Prognostic significance of refractory thrombus in STEMI patients and the role of red cell distribution width: A case-control study.

The high thrombus burden of the infarct-related artery (IRA) is associated with the adverse prognosis in ST-segment elevation myocardial infarction (STEMI) patients. Our objectives were to investigate the predictors and evaluate the prognosis of refractory thrombus in STEMI patients. A total of 1305 consecutive patients with STEMI who underwent primary percutaneous coronary intervention (pPCI) were screened. The refractory thrombus group (n = 15) was defined as IRA thrombolysis in myocardial infarction flow < grade 2 after multiple thrombus aspiration (TA). The control group (n = 45) was age- and sex-matched and was selected from the same batch of patients. Baseline hematologic indices were measured before the pPCI. The major adverse cardiovascular events (MACE) were recorded during follow-up. The refractory thrombus group had significantly higher red cell distribution width (RDW) at baseline compared with the control group (13.1 [12.4-13.7] vs 12.6 [12.3-12.8], P = .008). In multivariate logistic regression analysis, RDW was an independent predictor of refractory thrombus (odds ratio: 8.799, 95% CI: 1.240-62.454, P = .030). The area under the receiver-operating characteristic curve of the RDW was 0.730 (95%CI: 0.548-0.912, P = .008). During a mean period of 26 months follow-up, patients in the refractory thrombus group tended to have higher percent MACEs compared with patients in the control group (53.3% vs 6.7%, P < .001). In the present study, we found that the refractory thrombus in STEMI patients was associated with the worse prognosis and the increased RDW might be a potential independent predictor.

Intracoronary imaging-guided rotational atherectomy combined with intravascular lithotripsy in the treatment of severe coronary artery calcification-A case report.

Background: Severe coronary artery calcification increases the difficulty of percutaneous coronary intervention procedures and impairs stent expansion. Herein, we report a case of a patient who was successfully treated with rotational atherectomy using a stepped burr strategy combined with intravascular lithotripsy for plaque modification under intracoronary imaging. Case summary: A 65 year-old woman presented to our hospital with recurrent chest pain evolving for 1 year. Coronary angiography showed approximately 80% stenosis of the proximal mid-left anterior descending artery. Intravascular ultrasound (IVUS) and optical coherence tomography (OCT) revealed a 360° annular calcification. The calcification was rotablated with 1.5 and 1.75 burrs, and the lesion was undilatable with a 3.0 mm non-compliant balloon at 14 atm. Subsequently, the intravascular lithotripsy was reset for the modification of the calcified lesion. A shockwave balloon measuring 3.0 mm × 12 mm was delivered, and 40 pulses were performed at 6 atm. Intravascular imaging modalities (IVUS and OCT) revealed a circumferential calcified plaque with deep fractures. After post-balloon expansion followed by drug-eluting stent placement with a final stent expansion of 84%, there were no intraoperative complications and no major adverse cardiovascular events within 90 days postoperatively. Conclusion: A combination of rotational atherectomy and intravascular lithotripsy may be an effective and complementary strategy for the treatment of severely calcified lesions that cannot be resolved using a single procedure. However, more clinical studies are required to clarify this finding.

Association of Quantitative Flow Ratio with Lesion Severity and Its Ability to Discriminate Myocardial Ischemia.

