The effect of an initial catheter ablation with an adjunctive ethanol infusion into the vein of Marshall on persistent atrial fibrillation.

INTRODUCTION: Some previous studies have reported that a first-step ethanol infusion into the vein of Marshall (EIVOM) with touch-up radiofrequency (RF) ablation can facilitate mitral isthmus (MI) block and improves the ablation outcomes in persistent atrial fibrillation (PeAF) patients. However, the effect of an initial RF ablation with an adjunctive EIVOM has not been fully investigated. METHODS: This study enrolled 233 PeAF patients undergoing pulmonary vein isolation and linear ablation including an MI, roof line, and cavotricuspid isthmus ablation. An EIVOM was performed when endocardial ablation with or without coronary sinus ablation failed to create MI block. RESULTS: Bidirectional MI block was achieved in 224 patients (96.1%). Among them, MI block was obtained by only RF ablation in 174/224 patients (77.7%) (RF group) and an adjunctive EIVOM was needed in 50/224 (22.3%) (EIVOM group). During the follow-up, 113 (64.9%) RF group patients were free from AF/atrial tachycardia compared to 41 (82.0%) EIVOM group patients (log-rank p = .045). In a multivariate Cox regression analysis, an adjunctive EIVOM was associated with a lower recurrence rate (hazard ratio = 0.39, 95% confidence interval = 0.17-0.78, p = .006). CONCLUSION: An initial RF ablation with an adjunctive EIVOM strategy improved MI ablation's acute success rate and was associated with better clinical outcomes.

Iatrogenic Atrial Septal Defect Requiring Transcatheter Closure Following Transcatheter Mitral Valve Repair.

BACKGROUND: Transcatheter mitral valve repair with the MitraClip system has been established in selected high-risk patients. The MitraClip procedure results in a relatively large iatrogenic atrial septal defect (iASD). This study aimed to investigate the prevalence and clinical course of iASD requiring transcatheter closure following the MitraClip procedure.Methods and Results: This study was conducted at all 59 institutions that perform transcatheter mitral valve repair with the MitraClip system in Japan. The data of patients on whom transcatheter iASD closure was performed were collected. Of the 2,722 patients who underwent the MitraClip procedure, 30 (1%) required transcatheter iASD closure. The maximum iASD size was 9±4 mm (range, 3-18 mm). The common clinical course of transcatheter iASD closure was hypoxemia with right-to-left shunt or right-sided heart failure with left-to-right shunt. Of the 30 patients, 22 (73%) required transcatheter closure within 24 h following the MitraClip procedure, including 12 with hypoxemia and 5 with right-sided heart failure complicated with cardiogenic shock. Of the 5 patients, 2 required mechanical circulatory support devices. Twenty-one patients immediately underwent transcatheter iASD closure, and hemodynamic deteriorations were resolved; however, 1 patient died without having undergone transcatheter closure. CONCLUSIONS: Transcatheter iASD closure was required in 1% of patients who underwent the MitraClip procedure. Many of these patients immediately underwent transcatheter iASD closure because of hypoxemia with right-to-left shunt or right-sided heart failure with left-to-right shunt.

Clinical impact of left ventricular outflow tract obstruction in takotsubo cardiomyopathy.

BACKGROUND: A hyperdynamic state of the basal left ventricle sometimes results in obstruction of the left ventricular outflow tract (LVOT). However, the prevalence, clinical presentation, and prognostic effect of LVOT obstruction in takotsubo cardiomyopathy (TC) have not been fully evaluated. METHODS AND RESULTS: Among 933 consecutive patients who underwent emergency coronary angiography for suspected acute coronary syndrome, 35 patients (3.8%) were diagnosed as TC. The cumulative 3-year incidence of all-cause death, cardiac death, hospitalization for congestive heart failure (CHF), and recurrent TC was 24.2%, 0.0%, 6.5%, and 12.2%, respectively. Among 27 patients with information of a LVOT pressure gradient, LVOT obstruction was present in 9 (33%). The prevalence of moderate to severe mitral regurgitation (67% vs. 11%, P=0.003), CHF (78% vs. 28%, P=0.02), and hypotension (56% vs. 5.6%, P=0.008) was significantly higher in patients with LVOT obstruction than in those without. Nevertheless, the cumulative 3-year incidence of all-cause death was not significantly different between the 2 groups (49.2% vs. 23.0%, P=0.22) with no cardiac deaths in either group. Hospitalization for CHF and recurrent TC were significantly more frequent in patients with LVOT obstruction (25.0% vs. 0.0%, P=0.04, and 25.0% vs. 6.7%, P=0.02). CONCLUSIONS: In 35 consecutive patients with TC, those with significant LVOT obstruction (33%) had a more serious clinical presentation such as CHF and hypotension, but had similar 3-year mortality rate as compared with those without.

