Daniel J. Blackman

Long-term outcomes after transcatheter aortic valve implantation in high-risk patients with severe aortic stenosis: the U.K. TAVI (United Kingdom Transcatheter Aortic Valve Implantation) Registry.

OBJECTIVES The objective was to define the characteristics of a real-world patient population treated with transcatheter aortic valve implantation (TAVI), regardless of technology or access route, and to evaluate their clinical outcome over the mid to long term. BACKGROUND Although a substantial body of data exists in relation to early clinical outcomes after TAVI, there are few data on outcomes beyond 1 year in any notable number of patients. METHODS The U.K. TAVI (United Kingdom Transcatheter Aortic Valve Implantation) Registry was established to report outcomes of all TAVI procedures performed within the United Kingdom. Data were collected prospectively on 870 patients undergoing 877 TAVI procedures up until December 31, 2009. Mortality tracking was achieved in 100% of patients with mortality status reported as of December 2010. RESULTS Survival at 30 days was 92.9%, and it was 78.6% and 73.7% at 1 year and 2 years, respectively. There was a marked attrition in survival between 30 days and 1 year. In a univariate model, survival was significantly adversely affected by renal dysfunction, the presence of coronary artery disease, and a nontransfemoral approach; whereas left ventricular function (ejection fraction <30%), the presence of moderate/severe aortic regurgitation, and chronic obstructive pulmonary disease remained the only independent predictors of mortality in the multivariate model. CONCLUSIONS Midterm to long-term survival after TAVI was encouraging in this high-risk patient population, although a substantial proportion of patients died within the first year.

Randomized Trial of Complete Versus Lesion-Only Revascularization in Patients Undergoing Primary Percutaneous Coronary Intervention for STEMI and Multivessel Disease: The CvLPRIT Trial

Background The optimal management of patients found to have multivessel disease while undergoing primary percutaneous coronary intervention (P-PCI) for ST-segment elevation myocardial infarction is uncertain. Objectives CvLPRIT (Complete versus Lesion-only Primary PCI trial) is a U.K. open-label randomized study comparing complete revascularization at index admission with treatment of the infarct-related artery (IRA) only. Methods After they provided verbal assent and underwent coronary angiography, 296 patients in 7 U.K. centers were randomized through an interactive voice-response program to either in-hospital complete revascularization (n = 150) or IRA-only revascularization (n = 146). Complete revascularization was performed either at the time of P-PCI or before hospital discharge. Randomization was stratified by infarct location (anterior/nonanterior) and symptom onset (≤3 h or >3 h). The primary endpoint was a composite of all-cause death, recurrent myocardial infarction (MI), heart failure, and ischemia-driven revascularization within 12 months. Results Patient groups were well matched for baseline clinical characteristics. The primary endpoint occurred in 10.0% of the complete revascularization group versus 21.2% in the IRA-only revascularization group (hazard ratio: 0.45; 95% confidence interval: 0.24 to 0.84; p = 0.009). A trend toward benefit was seen early after complete revascularization (p = 0.055 at 30 days). Although there was no significant reduction in death or MI, a nonsignificant reduction in all primary endpoint components was seen. There was no reduction in ischemic burden on myocardial perfusion scintigraphy or in the safety endpoints of major bleeding, contrast-induced nephropathy, or stroke between the groups. Conclusions In patients presenting for P-PCI with multivessel disease, index admission complete revascularization significantly lowered the rate of the composite primary endpoint at 12 months compared with treating only the IRA. In such patients, inpatient total revascularization may be considered, but larger clinical trials are required to confirm this result and specifically address whether this strategy is associated with improved survival. (Complete Versus Lesion-only Primary PCI Pilot Study [CvLPRIT]; ISRCTN70913605)

Elective intra-aortic balloon counterpulsation during high-risk percutaneous coronary intervention: a randomized controlled trial.

