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Heart and Vascular Center, Semmelweis University, 68 Városmajor St, 1122, Budapest, HungaryMTA-SE Cardiovascular Imaging Research Group, Semmelweis University, 68 Városmajor St, 1122, Budapest, Hungary
Heart and Vascular Center, Semmelweis University, 68 Városmajor St, 1122, Budapest, HungaryMTA-SE Cardiovascular Imaging Research Group, Semmelweis University, 68 Városmajor St, 1122, Budapest, Hungary
Heart and Vascular Center, Semmelweis University, 68 Városmajor St, 1122, Budapest, HungaryMTA-SE Cardiovascular Imaging Research Group, Semmelweis University, 68 Városmajor St, 1122, Budapest, Hungary
Gottsegen National Cardiovascular Center, 29. Haller Street, 1096, Budapest, HungaryPhysiological Controls Research Center, University Research and Innovation Center, Óbuda University, 96/b Bécsi út, 1034, Budapest, Hungary
Heart and Vascular Center, Semmelweis University, 68 Városmajor St, 1122, Budapest, HungaryMTA-SE Cardiovascular Imaging Research Group, Semmelweis University, 68 Városmajor St, 1122, Budapest, Hungary
We aimed to evaluate whether invasive fractional flow reserve (FFRi) of non-infarction related (non-IRA) lesions changes over time in ST-elevation myocardial infarction (STEMI) patients. Moreover, we assessed the diagnostic performance of coronary CT angiography-derived FFR(FFRCT) following the index event in predicting follow-up FFRi.
Methods
We prospectively enrolled 38 STEMI patients (mean age 61.6 ± 9 years, 23.1% female) who underwent non-IRA baseline and follow-up FFRi measurements and a baseline FFRCT (within ≤10 days after STEMI). Follow-up FFRi was performed at 45–60 days (FFRi and FFRCT value of ≤0.8 was considered positive).
Results
FFRi values showed significant difference between baseline and follow-up (median and interquartile range (IQR) 0.85 [0.78–0.92] vs. 0.81 [0.73–0.90] p = 0.04, respectively). Median FFRCT was 0.81 [0.68–0.93]. In total, 20 lesions were positive on FFRCT. A stronger correlation and smaller bias were found between FFRCT and follow-up FFRi (ρ = 0.86,p < 0.001,bias:0.01) as compared with baseline FFRi (ρ = 0.68, p < 0.001,bias:0.04). Comparing follow-up FFRi and FFRCT, no false negatives but two false positive cases were found. The overall accuracy was 94.7%, with sensitivity and specificity of 100.0% and 90.0% for identifying lesions ≤0.8 on FFRi. Accuracy, sensitivity, and specificity were 81.5%, 93.3%, and 73.9%, respectively, for identifying significant lesions on baseline FFRi using index FFRCT.
Conclusion
FFRCT in STEMI patients close to the index event could identify hemodynamically relevant non-IRA lesions with higher accuracy than FFRi measured at the index PCI, using follow-up FFRi as the reference standard. Early FFRCT in STEMI patients might represent a new application for cardiac CT to improve the identification of patients who benefit most from staged non-IRA revascularization.
Around half of all ST-elevation myocardial infarction (STEMI) patients have non-infarction-related artery (non-IRA) disease detected by invasive coronary angiography (ICA).
According to recent trials, fractional flow reserve (FFR) guided intervention of non-IRA lesions might be superior to conservative therapy in preventing major adverse cardiac events (MACE).
Complete revascularisation versus treatment of the culprit lesion only in patients with ST-segment elevation myocardial infarction and multivessel disease (DANAMI-3—PRIMULTI): an open-label, randomised controlled trial.
Facing the complexity of ischaemic heart disease with intracoronary pressure and flow measurements: beyond fractional flow reserve interrogation of the coronary circulation.
Replacing baseline FFRi measurement with coronary CT angiography (CCTA) derived fractional flow reserve (FFRCT) would be a favorable alternative to define significant non-IRA lesions for staged revascularization. The accuracy of FFRCT in ischemia discrimination was rigorously validated in patients with chronic coronary syndrome.
Diagnosis of ischemia-causing coronary stenoses by noninvasive fractional flow reserve computed from coronary computed tomographic angiograms. Results from the prospective multicenter DISCOVER-FLOW (Diagnosis of Ischemia-Causing Stenoses Obtained via noninvasive Fractional Flow Reserve) study.
Diagnostic performance of noninvasive fractional flow reserve derived from coronary computed tomography angiography in suspected coronary artery disease: the NXT trial (Analysis of Coronary Blood Flow Using CT Angiography: next Steps).