First clinical experience of the looped Inoue balloon technique for antegrade percutaneous balloon aortic valvuloplasty.

Balloon aortic valvuloplasty (BAV) has played a limited role in the management of patients with severe aortic stenosis. However, BAV is being performed more frequently these days with the emergence of transcatheter aortic valve implantation (TAVI). We previously described a technique named "looped Inoue balloon technique" to simplify the antegrade transvenous BAV by making a loop in the left atrium using two stylets. We present a case in which the looped Inoue balloon technique was successfully applied. The patient was an 83-year-old woman with progressive dyspnea due to severe aortic stenosis. The aortic valve area was 0.39 cm(2) with a mean transvalvular gradient of 46 mmHg. The patient was deemed high risk for surgical aortic valve replacement or TAVI in view of the multiple comorbidities and frailty. Antegrade BAV using the looped Inoue balloon technique was performed. The procedure was successful without any complications. The post procedural aortic valve area increased to 1.15 cm(2) with a mean pressure gradient of 23 mmHg. This is the first report of clinical use of the looped Inoue balloon technique for antegrade BAV.

Noninvasive Detection of Functional Myocardial Ischemia: Multifunction Cardiogram Evaluation in Diagnosis of Functional Coronary Ischemia Study (MED-FIT).

BACKGROUND: Multifunction cardiogram (MCG) is a computer-enhanced, resting electrocardiogram analysis developed to detect hemodynamically relevant coronary artery disease (CAD). Based on data from previous studies suggesting excellent diagnostic accuracy in detecting CAD, MCG (approved by the Food and Drugs Administration) received a Current Procedure Terminology (CPT) code in 2010 in United States. However, there is no previous study validating MCG by using fractional flow reserve (FFR) as the reference standard. METHODS: Multifunction cardiogram Evaluation in Diagnosis of Functional coronary Ischemia sTudy (MED-FIT) was designed as a single-center, prospective study enrolling 100 stable patients with suspected CAD scheduled for coronary angiography. The primary and secondary analyses evaluated the diagnostic performance of the MCG severity score to detect functional myocardial ischemia by FFR ≤0.80, and angiographically significant coronary stenosis (percent diameter stenosis ≥50%) by quantitative coronary angiography. RESULTS: The current analysis set consisted of 91 patients in whom MCG data with adequate quality was obtained. The prevalence of positive functional myocardial ischemia and angiographically significant stenosis in the current study was 42.7% and 41.8%, respectively. Area under the receiver operating characteristics curve (AUC) of the MCG severity score for functional myocardial ischemia and angiographically significant stenosis was low (AUC 0.51, 95% confidence interval [CI] 0.38-0.63, and AUC 0.58, 95%CI 0.46-0.70, respectively). Sensitivity, and specificity of the MCG severity score for functional myocardial ischemia and angiographically significant stenosis was also low (32%/67%, and 37%/72%) using a cutoff value of 4.0. CONCLUSIONS: Diagnostic performance of the MCG severity score was poor for both functional myocardial ischemia, and angiographically significant stenosis.

Long-term efficacy and safety outcomes after unrestricted use of drug-eluting stents in patients with acute coronary syndrome: mortality and major bleeding in a single-center registry.

