John J. Graham

Characterization of Operator Learning Curve for Transradial Coronary Interventions

Background—Transradial percutaneous coronary intervention (TR-PCI) improves clinical outcomes compared to the transfemoral (TF) approach. However, inadequate training and experience has limited widespread adoption by interventional cardiologists. Methods and Results—Clinical and procedural characteristics for TR-PCI were prospectively collected from 1999 to 2008. To identify minimum case volume for optimum clinical benefit, single-vessel TR-PCI cases were chronologically ranked and stratified into 1 to 50, 51 to 100, 101 to 150 and 151 to 300 case volume groups for operators starting the TR approach at the study institution. Cases by operators with a >300 TR-PCI case volume comprised the control group. TR-PCI failure rates, contrast use, guide usage, and fluoroscopy time were compared among groups. A total of 1672 patients underwent TR-PCI by 28 operators. TR-PCI failure occurred in 4% and was higher in the 1 to 50 case volume group compared to the 51 to 100 (P=0.007) and control (P=0.01) groups. Contrast use was greater in the 1 to 50 group (180±79 mL) compared to the 151 to 300 (157±75 mL, P=0.02) and control (168±79 mL, P=0.05) groups. Fluoroscopy time was higher in the 1 to 50 group (15±10 minutes) compared to the 101 to 150 (13±10 minutes, P=0.04) and control (12±9 minutes, P=0.02) groups. Reasons for TR-PCI failure included spasm (38%), subclavian tortuousity (16%), poor guide support (16%), failed access (10%), and radial loop (7%). Case volume was significantly correlated with TR-PCI failure (&bgr;=−0.0076, P=0.0028), and odds of failure was reduced by 32% for each 50 increments in case volume. Conclusions—TR-PCI success depends on operator experience, and a case volume of ≥50 cases is required to achieve outcomes comparable to experienced operators. These findings have implications both for PCI operators looking to expand their skills and for defining standards for training.

Dual antiplatelet therapy in patients requiring urgent coronary artery bypass grafting surgery: A position statement of the Canadian Cardiovascular Society

UNLABELLED Acute coronary syndrome (ACS) guidelines recommend that most patients receive dual antiplatelet therapy with clopidogrel and acetylsalicylic acid (ASA) at the time of presentation to prevent recurrent ischemic events. Approximately 10% of ACS patients require coronary artery bypass grafting surgery (CABG) during the index admission. Most studies show that patients who receive ASA and clopidogrel within five days of CABG have an increase in operative bleeding. Current consensus guidelines recommend discontinuation of clopidogrel therapy at least five days before planned CABG to reduce bleeding-related events. However, high-risk individuals may require urgent surgery without delay, to reduce the risk of potentially fatal ischemic events. The present multidisciplinary position statement provides evidence- based recommendations for the optimal use of dual antiplatelet therapy to balance ischemic and bleeding risks in patients with recent ACS who may require urgent CABG. RECOMMENDATIONS 1. All ACS patients should be considered for dual antiplatelet therapy with ASA and clopidogrel at the earliest opportunity, despite the possibility of a need for urgent CABG. 2. For patients who have received clopidogrel and ASA, and require CABG: * Those at high risk of an early fatal event (eg, with refractory ischemia despite optimal medical treatment, and with high-risk coronary anatomy (eg, severe left main stenosis with severe right coronary artery disease), should be considered for early surgery without discontinuation of clopidogrel. * In patients with a high bleeding risk (eg, previous surgery, complex surgery) who are also at high risk for an ischemic event, consideration should be given to discontinuing clopidogrel for three to five days before surgery. * Patients at a lower risk for ischemic events (most patients) should have clopidogrel discontinued five days before surgery. 3. For patients who have CABG within five days of receiving clopidogrel and ASA, the risk of major bleeding and transfusion can be minimized by applying multiple strategies before and during surgery. 4. Patients who receive clopidogrel pre-CABG for a recent ACS indication should have clopidogrel restarted after surgery to decrease the risk of recurrent ACS. 5. For patients with a recent coronary stent, the decision to continue clopidogrel until the time of surgery or to discontinue will depend on the risk and potential impact of stent thrombosis. Restarting clopidogrel after CABG will depend on whether the stented vessel was revascularized, the type of stent and the time from stent implantation. Clopidogrel should be restarted when hemostasis is assured to prevent recurrent acute ischemic events.

