3 Clinical evidence

Summary of clinical evidence

3.1 The key clinical outcomes for the MiraQ system presented in the decision problem were:

  • incidence of graft failure

  • time to graft failure

  • peri- and postoperative clinical events associated with graft failure (including mortality)

  • frequency of the need for graft revision and changes in VeriQ measurements afterwards

  • the need for repeat coronary revascularisation procedures

  • long-term morbidity and mortality.

3.2 The evidence for the clinical effectiveness of the MiraQ system was based on 2 retrospective observational studies that examined surgical outcomes, and one comparative study that compared parameter values from the VeriQ system against another flowmeter. The studies were conducted in hospitals in Europe and Canada; there were none in the UK. All patients in the studies were treated by coronary artery bypass graft (CABG) surgery.

3.3 In a retrospective case study in Canada, Kieser et al. (2010) evaluated transit time flow measurement with the VeriQ system to detect technical errors in CABGs intra-operatively and to predict postoperative major adverse cardiac events. They assessed 1,000 arterial grafts in 336 consecutive patients. Three parameters of transit time flow (pulsatility index, flow and diastolic filling percentage) were measured in 990 (99%) of the grafts. A pulsatility index value of less than 5 was chosen as the principal measure of graft adequacy. In 82% of the patients (277 of 336), 93% of grafts (916 of 990) had a pulsatility index of less than or equal to 5. The remaining 74 (7%) grafts (in 59 patients, 18%) had a pulsatility index of greater than 5, but grafts were revised only when an abnormally high pulsatility index was accompanied by other indications of graft malfunction (abnormal electrocardiogram [ECG] changes, regional wall motion abnormality on transoesophageal echocardiography or haemodynamic compromise). On this basis, 20 grafts (in 14 patients, 4%) that were suspected to be problematic were revised.

3.4 For analysis of the findings, patients were divided into 2 groups: the 277 (82%) with at least one graft with a pulsatility index of less than 5, and 59 (18%) with at least one graft with a pulsatility index of greater than 5. Major adverse cardiac events (recurrent angina, perioperative myocardial infarction, postoperative angioplasty, re‑operation and/or perioperative death) occurred significantly more often in patients with a pulsatility index of greater than 5 (10 of 59, 17%) when compared with patients with a pulsatility index of less than 5 (15 of 277, 5.4%, p=0.005). Mortality following non-emergency surgery was significantly higher in the patient group with a pulsatility index of greater than 5 (5 of 54, 9%) than in the group with a pulsatility index of less than 5 (5 of 250, 2%, p=0.02).

3.5 Becit et al. (2007) evaluated the effect on the surgical results of CABG of detecting graft dysfunction by intraoperative transit time flow measurement using the VeriQ system in a
case–control study in Turkey. A pulsatility index of greater than 5 and diastolic filling percentage of less than 50% were used as the indicators of inadequate flow. The study compared the surgical outcomes for 2 matched series of consecutive patients whose operations were performed by the same surgeons. The study group (n=100) had transit time flow measurement during surgery and the control group (n=100) did not. Three per cent (9 of 303) of grafts in 9 (9%) patients in the study group were revised on the basis of abnormal transit time measurements, and after revision all flow values and flow patterns improved. No information was presented about graft revision in the control group. The incidence of intra-aortic balloon pump insertion for low cardiac output was significantly lower in the study group compared with the control group (1 of 100 versus 7 of 100, p<0.05). Also, perioperative myocardial infarction was significantly lower in the study group compared with the control group (0 of 100 versus 5 of 100, p<0.05). There was no statistically significant difference between the patient groups in intraoperative re-exploration for bleeding or deep sternal infection.

3.6 Nordgaard et al. (2010) investigated the variation in pulsatility index measurement between 2 different flowmeters (VeriQ and Transonic) and examined whether increasing filtering of the flowmeter signals influenced flow curves and pulsatility index. The VeriQ and Transonic flowmeters have default filter settings of 20 Hz and 10 Hz respectively. Flow patterns in 19 patients recorded simultaneously by both flowmeters during CABG surgery were analysed. This showed that the VeriQ system provided systematically higher pulsatility index values than the Transonic device (mean ± standard deviation [SD]: 2.7±1.2 versus 1.8±0.6 respectively, p<0.001).

3.7 Clinical evidence was also available from 26 studies on predecessor devices of the VeriQ system which were designed to evaluate the technical performance of devices, to compare them against the other methods of graft flow assessment such as intraoperative fluorescence imaging and postoperative X-ray angiography; and to assess the predictive value of abnormal transit time flow measurement on short and long-term clinical outcomes of CABG surgery. These were evaluated by the external assessment centre and, on balance, their opinion was that the studies showed that transit time flow measurements by the VeriQ system predecessor devices predicted short-term graft failure following CABG surgery and were easier to carry out than other methods. However, they also thought that assessing graft flow with transit time flow measurement alone may prompt unnecessary graft revision in some cases and there is inadequate evidence about whether transit time flow measurement predicts long-term patient survival.

Committee considerations

3.8 The committee recognised that graft dysfunction is a major determinant of perioperative morbidity and mortality after CABG. It was advised that the majority of graft failures in the perioperative period are due to technical imperfections which, if recognised, might be corrected at the time of surgery.

3.9 The committee noted that perioperative myocardial infarction resulting from graft failure may cause serious complications such as left ventricular dysfunction, ventricular arrhythmias and haemodynamic instability, which can necessitate prolonged intensive therapy unit stay. These complications may need interventions such as intra-aortic balloon pumping, coronary angiography and early reoperative CABG surgery. They may also lead to readmission to hospital.

3.10 The committee considered that the available evidence supported the claim that transit time flow measured by the VeriQ system can identify grafts that have reduced flow as a result of technical imperfections.

3.11 The committee recognised limitations in the available evidence. The main studies were observational, with potential for bias. The study by Kieser et al. (2010) investigated the VeriQ system on arterial grafts only, whereas in the NHS the majority of CABGs are vein grafts. Nevertheless, it judged that there was sufficient additional evidence relating to predecessor devices and sufficient expert advice to support the expectation that routinely revising all appropriate grafts on the basis of VeriQ measurements would result in reduced perioperative graft occlusions and consequent complications.

3.12 The committee noted from the study by Nordgaard et al. (2010) that pulsatility index values from the VeriQ system may differ from those of other machines and are influenced by filter settings. However, these differences are systematic and expected to be predictable.

3.13 The committee was advised that cardiac surgeons use a variety of methods to minimise and detect technical imperfections during CABG surgery but these may have limitations. On the basis of the evidence, it judged that the routine use of VeriQ, as an adjunct to other methods of assessment such as transoesophageal echocardiography, electrocardiography and clinical assessment, would be likely to detect technical problems in some grafts that appear to be satisfactory on clinical assessment alone.

3.14 The committee noted that recent joint guidelines on myocardial revascularisation issued by the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS) have recommended graft evaluation by objective methods before leaving the operating theatre after CABG surgery. These guidelines refer to flow less than 20 ml/minute and a pulsatility index of greater than 5 as predicting technically inadequate grafts that need revision before leaving the operating theatre.

3.15 The committee recognised that the clinical outcomes of CABG surgery have improved in the UK in the past 20 years and that complication rates are now very low. However it was advised that there is still a perioperative graft occlusion rate of 1–3%. The committee considered that the VeriQ system has potential to reduce this graft occlusion rate and so further reduce morbidity and mortality after CABG.

  • National Institute for Health and Care Excellence (NICE)