Hans Gustav Hørsted Thyregod

Transcatheter Versus Surgical Aortic Valve Replacement in Patients With Severe Aortic Valve Stenosis 1-Year Results From the All-Comers NOTION Randomized Clinical Trial

BACKGROUND Transcatheter aortic valve replacement (TAVR) is an option in certain high-risk surgical patients with severe aortic valve stenosis. It is unknown whether TAVR can be safely introduced to lower-risk patients. OBJECTIVES The NOTION (Nordic Aortic Valve Intervention Trial) randomized clinical trial compared TAVR with surgical aortic valve replacement (SAVR) in an all-comers patient cohort. METHODS Patients ≥ 70 years old with severe aortic valve stenosis and no significant coronary artery disease were randomized 1:1 to TAVR using a self-expanding bioprosthesis versus SAVR. The primary outcome was the composite rate of death from any cause, stroke, or myocardial infarction (MI) at 1 year. RESULTS A total of 280 patients were randomized at 3 Nordic centers. Mean age was 79.1 years, and 81.8% were considered low-risk patients. In the intention-to-treat population, no significant difference in the primary endpoint was found (13.1% vs. 16.3%; p = 0.43 for superiority). The result did not change in the as-treated population. No difference in the rate of cardiovascular death or prosthesis reintervention was found. Compared with SAVR-treated patients, TAVR-treated patients had more conduction abnormalities requiring pacemaker implantation, larger improvement in effective orifice area, more total aortic valve regurgitation, and higher New York Heart Association functional class at 1 year. SAVR-treated patients had more major or life-threatening bleeding, cardiogenic shock, acute kidney injury (stage II or III), and new-onset or worsening atrial fibrillation at 30 days than did TAVR-treated patients. CONCLUSIONS In the NOTION trial, no significant difference between TAVR and SAVR was found for the composite rate of death from any cause, stroke, or MI after 1 year. (Nordic Aortic Valve Intervention Trial [NOTION]; NCT01057173).

Two-Year Outcomes in Patients With Severe Aortic Valve Stenosis Randomized to Transcatheter Versus Surgical Aortic Valve Replacement The All-Comers Nordic Aortic Valve Intervention Randomized Clinical Trial

Background—The Nordic Aortic Valve Intervention (NOTION) trial was the first to randomize all-comers with severe native aortic valve stenosis to either transcatheter aortic valve replacement (TAVR) with the CoreValve self-expanding bioprosthesis or surgical aortic valve replacement (SAVR), including a lower-risk patient population than previous trials. This article reports 2-year clinical and echocardiographic outcomes from the NOTION trial. Methods and Results—Two-hundred eighty patients from 3 centers in Denmark and Sweden were randomized to either TAVR (n=145) or SAVR (n=135) with follow-up planned for 5 years. There was no difference in all-cause mortality at 2 years between TAVR and SAVR (8.0% versus 9.8%, respectively; P=0.54) or cardiovascular mortality (6.5% versus 9.1%; P=0.40). The composite outcome of all-cause mortality, stroke, or myocardial infarction was also similar (15.8% versus 18.8%, P=0.43). Forward-flow hemodynamics were improved following both procedures, with effective orifice area significantly more improved after TAVR than SAVR (effective orifice area, 1.7 versus 1.4 cm2 at 3 months). Mean valve gradients were similar after TAVR and SAVR. When patients were categorized according to Society of Thoracic Surgeons Predicted Risk of Mortality (STS-PROM) (<4% versus ≥4%), there was no statistically significant difference for TAVR and SAVR groups in the composite outcome for low-risk (14.7%, 95% confidence interval, 8.3–21.2 versus 16.8%; 95% confidence interval, 9.7–23.8; P=0.58) or intermediate-risk patients (21.1% versus 27.1%; P=0.59). Conclusions—Two-year results from the NOTION trial demonstrate the continuing safety and effectiveness of TAVR in lower-risk patients. Longer-term data are needed to verify the durability of this procedure in this patient population. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT01057173.

