European Journal of Cardiovascular Medicine

Coronary artery bypass graft (CABG) surgery outcomes have significantly improved over the last 50 years1, with this treatment remaining the optimal treatment for those with complex multivessel disease.2 Intraoperative graft patency is a primary determinant of the short- and long-term success of CAGB surgery.3 While coronary artery angiography (CAG) is the gold-standard approach used to assess graft patency, it can be an inconvenient and invasive procedure when conducted intraoperatively.

As such, intraoperative graft function is most often assessed based upon transit time flow measurement (TTFM) values, which have the potential to significantly improve CABG procedure quality and patient clinical outcomes.6 TTFM is typically used to evaluate intraoperative graft patency in accordance with guidelines published in 20104, which additional support from the 2018 ESC/EACTS Guidelines on myocardial revascularization that provided a class-IIa recommendation for the use of TTFM for intraoperative graft assessment.5

While clinical results following CABG are generally undisputed, there are patients in which graft occlusion can occur resulting in the inevitable recurrence of symptoms, the need for readmis-sion to hospital and coronary re-intervention and possibly even death While the mid-term and long-term graft failure are attributed to intimal hyperplasia, the peri-operative outcomes are directly linked to anastomotic quality of CABG. Consequently, it becomes imperative to determine the anastomotic quality so that problematic grafts can be identified and revised intra-operatively. Although most surgeons believe it to be a rare occurrence, the incidence of peri-operative graft failure has been estimated to be from 5 to 11%.7

TTFM is based on the principle that ultrasound waves passing from transducer to receiver will have a time delay or “transit time”. A coronary graft is placed into a flow probe in a perpendicular fashion between two ultrasonic transducers, which can also act as receivers, and a single reflector. Ultrasonic signals are then transmitted from the proximal transducer to the reflector and redirected to the distal transducer. The same signal redirection occurs from the more distal transducer to the more proximal. The time delay between transducer to reflector to receiver is the transit-time and is determined by the flow velocity in the graft. The flow meter then accurately and precisely calculates the flow volume in the graft based on the provided transit time.8

The aim of the present study was to optimize the off pump coronary artery bypass grafting by the use of graft flow meter based on transit time flow principle and revision of grafts when the values are abnormal and there is associated haemodynamic instability as seen on TEE, ECG changes and rise in Trop I levels.

75 patients undergoing isolated off-pump CABG at LPS Institute of Cardiology and Cardiac Surgery were included in the study from January 2017 to June 2018. The study was conducted on all the cases who were admitted for CABG and who met the inclusion criteria. The data was collected preoperatively from detailed history, clinical examination and investigations (laboratory and radiological, including angiography and 2 D echocardiography), intraoperatively by graft flow measurements and TEE findings, and in the immediate post-operative period by cardiac enzyme (Trop I) levels.

INCLUSION CRITERIA

1. Age > 18 years
2. Patients with class 1 indications for CABG were included in the surgery

Class 1 indications for CABG as given by American College of Cardiology (ACC) and American Heart Association (AHA) are as follows:

• Left main coronary artery stenosis > 50%
• Stenosis of proximal LAD and proximal LCX > 70%
• 3- vessel disease in asymptomatic patients or those with mild or stable angina
• 3- vessel disease with proximal LAD stenosis in patients with poor LV function
• 1- or            2-            vessel     disease   and         a              large       area        of            viable myocardium in high risk area in patients with stable angina
• 70% proximal LAD stenosis with either ejection fraction < 50% or demonstrabl ischaemia on noninvasive testing
• Other indications for CABG are:
• Disabling angina (Class I)
• Ongoing ischaemia in the setting of a non- ST segment elevation MI that is unresponsive to medical therapy (Class I)
• Poor left ventricular function but with viable, nonfunctioning myocardium above the anatomic stenosis that can be revascularised

3. Patients undergoing isolated CABG surgery (no concurrent cardiac surgery or carotid surgery)

EXCLUSION CRITERIA

1. Age > 80 years
2. Unstable angina or myocardial infarction < 2 days or < 7 days prior to surgery, respectively
3. Ejection fraction < 35%
4. Previous cardiac surgery
5. Additional surgery required
6. Patients having significant carotid artery disease
7. Renal dysfunction
8. Hepatic dysfunction
9. NYHA class IV

END POINT OF THE STUDY

The primary end point of the study was to assess the patency of graft intra operatively and to verify it by correlating it with intra operative ECG, TEE findings and in the immediate post operative period by measurement of Trop I levels. Secondary end point is to define the cut off values of mean graft flow and pulsatility index (PI) in Indian population.

