Objectives The American College of Surgeons Oncology Group trial Z0060 is a prospective multi-institutional trial with a primary objective to evaluate whether positron emission tomography (PET) with ...F-18 fluorodeoxyglucose (FDG) detects evidence of metastastic disease that precludes esophagectomy in patients with esophageal cancer who are surgical candidates after routine staging. Methods Patients with resectable, biopsy-proven carcinoma were enrolled after computed tomography of chest and abdomen demonstrated no evidence of metastasis. FDG-PET was performed according to specified standards. FDG-PET findings suggesting metastases required confirmation and patients without metastases on PET were expected to proceed to surgery. Results A total of 262 patients were registered. Of these, 199 were deemed eligible and of these, 189 patients were evaluable. Seventy-three patients were ineligible or unevaluable. Reasons for ineligibility included nonresectable disease by routine staging (39), missing or outdated staging procedures (12), PET technical protocol violations (10), no cancer (4), pre-PET induction therapy (3), claustrophobia (1), and other causes (4). There were 145 (78%) patients who went on to have surgery, 42 (22%) who did not, and 2 patients for whom the surgical status was not determined. The reasons for no resection included the following: M1 disease found by PET and confirmed (9), M1 disease found by PET and not confirmed (2), M1 disease at exploration not found by PET (7), decline or death before surgery (10), patient refusal of surgery (7), unresectable local tumor at exploration (5), and extensive N1 disease precluding operation (2). Eight (4.2%) patients undergoing resection had a recurrence in the first 6 months. Conclusions Although 22% of eligible patients did not undergo esophagectomy, FDG-PET after standard clinical staging for esophageal carcinoma identified confirmed M1b disease in at least 4.8% (95% confidence interval: 2.2%-8.9%) of patients before resection. Unconfirmed PET evidence of M1 disease and regional adenopathy (N1 disease) led to definitive nonsurgical or induction therapy in additional patients.
Determining right ventricular (RV) function is challenging because of the complex anatomy of the right ventricle. Three-dimensional echocardiography (3DE) has achieved better estimation, but ...underestimations of volumes and ejection fraction (EF) has often been reported, and no previous study has synthesized these data. The investigators performed a meta-analysis on the bias and examined the related factors.
Studies comparing RV volumes and/or EF between 3DE and magnetic resonance imaging were eligible. A meta-analysis was performed to evaluate the systematic bias. The related bias was investigated using univariate and multivariate regression analysis.
Twenty-three studies including 807 subjects revealed underestimation of RV volumes (P < .00001) and EF (P = .03). Larger volumes and EF were associated with more underestimation. Older patient age was associated with overestimation of volumes and underestimation of EF.
This meta-analysis found underestimation of RV volumes and EF by 3DE and factors affecting the bias. These data provide a more detailed basis for improving the accuracy of 3DE for further clinical application.
Objectives The EVEREST II (Endovascular Valve Edge-to-Edge Repair) High Risk Study (HRS) assessed the safety and effectiveness of the MitraClip device (Abbott Vascular, Santa Clara, California) in ...patients with significant mitral regurgitation (MR) at high risk of surgical mortality rate. Background Patients with severe MR (3 to 4+) at high risk of surgery may benefit from percutaneous mitral leaflet repair, a potentially safer approach to reduce MR. Methods Patients with severe symptomatic MR and an estimated surgical mortality rate of ≥12% were enrolled. A comparator group of patients screened concurrently but not enrolled were identified retrospectively and consented to compare survival in patients treated by standard care. Results Seventy-eight patients underwent the MitraClip procedure. Their mean age was 77 years, >50% had previous cardiac surgery, and 46 had functional MR and 32 degenerative MR. MitraClip devices were successfully placed in 96% of patients. Protocol-predicted surgical mortality rate in the HRS and concurrent comparator group was 18.2% and 17.4%, respectively, and Society of Thoracic Surgeons calculator estimated mortality rate was 14.2% and 14.9%, respectively. The 30-day procedure-related mortality rate was 7.7% in the HRS and 8.3% in the comparator group (p = NS). The 12-month survival rate was 76% in the HRS and 55% in the concurrent comparator group (p = 0.047). In surviving patients with matched baseline and 12-month data, 78% had an MR grade of ≤2+. Left ventricular end-diastolic volume improved from 172 ml to 140 ml and end-systolic volume improved from 82 ml to 73 ml (both p = 0.001). New York Heart Association functional class improved from III/IV at baseline in 89% to class I/II in 74% (p < 0.0001). Quality of life was improved (Short Form-36 physical component score increased from 32.1 to 36.1 p = 0.014 and the mental component score from 45.5 to 48.7 p = 0.065) at 12 months. The annual rate of hospitalization for congestive heart failure in surviving patients with matched data decreased from 0.59 to 0.32 (p = 0.034). Conclusions The MitraClip device reduced MR in a majority of patients deemed at high risk of surgery, resulting in improvement in clinical symptoms and significant left ventricular reverse remodeling over 12 months. (Pivotal Study of a Percutaneous Mitral Valve Repair System EVEREST II; NCT00209274 )
Multicenter clinical trials use echocardiographic core laboratories to ensure expertise and consistency in the assessment of imaging eligibility criteria, as well as safety and efficacy end points. ...The aim of this study was to report the real-world implementation of guidelines for best practices in echocardiographic core laboratories, including their feasibility and quality results, in a large, international multicenter trial.
