A randomised multicentre study of angiography- versus physiologyguided percutaneous coronary intervention in patients with coronary artery disease undergoing TAVI: design and rationale of the FAITAVI trial.

The treatment of coronary artery disease (CAD) in patients with severe aortic valve stenosis (AVS) eligible for transcatheter aortic valve implantation (TAVI) is not supported by clinical evidence, and the role of physiology over anatomy as well as the timing of coronary intervention are not defined. FAITAVI (ClinicalTrials.gov: NCT03360591) is a nationwide prospective, open-label, multicentre, randomised controlled study comparing the angiography-guided versus the physiology-guided coronary revascularisation strategy in patients with combined significant CAD and severe AVS undergoing TAVI. Significant CAD will be defined as coronary stenosis ≥50%, as assessed by visual estimation in vessels ≥2.5 mm. Physiology will be tested by fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR). The study will be conducted at 15 sites in Italy. In the angiography arm, percutaneous coronary intervention (PCI) will be performed either before TAVI, during the TAVI procedure - before or after the valve implantation - or within 1 month±5 days of the valve implantation, left to the operator's decision. In the physiology arm, FFR and iFR will be performed before TAVI, and PCI will be indicated for FFR ≤0.80, otherwise the intervention will be deferred. In case of borderline values (0.81-0.85), FFR and iFR will be repeated after TAVI, with PCI performed when needed. With a sample size of 320 patients, the study is powered to evaluate the primary endpoint (a composite of death, myocardial infarction, stroke, major bleeding, or ischaemia-driven target vessel revascularisation). TAVI indication, strategy and medical treatment will be the same in both groups. After discharge, patients will be contacted at 1, 6, 12 and 24 months after the procedure to assess their general clinical status, and at 12 months for the occurrence of events included in the primary and secondary endpoints. FAITAVI is the first randomised clinical trial to investigate "optimal" percutaneous coronary intervention associated with TAVI in patients with severe AVS and CAD.

Complete or Culprit-Only PCI in Older Patients with Myocardial Infarction.

BACKGROUND: The benefit of complete revascularization in older patients (≥75 years of age) with myocardial infarction and multivessel disease remains unclear. METHODS: In this multicenter, randomized trial, we assigned older patients with myocardial infarction and multivessel disease who were undergoing percutaneous coronary intervention (PCI) of the culprit lesion to receive either physiology-guided complete revascularization of nonculprit lesions or to receive no further revascularization. Functionally significant nonculprit lesions were identified either by pressure wire or angiography. The primary outcome was a composite of death, myocardial infarction, stroke, or any revascularization at 1 year. The key secondary outcome was a composite of cardiovascular death or myocardial infarction. Safety was assessed as a composite of contrast-associated acute kidney injury, stroke, or bleeding. RESULTS: A total of 1445 patients underwent randomization (720 to receive complete revascularization and 725 to receive culprit-only revascularization). The median age of the patients was 80 years (interquartile range, 77 to 84); 528 patients (36.5%) were women, and 509 (35.2%) were admitted for ST-segment elevation myocardial infarction. A primary-outcome event occurred in 113 patients (15.7%) in the complete-revascularization group and in 152 patients (21.0%) in the culprit-only group (hazard ratio, 0.73; 95% confidence interval [CI], 0.57 to 0.93; P = 0.01). Cardiovascular death or myocardial infarction occurred in 64 patients (8.9%) in the complete-revascularization group and in 98 patients (13.5%) in the culprit-only group (hazard ratio, 0.64; 95% CI, 0.47 to 0.88). The safety outcome did not appear to differ between the groups (22.5% vs. 20.4%; P = 0.37). CONCLUSIONS: Among patients who were 75 years of age or older with myocardial infarction and multivessel disease, those who underwent physiology-guided complete revascularization had a lower risk of a composite of death, myocardial infarction, stroke, or ischemia-driven revascularization at 1 year than those who received culprit-lesion-only PCI. (Funded by Consorzio Futuro in Ricerca and others; FIRE ClinicalTrials.gov number, NCT03772743.).