METHOD

A written informed consent was taken from all the patients. All the risks of surgery were explained. The patients included in the study were studied for graft patency using following modalities:-

• TTFM- using graft flow meter
• TEE (Trans Esophageal Echocardiography)
• Cardiac enzymes- Trop I

OPERATIVE TECHNIQUE

A median sternotomy was performed in all the patients, except in cases of SVD in whom LIMA had to be grafted to LAD, thoracotomy was performed. All procedures were done off- pump (beating heart).

After median sternotomy, left internal mammary artery (LIMA) was harvested and simultaneously, saphenous vein or radial artery harvesting was done in whom multiple grafts were planned. The choice of conduits and/or construction of composite grafts was based on surgeon preferences rather than fixed criteria. Arterial conduits were harvested with minimal trauma (non-skeletonized IMA) and were treated with papaverine solution prior to use.

GRAFTS USED IN THE STUDY

1. Internal Mammary Artery
2. Long Saphenous Vein
3. Radial Artery

Target vessel name, type of graft, flow rate in ml/min and flow curves were recorded. Pulsatility Index (PI) was calculated according to the following formula:

PI =         (max flow – min flow)

Mean flow

The patency of grafts was assessed using three variables:

1. Mean graft flow
2. Pulsatility index(PI)
3. Diastolic flow curve

For a patent graft, the flow curve show a small backflow during early systole and a predominantly forward flow during diastole. Mean flow is largely dependent on quality of the native coronary artery, and low mean flow can be expected in fully patent anastomoses whenever the target territory has a poor run off. Mean flow should be cautiously interpreted, as its value is not necessarily a good indicator of the quality of the anastomosis. PI is a good indicator of the flow pattern and consequently, of the quality of anastomosis. The PI value should ideally be between 1 and 5. The possibility of a technical error in anastomosis increases with higher PI values.

Intra – operative trans esophageal echocardiography (TEE) was performed in all the patients undergoing off-pump coronary artery bypass grafting. Left ventricular function and regional wall motion abnormalities (RWMA) were observed before and after the graft anastomoses. Cardiac muscle expresses the troponin T and I isoforms and are more specific than creatine kinase(CK) values for myocardial injury and owing to their high sensitivity, may rise when creatine kinase MB (CK-MB) concentrations do not. Although Trop T is more specific than Trop I, the assays for Trop I are more readily available, so Trop I has been used in our study to detect any PMI.

Baseline Trop I levels were noted on the morning of the surgery and to note any PMI, Trop I measurement was done within 24 hours of surgery. The data was recorded on the predesigned proforma and was compiled and analyzed statistically.

Table 1: Baseline characteristics

Out of 75 patients undergoing off pump CABG, 67 were males and 8 were females. The majority of patients (37.3%) were in the age group of 51 – 60 years followed by 32% patients in the age group of 61 - 70 years. Out of the total 182 conduits grafted in 75 patients, LIMA as a conduit was used in 64 grafts, RSVG was used in 116 grafts and RA was used in 2 grafts.

Table 2: Co-morbidities and pattern of vessel involvement in patients undergoing OPCABG

Out of the 75 patients 18 were suffering from Diabetes, 28 from hypertension, 12 were both diabetic as well as hypertensive, 3 had previous PTCA, 5 were suffering from COPD. Out of the total 75 patients 46 had triple vessel disease, 22 had double vessel disease and 7 had single vessel disease. 6 had significant LMCA disease. Thus, the majority (61%) of the patients undergoing off-pump CABG(OPCABG) had involvement of all the 3 vessels. LAD was involved in all the patients.

Table 3: Distribution of type of grafts and their respective coronary territories

A total of 185 normal graft flow variables were studied. Grafts, both arterial as well as venous, were analysed for flows and PI values to the right and the left coronary territories.

