Fractional Flow Reserve to Guide Treatment of Patients With Multivessel Coronary Artery Disease.

BACKGROUND: There is limited evidence that fractional flow reserve (FFR) is effective in guiding therapeutic strategy in multivessel coronary artery disease (CAD) beyond prespecified percutaneous coronary intervention or coronary graft surgery candidates. OBJECTIVES: The FUTURE (FUnctional Testing Underlying coronary REvascularization) trial aimed to evaluate whether a treatment strategy based on FFR was superior to a traditional strategy without FFR in the treatment of multivessel CAD. METHODS: The FUTURE trial is a prospective, randomized, open-label superiority trial. Multivessel CAD candidates were randomly assigned (1:1) to treatment strategy based on FFR in all stenotic (≥50%) coronary arteries or to a traditional strategy without FFR. In the FFR group, revascularization (percutaneous coronary intervention or surgery) was indicated for FFR ≤0.80 lesions. The primary endpoint was a composite of major adverse cardiac or cerebrovascular events at 1 year. RESULTS: The trial was stopped prematurely by the data safety and monitoring board after a safety analysis and 927 patients were enrolled. At 1-year follow-up, by intention to treat, there were no significant differences in major adverse cardiac or cerebrovascular events rates between groups (14.6% in the FFR group vs 14.4% in the control group; hazard ratio: 0.97; 95% confidence interval: 0.69-1.36; P = 0.85). The difference in all-cause mortality was nonsignificant, 3.7% in the FFR group versus 1.5% in the control group (hazard ratio: 2.34; 95% confidence interval: 0.97-5.18; P = 0.06), and this was confirmed with a 24 months' extended follow-up. FFR significantly reduced the proportion of revascularized patients, with more patients referred to exclusively medical treatment (P = 0.02). CONCLUSIONS: In patients with multivessel CAD, we did not find evidence that an FFR-guided treatment strategy reduced the risk of ischemic cardiovascular events or death at 1-year follow-up. (Functional Testing Underlying Coronary Revascularisation; NCT01881555).

Blunting periprocedural myocardial necrosis: Rationale and design of the randomized ALPHEUS study.

BACKGROUND: Clopidogrel associated with aspirin is the recommended treatment for patients undergoing elective percutaneous coronary intervention (PCI). Although severe PCI-related events are rare, evidence suggests that PCI-related myocardial infarction and myocardial injury are frequent complications that can impact the clinical prognosis of the patients. Antiplatelet therapy with a potent P2Y12 receptor inhibitor such as ticagrelor may reduce periprocedural ischemic complications while maintaining a similar safety profile as compared with conventional dual antiplatelet therapy by aspirin and clopidogrel in this setting. METHODS: Assessment of Loading with the P2Y12 inhibitor ticagrelor or clopidogrel to Halt ischemic Events in patients Undergoing elective coronary Stenting (ALPHEUS) (NCT02617290) is an international, multicenter, randomized, parallel-group, open-label study in patients with stable coronary artery disease who are planned for an elective PCI. In total, 1,900 patients will be randomized before a planned PCI to a loading dose of ticagrelor 180 mg or a loading dose of clopidogrel (300 or 600 mg) in addition to aspirin. Patients will then receive a dual antiplatelet therapy with aspirin and ticagrelor 90 mg twice daily or clopidogrel 75 mg once daily for 30 days. The primary ischemic end point is PCI-related myocardial infarction (myocardial infarction type 4a or 4b) or major myocardial injury within 48 hours (or at hospital discharge if earlier) after elective PCI/stent. Safety will be evaluated by major bleeding events (Bleeding Academic Research Consortium type 3 or 5) at 48 hours (or discharge if it occurs earlier). CONCLUSION: ALPHEUS is the first properly sized trial comparing ticagrelor to clopidogrel in the setting of elective PCI and is especially designed to show a reduction in periprocedural events, a surrogate end point for mortality.

Left Ventricular Rapid Pacing Via the Valve Delivery Guidewire in Transcatheter Aortic Valve Replacement.