However, we have limited information on the diagnostic value of FFRCT for predicting the need for non-IRA revascularization. Prior evidence suggests that FFRCT has moderate diagnostic accuracy for detecting an FFRi value of ≤0.8 one month after the index event.
We hypothesize that an FFRCT evaluation at hospital discharge after the acute event might better represent future FFRi values as vascular remodeling has not yet occurred. It could also outperform baseline FFRi measurements, and could improve decision-making by selecting appropriate patients for staged percutaneous coronary intervention (PCI) of non-IRA stenosis.
Therefore, in our study, we aimed to evaluate whether the non-IRA lesion's FFRi value changes between the index event and the follow-up evaluation in STEMI patients. Furthermore, we sought to assess the diagnostic accuracy of FFRCT as compared to the follow-up FFRi as the reference standard.
2. Methods
2.1 Study design, patient population
In the NeXt Generation PhEnotyping with Computed Tomography in Patients with Myocardial Infarction (XPECT-MI) study we prospectively enrolled hemodynamically stable patients with STEMI and non-IRA atherosclerotic plaques in a tertiary academic cardiology department.
The identification of the culprit lesion in STEMI patients was based on unequivocal ECG changes and plaque findings on ICA (including plaque burden, signs of plaque rupture/thrombotic occlusion). Whereas, the non-IRA lesion was identified based on diameter stenosis (30–90%). In the case of multiple non-IRA lesions the interventional cardiologist chose the non-IRA lesion with the highest diameter stenosis for staged ICA. Patients underwent baseline non-IRA FFRi measurement during the index PCI and an FFRCT within 10 days. Additionally, in 45–60 days, a follow-up ICA was carried out with repeated FFRi measurement. Patients with lesions of FFRi values ≤ 0.8 during follow-up measurements were treated with PCI.
2.2 The inclusion and exclusion criteria were the following
Inclusion: 1) above the age of 18, 2) symptoms of myocardial ischemia, presence of chest pain lasting ≥20 min within 24 h before enrollment, 3) electrocardiographic changes (ST-segment elevation of ≥1 mm in at least two extremity leads or ≥2 mm in at least two contiguous precordial leads or de novo left bundle-branch block),
4) the presence of at least one non-IRA lesion in the coronary tree on ICA, 5) informed consent obtained from the patient. Exclusions were as follows: 1) non-ST-segment myocardial infarction 2) hemodynamic instability during index event that prevents FFRi measurements, 3) prior myocardial infarction, 4) allergy to iodinated contrast material, 5) renal dysfunction (estimated glomerular filtration rate <30 ml/min/1,73 m3), 6) contraindications to β-blockers or nitroglycerin, 7) >35 kg/m2 body mass index (BMI).
We enrolled 54 consecutive patients in the trial after the inclusion and exclusion criteria evaluation. Subsequently, the HeartFlow core lab for FFRCT evaluation performed a quantitative criteria analysis. Additionally, seven patients were excluded because of inadequate image quality for FFRCT analysis and eight patients because of the stent implantations they received during the index event, which could have altered non-IRA FFRCT measurements (one patient was excluded due to a stent in the left main coronary artery (LM), and six patients because of multiple stents in the coronary tree). Overall, 38 STEMI patients were included in the analysis. The study flow chart is shown in Fig. 1.
Fig. 1Flow chart. During the PCI of the STEMI FFRi measurement was carried out of the non-IRA lesion if any was found. Within ten days, FFRCT was analyzed. A staged ICA was performed 45–60 after the index event. In case of the non-IRA lesion FFRi value was ≤0.8 a PCI was done. Abbreviations: AMI: acute myocardial infarction, BMI: body mass index, eGFR: estimated glomerular filtration rate, FFRCT: coronary CTA derived Fractional Flow Reserve, FFRi: invasive fractional flow reserve, LM: left main coronary artery, non-IRA: non-infarction related artery, non-STEMI: non-ST-elevation myocardial infarction, STEMI: ST-elevation myocardial infarction, PCI: percutaneous coronary intervention.
The study was approved by the local institutional and the national (Hungarian Institute of Pharmacy and Food Safety) (OGYÉI/-1420-4/2018) ethical committees. All procedures used in this study followed local and federal regulations and the Declaration of Helsinki. Written informed consent was obtained individually covering ICA and CCTA procedures and trail participation as well.