Processes and procedures were developed to optimize the acquisition and analysis of echocardiograms for the Placement of Aortic Transcatheter Valves (PARTNER) I trial of percutaneous aortic valve replacement for aortic stenosis. Comparison of baseline findings in the operative and nonoperative cohorts and reproducibility analyses were performed.
Echocardiography was performed in 1,055 patients (mean age, 83 years; 54% men) The average peak and mean aortic valve gradients were 73 ± 24 and 43 ± 15 mm Hg, and the average aortic valve area was 0.64 ± 0.20 cm(2). The average ejection fraction was 52 ± 13% by visual estimation and 53 ± 14% by biplane planimetry. The mean left ventricular mass index was 151 ± 42 g/m(2). The inoperable cohort had lower left ventricular mass and mass indexes and tended to have more severe mitral regurgitation. Core lab reproducibility was excellent, with intraclass correlation coefficients ranging from 0.92 to 0.99 and κ statistics from 0.58 to 0.85 for key variables. The image acquisition quality improvement process brought measurability to >85%, which was maintained for the duration of the study.
This real-world echocardiographic core lab experience in the PARTNER I trial demonstrates that a high standard of measurability and reproducibility can result from extensive quality assurance efforts in both image acquisition and analysis. These results and the echocardiographic data reported here provide a reference for future studies of aortic stenosis patients and should encourage the wider use of echocardiography in clinical research.
Significant mitral regurgitation (MR) constitutes an important co-existing valvular heart disease burden in the setting of aortic valve stenosis. There are conflicting reports on the impact of ...significant MR on outcomes after transcatheter aortic valve implantation (TAVI). We evaluated the impact of MR on outcomes after TAVI by performing a meta-analysis of 8 studies involving 8,927 patients reporting TAVI outcomes based on the presence or absence of moderate-severe MR. Risk ratios (RRs) were calculated using the inverse variance random-effects model. None-mild MR was present in 77.8% and moderate-severe MR in 22.2% of the patients. The presence of moderate-severe MR at baseline was associated with increased mortality at 30 days (RR 1.35, 95% confidence interval CI 1.14 to 1.59, p = 0.003) and 1 year (RR 1.24, 95% CI 1.13 to 1.37, p <0.0001). The increased mortality associated with moderate-severe MR was not influenced by the cause of MR (functional or degenerative MR; RR 0.90, 95% CI 0.62 to 1.30, p = 0.56). The severity of MR improved in 61 ± 6.0% of patients after TAVI. Moderate-severe residual MR, compared with none-mild residual MR after TAVI, was associated with significantly increased 1-year mortality (RR 1.48, 95% CI 1.31 to 1.68, p <0.00001). In conclusion, baseline moderate-severe MR and significant residual MR after TAVI are associated with an increase in mortality after TAVI and represent an important group to target with medical or transcatheter therapies in the future.
