COlchicine to Prevent PeriprocEdural Myocardial Injury in Percutaneous Coronary Intervention (COPE-PCI): Coronary Microvascular Physiology Pilot Substudy.

Aim: In this randomized pilot trial, we aimed to assess the anti-inflammatory effect of preprocedural colchicine on coronary microvascular physiology measurements before and after PCI. Methods: Patients undergoing PCI for stable angina (SA) or non-ST-elevation myocardial infarction (NSTEMI) were randomized to oral colchicine or placebo, 6- to 24-hours before the procedure. Strict prespecified inclusion/exclusion criteria were set to ensure all patients were given the study medication, had a PCI, and had pre- and post-PCI culprit vessel invasive coronary physiology measurements. Fractional flow reserve (FFR), Index of Microvascular Resistance (IMR), Coronary Flow Reserve (CFR), and Resistive Reserve Ratio (RRR) were measured immediately before and after PCI. CMVD was defined as any one of post-PCI IMR >32 or CFR <2 or RRR <2. High-sensitive-(hs)-troponin-I, hsCRP, and leucocyte count were measured before and 24 hours after PCI. Results: A total of 50 patients were randomized and met the strict prespecified inclusion/exclusion criteria: 24-colchicine and 26-placebo. Pre-PCI coronary physiology measurements, hs-troponin-I, and hsCRP were similar between groups. Although numerically lower in patients given colchicine, the proportion of patients who developed CMVD was not significantly different between groups (colchicine: 10 (42%) vs placebo: 16 (62%), p=0.16). Colchicine patients had higher post-PCI CFR and RRR vs placebo (respectively: 3.25 vs 2.00, p=0.03 & 4.25 vs 2.75, p < 0.01). Neutrophil count was lower after PCI in the colchicine arm (p=0.02), and hsCRP post-PCI remained low in both treatment arms (1.0 mg/L vs 1.7 mg/L, p=0.97). Patients randomized to colchicine had significantly less PCI-related absolute hs-troponin-I change (46 ng/L vs 152 ng/L, p=0.01). Conclusion: In this pilot randomized substudy, colchicine given 6 to 24 hours before PCI did not statistically impact the post-PCI CMVD definition used in this study, yet it did improve post-PCI RRR and CFR measurements, with less procedure-related troponin release and less inflammation.

COlchicine to Prevent PeriprocEdural Myocardial Injury in Percutaneous Coronary Intervention (COPE-PCI): A Descriptive Cytokine Pilot Sub-Study.

BACKGROUND: High levels of inflammation pre- and post-percutaneous coronary intervention (PCI) are associated with worse outcomes. Recent trials have suggested a benefit from treating inflammation with colchicine in coronary artery disease. In this randomised pilot COPE-PCI sub-study, we aimed to determine if administration of colchicine pre-PCI, would attenuate the inflammatory effect of PCI. METHODS: PCI patients were randomised to colchicine or placebo, 6 to 24-hours pre-procedure. Study blood samples were taken immediately pre-PCI, and 24-hours post-procedure. Samples were tested for a broad array of inflammatory biomarkers including high-sensitive(hs)-CRP, leucocyte counts, and hs-troponin-. Periprocedural Myocardial Injury (PM-Injury) was defined as per the ESC Third Universal Definitions of Myocardial Infarction. RESULTS: Thirty-six were randomised to colchicine and 39 to placebo. Treatment groups were similar for baseline variables. The median time from drug administration to pre-PCI blood sampling was 18-hours. Overall inflammation was low across the patient population, pre- & post-PCI hsCRP was <1.4 mg/L. Colchicine patients had numerically lower levels of pre-PCI cytokines: IL-1ß (p = 0.01), IL-6 (p = 0.02), IL-10 (p = 0.01), IFNγ (p = 0.01), TNFα (p = 0.02) and WBC-count (p = 0.04). Post-PCI (38-hours post-drug) measures of inflammation were similar between treatment arms. Absolute troponin change (post-PCI - pre-PCI levels) was less in colchicine patients (p = 0.02). CONCLUSION: The reduction in PCI-related myocardial injury that resulted from colchicine given on median 18 h pre-PCI, was associated with numerically lower levels of inflammation pre-PCI but no difference one day post-PCI in the colchicine vs placebo groups. CLINICAL TRIAL REGISTRATION: The trial was publicly registered at www.anzctr.org.au, Trial ID: ACTRN12615000485538.

Colchicine to Prevent Periprocedural Myocardial Injury in Percutaneous Coronary Intervention: The COPE-PCI Pilot Trial.

