Setting Up an Efficient Therapeutic Hypothermia Team in Conscious ST Elevation Myocardial Infarction Patients: A UK Heart Attack Center Experience

Patients presenting with ST elevation myocardial infarction (STEMI) are routinely treated with percutaneous coronary intervention to restore blood flow in the occluded artery to reduce infarct size (IS). However, there is evidence to suggest that the restoration of blood flow can cause further damage to the myocardium through reperfusion injury (RI). Recent research in this area has focused on minimizing damage to the myocardium caused by RI. Therapeutic hypothermia (TH) has been shown to be beneficial in animal models of coronary artery occlusion in reducing IS caused by RI if instituted early in an ischemic myocardium. Data in humans are less convincing to date, although exploratory analyses suggest that there is significant clinical benefit in reducing IS if TH can be administered at the earliest recognition of ischemia in anterior myocardial infarction. The Essex Cardiothoracic Centre is the first UK center to have participated in administering TH in conscious patients presenting with STEMI as part of the COOL-AMI case series study. In this article, we outline our experience of efficiently integrating conscious TH into our primary percutaneous intervention program to achieve 18 minutes of cooling duration before reperfusion, with no significant increase in door-to-balloon times, in the setting of the clinical trial

Stress perfusion cardiovascular magnetic resonance and serial fractional flow reserve assessment of the left anterior descending artery in patients undergoing right coronary artery chronic total occlusion revascularization

Background: Fractional flow reserve (FFR) assessment of remote arteries, in the context of a bystander chronic total occlusion (CTO), can lead to false positive results. Adenosine stress cardiovascular magnetic resonance (CMR) evaluates perfusion defects across the entire myocardium and may therefore be a reliable tool in the work-up of remote lesions in CTO patients. The IMPACT-CTO study investigated donor artery invasive physiology before, immediately post, and at 4 months following right coronary artery (RCA) CTO percutaneous coronary intervention (PCI). The aim of this subanalysis was to assess the concordance between baseline perfusion CMR and serial FFR evaluation of left anterior descending artery (LAD) ischemia in patients from the IMPACT-CTO study.Methods: Baseline adenosine stress CMR examinations from 26 patients were analyzed for qualitative evidence of LAD ischemia. The results were correlated with the serial LAD FFR measurements.Results: The present findings demonstrated that before RCA CTO PCI, there was 62% agreement between perfusion CMR and FFR (ischemic threshold £ 0.8) in the assessment of LAD ischemia (k = 0.29; fair concordance). At 4 months after revascularization, there was 77% agreement (k = 0.52; moderate concordance) between the index CMR assessment of LAD ischemia and the follow-up LAD FFR. Concordance was improved at a LAD FFR ischemic threshold of £ 0.75.Conclusions: In this hypothesis generating study, baseline CMR assessment of LAD ischemia correlated better with the 4 months LAD FFR data (threshold £ 0.8) as compared to the FFR measurements taken prior to RCA CTO revascularization

Eosinophil deficiency promotes aberrant repair and adverse remodelling following acute myocardial infarction

In ST-segment elevation myocardial infarction of both patients and mice, there was a decline in blood eosinophil count, with activated eosinophils recruited to the infarct zone. Eosinophil deficiency resulted in attenuated anti-inflammatory macrophage polarization, enhanced myocardial inflammation, increased scar size, and deterioration of myocardial structure and function. Adverse cardiac remodeling in the setting of eosinophil deficiency was prevented by interleukin-4 therapy

Recovery of Absolute Coronary Blood Flow and Microvascular Resistance After Chronic Total Occlusion Percutaneous Coronary Intervention: An Exploratory Study

