Impact of sex on myocardial perfusion following percutaneous coronary intervention of chronic total coronary occlusions.

OBJECTIVES: We sought to investigate the impact of sex on myocardial perfusion changes following chronic total coronary occlusion (CTO) percutaneous coronary intervention (PCI) as measured by [15O]H2O positron-emission tomography (PET) perfusion imaging. BACKGROUND: CTO PCI has been associated with an increase in myocardial perfusion, yet females are less likely to undergo revascularization. As such, data on the impact of sex on myocardial perfusion following CTO PCI is scarce. METHODS: A total of 212 patients were prospectively enrolled and underwent CTO PCI combined with [15O]H2O PET perfusion imaging prior to and 3 months after PCI. Hyperemic myocardial blood flow (hMBF, mL·min-1·g-1) and coronary flow reserve (CFR) allocated to the CTO territory were quantitatively assessed. RESULTS: This study comprised 34 (16 %) females and 178 (84 %) males. HMBF at baseline did not differ between sexes. Females showed a higher increase in hMBF than males (Δ1.34 ± 0.67 vs. Δ1.06 ± 0.74, p = 0.044), whereas post-PCI hMBF was comparable (2.59 ± 0.85 in females vs. 2.28 ± 0.84 in males, p = 0.052). Female sex was independently associated with a higher increase in hMBF after correction for clinical covariates. CFR increase after revascularization was similar in females and males (Δ1.47 ± 0.99 vs. Δ1.30 ± 1.14, p = 0.711). CONCLUSIONS: The present study demonstrates a greater recovery of stress perfusion in females compared to males as measured by serial [15O]H2O PET imaging. In addition, a comparable increase in CFR was found in females and males. These results emphasize the benefit of performing CTO PCI in both sexes. CLINICAL PERSPECTIVE: What is new? What are the clinical implications?

The impact of coronary revascularization on vessel-specific coronary flow capacity and long-term outcomes: a serial [15O]H2O positron emission tomography perfusion imaging study.

AIMS: Coronary flow capacity (CFC) integrates quantitative hyperaemic myocardial blood flow (hMBF) and coronary flow reserve (CFR) to comprehensively assess physiological severity of coronary artery disease (CAD). This study evaluated the effects of revascularization on CFC as assessed by serial [15O]H2O positron emission tomography (PET) perfusion imaging. METHODS AND RESULTS: A total of 314 patients with stable CAD underwent [15O]H2O PET imaging at baseline and after myocardial revascularization to assess changes in hMBF, CFR, and CFC in 415 revascularized vessels. Using thresholds for ischaemia and normal perfusion, vessels were stratified in five CFC categories: myocardial steal, severely reduced CFC, moderately reduced CFC, minimally reduced CFC, and normal flow. Additionally, the association between CFC increase and the composite endpoint of death and non-fatal myocardial infarction (MI) was studied. Vessel-specific CFC improved after revascularization (P < 0.01). Furthermore, baseline CFC was an independent predictor of CFC increase (P < 0.01). The largest changes in ΔhMBF (0.90 ± 0.74, 0.93 ± 0.65, 0.79 ± 0.74, 0.48 ± 0.61, and 0.29 ± 0.66 mL/min/g) and ΔCFR (1.01 ± 0.88, 0.99 ± 0.69, 0.87 ± 0.88, 0.66 ± 0.91, and -0.01 ± 1.06) were observed in vessels with lower baseline CFC (P < 0.01 for both). During a median follow-up of 3.5 (95% CI 3.1-3.9) years, an increase in CFC was independently associated with lower rates of death and non-fatal MI (HR 0.43, 95% CI 0.19-0.98, P = 0.04). CONCLUSION: Successful revascularization results in an increase in CFC. Furthermore, baseline CFC was an independent predictor of change in hMBF, CFR, and subsequently CFC. In addition, an increase in CFC was associated with a favourable outcome in terms of death and non-fatal MI.

Impact of percutaneous coronary intervention of chronic total occlusions on absolute perfusion in remote myocardium.

