The Effect of Hydrostatic Pressure on Coronary Flow and Pressure-Based Indices of Coronary Stenosis Severity.

Background: To assess whether hydrostatic pressure gradients caused by coronary height differences in supine versus prone positioning during invasive physiological stenosis assessment affect resting and hyperaemic pressure-based indices or coronary flow. Methods: Twenty-three coronary stenoses were assessed in twenty-one patients with stable coronary artery disease. All patients had a stenosis of at least 50% visually defined on previous coronary angiography. Pd/Pa, iFR, FFR, and coronary flow velocity (APV) measured using a Doppler were recorded across the same stenosis, with the patient in the prone position, followed by repeat measurements in the standard supine position. Results: When comparing prone to supine measurements in the same stenosis, in the LAD, there was a significant change in mean Pd/Pa of 0.08 ± 0.04 (p = 0.0006), in the iFR of 0.06 ± 0.07 (p = 0.02), and in the FFR of 0.09 ± 0.07 (p = 0.003). In the Cx, there was a change in mean Pd/Pa of 0.05 ± 0.04 (p = 0.009), iFR of 0.07 ± 0.04 (p = 0.01), and FFR of 0.05 ± 0.03 (p = 0.006). In the RCA, there was a change in Pd/Pa of 0.05 ± 0.04 (p = 0.032), iFR of 0.04 ± 0.05 (p = 0.19), and FFR of 0.04+-0.03 (p = 0.004). Resting and hyperaemic coronary flow did not change significantly (resting delta APV = 1.6 cm/s, p = 0.31; hyperaemic delta APV = 0.9 cm/s, p = 0.85). Finally, 36% of iFR measurements and 26% of FFR measurements were re-classified across an ischaemic threshold when prone and supine measurements were compared across the same stenosis. Conclusions: Pd/Pa, iFR, and FFR were affected by hydrostatic pressure variations caused by coronary height differences in prone versus supine positioning. Coronary flow did not change signifying a purely pressure-based phenomenon.

Coronary artery height differences and their effect on fractional flow reserve.

BACKGROUND: Fractional flow reserve (FFR) uses pressure-based measurements to assess the severity of a coronary stenosis. Distal pressure (Pd) is often at a different vertical height to that of the proximal aortic pressure (Pa). The difference in pressure between Pd and Pa due to hydrostatic pressure, may impact FFR calculation. METHODS: One hundred computed tomography coronary angiographies were used to measure height differences 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. This was tested in a simulation of intermediate coronary stenosis to give the "corrected FFR" (cFFR) and percentage 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 treatment threshold 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.

Effects of stent postdilatation during primary PCI for STEMI: Insights from coronary physiology and optical coherence tomography.

OBJECTIVES: This study aimed to assess the impact of stent optimization by NC-balloon postdilatation (PD) during primary-PCI for STEMI with the use of coronary physiology and intracoronary imaging. METHODS: This was a prospective observational study (ClinicalTrials.gov:NCT02788396). Optical coherence tomography (OCT) and physiological measurements were performed immediately before and after PD with the operators blinded to all measurements. The index of microcirculatory resistance (IMR), coronary flow reserve (CFR) and fractional flow reserve (FFR) were measured. OCT analysis was performed for assessment of stent expansion, malapposition, in-stent plaque-thrombus prolapse (PTP) and stent-edge dissections (SED). The change in IMR before and after PD as a measure of microvascular injury was the primary objective of the study. RESULTS: Thirty-two STEMI patients undergoing primary-PCI had physiological measurements before and after PD. All patients received second-generation DES (diameter 3.1 ± 0.5 mm, length 29.9 ± 10.7 mm) and postdilatation with NC-balloons (diameter 3.6 ± 0.6 mm, inflation pressure 19.3 ± 2.0 atm). IMR (44.9 ± 25.6 vs. 48.8 ± 34.2, p = 0.26) and CFR (1.60 ± 0.89 vs. 1.58 ± 0.71, p = 0.87) did not change, while FFR increased after PD (0.91 ± 0.08 vs. 0.93 ± 0.06, p = 0.037). At an individual patient level, IMR increased in half of the cases. PD improved significantly absolute and relative stent expansion, reduced malapposition, and increased PTP. There was no difference in clinically relevant SED. CONCLUSION: In this exploratory, hypothesis-generating study, postdilatation during primary-PCI for STEMI improved stent expansion, apposition and post-PCI FFR, without a significant effect on coronary microcirculation overall. Nevertheless, IMR increased in a group of patients and larger studies are warranted to explore predictors of microcirculatory response to postdilatation.