BACKGROUND AND OBJECTIVES: Quantitative flow ratio (QFR) is an angiography-based technique for functional assessment of coronary artery stenosis. This study investigated the response of QFR to different degree of stenosis severity and its ability to predict the positron emission tomography (PET)-defined myocardial ischemia. METHODS: From 109 patients with 185 vessels who underwent both 13N-ammonia PET and invasive physiological measurement, we compared QFR, fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) for the responses to the different degree of anatomical (percent diameter stenosis [%DS]) and hemodynamic (relative flow reserve [RFR], coronary flow reserve, hyperemic stenosis resistance, and stress myocardial flow) stenosis severity and diagnostic performance against PET-derived parameters. RESULTS: QFR, FFR, and iFR showed similar responses to both anatomic and hemodynamic stenosis severity. Regarding RFR, the diagnostic accuracy of QFR was lower than FFR (76.2% vs. 83.2%, p=0.021) and iFR (76.2% vs. 84.3%, p=0.031). For coronary flow capacity (CFC), QFR showed a lower accuracy than iFR (74.1% vs. 82%, p=0.031) and lower discriminant function than FFR (area under curve: 0.74 vs. 0.79, p=0.044). Discordance between QFR and FFR or iFR was shown in 14.6% of cases and was driven by the difference in %DS and heterogeneous distribution of PET-derived RFR and stress myocardial blood flow. CONCLUSIONS: QFR demonstrated a similar response to different anatomic and hemodynamic stenosis severity as FFR or iFR. However, its diagnostic performance was inferior to FFR and iFR when PET-derived RFR and CFC were used as a reference.

A novel nonsense mutation in TNNT2 in a Chinese pedigree with hypertrophic cardiomyopathy: A case report.

RATIONALE: Hypertrophic cardiomyopathy (HCM) is an inherited myocardial disease and a common cause of sudden cardiac death, heart failure, atrial fibrillation and stroke. In families affected by HCM, genotyping is useful for identifying susceptible relatives. In the present study, we investigated the disease-causing mutations in a three-generation Chinese family with HCM using whole exome sequencing (WES). PATIENT CONCERNS: The proband, a 50-year-old man, was diagnosed with HCM at the age of 41 years. He presented with an asymmetric hypertrophic interventricular septum and a maximum interventricular septum thickness of 18.04 mm. His third elder sister, niece and daughter were also clinically affected by HCM. DIAGNOSIS: Autosomal dominant HCM. INTERVENTIONS: Seven family members, including 4 affected members, accepted WES. The genetic variants were subsequently called using Genome Analysis Toolkit and annotated using the InterVar program. Following frequency filtration by the Genome Aggregation Database, the variants were evaluated using an in-house bioinformatics analysis pipeline. OUTCOMES: HCM was transmitted as an autosomal dominant trait in the family. An extremely rare stop gained mutation, rs796925245 (g.1:201359630G>A, c.835C>T, p.Gln279Ter) in the troponin T2 (TNNT2) gene was identified as the disease-causing mutation. The stop gained mutation was predicted to result in a truncated troponin T protein in cardiac sarcomere. An adolescent family member who had normal echocardiographic measurements was found to carry the same disease-causing mutation. LESSONS: A novel nonsense TNNT2 mutation was identified as the HCM-causing mutation in this Chinese pedigree. Since HCM shows a low penetrance by clinical criteria in adolescents, the adolescent mutation carrier, who is still clinically unaffected, should be offered routine follow-ups and sport activity recommendations to prevent adverse events including sudden cardiac death in the future.

Optical coherence tomography guided treatment avoids stenting in an antiphospholipid syndrome patient: A case report.

BACKGROUND: Increasing attention has been paid to acute myocardial infarction (AMI) in young female patients for whom secondary factors should be considered during the diagnostic process. Anti-phospholipid syndrome (APS), a rare autoimmune disease that is most common in young female patients, is reportedly related to AMI. To date, coronary interventions, particularly stenting, remains controversial in this special clinical scenario. CASE SUMMARY: A 26-year-old female patient was admitted to hospital for acute chest pain, palpitations, and dyspnea. She had a past medical history of APS and pulmonary embolism. Coronary angiography showed acute occlusion of the proximal left anterior descending artery. After repeated thrombus aspirations, residual thrombus and mild stenosis were found in the proximal left anterior descending artery. Optical coherence tomography (OCT) was done, which confirmed the non-atherosclerosis coronary thrombosis and an intact intima in this patient. Deferring or avoiding stenting based on follow-up intracoronary findings with intensified antithrombotic treatment was chosen. One week later, coronary angiography and OCT confirmed an intact intima with no injury and no residual thrombus. The 3-mo telephone follow-up reported a good prognosis. CONCLUSION: APS can cause acute non-atherosclerosis coronary thrombosis which presents as an AMI in young female patients. Intracoronary OCT findings can guide interventional strategies in this special clinical scenario.