Table 4: Comparison of normal graft flow variables between Right & Left coronary artery territories

It was observed that pattern of flow in both the left as well as right coronary territory was mainly diastolic. The mean flow with standard deviation in the left coronary territory was 35.54 + 16.35 ml/min and in the right coronary territory was 31.05 +15.12 ml/min with a p value of 0.4 which is not significant. The Pulsatility index (PI) in the left coronary territory was 1.99 + 0.75 and in right coronary territory was 1.94 + 0.81 with a p value of 0.06 which is not significant.

Table 5: Comparison of normal graft flow to LAD by LIMA and SVG

Mean flows and mean PI for LAD were compared between LIMA and SVG conduits and it was observed that mean flow with standard deviation using LIMA as conduit was 40.42 + 17.79 ml/min whereas in SVG conduit it was 28.8 + 14.77 ml/min and the p value was 0.4 which is not significant. Mean PI with standard deviation in LIMA conduit was 2.03 + 0.77 and in the SVG conduit was 1.9 + 0.74 with a p value of 0.05 which is statistically not significant.

Table 6: Obstruction and mean flow and PI in suboptimal grafts

A total of 4 grafts showed suboptimal flows and raised PI and these grafts were revised. Problems encountered were LIMA dissection, kinking, poor native coronary runoff and anastomotic stenosis at the heel. LIMA graft was revised by placing the anastomosis beyond the dissection. Kinking was due to extra length of the saphenous vein graft and the graft was shortened. There was problem with the native coronary artery (RCA) in one graft and the anastomosis was revised by making a y – graft to PDA. In the graft in which there was anastomotic stenosis at the heel, the anastomosis was revised. In the grafts that were revised, mean flows significantly increased from 7.25 + 4.8 ml/min to 30.25 + 8.7 ml/min (p< 0.05). The PI significantly decreased after correction from 7.1 + 1.7 to 2.35 + 0.36 (p< 0.05).

Table 7: Comparison of mean flow and PI between patent and suboptimal grafts

Mean graft flow of 34.41 + 16.32 ml/min in patent grafts was not significantly more than that of mean flow of 7.25 + 4.8 ml/min in suboptimal grafts (p >0.05). The PI in suboptimal grafts was 6.8 + 0.79 which was significantly more than that in patent grafts which was 1.96 + 0.76 (p<0.05).

Despite the trend towards minimally invasive procedures, coronary artery bypass graft surgery (CABG) still remains the most common cardiac surgery performed worldwide.9 from its infancy in the 1950s till today, CABG has undergone many developments, both technically and clinically. With improvements in intraoperative technique and perioperative care, CABG is now being offered to a more broad patient profile with lesser complications and major adverse events. Coronary artery bypass grafting (CABG) is defined as “open- heart surgery in which a section of a blood vessel is grafted from the aorta to the coronary artery to bypass the blocked section of the coronary artery and improve the blood supply to the heart.”

The pathophysiology of coronary artery disease was established in 1876 by Adam Hammer when he postulated that angina (imbalance of coronary supply and demand) was caused by interruption of coronary blood supply and that myocardial infarction occurred after the occlusion of at least one coronary artery.10

There is a marked difference in prevalence of coronary artery disease between gender.11-14 Among middle-aged people, coronary artery disease is 2 to 5 times more common in men than in women, and this sex ratio varies between populations.14 Of the 75 patients who underwent OPCABG for coronary artery disease in our study the majority of the patients (89%) were male. Most of the patients were predominantly between 51-70 years of age with most of the patients between 51-60 years of age, followed by the age-groups 61-70 years and 41-50 years respectively.

In our study, it was observed that pattern of flow in both the left as well as right coronary territory was mainly diastolic. The mean flow with standard deviation in the left coronary territory was 35.54 + 16.35 ml/min and in the right coronary territory was 31.05 + 15.12 ml/min. The Pulsatility index (PI) in the left coronary territory was 1.99 + 0.75 and in right coronary territory was 1.94 + 0.81. Kim et al in 2005 examined 58 patients who underwent total arterial off-pump CABG with intraoperative TTFM assessment.15 their study revealed that the flow patterns of patent grafts as measured by TTFM were different between right and left coronary territories. In the left coronary territory mean graft flow was 34.1 + 18.3 ml/min with PI of 2.4 + 1.3 whereas in the right coronary territory, mean graft flow was 25.7 + 12.6 ml/min and PI was 3. 1 + 1.6. In 2012, Basel Harahsheh assessed 436 patients undergoing CABG for intraoperative graft flow patency using transit time flowmetry machine.16 there were a total of 1394 grafts in 436 patients. MGF for LAD system was 33.4 + 5.3 ml/min with a PI of 2.4 + 0.4, while for the LCX system, a mean flow of 33.4 + 5.3 l/min with a PI of 3.5 + 0.7 was observed. For the right coronary system, a flow of 38.4 + 5.9 ml/ min with a PI of 2.6 + 0.6 was reported.