Background: This study aimed to investigate longitudinal physiological changes in the recanalized coronary chronic total occlusion (CTO) vessel and its dependent myocardium after successful percutaneous coronary intervention (PCI). Methods and Results: In this pilot study, 25 patients scheduled for elective CTO PCI with viable myocardium and angiographically visible collaterals were included. Absolute coronary blood flow and absolute microvascular resistance were measured invasively using continuous thermodilution. Measurements were performed immediately after successful CTO PCI and at short‐term follow‐up. In a subgroup of patients, physiological measurements were performed at the predominant donor vessel before CTO PCI, immediately afterwards, and at follow‐up. Absolute coronary blood flow in the recanalized CTO artery increased from 148±53 mL/min immediately after PCI to 221±77 mL/min at follow‐up (P<0.001). In agreement, absolute resistance in the myocardial territory perfused by the CTO artery, decreased from 545±255 Wood units immediately after the procedure to 387±128 Wood units at follow‐up (P=0.014). There were no significant changes in the absolute coronary blood flow and resistance in the predominant donor between baseline and follow‐up. Positive remodeling of the distal CTO vessel with an increase in lumen diameter was observed. Conclusions: After successful CTO PCI, blood flow in the recanalized artery and microvascular function of the dependent myocardium are not immediately normal but recover over time

Coronary artery height differences and their effect on fractional flow reserve

Background: Fractional flow reserve (FFR) uses pressure-based measurements to assess the severityof a coronary stenosis. Distal pressure (Pd) is often at a different vertical height to that of the proximalaortic pressure (Pa). The difference in pressure between Pd and Pa due to hydrostatic pressure, mayimpact FFR calculation.Methods: One hundred computed tomography coronary angiographies were used to measure heightdifferences between the coronary ostia and points in the coronary tree. Mean heights were used to calculate the hydrostatic pressure effect in each artery, using a correction factor of 0.8 mmHg/cm. Thiswas tested in a simulation of intermediate coronary stenosis to give the “corrected FFR” (cFFR) andpercentage of values, which crossed a threshold of 0.8.Results: The mean height from coronary ostium to distal left anterior descending (LAD) was +5.26 cm,distal circumflex (Cx) –3.35 cm, distal right coronary artery-posterior left ventricular artery (RCA-PLV)–5.74 cm and distal RCA-posterior descending artery (PDA) +1.83 cm. For LAD, correction resulted in a mean change in FFR of +0.042, –0.027 in the Cx, –0.046 in the PLV and +0.015 in the PDA. Using 200 random FFR values between 0.75 and 0.85, the resulting cFFR crossed the clinical treatmentthreshold of 0.8 in 43% of LAD, 27% of Cx, 47% of PLV and 15% of PDA cases.Conclusions: There are significant vertical height differences between the distal artery (Pd) and its point of normalization (Pa). This is likely to have a modest effect on FFR, and correcting for this results in a proportion of values crossing treatment thresholds. Operators should be mindful of this phenomenon when interpreting FFR values

Impact of intravascular ultrasound on chronic total occlusion percutaneous revascularization

Aim: We sought to investigate the impact of IVUS use on chronic total occlusion (CTO) PCI using data from a contemporary registry of consecutive patients and applying a propensity score matching analysis. Methods and results: We evaluated 514 successful CTO-PCIs, median age: 67 years (IQR: 58–73), 83.5% males. IVUS-guided PCI was performed in 184 (35.8%) of cases. After using 1:1 propensity matching score analysis, two groups of 182 patients each (IVUS-guided vs. angiography-guided CTO-PCI group) were produced to form the study population. In the IVUS-guided group the median maximum stent diameter was larger and the median total stented segment was longer compared to the angiography-guided group [(3.5 mm, IQR: 3.0–4.0 vs. 3.2 mm, IQR: 3.0–3.5, p < 0.001) and (60.0 mm, IQR: 38.0–91.3 vs. 38.0 mm, IQR: 32.0–70.5, p < 0.001), respectively]. In the IVUS-guided group, retrograde recanalization was more frequently encountered compared to the angiography-guided PCI group (30.2% vs. 20.9%, p = 0.04). Procedural time was significantly longer in the IVUS-guided group, without any difference in fluoroscopy time, radiation dose and contrast volume. Multivariate linear regression analysis showed that IVUS use was the strongest independent factor associated with larger maximum diameter stents (p < 0.001) and a strong independent predictor for total stented segment length during CTO-PCI (p < 0.001). Up to 8 years follow-up, there was no difference in the incidence of the composite endpoint of all-cause death, cardiac death, myocardial infarction and target vessel revascularization between the IVUS-guided PCI and the angiography-guided PCI groups (hazard ratio: 13.7% vs. 15.9%, respectively, log-rank: p = 0.67, median follow-up time: 49.0 months, IQR: 33.0–67.0). Conclusions: Use of IVUS in CTO-PCI was associated with larger stent diameter and longer stented segments. Despite more frequent use of IVUS in retrograde CTO-PCI, there was no difference in long-term adverse events between IVUS and angiography CTO-PCI groups; nevertheless, the study was not powered to assess clinical outcomes