OBJECTIVES: This study investigated whether left ventricular (LV) stimulation via a guidewire-reduced procedure duration while maintaining efficacy and safety compared with standard right ventricular (RV) stimulation. BACKGROUND: Rapid ventricular pacing is necessary to ensure cardiac standstill during transcatheter aortic valve replacement (TAVR). METHODS: This is a prospective, multicenter, single-blinded, superiority, randomized controlled trial. Patients undergoing transfemoral TAVR with a SAPIEN valve (Edwards Lifesciences, Irvine, California) were allocated to LV or RV stimulation. The primary endpoint was procedure duration. Secondary endpoints included efficacy, safety, and cost at 30 days. RESULTS: Between May 2017 and May 2018, 307 patients were randomized, but 4 were excluded because they did not receive the intended treatment: 303 patients were analyzed in the LV (n = 151) or RV (n = 152) stimulation groups. Mean procedure duration was significantly shorter in the LV stimulation group (48.4 ± 16.9 min vs. 55.6 ± 26.9 min; p = 0.0013), with a difference of -0.12 (95% confidence interval: -0.20 to -0.05) in the log-transformed procedure duration (p = 0.0012). Effective stimulation was similar in the LV and RV stimulation groups: 124 (84.9%) versus 128 (87.1%) (p = 0.60). Safety of stimulation was also similar in the LV and RV stimulation groups: procedural success occurred in 151 (100%) versus 151 (99.3%) patients (p = 0.99); 30-day MACE-TAVR (major adverse cardiovascular event-transcatheter aortic valve replacement) occurred in 21 (13.9%) versus 26 (17.1%) patients (p = 0.44); fluoroscopy time (min) was lower in the LV stimulation group (13.48 ± 5.98 vs. 14.60 ± 5.59; p = 0.02), as was cost (€18,807 ± 1,318 vs. €19,437 ± 2,318; p = 0.001). CONCLUSIONS: Compared with RV stimulation, LV stimulation during TAVR was associated with significantly reduced procedure duration, fluoroscopy time, and cost, with similar efficacy and safety. (Direct Left Ventricular Rapid Pacing Via the Valve Delivery Guide-wire in TAVR [EASY TAVI]; NCT02781896).

Characteristics and outcomes of patients ≤ 75 years who underwent transcatheter aortic valve implantation: insights from the SOURCE 3 Registry.

BACKGROUND: Current trials and registries of transcatheter valve implantation (TAVI) mostly include patients older than 75 years. Little is known about younger patients who undergo this treatment. We investigated comorbidities among patients < 75 years old who underwent TAVI in the SAPIEN 3™ European post-approval SOURCE 3 Registry, and analysed outcomes at 30 days and 1 year. METHODS AND RESULTS: Three age groups of patients were analysed for outcomes and characteristics: < 75 (n = 235), 75-80 (n = 391) and ≥ 80 years (n = 1320). Overall, the mean age was 81.6 ± 6.7 years; transfemoral access was used in 87.1% of patients treated with SAPIEN 3 transcatheter heart valves. The mean logistic EuroSCORE increased according to age group (12.6%, 17.3% and 19.7%, respectively, p < 0.001). Younger patients had a higher incidence of comorbidities, particularly those not included in surgical risk score assessment tools, e.g., severe liver disease, previous radiation therapy, and porcelain aorta. Mortality rates were similar between age groups at 30 days (1.7%, 2.0% and 2.3%, respectively, p = 0.79) and 1 year (14.2%, 9.3% and 13.3%, respectively, p = 0.08). However, sudden cardiac death rates were higher in the < 75 years age group compared with the ≥ 85 years age group (20.7% vs. 4.8%, p = 0.010). CONCLUSIONS: In current TAVI practice, patients younger than 75 years are a minority (12%). Despite younger age and lower surgical risk scores, this cohort was characterized by comorbidities not accounted for by traditional surgical risk scores. More data are needed for this age group to guide the appropriate decision between surgery and TAVI. CLINICALTRIAL. GOV NUMBER: NCT02698956.

Time-Course Reduction in Patient Exposure to Radiation From Coronary Interventional Procedures: The Greater Paris Area Percutaneous Coronary Intervention Registry.