2.3 Demographics and comorbidities
Patients underwent detailed interviews evaluating cardiovascular risk factors, medical history, and medication at baseline and follow-up. Hypertensive patients were defined as those with systolic blood pressure values > 140 mmHg or diastolic blood pressure values > 90 mmHg or antihypertensive medication use. Diagnosis of diabetes mellitus (DM) was confirmed based on elevated plasma glucose levels (fasting plasma glucose ≥126 mg/dL; HbA1c ≥ 6.5%) or antidiabetic medication use or insulin therapy. Hyperlipidemia was classified as having elevated plasma cholesterol levels (total cholesterol >200 mg/dL) or using lipid-lowering treatment. Smoking was defined as prior tobacco use for at least one year. All ECG-s were evaluated to define the location and characteristics of the ST segment changes.
2.4 Invasive angiography and FFRi measurements
After PCI of the culprit lesion, if a non-IRA lesion was detected (stenosis severity 30–90%), intravenous adenosine was administered to achieve maximal hyperemia to measure non-IRA FFRi values. FFRi was measured using the OptoWire Deux FFRi pressure guidewire and OptoMonitor system (Opsens Inc., 750 bouls. du Parc Technologique, Quebec, QC G1P 4S3, Canada). A pressure wire was used to derive distal coronary and aortic pressure measurements during maximal hyperemia. The mean pressure was evaluated from the pressure signal (OptoMonitor™ Smart Integration). The measurements were carried out three times, and their mean values were given as FFRi. If more than one non-IRA lesion was detected, the most severe one was selected for FFRi analysis. All patients underwent follow-up non-IRA FFRi measurement 45–60 days after the index event, and staged PCI was performed if the FFRi was ≤0.8. A representative case is shown in Fig. 2.
Fig. 2A representative case demonstrating the role of FFRCT in detecting lesion-specific ischemia for the non-IRA lesions after STEMI. A representative case of a 63 years old male patient with 3 h STEMI. The patient has hypertension and type two diabetes. During ICA, an IRA lesion was found on the RCA and a non-IRA lesion on the LCX (A, B). The FFRi value of the LCX was 0,81. Three days later, CCTA was carried out; the FFRCT value was 0,63 (C). Forty-five days after the index event, another ICA and FFRi simulation in the non-IRA lesion was carried out. FFRi value was 0,65; hence the FFRCT values could better predict the follow-up FFRi values than the baseline FFRi measurement. Due to the positive follow-up, FFRi value PCI was carried out on the LCX (D). Abbreviations: FFRCT: coronary CTA derived fractional flow reserve, FFRi: invasive fractional flow reserve, ICA: invasive coronary angiography, IRA: Infarction Related Artery, LCX: left circumflex artery, non-IRA: non-infarction related artery, PCI: percutaneous coronary intervention, RCA: right coronary artery, STEMI: ST-elevation myocardial infarction.
We performed prospectively triggered CCTA (Philips iCT, Philips Healthcare, Best, The Netherlands) of all patients according to the Society of Cardiovascular Computed Tomography guidelines.
SCCT guidelines for the performance and acquisition of coronary computed tomographic angiography: a report of the society of cardiovascular computed tomography guidelines committee: endorsed by the North American society for cardiovascular imaging (NASCI).
If the heart rate exceeded 65 beats per minute, β-blocker was administered before the examination (if no contraindication was noted). In addition, all patients received sublingual nitroglycerine (0.8 mg) before CCTA. After premedication, if the heart rate was still above 70 beats per minute, patients were scanned during the systolic phase (37–43% of the R–R interval). Image acquisition was performed during the end-diastolic or end-systolic phase of the cardiac cycle, depending on heart rate. Based on patient anthropometrics, tube voltage was set to 100–120 kVp and tube current to 200–360 mAs. 0.5 mm slice thickness with iterative reconstructions was used for axial image reconstructions.
The images of the patients were sent to a core laboratory for FFRCT analysis (HeartFlow Inc., Redwood City, California, software version 1.4 approved by the American Food and Drug Administration).
Diagnostic performance of noninvasive fractional flow reserve derived from coronary computed tomography angiography in suspected coronary artery disease: the NXT trial (Analysis of Coronary Blood Flow Using CT Angiography: next Steps).
A quantitative anatomical 3-dimensional model was generated for every patient who met all the analysis requirements. Under simulated maximal hyperemic conditions, coronary blood flow and pressure were calculated based on computational fluid dynamics principles.
Diagnostic performance of noninvasive fractional flow reserve derived from coronary computed tomography angiography in suspected coronary artery disease: the NXT trial (Analysis of Coronary Blood Flow Using CT Angiography: next Steps).