In our study, we observed that mean graft flow with LIMA as conduit was 40.42 + 17.79 ml/min whereas in SVG conduit it was 28.8 + 14.77 ml/min. Mean PI with standard deviation in LIMA conduit was 2.03 + 0.77 and in the SVG conduit it was 1.9+ 0.74. Therefore, there is no significant difference in the graft flow variables between LIMA and SVG conduits to LAD. In 2005 Leong et al17 published their study which compared normal graft flow to LAD by LIMA and SVG and observed that mean flow was 39.6 + 21.9 ml/min for LAD to LIMA grafts, and for LAD to SVG was 35.5 + 19.9 ml/min. Average PI of LIMA-LAD grafts was 2.5 + 1.0 and that for SVG- LAD was 3.7+ 4.3. There were no statistically significant differences in mean flow or pulsatility index between arterial and vein grafts. Internal mammary grafts compared with SVGs did not show significant differences early after operation in mean blood flow or PI.

To correctly interpret TTFM, flow curves, PI, and mean flow values should be evaluated simultaneously. In a patent coronary graft, the hemodynamics are similar to those physiologically observed in the coronary circulation: blood flow should be mainly diastolic with minimal systolic peaks taking place during the is volumetric ventricular contraction (QRS complex). To have a correct interpretation of blood flow patterns, curves should always be coupled with the ECG tracing to differentiate the systolic from the diastolic component. The PI, expressed as an absolute number, is a good indicator of the blood flow pattern and, consequently, of the quality of the anastomosis. This number is obtained by dividing the difference between the maximum and the minimum flow by the value of the mean flow. In our experience, optimum PI should be between 1 and 5. The possibility of a technical error in the anastomosis increases for higher PI values.18

To improve the applicability of TTFM, flow patterns, PI values, flow values, and clinical findings (for example, ECG tracing, hemodynamic values) should always be evaluated simultaneously. Specific features should always be recognized in a flow curve. In patent grafts, flow curves should have a diastolic Pattern with a small component of negative systolic flow.  The flow in the coronary grafts follows the same hemodynamic rules as the flow in the native coronary arteries. During diastole, blood flows into the graft and is directed to the coronary artery; during systole, the coronary artery is compressed and retrograde blood flow is detected in the graft. If the anastomosis is stenotic, the flow curve becomes spiky and mainly systolic. In this situation the only flow through the graft is negative systolic flow since there is no perfusion of the coronary artery during diastole. The right coronary system follows different rules: a good quantity of blood flows in the right coronary during systole due to less compression of the epicardial vessels during right ventricular contraction. For this reason, whenever testing patent grafts to the right coronary system, a larger component of positive systolic flow may be recorded. Ironically, clinical experience has shown that absolute flow value per se is not a good indicator of the quality of the anastomosis and cannot justify graft revision. There are too many variables influencing absolute flow. Even though an absolute PI value has not been defined, we have empirically selected the limit of 5 on the basis of our clinical experience with TTFM. Di Giammarco and associates proposed a value of 2.5 as the limit PI above which an anastomosis should be revised. Again this value was derived from their clinical experience.

The present study concluded that transit time flow measurement is simple, reliable and easy to perform. Low flow and raised PI require reexploration of the anastomosis unless severe spasm of the conduit or poor runoff is strongly suspected. Redoing the distal anastomosis leads to significant improvement in flow and decreases pulsatility index in the presence of anastomotic failure. Mean graft flow of >10 ml/min can be considered satisfactory in Indian population where the native coronary size ranges between 1- 2mm , whereas in Western population it is between 3 to 4mm, cutoff value of >20 ml/min has been described. In this light, heamodynamic stability as assessed by intraoperative ECG and TEE, is important as low flow per se does not signify graft failure. Thus, graft failure can be defined based on the criteria of mean graft flow < 10 ml/min and PI > 5 with manly systolic pattern.

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