BACKGROUND: Recent randomized clinical trials have reported favorable clinical outcomes after the use of drug-eluting stents (DES) in patients with acute coronary syndrome (ACS). However, the long-term efficacy and safety outcomes, bleeding outcome in particular, after DES implantation in ACS patients have not been thoroughly evaluated in a real-world population. METHODS AND RESULTS: We evaluated long-term clinical outcomes in 565 consecutive ACS patients who underwent DES implantation in an emergency setting between 2004 and 2011 (ST-segment elevation acute myocardial infarction [STEMI]: n=269, non-STEMI/unstable angina pectoris: n=296). Mean clinical follow-up period in this study was 4.6±2.0 years. The cumulative incidence of all-cause death, cardiac death, myocardial infarction, stent thrombosis and target-lesion revascularization was 6.9%, 4.0%, 2.2%, 1.3% and 8.4% at 1 year, and 19.6%, 6.7%, 5.6%, 3.0% and 13.9% at 5 years, respectively. The cumulative 5-year incidence of major bleeding events was 8.4% (n=42). Fatal bleeding events, however, occurred in only 4 patients, even including 2 patients who required resuscitation upon arrival at the hospital. Of the 42 patients with major bleeding events, 39 were taking dual antiplatelet therapy (DAPT) at the time of bleeding. CONCLUSIONS: DES implantation provided favorable long-term clinical outcomes with an acceptably low incidence of fatal bleeding in a real-world population of ACS patients. However, prolonged DAPT seems to be associated with major bleeding after DES implantation.

Percutaneous balloon valvuloplasty for bioprosthetic mitral valve stenosis.

Percutaneous transcatheter mitral valvuloplasty is the indicated treatment of choice for symptomatic native mitral valve stenosis, but there have been limited reports of successful procedures of balloon valvuloplasty for bioprosthetic mitral valve stenosis. We present the case of a 62-year-old woman suffering from progressive dyspnea due to bioprosthetic mitral valve stenosis. The measured mean pressure gradient across the mitral valve was 30 mmHg and the mitral valve area was 0.73 cm(2). Redoing mitral replacement was considered high risk and was refused by the patient. Percutaneous balloon valvuloplasty was performed with an Inoue balloon catheter inflated to 20 mm. The patient's symptoms immediately improved after the procedure, with no procedure-related complications. The mean pressure gradient across the valve decreased to 19 mmHg, and the mitral valve area increased to 1.21 cm(2) in postprocedural echocardiography. We conducted a literature search and identified 26 cases of balloon valvuloplasty for degenerated bioprosthetic valves. Of these, 14 cases were bioprosthetic mitral valves, and the results were favorable. However, more case reports are required to establish an evidence base for future expert recommendation of balloon valvuloplasty of prosthetic mitral valve. Meanwhile, balloon valvuloplasty will serve a niche role in highly selected patients with prosthetic mitral valve stenosis.

Post-contrast Acute Kidney Injury After Emergent and Elective Percutaneous Coronary Intervention (from the CREDO-Kyoto PCI/CABG Registry Cohort 3).

Post-contrast acute kidney injury (PC-AKI) is a common complication after percutaneous coronary intervention (PCI). However, it is unclear whether or not the effects of PC-AKI on long-term clinical outcomes were different between emergent and elective procedures. Among patients enrolled in the CREDO-Kyoto PCI/CABG (Coronary Revascularization Demonstrating Outcome Study in Kyoto Percutaneous Coronary Intervention/Coronary Artery Bypass Grafting) registry cohort 3, we identified 10,822 patients treated using PCI (emergent PCI stratum: n = 5,022 [46%] and elective PCI stratum: n = 5,860 [54%]). PC-AKI was defined as ≥0.3 mg/100 ml absolute or 1.5-fold relative increase of serum creatinine within 72 hours after PCI. The incidence of PC-AKI was significantly higher after emergent PCI than after elective PCI (10.5% vs 3.7%, p <0.001). In the multivariable logistic regression model, emergent PCI was the strongest independent risk factor for PC-AKI in the entire study population. The excess adjusted risk of patients with PC-AKI relative to those without remained significant for all-cause death in both the emergent and elective PCI strata (hazard ratio 1.87, 95% confidence interval 1.59 to 2.21, p <0.001 and hazard ratio 1.31, 95% confidence interval 1.03 to 1.68, p = 0.03, respectively). There was a significant interaction between the PCI setting (emergent and elective) and the effect of PC-AKI on all-cause death, with a greater magnitude of effect in the emergent PCI stratum than in the elective PCI stratum (p for interaction = 0.01). In conclusion, the incidence of PC-AKI was 2.8 times higher after emergent PCI than after elective PCI. The excess mortality risk of PC-AKI relative to no PC-AKI was greater after emergent PCI than after elective PCI.

Incidence, risk factors, and clinical sequelae of angiographic peri-stent contrast staining after sirolimus-eluting stent implantation.