Continuous variables are presented as mean and standard deviation or median and interquartile range, whereas categorical parameters are presented as the frequency with percentages. Wilcoxon signed-rank test was used in pairwise comparisons, including baseline FFRi, follow-up FFRi or FFRCT. We used the Spearman correlation test and the Bland-Altman plot to evaluate the correlation between baseline FFRi and FFRCT values and follow-up FFRi values and FFRCT values and to define the agreement and bias between modalities.
All analyses were conducted using GraphPad Prism 6 and SPSS v. 22 software. The statistical analysis was based on the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) and the Standard for Reporting of Diagnostic Accuracy Studies (STARD) guidelines. A 2-sided p-value smaller than 0.05 was considered statistically significant.
3. Results
3.1 Patient characteristics at the index event
The baseline characteristics are summarized in Table 1. The mean age was 61.6 ± 9 years, the mean BMI was 28.8 ± 4.8 kg/m2, and 8 (23.1%) of the patients were female.
Table 1Patient characteristics.
Parameters
Total n = 38
Clinical characteristics
Age [years]
61.6 ± 9.0
BMI [kg/m2]
28.8 ± 4.8
Male sex
30 (76.9)
Hypertension
29 (74.4)
Diabetes
8 (20.5)
Dyslipidemia
6 (15.4)
Smoking
9 (23.1)
Stroke
1 (2.6)
Arrhythmia
0 (0.0)
Prior cancer diagnosis
0 (0.0)
Peripheral vascular disease
0 (0.0)
Positive family history
2 (5.5)
Left ventricular EF on echocardiography
53.0 ± 5.6
Prior medication usage:
stain
4 (10.5)
ASA
2 (5.3)
ADP inhibitor
0 (0.0)
ACE inhibitor
12 (31.6)
ARB inhibitor
5 (13.2)
β-blocker
7 (18.4)
Continuous variables are described as mean ± SD, whereas categorical variables are represented as frequencies and percentages, n (%).
Abbreviations: ACE inhibitor: angiotensin-converting enzyme inhibitor, ADP inhibitor: adenosine-diphosphate inhibitor, ARB inhibitor: angiotensin II receptor inhibitor. ASA: acetylsalicylic acid, BMI: Body Mass Index, EF: ejection fraction.
Based on the primary ECG changes, 17 (44,7%) anterior, 20 (52,6%) inferior, and 1 (2,6%) posterior STEMI were diagnosed. All IRA lesions were treated with successfully performed primary PCI with good angiographic results (thrombolysis in myocardial infarction grade 3 flow). The locations of the non-IRA lesions were as follows: LM: 1 (2,6%), left anterior descending artery: 17 (39,5%), inter medius coronary artery: 4 (10,5%) left circumflex artery: 12 (18,4%), obtuse marginal coronary artery: 3 (7,9%) right coronary artery: 8 (21,1%). CCTA and ICA parameters are shown in Table 2.
Table 2Coronary CT angiography and invasive coronary angiography parameters.
Parameters
Total n = 38
Coronary CTA parameters
Heart rate [beats/min]
63.8 ± 8.5
Tube voltage [kVp]
- 100 kVp
1 (2.6)
- 120 kVp
37 (94.9)
Tube current [mAs]
302.2 ± 64.7
Contrast volume [mm3]
89.1 ± 5.2
Radiation dose of coronary CTA [mGy∗cm]
356.0 ± 225.2
Total effective dose [mSv]
6.6 ± 8.2
Baseline ICA parameters
Contrast volume [mm3]
168.4 ± 51.2
Radiation dose [mGy]
866.6 ± 629.3
Radiation time [min]
10.6 ± 5.1
Procedure time [min]
52.1 ± 90.0
Stent length [mm]
44.2 ± 19.9
Location of IRA based on ICA
LAD
17 (44.7)
LCX
3 (7.89)
RCA
18 (47.37)
Location of the non-IRA lesion based on ICA
LM
1 (2.63)
LAD
15 (39.47)
IM
4 (10.51)
LCX
7 (18.42)
OM
3 (7.89)
RCA
8 (21.05)
Non-IRA plaque stenosis severity on ICA
30–49% stenosis
17 (43.6)
50–69% stenosis
8 (20.5)
70–99% stenosis
13 (33.3)
Non-IRA PCI at follow-up
20 (51.3)
Follow-up ICA parameters
Contrast volume
98.4 ± 58.7
Radiation dose [mGy]
504.9 ± 526.5
Radiation time [min]
6.8 ± 6.1
Procedure time [min]
26.2 ± 16.7
Stent length [mm]
35.3 ± 19.9
Continuous variables are described as mean ± SD, whereas categorical variables are represented as frequencies and percentages, n (%).
