Effect of remote ischaemic conditioning on infarct size and remodelling in ST-segment elevation myocardial infarction patients: the CONDI-2/ERIC-PPCI CMR substudy.

The effect of limb remote ischaemic conditioning (RIC) on myocardial infarct (MI) size and left ventricular ejection fraction (LVEF) was investigated in a pre-planned cardiovascular magnetic resonance (CMR) substudy of the CONDI-2/ERIC-PPCI trial. This single-blind multi-centre trial (7 sites in UK and Denmark) included 169 ST-segment elevation myocardial infarction (STEMI) patients who were already randomised to either control (n = 89) or limb RIC (n = 80) (4 × 5 min cycles of arm cuff inflations/deflations) prior to primary percutaneous coronary intervention. CMR was performed acutely and at 6 months. The primary endpoint was MI size on the 6 month CMR scan, expressed as median and interquartile range. In 110 patients with 6-month CMR data, limb RIC did not reduce MI size [RIC: 13.0 (5.1-17.1)% of LV mass; control: 11.1 (7.0-17.8)% of LV mass, P = 0.39], or LVEF, when compared to control. In 162 patients with acute CMR data, limb RIC had no effect on acute MI size, microvascular obstruction and LVEF when compared to control. In a subgroup of anterior STEMI patients, RIC was associated with lower incidence of microvascular obstruction and higher LVEF on the acute scan when compared with control, but this was not associated with an improvement in LVEF at 6 months. In summary, in this pre-planned CMR substudy of the CONDI-2/ERIC-PPCI trial, there was no evidence that limb RIC reduced MI size or improved LVEF at 6 months by CMR, findings which are consistent with the neutral effects of limb RIC on clinical outcomes reported in the main CONDI-2/ERIC-PPCI trial.

Effect of remote ischaemic conditioning on clinical outcomes in patients with acute myocardial infarction (CONDI-2/ERIC-PPCI): a single-blind randomised controlled trial.

BACKGROUND: Remote ischaemic conditioning with transient ischaemia and reperfusion applied to the arm has been shown to reduce myocardial infarct size in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). We investigated whether remote ischaemic conditioning could reduce the incidence of cardiac death and hospitalisation for heart failure at 12 months. METHODS: We did an international investigator-initiated, prospective, single-blind, randomised controlled trial (CONDI-2/ERIC-PPCI) at 33 centres across the UK, Denmark, Spain, and Serbia. Patients (age >18 years) with suspected STEMI and who were eligible for PPCI were randomly allocated (1:1, stratified by centre with a permuted block method) to receive standard treatment (including a sham simulated remote ischaemic conditioning intervention at UK sites only) or remote ischaemic conditioning treatment (intermittent ischaemia and reperfusion applied to the arm through four cycles of 5-min inflation and 5-min deflation of an automated cuff device) before PPCI. Investigators responsible for data collection and outcome assessment were masked to treatment allocation. The primary combined endpoint was cardiac death or hospitalisation for heart failure at 12 months in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02342522) and is completed. FINDINGS: Between Nov 6, 2013, and March 31, 2018, 5401 patients were randomly allocated to either the control group (n=2701) or the remote ischaemic conditioning group (n=2700). After exclusion of patients upon hospital arrival or loss to follow-up, 2569 patients in the control group and 2546 in the intervention group were included in the intention-to-treat analysis. At 12 months post-PPCI, the Kaplan-Meier-estimated frequencies of cardiac death or hospitalisation for heart failure (the primary endpoint) were 220 (8·6%) patients in the control group and 239 (9·4%) in the remote ischaemic conditioning group (hazard ratio 1·10 [95% CI 0·91-1·32], p=0·32 for intervention versus control). No important unexpected adverse events or side effects of remote ischaemic conditioning were observed. INTERPRETATION: Remote ischaemic conditioning does not improve clinical outcomes (cardiac death or hospitalisation for heart failure) at 12 months in patients with STEMI undergoing PPCI. FUNDING: British Heart Foundation, University College London Hospitals/University College London Biomedical Research Centre, Danish Innovation Foundation, Novo Nordisk Foundation, TrygFonden.