Idiopathic hypereosinophilic syndrome associated with rapid progression of cardiac, pulmonary and skin infiltration.

Idiopathic hypereosinophilic syndrome (IHES) is a rare myeloproliferative disease characterised by multisystem dysfunction and persistent, extreme eosinophilia of unknown cause. Here we present a 42-year-old patient complaining of moderate to severe chest pain and shortness of breath, and typical ischaemic electrocardiography changes were recorded. He was initially suspected of having acute coronary syndrome, however the coronary angiogram excluded coronary abnormalities. Bone marrow biopsy, left ventriculography, transthoracic echocardiography and cardiac magnetic resonance examinations confirmed the diagnosis of IHES and IHES-mediated cardiac involvement. The patient's illness was alleviated during the first hospitalisation, whereas it had rapidly worsened one month after discharge. In addition, simultaneous pulmonary and skin-infiltrating lesions occurred during the second hospitalisation. The patient's condition improved markedly with combined glucocorticoid, hydroxyurea and warfarin therapy, as well as treatment for heart failure. In this report the diagnostic modalities and treatment strategies for IHES are discussed and reviewed.

Rescue treatment and follow-up intervention of a left main acute myocardial infarction with typical carina shift under 3D optical coherence tomography: A case report.

BACKGROUND: Coronary intervention for bifurcation lesions is still challenging for interventional cardiologists. Left main (LM) bifurcation lesions have a higher risk due to the vast blood supply in this area and treatment choice is difficult. Ostial compromise of the side branch decreases patient prognosis, and its management is still an issue despite the different strategies and devices available. CASE SUMMARY: A 42-year-old male patient was admitted to hospital due to chest pain and syncope. Coronary angiography showed acute LM occlusion. Following thrombus aspiration, a LM bifurcation lesion remained. Coronary angiography was repeated one week later, and at the same time, 3D optical coherence tomography (OCT) was carried out to better show the geometry of the bifurcation, which confirmed that the stenosis in the ostial left circumflex artery was caused by a long carina. After assessment of the plaque characteristics and the minimum lumen area, the cross-over strategy, kissing balloon inflation and proximal optimization technique were chosen to treat the bifurcation lesion. A "moving" carina was found twice during the intervention. Good stent apposition and expansion were confirmed by OCT after proximal optimization technique. The three-month follow-up showed good recovery and normal cardiac function. CONCLUSION: 3D-OCT can facilitate decision-making for coronary interventions in patients with critical bifurcation lesions.

In-stent restenosis and longitudinal stent deformation: a case report.

BACKGROUND: Longitudinal stent deformation (LSD) is an infrequent complication of percutaneous coronary intervention (PCI), and it may lead to catastrophic clinical outcomes. However, reports of cardiac adverse events associated with LSD are rare. CASE PRESENTATION: A 55-year-old man with chest pain was treated for a severe left anterior descending branch (LAD)-diagonal 1 (D1) bifurcation lesion by PCI with two stents in the proximal LAD. LSD occurred during the withdrawal of the trapped D1 wire. High-pressure balloon dilatation was performed in the deformed stent, and the end-angiographic appearance was acceptable, but no additional corrective measures were implemented. Ten months later, the patient represented with acute coronary syndrome. Severe in-stent restenosis (ISR) had suboccluded the proximal LAD, and optical coherence tomography (OCT) visualized multilayered stent struts protruding into the lumen at the compressed segment of the stent. Following complete apposition with balloon dilation, a drug-coated balloon (DCB) was used to avoid an additional permanent metallic layer. He remained angina free, and the angiographic result demonstrated no residual stenosis at the six-month follow-up. To our knowledge, this case demonstrates the first report of ISR triggered by LSD in patients treated with DCBs under the guidance of OCT. CONCLUSIONS: The current report underscores the importance of awareness of LSD, and OCT seems to be the preferred modality to confirm complete apposition. If left without performing additional corrective measures, LSD may be associated with a risk of ISR. Complete apposition with balloon dilation followed by a DCB is a feasible treatment option.