CONTEXT Observational studies have previously reported that elective intra-aortic balloon pump (IABP) insertion may improve outcomes following high-risk percutaneous coronary intervention (PCI). To date, this assertion has not been tested in a randomized trial. OBJECTIVE To determine whether routine intra-aortic balloon counterpulsation before PCI reduces major adverse cardiac and cardiovascular events (MACCE) in patients with severe left ventricular dysfunction and extensive coronary disease. DESIGN, SETTING, AND PATIENTS The Balloon Pump-Assisted Coronary Intervention Study, a prospective, open, multicenter, randomized controlled trial conducted in 17 tertiary referral cardiac centers in the United Kingdom between December 2005 and January 2009. Patients (n = 301) had severe left ventricular dysfunction (ejection fraction < or = 30%) and extensive coronary disease (Jeopardy Score > or = 8/12); those with contraindications to or class I indications for IABP therapy were excluded. INTERVENTION Elective insertion of IABP before PCI. MAIN OUTCOME MEASURES Primary end point was MACCE, defined as death, acute myocardial infarction, cerebrovascular event, or further revascularization at hospital discharge (capped at 28 days). Secondary end points included all-cause mortality at 6 months, major procedural complications, bleeding, and access-site complications. RESULTS MACCE at hospital discharge occurred in 15.2% (23/151) of the elective IABP and 16.0% (24/150) of the no planned IABP groups (P = .85; odds ratio [OR], 0.94 [95% confidence interval {CI}, 0.51-1.76]). All-cause mortality at 6 months was 4.6% and 7.4% in the respective groups (P = .32; OR, 0.61 [95% CI, 0.24-1.62]). Fewer major procedural complications occurred with elective IABP insertion compared with no planned IABP use (1.3% vs 10.7%, P < .001; OR, 0.11 [95% CI, 0.01-0.49]). Major or minor bleeding occurred in 19.2% and 11.3% (P = .06; OR, 1.86 [95% CI, 0.93-3.79]) and access-site complications in 3.3% and 0% (P = .06) of the elective and no planned IABP groups, respectively. CONCLUSIONS Elective IABP insertion did not reduce the incidence of MACCE following PCI. These results do not support a strategy of routine IABP placement before PCI in all patients with severe left ventricular dysfunction and extensive coronary disease. TRIAL REGISTRATION isrctn.org Identifier: ISRCTN40553718; clinicaltrials.gov Identifier: NCT00910481.

Transcatheter aortic valve replacement for severe symptomatic aortic stenosis using a repositionable valve system: 30-day primary endpoint results from the REPRISE II study.

BACKGROUND Transcatheter aortic valve replacement provides results comparable to those of surgery in patients at high surgical risk, but complications can impact long-term outcomes. The Lotus valve, designed to improve upon earlier devices, is fully repositionable and retrievable, with a unique seal to minimize paravalvular regurgitation (PVR). OBJECTIVES The prospective, single-arm, multicenter REPRISE II study (REpositionable Percutaneous Replacement of Stenotic Aortic Valve Through Implantation of Lotus Valve System: Evaluation of Safety and Performance) evaluated the transcatheter valve system for treatment of severe symptomatic calcific aortic valve stenosis. METHODS Patients (n = 120; aortic annulus 19 to 27 mm) considered by a multidisciplinary heart team to be at high surgical risk received the valve transfemorally. The primary device performance endpoint, 30-day mean pressure gradient, was assessed by an independent echocardiographic core laboratory and compared with a pre-specified performance goal. The primary safety endpoint was 30-day mortality. Secondary endpoints included safety/effectiveness metrics per Valve Academic Research Consortium criteria. RESULTS Mean age was 84.4 years, 57% of the patients were female, and 76% were New York Heart Association functional class III/IV. Mean aortic valve area was 0.7 ± 0.2 cm(2). The valve was successfully implanted in all patients, with no cases of valve embolization, ectopic valve deployment, or additional valve implantation. All repositioning (n = 26) and retrieval (n = 6) attempts were successful; 34 patients (28.6%) received a permanent pacemaker. The primary device performance endpoint was met, because the mean gradient improved from 46.4 ± 15.0 mm Hg to 11.5 ± 5.2 mm Hg. At 30 days, the mortality rate was 4.2%, and the rate of disabling stroke was 1.7%; 1 (1.0%) patient had moderate PVR, whereas none had severe PVR. CONCLUSIONS REPRISE II demonstrates the safety and effectiveness of the Lotus valve in patients with severe aortic stenosis who are at high surgical risk. The valve could be positioned successfully with minimal PVR. (REPRISE II: REpositionable Percutaneous Replacement of Stenotic Aortic Valve Through Implantation of Lotus™ Valve System - Evaluation of Safety and Performance; NCT01627691).

Neutrophil superoxide anion--generating capacity, endothelial function and oxidative stress in chronic heart failure:effects of short- and long-term vitamin C therapy