Abbreviations: Coronary CTA: coronary CT angiography, ICA: invasive coronary angiography, IM: inter medius coronary artery, non-IRA: non-infarction related artery, LM: left main coronary artery, LAD: left anterior descending coronary artery, LCX: left circumflex coronary artery, kVp: kilovoltage peak, mAs: Milliampere-seconds, mGy: milligray, mSv: millisievert, OM: obtuse marginal coronary artery, PCI: percutaneous coronary intervention, RCA: right coronary artery.
Positive FFRi value was detected in 39.5% of the patients at baseline vs. 50.0% at follow-up. FFRi measurements showed a significant change in hemodynamics over time: median FFRi values at baseline and follow-up were 0.85 [0.78–0.92] vs. 0.81 [0.73–0.90] p = 0.04. A spaghetti plot depicting the temporal changes between baseline and follow-up FFRi is shown in Fig. 3. To display the overall change between baseline and follow-up FFRi and FFRCT a box-plot analysis was also calculated that is shown in Supplementary figure 1.
Fig. 3Temporal changes in FFRi and its relationship to FFRCT. Spaghetti plot of the temporal changes between baseline and follow-up non-IRA FFRi and baseline FFRCT and follow-up FFRi. We detected a significant reduction in median FFRi values at baseline and follow-up: median FFRi values and their IQR at baseline and follow-up were 0.85 [0.78–0.92] vs. 0.81 [0.73–0.90] p = 0.04. (left panel). The right panel depicts the relationship between baseline FFRCT to follow-up FFRi. The median FFRCT value was 0.81 [0.68–0.93]. The red lines represent the 0.8 cut-off FFRi and FFRCT values. The green lines display the median changes. Abbreviations: FFR: fractional flow reserve, FFRCT: coronary CTA derived fractional flow reserve, FFRi: invasive fractional flow reserve, non-IRA: non-infarction related artery. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)
3.3 FFRCT in STEMI patients and its relationship to FFRi
A median of 2.0 [1.00–5.30] days has passed between the baseline FFRi and FFRCT examinations, and a median of 51.0 [49.00–57.50] days between the FFRCT and follow-up FFRi examinations. The median FFRCT value was 0.81 [0.68–0.93]. FFRCT correlated strongly with both baseline and follow-up FFRi. The correlation was more robust with follow-up FFRi: inter-modality correlation coefficients were 0.68 (p < 0.001) with baseline FFRi and 0.86 (p < 0.001) with follow-up FFRi, respectively. When considering a baseline FFRi value of ≤0.8 as a reference for significant non-IRA lesions based on FFRCT, one patient had a false negative result, whereas the number of false positive cases was six. We detected an overall accuracy, sensitivity, and specificity of 81.5% (95% CI: [65.7%–92.3%]), 93.3% (95% CI: [68.1%–99.3%]), and 73.9% (95% CI: [51.6%–89.8%]), respectively. Comparing follow-up FFRi and FFRCT, no false negative case was detected, while two false positive cases were recorded. The overall accuracy of FFRCT as compared to the follow-up FFRi was 94.7% (95% CI: [82.3%–99.4%]) with a sensitivity and specificity of 100.0% (95% CI: [81.5%–100.0%]) and 90.0% (95% CI: [68.3%–98.8%]) for the identification of hemodynamically relevant lesions, respectively (Fig. 4.).
Fig. 4Correlation plots for FFRCT vs. FFRi. Scatter plot analysis of baseline FFRi and FFRCT and follow-up FFRi and FFRCT. FFRCT yielded better accuracy in detecting significant non-IRA lesions (≤0.8) on follow-up FFRi than the FFRi performed during the acute event. FFRCT saw no false negative cases with follow-up FFRi as a reference standard. Abbreviations: FFR: fractional flow reserve FFRCT: coronary CTA derived fractional flow reserve, FFRi: invasive fractional flow reserve, non-IRA: non-infarction related artery.
Based on Bland-Altman analysis, a mean bias of 0.04 was found between the baseline FFRi and FFRCT, with 95% of limits of agreement between −0.14 – 0.22. In comparison, a stronger association was found between follow-up FFRi and FFRCT, as the mean bias was 0.01 with a 95% limit of agreement between −0.14 and 0.16. (Fig. 5.).
Fig. 5Bland-Altman plots for FFRCT vs. FFRi. Bland-Altman plot of baseline FFRi and FFRCT values and follow-up FFRi and FFRCT values. A bias of 0.04 was found between the baseline FFRi and FFRCT (with 95% of limits of agreement between −0.14 – 0.22), while it decreased to 0.01 when the analysis was made for follow-up FFRi and FFRCT (with 95% limit of agreement between −0.14 and 0.16). Abbreviations: FFR: fractional flow reserve, FFRCT: coronary CTA derived fractional flow reserve, FFRi: invasive fractional flow reserve.