RIANet: Recurrent interleaved attention network for cardiac MRI segmentation.

BACKGROUND: Segmentation of anatomical structures of the heart from cardiac magnetic resonance images (MRI) has a significant impact on the quantitative analysis of the cardiac contractile function. Although deep convolutional neural networks (ConvNets) have achieved considerable success in medical imaging segmentation, it is still a challenging task for existing deep ConvNets to precisely and automatically segment multiple heart structures from cardiac MRI. This paper presents a novel recurrent interleaved attention network (RIANet) to comprehensively tackle this issue. METHOD: The proposed RIANet can efficiently reuse parameters to encode richer representative features via introducing a recurrent feedback structure, Clique Block, which incorporates both forward and backward connections between different layers with the same resolution. Further, we integrate a plug-and-play interleaved attention (IA) block to modulate the information passed to the decoding stage of RIANet by effectively fusing multi-level contextual information. In addition, we improve the discrimination capability of our RIANet through a deep supervision mechanism with weighted losses. RESULTS: The performance of RIANet has been extensively validated in the segmentation contest of the ACDC 2017 challenge held in conjunction with MICCAI 2017, with mean Dice scores of 0.942 (left ventricular), 0.923 (right ventricular) and 0.910 (myocardium) for cardiac MRI segmentation. Besides, we visualize intermediate features of our RIANet using guided backpropagation, which can intuitively depict the effects of our proposed components in feature representation. CONCLUSION: Experimental results demonstrate that our RIANet have achieved competitive segmentation results with fewer parameters compared with the state-of-the-art approaches, corroborating the effectiveness and robustness of our proposed RIANet.

Relevance of anatomical, plaque, and hemodynamic characteristics of non-obstructive coronary lesions in the prediction of risk for acute coronary syndrome.

OBJECTIVES: We explored the anatomical, plaque, and hemodynamic characteristics of high-risk non-obstructive coronary lesions that caused acute coronary syndrome (ACS). METHODS: From the EMERALD study which included ACS patients with available coronary CT angiography (CCTA) before the ACS, non-obstructive lesions (percent diameter stenosis < 50%) were selected. CCTA images were analyzed for lesion characteristics by independent CCTA and computational fluid dynamics core laboratories. The relative importance of each characteristic was assessed by information gain. RESULTS: Of the 132 lesions, 24 were the culprit for ACS. The culprit lesions showed a larger change in FFRCT across the lesion (ΔFFRCT) than non-culprit lesions (0.08 ± 0.07 vs 0.05 ± 0.05, p = 0.012). ΔFFRCT showed the highest information gain (0.051, 95% confidence interval [CI] 0.050-0.052), followed by low-attenuation plaque (0.028, 95% CI 0.027-0.029) and plaque volume (0.023, 95% CI 0.022-0.024). Lesions with higher ΔFFRCT or low-attenuation plaque showed an increased risk of ACS (hazard ratio [HR] 3.25, 95% CI 1.31-8.04, p = 0.010 for ΔFFRCT; HR 2.60, 95% CI 1.36-4.95, p = 0.004 for low-attenuation plaque). The prediction model including ΔFFRCT, low-attenuation plaque and plaque volume showed the highest ability in ACS prediction (AUC 0.725, 95% CI 0.724-0.727). CONCLUSION: Non-obstructive lesions with higher ΔFFRCT or low-attenuation plaque showed a higher risk of ACS. The integration of anatomical, plaque, and hemodynamic characteristics can improve the noninvasive prediction of ACS risk in non-obstructive lesions. KEY POINTS: • Change in FFR CT across the lesion (ΔFFR CT ) was the most important predictor of ACS risk in non-obstructive lesions. • Non-obstructive lesions with higher ΔFFR CT or low-attenuation plaque were associated with a higher risk of ACS. • The integration of anatomical, plaque, and hemodynamic characteristics can improve the noninvasive prediction of ACS risk.

Identification of High-Risk Plaques Destined to Cause Acute Coronary Syndrome Using Coronary Computed Tomographic Angiography and Computational Fluid Dynamics.