OBJECTIVES First, we sought to study the effects of short- and long-term vitamin C therapy on oxidative stress and endothelial dysfunction in chronic heart failure (CHF), and second, we sought to investigate the role of neutrophils as a cause of oxidative stress in CHF. BACKGROUND Oxidative stress may contribute to endothelial dysfunction in CHF. Vitamin C ameliorates endothelial dysfunction in CHF, presumably by reducing oxidative stress, but this is unproven. METHODS We studied 55 patients with CHF (ischemic and nonischemic etiologies) and 15 control subjects. Flow-mediated dilation (FMD) in the brachial artery was measured by ultrasound wall-tracking, neutrophil superoxide anion (O2-) generation by lucigenin-enhanced chemiluminescence and oxidative stress by measurement of free radicals (FRs) in venous blood using electron paramagnetic resonance (EPR) spectroscopy and plasma thiobarbituric acid reactive substances (TBARS). Measurements were performed at baseline in all subjects. The effects of short-term (intravenous) and long-term (oral) vitamin C therapy versus placebo were tested in patients with nonischemic CHF. RESULTS At baseline, FRs were higher in patients with CHF than in control subjects (p < 0.01), TBARS were greater (p < 0.005), neutrophil O2- -generating capacity was enhanced (p < 0.005) and FMD was lower (p < 0.0001). Compared with placebo, short-term vitamin C therapy reduced FR levels (p < 0.05), tended to reduce TBARS and increased FMD (p < 0.05), but did not affect neutrophil O2- -generating capacity. Long-term vitamin C therapy reduced FR levels (p < 0.05), reduced TBARS (p < 0.05) and improved FMD (p < 0.05), but also reduced neutrophil O2- -generating capacity (p < 0.05). Endothelial dysfunction was not related to oxidative stress, and improvements in FMD with vitamin C therapy did not relate to reductions in oxidative stress. CONCLUSIONS Oxidative stress is increased in ischemic and nonischemic CHF, and neutrophils may be an important cause. Vitamin C reduces oxidative stress, increases FMD and, when given long term, decreases neutrophil O2- generation, but the lack of a correlation between changes in endothelial function and oxidative stress with vitamin C implies possible additional non-antioxidant benefits of vitamin C.

Transcatheter Aortic Valve Implantation in the United Kingdom Temporal Trends, Predictors of Outcome, and 6-Year Follow-Up: A Report From the UK Transcatheter Aortic Valve Implantation (TAVI) Registry, 2007 to 2012

Background— We assessed trends in the performance of transcatheter aortic valve implantation in the United Kingdom from the first case in 2007 to the end of 2012. We analyzed changes in case mix, complications, outcomes to 6 years, and predictors of mortality. Methods and Results— Annual cohorts were examined. Mortality outcomes were analyzed in the 92% of patients from England and Wales for whom independent mortality tracking was available. A total of 3980 transcatheter aortic valve implantation procedures were performed. In successive years, there was an increase in frequency of impaired left ventricular function, but there was no change in Logistic EuroSCORE. Overall 30-day mortality was 6.3%; it was highest in the first cohort (2007–2008), after which there were no further significant changes. One-year survival was 81.7%, falling to 37.3% at 6 years. Discharge by day 5 rose from 16.7% in 2007 and 2008 to 28% in 2012. The only multivariate preprocedural predictor of 30-day mortality was Logistic EuroSCORE ≥40. During long-term follow-up, multivariate predictors of mortality were preprocedural atrial fibrillation, chronic obstructive pulmonary disease, creatinine >200 μmol/L, diabetes mellitus, and coronary artery disease. The strongest independent procedural predictor of long-term mortality was periprocedural stroke (hazard ratio=3.00; P <0.0001). Nonfemoral access and postprocedural aortic regurgitation were also significant predictors of adverse outcome. Conclusions— We analyzed transcatheter aortic valve implantation in an entire country, with follow-up over 6 years. Although clinical profiles of enrolled patients remained unchanged, longer-term outcomes improved, and patients were discharged earlier. Periprocedural stroke, nonfemoral access, and postprocedural aortic regurgitation are predictors of adverse outcome, along with intrinsic patient risk factors. # CLINICAL PERSPECTIVE {#article-title-29}Background— We assessed trends in the performance of transcatheter aortic valve implantation in the United Kingdom from the first case in 2007 to the end of 2012. We analyzed changes in case mix, complications, outcomes to 6 years, and predictors of mortality. Methods and Results— Annual cohorts were examined. Mortality outcomes were analyzed in the 92% of patients from England and Wales for whom independent mortality tracking was available. A total of 3980 transcatheter aortic valve implantation procedures were performed. In successive years, there was an increase in frequency of impaired left ventricular function, but there was no change in Logistic EuroSCORE. Overall 30-day mortality was 6.3%; it was highest in the first cohort (2007–2008), after which there were no further significant changes. One-year survival was 81.7%, falling to 37.3% at 6 years. Discharge by day 5 rose from 16.7% in 2007 and 2008 to 28% in 2012. The only multivariate preprocedural predictor of 30-day mortality was Logistic EuroSCORE ≥40. During long-term follow-up, multivariate predictors of mortality were preprocedural atrial fibrillation, chronic obstructive pulmonary disease, creatinine >200 &mgr;mol/L, diabetes mellitus, and coronary artery disease. The strongest independent procedural predictor of long-term mortality was periprocedural stroke (hazard ratio=3.00; P<0.0001). Nonfemoral access and postprocedural aortic regurgitation were also significant predictors of adverse outcome. Conclusions— We analyzed transcatheter aortic valve implantation in an entire country, with follow-up over 6 years. Although clinical profiles of enrolled patients remained unchanged, longer-term outcomes improved, and patients were discharged earlier. Periprocedural stroke, nonfemoral access, and postprocedural aortic regurgitation are predictors of adverse outcome, along with intrinsic patient risk factors.