In our longitudinal observational cohort study, we prospectively evaluated the change in FFRi values between the index and follow-up FFRi measurements and the diagnostic accuracy of FFRCT values of non-IRA lesions in STEMI patients. The main findings of our study were: firstly, there was a significant change in non-IRA FFRi between baseline and follow-up at 45–60 days. Secondly, regarding overall accuracy, sensitivity, and specificity, FFRCT performed within ten days after the acute event had higher diagnostic accuracy than baseline FFRi in identifying follow-up FFRi positivity. Thirdly the mean bias of FFRCT vs. follow-up FFRi was smaller than FFRCT vs. baseline FFRi.
Prior investigations have reported that myocardial infarction triggers compensatory remodeling and hypertrophy of the non-IRA-related vasculature and myocardium.
Impact of microvascular obstruction on the assessment of coronary flow reserve, index of microcirculatory resistance, and fractional flow reserve after ST-segment elevation myocardial infarction.
These changes might be due to several factors, such as neurohormonal activation and the increased level of catecholamines, fibrogenic growth factors (cytokines and TGF-β), and endothelins.
Vascular remodeling as a response to injury during an acute event can alter FFRi values. Also, submaximal hyperemia due to the increased sympathetic tone and alterations in microcirculatory response to adenosine during the acute phase could influence FFRi assessment.
Facing the complexity of ischaemic heart disease with intracoronary pressure and flow measurements: beyond fractional flow reserve interrogation of the coronary circulation.
Our study found a significant change in FFRi at 45–60 days follow-up compared to the baseline measurements.
The appropriateness of intervening on non-IRA lesions during primary PCI and the effectiveness of using FFRi as a determinant are still being debated, owing to the contentious results of clinical studies. Notably, there is no I/A recommendation in current guidelines regarding the exact timing and completeness of the PCI.
The DANAMI3-PRIMULTI (Complete Revascularization versus Treatment of the Culprit Lesion Only in Patients with ST-Segment Elevation Myocardial Infarction and Multivessel Disease) study demonstrated that in STEMI patients with multivessel disease, the complete FFRi guided revascularization significantly decreased the risk of future MACE compared to the group with no further intervention after primary PCI.
Complete revascularisation versus treatment of the culprit lesion only in patients with ST-segment elevation myocardial infarction and multivessel disease (DANAMI-3—PRIMULTI): an open-label, randomised controlled trial.
These results were strengthened by the CompareAcute (Comparison Between FFR Guided Revascularization Versus Conventional Strategy in Acute STEMI Patients With MVD) trial as complete FFRi-guided revascularization in the acute phase reduced the risk of a composite cardiovascular outcome.
It is essential to highlight that instant multivessel PCI has several risks, such as volume overload and renal impairment due to the increased use of contrast material and further ischemia induction.
In addition, in these studies FFRi measurements were done two days after or at the time of the primary PCI; hence, they were affected by local edema and microvascular dysfunction with submaximal hyperemia after the administration of adenosine. Therefore, FFRi performed at an early stage may provide inaccurate flow measurements.
Moreover, other clinical trials seem to challenge the concept of complete revascularization and a conservative approach for treating non-IRA lesions is highly emphasized.
Culprit vessel only versus multivessel and staged percutaneous coronary intervention for multivessel disease in patients presenting with ST-segment elevation myocardial infarction: a pairwise and network meta-analysis.
The results from the BIOVASC trial indicated that complete revascularization during primary PCI was non-inferior to staged revascularization in reducing major adverse cardiovascular events at the 1-year mark after the initial procedure.
BIOVASC trial in perspective: complete revascularization strategies in patients presenting with acute coronary syndromes and multi-vessel coronary disease.
European Heart J. Acute Cardiovascular Care.2023; 12: 217-218
This finding is in line with the COMPLETE Timing sub-study, which showed that treating non-IRA lesions either during the index hospitalization or within 45 days after discharge had similar positive effects on both co-primary end points.
Furthermore, as FFRCT analysis is increasingly utilized for assessing coronary lesions, it might also serve as a reliable tool in the decision-making of non-IRA lesion revascularization after the index event.
The clinical value of FFRCT in patients with myocardial infarction, especially regarding non-IRA lesions, still has limited literature. Histopathological studies suggested that substantial changes occur in the vascular bed after an acute event, including vascular remodeling processes, endothelial function, and perivascular inflammation.