BACKGROUND: Revascularisation of a chronic total coronary occlusion (CTO) impacts the coronary physiology of the remote myocardial territory. AIMS: This study aimed to evaluate the intrinsic effect of CTO percutaneous coronary intervention (PCI) on changes in absolute perfusion in remote myocardium. METHODS: A total of 164 patients who underwent serial [15O]H2O positron emission tomography (PET) perfusion imaging at baseline and three months after successful single-vessel CTO PCI were included to evaluate changes in hyperaemic myocardial blood flow (hMBF) and coronary flow reserve (CFR) in the remote myocardium supplied by both non-target coronary arteries. RESULTS: Perfusion indices in CTO and remote myocardium showed a positive correlation before (resting MBF: r=0.84, hMBF: r=0.75, and CFR: r=0.77, p<0.01 for all) and after (resting MBF: r=0.87, hMBF: r=0.87, and CFR: r=0.81, p<0.01 for all) CTO PCI. Absolute increases in hMBF and CFR were observed in remote myocardium following CTO revascularisation (from 2.29±0.67 to 2.48±0.75 mL·min-1·g-1 and from 2.48±0.76 to 2.74±0.85, respectively, p<0.01 for both). Improvements in remote myocardial perfusion were largest in patients with a higher increase in hMBF (ß 0.58, 95% CI: 0.48-0.67, p<0.01) and CFR (ß 0.54, 95% CI: 0.44-0.64, p<0.01) in the CTO territory, independent of clinical, angiographic and procedural characteristics. CONCLUSIONS: CTO revascularisation resulted in an increase in remote myocardial perfusion. Furthermore, the quantitative improvement in hMBF and CFR in the CTO territory was independently associated with the absolute perfusion increase in remote myocardial regions. As such, CTO PCI may have a favourable physiologic impact beyond the intended treated myocardium.

Defining the prognostic value of [15O]H2O positron emission tomography-derived myocardial ischaemic burden.

AIMS: Myocardial ischaemic burden (IB) is used for the risk stratification of patients with coronary artery disease (CAD). This study sought to define a prognostic threshold for quantitative [15O]H2O positron emission tomography (PET)-derived IB. METHODS AND RESULTS: A total of 623 patients with suspected or known CAD who underwent [15O]H2O PET perfusion imaging were included. The endpoint was a composite of death and non-fatal myocardial infarction (MI). A hyperaemic myocardial blood flow (hMBF) and myocardial flow reserve (MFR)-derived IB were determined. During a median follow-up time of 6.7 years, 62 patients experienced an endpoint. A hMBF IB of 24% and MFR IB of 28% were identified as prognostic thresholds. Patients with a high hMBF or MFR IB (above threshold) had worse outcome compared to patients with a low hMBF IB [annualized event rates (AER): 2.8% vs. 0.6%, P < 0.001] or low MFR IB [AER: 2.4% vs. 0.6%, P < 0.001]. Patients with a concordant high IB had the worst outcome (AER: 3.1%), whereas patients with a concordant low or discordant IB result had similar and low AERs of 0.5% and 0.9% (P = 0.953), respectively. Both thresholds were of prognostic value beyond clinical characteristics, however, only the hMBF IB threshold remained predictive when adjusted for clinical characteristics and combined use of the hMBF and MFR thresholds. CONCLUSION: A hMBF IB ≥24% was a stronger predictor of adverse outcome than an MFR IB ≥28%. Nevertheless, classifying patients according to concordance of IB result allowed for the identification of low- and high-risk patients.

Comparison Between the Performance of Quantitative Flow Ratio and Perfusion Imaging for Diagnosing Myocardial Ischemia.

OBJECTIVES: This study compared the performance of the quantitative flow ratio (QFR) with single-photon emission computed tomography (SPECT) and positron emission tomography (PET) myocardial perfusion imaging (MPI) for the diagnosis of fractional flow reserve (FFR)-defined coronary artery disease (CAD). BACKGROUND: QFR estimates FFR solely based on cine contrast images acquired during invasive coronary angiography (ICA). Head-to-head studies comparing QFR with noninvasive MPI are lacking. METHODS: A total of 208 (624 vessels) patients underwent technetium-99m tetrofosmin SPECT and [15O]H2O PET imaging before ICA in conjunction with FFR measurements. ICA was obtained without using a dedicated QFR acquisition protocol, and QFR computation was attempted in all vessels interrogated by FFR (552 vessels). RESULTS: QFR computation succeeded in 286 (52%) vessels. QFR correlated well with invasive FFR overall (R = 0.79; p < 0.001) and in the subset of vessels with an intermediate (30% to 90%) diameter stenosis (R = 0.76; p < 0.001). Overall, per-vessel analysis demonstrated QFR to exhibit a superior sensitivity (70%) in comparison with SPECT (29%; p < 0.001), whereas it was similar to PET (75%; p = 1.000). Specificity of QFR (93%) was higher than PET (79%; p < 0.001) and not different from SPECT (96%; p = 1.000). As such, the accuracy of QFR (88%) was superior to both SPECT (82%; p = 0.010) and PET (78%; p = 0.004). Lastly, the area under the receiver operating characteristics curve of QFR, in the overall sample (0.94) and among vessels with an intermediate lesion (0.90) was higher than SPECT (0.63 and 0.61; p < 0.001 for both) and PET (0.82; p < 0.001 and 0.77; p = 0.002), respectively. CONCLUSIONS: In this head-to-head comparative study, QFR exhibited a higher diagnostic value for detecting FFR-defined significant CAD compared with perfusion imaging by SPECT or PET.