BACKGROUND: The frequency of complex percutaneous coronary interventions (PCIs) has increased in the last few years, with a growing concern on the radiation dose received by the patients. Multicenter data from large unselected populations on patients' radiation doses during coronary angiography (CA) and PCI and temporal trends are lacking. This study sought to evaluate the temporal trends in patients' exposure to radiation from CA and PCI. METHODS AND RESULTS: Data were taken from the CARDIO-ARSIF registry that prospectively collects data on all CAs and PCIs performed in the 36 catheterization laboratories in the Greater Paris Area, the most populated regions in France with about 12 million inhabitants. Kerma area product and Fluoroscopy time from 152 684 consecutive CAs and 103 177 PCIs performed between 2009 and 2013 were analyzed. A continuous trend for a decrease in median [interquartile range] Kerma area product was observed, from 33 [19-55] Gy cm2 in 2009 to 27 [16-44] Gy cm2 in 2013 for CA (P<0.0001), and from 73 [41-125] to 55 [31-91] Gy cm2 for PCI (P<0.0001). Time-course differences in Kerma area product remained highly significant after adjustment on Fluoroscopy time, PCI procedure complexity, change of x-ray equipment, and other patient- and procedure-related covariates. CONCLUSIONS: In a large patient population, a steady temporal decrease in patient radiation exposure during CA and PCI was noted between 2009 and 2013. Kerma area product reduction was consistent in all types of procedure and was independent of patient-related factors and PCI procedure complexity.

Myocardial Fractional Flow Reserve Measurement Using Contrast Media as a First-Line Assessment of Coronary Lesions in Current Practice.

BACKGROUND: Fractional flow reserve (FFR) measurement requires adenosine injection. However, adenosine can induce conductive and rhythmic complications, or be contraindicated in some patients. Contrast-induced hyperemia could provide a simple first-line method (contrast-enhanced FFR; cFFR) to assess coronary lesions. In this study we evaluated the accuracy of cFFR to predict lesion significance. METHODS: This prospective study included 104 patients with 138 coronary lesions. Each stenosis was evaluated using resting distal coronary pressure to aortic pressure ratio (Pd/Pa) measurements using intracoronary iodixanol (cFFR) and adenosine (FFR) injection. An FFR value ≤ 0.8 defined a significant lesion. RESULTS: Dose-ranging analysis (n = 12 lesions) showed that 10 mL iodixanol was required to obtain the lowest cFFR value. Intermeasurement reproducibility of cFFR (n = 18 lesions) showed limited variability and small mean estimated bias (0.001 ± 0.014). Values of cFFR and FFR were highly correlated in a first series of n = 36 lesions (r = 0.9; P < 0.001). Receiver-operating characteristic curve analysis showed an excellent accuracy of cFFR cutoff value of ≤ 0.85 in predicting FFR value ≤ 0.80 (area under the curve, 0.94; 95% confidence interval, 0.90-0.98; sensitivity, 95%; specificity, 73%). This threshold was then tested prospectively in an independent cohort of n = 72 lesions. A cFFR value ≤ 0.85 correctly identified hemodynamically significant lesions with a sensitivity of 100%, specificity of 78%, positive predictive value of 78%, and negative predictive value of 100%. CONCLUSIONS: cFFR is reproducible and can be achieved with usual volumes of contrast. A cFFR threshold value of 0.85 provides excellent sensitivity and negative predictive value in coronary artery stenosis.

Spontaneous Coronary Artery Dissection Associated With Ascending Aortic Dystrophy: A Tear for Fear.

A 36-year-old man with a recent history of surgery for an aortic valve ascending aortic aneurysm was admitted for non-ST-elevation myocardial infarction. Cardiac magnetic resonance imaging showed a limited necrotic lesion in the anterior wall. Coronary angiography showed no significant stenosis, but a mild distal dynamic tortuosity was seen on the left anterior descending artery. Optical coherence tomography analysis confirmed the absence of any significant atherosclerotic infiltration but revealed the presence of a localized short arterial dissection within the kinked zone. The patient was managed with a conservative medical approach. The subsequent evolution was uneventful.