Intracoronary physiology-guided percutaneous coronary intervention in patients with diabetes.

OBJECTIVE: The risk of vessel-oriented cardiac adverse events (VOCE) in patients with diabetes mellitus (DM) undergoing intracoronary physiology-guided coronary revascularization is poorly defined. The purpose of this work is to evaluate the risk of VOCE in patients with and without DM in whom percutaneous coronary intervention (PCI) was performed or deferred based on pressure-wire functional assessment. METHODS: This is a retrospective analysis of a multicenter registry of patients evaluated with fractional flow reserve (FFR) and/or non-hyperaemic pressure ratio (NHPR). Primary endpoint was a composite of VOCE including cardiac death, vessel-related myocardial infarction (MI), and ischemia-driven target vessel revascularization (TVR). RESULTS: A large cohort of 2828 patients with 3353 coronary lesions was analysed to assess the risk of VOCE at long-term follow-up (23 [14-36] months). Non-insulin-dependent-DM (NIDDM) was not associated with the primary endpoint in the overall cohort (adjusted Hazard Ratio [aHR] 1.18, 95% CI 0.87-1.59, P = 0.276) or in patients with coronary lesions treated with PCI (aHR = 1.30, 95% CI 0.78-2.16, P = 0.314). Conversely, insulin-dependent diabetes mellitus (IDDM) demonstrated an increased risk of VOCE in the overall cohort (aHR 1.76, 95% CI 1.07-2.91, P = 0.027), but not in coronary lesions undergoing PCI (aHR 1.26, 95% CI 0.50-3.16, P = 0.621). Importantly, in coronary lesions deferred after functional assessment IDDM (aHR 2.77, 95% CI 1.11-6.93, P = 0.029) but not NIDDM (aHR = 0.94, 95% CI 0.61-1.44, P = 0.776) was significantly associated with the risk of VOCE. IDDM caused a significant effect modification of FFR-based risk stratification (P for interaction < 0.001). CONCLUSION: Overall, DM was not associated with an increased risk of VOCE in patients undergoing physiology-guided coronary revascularization. However, IDDM represents a phenotype at high risk of VOCE.

Clinical outcomes of left atrial appendage occlusion in patients with previous intracranial or gastrointestinal bleeding: Insights from the LOGIC (Left atrial appendage Occlusion in patients with Gastrointestinal or IntraCranial bleeding) International Multicenter Registry.

AIMS: To compare outcomes of patients who underwent left atrial appendage occlusion (LAAO) for nonvalvular atrial fibrillation (NVAF) and contraindication to anticoagulants due to history of either gastrointestinal (GI) or intracranial (IC) bleeding. METHODS: Patients with NVAF that underwent LAAO for GI or IC bleeding from seven centers were included in this observational study. Baseline characteristics, procedural features, and follow-up data were collected, and compared between the two groups. The primary outcomes were incidence of ischemic and hemorrhagic events at 12-month. RESULTS: Six hundred twenty-eight patients were included, 57% with previous GI-bleeding, and 43% with previous IC-bleeding. Median CHA 2 DS 2-VASc score was 4 (interquartile range [IQRs]: 3-5) for both GI-bleeding and IC-bleeding patients, while GI-bleeding patients had a higher HAS-BLED score (4 [IQRs: 3-4] vs. 3 [IQRs]: 2-3]; p = 0.001). At 12-month follow-up, relative risk reduction for stroke was similar between the two groups. The GI-bleeding group had more hemorrhagic events compared to IC-bleeding group (any bleeding 8.4% vs. 3.2%; p = 0.012; major bleeding BARC 3-5: 4.3% vs. 1.8; p = 0.010). At multivariate analysis history of GI bleeding was an independent predictor of hemorrhagic events (adjusted HR: 2.39, 95% confidence interval: 1.02-5.63; p = 0.047). CONCLUSIONS: Outcomes after LAAO may be affected by the different indications for the procedure. In our study, GI-bleeding and IC-bleeding as indication to LAAO differ in their baseline characteristics. LAAO confirms its efficacy in ischemic risk reduction in both groups, while GI bleeding seems to be an independent predictor of bleeding recurrence at 12 months behind the antithrombotic regimen.

