Waldemar Bojara

Use of the Instantaneous Wave-free Ratio or Fractional Flow Reserve in PCI

Background Coronary revascularization guided by fractional flow reserve (FFR) is associated with better patient outcomes after the procedure than revascularization guided by angiography alone. It is unknown whether the instantaneous wave‐free ratio (iFR), an alternative measure that does not require the administration of adenosine, will offer benefits similar to those of FFR. Methods We randomly assigned 2492 patients with coronary artery disease, in a 1:1 ratio, to undergo either iFR‐guided or FFR‐guided coronary revascularization. The primary end point was the 1‐year risk of major adverse cardiac events, which were a composite of death from any cause, nonfatal myocardial infarction, or unplanned revascularization. The trial was designed to show the noninferiority of iFR to FFR, with a margin of 3.4 percentage points for the difference in risk. Results At 1 year, the primary end point had occurred in 78 of 1148 patients (6.8%) in the iFR group and in 83 of 1182 patients (7.0%) in the FFR group (difference in risk, ‐0.2 percentage points; 95% confidence interval [CI], ‐2.3 to 1.8; P<0.001 for noninferiority; hazard ratio, 0.95; 95% CI, 0.68 to 1.33; P=0.78). The risk of each component of the primary end point and of death from cardiovascular or noncardiovascular causes did not differ significantly between the groups. The number of patients who had adverse procedural symptoms and clinical signs was significantly lower in the iFR group than in the FFR group (39 patients [3.1%] vs. 385 patients [30.8%], P<0.001), and the median procedural time was significantly shorter (40.5 minutes vs. 45.0 minutes, P=0.001). Conclusions Coronary revascularization guided by iFR was noninferior to revascularization guided by FFR with respect to the risk of major adverse cardiac events at 1 year. The rate of adverse procedural signs and symptoms was lower and the procedural time was shorter with iFR than with FFR. (Funded by Philips Volcano; DEFINE‐FLAIR ClinicalTrials.gov number, NCT02053038.)

Short-term effects of transcatheter aortic valve implantation on neurohormonal activation, quality of life and 6-minute walk test in severe and symptomatic aortic stenosis

Objective This prospective study aimed to determine to what extent clinical symptoms and neurohumoral activation are improved in patients with severe aortic valve stenosis after transcatheter aortic valve implantation (TAVI) with the CoreValve prosthesis. Methods From June 2008 to June 2009 consecutive patients with symptomatic severe aortic valve stenosis (area<1 cm2), age≥75 years with a logistic EuroSCORE ≥15% or age>60 years plus additional specified risk factors were evaluated for TAVI. Examinations of study patients were performed before and 30 days after TAVI and comprised assessment of quality of life (Minnesota living with heart failure questionnaire, [MLHFQ]) 6-minute walk test, measurement of B-type natriuretic peptide and echocardiography. Aortic valve prosthesis was inserted retrograde using a femoral arterial or a subclavian artery approach. Results In 44 consecutive patients (mean age 79.1±7 years, 50% women, mean left ventricular ejection fraction 55.8±8.5%) TAVI was successfully performed. Follow-up 30 days after TAVI showed a significantly improved quality of life (baseline 44±19.1 vs 28±17.5 MLHFQ Score, p<0.001) and an enhanced distance in the 6-minute walk test (baseline 204±103 vs 266±123 m, p<0.001). B-type natriuretic peptide levels were reduced (baseline 725±837 vs 423±320 pg/ml, p=0.005). Conclusions Our preliminary results show a significant clinical benefit and a reduction of neurohormonal activation in patients with severe and symptomatic aortic valve stenosis early after TAVI.

Long-term outcome of patients with moderate and severe prosthetic aortic valve regurgitation after transcatheter aortic valve implantation.