Inversion‐recovery‐prepared SSFP for cardiac‐phase‐resolved delayed‐enhancement MRI

Delayed‐enhancement magnetic resonance imaging (DE‐MRI) can be used to visualize myocardial infarction (MI). DE‐MRI is conventionally acquired with an inversion‐recovery gradient‐echo (IR‐GRE) pulse sequence that yields a single bright‐blood image. IR‐GRE imaging requires an accurate estimate of the inversion time (TI) to null the signal from the myocardium, and a separate cine acquisition is required to visualize myocardial wall motion. Simulations were performed to examine the effects of a steady‐state free precession (SSFP) readout after an inversion pulse in the setting of DE‐MRI. Using these simulations, a segmented IR‐SSFP sequence was optimized for infarct visualization. This sequence yields both viability and wall motion images over the cardiac cycle in a single breath‐hold. Viability images at multiple effective TIs are produced, providing a range of image contrasts. In a study of 11 patients, IR‐SSFP yielded infarct sizes and left ventricular ejection fractions (LVEFs) similar to those obtained by IR‐GRE and standard SSFP, respectively. IR‐SSFP images yielded improved visualization of the infarct‐blood border because of the simultaneous nulling of healthy myocardium and blood. T  1* recovery curves were extracted from IR‐SSFP images and showed excellent qualitative agreement with theoretical simulations. Magn Reson Med 58:365–372, 2007.

Characterization of clopidogrel hypersensitivity reactions and management with oral steroids without clopidogrel discontinuation.

OBJECTIVES The purpose of this study was to characterize clopidogrel hypersensitivity and describe its successful management with oral steroids without clopidogrel discontinuation. BACKGROUND Hypersensitivity reactions to clopidogrel are poorly understood and present difficulty in management. METHODS Patients diagnosed with clopidogrel hypersensitivity after percutaneous coronary intervention underwent evaluation and received oral prednisone without clopidogrel discontinuation. Cutaneous testing was performed after completion of clopidogrel therapy for diagnosis and assessment of cross-reactivity. RESULTS Sixty-two patients representing 1.6% of the percutaneous coronary intervention population developed clopidogrel hypersensitivity during the study period. The mean age was 62 ± 11 years, 71% of patients were male, and 35% reported prior adverse drug reaction. Clopidogrel hypersensitivity manifested as generalized exanthema in 79%, localized skin reaction in 16%, and angioedema or urticaria in 5% of patients. Biopsy of affected areas demonstrated a lymphocyte-mediated delayed hypersensitivity reaction. Complete resolution of hypersensitivity reaction was observed in 61 patients (98%) with a short course of oral prednisone. Cutaneous testing confirmed delayed hypersensitivity reaction to clopidogrel in 34 (81%) and immediate hypersensitivity in 3 of 42 patients (7%) tested. Allergenic cross-reactivity was observed for ticlopidine in 10 (24%), prasugrel in 7 (17%), and both ticlopidine and prasugrel in 3 patients (7%). Histological examination showed lymphocyte-mediated hypersensitivity in abnormal patch test areas. CONCLUSIONS Clopidogrel hypersensitivity is manifested as generalized exanthema and is caused by a lymphocyte-mediated delayed hypersensitivity in most patients. This can be managed with oral steroids without clopidogrel discontinuation. Allergenic cross-reactivity with ticlopidine, prasugrel, or both is present in a significant number of patients with clopidogrel hypersensitivity.