Transcatheter aortic valve implantation through carotid artery access under local anaesthesia.

OBJECTIVES: Trans-femoral and transapical are the most commonly used accesses for transcatheter aortic valve implantation (TAVI). However, when these approaches are unsuitable, alternative accesses are needed. We report a series of 19 patients undergoing TAVI through common carotid artery (CCA) access under local anaesthesia in order to assess its feasibility and safety. METHODS: From November 2008 to September 2013, 361 patients underwent TAVI at our institution. Nineteen of them (14 men) with mean age 82.2 ± 6.2 years, EuroSCORE 25.2 ± 15.7, Society of Thoracic Surgeons score 11.9 ± 5.1 and with severe peripheral arteriopathy were unsuitable for usual approaches and underwent TAVI through CCA access under local anaesthesia. Preoperative computed tomography assessed suitable carotid artery anatomy. Common carotid cross-clamping test allowed verifying patient's neurological status stability. An 18-Fr or 20-Fr sheath inserted into the CCA down into the ascending aorta was used for the delivery catheter. Valve implantation procedures were as usual. After sheath removal, the CCA was surgically purged and repaired. Feasibility and safety end points (VARC-2) were collected up to 30 days. RESULTS: Transcarotid insertion of the delivery sheath was successful in all cases (8 right, 11 left) and accurate deployment of the device was achieved in 18 patients (4 Edwards SAPIEN XT and 14 Medtronic CoreValve). There was 1 intraoperative death by annulus rupture during preimplant balloon valvuloplasty, and 1 in-hospital death due to multisystem organ failure. There was no myocardial infarction, stroke or major bleeding. Third-degree atrioventricular block requiring pacemaker implantation occurred in 3 patients. No vascular access-site, access-related or other TAVI-related complication occurred. Echocardiography revealed good prosthesis functioning with none, mild and moderate paravalvular leak in, respectively, 8, 9 and 1 patients. Patient ambulation was immediate after TAVI and hospital stay was 4.6 ± 2.3 days. CONCLUSIONS: TAVI through the CCA approach under local anaesthesia is feasible and safe. It allows continuous clinical neurological status monitoring with low risk of stroke, bleeding events, vascular access-site and access-related complications and immediate patient ambulation. It appears to be a valuable alternative access for patients who cannot undergo trans-femoral TAVI.

Patient exposure to X-rays during coronary angiography and percutaneous transluminal coronary intervention: results of a multicenter national survey.

OBJECTIVES: To evaluate practices for the protection from radiation of patients during coronary angiography (CA) and percutaneous coronary intervention (PCI), and to update reference values for the main radiation dose parameters. BACKGROUND: Few multicenter data from large populations exist on radiation doses to patients during CA and PCI. METHODS: RAY'ACT is a multicenter, nationwide French survey, with retrospective analysis of radiation parameters routinely registered in professional software from 33,937 CAs and 27,826 PCIs performed at 44 centers from January 1, through December 31, 2010. RESULTS: Kerma-area product (KAP) was registered in 91.7% (44/48) of centers and in 91.5% of procedures for CA (median, 27.2 Gy·cm(2) , interquartile range [IQR], 15.5-45.2) and 91.1% for PCI (median, 56.8 Gy·cm(2) , IQR, 32.8-94.6). Fluoroscopy time was registered in 87.5% (42/48) of centers and in 83.1% of procedures (median, 3.7 min, IQR, 2.3-6.3 for CA; 10.3 min, 6.7-16.2 for PCI). Variability across centers was high. Old equipment and routine left ventriculography were more common and number of registered frames and frame rate were higher in centers delivering high doses. The radial route was associated with lower doses than the femoral route (median KAP 26.8 Gy·cm(2) [15.1-44.25] vs. 28.1 [16.4-46.9] for CA, respectively; and 55.6 Gy·cm(2) [32.2-92.1] vs. 59.4 [24.6-99.9] for PCI, respectively; P < 0.01). CONCLUSIONS: This survey showed a very high rate of compliance with dose registration during CA and PCI in French nonacademic hospitals. Updated diagnostic reference values are established for the main dose parameters (KAP, 45 Gy·cm(2) for CA, 95 Gy·cm(2) for PCI).