Recently, moderate and severe postprocedure aortic regurgitations (ARs) have been identified as independent risk factors for short- and midterm mortality after transcatheter aortic valve implantation (TAVI). However, very few data exist on the long-term outcome of postprocedure AR. From 2008 to 2011, 198 consecutive patients with severe aortic stenosis successfully underwent TAVI with the CoreValve prosthesis (Medtronic CV, Minneapolis, Minnesota). After the procedure, patients were subdivided into groups depending on the presence of moderate/severe AR. The primary study end point was death from any cause after TAVI. The secondary end point was defined as cardiovascular death. In study patients (80 ± 6 years old, logistic European System for Cardiac Operative Risk Evaluation 22 ± 16%, left ventricular ejection fraction 53 ± 13%), moderate/severe AR occurred in 28 patients (14%). Despite similar baseline characteristics, patients with moderate/severe AR had higher 30-day and 1-year mortality rates than patients with none/mild AR (21% vs 6%, p = 0.019; 57% vs 16%, p <0.001, respectively). During a mean follow-up of 535 ± 333 days, the primary end point was reached in 54 and the secondary end point in 33 patients. Moderate/severe AR was the strongest independent risk factor of all-cause-mortality (hazard ratio 4.89, 95% confidence interval 2.78 to 8.56, p <0.001) and the strongest independent risk factor of cardiovascular mortality (hazard ratio 7.90, 95% confidence interval 3.95 to 15.81, p <0.001). In conclusion, moderate and severe postprocedure ARs are not uncommon complications after TAVI. Although long-term outcome of patients with none/mild AR is favorable, outcome of patients with moderate/severe AR is dismal.

One-Year Results of Transcatheter Aortic Valve Implantation in Severe Symptomatic Aortic Valve Stenosis

Transcatheter aortic valve implantation (TAVI) is an alternative therapy for symptomatic severe aortic valve stenosis in high-risk patients with several co-morbidities. We evaluated the 1-year effects of TAVI on quality of life, exercise capacity, neurohormonal activation, and myocardial hypertrophy. From June 2008 to October 2009, consecutive patients aged ≥75 years with symptomatic severe aortic valve stenosis (area <1 cm(2)) and a logistic euroSCORE ≥15% or aged >60 years with additional specified risk factors underwent TAVI. An aortic valve prosthesis (CoreValve) was inserted in a retrograde fashion. Examinations were performed before and 30 days and 1 year after TAVI. An assessment of the quality of life (Minnesota Living with Heart Failure Questionnaire), a 6-minute walking test, measurement of B-type natriuretic peptide, and echocardiography were performed. In 51 patients (mean age 78 ± 6.6 years, mean left ventricular ejection fraction 58.4 ± 12.2%), the follow-up examinations were performed after TAVI. The 1-year follow-up visit after TAVI revealed significantly improved quality of life (baseline Minnesota Living with Heart Failure Questionnaire score 39.6 ± 19 vs 26.1 ± 18, p <0.001) and more distance covered in the 6-minute walking test (baseline 185 ± 106 vs 266 ± 118 m, p <0.001). The B-type natriuretic peptide level had decreased (baseline 642 ± 634 vs 323 ± 266 pg/ml, p <0.001), and the left ventricular mass index had decreased (156 ± 45 vs 130 ± 42 g/m(2), p <0.001). The left ventricular diameter and ejection fraction remained unchanged. In conclusion, TAVI leads to significantly reduced neurohormonal activation, regression of myocardial hypertrophy, and lasting enhancement of quality of life and exercise capacity in patients with symptomatic and severe aortic stenosis 1 year after intervention.

Transcatheter aortic valve implantation for treatment of patients with degenerated aortic bioprostheses--valve-in-valve technique.

Background: The management of patients with degeneration of surgical bioprosthetic valve replacement remains a challenge because of the higher risk of re‐do aortic valve replacement. We present a case series of five patients with degenerated aortic bioprostheses treated with transfemoral transcatheter aortic valve implantation (TAVI). Methods: From December 2009 to May 2010, five patients with degenerated aortic valve bioprostheses (aortic valve area < 1 cm2 or severe aortic regurgitation), an excessive operative risk (EuroSCORE ≥ 30%), symptoms of heart failure (NYHA ≥ III) and an internal diameter of bioprosthetic aortic valve 20.5 ± 0.5 mm were included. Procedures were performed without hemodynamic support using femoral arteries. Balloon valvuloplasty with a 20‐mm balloon under rapid pacing was carried out before valve implantation. The 26‐mm CoreValve prosthesis, 18‐F‐generation (Medtronic, Minneapolis, Minnesota) was inserted retrograde under fluoroscopic guidance. Invasive and echocardiographic measurements were done immediately before and after TAVI. Clinical followup and echocardiography were performed after procedure (mean followup 72 days ± 60, range: 176–30 days). Results: In all patients TAVI was successful with immediate decrease of transaortic peak‐to‐peak pressure (P = 0.002). Mild aortic regurgitation occurred in two patients and one patient received a new permanent pacemaker. Major adverse cardiac and cerebrovascular events did not arise. NYHA functional class improved in all patients and left ventricular ejection fraction increased (P = 0.019). Conclusion: Our experiences with the valve‐in‐valve technique using the CoreValve prosthesis suggest that transfemoral TAVI is feasible in high risk patients with degenerated aortic bioprostheses.

