2.1

Patient selection and inclusion criteria

STEMI patients < 75 years of age admitted for PPCI with a total ST-segment deviation of more than 10 mm were eligible if they presented within 12 h of symptom onset and had a culprit lesion in the proximal or mid segment of a coronary artery whose reference diameter was ≥ 3.0 mm by visual estimation. Patients with previous myocardial infarction in the culprit area or with previous bypass surgery were excluded. Other exclusion criteria were cardiogenic shock, inability to obtain femoral access to the arterial circulation, tortuous coronary arteries, complex or long-lasting PPCI, inability to understand and give informed consent, severe concomitant disease or conditions with a life expectancy of less than one year, other known myocardial diseases such as cardiomyopathy or left ventricular hypertrophy, and pregnancy.

Oral informed consent was obtained by the interventional cardiologist immediately after successful PPCI. A more extensive written informed consent was obtained after the procedure, either in the catheterization laboratory or in the coronary care unit. Twenty patients were permitted to be included by the institutional review board of the Catharina Hospital Eindhoven.

2.2

PPCI Procedure

Patients received aspirin (300 mg) and a loading dose of clopidogrel, ticagrelor or prasugrel in the ambulance according to routine. Before angiography, all patients received heparin (5000 IU). Primary PCI was performed according to standard clinical practice. Use of thrombosuction or adjunctive pharmacology such as glycoprotein IIb/IIIa receptor inhibitors was left to the discretion of the operator. When, immediately following successful PPCI, the patient met the inclusion criteria and had given informed consent, measurements of distal coronary pressure and absolute coronary blood flow and resistance were performed as described below.

2.3

Invasive hemodynamic measurements

After successful PPCI of the culprit vessel, the guide wire was exchanged for one with distal pressure and temperature sensors (St Jude Medical, Minneapolis), whereafter distal coronary pressure, the index of microvascular resistance (IMR) and absolute flow were measured in the infarct-related artery as previously described in stable patients . Maximal hyperemia, and thereby minimal microvascular resistance, was induced by using 140 μg/kg/min of intravenous adenosine via a central venous catheter. Absolute minimal resistance was calculated by dividing distal pressure by the absolute flow and expressed in dyne.sec.cm-5 per gram of tissue in the area at risk.

For determination of IMR, small bolus injections of 3cm ³ of saline were given into the infarct-related artery as described by Fearon et al. . This was done three times at hyperemia. Mean transit time (Tmn) and Pd were measured simultaneously. IMR was calculated by multiplying the mean P _d by the hyperaemic T _mn . IMR was taken as the average of the three consecutive measurements at hyperemia as described before .

2.4

Measurement of absolute coronary blood flow

Thereafter, absolute flow was measured. A small specially designed infusion catheter with four side holes in its most distal part was advanced over the pressure guide wire through the Y-connector. The tip of the infusion catheter was placed in the stent, i.e. at the level of the previous occlusion, and the sensor was placed in the distal part of the infarct related artery. The infusion catheter was then connected to an infusion pump by a second Y connector, enabling continuous infusion of saline at a rate of 20–30 ml/min ( Fig. 1 ). The sensor-tipped guide wire was connected to the interface (Analyzer, St Jude Medical), and distal coronary pressure (P _d ) and temperature were displayed simultaneously. The exact infusion rate was chosen depending on the size of the artery and at the discretion of the operator. Next, a continuous recording was made of P _d and distal blood temperature after complete mixing during constant saline infusion ( Fig. 2 ). After a steady state had been achieved, the pressure/temperature sensor was pulled back into the infusion catheter so that the temperature of the saline (T _i ) at the location of the most proximal side hole could be measured ( Fig. 2 ). Using the technology of continuous infusion of saline at a low rate, absolute hyperaemic blood flow (Q _b ) can be calculated by the infusion rate of saline (Q _i ), temperature of the infused saline (T _i ) and distal blood temperature after complete mixing (T), using the following equation:

Set-up for measuring absolute coronary blood flow during catheterization using the technology of continuous saline infusion at a low rate.

A guide wire with distal pressure and temperature sensors is positioned in the distal part of the coronary artery. Next, a special infusion catheter with four small side holes in the last 5 mm proximal to its tip is advanced over the guide wire. This catheter is designed to ensure adequate mixing of blood and saline and has to be placed in the coronary artery. The infusion catheter is connected to an infusion pump. The distance between the distal tip of the infusion catheter and the position of the pressure/temperature sensor must be 3–6 cm. The sensor-equipped guide wire can then be connected to the interface for recording pressure and temperature (Analyzer; St Jude Medical Systems).