Abstract Background In EVEREST II (Endovascular Valve Edge-to-Edge Repair Study), treatment of mitral regurgitation (MR) with a novel percutaneous device showed superior safety compared with surgery, ...but less effective reduction in MR at 1 year. Objectives This study sought to evaluate the final 5-year clinical outcomes and durability of percutaneous mitral valve (MV) repair with the MitraClip device compared with conventional MV surgery. Methods Patients with grade 3+ or 4+ MR were randomly assigned to percutaneous repair with the device or conventional MV surgery in a 2:1 ratio (178:80). Patients prospectively consented to 5 years of follow-up. Results At 5 years, the rate of the composite endpoint of freedom from death, surgery, or 3+ or 4+ MR in the as-treated population was 44.2% versus 64.3% in the percutaneous repair and surgical groups, respectively (p = 0.01). The difference was driven by increased rates of 3+ to 4+ MR (12.3% vs. 1.8%; p = 0.02) and surgery (27.9% vs. 8.9%; p = 0.003) with percutaneous repair. After percutaneous repair, 78% of surgeries occurred within the first 6 months. Beyond 6 months, rates of surgery and moderate-to-severe MR were comparable between groups. Five-year mortality rates were 20.8% and 26.8% (p = 0.4) for percutaneous repair and surgery, respectively. In multivariable analysis, treatment strategy was not associated with survival. Conclusions Patients treated with percutaneous repair more commonly required surgery for residual MR during the first year after treatment, but between 1- and 5-year follow-up, comparably low rates of surgery for MV dysfunction with either percutaneous or surgical therapy endorse the durability of MR reduction with both repair techniques. (EVEREST II Pivotal Study High Risk Registry; NCT00209274 )
Low-flow low-gradient aortic stenosis with normal ejection fraction (LFLGNEF AS) is a newly characterized poorly understood entity within the AS spectrum. Whether LFLGNEF AS has a worse prognosis ...than typical AS remains controversial. We retrospectively identified 4,546 individual patients with any type of AS on echocardiogram from 2003 through 2013 and categorized them into 5 cohorts: (1) mild AS, (2) moderate AS, (3) severe AS, (4) LFLGNEF AS (ejection fraction ≥55%), and (5) low-flow low-gradient low ejection fraction AS (LFLGLEF AS; ejection fraction <55%). Survival analysis was used to compare outcomes of LFLGNEF AS with those of the other cohorts. AS was classified as mild in 591 patients, moderate in 2,358, severe in 500, LFLGNEF in 776, and LFLGLEF in 318. The study group had a mean age of 80.5 years, 61% were women, and the patients were followed for 2.26 ± 1.16 years. Among subjects managed without valve replacement, total mortality for the LFLGNEF AS group was lower compared with that in both the severe AS and the LFLGLEF AS groups (p = 0.007 and p <0.001, respectively). The prognosis for LFLGNEF AS was worse, however, compared with those with mild and moderate AS (p <0.001, both). In conclusion, no survival differences were found among AS types among those who received valve replacement. The survival rate in LFLGNEF is better than that in severe AS or LFLGLEF but is worse than that in mild or moderate AS. Valve replacement seems reasonable to pursue in select patients.
Inoperable aortic stenosis may be treated with either transcatheter aortic valve replacement (TAVR) or medical management (MM) with or without balloon aortic valvuloplasty (BAV). The aim of this ...study was to compare the long-term echocardiographic findings among TAVR, MM, and BAV in patients with severe, inoperable aortic stenosis.
A total of 358 inoperable patients in the Placement of Aortic Transcatheter Valves trial were randomized to MM or TAVR. Echocardiograms obtained at baseline, 30 days, and 1, 2, and 3 years were analyzed by a central core laboratory.
At baseline, TAVR and MM were similar, with more frequent Society of Thoracic Surgeons score > 10 (51.7% vs 65.0%, P = .03) and larger end-systolic volumes (54.5 ± 29.3 vs 69.1 ± 48.0 mL, P = .03) in MM. By 30 days after TAVR, mean aortic valve gradient had decreased (from 43.8 ± 14.7 to 10.0 ± 4.3 mm Hg, P < .001), ejection fraction had increased (from 53.2 ± 12.4% to 56.7 ± 10.0%, P < .001), and left ventricular (LV) mass index had decreased (from 144.7 ± 36.1 to 140.0 ± 37.9 gm/m(2), P < .05). After 1 year, aortic valve gradients and area were unchanged, while LV mass index had decreased by another 16 gm/m(2) (to 124 gm/m(2)). By 30 days after BAV, mean aortic valve gradient had decreased from 43.4 ± 15.0 to 31.9 ± 11.1 mm Hg, while ejection fraction and LV mass index were unchanged; gradient reverted to baseline at 1 year. No changes in gradients or mass were seen in MM patients.
TAVR results in immediate and sustained relief in pressure overload and improved LV systolic function, with continued regression of hypertrophy over 3 years. Poor clinical results with BAV are explained by the modest and transient reductions in pressure overload with BAV, which were not accompanied by improved LV function or remodeling. TAVR is the preferred treatment in eligible inoperable patients (ClinicalTrials.gov identifier NCT00530894).
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