Real-time use of instantaneous wave–free ratio: Results of the ADVISE in-practice: An international, multicenter evaluation of instantaneous wave–free ratio in clinical practice

Objectives To evaluate the first experience of real-time instantaneous wave–free ratio (iFR) measurement by clinicians. Background The iFR is a new vasodilator-free index of coronary stenosis severity, calculated as a trans-lesion pressure ratio during a specific period of baseline diastole, when distal resistance is lowest and stable. Because all previous studies have calculated iFR offline, the feasibility of real-time iFR measurement has never been assessed. Methods Three hundred ninety-two stenoses with angiographically intermediate stenoses were included in this multicenter international analysis. Instantaneous wave–free ratio and fractional flow reserve (FFR) were performed in real time on commercially available consoles. The classification agreement of coronary stenoses between iFR and FFR was calculated. Results Instantaneous wave–free ratio and FFR maintain a close level of diagnostic agreement when both are measured by clinicians in real time (for a clinical 0.80 FFR cutoff: area under the receiver operating characteristic curve [ROCAUC] 0.87, classification match 80%, and optimal iFR cutoff 0.90; for a ischemic 0.75 FFR cutoff: iFR ROCAUC 0.90, classification match 88%, and optimal iFR cutoff 0.85; if the FFR 0.75-0.80 gray zone is accounted for: ROCAUC 0.93, classification match 92%). When iFR and FFR are evaluated together in a hybrid decision-making strategy, 61% of the population is spared from vasodilator while maintaining a 94% overall agreement with FFR lesion classification. Conclusion When measured in real time, iFR maintains the close relationship to FFR reported in offline studies. These findings confirm the feasibility and reliability of real-time iFR calculation by clinicians.

Clinical outcome of transcatheter aortic valve implantation in patients with low‐flow, low gradient aortic stenosis

Background: Low‐flow, low‐gradient aortic stenosis is associated with relevant postoperative mortality whereas conservative management results in dismal prognosis. We present the initial experience of low‐flow, low‐gradient aortic stenosis treated with transcatheter aortic valve implantation (TAVI). Methods: From June 2008 to December 2010 167 consecutive patients with native severe aortic stenosis and an excessive operative risk underwent TAVI. Of these, 15 patients presented with low‐flow, low‐gradient aortic stenosis (aortic valve area < 1 cm2, left ventricular (LV) ejection fraction < 40%, aortic mean gradient < 40 mm Hg). The CoreValve prosthesis 18‐F‐generation (Medtronic, Minneapolis, Minnesota) was inserted retrograde. Clinical follow‐up and echocardiography were performed 6 months after procedure. Results: Patients with low‐flow, low‐gradient aortic stenosis (mean LV ejection fraction 32 ± 6%, mean aortic gradient 27 ± 7 mm Hg) had higher all‐cause mortality 6 months after TAVI compared to patients without low‐flow, low‐gradient aortic stenosis (33% vs. 13%, P = 0.037). In the surviving 10 patients with low‐flow, low‐gradient aortic stenosis, LV ejection fraction increased (34 ± 6% before vs. 46 ± 11% 6 months after TAVI, p = 0.005) and more distance covered in the 6‐minute walk test (218 ± 102 meters before vs. 288 ± 129 meters 6 months after TAVI, p = 0.038). Conclusion: Our study suggests that TAVI is feasible in patients with severe co‐morbidities and low‐flow, low‐gradient aortic stenosis. Within the first 6 months after treatment all‐cause mortality was considerable high, but the surviving patients showed symptomatic benefit and significant improvement of myocardial function and exercise capacity.