Prosthetic Valve Endocarditis After Transcatheter Aortic Valve Implantation

Background—Transcatheter aortic valve implantation (TAVI) is an advancing mode of treatment for inoperable or high-risk patients with aortic stenosis. Prosthetic valve endocarditis (PVE) after TAVI is a serious complication, but only limited data exist on its incidence, outcome, and procedural risk factors. Methods and Results—Observational single-center study of 509 consecutive patients treated with a transcatheter implanted self-expandable aortic valve prosthesis (Medtronic CoreValve). We identified 18 patients diagnosed with TAVI-PVE during a median follow-up period of 1.4 years (interquartile range, 0.5–2.5 years; longest follow-up was 6.3 years). TAVI-PVE was most frequent in the first year after implantation (first-year incidence, 3.1% [confidence interval, 1.4%–4.8%]); the overall annualized rate was 2.1% per patient-year (confidence interval, 1.2%–3.3%). Seventeen patients (94%) were treated conservatively and 1 with surgery. Four patients (22%) died from endocarditis or complications to treatment, 2 of those (11%) during initial hospitalization for PVE. An increased risk of TAVI-PVE was seen in patients with low implanted valve position (hazard ratio, 2.8 [1.1–7.2]), moderate or worse postprocedural paravalvular regurgitation (hazard ratio, 4.0 [1.5–11]), implantation of >1 prosthesis (hazard ratio, 5.2 [1.5–18]), and any vascular complication (hazard ratio, 3.8 [1.5–9.8]). Conclusions—TAVI-PVE occurred at a slightly higher rate than reported for surgically implanted valves. Conservative treatment was associated with an acceptable outcome. Suboptimal valve deployment and vascular complications were associated with an increased risk of TAVI-PVE.

The Nordic Aortic Valve Intervention (NOTION) trial comparing transcatheter versus surgical valve implantation: study protocol for a randomised controlled trial

BackgroundDegenerative aortic valve (AV) stenosis is the most prevalent heart valve disease in the western world. Surgical aortic valve replacement (SAVR) has until recently been the standard of treatment for patients with severe AV stenosis. Whether transcatheter aortic valve implantation (TAVI) can be offered with improved safety and similar effectiveness in a population including low-risk patients has yet to be examined in a randomised setting.Methods/DesignThis randomised clinical trial will evaluate the benefits and risks of TAVI using the transarterial CoreValve System (Medtronic Inc., Minneapolis, MN, USA) (intervention group) compared with SAVR (control group) in patients with severe degenerative AV stenosis. Randomisation ratio is 1:1, enrolling a total of 280 patients aged 70 years or older without significant coronary artery disease and with a low, moderate, or high surgical risk profile. Trial outcomes include a primary composite outcome of myocardial infarction, stroke, or all-cause mortality within the first year after intervention (expected rates 5% for TAVI, 15% for SAVR). Exploratory safety outcomes include procedure complications, valve re-intervention, and cardiovascular death, as well as cardiac, cerebral, pulmonary, renal, and vascular complications. Exploratory efficacy outcomes include New York Heart Association functional status, quality of life, and valve prosthesis and cardiac performance. Enrolment began in December 2009, and 269 patients have been enrolled up to December 2012.DiscussionThe trial is designed to evaluate the performance of TAVI in comparison with SAVR. The trial results may influence the choice of treatment modality for patients with severe degenerative AV stenosis.Trial registrationClinicalTrials.gov: NCT01057173

Temporal changes of new-onset atrial fibrillation in patients randomized to surgical or transcatheter aortic valve replacement

BACKGROUND Temporal development of new-onset atrial fibrillation (NOAF) after aortic valve replacement is unclear, and opportunistic screening has limited diagnostic accuracy. This is the first study to investigate the incidence and temporal development of NOAF detected by implantable loop recorder (ILR) in patients with aortic stenosis, randomized to surgical aortic valve replacement (SAVR) or transcatheter aortic valve replacement (TAVR). METHOD An ILR was implanted in a subgroup of patients without pre-procedural atrial fibrillation (AF), randomized to SAVR or TAVR in the NOTION trial. Data from the ILR were transmitted in intervals of 2weeks for 12weeks post-procedurally and analyzed. RESULTS The study included 25 and 27 patients who underwent SAVR and TAVR, respectively. The cumulative rate of NOAF was 100% and 81.5% for patients undergoing SAVR and TAVR, respectively (P=0.06). TAVR patients without NOAF 6weeks post-procedurally remained free from NOAF. The prevalence of AF after SAVR decreased significantly after 8weeks when compared with the first 2weeks (50.0% vs. 84.0%, respectively; P<0.05). The prevalence of AF after TAVR did not change significantly during follow-up. The median AF burden (percentage of time with AF) was 2.8% and 0.04% during the first 2weeks after SAVR and TAVR, respectively (P=0.01) and it decreased significantly over time after SAVR but not after TAVR. CONCLUSION NOAF subsided 6weeks after TAVR. AF prevalence and burden decreased significantly over time after SAVR, but remained stable after TAVR. These findings may be considered for post-procedural anti-coagulation strategy.