BACKGROUND: Periprocedural myocardial infarction and injury (PM-injury) are the most common complications of percutaneous coronary intervention (PCI) and are associated with future adverse cardiac events. Inflammation plays a pivotal role in the development of PM-injury. In this randomized pilot trial, we assessed the effect of an anti-inflammatory medication colchicine on periprocedural myocardial injury. METHODS: Patients undergoing PCI for stable angina or non­ST-segment­elevation myocardial infarction were randomized to oral colchicine (1 mg followed by 0.5 mg 1 hour later) or placebo, 6 to 24 hours preprocedure. Blood samples were taken immediately pre- and 24-hours post-PCI. The primary outcome, periprocedural myocardial infarction, was defined by an increase in post-PCI troponin >5×99th% upper reference limit when the pre-PCI troponin was normal, or >20% increase in post-PCI troponin when the pre-PCI troponin was raised, including supporting evidence of new myocardial ischemia. Major PM-injury was defined as per periprocedural myocardial infarction without supporting evidence of new myocardial ischemia. Minor PM-injury was defined by post-PCI troponin increase >99th% upper reference limit but ≤5×99th% upper reference limit. RESULTS: A total of 196 patients met inclusion criteria and were randomized. One hundred twenty-one patients were excluded (no PCI, unstable troponin before PCI, or poor-quality measurements) leaving a study population of 75 patients. Thirty-six patients were randomized to colchicine and 39 to placebo preprocedure. Forty-four presented with non­ST-segment­elevation myocardial infarction and 31 with stable angina. High-sensitive (hs) troponin-I pre-PCI was similar between treatment groups (colchicine: 79 ng/L [4­1336] versus placebo: 35 [5­448], P=0.42). Absolute change in hs-troponin-I (calculated as 24-hour post-PCI minus pre-PCI measurements) was significantly lower in the colchicine group: 59 (1­221) versus placebo: 166 (53­530), P=0.02. No patients developed periprocedural myocardial infarction in either group. Significantly fewer patients developed major PM-injury: 11 (31%) versus 21 (54%), P=0.04 or minor PM-injury: 21 (58%) versus 33 (85%), P=0.01, if given colchicine pre-PCI. CONCLUSIONS: In this randomized pilot trial, colchicine given 6 to 24 hours pre-PCI reduces periprocedural myocardial injury.

The "bladder sign"--an important early marker of retroperitoneal hemorrhage.

Retroperitoneal hemorrhage remains one of the major complications of cardiac and peripheral vascular catheterization. Its high associated morbidity and mortality require vigilance and early intervention. We report six cases of retroperitoneal hemorrhage featuring a "bladder sign." The compression of the bladder described in this series can be visualized on the incidental cystogram that results from contrast given during catheterization. Its significance as a highly specific marker of retroperitoneal hemorrhage should be appreciated.

Comparison of procedural times, success rates, and safety between left versus right radial arterial access in primary percutaneous coronary intervention for acute ST-segment elevation myocardial infarction.

OBJECTIVE: To evaluate if there are differences in procedural times, success rates, and safety between left and right radial approach (LRA and RRA, respectively) in primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI). BACKGROUND: Given conflicting reports of different procedural success with LRA vs. RRA, it is unclear if the side of radial access impacts in-room procedural times and success rates in primary PCI. At our institution the LRA has been commonly used in certain STEMI patients. Our clinical database was reviewed to see if routine use of the LRA could generate favorable technical success and reperfusion times as compared to the RRA. METHODS: We retrospectively analyzed 135 consecutive STEMI patients treated with primary PCI performed via the left and right radial approach at our institution. RESULTS: There were 50 cases in the LRA group and 85 in the RRA group. There was no difference in median procedural times including total procedure time (LRA 53.5 mins vs. RRA 52 mins, P = 0.95), room-to-cannulation (LRA 12 min vs. RRA 13 min, P = 0.40) or room-to-balloon times (LRA 30 min vs. RRA 31 min, P = 0.74). There were no significant differences in procedural success rates (LRA 100% vs. RRA 97.6%, P = 0.27), or procedure-related complications or death between the two groups. CONCLUSIONS: Left and right trans-radial approach for primary PCI have similar in room procedural times, success rates, and comparable safety. Trans-radial PCI through either arm is a feasible and safe approach in patients with STEMI.

An automatic image processing algorithm for initiating and terminating intracoronary OFDI pullback.