Clinical effectiveness of thrombus aspiration during percutaneous coronary intervention for stent thrombosis in a contemporary setting

Objective- The impact of adjunctive manual thrombus aspiration (TA) in patients with stent thrombosis (ST) treated with percutaneous intervention has not been evaluated in the current era of potent P2Y12 agents and new-generation drug-eluting stents. We sought to assess the effect of TA using data from a large contemporary registry. Methods- The study population was derived from the Essex ST Investigation Registry (ESTHIR), which contains all consecutive cases of angiographically determined definite ST undergoing interventional treatment in a tertiary cardiac centre between November 2015 and June 2018. Propensity score matching was performed to match patients who underwent TA (TA group) to those who did not (n-TA group). The study endpoints were final TIMI flow and survival free of cardiovascular death (CD) or target lesion revascularisation (TLR). Results- A total of 128 ST patients were included in the present analysis. The mean age was 65 ± 11 years, and 84% were male. About 90% of the patients presented with STEMI, and 85% had very late ST. Seventy-two patients (56%) underwent TA. After propensity score matching, 30 patients were included in each study group. A higher rate of final TIMI III flow was observed in the TA group (TA vs n-TA group, 100% vs 83%), but this difference did not reach statistical significance (p = 0.052). At 1000 days of follow-up, survival free of CD or TLR was not different between the two groups (p = 0.8). Conclusion- In a propensity-matched population of ST patients undergoing PCI in a contemporary setting, TA was not associated with improved final TIMI flow or long-term cardiovascular outcomes

Percutaneous coronary intervention in stable angina (ORBITA): a double-blind, randomised controlled trial

Background: Symptomatic relief is the primary goal of percutaneous coronary intervention (PCI) in stable angina and is commonly observed clinically. However, there is no evidence from blinded, placebo-controlled randomised trials to show its efficacy. Methods: ORBITA is a blinded, multicentre randomised trial of PCI versus a placebo procedure for angina relief that was done at five study sites in the UK. We enrolled patients with severe (≥70%) single-vessel stenoses. After enrolment, patients received 6 weeks of medication optimisation. Patients then had pre-randomisation assessments with cardiopulmonary exercise testing, symptom questionnaires, and dobutamine stress echocardiography. Patients were randomised 1:1 to undergo PCI or a placebo procedure by use of an automated online randomisation tool. After 6 weeks of follow-up, the assessments done before randomisation were repeated at the final assessment. The primary endpoint was difference in exercise time increment between groups. All analyses were based on the intention-to-treat principle and the study population contained all participants who underwent randomisation. This study is registered with ClinicalTrials.gov, number NCT02062593. Findings: ORBITA enrolled 230 patients with ischaemic symptoms. After the medication optimisation phase and between Jan 6, 2014, and Aug 11, 2017, 200 patients underwent randomisation, with 105 patients assigned PCI and 95 assigned the placebo procedure. Lesions had mean area stenosis of 84·4% (SD 10·2), fractional flow reserve of 0·69 (0·16), and instantaneous wave-free ratio of 0·76 (0·22). There was no significant difference in the primary endpoint of exercise time increment between groups (PCI minus placebo 16·6 s, 95% CI −8·9 to 42·0, p=0·200). There were no deaths. Serious adverse events included four pressure-wire related complications in the placebo group, which required PCI, and five major bleeding events, including two in the PCI group and three in the placebo group. Interpretation: In patients with medically treated angina and severe coronary stenosis, PCI did not increase exercise time by more than the effect of a placebo procedure. The efficacy of invasive procedures can be assessed with a placebo control, as is standard for pharmacotherapy