Incidence, predictors and prognostic value of serious hemorrhagic complications following transcatheter aortic valve implantation.

BACKGROUND: TAVI is an alternative solution for patients with aortic valve stenosis (AS) who are refused for conventional surgery. We sought to evaluate the incidence, characteristics, predictors and prognosis impact of serious hemorrhagic complications following transcatheter aortic valve implantation (TAVI). METHODS: One hundred and seventy one consecutive patients with symptomatic severe AS (83.5 ± 6.1 y; 53% women; mean EuroSCORE=22.1 ± 12.3) underwent transapical (TA) or transfemoral (TF) TAVI in our institution using Edwards SAPIEN© and Medtronic CoreValve© devices. The primary evaluated criterion was the incidence of any bleeding complication, according to the Valve Academic Research Consortium (VARC) criteria. RESULTS: VARC serious hemorrhagic complications occurred in 34.5% of patients (n=23 life-threatening/disabling (LT/D) and n=36 major bleedings). Most of these complications were related to access site complications (69%). Multivariable analysis revealed that TA access, low weight and underlying coronary artery diseases were independent predictors for development of serious bleeding. The mortality was significantly higher in patients with serious events compared to patients without bleeding (p=0.008, log-rank analysis). Although the survival didn't significantly differ in patients with major hemorrhagic events, subjects with LT/D bleeding events had a higher mortality than the subjects with no hemorrhagic complications (p<0.001, log-rank analysis). Occurrence of VARC LT/D event independently predicted all-cause mortality (HR=5.35 [2.51-11.43], p<0.001) during the first year following TAVI in multivariate Cox regression analysis. CONCLUSION: Severe bleeding is frequent following TAVI procedure and is mainly related to local hemorrhage. VARC LT/D events are associated with decreased survival after AS correction.

Transfemoral aortic valve implantation in a renal transplant patient with a Dacron aorto-bi-iliac bypass.

Transcatheter aortic valve implantation (TAVI) is becoming the standard of care for inoperable patients with symptomatic severe aortic stenosis and the transfemoral approach is generally the first option chosen. However, transfemoral aortic valve replacement is contraindicated in patients with a Dacron aorto-bi-iliac bypass. To the best of our knowledge, we present the first case report of transfemoral aortic valve implantation in a kidney transplant patient with a history of aorto-bi-iliac bypass. His predicted operative mortality of 45% for aortic valve replacement was prohibitive according to the Society of Thoracic Surgeons score. A 26 mm Sapien XT valve (Edwards) was successfully implanted. Inotropic support was required for the four days following the procedure, after which, he was weaned uneventfully. A permanent pacemaker implantation was necessary at day six to treat a symptomatic paroxysmal complete atrio-ventricular block. The patient made an excellent recovery with no further complications and has remained asymptomatic at six months. This case highlights the importance of a detailed anatomic vascular assessment combined with a multidisciplinary evaluation of the access site in patients evaluated for TAVI. We used multi-slice computed tomography scans of the iliofemoral arteries, the aorto-bi-iliac bypass and the thoraco-abdominal aorta to predict the potential pitfalls of a fully percutaneous transfemoral aortic valve implantation. The transfemoral approach was finally chosen in this case after considering the patient's suitable aorto-iliofemoral vasculature, his patent coronary artery bypass grafts and his predisposition for severe acute kidney injury.

Non-invasive diagnosis of ischaemic heart failure using 64-slice computed tomography.

AIMS: We evaluated the accuracy of 64-slice computed tomography (CT) to identify ischaemic aetiology of heart failure (IHF). METHODS AND RESULTS: Ninety-three consecutive patients in sinus rhythm with dilated cardiomyopathy but without suspicion of coronary artery disease (CAD) were enrolled when admitted for angiography. Accuracy of CT to detect significant stenosis (>50% lumen narrowing) was compared with quantitative coronary angiography. IHF was defined as a significant stenosis on left main or proximal left anterior descending artery or two or more vessels. Forty-three out of 1395 segments (3%) were heavily calcified and excluded. CT correctly assessed 103 of 142 (73%) significant stenosis and identified 46 of 50 (92%) patients without and 42 of 43 (98%) patients with CAD, 60 of 62 (97%) patients without and 28 of 31 (90%) patients with IHF. Overall, accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of CT for identifying CAD by segment was 96, 73, 99, 92, and 97%, respectively; by patient was 95, 98, 92, 91, and 98%, respectively; and for identifying IHF was 95, 90, 97, 93, and 95%, respectively. CONCLUSION: Non-invasive 64-slice CT assessment of the extent of CAD may offer a valid alternative to angiography for the diagnosis of IHF.