Absolute microvascular resistance by continuous thermodilution predicts microvascular dysfunction after ST-elevation myocardial infarction.

AIMS: Continuous thermodilution using intracoronary saline infusion is a novel technique able to provide accurate measurements of absolute coronary blood flow and microvascular resistance (Rmicro). The aim of this study was to assess the ability of Rmicro, measured by continuous thermodilution, to predict microvascular dysfunction in patients with ST-elevation myocardial infarction. METHODS AND RESULTS: In this prospective observational study, continuous thermodilution was used to measure Rmicro in the culprit coronary artery of 32 patients with STEMI (mean age ± SD, 66 ± 10 years; 78% male) immediately post-primary percutaneous coronary intervention (PCI). Concomitant measurements of the index of microvascular resistance (IMR) and coronary flow reserve (CFR) were obtained by bolus thermodilution. Microvascular dysfunction was defined as an IMR > 40 or a CFR < 2. Rmicro was higher in patients with microvascular dysfunction based on the predefined thresholds; for IMR: 863 (IQR, 521-1079) vs 474 (IQR, 337-616) Wood units, p = .004 and for CFR: 633 (IQR, 455-1039) vs 474 (IQR, 271-579) Wood units, p = .02. Receiver-operator characteristic analysis demonstrated that Rmicro was predictive of microvascular dysfunction; area under curve (AUC) 0.800 (95% CI: 0.637-0.963, p = .005) for IMR-defined microvascular dysfunction and AUC 0.758 (95% CI: 0.593-0.924, p = .02) for CFR-defined microvascular dysfunction. An Rmicro threshold of greater than 552 Wood units was optimal for predicting microvascular dysfunction defined by IMR > 40. CONCLUSIONS: Rmicro is able to identify STEMI patients in whom IMR and CFR measurements suggest significant microvascular dysfunction at the end of primary PCI.

Contemporary management of stent thrombosis: Predictors of mortality and the role of new-generation drug-eluting stents.

OBJECTIVES: We sought to evaluate mortality predictors and the role of new-generation drug-eluting stents (NG-DES) in stent thrombosis (ST) management. BACKGROUND: No data are available regarding the outcome of patients with ST after interventional management that includes exclusively NG-DES. METHODS: Patients with definite ST of DES or BMS who underwent urgent/emergent angiography between 2015 and 2018 at our institution were considered for the study. After excluding patients who achieved TIMI-flow<2 after intervention or received an old-generation stent, 131 patients were included. Management classification was stent or non-stent treatment (medical management, thromboaspiration, balloon-angioplasty). Follow-up was performed to document all-cause death (ACD) and target-lesion-revascularization (TLR) that was used for censorship. RESULTS: Mode of presentation was STEMI in 88% and UA/NSTEMI in 12%. Type of ST was early, late, and very late in 11, 4, and 85%, respectively. Eighty four patients received stent and 47 non-stent treatment. After 926 ± 34 days, 21 ACDs, 7 TLRs and no cases of definite, recurrent ST were observed. Univariate predictors of in-hospital mortality were LVEF and presentation with shock or cardiac arrest. For patients discharged alive, non-stent treatment (HR 4.2, p = .01), TIMI-2 flow (HR 7.4, p = .002) and GFR < 60 mL/min (HR 3.8, p = .01) were independent predictors of ACD. The stent-treatment group had significantly better ACD-free survival after discharge, both unadjusted (p = .022) and adjusted (p = .018). CONCLUSIONS: After ST management, different predictors were observed for in-hospital mortality and mortality in patients discharged alive. The better outcome with NG-DES treatment is a novel observation, warranting further studies to elucidate if it is associated with stent-related or patient-related factors.