Balloon-Assisted Crossing of a Severely Calcified Aortic Valve During Transcatheter Balloon-Expandable Bioprosthesis Implantation.

A 91-year-old man presented with syncope secondary to severe aortic stenosis. A transthoracic echocardiogram revealed a calcified stenotic trileaflet aortic valve (AV) with a mean gradient of 60 mm Hg and cardiac computed tomography demonstrated a heavily calcified trileaflet AV without commissural fusion. Following heart team discussion, transfemoral transcatheter AV replacement (TAVR) was the preferred option in view of the patient's age. Due to the severe aortic leaflet calcifications, a balloon-expandable 32-mm Myval transcatheter heart valve (Meril Life Sciences) implantation preceded by balloon predilation was planned. After numerous catheter and wire exchanges, the transcatheter heart valve was finally implanted with a good final result.

Procedural outcomes of the 34 mm EvolutR Transcatheter valve in a real-world population insights from the HORSE multicenter collaborative registry.

OBJECTIVES: The aim of this study was to evaluate outcomes of real-world patients with aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR) with the 34 mm Evolut R (Medtronic, Minneapolis, Minnesota). BACKGROUND: Larger aortic annulus has been associated with increased incidence of paravalvular leaks (PVLs) after TAVR. However, little is known, so far, about the performance of the 34 mm Evolut R in this setting. METHODS: From the multicenter, international, retrospective Horizontal Aorta in Transcatheter Self-expanding Valves (HORSE) registry, including patients who underwent TAVR for native severe AS, we selected patients treated with the 34 mm Evolut R evaluating procedural characteristics and VARC-2 defined device success. We also compared 34 mm Evolut R with other Evolut R sizes. RESULTS: Among the 4434 patients included in the registry, 572 (13%) received the 34 mm Evolut R valve. Mean age was 80.8 ± 6.5 years and the median STS PROM score was 4 [interquartile range 2-6]. Device success was achieved in 87.4% with 7.7% of PVLs; moreover, the rate of permanent pacemaker implantation (PPMI) was 22.4%. Patients who underwent 34 mm Evolut R implantation experienced more in-hospital permanent pacemaker implantation (22.4% vs. 15%; p < 0.001). At multivariate analysis, 34 mm Evolut R did not affect device success (OR: 0.81 [0.60-1.09]; p = 0.151). Device success was consistent with other THVs sizes (87.4% vs. 89.6%; p = 0.157). CONCLUSIONS: THV replacement in patients requiring 34 mm Evolut R has an acceptable performance. Compared to other Medtronic sizes it demonstrated to be comparable in terms of device success, despite an increased rate of pacemaker implantation.

Surgical redo versus transseptal or transapical transcatheter mitral valve-in-valve implantation for failed mitral valve bioprosthesis.

