-of-interest in remote and injured myocardium. Infarction was depicted on late gadolinium contrast enhancement imaging. Adverse remodeling was defined as an increase in left ventricular end-diastolic volume ≥ 20% at 6 months. Major adverse cardiac events (MACE) were defined as cardiac death or hospitalization for non-fatal MI or heart failure. Results are mean±SD unless specified. Results: 300 STEMI patients (mean age 59 years, 74% male) gave informed consent (14 July 2011 - 21 November 2012). Of these, 288 STEMI patients had evaluable native T1 CMR and follow-up data (median duration 845 days). Infarct size was 18±14% of left ventricular mass. Two days post-STEMI, native T1 in remote myocardium was lower than native T1 in the infarct zone (961±25 ms vs. 1097±52 ms; p<0.01). In multivariable linear regression, remote zone native T1 was independently associated with incomplete ST-segment resolution (9.42 (2.37 to 16.47); p=0.009), the log of the initial CRP concentration (regression coefficient 3.01 (95% CI 0.016 to 5.55); p=0.038) and the peak monocyte count within 2 days of admission (10.20 (0.74, 19.67); p=0.035). At 6 months, left ventricular end-diastolic volume increased by 5 (25) ml (n=262 patients with evaluable data) overall, and adverse remodeling occurred in 30 (12%) patients. Remote zone native T1 was a multivariable predictor of the change in left ventricular end-diastolic volume from baseline (0.13 (0.01, 0.24); p=0.035). 39 (13.5%) patients experienced a MACE including 20 (6.9%) patients with a post-discharge MACE. Remote zone native T1 was an independent predictor of post-discharge MACE (hazard ratio 1.016, 95% CI 1.000, 1.032; p=0.048) including after adjustment for changes in LVEF (p=0.032), LV end-diastolic volume (p=0.053), and monocyte count (p=0.036). Conclusions: Remote zone tissue characteristics early post-MI are temporally linked with reperfusion injury and inflammation and independently predict left ventricular remodeling and MACE in STEMI survivors

Percutaneous coronary intervention versus medical therapy in patients with angina and grey-zone fractional flow reserve values: a randomised clinical trial

Introduction: There is conflicting evidence regarding the benefits of percutaneous coronary intervention (PCI) in patients with grey zone fractional flow reserve (GZFFR artery) values (0.75–0.80). The prevalence of ischaemia is unknown. We wished to define the prevalence of ischaemia in GZFFR artery and assess whether PCI is superior to optimal medical therapy (OMT) for angina control. Methods: We enrolled 104 patients with angina with 1:1 randomisation to PCI or OMT. The artery was interrogated with a Doppler flow/pressure wire. Patients underwent Magnetic Resonance Imaging (MRI) with follow-up at 3 and 12 months. The primary outcome was angina status at 3 months using the Seattle Angina Questionnaire (SAQ). Results: 104 patients (age 60±9 years), 79 (76%) males and 79 (76%) Left Anterior Descending (LAD) stenoses were randomised. Coronary physiology and SAQ were similar. Of 98 patients with stress perfusion MRI data, 17 (17%) had abnormal perfusion (≥2 segments with ≥25% ischaemia or ≥1 segment with ≥50% ischaemia) in the target GZFFR artery. Of 89 patients with invasive physiology data, 26 (28%) had coronary flow velocity reserve <2.0 in the target GZFFR artery. After 3 months of follow-up, compared with patients treated with OMT only, patients treated by PCI and OMT had greater improvements in SAQ angina frequency (21 (28) vs 10 (23); p=0.026) and quality of life (24 (26) vs 11 (24); p=0.008) though these differences were no longer significant at 12 months. Conclusions: Non-invasive evidence of major ischaemia is uncommon in patients with GZFFR artery. Compared with OMT alone, patients randomised to undergo PCI reported improved symptoms after 3 months but these differences were no longer significant after 12 months

Prognostic significance of infarct core pathology in ST-elevation myocardial infarction survivors revealed by non-contrast T1 mapping cardiac magnetic resonance

Background: Myocardial longitudinal relaxation time (T1, ms) is a fundamental magnetic property of tissue that is related to water content and mobility. The pathophysiological and prognostic importance of native myocardial T1 values in acute ST-elevation myocardial infarction (STEMI) patients is unknown. We aimed to assess the clinical significance of infarct core native T1. Methods: We performed a prospective single center cohort study in reperfused STEMI patients who underwent CMR 2 days and 6 months post-MI. Native T1 CMR (MOLLI investigational prototype sequence: 3 (3) 3 (3) 5) was measured in myocardial regions-of-interest. The infarct territory and microvascular obstruction (MVO) were depicted with late gadolinium enhancement CMR. Adverse remodeling was defined as an increase in LV end-diastolic volume (LVEDV) ≥ 20% at 6 months. All-cause death or heart failure hospitalization was a pre-specified outcome that was assessed during follow-up. Results: 300 STEMI patients (mean±SD age 59±12 years, 74% male, 114 with anterior STEMI) gave informed consent and had CMR (14 July 2011 - 22 November 2012). Of these, 288 STEMI patients had evaluable T1 maps. Infarct size was 18 ±14% of LV mass. One hundred and forty five (50%) of 288 patients had late MVO, whereas 160 (56%) patients had infarct core pathology revealed by native T1. Native T1 within the infarct core (996.9±57.3; p<0.01) was higher than in the remote zone (961±25 ms; p<0.01) but lower than in the area-at-risk (1097 ±52 ms). In multivariable linear regression, native T1 in the infarct core was negatively associated with age, initial systolic blood pressure, TIMI coronary flow grade at initial angiography, Killip class at presentation and neutrophil count (all p<0.05), independent of LVEF, LVEDV or infarct size. At 6 months, LVEDV increased by 5 (25) ml (n=262 patients with evaluable data). Adverse remodeling occurred in 30 (12%) patients and 23 (76.7%) of these patients MVO at baseline. T1 in the infarct core was a multivariable predictor of adverse remodeling (-0.01 (-0.02, -0.00); p=0.048). 288 (100%) patients were followed-up for a median of 845 days. Thirty (10.4%) patients died or experienced a heart failure event and 13 (4.5%) of these patients experienced the event post-discharge. Infarct core native T1 predicted all-cause death or heart failure post-discharge (hazard ratio 0.969, 95% CI 0.953, 0.985; p<0.001) including after adjustment for LVEF (p<0.001) and LVEDV at baseline (p<0.001), and was comparable with MVO

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