These vascular and myocardial changes after the index event might lead to changes in FFRi values in a later stage of recovery, presumably a few months after STEMI; therefore, the proper timing of FFRi measurement is still unknown. It is hypothesized that vessel wall hypertrophy develops at least one week after the myocardial infarction, while vascular growth in non-IRAs occurs even later, which could explain the results based on the one-month FFRCT values in a previous study.
Based on Gaur et al. the sensitivity (83%, p = 0.46) specificity (66%, p = 0.54) and accuracy (72%, p = 1.0) of FFRCT vs. FFRi were moderate. However, it was performed one month after STEMI, thus still during a transitional phase when microvascular remodeling mainly occurs. Based on our study, FFRCT values measured a few days after the index event might better represent the FFRi values 1.5–2 months after the index event than that of the FFRi measurements at baseline or one month after the index event
as computational flow dynamic models assume a normal vasodilator response.
Several studies demonstrated that CCTA could be considered a competitive or even a superior imaging technique to ICA as a gatekeeper in stable chest pain patients.
Coronary computed tomographic angiography as a gatekeeper to invasive diagnostic and surgical procedures: results from the multicenter CONFIRM (Coronary CT Angiography Evaluation for Clinical Outcomes: an International Multicenter) registry.
Stress myocardial perfusion imaging vs coronary computed tomographic angiography for diagnosis of invasive vessel-specific coronary physiology: predictive modeling results from the computed tomographic evaluation of atherosclerotic determinants of myocardial ischemia (CREDENCE) trial.
Diagnosis of ischemia-causing coronary stenoses by noninvasive fractional flow reserve computed from coronary computed tomographic angiograms. Results from the prospective multicenter DISCOVER-FLOW (Diagnosis of Ischemia-Causing Stenoses Obtained via noninvasive Fractional Flow Reserve) study.
Diagnostic performance of noninvasive fractional flow reserve derived from coronary computed tomography angiography in suspected coronary artery disease: the NXT trial (Analysis of Coronary Blood Flow Using CT Angiography: next Steps).
Noninvasive fractional flow reserve derived from computed tomography angiography for coronary lesions of intermediate stenosis severity: results from the DeFACTO study.
However, data on the clinical value of combined anatomical and functional CT strategy in acute settings are limited.
In the 1-year data of the ADVANCE (Assessing Diagnostic Value of Non-invasive FFRCT in Coronary Care) registry, FFRCT was evaluated in terms of clinical outcome among patients with stable angina. The registry showed a lower rate of events with less ICA and revascularization among patients with higher FFRCT values
Furthermore, in the SYNTAX III (A Randomized Study Investigating the Use of CT Scan and Angiography of the Heart to Help the Doctors Decide Which Method is the Best to Improve Blood Supply to the Heart in Patients With Complex Coronary Artery Disease) trial, FFRCT changed patients’ treatment decisions and the selection of vessels for PCI.
Impact of fractional flow reserve derived from coronary computed tomography angiography on heart team treatment decision-making in patients with multivessel coronary artery disease: insights from the SYNTAX III REVOLUTION trial.
Although these studies represented different, stable chest pain, study populations compared to our current analysis, these trials incorporated FFRCT in the decision-making and showed promising results. Using FFRCT measurement early after STEMI may provide better guidance regarding the need for staged PCI of non-IRA lesions than the FFRi measurement performed during the acute phase of STEMI. The reason may be that the FFRCT simulation assumes normal microvasculature. Therefore, FFRCT might better predict the FFRi value after cardiac recovery, as demonstrated in our patient cohort. FFRCT at baseline vs. follow-up in the post-STEMI setting should be evaluated in multicenter trials to better understand the clinical value of this new technique and the changes in FFRCT before and after the vascular remodeling process.
Despite the significant number of advantages favoring FFRCT, implementing this modality in clinical practice still has limitations. It requires high-image-quality CCTA scans and the post-processing time might be lengthy. Moreover, patients with LM or multiple stents in the analyzed vessels preclude an FFRCT simulation. However, these limitations can be tackled with the recent improvement of CCTA technology and improved machine learning models.
Diagnostic accuracy of a machine-learning approach to coronary computed tomographic angiography-based fractional flow reserve: result from the MACHINE consortium.
We acknowledge the limitations of our study. Firstly, we excluded a relatively large number of patients, which could introduce selection bias. Secondly, our study was underpowered to analyze patient outcomes. It is a single-center trial with a relatively small number of patients, and more extensive multicenter trials are warranted to reinforce the role of FFRCT in this patient population. In addition, the observation period with 45–60 days might have been too short of investigating relevant changes, although the optimal timing of FFRi measurements in non-IRA lesions is still controversial.
