Comparison of bolus versus continuous thermodilution derived indices of microvascular dysfunction in revascularized coronary syndromes.

Background: The assessment of coronary microvascular dysfunction (CMD) using invasive methods is a field of growing interest, however the preferred method remains debated. Bolus and continuous thermodilution are commonly used methods, but weak agreement has been observed in patients with angina with non-obstructive coronary arteries (ANOCA). This study examined their agreement in revascularized acute coronary syndromes (ACS) and chronic coronary syndromes (CCS) patients. Objective: To compare bolus thermodilution and continuous thermodilution indices of CMD in revascularized ACS and CCS patients and assess their diagnostic agreement at pre-defined cut-off points. Methods: Patients from two centers underwent paired bolus and continuous thermodilution assessments after revascularization. CMD indices were compared between the two methods and their agreements at binary cut-off points were assessed. Results: Ninety-six patients and 116 vessels were included. The mean age was 64 ± 11 years, and 20 (21 %) were female. Overall, weak correlations were observed between the Index of Microcirculatory Resistance (IMR) and continuous thermodilution microvascular resistance (Rµ) (rho = 0.30p = 0.001). The median coronary flow reserve (CFR) from continuous thermodilution (CFRcont) and bolus thermodilution (CFRbolus) were 2.19 (1.76-2.67) and 2.55 (1.50-3.58), respectively (p < 0.001). Weak correlation and agreement were observed between CFRcont and CFRbolus (rho = 0.37, p < 0.001, ICC 0.228 [0.055-0.389]). When assessed at CFR cut-off values of 2.0 and 2.5, the methods disagreed in 41 (35 %) and 45 (39 %) of cases, respectively. Conclusions: There is a significant difference and weak agreement between bolus and continuous thermodilution-derived indices, which must be considered when diagnosing CMD in ACS and CCS patients.

The challenges of a randomised placebo-controlled trial of CTO PCI vs. placebo with optimal medical therapy: The ORBITA-CTO pilot study design and protocol.

Background: Percutaneous coronary intervention (PCI) for coronary chronic total occlusion (CTO) has been performed for the improvement of symptoms and quality of life in patients with stable angina. The ORBITA study demonstrated the role of the placebo effect in contemporary PCI in non-CTO chronic coronary syndromes. However, the benefit of CTO PCI beyond that of a placebo has not been demonstrated. Aims: The ORBITA-CTO pilot study will be a double-blind, placebo-controlled study of CTO PCI randomising patients who have: (1) been accepted by a CTO operator for PCI; (2) experienced symptoms due to a CTO; (3) evidence of ischaemia; (4) evidence of viability within the CTO territory; and (5) a J-CTO score ≤3. Methods: Patients will undergo medication optimisation that will ensure they are on at least a minimum amount of anti-anginals and complete questionnaires. Patients will record their symptoms on an app daily throughout the study. Patients will undergo randomisation procedures, including an overnight stay, and be discharged the following day. All anti-anginals will be stopped after randomisation and re-initiated on a patient-led basis during the 6-month follow-up period. At follow-up, patients will undergo repeat questionnaires and unblinding, with a further 2-week unblinded follow-up. Results: The co-primary outcomes are feasibility (blinding) in this cohort and angina symptom score using an ordinal clinical outcome scale for angina. Secondary outcomes include changes in quality-of-life measures, Seattle Angina Questionnaire (SAQ), peak VO2, and anaerobic threshold on the cardiopulmonary exercise test. Conclusion: The feasibility of a placebo-controlled CTO PCI study will lead to future studies assessing efficacy. The impact of CTO PCI on angina measured using a novel daily symptom app may provide improved fidelity in assessing symptoms in patients with CTO's.

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.

Comparing invasive hemodynamic responses in adenosine hyperemia versus physical exercise stress in chronic coronary syndromes.

