Thrombus aspiration during primary percutaneous coronary intervention is associated with reduced myocardial edema, hemorrhage, microvascular obstruction and left ventricular remodeling

Sixty patients presenting to Sunnybrook Health Sciences Centre in Toronto, with STEMI between July 2009 and March 2011 were enrolled. The main inclusion criteria were patients that met the standard diagnostic criteria for STEMI [25]. All patients had undergone primary PCI as part of a regional program that triages patients with STEMI to our centre for early revascularization. Exclusion criteria included hemodynamic instability (defined as systolic blood pressure < 90 mmHg, use of inotropic agents or an intraortic balloon pump), significant arrhythmias, significant renal dysfunction (estimated glomerular filtration rate < 30 mL/min), and typical contraindications to CMR such as pacemakers and implantable cardioverter-defibrillators. We obtained written consent from all patients, and the study was approved by the ethics review board of Sunnybrook Health Sciences Centre.

All patients were pretreated prior to revascularization with aspirin 162 mg and clopidogrel 600 mg. Choice of anticoagulant (intravenous heparin or bivalirudin) and optional use of glycoprotein IIb/IIIa inhibitor were left to operator discretion. TA was performed with an Export Medtronic device (Medtronic Inc., Minneapolis, Minnesota) and its use was also left to operator discretion. Factors influencing the use of TA included target vessel size, degree of thrombus burden, no reflow phenomenon and clinical instability. Subsequently patients received aspirin, clopidogrel, beta-blockers, angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers and statins as per standard of care.

Thrombolysis In Myocardial Infarction (TIMI) flow grade, myocardial blush grade and thrombus score were estimated visually using previously described methods by 2 experienced observers who were blinded to use of TA [26‐28]. ST-segment resolution, defined as ≥70% reduction in the sum of the ST-segment elevation score between electrocardiograms obtained before primary PCI and immediately after the procedure, was also recorded [29].

Each patient was imaged at 2 time points: within 48 hours and 6 months post STEMI. Studies were performed on a 1.5 T clinical scanner (Signa Twinspeed HDx, GE Healthcare, Waukesha, WI) with commercially available CMR software, electrocardiographic triggering, 8-channel receive coil and breath holds at end-expiration. After performing a localizer scan, short-axis cine CMR (10-12 slices) was performed with a balanced steady-state-free-precession sequence (FIESTA, GE Healthcare) with the following parameters: repetition time = 3.7 ms and echo time = 1.6 ms, flip angle = 45°, slice thickness = 8 mm, acquisition matrix = 256 × 192, field of view = 35 cm, bandwidth = 125 kHz, 20 cardiac phases per slice.

Myocardial edema was assessed by T2 quantification using a previously validated free-breathing cardiac-gated spiral imaging sequence with T2 preparation [30, 31], 8-10 contiguous slices from base to apex and the following typical parameters: echo times = 2.9, 24.3, 88.2, 184.2 ms, 12 spiral interleaves with 4096 points each (16.4 ms duration), slice thickness = 6 mm, bandwidth = 125 kHz. Myocardial hemorrhage was assessed by T2* quantification using a cardiac-gated spoiled gradient echo sequence with multiple echoes, 8-10 contiguous slices from base to apex, and the following typical parameters: 8 echoes (1.4-12.7 ms), repetition time = 14.6 ms, flip angle = 30°, acquisition matrix = 128 × 128, 8 views-per-segment, slice thickness = 8 mm, bandwidth = 100 kHz [31]. All echoes for a single slice were acquired in a single breath hold. Finally, a breath-hold, contrast-enhanced T1-weighted inversion recovery gradient-echo sequence was used to depict the presence, location, and extent of myocardial infarction and MVO using the following parameters: repetition time/echo time = 5.4/2.5 ms, flip angle = 30°, 8-10 contiguous slices from base to apex, slice thickness = 8 mm, acquisition matrix = 192 × 128, field of view = 35 cm. The inversion time was manually adjusted to null signal from normal myocardium. Short axis images were obtained 10 minutes after intravenous administration of Gadolinium-diethylene triamine pentaacetic acid (0.2 mmol/kg; Gadovist, Bayer Healthcare, Wayne, NJ).