Absolute hyperaemic coronary blood flow (Q _b ) can be calculated by the infusion rate (Q _i ), temperature of the infused saline (T _i ) and distal blood temperature after complete mixing (T). (See equation in text).

Example of absolute flow measurement by continuous thermodilution and saline infusion in a STEMI patient. On the left, blood temperature at steady state hyperaemia (T _b ) is set to zero (corresponding to normal blood temperature). Next, saline infusion is started (arrow) at the location of the previous occlusion (stent) and temperature T in the distal coronary artery after complete mixing is recorded during steady state infusion. Finally, the sensor is pulled back into the tip of the infusion catheter (asterisk) to measure the temperature of the infused saline (T _i ). Absolute flow is then easily calculated according to the equation. These measurements can be continued for an arbitrary time and are completely operator independent. Notice that aortic pressure (P _a ) via the guiding catheter and distal coronary pressure (P _d ) via the guide wire’s pressure sensor are also measured. Notice also that withdrawal of the pressure sensor into the infusion catheter is marked by the sudden increase of the pressure signal.

The factor 1.08 corrects for the differences in specific heat between blood and saline. The protocol of absolute flow measurement was performed again at hyperemia after an interval of 5 min. The exact position of the sensor-tipped wire during measurements was documented on cine-angiography to make sure that the same position was chosen at the second exam 5 days later. All data were analyzed off line. Blood flow was expressed as ml/min and by adding the area at risk from CMR, blood flow per gram of tissue was calculated in ml/min/g for the area at risk.

After three to five days, control angiography of the infarct-related artery was performed followed by measurements of FFR, IMR and absolute flow using exactly the same position of the wire and infusion catheter as in the first procedure.

2.5

Cardiovascular magnetic resonance (CMR)

CMR was performed 3–5 days after the index procedure, preferably on the same day as the second invasive procedure. CMR was performed on either of two 1.5 T systems: Siemens or Magnetom Vision. Cine images were acquired on a 1.5 T scanner (Ingenia CV, Release 4.1.3.0 Philips Medical Systems, Best, The Netherlands) with electrocardiographic gating.

All subjects were placed in a supine position and short-axis, four-chamber, two-chamber and 3-chamber views were acquired during an end expiratory breath hold. Left ventricular function was assessed by a standard steady-state free precession technique (repetition time 3.3 ms, echo time 70 ms, flip angle 60 degrees, slice thickness 8 mm, slice gap 0 mm). An example of a mid LV short-axis image is shown in Fig. 3 .

Corresponding mid-ventricular short-axis slices in a single patient with an occlusion of the left anterior descending coronary artery. The endocardium is traced in red and the epicardium is traced in green. Left: The myocardium at risk is traced in white on the T2-weighted CMR image. Right: The infarcted region is traced in yellow/pink on the late gadolinium enhanced (LGE) CMR image. Within the infarct a hypointense region (dashed red line) can be seen without the presence of gadolinium, representing an area of no-reflow or microvascular obstruction.

For determination of the area at risk, we obtained short-axis slices covering the whole ventricle using a T2-weighted triple inversion recovery breath-hold pulse sequence (repetition time 2000 ms, echo time 70 ms, flip angle 90 degrees, slice thickness 8 mm, slice gap 0 mm).

All CMR images were analyzed using the freely available software Segment v 1.8 http://segment.heiberg.se (Heiberg et al. Bmc med imaging 10: 1, 2010).

The left ventricular (LV) mass was assessed on the cine images by manual tracing of the endocardial and epicardial borders with exclusion of the papillary muscles.

The AR was derived from the T2-weighted imaging and defined as the total amount of hyperintensive myocardium in all short-axis slices and expressed as a percentage of LV mass. All endocardial and epicardial tracings were performed by two observers blinded to the clinical data. They had to agree and provide the final percentage of the area at risk. Offline recalculation was done to obtain the AR and LV mass in grams.

2.6

Statistical analysis

Data are presented as mean ± standard deviation (SD), or median and interquartile range (IQR), as appropriate. Flow was expressed as ml/min/g. Resistance was expressed as dyne.sec.cm-5/g. IMR was expressed as dimensionless index (arbitrary units). Due to the maximal vasodilated state of the coronary circulation, a linear relationship was assumed to exist between perfusion pressure and blood flow . To compare the multiple measurements of flow over time within the same patient at different perfusion pressures, pressures were normalized to the initial aortic pressure (P _a ) as proposed by Fearon et al. . IMR values at the initial measurement in the hyperacute phase of STEMI were divided in two groups, high and low, separated by the median value.