OBJECTIVES: Adenosine hyperemia is an integral component of the physiological assessment of obstructive coronary artery disease in patients with chronic coronary syndrome (CCS). The aim of this study was to compare systemic, coronary and microcirculatory hemodynamics between intravenous (IV) adenosine hyperemia versus physical exercise stress in patients with CCS and coronary stenosis. METHODS: Twenty-three patients (mean age, 60.6 ± 8.1 years) with CCS and single-vessel coronary stenosis underwent cardiac catheterization. Continuous trans-stenotic coronary pressure-flow measurements were performed during: i) IV adenosine hyperemia, and ii) physical exercise using a catheter-table-mounted supine ergometer. Systemic, coronary and microcirculatory hemodynamic responses were compared between IV adenosine and exercise stimuli. RESULTS: Mean stenosis diameter was 74.6% ± 10.4. Median (interquartile range) FFR was 0.54 (0.44-0.72). At adenosine hyperemia versus exercise stress, mean aortic pressure (Pa, 91 ± 16 mmHg vs 99 ± 15 mmHg, p < 0.0001), distal coronary pressure (Pd, 58 ± 21 mmHg vs 69 ± 24 mmHg, p < 0.0001), trans-stenotic pressure ratio (Pd/Pa, 0.63 ± 0.18 vs 0.69 ± 0.19, p < 0.0001), microvascular resistance (MR, 2.9 ± 2.2 mmHg.cm-1.sec-1 vs 4.2 ± 1.7 mmHg.cm-1.sec-1, p = 0.001), heart rate (HR, 80 ± 15 bpm vs 85 ± 21 bpm, p = 0.02) and rate-pressure product (RPP, 7522 ± 2335 vs 9077 ± 3200, p = 0.0001) were all lower. Conversely, coronary flow velocity (APV, 23.7 ± 9.5 cm/s vs 18.5 ± 6.8 cm/s, p = 0.02) was higher. Additionally, temporal changes in Pa, Pd, Pd/Pa, MR, HR, RPP and APV during IV adenosine hyperemia versus exercise were all significantly different (p < 0.05 for all). CONCLUSIONS: In patients with CCS and coronary stenosis, invasive hemodynamic responses differed markedly between IV adenosine hyperemia versus physical exercise stress. These differences were observed across systemic, coronary and microcirculatory hemodynamics.

Association Between Physiological Stenosis Severity and Angina-Limited Exercise Time in Patients With Stable Coronary Artery Disease.

Importance: Physiological stenosis assessment is recommended to guide percutaneous coronary intervention (PCI) in patients with stable angina. Objective: To determine the association between all commonly used indices of physiological stenosis severity and angina-limited exercise time in patients with stable angina. Design, Setting, and Participants: This cohort study included data (without follow-up) collected over 1 year from 2 cardiac hospitals. Selected patients with stable angina and physiologically severe single-vessel coronary artery disease presenting for clinically driven elective PCI were included. Exposures: Fractional flow reserve (FFR), instantaneous wave-free ratio (iFR), hyperemic stenosis resistance (HSR), and coronary flow reserve (CFR) were measured invasively. Immediately after this, patients maximally exercised on a catheter-table-mounted supine ergometer until they developed rate-limiting angina. Subsequent PCI was performed in most patients, followed by repeat maximal supine exercise testing. Main Outcomes and Measures: Associations between FFR, iFR, HSR, CFR, and angina-limited exercise time were assessed using linear regression and Pearson correlation coefficients. Additionally, the associations between the post-PCI increment in exercise time and baseline FFR, iFR, HSR, and CFR were assessed. Results: Twenty-three patients (21 [91.3%] of whom were male; mean [SD] age, 60.6 [8.1] years) completed the pre-PCI component of the study protocol. Mean (SD) stenosis diameter was 74.6% (10.4%). Median (interquartile range [IQR]) values were 0.54 (0.44-0.72) for FFR, 0.53 (0.38-0.83) for iFR, 1.67 (0.84-3.16) for HSR, and 1.35 (1.11-1.63) for CFR. Mean (SD) angina-limited exercise time was 144 (77) seconds. Anatomical stenosis characteristics were not significantly associated with angina-limited exercise time. Conversely, FFR (R2 = 0.27; P = .01), iFR (R2 = 0.46; P < .001), HSR (R2 = 0.39; P < .01), and CFR (R2 = 0.16; P < .05) were all associated with angina-limited exercise time. Twenty-one patients (19 [90.5%] of whom were male; mean [SD] age, 60.1 [8.2] years) competed the full protocol of PCI, post-PCI physiological assessment, and post-PCI maximal exercise. After PCI, the median (IQR) FFR rose to 0.91 (0.85-0.96), median (IQR) iFR to 0.98 (0.94-0.99), and median (IQR) CFR to 2.73 (2.50-3.12), while the median (IQR) HSR fell to 0.16 (0.06-0.37) (P < .001 for all). The post-PCI increment in exercise time was most significantly associated with baseline iFR (R2 = 0.26; P = .02). Conclusions and Relevance: In a selected group of patients with severe, single-vessel stable angina, FFR, iFR, HSR, and CFR were all modestly correlated with angina-limited exercise time to varying degrees. Notwithstanding the limited sample size, no clear association was demonstrated between anatomical stenosis severity and angina-limited exercise time.