All cine CMR images were analyzed using QMass^® MR software (Medis, Netherlands), and the results were the consensus of a minimum of 2 experienced observers who were blinded to use of TA. Endocardial and epicardial borders were delineated on the end-diastolic and end-systolic phases of short-axis slices for quantification of left ventricular volumes, function, mass, and infarct segment systolic wall thickening. Measurements were indexed for body surface area. End-diastolic wall thickness was measured in the infarct segment as an indicator of myocardial edema in the acute phase and wall thinning in the chronic phase. Myocardial T2 and T2* maps were constructed by fitting signal intensities at each pixel with an exponential model for the given echo times. Hemorrhage was identified as an area of hypointensity on T2-weighted images within the infarcted segment. Infarct size was quantified in a contrast-enhanced T1-weighted image using the full-width-half-maximum technique as previously described [32] while MVO was identified as a region of hypoenhancement within the region of the hyperenhanced infarct, 10 minutes post contrast administration. Infarct size, hemorrhage, and MVO were expressed as a percentage of total myocardium. Data fitting for T2/T2* maps, infarct, hemorrhage and MVO size computation were performed with custom-written scripts developed in MATLAB^® (The Mathworks, Natick, MA). MVO was also recorded as a binary variable of being present or absent, based on the contrast-enhanced images [33].

Eighty-five patients with STEMI were screened, 25 patients were excluded and 60 patients were included in the study. Reasons for exclusion included severe renal insufficiency, claustrophobia, hemodynamic instability and presence of permanent pacemaker. Clinical characteristics of both the TA and NTA group are shown in Table 1 and appear to be well matched in both groups. No difference in symptom to balloon time or door to balloon time was observed between groups. Reasons for not using TA by the operators included minimal thrombus burden visualized on the coronary angiogram, small vessel size, or preserved distal flow throughout the procedure. Glycoprotein IIb/IIIa inhibitor use was similar in both groups (NTA 52% vs. TA 62.9%, p = 0.514).

TA was associated with more frequent final myocardial blush grade ≥ 2 (NTA 44% vs. TA 88.6%, p < 0.01) and ST-segment resolution (NTA 40% vs. TA 68.6%, p = 0.036) post primary PCI (Table 2). Final TIMI flow ≥ 2 was equivalent in both groups (NTA 96% vs. TA 97.1%, p = NS).

The initial CMR scan was performed at a mean of 34.4 hours post primary PCI and the second scan at a mean of 243 days post primary PCI in the overall group. Table 3 shows the CMR outcomes for both time points.

Figure 1 demonstrates the myocardial T2 and T2* maps along with late gadolinium enhancement (LGE) images in short-axis views from representative patients in the NTA and TA groups at 48 hours. In this acute phase, both measures of myocardial edema, i.e. infarct segment T2 (NTA 57.9 ms vs. TA 52.1 ms, p = 0.022) and infarct segment end-diastolic wall thickness (NTA 11.4 mm vs. TA 9.3 mm, p < 0.01), were lower in the TA group (Table 3). Infarct segment T2* was higher, indicative of reduced myocardial hemorrhage, in the TA group (NTA 29.3 ms vs. TA 37.8 ms, p = 0.007). MVO incidence was also lower in the TA group (NTA 88% vs. TA 54.3%, p = 0.013).

Figure 2 demonstrates the LVEDVI and LVESVI measurements along with LGE images in short-axis views from patients in both treatment groups at 6 months. Baseline LVEDVI, LVESVI, LVSVI, infarct segment systolic wall thickening, and left ventricular ejection fraction measurements were similar in both treatment groups. At 6 months, LVEDVI (NTA 91.9 ml/m2 vs. TA 68.3 ml/m2, p = 0.013) and LVESVI (NTA 52.1 ml/m2 vs. TA 32.4 ml/m2, p = 0.008) were lower in the TA group (Table 3). LVSVI (NTA 40.4 ml/m2 vs. TA 35.8 ml/m2, p = 0.30) and left ventricular ejection fraction (NTA 46.8% vs. TA 53.8%, p = 0.11) were equivalent in both groups. Infarct segment systolic wall thickening (NTA 3.5% vs. TA 74.8%, p = 0.003) and end diastolic wall thickness (NTA 4 mm vs. TA 5.7 mm, p = 0.008) were both greater in the TA group at 6 months.

This study represents a single-centre non-randomized experience with a limited number of patients. However, baseline demographic and angiographic characteristics appear to be well matched in our 2 study groups. In particular, time to reperfusion, culprit vessel distribution, thrombus burden, enzymatic infarct size and adjunctive glycoprotein IIb/IIIa inhibitor use were similar in both groups. The sample size is similar to published CMR studies that have investigated myocardial edema, myocardial hemorrhage and MVO in other clinical settings. TA use was left to operator discretion, which can lead to a selection bias that may impact outcomes. However, the lack of a trend towards a higher thrombus burden in the TA group suggests that most of the TA use was based on a routine use policy. Lastly, we used a surface coil which can decrease the sensitivity for detecting inferolateral edema and infarction with an opposite effect in the anteroseptal region, due to an inhomogeneous coil sensitivity profile.