OBJECTIVES: The authors investigated the utility of noninvasive hemodynamic assessment in the identification of high-risk plaques that caused subsequent acute coronary syndrome (ACS). BACKGROUND: ACS is a critical event that impacts the prognosis of patients with coronary artery disease. However, the role of hemodynamic factors in the development of ACS is not well-known. METHODS: Seventy-two patients with clearly documented ACS and available coronary computed tomographic angiography (CTA) acquired between 1 month and 2 years before the development of ACS were included. In 66 culprit and 150 nonculprit lesions as a case-control design, the presence of adverse plaque characteristics (APC) was assessed and hemodynamic parameters (fractional flow reserve derived by coronary computed tomographic angiography [FFRCT], change in FFRCT across the lesion [△FFRCT], wall shear stress [WSS], and axial plaque stress) were analyzed using computational fluid dynamics. The best cut-off values for FFRCT, △FFRCT, WSS, and axial plaque stress were used to define the presence of adverse hemodynamic characteristics (AHC). The incremental discriminant and reclassification abilities for ACS prediction were compared among 3 models (model 1: percent diameter stenosis [%DS] and lesion length, model 2: model 1 + APC, and model 3: model 2 + AHC). RESULTS: The culprit lesions showed higher %DS (55.5 ± 15.4% vs. 43.1 ± 15.0%; p < 0.001) and higher prevalence of APC (80.3% vs. 42.0%; p < 0.001) than nonculprit lesions. Regarding hemodynamic parameters, culprit lesions showed lower FFRCT and higher △FFRCT, WSS, and axial plaque stress than nonculprit lesions (all p values <0.01). Among the 3 models, model 3, which included hemodynamic parameters, showed the highest c-index, and better discrimination (concordance statistic [c-index] 0.789 vs. 0.747; p = 0.014) and reclassification abilities (category-free net reclassification index 0.287; p = 0.047; relative integrated discrimination improvement 0.368; p < 0.001) than model 2. Lesions with both APC and AHC showed significantly higher risk of the culprit for subsequent ACS than those with no APC/AHC (hazard ratio: 11.75; 95% confidence interval: 2.85 to 48.51; p = 0.001) and with either APC or AHC (hazard ratio: 3.22; 95% confidence interval: 1.86 to 5.55; p < 0.001). CONCLUSIONS: Noninvasive hemodynamic assessment enhanced the identification of high-risk plaques that subsequently caused ACS. The integration of noninvasive hemodynamic assessments may improve the identification of culprit lesions for future ACS. (Exploring the Mechanism of Plaque Rupture in Acute Coronary Syndrome Using Coronary CT Angiography and Computational Fluid Dynamic [EMERALD]; NCT02374775).

A new technique to salvage myocardium following the failure of thrombus aspiration in acute myocardial infarction: a case report.

BACKGROUND: The failure of aspiration thrombectomy may negatively impact outcomes in patients with acute myocardial infarction (AMI), but the available options are limited. CASE PRESENTATION: A 41-year-old man with chest pain for 2 h presented with ST-segment elevation myocardial infarction. Coronary angiography revealed a large filling defect extending from the distal left main (LM) coronary artery into the proximal left circumflex (LCX) coronary artery. The whole thrombus moved and occluded the proximal left anterior descending (LAD) artery, while the guidewire crossed the lesion. Dedicated manual aspiration thrombectomy (MAT) and balloon dilation failed to reduce thrombus burden. We considered thrombus extraction as impossible when it moved forward to occlude the middle LAD. To reduce infarct size, a new balloon-pushing technique was successfully performed to move the thrombus to the terminal LAD based on the actual condition of the LAD. The final angiogram demonstrated no stenosis in the LM artery and stent deployment was not performed. A 1-week follow-up coronary angiography revealed the complete resolution of thrombus and flow restoration in the left coronary artery. Intravascular ultrasound (IVUS) showed nonsignificant residual stenosis of the LM artery. No adverse events occurred during a 12-month follow-up period. CONCLUSION: This case suggests that the new balloon-pushing technique is a useful remedy if repeated MAT fails during AMI.