Impact of point-of-care pre-procedure creatinine and eGFR testing in patients with ST segment elevation myocardial infarction undergoing primary PCI: The pilot STATCREAT study

Background: Contrast-induced acute kidney injury (CI-AKI) is a recognised complication during primary PCI that affects short and long term prognosis. The aim of this study was to assess the impact of point-of-care (POC) pre-PPCI creatinine and eGFR testing in STEMI patients. Methods 160 STEMI patients (STATCREAT group) with pre-procedure POC testing of Cr and eGFR were compared with 294 consecutive retrospective STEMI patients (control group). Patients were further divided into subjects with or without pre-existing CKD. Results: The incidence of CI-AKI in the whole population was 14.5% and not different between the two overall groups. For patients with pre-procedure CKD, contrast dose was significantly reduced in the STATCREAT group (124.6 ml vs. 152.3 ml, p = 0.015). The incidence of CI-AKI was 5.9% (n = 2) in the STATCREAT group compared with 17.9% (n = 10) in the control group (p = 0.12). There was no difference in the number of lesions treated (1.118 vs. 1.196, p = 0.643) or stents used (1.176 vs. 1.250, p = 0.78). For non-CKD patients, there was no significant difference in contrast dose (172.4 ml vs. 158.4 ml, p = 0.067), CI-AKI incidence (16.7% vs. 13.4%, p = 0.4), treated lesions (1.167 vs. 1.164, p = 1.0) or stents used (1.214 vs. 1.168, p = 0.611) between the two groups. Conclusions: Pre-PPCI point-of-care renal function testing did not reduce the incidence of CI-AKI in the overall group of STEMI patients. In patients with CKD, contrast dose was significantly reduced, but a numerical reduction in CI-AKI was not found to be statistically significant. No significant differences were found in the non-CKD group

Achieving Optimal Medical Therapy: Insights From the ORBITA Trial

Background: In stable coronary artery disease, medications are used for 2 purposes: cardiovascular risk reduction and symptom improvement. In clinical trials and clinical practice, medication use is often not optimal. The ORBITA (Objective Randomised Blinded Investigation With Optimal Medical Therapy of Angioplasty in Stable Angina) trial was the first placebo-controlled trial of percutaneous coronary intervention. A key component of the ORBITA trial design was the inclusion of a medical optimization phase, aimed at ensuring that all patients were treated with guideline-directed truly optimal medical therapy. In this study, we report the medical therapy that was achieved. Methods and Results: After enrollment into the ORBITA trial, all 200 patients entered a 6-week period of intensive medical therapy optimization, with initiation and uptitration of risk reduction and antianginal therapy. At the prerandomization stage, the median number of antianginals established was 3 (interquartile range, 2-4). A total of 195 patients (97.5%) reached the prespecified target of ≥2 antianginals; 136 (68.0%) did not stop any antianginals because of adverse effects, and the median number of antianginals stopped for adverse effects per patient was 0 (interquartile range, 0-1). Amlodipine and bisoprolol were well tolerated (stopped for adverse effects in 4/175 [2.3%] and 9/167 [5.4%], respectively). Ranolazine and ivabradine were also well tolerated (stopped for adverse effects in 1/20 [5.0%] and 1/18 [5.6%], respectively). Isosorbide mononitrate and nicorandil were stopped for adverse effects in 36 of 172 (20.9%) and 32 of 141 (22.7%) of patients, respectively. Statins were well tolerated and taken by 191 of 200 (95.5%) patients. Conclusions: In the 12-week ORBITA trial period, medical therapy was successfully optimized and well tolerated, with few drug adverse effects leading to therapy cessation. Truly optimal medical therapy can be achieved in clinical trials, and translating this into longer-term clinical practice should be a focus of future study. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02062593