Mineralocorticoid receptor antagonist pre-treatment and early post-treatment to minimize reperfusion injury after ST-elevation myocardial infarction: The MINIMIZE STEMI trial.

BACKGROUND: Mineralocorticoid receptor antagonist (MRA) therapy has been shown to prevent adverse left ventricular (LV) remodeling in ST-segment elevation myocardial infarction (STEMI) patients with heart failure. Whether initiating MRA therapy prior to primary percutaneous coronary intervention (PPCI) accrues additional benefit of reducing myocardial infarct size and preventing adverse LV remodeling is not known. We aimed to investigate whether MRA therapy initiated prior to reperfusion reduces myocardial infarct (MI) size and prevents adverse LV remodeling in STEMI patients. METHODS: STEMI patients presenting within 12 hours and with a proximal coronary artery occlusion with Thrombolysis In Myocardial Infarction flow grade 0 were consented and randomized to either an intravenous bolus of potassium canrenoate, followed by oral spironolactone for 3 months or matching placebo. The primary endpoint was MI size by cardiovascular magnetic resonance at 3 months. RESULTS: Sixty-seven patients completed the study. There was no significant difference in the final MI size at 3 months between the 2 groups (placebo: 17 ± 11%, MRA: 16 ± 10%, P = .574). There was also no difference in acute MI size (26 ± 16% versus 23 ± 14%, P = .425) or myocardial salvage (26 ± 12% versus 24 ± 8%, P = .456). At follow-up, there was a trend towards an improvement in LVEF (placebo: 49 ± 8%, MRA: 54 ± 11%, P = .053), and the MRA group had significantly greater percentage decrease in LVEDV (mean difference: -12.2 (95% CI -20.3 to -4.4)%, P = .003) and LVESV (mean difference: -18.2 (95% CI -30.1 to -6.3)%, P = .003). CONCLUSION: This pilot study showed no benefit of MRA therapy in reducing MI size in STEMI patients when initiated prior to reperfusion, but there was an improvement in LV remodeling at 3 months. Adequately powered studies are warranted to confirm these findings.

Serial Fractional Flow Reserve Measurements Post Coronary Chronic Total Occlusion Percutaneous Coronary Intervention.

Background The aim of this study was to evaluate the functional result of chronic total occlusion percutaneous coronary intervention (PCI) measured by fractional flow reserve (FFR) immediately post the index procedure and at short-term follow-up. Methods and Results This was a prospective single-center observational study. Consecutive patients with right coronary artery chronic total occlusion scheduled for elective PCI were included. FFR measurements were performed immediately after successful PCI and at 4 months follow-up. Twenty-six patients completed baseline and follow-up measurements. Mean age was 61.2±9.7 years, 88.5% of the patients were male, and 19.2% were diabetic. The mean FFR immediately after successful chronic total occlusion PCI was 0.82±0.10 and significantly increased to 0.89±0.07 at 4 months ( P<0.001). The FFR increased in 77% of the patients with a mean absolute increase of 0.07±0.08. The incidence of FFR ≤0.80 immediately after PCI was significantly higher amongst patients with subintimal versus intraplaque recanalization (23% versus 12%; P=0.03). At 4 months, FFR ≤0.80 was found only in 2 patients with subintimal recanalization. At follow-up, 42.7% of the patients continued to have an FFR <0.90. Conclusions Post chronic total occlusion PCI, FFR increased significantly at short-term follow-up compared with measurements post index procedure. Because FFR remained <0.90 in many cases, further efforts should be made to optimize procedural results.