Rotational atherectomy ablation for an unexpandable stent under the guide of IVUS: A case report.

RATIONALE: Inadequate stent expansion due to rigid calcified may result in restenosis lesions, but the available options are limited. PATIENT CONCERNS: We report a case via the trans-radial approach of the severely underexpanded freshly deployed stent due to heavily calcified plaques DIAGNOSES:: Coronary angiography revealed that there was no adequate expansion of the freshly deployed stent. INTERVENTIONS: Under the guide of intravascular ultrasound (IVUS), rotational atherectomy (RA) successfully ablated the stent layers and the protruding calcified plaque. Followed by balloon angioplasty, the ablated segment was scaffolded with another stent, well expanded and documented by IVUS. OUTCOMES: The patient was uneventful during the procedure and remained angina free at the point of one year of clinical follow-up. LESSONS: This case indicated that RA via the trans-radial approach could be a useful remedy in the situation of under-expansion of implanted stents, and the debulking should be performed under IVUS-guidance.

Knockdown of long non-coding RNA MEG3 protects H9c2 cells from hypoxia-induced injury by targeting microRNA-183.

Acute myocardial infarction (AMI) occurs when blood supply to the heart is diminished (ischemia) for long time, and ischemia is primarily caused due to hypoxia. This study evaluated the effects of long non-coding RNA maternally expressed gene 3 (MEG3) on hypoxic rat cardiomyocyte-drived H9c2 cells. Hypoxic injury was confirmed by alterations of cell viability, migration, invasion, apoptosis, and hypoxia-inducible factor 1α (HIF-1α) expression. MEG3 level in hypoxic cells and effects of its knockdown on hypoxic cells were assessed. The interactions between MEG3 and miR-183 as well as miR-183 and p27 were investigated. In addition, the effects of aberrantly expressed MEG3, miR-183, and p27 on hypoxic cells along with the activation of PI3K/AKT/FOXO3a signaling pathway were all assessed. Results showed that hypoxia induced decreases of cell viability, migration and invasion, and increases of apoptosis and expressions of HIF-1α and MEG3. Knockdown of MEG3 decreased hypoxia-induced injury in H9c2 cells. Knockdown of MEG3 also increased miR-183 expression, which was identified as a target of MEG3. The effects of MEG3 knockdown on the hypoxic cells were reversed by miR-183 silence. p27 was identified as a target gene of miR-183, and its expression negatively regulated by miR-183. The mechanistic studies revealed that knockdown of p27 decreased hypoxia-induced H9c2 cell injury by activating PI3K/AKT/FOXO3a signal pathways. These findings suggest that knockdown of MEG3 alleviates hypoxia-induced H9c2 cell injury by miR-183-mediated suppression of p27 through activation of PI3K/AKT/FOXO3a signaling pathway.

Unique Ventricular Tachycardia Originating from the Right Bundle Branch.

Ventricular tachycardia (VT), a common arrhythmia, frequently originates from in the right ventricular outflow tract, left ventricular outflow tract, aortic sinus, and left ventricular papillary muscle but infrequently from the His-Purkinje system, whereas the VT stemming from the right bundle branch has rarely been reported. Here we reported a case with of VT originating from the right bundle branch which was subsequently successfully treated with radiofrequency ablation and demonstrated the electrocardiac features of VT using an electrophysiological examination.

Similarity and Difference of Resting Distal to Aortic Coronary Pressure and Instantaneous Wave-Free Ratio.