BACKGROUND: We have noted abnormal angiographic findings--at the sites of drug-eluting stent implantation, suggesting contrast staining outside the stent struts--that do not fulfill the classic definition of coronary artery aneurysm. We propose a new term, peri-stent contrast staining (PSS), for these abnormal angiographic findings and assess their incidence, risk factors, and clinical sequelae. METHODS AND RESULTS: Peri-stent contrast staining was defined as contrast staining outside the stent contour extending to ≥20% of the stent diameter. The study population consisted of 3081 lesions (1998 patients) that were treated exclusively with sirolimus-eluting stents and were evaluated by follow-up angiography within 12 months after sirolimus-eluting stent implantation in a single center. Late acquired PSS was observed in 58 lesions (1.9%) in 49 patients (2.5%). Independent risk factors of PSS included chronic total occlusion, whereas negative risk factors for PSS were left circumflex coronary artery lesion and in-stent restenosis lesion. Stent fracture was more frequently observed in lesions with PSS than in lesions without PSS (43.1% versus 5.4%, P<0.0001). Excluding 269 lesions with target-lesion revascularization within 12 months, the study population for long-term follow-up consisted of 51 lesions (42 patients) with PSS and 2761 lesions (1751 patients) without PSS. Cumulative incidence of target-lesion revascularization and definite very late stent thrombosis at 3 years in the PSS group was higher than that in the non-PSS group (15.0% versus 6.5%, and 8.2% versus 0.2%, respectively). CONCLUSIONS: Peri-stent contrast staining found within 12 months after sirolimus-eluting stent implantation appeared to be associated with subsequent target-lesion revascularization and very late stent thrombosis.

Efficacy of treat-and-repair strategy for atrial septal defect with pulmonary arterial hypertension.

OBJECTIVE: Therapeutic strategies for atrial septal defect (ASD) with severe pulmonary arterial hypertension (PAH) are controversial. This study aimed to evaluate the efficacy of PAH-specific medications and subsequent transcatheter closure (ie, treat-and-repair strategy) on clinical outcomes. METHODS: We enrolled 42 patients who were referred to 13 institutions for consideration of ASD closure with concomitant PAH and underwent the treat-and-repair strategy. The endpoint was cardiovascular death or hospitalisation due to heart failure or exacerbated PAH. RESULTS: At baseline prior to PAH-specific medications, pulmonary to systemic blood flow ratio (Qp:Qs), pulmonary vascular resistance (PVR), and mean pulmonary artery pressure (PAP) were 1.9±0.8, 6.9±3.2 Wood units and 45±15 mm Hg. Qp:Qs was increased to 2.4±1.2, and PVR and mean PAP were decreased to 4.0±1.5 Wood units and 35±9 mm Hg at the time of transcatheter ASD closure after PAH-specific medications. Transcatheter ASD closure was performed without any complications. During a median follow-up period of 33 months (1-126 months) after transcatheter ASD closure, one older patient died and one patient was hospitalised due to heart failure, but the other patients survived with an improvement in WHO functional class. PAP was further decreased after transcatheter ASD closure. CONCLUSIONS: The treat-and-repair strategy results in low complication and mortality rates with a reduction in PAP in selected patients with ASD complicated with PAH who have a favourable response of medical therapy.

Sirolimus-eluting stent versus balloon angioplasty for sirolimus-eluting stent restenosis: Insights from the j-Cypher Registry.

BACKGROUND: Optimal treatment strategies for restenosis of sirolimus-eluting stents (SES) have not been adequately addressed yet. METHODS AND RESULTS: During the 3-year follow-up of 12 824 patients enrolled in the j-Cypher registry, 1456 lesions in 1298 patients underwent target-lesion revascularization (TLR). Excluding 362 lesions undergoing TLR for stent thrombosis or TLR using treatment modalities other than SES or balloon angioplasty (BA), 1094 lesions with SES-associated restenosis in 990 patients treated with either SES (537 lesions) or BA (557 lesions) constituted the study population for the analysis of recurrent TLR and stent thrombosis after the first TLR. Excluding 24 patients with both SES- and BA-treated lesions, 966 patients constituted the analysis set for the mortality outcome. Cumulative incidence of recurrent TLR in the SES-treated restenosis lesions was significantly lower than that in the BA-treated restenosis lesions (23.8% versus 37.7% at 2 years after the first TLR; P<0.0001). Among 33 baseline variables evaluated, only hemodialysis was identified to be the independent risk factor for recurrent TLR by a multivariable logistic regression analysis. After adjusting for confounders, repeated SES implantation was associated with a strong treatment effect in preventing recurrent TLR over BA (odds ratio, 0.44; 95% confidence interval, 0.32 to 0.61; P<0.0001). The 2-year mortality and stent thrombosis rates between the SES- and the BA-treated groups were 10.4% versus 10.8% (P=0.4) and 0.6% versus 0.6%, respectively. CONCLUSIONS: Repeated implantation of SES for SES-associated restenosis is more effective in preventing recurrent TLR than treatment with BA, without evidence of safety concerns.