Adenosine single-photon emission computed tomography-derived transient ischemic dilatation and ejection fraction reserve fail to predict multivessel coronary artery disease.

Next to myocardial perfusion, single-photon emission computed tomography (SPECT) also allows for the assessment of nonperfusion parameters such as transient ischemic dilatation (TID) and a reduction of ejection fraction (EF) with stress imaging. This study aimed to evaluate the diagnostic value of TID and EF reserve for the detection of significant multivessel coronary artery disease (CAD). A total of 206 patients with suspected stable CAD prospectively underwent gated stress-rest Tc-tetrofosmin SPECT and invasive coronary angiography with routine fractional flow reserve (FFR) measurements, irrespective of imaging results. Left ventricular volumes, TID, and EF reserve were assessed and compared with FFR-defined severity of CAD. According to FFR, 92 (45%) patients had significant CAD, whereas 25 (12%) showed 2-vessel disease (VD) and 22 (11%) showed 3-VD. With an increasing extent of CAD, TID values and EF reserve did not change significantly (P=0.07 and 0.42 for trend, respectively). Conversely, absolute left ventricular volumes and EF differed significantly among groups of CAD severity (P<0.01 for all trends). SPECT-derived TID and EF reserve did not differ between patients with high-risk CAD (3-VD) and low risk or no significant CAD. Therefore, the present results advocate exerting caution when using these ancillary findings in clinical practice.

Diagnostic Value of Transluminal Attenuation Gradient for the Presence of Ischemia as Defined by Fractional Flow Reserve and Quantitative Positron Emission Tomography.

OBJECTIVES: The aim of this study was to investigate the incremental diagnostic value of transluminal attenuation gradient (TAG), TAG with corrected contrast opacification (TAG-CCO), and transluminal diameter gradient (TDG) over coronary computed tomography angiography (CTA)-derived diameter stenosis alone for the identification of ischemia as defined by both the invasive reference standard fractional flow reserve (FFR) and the noninvasive reference standard quantitative positron emission tomography (PET). BACKGROUND: In addition to anatomic information obtained by coronary CTA, several functional CT parameters have been proposed to identify hemodynamically significant lesions more accurately, such as TAG, TAG-CCO, and more recently TDG. However, clinical validation studies have reported conflicting results, and a recent study has suggested that TAG may be affected by changes in vessel diameter. METHODS: Patients with suspected coronary artery disease underwent coronary CTA and [15O]H2O PET followed by invasive coronary angiography with FFR of all major coronary arteries. TAG, TAG-CCO, and TDG were assessed, and the incremental diagnostic value of these parameters over coronary CTA-derived diameter stenosis alone for ischemia as defined by PET (hyperemic myocardial blood flow ≤2.30 ml/min/g) and FFR (≤0.80) was determined. RESULTS: A total of 557 (91.9%) coronary arteries of 201 patients were included for analysis. TAG, TAG-CCO, and TDG did not discriminate between vessels with or without ischemia as defined by either PET or FFR. Furthermore, these parameters did not have incremental diagnostic accuracy over coronary CTA alone for the presence of ischemia as defined by PET and FFR. There was a significant correlation between TDG and TAG (r = 0.47; p < 0.001) and between TDG and TAG-CCO (r = 0.37; p < 0.001). CONCLUSIONS: TAG, TAG-CCO, and TDG do not provide incremental diagnostic value over coronary CTA alone for the presence of ischemia as defined by [15O]H2O PET and/or FFR. The lack of diagnostic value of contrast enhancement-based flow estimations appears related to coronary luminal dimension variability.

Comparison of Coronary CT Angiography, SPECT, PET, and Hybrid Imaging for Diagnosis of Ischemic Heart Disease Determined by Fractional Flow Reserve.