Impact of Percutaneous Revascularization on Exercise Hemodynamics in Patients With Stable Coronary Disease.

BACKGROUND: Recently, the therapeutic benefits of percutaneous coronary intervention (PCI) have been challenged in patients with stable coronary artery disease (SCD). OBJECTIVES: The authors examined the impact of PCI on exercise responses in the coronary circulation, the microcirculation, and systemic hemodynamics in patients with SCD. METHODS: A total of 21 patients (mean age 60.3 ± 8.4 years) with SCD and single-vessel coronary stenosis underwent cardiac catheterization. Pre-PCI, patients exercised on a supine ergometer until rate-limiting angina or exhaustion. Simultaneous trans-stenotic coronary pressure-flow measurements were made throughout exercise. Post-PCI, this process was repeated. Physiological parameters, rate-limiting symptoms, and exercise performance were compared between pre-PCI and post-PCI exercise cycles. RESULTS: PCI reduced ischemia as documented by fractional flow reserve value (pre-PCI 0.59 ± 0.18 to post-PCI 0.91 ± 0.07), instantaneous wave-free ratio value (pre-PCI 0.61 ± 0.27 to post-PCI 0.96 ± 0.05) and coronary flow reserve value (pre-PCI 1.7 ± 0.7 to post-PCI 3.1 ± 1.0; p < 0.001 for all). PCI increased peak-exercise average peak coronary flow velocity (p < 0.0001), coronary perfusion pressure (distal coronary pressure; p < 0.0001), systolic blood pressure (p = 0.01), accelerating wave energy (p < 0.001), and myocardial workload (rate-pressure product; p < 0.01). These changes observed immediately following PCI resulted from the abolition of stenosis resistance (p < 0.0001). PCI was also associated with an immediate improvement in exercise time (+67 s; 95% confidence interval: 31 to 102 s; p < 0.0001) and a reduction in rate-limiting angina symptoms (81% reduction in rate-limiting angina symptoms post-PCI; p < 0.001). CONCLUSIONS: In patients with SCD and severe single-vessel stenosis, objective physiological responses to exercise immediately normalize following PCI. This is seen in the coronary circulation, the microcirculation, and systemic hemodynamics.

Pre-Angioplasty Instantaneous Wave-Free Ratio Pullback Predicts Hemodynamic Outcome In Humans With Coronary Artery Disease: Primary Results of the International Multicenter iFR GRADIENT Registry.

OBJECTIVES: The authors sought to evaluate the accuracy of instantaneous wave-Free Ratio (iFR) pullback measurements to predict post-percutaneous coronary intervention (PCI) physiological outcomes, and to quantify how often iFR pullback alters PCI strategy in real-world clinical settings. BACKGROUND: In tandem and diffuse disease, offline analysis of continuous iFR pullback measurement has previously been demonstrated to accurately predict the physiological outcome of revascularization. However, the accuracy of the online analysis approach (iFR pullback) remains untested. METHODS: Angiographically intermediate tandem and/or diffuse lesions were entered into the international, multicenter iFR GRADIENT (Single instantaneous wave-Free Ratio Pullback Pre-Angioplasty Predicts Hemodynamic Outcome Without Wedge Pressure in Human Coronary Artery Disease) registry. Operators were asked to submit their procedural strategy after angiography alone and then after iFR-pullback measurement incorporating virtual PCI and post-PCI iFR prediction. PCI was performed according to standard clinical practice. Following PCI, repeat iFR assessment was performed and the actual versus predicted post-PCI iFR values compared. RESULTS: Mean age was 67 ± 12 years (81% male). Paired pre- and post-PCI iFR were measured in 128 patients (134 vessels). The predicted post-PCI iFR calculated online was 0.93 ± 0.05; observed actual iFR was 0.92 ± 0.06. iFR pullback predicted the post-PCI iFR outcome with 1.4 ± 0.5% error. In comparison to angiography-based decision making, after iFR pullback, decision making was changed in 52 (31%) of vessels; with a reduction in lesion number (-0.18 ± 0.05 lesion/vessel; p = 0.0001) and length (-4.4 ± 1.0 mm/vessel; p < 0.0001). CONCLUSIONS: In tandem and diffuse coronary disease, iFR pullback predicted the physiological outcome of PCI with a high degree of accuracy. Compared with angiography alone, availability of iFR pullback altered revascularization procedural planning in nearly one-third of patients.