BACKGROUND: Redo surgical mitral valve replacement (SMVR) is the current standard of care for patients with failed bioprosthetic mitral valve (MV). Transcatheter mitral valve-in-valve replacement (TMViV) is arising as an alternative to SMVR in high risk patients. We sought to evaluate procedural safety, early and mid-term outcomes of patients who underwent transseptal TMViV (TS-TMViV), transapical TMViV (TA-TMViV), or redo-SMVR. METHODS: We identified patients with failed bioprosthetic MV who underwent TS-TMViV, TA-TMViV, or SMVR at four Italian Centers. Clinical and echocardiographic data were codified according to Mitral Valve Academic Research Consortium definition (MVARC), except for significant valve stenosis. RESULTS: Between December 2012 and September 27, 2019 patients underwent TS-TMViV, 22 TA-TMViV, and 29 redo-SMVR. TS-TMViV and TA-TMViV patients presented higher mean age and surgical risk scores compared with SMVR group (77.8 ± 12 years, 77.3 ± 7.3 years, 67.8 ± 9.4 years, p < .001; STS PROM 8.5 ± 7.2; 8.9 ± 4.7; 3.6 ± 2.6, p < .001). TS-TMViV procedure was associated with shorter intensive care unit time and total length of stay (LOS) compared with TA-TMViV and SMVR group. There were no differences in MVARC procedural success at 30-days (74.1, 72.7, and 51.7%, p = .15) and one-year all-cause mortality between groups (14.8, 18.2, and 17.2%, p = 1.0). MV mean gradient was similar between TS-TMViV, TA-TMViV, and SMVR groups at 30 days and 12 months. CONCLUSIONS: For the selected patients, TS-TMViV and TA-TMViV are to be considered a valid alternative to redo-SMVR with comparable 1-year survival. TS-TMViV is the less invasive strategy and has the advantage of shortening the LOS compared with TA-TMViV.

Left atrial appendage occlusion in atrial fibrillation patients with previous intracranial bleeding: A national multicenter study.

BACKGROUND: Intracranial hemorrhage (ICH) represents the most serious complication of oral anticoagulant therapy (OAT) in patients with atrial fibrillation (AF), and AF patients with previous ICH are a challenge for clinicians. Left atrial appendage (LAA) occlusion has emerged as an alternative option for AF patients not suitable for OAT. Currently, few data are available on long term outcomes after LAA occlusion in this population. We evaluated the safety and efficacy of LAA occlusion in a cohort of patients with AF and previous ICH. METHODS: This is a multicenter, observational, retrospective study involving 5 LAA occlusion centers in Italy. It includes all consecutive patients (n = 120) with previous ICH who underwent LAA occlusion for nonvalvular AF and high thromboembolic risk. Procedural outcomes, post-procedural therapies and 12-months follow-up data were analyzed. RESULTS: The device was successfully implanted in 100% of cases, with a 6% of major peri-procedural complications. 59% had a prior ICH during OAT. The sample had a high risk of stroke (5.18%/year) and bleeding (6.62%/year). 30% were discharged on single and 54.2% on dual antiplatelet therapy. The expected annual risk for thromboembolism was 5.1%. Excluding periprocedural ischemic complications, the stroke annual rate was 1.8%. The expected annual risk of bleeding was 6.7%. The observed annual bleeding rate was 5.45%. CONCLUSIONS: Percutaneous LAA occlusion is an effective option for AF patients and previous intracranial hemorrhage. After LAA occlusion, a single antiplatelet therapy strategy could be considered for patients with the highest risk of recurrent bleeding.

Transcatheter aortic valve implantation (TAVI) in cardiogenic shock: TAVI-shock registry results.

OBJECTIVES: Aim of this study is to evaluate safety, feasibility, and mid-term outcome of transcatheter aortic valve implantation (TAVI) in cardiogenic shock (CS). BACKGROUND: Balloon aortic valvuloplasty in patients with severe aortic valve stenosis (SAS) complicated by CS is indicated but associated with a grim prognosis. TAVI might be a more reasonable treatment option in this setting but data are scant. METHODS: From March 2008 to February 2019, 51 patients with severe aortic valvulopathy (native SAS or degenerated aortic bioprosthesis) and CS treated by TAVI in 11 European centers were included in this multicenter registry. Demographic, clinical, and procedural data were collected, as well as clinical and echocardiographic follow-up. RESULTS: The mean age of our study population was 75.8 ± 13, 49% were women, and mean Society of Thoracic Surgeons (STS) score was 19 ± 15%. Device success was achieved in 94.1%, with a 5% incidence of moderate/severe paravalvular leak. The 30-day events were mortality 11.8%, stroke 2.0%, vascular complications 5.9%, and acute kidney injury 34%. Valve Academic Research Consortium-2 early safety endpoint was reached in 35.3% of cases. At 1-year of follow-up, the mortality rate was 25.7% and the readmission for congestive heart failure was 8.6%. CONCLUSIONS: TAVI seems to be a therapeutic option for patients with CS and SAS or degenerated aortic bioprosthesis in terms of both safety and efficacy at early and long-term follow-up.