MRI relaxation fluctuations in acute reperfused hemorrhagic infarction

MRI evaluations of intramyocardial hemorrhage in acute infarction have relied on T2 and T  2* shortening only. We propose a more comprehensive evaluation of hemorrhagic infarction based on the concept that fluctuations in T2 and T1 relaxation in acute reperfused infarction will reflect transient edema and hemoglobin oxidative denaturation to uncompartmentalized methemoglobin. Anteroapical infarction was created via percutaneous balloon in young swine (22–25 kg, N = 12). T2, T1, diastolic wall thickness (DWT), and the Gd‐DTPA partition coefficient (λ) were measured on days 0, 2, and 7. DWT was elevated at 1 hr postreperfusion (128% ± 53%, P = 0.0001), and alleviated on days 2 and 7 (48% ± 10%, P = 0.008; 53% ± 24%, P = 0.003). T2 and T1 elevations were coincident with early edema (ΔT2 = 55% ± 24%, P < 0.0001; ΔT1 = 27% ± 18%, P < 0.04). T2 and T1 were nearly normal on day 2 (ΔT2 = 8% ± 8%, P = 0.27; ΔT1 = 0% ± 1%, P = 0.65). On day 7, T2 increased while T1 decreased (ΔT2 = 27% ± 16%, P = 0.005; ΔT1 = −14% ± 10%, P = 0.02). λ was elevated by >150% at all time points (P ≤ 0.002). Histology verified hemorrhagic injury. T1 and T2 fluctuations are consistent with transient edema, as well as hemoglobin oxidative denaturation to decompartmentalized methemoglobin. This methodological development may broaden our understanding of hemorrhagic microvascular injury and improve its detection in clinical populations. Magn Reson Med, 2006.

Long-term tracking of bone marrow progenitor cells following intracoronary injection post-myocardial infarction in swine using MRI

Magnetic resonance imaging (MRI) can track progenitor cells following direct intramyocardial injection. However, in the vast majority of post-myocardial infarction (MI) clinical trials, cells are delivered by the intracoronary (IC) route, which results in far greater dispersion within the myocardium. Therefore, we assessed whether the more diffuse distribution of cells following IC delivery could be imaged longitudinally with MRI. In 11 pigs (7 active, 4 controls), MI was induced by 90-min balloon occlusion of the left anterior descending coronary artery. Seven (0) days [median (interquartile range)] following MI, bone marrow progenitor cells (BMCs) were colabeled with an iron-fluorophore and a cell viability marker and delivered to the left anterior descending coronary artery distal to an inflated over-the-wire percutaneous transluminal coronary angioplasty balloon. T2*-weighted images were used to assess the location of the magnetically labeled cells over a 6-wk period post-MI. Immediately following cell delivery, hypointensity characteristic of the magnetic label was observed in the infarct border rather than within the infarct itself. At 6 wk, the cell signal hypointensity persisted, albeit with significantly decreased intensity. BMC delivery resulted in significant improvement in infarct volume and ejection fraction (EF): infarct volume in cell-treated animals decreased from 7.1 +/- 1.5 to 4.9 +/- 1.0 ml (P < 0.01); infarct volume in controls was virtually unchanged at 4.64 +/- 2.1 to 4.39 +/- 2.1 ml (P = 0.7). EF in cell-treated animals went from 30.4 +/- 5.2% preinjection to 34.5 +/- 2.5% 6 wk postinjection (P = 0.013); EF in control animals went from 34.3 +/- 4.7 to 31.9 +/- 6.8% (P = 0.5). Immunohistochemical analysis revealed intracellular colocalization of the iron fluorophore and cell viability dye with the labeled cells continuing to express the same surface markers as at baseline. MRI can track the persistence and distribution of magnetically labeled BMCs over a 6-wk period following IC delivery. Signal hypointensity declines with time, particularly in the first week following delivery. These cells maintain their original phenotype during this time course. Delivery of these cells appears safe and results in improvement in infarct size and left ventricular ejection fraction.

Multicontrast late gadolinium enhancement imaging enables viability and wall motion assessment in a single acquisition with reduced scan times.

To determine the accuracy of multicontrast late enhancement imaging (MCLE) in the assessment of myocardial viability and wall motion compared to the conventional wall motion and viability cardiac magnetic resonance imaging (MRI) pulse sequences.

Reproducibility study for free-breathing measurements of pyruvate metabolism using hyperpolarized (13) C in the heart.