Implantation of the CoreValve self-expanding valve prosthesis via a subclavian artery approach: a case report

an alternative technique for treatment of aortic stenosis in patients with an excessive surgical risk [8]. In 2002, Cribier and coworkers [2] performed the first in man implantation of a bovine pericardial prosthesis in a 57-year-old man with calcified aortic stenosis and cardiogenic shock, using an antegrade transseptal approach. Recently, they summarized their experience in a small series of patients [3]. Of the 36 patients taken to the catheterization laboratory, 27 patients underwent successfully aortic valve implantation [3]. In 23 cases, Cribier’s group used an antegrade, transseptal approach, in four patients a retrograde approach. Although not specifically emphasized by the authors, the differences in their methods are relevant. The antegrade approach demands a transseptal puncture, and the stiff guiding wire that loops from the left atrium to the ascending aorta may cause severe intraprocedural mitral regurgitation. Webb and coworkers reported about their experience in 18 patients with this technique, however, they preferred a retrograde approach for delivery of the Cribier–Edwards valve [9]. They advanced 22 F and 24 F sheaths from the femoral artery to the aorta, and successfully delivered the prosthesis in 14 cases. Of note, iliac injury occurred in two patients requiring surgery. In Germany, a first series of patients was reported by a group from Siegburg [5]. They used a CoreValve self-expanding valve prosthesis, delivered by first (24 F) and second (21 F) generation sheaths via a retrograde approach. Device success and procedural success were achieved in 88% and 84%, respectively. Of note, they discussed the advantages of this approach on account of procedural simplicity, but they also addressed the technical problems tracking a relatively long and high-profile stent valve apparatus through small-diameter, tortuous or heavily atherosclerotic aortas. Most recently in this context, Jilaihawi and coworkers illustrated that Waldemar Bojara Achim Mumme Ulrich Gerckens Michael Lindstaedt Michael Gotzmann Alfried Germing Markus Fritz Werner Pennekamp Andreas Mügge Implantation of the CoreValve self-expanding valve prosthesis via a subclavian artery approach: a case report

Comparison of instantaneous wave-free ratio (iFR) and fractional flow reserve (FFR) - First real world experience

BACKGROUND The instantaneous wave-free ratio (iFR) is a new adenosine-independent index of coronary stenosis severity. Most published data have been based on off-line analyses of pressure recordings in a core laboratory. We prospectively compared real-time iFR and fractional flow reserve (FFR) measurements. METHODS AND RESULTS iFR and FFR were measured in 151 coronary stenoses in 108 patients. Repeated iFR measurements were technically simple, showed excellent agreement [rs=0.99; p<0.0001], and the mean difference between consecutive iFR values was 0.0035 (limits of agreement: -0.019, 0.026). Mean iFR showed a significant correlation with FFR [rs=0.81; p<0.0001]. Receiver-operating characteristic analysis identified an optimal iFR cut-off value of 0.896 for categorization based on an FFR cut-off value 0.8. We compared two different iFR-based diagnostic strategies (iFR-only and hybrid iFR-FFR) with standard FFR: The iFR-only strategy showed good classification agreement (83.4%) with standard FFR. Use of the hybrid iFR-FFR strategy, assessing lesions in an iFR-gray zone of 0.86-0.93 by FFR, improved classification accuracy to 94.7%, and diagnosis would have been established in 61% of patients without adenosine-induced hyperemia. Notably, both iFR and FFR values were significantly higher in the posterior coronary vessels. CONCLUSIONS Real-time iFR measurements are easily performed, have excellent diagnostic performance and confirm available off-line core laboratory data. The excellent agreement between repeated iFR measurements demonstrates the reliability of single measurements. Combining iFR with FFR in a hybrid strategy enhances diagnostic accuracy, exposing fewer patients to adenosine. Overall, iFR is a promising method, but still requires prospective clinical endpoint trial evaluation.

Clinical Outcome Following Conservative vs Revascularization Therapy in Patients With Stable Coronary Artery Disease and Borderline Fractional Flow Reserve Measurements

Fractional flow reserve (FFR) measurements in the so‐called gray‐zone range of ≥ 0.75 and ⩽0.80 are associated with uncertainty concerning the guidance of patient therapy. It is unclear whether any difference in clinical outcome exists when revascularization treatment of FFR‐evaluated lesions in this borderline range is deferred or performed. The objective of this study is to compare the clinical outcome of these patients with respect to their recommended treatment strategy.