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.

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.

Comparison of clinical characteristics and outcomes in patients with left bundle branch block versus ST-elevation myocardial infarction referred for primary percutaneous coronary intervention.

AIMS: Recent studies have suggested that a low proportion of patients presenting with left bundle branch block (LBBB) require emergency intervention. In this study, we have compared baseline clinical characteristics, angiographic findings and subsequent outcomes in patients with LBBB versus ST-elevation myocardial infarction (STEMI) referred to our tertiary centre for primary percutaneous coronary intervention (PCI). METHODS AND RESULTS: A large retrospective observational study was performed involving 1875 consecutive patients presenting to our single tertiary cardiac centre for primary PCI over a 27-month period. Patients presenting with LBBB (n=155, 8.3%) were significantly older (P<0.0001) and were more likely to be female (P<0.0001) and have a prior history of myocardial infarction (P<0.0001) or coronary artery bypass graft surgery (P=0.005). Rates of acute occlusion (12.2 vs. 63%; P<0.0001) and PCI (26 vs. 83%; P<0.0001) were significantly lower in LBBB patients compared with STEMI patients. Although the 30-day mortality was similar, overall mortality during the 2 years of follow-up was significantly higher in the LBBB group compared with the STEMI group (27.8 vs. 13.9%; P=0.023). CONCLUSION: The incidence of an acutely occluded vessel is low in LBBB when compared with STEMI, but the long-term outcome is significantly worse. Patients with LBBB referred for primary PCI need better risk stratification, and further work is needed to identify potential diagnostic and management strategies.

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.

Comparison of bivalirudin with heparin versus abciximab with heparin for primary percutaneous coronary intervention in "Real World" practice.

OBJECTIVE: We aimed to carry out a "real world" comparison of bivalirudin plus unfractionated heparin (UFH) versus abciximab plus UFH in patients undergoing primary percutaneous coronary intervention (PPCI) for ST elevation myocardial infarction (STEMI). METHODS: We included patients who had abciximab or bivalirudin during their PPCI in our unit between Sept 2009 and Nov 2011. RESULTS: The study included 516 and 484 patients in the bivalirudin and abciximab group respectively. There were more women in the bivalirudin group (29% vs 20%, p 0.001), while cardiogenic shock (6.4% vs 10.1%, p 0.04) and thrombectomy device use (76.6% vs 82%, p 0.04) were lower in the bivalirudin group. The primary composite end point of 30-day mortality, 30-day definite stent thrombosis or non-CABG major bleeding was similar between the bivalirudin and abciximab groups (7.8% vs 9.5%, OR 0.8, 95% CI 0.5 to 1.2, p 0.4). There was also no difference in in-hospital mortality (4.1% vs 4.3%, p 0.9), 30-day mortality (5.2% vs 6.4%, p 0.5), 1-year mortality (9.1% vs 9.9%, p 0.7), 30-day stent thrombosis (1% vs 0.4%, p 0.5) and non-CABG bleeding (2.7 vs 3.7%, p 0.4) between the bivalirudin and abciximab group respectively. On Cox proportional hazard analysis after adjusting for all the co-variates, the use of bivalirudin was not a predictor of 30-day mortality (HR 1.13, 95% CI 0.7-1.9, p 0.7). CONCLUSION: In this "real-world" observational study, there was no significant difference in the clinical outcome of PPCI for patients who had abciximab or bivalirudin after initial pre-treatment with UFH.