The impact of coronary chronic total occlusion percutaneous coronary intervention upon donor vessel fractional flow reserve and instantaneous wave-free ratio: Implications for physiology-guided PCI in patients with CTO.

OBJECTIVE: To investigate the immediate and short term impact of right coronary artery (RCA) chronic total coronary occlusion (CTO) percutaneous coronary intervention (PCI) upon collateral donor vessel fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR). BACKGROUND: CTO PCI influences collateral donor vessel physiology, making the indication and/or timing of donor vessel revascularization difficult to determine. METHODS: In patients with RCA CTO, FFR, iFR, and collateral function index (FFRcoll ) were measured in LAD and LCx pre-CTO PCI, immediately post and at 4 month follow-up. RESULTS: 34 patients underwent successful PCI. In the predominant donor vessel immediately post PCI, FFR, and FFRcoll did not change (0.76 ± 0.12 to 0.75 ± 0.13, P = 0.267 and 0.31 ± 0.10 vs. 0.34 ± 0.11, P = 0.078), but iFR increased significantly (0.86 ± 0.10 to 0.88 ± 0.10, P = 0.012). At follow-up, there was a significant increase in predominant donor FFR and iFR (0.76 ± 0.12 to 0.79 ± 0.11, P = 0.047 and 0.86 ± 0.10 to 0.90 ± 0.07, P = 0.003), accompanied by a significant reduction in FFRcoll (0.31 ± 0.10 to 0.18 ± 0.07 P < 0.0001). These changes resulted in a reclassification of the predominant donor vessel from ischemic to nonischemic in 18% (FFR) and 25% (iFR) of the cases, respectively. CONCLUSIONS: Successful recanalization of an RCA CTO resulted in a modest but statistically significant increase in the predominant donor vessel immediately post CTO PCI in the case of iFR and at 4-month follow-up for FFR and iFR compared to pre-PCI with a concomitant reduction in collateral function.

Impact of right atrial pressure on fractional flow reserve calculation in the presence of a chronic total occlusion.

BACKGROUND: The aim of this study was to assess the impact of right atrial pressure (Pra) on non-CTO vessels FFR measurements in patients with a chronic total occlusion. METHODS: Consecutive patients who underwent PCI for a CTO of the right coronary artery (RCA) were included. Prior to RCA recanalization, FFR and FFRmyo were measured in non-CTO vessels. FFR was calculated using the Pd/Pa equation during maximum hyperaemia and also accounting for right atrial pressure (Pd-Pra/Pa-Pra). Non-CTO vessels were characterised as major or minor donors based on angiographic assessment of provided collaterals. RESULTS: FFR and FFRmyo were measured in 68 arteries (34 LAD and 34 Cx) in 34 consecutive patients with successful RCA CTO PCI. Patients' mean age was 62 ±â€¯10 years old and 88% were male. Mean left ventricular ejection fraction was 51% ±â€¯20. During maximum hyperaemia, mean Pra, Pa, and Pd were 4.1 ±â€¯3.8 mm Hg, 82.6 ±â€¯12.2 mm Hg, and 63.8 ±â€¯14.3 mm Hg, respectively. In the major donor vessel, FFRmyo showed a difference of 0.007 to FFR (0.760 ±â€¯0.113 vs. 0.767 ±â€¯0.112, p = 0.004). In the minor donor vessel the difference was 0.004 (0.895 ±â€¯0.067 vs. 0.899 ±â€¯0.065, p < 0.001). There was a strong positive correlation between the FFR and FFRmyo in both the major and minor donor vessel groups (r = 0.993, p < 0.001 and r = 0.996, p < 0.001 respectively). CONCLUSION: In the presence of a CTO, RA pressure adjustment of FFR in the non-CTO vessels leads to trivial numerical changes, which are statistically significant but clinically negligible.

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 (124.6ml vs. 152.3ml, 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 (172.4ml vs. 158.4ml, 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.

Fractional Flow Reserve: Does a Cut-off Value add Value?