Comparison of 64-slice computed tomography planimetry and Doppler echocardiography in the assessment of aortic valve stenosis.

BACKGROUND AND AIM OF THE STUDY: The study aim was to compare, prospectively, the planimetry of aortic stenosis on 64-slice computed tomography (CT), with the area calculated by Doppler transthoracic echocardiography (TTE) in symptomatic patients evaluated before potential aortic valve replacement. METHODS: Fifty-two consecutive patients (27 males, 25 females; mean age 74 +/- 10 years) admitted to the authors' institution during 2005 were evaluated with 64-slice CT and Doppler TTE. The time interval between the two evaluations was 2 +/- 1 weeks. Planimetry of the anatomic orifice area (AOA) drawn on 64-slice CT was compared to the effective area determined by Doppler TTE by Bland and Altman analysis, and the anatomic area threshold value corresponding to a significant effective aortic stenosis (50.75 cm2) was determined by receiver operating characteristic (ROC) analysis. RESULTS: The aortic orifice area measured by 64-slice CT correlated well with the effective area (r = 0.76; p <0.0001), but was significantly greater, with a systematic overestimation (0.132 cm(2)) and a variability of 0.239 cm(2). There was good agreement between planimetry determined by two independent radiologists (difference = 0.002, variability = 0.115 cm(2)). ROC analysis showed that a threshold value of 0.95 cm(2) as measured by 64-slice CT planimetry identifies significant aortic stenosis with sensitivity, specificity, accuracy, positive and negative predictive values of 82%, 77%, 81%, 91% and 59%, respectively. CONCLUSION: 64-slice CT is a reproducible and reliable non-invasive method to evaluate aortic valve stenosis compared to the reference method of Doppler TTE. Indeed, the CT approach could replace the latter evaluation when measurements used in the continuity equation are inadequate.

Exclusive internal thoracic artery grafting in triple-vessel-disease patients: angiographic control.

BACKGROUND: The internal thoracic artery (ITA) is considered to be the conduit of choice for coronary artery bypass grafting surgery (CABG). In triple-vessel-disease patients, CABG can be performed exclusively using both ITAs in a Y fashion with multiple sequential side-to-side coronary anastomoses. The aim of this prospective study was to evaluate by early postoperative angiographic control, the patency and particularly the quality of ITA grafts and coronary anastomoses in this configuration. METHODS: Between October 2002 and October 2003, 92 triple-vessel-disease patients underwent CABG with this technique and consented to immediate postoperative angiographic control. The right ITA was divided at its origin and connected to the in-situ left ITA (ITA-Y anastomosis). The left ITA was anastomosed to anterior coronary arteries and the right ITA was anastomosed to lateral and inferior coronary arteries, for a total of 374 coronary anastomoses (4.1 anastomoses per patient; range, 3 to 6). RESULTS: There was 1 hospital death by septic shock. Two patients were reoperated on for superficial wound infection. There was no postoperative myocardial infarction or stroke. On postoperative angiograms, all ITA-Y (92) and ITA-coronary anastomoses (374) were patent. Competition of flow in right ITA to the moderately stenosed right coronary artery was observed in 9 patients, and there were 4 distal ITA-coronary stenoses, both without clinical consequences. CONCLUSIONS: In triple-vessel-disease patients, this procedure allows CABG without increasing operative risk. ITA-Y anastomoses and multiple sequential side-to-side ITA-coronary anastomoses are safe to perform and demonstrate excellent patency and quality in early postoperative angiographic control, particularly when coronary artery stenoses are significant (>70%).