BACKGROUND: Instantaneous wave-free ratio (iFR) has been used in clinical practice to identify functionally significant stenosis and to guide treatment strategy. However, there are limited clinical data regarding another resting pressure-derived index, resting distal to aortic coronary pressure (Pd/Pa), and similarities and differences between resting Pd/Pa and iFR. OBJECTIVES: The authors investigated the changes in resting Pd/Pa and iFR according to anatomic and hemodynamic stenosis severity and their prognostic implications. METHODS: From the 3V FFR-FRIENDS (Clinical Implication of 3-vessel Fractional Flow Reserve) and the IRIS-FFR (Study of the Natural History of FFR Guided Percutaneous Coronary Intervention) studies, 1,024 vessels (n = 435) with available pre-intervention resting Pd/Pa and iFR were used to explore the changes in resting physiological indices according to percent diameter stenosis. Among 115 patients who underwent 13N-ammonia positron emission tomography, the changes in those indices according to basal and hyperemic stenosis resistance and absolute hyperemic myocardial blood flow were compared. The association between physiological indices and the risk of 2-year major adverse cardiac events (MACE) (a composite of cardiac death, myocardial infarction, and ischemia-driven revascularization) were analyzed among 375 deferred patients. RESULTS: There was a significant linear correlation between resting Pd/Pa and iFR (R = 0.970; p < 0.001, iFR = 1.370 × resting Pd/Pa - 0.370). Both resting Pd/Pa and iFR changed significantly according to percent diameter stenosis, basal and hyperemic stenosis resistance, and hyperemic absolute myocardial blood flow (all p values <0.001). Percent difference of iFR according to the increase in anatomic and hemodynamic severity was higher than that of resting Pd/Pa. Both resting Pd/Pa and iFR showed a significant association with the risk of 2-year MACE (resting Pd/Pa hazard ratio [per 0.10 increase]: 0.480; 95% confidence interval: 0.250 to 0.923; p = 0.027; iFR hazard ratio [per 0.1 increase]: 0.586; 95% confidence interval: 0.373 to 0.919; p = 0.020) in deferred patients. However, the difference between the upper- and lower-bound estimated MACE rates according to the approximate measurement variability of each index was significantly higher with resting Pd/Pa compared with iFR (resting Pd/Pa 3.85 ± 4.00% and iFR 3.27 ± 3.39%; p < 0.001). CONCLUSIONS: Both resting Pd/Pa and iFR showed similar associations with anatomic and hemodynamic stenosis severity and the risk of MACE. However, iFR was more sensitive to the difference in stenosis severity and showed a lower maximum difference in estimated MACE risk influenced by the measurement variability compared with resting Pd/Pa. (Clinical Implication of 3-Vessel Fractional Flow Reserve [3V FFR-FRIENDS]; NCT01621438; and Study of the Natural History of FFR Guided Percutaneous Coronary Intervention [IRIS-FFR]; NCT01366404).

Exploring Coronary Circulatory Response to Stenosis and Its Association With Invasive Physiologic Indexes Using Absolute Myocardial Blood Flow and Coronary Pressure.

BACKGROUND: Although invasive physiological assessment for coronary stenosis has become a standard practice to guide treatment strategy, coronary circulatory response and changes in invasive physiological indexes, according to different anatomic and hemodynamic lesion severity, have not been fully demonstrated in patients with coronary artery disease. METHODS: One hundred fifteen patients with left anterior descending artery stenosis who underwent both 13N-ammonia positron emission tomography and invasive physiological measurement were analyzed. Myocardial blood flow (MBF) measured with positron emission tomography and invasively measured coronary pressures were used to calculate microvascular resistance and stenosis resistance. RESULTS: With progressive worsening of angiographic stenosis severity, both resting and hyperemic transstenotic pressure gradient and stenosis resistance increased (P<0.001 for all) and hyperemic MBF (P<0.001) and resting microvascular resistance (P=0.012) decreased. Resting MBF (P=0.383) and hyperemic microvascular resistance (P=0.431) were not changed and maintained stable. Both fractional flow reserve and instantaneous wave-free ratio decreased as angiographic stenosis severity, stenosis resistance, and transstenotic pressure gradient increased and hyperemic MBF decreased (all P<0.001). When the presence of myocardial ischemia was defined by both low hyperemic MBF and low coronary flow reserve, the diagnostic accuracy of fractional flow reserve and instantaneous wave-free ratio did not differ, regardless of cutoff values of hyperemic MBF and coronary flow reserve. CONCLUSIONS: This study demonstrated how the coronary circulation changes in response to increasing coronary stenosis severity using 13N-ammonium positron emission tomography-derived MBF and invasively measured pressure data. Currently used resting and hyperemic pressure-derived invasive physiological indexes have similar patterns of relationships to the different anatomic and hemodynamic lesion severities. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01366404.