Tailored antiplatelet therapy to improve prognosis in patients exhibiting clopidogrel low-response prior to percutaneous coronary intervention for stable angina or non-ST elevation acute coronary syndrome.

AIM: To investigate whether an intensified antiplatelet regimen could improve prognosis in stable or non-ST elevation in acute coronary syndrome (ACS) patients exhibiting high on-treatment platelet reactivity (HTPR) on clopidogrel and treated with percutaneous coronary intervention (PCI). There is a wide variability in the platelet reactivity to clopidogrel and HTPR has been associated with a poor prognosis. METHODS: In this observational study, 923 consecutive patients without ST-elevation myocardial infarction (STEMI) and adequately pre-treated with clopidogrel were screened for HTPR with multiple electrode aggregometry after assessment of the coronary anatomy. Patients were grouped based on their response to clopidogrel and the assigned antiplatelet strategy. The primary endpoint was a composite of cardiovascular death, myocardial infarction, stroke, or stent thrombosis. RESULTS: HTPR was demonstrated in 237 patients (25.7%). Of these, 114 continued on conventional clopidogrel therapy, while the remaining 123 received intensified antiplatelet therapy with either double-dose clopidogrel (150 mg daily, n = 55) or the newer P2Y12-inhibitors, prasugrel or ticagrelor (n = 68) for at least 30 days after the index procedure. The median follow-up was 571 days (interquartile range, 373-746). Intensifying antiplatelet therapy reduced the rate of the composite endpoint (p < 0.001). After adjustment for potential confounders, HTPR in combination with conventional clopidogrel therapy remained independently associated with an increased risk of cardiovascular events (hazard ratio (HR), 2.92; 95% CI, 1.90-4.48), whereas intensified treatment reduced the risk to a level equivalent to that of patients exhibiting normal platelet reactivity (HR, 1.08; 95% CI, 0.59-1.99). CONCLUSION: Tailored antiplatelet therapy significantly reduced the event rate in patients exhibiting HTPR prior to PCI.

Prognostic differences between physiology-guided percutaneous coronary intervention and optimal medical therapy in coronary artery disease: A systematic review and meta-analysis.

Background: Intracoronary physiology, particularly fractional flow reserve (FFR), has been used as a guide for revascularization for patients with coronary artery disease (CAD). The optimal treatment in the physiological grey-zone area has been unclear and remains subject to ongoing debate. Methods: We conducted a systematic review of randomized controlled trials and observational studies comparing the prognostic effect of percutaneous coronary revascularization (PCI) and optimal medical therapy (OMT) in patients with CAD. Studies were identified by medical literature databases. The outcomes of interest were major adverse cardiac events (MACE) and its components, death, myocardial infarction (MI), and repeat revascularization. Results: A total of 16 studies with 27,451 patients were included. The pooled analysis demonstrated that PCI was associated with a prognostic advantage over OMT in patients with FFR value ≤0.80 (RR: 0.64, 95 % CI: 0.45-0.90, p < 0.01). Patients with an FFR value >0.80 were shown to benefit more from OMT (RR 1.38, 95 % CI 1.24-1.53, p < 0.01). The analysis also showed that there was no significant difference in MACE in the grey-zone area (FFR 0.75-0.80) (RR 0.64, 95 % CI: 0.35-1.16, p = 0.14), but a significant reduction in repeat revascularization (RR 0.54, 95 % CI, 0.31-0.91, p < 0.01) when patients were treated with PCI. Conclusions: Among patients with CAD and FFR values >0.80, OMT was associated with favorable outcomes over PCI in reducing the risk of MACE. However, among patients with FFR values ≤0.80, revascularization was superior in terms of reducing MACE. The available evidence supports the guideline-recommended use of an FFR cut-off of ≤0.80.