Measures of right ventricular function after transcatheter versus surgical aortic valve replacement

Objectives Describe changes in measures of right ventricular (RV) function in patients treated for aortic stenosis using open-chest surgery (SAVR) or transcatheter treatment (TAVR). Methods Patients in the Nordic Aortic Valve Intervention (NOTION) trial were randomized 1:1 to TAVR (n = 114) or SAVR (n = 106). Echocardiography was performed at baseline and 3 and 12 months post-procedure. Tricuspid annular plane systolic excursion (TAPSE) and right ventricular fractional area change (RVFAC) were used as measures of longitudinal and transverse RV contraction. Left ventricular ejection fraction (LVEF) and LV atrioventricular plane displacement (AVPD) were recorded as measures of LV function. Association to NYHA class was examined. Results There were no differences in echocardiographic measurements between TAVR and SAVR at baseline. In the SAVR group, TAPSE was reduced after 3 months (2.4 ± 0.5 cm vs 1.6 ± 0.4 cm; P < 0.001), and 12 months (2.4 ± 0.5 cm vs 1.7 ± 0.4 cm; P < 0.001). RVFAC was reduced after 3 months (44% ± 11% vs 39% ± 10%; P = 0.001), but recovered at 12 months (43% ± 10%; P = 0.39). AVPD lateral increased during follow-up (1.4 ± 0.3 cm vs 1.6 ± 0.4 cm (P = 0.001) and 1.7 ± 0.4 cm, respectively; P < 0.001), whereas AVPD medial remained stable (baseline vs 3 months: P = 0.06 and baseline vs 12 months: P = 0.59). In the TAVR group, all echocardiographic measures remained unchanged from baseline to 12 months postoperatively. We found no association between echocardiographic changes and NYHA class. Conclusions TAPSE and AVPD lateral differed between TAVR and SAVR at 3 and 12 months follow-up, but these findings were not related to any changes in NYHA class. These observations indicate that following SAVR, echocardiographic changes may not reflect right ventricular function, but merely a change in the physiological conditions. Clinicaltrials.gov identifier NCT01057173.

Exploring the Role of Transcatheter Aortic Valve Replacement as the Preferred Treatment for Lower-Risk Patients.

In the NOTION (Nordic Aortic Valve Intervention) trial [(1)][1], we included all eligible patients with stand-alone severe aortic valve stenosis. This resulted in a patient population with a mean Society of Thoracic Surgeons Predicted Risk of Mortality score of 3.0% and 82% considered at low

Female-specific survival advantage from transcatheter aortic valve implantation over surgical aortic valve replacement: Meta-analysis of the gender subgroups of randomised controlled trials including 3758 patients

Transcatheter aortic valve implantation (TAVI) for severe aortic stenosis (AS) is the first area of interventional cardiology where women are treated as often as men. In this analysis of the gender specific results of randomised controlled trials (RCTs) comparing TAVI with surgical aortic valve replacement (SAVR) we aimed to determine whether gender affects the survival comparison between TAVI and SAVR. We identified all RCTs comparing TAVI versus SAVR for severe AS and reporting 1 and/or 2year survival. Summary odds ratios (ORs) were obtained using a random-effects model. Heterogeneity was assessed using the Q statistic and I2. Four RCTs met the criteria, totalling 3758 patients, 1706 women and 2052 men. Amongst females, TAVI recipients had a significantly lower mortality than SAVR recipients, at 1year (OR 0.68; 95%CI 0.50 to 0.94) and at 2years (OR 0.74; 95%CI 0.58 to 0.95). Amongst males there was no difference in mortality between TAVI and SAVR, at 1year (OR 1.09; 95%CI 0.86 to 1.39) or 2years (OR 1.05; 95%CI 0.85 to 1.3). The difference in treatment effect between genders was significant at both 1year (pinteraction=0.02) and 2years (pinteraction=0.04). In women TAVI has a 26 to 31% lower mortality odds than SAVR. In men, there is no difference in mortality between TAVI and SAVR.

Reply: 1-Year Results From the NOTION Randomized Clinical Trial: Weighing Complications Against Functional Outcomes

To our knowledge, no randomized trials comparing transcatheter aortic valve replacement (TAVR) versus surgical aortic valve replacement (SAVR) in an all-comers population including intermediate- and low-risk patients had been conducted before the NOTION (Nordic Aortic Valve Intervention) trial.