Comparative pathological findings between coronary bare-metal stent implantation and balloon angioplasty over 16 years.

A 68-year old man underwent bare metal stent (BMS; Palmaz-Shatz stent) implantation in the distal right coronary artery (RCA; #4PL) and balloon angioplasity (BA) in the proximal left circumflex coronary artery (LCX; #11) for stable angina. After 5 years after initial stent implantation, de novo lesion located in mid RCA was treated by BMS (NIR stent) implantation additionally. After 16 years from first BMS implantation, the patient died from heart failure due to cardiac amyloidosis, and pathologic examination was performed for the specimen of stented RCA segment and LCX BA segment. An autopsy demonstrated that the lesions of stented site at RCA and BA site LCX were histopathologically different. In the stented segment, severe luminal stenosis is observed due to marked proliferation of the neointima in all stented sites. In addition, neovascularization and spotty calcification with mild lymphocyte infiltration were observed especially around the struts. In contrast, at the BA site of the proximal LCX lesion, in the neointima, the smooth muscle cells were rather atrophic and abundant collagen fibers were evident in the intercellular spaces, which showed very stable findings. Compared with these BMS implanted portions, the site of BA was associated with a trend for smaller late lumen loss. These findings suggested that in the stented site, chronic inflammatory reaction to the stent struts could evoke continuous proliferation of neointima resulting in severe late lumen loss. .

Utility of copeptin for predicting long-term clinical outcomes in patients with heart failure.

BACKGROUND: Copeptin, a surrogate marker of pro-arginine vasopressin, is expected to be a marker in cardiovascular diseases. Its utility for predicting long-term clinical outcomes in heart failure (HF), however, has not been adequately evaluated in daily clinical practice in Japan. METHODS: To assess the relationship of serum copeptin at admission with long-term clinical outcomes, we evaluated serum copeptin at admission in consecutive 107 patients hospitalized for HF between April 2011 and July 2012. The primary outcome measure was defined as a composite of all-cause death and re-admission for HF (all-cause death/HF). RESULTS: In this study population, median serum copeptin at admission was 15.5 (6.7-32.0)pmol/L. As compared with the low-copeptin group (<18pmol/L, N=60), the high-copeptin group (≥18pmol/L, N=47) included more male patients and those with prior myocardial infarction, prior HF, low left ventricular ejection fraction, and chronic kidney disease. During median 4.5 (1.0-5.5) years of clinical follow-up, the cumulative incidence of all-cause death/HF was significantly higher in the high-copeptin than in the low-copeptin group (63.4% versus 33.0% at 1 year, and 85.2% versus 77.2% at 5 years, log-rank p=0.03). After adjusting for confounders, high-copeptin was still an independent predictor for all-cause death/HF [hazard ratio (95% confidence interval): 1.77 (1.04-3.01), p=0.03]. CONCLUSION: Copeptin was suggested as a useful marker for predicting long-term clinical outcomes in patients with HF.

Maintenance electroconvulsive therapy (ECT) for treatment-resistant disorganized schizophrenia.

Patients who have not responded to recommended antipsychotic medications should be considered for electroconvulsive therapy (ECT). However, there has been controversy about the standardized methods of continuation and maintenance ECT in the management of treatment-resistant schizophrenia. We describe a patient with a serious case of disorganized schizophrenia who had not responded well with any typical and atypical antipsychotic drug for seven years, but responded remarkably to acute ECT. Continuation ECT was necessary to sustain a positive therapeutic response. The patient showed dramatic improvement from 70 to 20 in the 18-item Brief Psychiatric Rating Scale (BPRS) score (71% reduction) after acute ECT and continuation ECT. Using maintenance ECT, she was able to live in the custody of her parents after 7-years hospitalization. This case report suggests that continuation and maintenance ECT benefits patients with serious cases of refractory schizophrenia.