Termination of dobutamine infusion causes transient rebound left heart diastolic dysfunction in healthy elderly women but not in men: a cardiac magnetic resonance study.

Men and women are known to react differently to stress. Thus, stress cardiomyopathy almost solely strikes women. Stress cardiomyopathy is suggested to relate to sex differences in catecholamine reaction. Left heart function during dobutamine stress is well described, but sex-specific inotropic and lusitropic response to abrupt termination of dobutamine stress is not. We aimed to investigate sex differences in left ventricular (LV) and atrial (LA) function during and after dobutamine stress. We enrolled 20 healthy elderly subjects (60-70 yr, 10 females) and measured their LV and LA volumes throughout the cardiac cycle by cardiac magnetic resonance imaging at rest, during dobutamine stress (15 µg·kg(-1)·min(-1)), 15 min after termination (T15), and 30 min after termination (T30) of dobutamine stress. We calculated LV ejection fractions, LV stroke volumes, LV peak filling rates, and LA passive, active, and conduit volumes. Sex differences were not observed at rest or during dobutamine stress. Compared with prestress values, at T15 a rebound decrease in LV peak filling rate was observed in women (-22 ± 3%, P < 0.001) but not in men. This was reflected in reduced LA passive emptying volume (-40 ± 3%, P < 0.001) and a corresponding increase in LA active emptying volume (36 ± 2%, P < 0.001). At T30 there were no differences between the sexes. We conclude that dobutamine causes greater stress to the female heart. This is revealed after termination of dobutamine stress where the left heart recovers in men, whereas women experience rebound LV stiffening with reduced diastolic relaxation. This is the first report of a sex-specific transient rebound phenomenon in cardiovascular response to catecholamines.

Left atrial and ventricular function during dobutamine and glycopyrrolate stress in healthy young and elderly as evaluated by cardiac magnetic resonance.

The aim of this study is to describe phasic volume changes of the left atrium (LA) in healthy young and elderly subjects at rest and during pharmacological stress (PS). LA maximum size is related to cardiovascular mortality. LA has passive, active, and conduit function for left ventricular (LV) filling. We hypothesized that changes in LV compliance from normal aging are reflected in LA volume changes and that PS will augment these differences. We enrolled twenty young (20-30 yr) and twenty elderly (60-70 yr) healthy subjects and measured their LV and LA volumes by cardiac magnetic resonance imaging at rest and during dobutamine and glycopyrrolate stress. We identified LA minimum, maximum, and middiastolic volumes and the volume before atrial contraction. LA emptying volumes were calculated as LA passive and active emptying volumes and LA conduit volume. We also calculated LV peak filling rates (LVPFRs). Both at rest and during PS, LA maximum and minimum volumes were similar in the groups, whereas middiastolic volume was higher in the elderly. During PS, a marked decrease in LA passive emptying function and a corresponding increase in LA active emptying function were seen in the elderly but not in the young. At rest, LVPFR was lower in the elderly, and during PS this difference was augmented. The aging heart has reduced LVPFR, which is reflected in reduced LA passive and compensatory increased LA active volumetric contribution to LV stroke volume. These age-related differences are evident at rest and highly augmented during both dobutamine and glycopyrrolate stress.

Safety of Selective Intracoronary Hypothermia During Primary Percutaneous Coronary Intervention in Patients With Anterior STEMI.