Physiological Versus Angiographic Guidance for Myocardial Revascularization in Patients Undergoing Transcatheter Aortic Valve Implantation.

Background Management of coronary artery disease in patients undergoing transcatheter aortic valve implantation is uncertain. Fractional flow reserve (FFR) has never been clinically validated in aortic stenosis. The study aim was to analyze the clinical outcome of FFR-guided revascularization in patients undergoing transcatheter aortic valve implantation. Methods and Results Patients with severe aortic stenosis and coronary artery disease at coronary angiography were included in this retrospective analysis and divided in 2 groups: angiography guided (122/216; 56.5%) versus FFR-guided revascularization (94/216; 43.5%). Patients were clinically followed up and evaluated for the occurrence of major adverse cardiac and cerebrovascular events at 2-year follow-up. Most lesions in the FFR group resulted negative according to the conventional 0.80 cutoff value (111/142; 78.2%) and were deferred. The FFR-guided group showed a better major adverse cardiac and cerebrovascular event-free survival compared with the angio-guided group (92.6% versus 82.0%; hazard ratio, 0.4; 95% CI, 0.2-1.0; P=0.035). Patients with deferred lesions based on FFR presented better outcome compared with patients who underwent angio-guided percutaneous coronary intervention (91.4% versus 68.1%; hazard ratio, 0.3; 95% CI, 0.1-0.6; P=0.001). Conclusions FFR guidance was associated with favorable outcome in this observational study in patients undergoing transcatheter aortic valve implantation. Randomized trials are needed to investigate the long-term effects of FFR-guided revascularization against angiographic guidance alone in patients with aortic stenosis.

Diagnostic Performance of In-Procedure Angiography-Derived Quantitative Flow Reserve Compared to Pressure-Derived Fractional Flow Reserve: The FAVOR II Europe-Japan Study.

BACKGROUND: Quantitative flow ratio (QFR) is a novel modality for physiological lesion assessment based on 3-dimensional vessel reconstructions and contrast flow velocity estimates. We evaluated the value of online QFR during routine invasive coronary angiography for procedural feasibility, diagnostic performance, and agreement with pressure-wire-derived fractional flow reserve (FFR) as a gold standard in an international multicenter study. METHODS AND RESULTS: FAVOR II E-J (Functional Assessment by Various Flow Reconstructions II Europe-Japan) was a prospective, observational, investigator-initiated study. Patients with stable angina pectoris were enrolled in 11 international centers. FFR and online QFR computation were performed in all eligible lesions. An independent core lab performed 2-dimensional quantitative coronary angiography (2D-QCA) analysis of all lesions assessed with QFR and FFR. The primary comparison was sensitivity and specificity of QFR compared with 2D-QCA using FFR as a reference standard. A total of 329 patients were enrolled. Paired assessment of FFR, QFR, and 2D-QCA was available for 317 lesions. Mean FFR, QFR, and percent diameter stenosis were 0.83±0.09, 0.82±10, and 45±10%, respectively. FFR was ≤0.80 in 104 (33%) lesions. Sensitivity and specificity by QFR was significantly higher than by 2D-QCA (sensitivity, 86.5% (78.4-92.4) versus 44.2% (34.5-54.3); P<0.001; specificity, 86.9% (81.6-91.1) versus 76.5% (70.3-82.0); P=0.002). Area under the receiver curve was significantly higher for QFR compared with 2D-QCA (area under the receiver curve, 0.92 [0.89-0.96] versus 0.64 [0.57-0.70]; P<0.001). Median time to QFR was significantly lower than median time to FFR (time to QFR, 5.0 minutes [interquartile range, -6.1] versus time to FFR, 7.0 minutes [interquartile range, 5.0-10.0]; P<0.001). CONCLUSIONS: Online computation of QFR in the catheterization laboratory is clinically feasible and is superior to angiographic assessment for evaluation of intermediary coronary artery stenosis using FFR as a reference standard. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02959814.