Physiologic mechanism of discordance between instantaneous wave-free ratio and fractional flow reserve: Insight from 13N-ammonium positron emission tomography.

BACKGROUND: Invasive physiologic indices, such as fractional flow reserve (FFR) or instantaneous wave-free ratio (iFR), are used in clinical practice. We sought to evaluate the physiological mechanism of discordance between iFR and FFR using 13N-ammonia positron emission tomography (PET)-derived quantitative parameters. METHODS: Data from 113 patients, who underwent both 13N-ammonia PET and invasive FFR and iFR measurement, were analyzed. Coronary circulatory indices, such as myocardial blood flow (MBF), coronary flow reserve (CFR), microvascular resistance, and trans-stenosis resistance were compared between patients with discordant results (low FFR despite high iFR) and those with concordant abnormal results (low FFR and low iFR), using cut-off values of FFR≤0.80 and iFR<0.90, respectively. RESULTS: Among the 113 patients, 39 (34.5%) showed concordant abnormal results in FFR and iFR measurement, and 17 (15.0%) showed discordant results between FFR and iFR (low FFR and high iFR). In comparison of coronary circulatory indices between discordant group and concordant abnormal group, both showed similar resting MBF (p=0.360), however, the discordant group showed higher hyperemic MBF and CFR, compared with the concordant abnormal group (p=0.003 and p<0.001, respectively). Trans-stenosis resistance was lower in the discordant group, in both resting and hyperemic status (p<0.001 for both). Although the discordant group showed higher resting microvascular resistance, these patients showed significantly higher reduction of microvascular resistance at hyperemia. CONCLUSIONS: Patients with low FFR despite high iFR showed significant differences in microvascular resistance, trans-stenosis resistance, absolute MBF, and CFR compared to those with concordant abnormal results between FFR and iFR.

Diagnostic Performance of Resting and Hyperemic Invasive Physiological Indices to Define Myocardial Ischemia: Validation With 13N-Ammonia Positron Emission Tomography.

OBJECTIVES: The authors sought to compare the diagnostic performance of fractional flow reserve (FFR), instantaneous wave-free ratio (iFR), and resting distal coronary artery pressure/aortic pressure (Pd/Pa) using 13N-ammonia positron emission tomography (PET). BACKGROUND: The diagnostic performance of invasive physiological indices was reported to be different according to the reference to define the presence of myocardial ischemia. METHODS: A total of 115 consecutive patients with left anterior descending artery stenosis who underwent both 13N-ammonia PET and invasive physiological measurement were included. Optimal cutoff values and diagnostic performance of FFR, iFR, and resting Pd/Pa were assessed using PET-derived coronary flow reserve (CFR) and relative flow reserve (RFR) as references. To compare discrimination and reclassification ability, each index was compared with integrated discrimination improvement (IDI) and category-free net reclassification index (NRI). RESULTS: All invasive physiological indices correlated with CFR and RFR (all p values <0.001). The overall diagnostic accuracies of FFR, iFR, and resting Pd/Pa were not different for CFR <2.0 (FFR 69.6%, iFR 73.9%, and resting Pd/Pa 70.4%) and RFR <0.75 (FFR 73.9%, iFR 71.3%, and resting Pd/Pa 74.8%). Discrimination and reclassification abilities of invasive physiological indices were comparable for CFR. For RFR, FFR showed better discrimination and reclassification ability than resting indices (IDI = 0.170 and category-free NRI = 0.971 for iFR; IDI = 0.183 and category-free NRI = 1.058 for resting Pd/Pa; all p values <0.001). CONCLUSIONS: The diagnostic performance of invasive physiological indices showed no differences in the prediction of myocardial ischemia defined by CFR. Using RFR as a reference, FFR showed a better discrimination and reclassification ability than resting indices.