Spatially resolved images of hyperpolarized 13C substrates and their downstream products provide insight into real‐time metabolic processes occurring in vivo. Recently, hyperpolarized 13C pyruvate has been used to characterize in vivo cardiac metabolism in the rat and pig, but accurate and reproducible measurements remain challenging due to the limited period available for imaging as well as physiological motion. In this article, time‐resolved cardiac‐ and respiratory‐gated images of [1‐13C] pyruvate, [1‐13C] lactate, and 13C bicarbonate in the heart are acquired without the need for a breathhold. The robustness of these free‐breathing measurements is demonstrated using the time‐resolved data to produce a normalized metric of pyruvate dehydrogenase and lactate dehydrogenase activity in the heart. The values obtained are reproducible in a controlled metabolic state. In a 60‐min ischemia/reperfusion model, significant differences in hyperpolarized bicarbonate and lactate, normalized using the left ventricular pyruvate signal, were detected between scans performed at baseline and 45 min after reperfusion. The sequence is anticipated to improve quantitative measurements of cardiac metabolism, leading to feasible validation studies using fewer subjects, and potentially improved diagnosis, serial monitoring, and treatment of cardiac disease in patients. Magn Reson Med 69:1063–1071, 2013.

Correlation of late gadolinium enhancement MRI and quantitative T2 measurement in cardiac sarcoidosis

To investigate the potentially improved detection and quantification of cardiac involvement using novel late‐gadolinium‐enhancement (LGE) cardiac magnetic resonance imaging (MRI) and quantitative T2 measurement to achieve better myocardial tissue characterization in systemic sarcoidosis.

Relationship between time to invasive assessment and clinical outcomes of patients undergoing an early invasive strategy after fibrinolysis for ST-segment elevation myocardial infarction: a patient-level analysis of the randomized early routine invasive clinical trials

OBJECTIVES This study investigated the relationship between time to invasive assessment and outcomes among ST-segment elevation myocardial infarction patients randomized to early angiography after fibrinolysis. BACKGROUND The optimal timing of coronary angiography after fibrinolysis and the association with clinical outcomes is uncertain. METHODS Patient-level data from 6 randomized trials, with a median time to angiography <12 h after fibrinolysis, were pooled. The primary endpoint was 30-day death or reinfarction. The key secondary endpoint was in-hospital major bleeding. The relationship between fibrinolysis to angiography time and symptom onset to angiography time with outcomes was studied using 2- and 4-h intervals, respectively, and in multivariable models. RESULTS Among 1,238 patients, the median fibrinolysis to angiography time was 165 min, and the median symptom onset to angiography time was 5.33 h. The primary and key secondary endpoints occurred in 5.7% and 4.7%, respectively. These main endpoints did not vary significantly with increasing fibrinolysis to angiography time. Early angiography (<2 h) after fibrinolysis was not associated with increased bleeding. Recurrent ischemia increased with increasing fibrinolysis to angiography time (3.7% to 7.9%, p for trend = 0.02). Thirty-day and 1-year death/reinfarction and 30-day recurrent ischemia increased significantly with increasing symptom onset to angiography time. Neither fibrinolysis to angiography time nor symptom onset to angiography time was an independent predictor of the primary endpoint. Only symptom onset to angiography time was an independent predictor of 1-year death/reinfarction (hazard ratio: 1.07, 95% confidence interval: 1.02 to 1.12, p = 0.01). CONCLUSIONS Very early angiography (<2 h) after fibrinolysis was not associated with an increased risk of 30-day death/reinfarction or in-hospital major bleeding, and angiography within 4 h after fibrinolysis was associated with reduced 30-day recurrent ischemia. A shorter symptom onset to angiography time (<4 h) was associated with reduced 30-day and 1-year death/reinfarction and 30-day recurrent ischemia. In the current environment of regional networks of 24/7 primary percutaneous coronary intervention (PCI) centers, the clinical implication of these findings is that patients initially treated with fibrinolysis should also be promptly transferred to the nearest PCI center for immediate angiography and PCI. (Early Percutaneous Coronary Intervention [PCI] After Fibrinolysis Versus Standard Therapy in ST Segment Elevation Myocardial Infarction [STEMI] Patients; NCT01014182).