For evaluation of absolute flow and resistance over time within the same patient, each patient was his own control after normalization for aortic pressure. For comparison of flow and resistance between different patients, AR by CMR was used to calculate flow in ml/min/g of tissue, by dividing absolute flow and resistance by the mass of the AR. Differences between groups were assessed by the paired t-test for continuous data with a normal distribution. Otherwise, the nonparametric Wilcoxon rank-sum test was used.

2.1

Patient selection and inclusion criteria

STEMI patients < 75 years of age admitted for PPCI with a total ST-segment deviation of more than 10 mm were eligible if they presented within 12 h of symptom onset and had a culprit lesion in the proximal or mid segment of a coronary artery whose reference diameter was ≥ 3.0 mm by visual estimation. Patients with previous myocardial infarction in the culprit area or with previous bypass surgery were excluded. Other exclusion criteria were cardiogenic shock, inability to obtain femoral access to the arterial circulation, tortuous coronary arteries, complex or long-lasting PPCI, inability to understand and give informed consent, severe concomitant disease or conditions with a life expectancy of less than one year, other known myocardial diseases such as cardiomyopathy or left ventricular hypertrophy, and pregnancy.

Oral informed consent was obtained by the interventional cardiologist immediately after successful PPCI. A more extensive written informed consent was obtained after the procedure, either in the catheterization laboratory or in the coronary care unit. Twenty patients were permitted to be included by the institutional review board of the Catharina Hospital Eindhoven.

2.2

PPCI Procedure

Patients received aspirin (300 mg) and a loading dose of clopidogrel, ticagrelor or prasugrel in the ambulance according to routine. Before angiography, all patients received heparin (5000 IU). Primary PCI was performed according to standard clinical practice. Use of thrombosuction or adjunctive pharmacology such as glycoprotein IIb/IIIa receptor inhibitors was left to the discretion of the operator. When, immediately following successful PPCI, the patient met the inclusion criteria and had given informed consent, measurements of distal coronary pressure and absolute coronary blood flow and resistance were performed as described below.

2.3

Invasive hemodynamic measurements

After successful PPCI of the culprit vessel, the guide wire was exchanged for one with distal pressure and temperature sensors (St Jude Medical, Minneapolis), whereafter distal coronary pressure, the index of microvascular resistance (IMR) and absolute flow were measured in the infarct-related artery as previously described in stable patients . Maximal hyperemia, and thereby minimal microvascular resistance, was induced by using 140 μg/kg/min of intravenous adenosine via a central venous catheter. Absolute minimal resistance was calculated by dividing distal pressure by the absolute flow and expressed in dyne.sec.cm-5 per gram of tissue in the area at risk.

For determination of IMR, small bolus injections of 3cm ³ of saline were given into the infarct-related artery as described by Fearon et al. . This was done three times at hyperemia. Mean transit time (Tmn) and Pd were measured simultaneously. IMR was calculated by multiplying the mean P _d by the hyperaemic T _mn . IMR was taken as the average of the three consecutive measurements at hyperemia as described before .

2.4

Measurement of absolute coronary blood flow

Thereafter, absolute flow was measured. A small specially designed infusion catheter with four side holes in its most distal part was advanced over the pressure guide wire through the Y-connector. The tip of the infusion catheter was placed in the stent, i.e. at the level of the previous occlusion, and the sensor was placed in the distal part of the infarct related artery. The infusion catheter was then connected to an infusion pump by a second Y connector, enabling continuous infusion of saline at a rate of 20–30 ml/min ( Fig. 1 ). The sensor-tipped guide wire was connected to the interface (Analyzer, St Jude Medical), and distal coronary pressure (P _d ) and temperature were displayed simultaneously. The exact infusion rate was chosen depending on the size of the artery and at the discretion of the operator. Next, a continuous recording was made of P _d and distal blood temperature after complete mixing during constant saline infusion ( Fig. 2 ). After a steady state had been achieved, the pressure/temperature sensor was pulled back into the infusion catheter so that the temperature of the saline (T _i ) at the location of the most proximal side hole could be measured ( Fig. 2 ). Using the technology of continuous infusion of saline at a low rate, absolute hyperaemic blood flow (Q _b ) can be calculated by the infusion rate of saline (Q _i ), temperature of the infused saline (T _i ) and distal blood temperature after complete mixing (T), using the following equation:

Stay updated, free articles. Join our Telegram channel

Join