Intracoronary optical frequency domain imaging (OFDI) provides high resolution, three-dimensional views of coronary artery microstructure, but requires a non-occlusive saline/contrast purge to displace blood for clear artery views. Recent studies utilized manual pullback initiation/termination based on real-time image observation. Automated pullback initiation/termination by real-time OFDI signal analysis would enable more efficient data acquisition. We evaluate the use of simple imaging parameters to automatically and robustly differentiate between diagnostic-quality clear artery wall (CAW) versus blood-obstructed fields (BOF). Algorithms are tested using intracoronary OCT human data retrospectively and intracoronary OFDI swine and human data prospectively. In prospective analysis of OFDI swine data, the sensitivity and specificity of the ratio of second and first moments (contrast parameter) were 99.6% and 97.2%, respectively. In prospective analysis of OFDI clinical data, the contrast parameter yielded 96.0% sensitivity and 94.5% specificity. Accuracy improved further by analyzing sequential frames. These results indicate the algorithm may be utilized with intracoronary OFDI for initiating and terminating automated pullback and digital data recording.

Performance of reduced bit-depth acquisition for optical frequency domain imaging.

High-speed optical frequency domain imaging (OFDI) has enabled practical wide-field microscopic imaging in the biological laboratory and clinical medicine. The imaging speed of OFDI, and therefore the field of view, of current systems is limited by the rate at which data can be digitized and archived rather than the system sensitivity or laser performance. One solution to this bottleneck is to natively digitize OFDI signals at reduced bit depths, e.g., at 8-bit depth rather than the conventional 12-14 bit depth, thereby reducing overall bandwidth. However, the implications of reduced bit-depth acquisition on image quality have not been studied. In this paper, we use simulations and empirical studies to evaluate the effects of reduced depth acquisition on OFDI image quality. We show that image acquisition at 8-bit depth allows high system sensitivity with only a minimal drop in the signal-to-noise ratio compared to higher bit-depth systems. Images of a human coronary artery acquired in vivo at 8-bit depth are presented and compared with images at higher bit-depth acquisition.

Recovery from anthracycline cardiomyopathy after long-term support with a continuous flow left ventricular assist device.

We report the clinical course of a 16-year-old girl in remission from non-Hodgkin's lymphoma who presented in cardiogenic shock due to a severe anthracycline cardiomyopathy. The patient was initially stabilized using central extracorporeal membrane oxygenation support, followed by conversion to a left ventricular assist device. Unexpected evidence of cardiac recovery 9 months after implant enabled device weaning during a 3-month period, culminating in successful device explantation 1 year after implant. The patient survives 18 months after explant in New York Heart Association class I, on conventional heart failure medical management and metabolic therapy.

Three-dimensional coronary artery microscopy by intracoronary optical frequency domain imaging.

OBJECTIVES: We present the first clinical experience with intracoronary optical frequency domain imaging (OFDI) in human patients. BACKGROUND: Intracoronary optical coherence tomography (OCT) is a catheter-based optical imaging modality that is capable of providing microscopic (approximately 7-microm axial resolution, approximately 30-microm transverse resolution), cross-sectional images of the coronary wall. Although the use of OCT has shown substantial promise for imaging coronary microstructure, blood attenuates the OCT signal, necessitating prolonged, proximal occlusion to screen long arterial segments. OFDI is a second-generation form of OCT that is capable of acquiring images at much higher frame rates. The increased speed of OFDI enables rapid, 3-dimensional imaging of long coronary segments after a brief, nonocclusive saline purge. METHODS: Volumetric OFDI images were obtained in 3 patients after intracoronary stent deployment. Imaging was performed in the left anterior descending and right coronary arteries with the use of a nonocclusive saline purge rates ranging from 3 to 4 ml/s and for purge durations of 3 to 4 s. After imaging, the OFDI datasets were segmented using previously documented criteria and volume rendered. RESULTS: Good visualization of the artery wall was obtained in all cases, with clear viewing lengths ranging from 3.0 to 7.0 cm at pullback rates ranging from 5 to 20 mm/s. A diverse range of microscopic features were identified in 2 and 3 dimensions, including thin-capped fibroatheromas, calcium, macrophages, cholesterol crystals, bare stent struts, and stents with neointimal hyperplasia. There were no complications of the OFDI procedure. CONCLUSIONS: Our results demonstrate that OFDI is a viable method for imaging the microstructure of long coronary segments in patients. Given its ability to provide microscopic information in a practical manner, this technology may be useful for studying human coronary pathophysiology in vivo and as a clinical tool for guiding the management of coronary artery disease.