It is important to note that our results are hypothesis-generating. Therefore, further investigations should focus on defining the temporal changes in vasculature and FFRi and FFRCT values. Also, further studies are warranted to define the diagnostic value of FFRCT for the evaluation of non-IRA lesions after STEMI.
5. Conclusion
Non-invasive assessment of FFRCT after the acute event leads to better diagnostic performance for the identification of hemodynamically relevant non-IRA lesions as compared with baseline FFRi. FFRCT measurements might improve decision-making by selecting patients with STEMI and non-IRA atherosclerotic lesions for staged PCI. The early FFRCT in patients with STEMI might represent a new application for cardiac CT to improve the identification of patients who benefit most from staged non-IRA revascularization.
Funding
Project no. NVKP_16-1–2016-0017 (‘National Heart Program’) has been implemented with the support provided from the National Research, Development and Innovation Fund of Hungary, financed under the NVKP_16 funding scheme. The research was financed by the Thematic Excellence Programme (2020–4.1.1.-TKP2020) of the Ministry for Innovation and Technology in Hungary, within the framework of the Therapeutic Development and Bioimaging thematic programmes of the Semmelweis University. Melinda Boussoussou MD was supported by the ÚNKP-22-3-II-SE-51, New National Excellence Program of the Ministry for Innovation and Technology from the source of the National Research, Development and Innovation fund and by the EFOP-3.6.3-VEKOP-16-2017-00009 project fund. Dr. Drobni was supported by the ÚNKP-22-4-II-SE, New National Excellence Program of the Ministry for Innovation and Technology from the source of the National Research, Development and Innovation fund.
Declaration of competing interest
Campbell Rogers and Amy Collinsworth are HeartFlow employees, Dr. Leipsic serves as a consultant at HeartFlow.
Appendix A. Supplementary data
The following is/are the supplementary data to this article.
Complete revascularisation versus treatment of the culprit lesion only in patients with ST-segment elevation myocardial infarction and multivessel disease (DANAMI-3—PRIMULTI): an open-label, randomised controlled trial.
Facing the complexity of ischaemic heart disease with intracoronary pressure and flow measurements: beyond fractional flow reserve interrogation of the coronary circulation.
Diagnosis of ischemia-causing coronary stenoses by noninvasive fractional flow reserve computed from coronary computed tomographic angiograms. Results from the prospective multicenter DISCOVER-FLOW (Diagnosis of Ischemia-Causing Stenoses Obtained via noninvasive Fractional Flow Reserve) study.
Diagnostic performance of noninvasive fractional flow reserve derived from coronary computed tomography angiography in suspected coronary artery disease: the NXT trial (Analysis of Coronary Blood Flow Using CT Angiography: next Steps).
SCCT guidelines for the performance and acquisition of coronary computed tomographic angiography: a report of the society of cardiovascular computed tomography guidelines committee: endorsed by the North American society for cardiovascular imaging (NASCI).
Impact of microvascular obstruction on the assessment of coronary flow reserve, index of microcirculatory resistance, and fractional flow reserve after ST-segment elevation myocardial infarction.
Culprit vessel only versus multivessel and staged percutaneous coronary intervention for multivessel disease in patients presenting with ST-segment elevation myocardial infarction: a pairwise and network meta-analysis.
BIOVASC trial in perspective: complete revascularization strategies in patients presenting with acute coronary syndromes and multi-vessel coronary disease.
European Heart J. Acute Cardiovascular Care.2023; 12: 217-218
Coronary computed tomographic angiography as a gatekeeper to invasive diagnostic and surgical procedures: results from the multicenter CONFIRM (Coronary CT Angiography Evaluation for Clinical Outcomes: an International Multicenter) registry.
Stress myocardial perfusion imaging vs coronary computed tomographic angiography for diagnosis of invasive vessel-specific coronary physiology: predictive modeling results from the computed tomographic evaluation of atherosclerotic determinants of myocardial ischemia (CREDENCE) trial.
Noninvasive fractional flow reserve derived from computed tomography angiography for coronary lesions of intermediate stenosis severity: results from the DeFACTO study.
Impact of fractional flow reserve derived from coronary computed tomography angiography on heart team treatment decision-making in patients with multivessel coronary artery disease: insights from the SYNTAX III REVOLUTION trial.
Diagnostic accuracy of a machine-learning approach to coronary computed tomographic angiography-based fractional flow reserve: result from the MACHINE consortium.
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