Importance: At present, the choice of noninvasive testing for a diagnosis of significant coronary artery disease (CAD) is ambiguous, but nuclear myocardial perfusion imaging with single-photon emission tomography (SPECT) or positron emission tomography (PET) and coronary computed tomography angiography (CCTA) is predominantly used for this purpose. However, to date, prospective head-to-head studies are lacking regarding the diagnostic accuracy of these imaging modalities. Furthermore, the combination of anatomical and functional assessments configuring a hybrid approach may yield improved accuracy. Objectives: To establish the diagnostic accuracy of CCTA, SPECT, and PET and explore the incremental value of hybrid imaging compared with fractional flow reserve. Design, Setting, and Participants: A prospective clinical study involving 208 patients with suspected CAD who underwent CCTA, technetium 99m/tetrofosmin-labeled SPECT, and [15O]H2O PET with examination of all coronary arteries by fractional flow reserve was performed from January 23, 2012, to October 25, 2014. Scans were interpreted by core laboratories on an intention-to-diagnose basis. Hybrid images were generated in case of abnormal noninvasive anatomical or functional test results. Main Outcomes and Measures: Hemodynamically significant stenosis in at least 1 coronary artery as indicated by a fractional flow reserve of 0.80 or less and relative diagnostic accuracy of SPECT, PET, and CCTA in detecting hemodynamically significant CAD. Results: Of the 208 patients in the study (76 women and 132 men; mean [SD] age, 58 [9] years), 92 (44.2%) had significant CAD (fractional flow reserve ≤0.80). Sensitivity was 90% (95% CI, 82%-95%) for CCTA, 57% (95% CI, 46%-67%) for SPECT, and 87% (95% CI, 78%-93%) for PET, whereas specificity was 60% (95% CI, 51%-69%) for CCTA, 94% (95% CI, 88%-98%) for SPECT, and 84% (95% CI, 75%-89%) for PET. Single-photon emission tomography was found to be noninferior to PET in terms of specificity (P < .001) but not in terms of sensitivity (P > .99) using the predefined absolute margin of 10%. Diagnostic accuracy was highest for PET (85%; 95% CI, 80%-90%) compared with that of CCTA (74%; 95% CI, 67%-79%; P = .003) and SPECT (77%; 95% CI, 71%-83%; P = .02). Diagnostic accuracy was not enhanced by either hybrid SPECT and CCTA (76%; 95% CI, 70%-82%; P = .75) or by PET and CCTA (84%; 95% CI, 79%-89%; P = .82), but resulted in an increase in specificity (P = .004) at the cost of a decrease in sensitivity (P = .001). Conclusions and Relevance: This controlled clinical head-to-head comparative study revealed PET to exhibit the highest accuracy for diagnosis of myocardial ischemia. Furthermore, a combined anatomical and functional assessment does not add incremental diagnostic value but guides clinical decision-making in an unsalutary fashion.

Impact of right ventricular side branch occlusion during percutaneous coronary intervention of chronic total occlusions on right ventricular function.

OBJECTIVE: To determine the impact of right ventricular side branch (RVB) occlusion, during percutaneous coronary interventions (PCIs) of chronic total occlusions (CTOs) of the right coronary artery (RCA), on right ventricular (RV) function. BACKGROUND: Developments in PCI techniques have expanded PCI CTO feasibility. However, the utilization of dissection and reentry techniques and extensive stent implantation increases the risk of coronary side branch occlusion. METHODS: Fifty-four patients (80% male, 63±10years) evaluated with cardiac magnetic resonance imaging (CMR) prior and three months after successful PCI CTO RCA (median: 99days, IQR: 92-105days) were included. Right ventricular end-diastolic volume (RVEDV), end-systolic volume (RVESV), and ejection fraction (RVEF) were quantified on CMR images. Occurrence of RVB occlusion and/or RVB recruitment was assessed using procedural angiograms. RESULTS: RVB occlusion was observed in 12 patients (22%), while RVB recruitment occurred in seven patients (13%). Overall, RVEF was comparable between baseline and follow-up (53.8±5.8 vs. 53.9±5.8%, p=0.95). RVB occlusion was not associated with a significant change in RVEDV or RVEF (156.9±36.3 vs. 162.1±35.5mL, p=0.30 and 54.2±3.9 vs. 52.7±4.4%, p=0.19, respectively); however a trend was observed for an increase of RVESV (72.5±20.0 vs. 77.4±20.7mL, p=0.05) at follow-up. RVB recruitment did not result in a significant improvement of RVEF (55.4±4.6 vs. 56.1±5.3%, p=0.75). CONCLUSION: RVB occlusion was not associated with a significant decreased RVEF at follow-up, although the results suggested a limited increase of RVESV.