Fractional flow reserve (FFR) has been shown to improve outcomes when used to guide percutaneous coronary intervention (PCI). There have been two proposed cut-off points for FFR. The first was derived by comparing FFR against a series of non-invasive tests, with a value of ≤0.75 shown to predict a positive ischaemia test. It was then shown in the DEFER study that a vessel FFR value of ≥0.75 was associated with safe deferral of PCI. During the validation phase, a 'grey zone' for FFR values of between 0.76 and 0.80 was demonstrated, where a positive non-invasive test may still occur, but sensitivity and specificity were sub-optimal. Clinical judgement was therefore advised for values in this range. The FAME studies then moved the FFR cut-off point to ≤0.80, with a view to predicting outcomes. The ≤0.80 cut-off point has been adopted into clinical practice guidelines, whereas the lower value of ≤0.75 is no longer widely used. Here, the authors discuss the data underpinning these cut-off values and the practical implications for their use when using FFR guidance in PCI.

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.

Mineralocorticoid receptor antagonist pretreatment to MINIMISE reperfusion injury after ST-elevation myocardial infarction (the MINIMISE STEMI Trial): rationale and study design.

Novel therapies capable of reducing myocardial infarct (MI) size when administered prior to reperfusion are required to prevent the onset of heart failure in ST-segment elevation myocardial infarction (STEMI) patients treated by primary percutaneous coronary intervention (PPCI). Experimental animal studies have demonstrated that mineralocorticoid receptor antagonist (MRA) therapy administered prior to reperfusion can reduce MI size, and MRA therapy prevents adverse left ventricular (LV) remodeling in post-MI patients with LV impairment. With these 2 benefits in mind, we hypothesize that initiating MRA therapy prior to PPCI, followed by 3 months of oral MRA therapy, will reduce MI size and prevent adverse LV remodeling in STEMI patients. The MINIMISE-STEMI trial is a prospective, randomized, double-blind, placebo-controlled trial that will recruit 150 STEMI patients from four centers in the United Kingdom. Patients will be randomized to receive either an intravenous bolus of MRA therapy (potassium canrenoate 200 mg) or matching placebo prior to PPCI, followed by oral spironolactone 50 mg once daily or matching placebo for 3 months. A cardiac magnetic resonance imaging scan will be performed within 1 week of PPCI and repeated at 3 months to assess MI size and LV remodeling. Enzymatic MI size will be estimated by the 48-hour area-under-the-curve serum cardiac enzymes. The primary endpoint of the study will be MI size on the 3-month cardiac magnetic resonance imaging scan. The MINIMISE STEMI trial will investigate whether early MRA therapy, initiated prior to reperfusion, can reduce MI size and prevent adverse post-MI LV remodeling.

Impact of a chronic total occlusion in a non-infarct related artery on clinical outcomes following primary percutaneous intervention in acute ST-elevation myocardial infarction.

AIMS: We aimed to assess the impact of a non-infarct related artery (IRA) chronic total occlusion (CTO) on clinical outcomes following primary percutaneous coronary intervention (PPCI) for ST-elevation myocardial infarction (STEMI) in a real-world cohort of patients. METHODS AND RESULTS: This is a retrospective observational study of 1435 patients treated at a large single tertiary cardiac center providing a high-volume PPCI service. Patients with coexisting CTO (4.7%) were significantly more likely to have presented in cardiogenic shock and less likely to achieve TIMI 2/3 flow in the IRA post procedure resulting in lower ejection fraction and higher peak troponin-T levels. A concurrent CTO in a non-IRA was associated with higher in-hospital mortality (16.4% vs 3.1%; P<.001), 30-day mortality (19.4% vs 5.9%; P<.001) and long-term mortality (23.9% vs 12.2%; P=.01). Binary logistic regression analysis showed that the presence of a non-IRA CTO was independently predictive of mortality at 30 days (odds ratio, 3.2; 95% confidence interval, 1.2-8.1) but not for long-term mortality. CONCLUSION: The presence of a coexisting CTO in patients undergoing PPCI for STEMI is associated with adverse clinical outcomes; further work is required to improve prognosis in these patients, which may include early staged revascularization of the non-IRA CTO.