Coronary physiology in patients with severe aortic stenosis: Comparison between fractional flow reserve and instantaneous wave-free ratio.

BACKGROUND: The functional assessment of coronary artery disease (CAD) in patients with aortic stenosis (AS) has not been validated so far, and the best strategy to physiologically investigate the relevance of coronary stenosis in this specific setting of patients remains undetermined. The aim of the study is to compare the diagnostic performance of instantaneous wave-free ratio (iFR) and fractional flow reserve (FFR) in patients with severe AS. METHODS: The functional significance of 179 coronary lesions was investigated with on-line iFR and FFR measurements in 85 AS patients and compared with a control group formed by 167 patients (290 lesions) with stable CAD and without AS. The iFR-FFR diagnostic agreement has been tested using the conventional 0.80 FFR cut-off. RESULTS: The correlation between iFR and FFR was similar between AS and CAD patients, as well as the area under the curve at ROC curve analysis (0.97 vs 0.96, p=0.88). However, using the standard iFR 0.89 threshold, the diagnostic accuracy of iFR was significantly lower in AS compared with CAD (76.3% vs 86.1%, p=0.009). According to ROC analysis, the best iFR cut-off in predicting FFR≤0.8 was lower in AS (0.83, J=0.82) compared with CAD (0.89, J=0.81). Using the ROC derived cut-off of 0.83, the iFR accuracy increased significantly (91.3%, p=0.003) while maintaining an elevated negative predictive value (95.5%). CONCLUSIONS: In the presence of severe AS, conventional iFR cut-off had lower diagnostic agreement with FFR classification of coronary lesions compared to stable CAD patients. AS seems to influence iFR cut-off ischemic thresholds and deserves further comparative studies.

Percutaneous left atrial appendage closure in awake non intubated patient: Multimodality intraprocedural imaging.

We present a case of percutaneous left atrial appendage closure in awake non intubated patient, in which Intraprocedural ultrasound images were obtained with a micro transesophageal echocardiographic probe (MTEE) and intracardiac echocardiography (ICE) together with angiography.

Left ventricular apical ballooning syndrome in men: a case series.

OBJECTIVES: Apical ballooning syndrome usually involves elderly women. We reported the profile of this syndrome in men. METHODS: We identified 54 consecutive patients with the syndrome: among them, seven were men (13%, group M) and 47 were women (87%, group F). RESULTS: Men were younger than women (group M 61.7 years vs. group F 72.8 years, median age, P < 0.01) and emotional triggers predominated in women ( group M 14.3% vs. group F 44.7%, P = 0.01) compared with physiological ones which were more frequent in men (group M 42.9% vs. group F 19.1%, P = 0.02). At onset, men were more compromised than women (group M 42.9% vs. group F 6.4%, P = 0.004). At the median follow-up of 18.5 months, more men died than women (group M 28.6% vs. group F 8.5%, P = NS), but only women had cardiac-related deaths (group M 0% vs. group F 6.4%, P = NS). Cardiac outcome was similar in both groups (group M 14.3% vs. group F 23.4%, P = NS). Left ventricular ejection fraction increased in both sexes from 41% to more than 56% (P < 0.01). CONCLUSION: In this small case series, left ventricular apical ballooning syndrome showed similar features in both sexes. However, men seemed to be more affected at younger age, presented more physiological triggers and more compromised clinical status at admission. Despite this, cardiac outcome was good in both sexes.

Mitral valve repair complicated by iatrogenic coronary artery lesion treated with percutaneous coronary intervention.

We report a case of mitral valve repair complicated by iatrogenic coronary artery lesion. This rare coronary injury caused an acute ST-elevation myocardial infarction and it was treated successfully with a percutaneous coronary intervention.