OBJECTIVES: The aim of this study was to determine the safety of selective intracoronary hypothermia during primary percutaneous coronary intervention (PPCI) in patients with anterior ST-segment elevation myocardial infarction (STEMI). BACKGROUND: Selective intracoronary hypothermia is a novel treatment designed to reduce myocardial reperfusion injury and is currently being investigated in the ongoing randomized controlled EURO-ICE (European Intracoronary Cooling Evaluation in Patients With ST-Elevation Myocardial Infarction) trial (NCT03447834). Data on the safety of such a procedure during PPCI are still limited. METHODS: The first 50 patients with anterior STEMI treated with selective intracoronary hypothermia during PPCI were included in this analysis and compared for safety with the first 50 patients randomized to the control group undergoing standard PPCI. In-hospital mortality, occurrence of rhythm or conduction disturbances, stent thrombosis, onset of heart failure during the procedure, and subsequent hospital admission were assessed. RESULTS: In-hospital mortality was 0%. One patient in both groups developed cardiogenic shock. Atrial fibrillation occurred in 0 and 3 patients (P = 0.24), and ventricular fibrillation occurred in 5 and 3 patients (P = 0.72) in the intracoronary hypothermia group and control group, respectively. Stent thrombosis occurred in 2 patients in the intracoronary hypothermia group; 1 instance was intraprocedural, and the other occurred following interruption of dual-antiplatelet therapy consequent to an intracranial hemorrhage 6 days after enrollment. No stent thrombosis was observed in the control group (P = 0.50). CONCLUSIONS: Selective intracoronary hypothermia during PPCI in patients with anterior STEMI can be implemented within the routine of PPCI and seems to be safe. The final safety results will be reported at the end of the trial.

Hypercoagulation assessed by thromboelastography is neither related to infarct size nor to clinical outcome after primary percutaneous coronary intervention.

OBJECTIVES: We investigated the relationship between coagulation assessed by thromboelastography (TEG) and myocardial damage in ST-segment elevation myocardial infarction (STEMI). METHODS: We measured platelet activity with TEG-maximum amplitude (TEG-MA) in 233 patients undergoing urgent percutaneous coronary intervention (PCI). Infarct size and myocardial salvage index were evaluated using cardiac magnetic resonance, and the relation of these parameters to posttreatment coagulation was examined retrospectively. Adverse events were adjudicated and related to the coagulation status during the index event. RESULTS: Hypercoagulation was found in 82 (35.2%) patients and was neither correlated to infarct size nor correlated to myocardial salvage index (P = .28 and .65, respectively) or clinical adverse events. Patients who experienced an adverse event during follow-up had a slightly higher TEG-MA value than patients with an event-free follow-up, but this was not statistically significant (68.1 vs 67.3, P = .44). CONCLUSIONS: The TEG-MA does not appear to be a sensitive predictor of reperfusion success and prognosis in urgent PCI for STEMI.

A method for coronary artery calcium scoring using contrast-enhanced computed tomography.

BACKGROUND: Limitations to the coronary calcium score include its requirement for noncontrast imaging and radiation exposure that approaches current methods for contrast-enhanced CT angiography. OBJECTIVES: We sought to derive and validate a method of measuring the coronary artery calcium score (CACS) from standard contrast-enhanced CT, obviating the need for a second non-contrast calcium scan. METHODS: The volume of intramural calcium of >320 HU in major coronary vessels was measured in 90 contrast-enhanced and traditional non-contrast calcium scan pairs. An empiric conversion factor was derived to convert the small voxel contrast-enhanced calcium volume to an Agatston calcium score. The accuracy of this technique was then prospectively validated in 120 consecutive patients undergoing clinical calcium scans and contrasted-enhanced coronary CT. Eleven patients were excluded from analysis because of the prespecified criteria of excessive noise in the contrast-enhanced CT or total coronary artery occlusion. RESULTS: The Pearson correlation of the contrast scan-derived calcium score with the measured CACS was r2 = 0.99. With standard CACS risk bands, agreement of the contrast-enhanced calcium score estimate with the measured CAC by quadratic weighted κ was 0.96. The 95% limits of agreement (Agatston units) were given by ±(3.2 + 0.14 × CACS + 4.44 mean square root of CACS). Inter-observer and intra-observer reliability with the intraclass correlation was 0.99. CONCLUSION: The calcium score can be accurately measured from contrast-enhanced cardiac CT scans with the use of a Hounsfield unit threshold of 320.