Antegrade wire escalation for chronic total occlusions in coronary arteries: simple algorithms as a key to success.

AIMS: Antegrade wire escalation (AWE) remains the method of choice for tackling chronic total occlusions (CTOs), especially for lesions with low J-CTO score. To increase the number of operators which treat CTOs and increase AWE success rates, there is a need for a clear, algorithmic approach. We report the results of a simple AWE algorithm with new guidewire technology in coronary CTOs. METHODS: Hundred consecutive CTO lesions selected for AWE as the primary strategy were included in five Benelux centers. The algorithm follows a step-wise increase in guidewire tip load. Lesions were categorized according to the J-CTO score. Primary endpoint was successful guidewire crossing. RESULTS: No differences in baseline demographics were present between successful and unsuccessful procedures. Overall, in 75% of the lesions AWE resulted in successful crossing. AWE success rates in easy, intermediate, difficult and very difficult CTOs were 83, 86, 71 and 43%, respectively. 46% could be crossed using a soft guidewire only. An additional success of 34 and 60% could be reached with an intermediate and stiff guidewire, respectively. Adding additional techniques resulted in 88% overall success. Procedure and fluoroscopy times, radiation doses and use of contrast were within highly acceptable ranges (67 ±â€Š39 min, 27 ±â€Š19 min, 1.7 ±â€Š1.3 Gy, 264 ±â€Š123 ml). CONCLUSION: The algorithm and new wire technologies led to high success rates. AWE as a standalone procedure is highly successful in J-CTO 0-1. Low- and intermediate-volume CTO operators should try to implement a systematic approach in their CTO procedures, especially for lesions with low J-CTO scores. Adding additional techniques further increases these success rates.

Additional value of transluminal attenuation gradient in CT angiography to predict hemodynamic significance of coronary artery stenosis.

OBJECTIVES: The current study evaluates the incremental value of transluminal attenuation gradient (TAG), TAG with corrected contrast opacification (CCO), and TAG with exclusion of calcified coronary segments (ExC) over coronary computed tomography angiogram (CTA) alone using fractional flow reserve (FFR) as the gold standard. BACKGROUND: TAG is defined as the contrast opacification gradient along the length of a coronary artery on a coronary CTA. Preliminary data suggest that TAG provides additional functional information. Interpretation of TAG is hampered by multiple heartbeat acquisition algorithms and coronary calcifications. Two correction models have been proposed based on either dephasing of contrast delivery by relating coronary density to corresponding descending aortic opacification (TAG-CCO) or excluding calcified coronary segments (TAG-ExC). METHODS: Eighty-five patients with intermediate probability of coronary artery disease were prospectively included. All patients underwent step-and-shoot 256-slice coronary CTA. TAG, TAG-CCO, and TAG-ExC analyses were performed followed by invasive coronary angiography in conjunction with FFR measurements of all major coronary branches. RESULTS: Thirty-four patients (40%) were diagnosed with hemodynamically-significant coronary artery disease (i.e., FFR ≤0.80). On a per-vessel basis (n = 253), 59 lesions (23%) were graded as hemodynamically significant, and the diagnostic accuracy of coronary CTA (diameter stenosis ≥50%) was 95%, 75%, 98%, and 54% for sensitivity, specificity, negative predictive value, and positive predictive value, respectively. TAG and TAG-ExC did not discriminate between vessels with or without hemodynamically significant lesions (-13.5 ± 17.1 HU [Hounsfield units] × 10 mm(-1) vs. -11.6 ± 13.3 HU × 10 mm(-1), p = 0.36; and 13.1 ± 15.9 HU × 10 mm(-1) vs. -11.4 ± 11.7 HU × 10 mm(-1), p = 0.77, respectively). TAG-CCO was lower in vessels with a hemodynamically-significant lesion (-0.050 ± 0.051 10 mm(-1) vs. -0.036 ± 0.034 10 mm(-1), p = 0.03) and TAG-ExC resulted in a slight improvement of the net reclassification index (0.021, p < 0.05). CONCLUSIONS: TAG did not provide incremental diagnostic value over 256-slice coronary CTA alone in assessing the hemodynamic consequences of a coronary stenosis. Correction for temporal nonuniformity of contrast delivery or exclusion of calcified coronary segments slightly enhanced the results.