Transfemoral transcatheter aortic valve implantation in the presence of a mechanical mitral valve prosthesis using a dedicated TAVI guidewire: utility of a patient-specific three-dimensional heart model.

An 82-year-old woman with severe aortic stenosis was referred. She had previously undergone mitral valve replacement. We planned transcatheter aortic valve implantation (TAVI) with transfemoral approach. We planned to use the Safari-dedicated TAVI guidewire. No studies have reported clinical application of the dedicated TAVI guidewire in a patient with the previous mitral valve replacement. Thus, we conducted a simulation using a three-dimensional heart model to confirm the safety of the procedure. The procedure was successful without any complications. This case is the first to show that the dedicated TAVI guidewire can be safely used in patients with preexisting mitral valve.

Use of extracorporeal membrane oxygenation in complicated transcatheter aortic valve replacement.

OBJECTIVES: Although transcatheter aortic valve replacement (TAVR) is an excellent alternative procedure for high-risk patients with severe symptomatic aortic stenosis, it is often associated with life-threatening complications. We report on the emergency or elective use of veno-arterial extracorporeal membrane oxygenation (ECMO) to manage these complications. METHODS: Between December 2013 and February 2016, 46 patients underwent TAVR at our institution. Of these, 4 patients required emergency ECMO support and another 3 patients were electively placed on ECMO support at the start of the procedure. The mean age of the ECMO patients was 87.3 ± 3.6 years and all were female. The Society of Thoracic Surgeons-predicted risk of mortality score in these patients was 12.2 ± 6.2%. RESULTS: TAVR with ECMO was completed through the transapical approach in 6 patients, and the transfemoral approach in 1 patient. The arterial access route for ECMO was the femoral artery in 5, the external iliac artery in 1, and the subclavian artery in 1. Indications for the use of emergency ECMO were hemodynamic instability in 2, cardiogenic shock in 2, while indications for elective ECMO were severe pulmonary hypertension, impaired left ventricular function and a combination of these. There was no 30-day mortality, and the 1-year survival rate was 83.3% with no significant difference compared to patients without ECMO support. CONCLUSION: The use of ECMO in very high-risk patients undergoing TAVR may increase safety and contribute to excellent outcomes. Although ECMO support is rarely needed in TAVR, a well-prepared treatment strategy by the heart team is mandatory.

Feasibility and diagnostic performance of fractional flow reserve measurement derived from coronary computed tomography angiography in real clinical practice.

Non-invasive fractional flow reserve measured by coronary computed tomography angiography (FFRCT) has demonstrated a high diagnostic accuracy for detecting coronary artery disease (CAD) in selected patients in prior clinical trials. However, feasibility of FFRCT in unselected population have not been fully evaluated. Among 60 consecutive patients who had suspected significant CAD by coronary computed tomography angiography (CCTA) and were planned to undergo invasive coronary angiography, 48 patients were enrolled in this study comparing FFRCT with invasive fractional flow reserve (FFR) without any exclusion criteria for the quality of CCTA image. FFRCT was measured in a blinded fashion by an independent core laboratory. FFRCT value was evaluable in 43 out of 48 (89.6 %) patients with high prevalence of severe calcification in CCTA images [calcium score (CS) >400: 40 %, and CS > 1000: 19 %). Per-vessel FFRCT value showed good correlation with invasive FFR value (Spearman's rank correlation = 0.69, P < 0.001). The area under the receiver operator characteristics curve (AUC) of FFRCT was 0.87. Per-vessel accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were 68.6, 92.9, 52.4, 56.5, and 91.7 %, respectively. Even in eight patients (13 vessels) with extremely severely calcified lesions (CS > 1000), per-vessel FFRCT value showed a diagnostic performance similar to that in patients with CS ≤ 1000 (Spearman's rank correlation = 0.81, P < 0.001). FFRCT could be measured in the majority of consecutive patients who had suspected significant CAD by CCTA in real clinical practice and demonstrated good diagnostic performance for detecting hemodynamically significant CAD even in patients with extremely severe calcified vessels.