Diffusion-weighted MRI determined cerebral embolic infarction following transcatheter aortic valve implantation: assessment of predictive risk factors and the relationship to subsequent health status

Background ‘Silent’ cerebral infarction and stroke are complications of transcatheter aortic valve implantation (TAVI). Objective To assess the occurrence of cerebral infarction, identify predictive risk factors and examine the impact on patient health-related quality of life (HRQoL). Methods Cerebral diffusion weighted MRI of 31 patients with aortic stenosis undergoing CoreValve TAVI was carried out. HRQoL was assessed at baseline and at 30 days by SF-12v2 and EQ5D questionnaires. Results New cerebral infarcts occurred in 24/31 patients (77%) and stroke in 2 (6%). Stroke was associated with a greater number and volume of cerebral infarcts. Age (r=0.37, p=0.042), severity of atheroma (arch and descending aorta; r=0.91, p<0.001, r=0.69, p=0.001, respectively) and catheterisation time (r=0.45, p=0.02) were predictors of the number of new cerebral infarcts. HRQoL improved overall: SF-12v2 physical component summary increased significantly (32.4±6.2 vs 36.5±7.2; p=0.03) with no significant change in mental component summary (43.5±11.7 vs 43.1±14.3; p=0.85). The EQ5D score and Visual Analogue Scale showed no significant change (0.56±0.26 vs 0.59±0.31; p=0.70, and 54.2±19 vs 58.2±24; p=0.43). Conclusion Multiple small cerebral infarcts occurred in 77% of patients with TAVI. The majority of infarcts were ‘silent’ with clinical stroke being associated with a both higher infarct number and volume. Increased age and the severity of aortic arch atheroma were independent risk factors for the development of new cerebral infarcts. Overall HRQoL improved and there was no association between the number of new cerebral infarcts and altered health status.

Treatment of Symptomatic Severe Aortic Stenosis With a Novel Resheathable Supra-Annular Self-Expanding Transcatheter Aortic Valve System

OBJECTIVES The purpose of this study was to prospectively evaluate the safety and clinical performance of the CoreValve Evolut R transcatheter aortic valve replacement (TAVR) system (Medtronic, Inc., Minneapolis, Minnesota) in a single-arm, multicenter pivotal study in high- or extreme-risk patients with symptomatic aortic valve stenosis. BACKGROUND Although outcomes following TAVR are improving, challenges still exist. The repositionable 14-F equivalent CoreValve Evolut R TAVR system was developed to mitigate some of these challenges. METHODS Suitable patients (n = 60) underwent TAVR with a 26- or 29-mm Evolut R valve. Primary safety endpoints were mortality and stroke at 30 days. Primary clinical performance endpoints were device success per the VARC-2 (Valve Academic Research Consortium-2) and the percent of patients with mild or less aortic regurgitation 24 h to 7 days post-procedure. RESULTS Patients (66.7% female; mean age 82.8 ± 6.1 years; Society of Thoracic Surgeons Score 7.0 ± 3.7%) underwent TAVR via the transfemoral route in 98.3%, using a 29-mm valve in 68.3% of patients. All attempts at repositioning were successful. No death or stroke was observed up to 30 days. The VARC-2 overall device success rate was 78.6%. Paravalvular regurgitation post TAVR was mild or less in 96.6%, moderate in 3.4%, and severe in 0% at 30 days. Major vascular complications occurred in 8.3%, and permanent pacemaker implantation was required in 11.7% of patients. CONCLUSIONS The repositionable 14-F equivalent Evolut R TAVR system is safe and effective at treating high-risk symptomatic aortic stenosis patients. Repositioning was successful when required in all patients, with low rates of moderate or severe paravalvular aortic regurgitation and low permanent pacemaker implantation. (The Medtronic CoreValve™ Evolut R™ CE Mark Clinical Study; NCT01876420).

Direct ambulance admission to the cardiac catheterization laboratory significantly reduces door-to-balloon times in primary percutaneous coronary intervention.

BACKGROUND Primary percutaneous coronary intervention (PCI) is the preferred treatment for ST-segment elevation myocardial infarction (STEMI) provided it can be delivered within 90 minutes of hospital admission. In clinical practice this target is difficult to achieve. We aimed to determine the effect of direct ambulance admission to the cardiac catheterization laboratory on door-to-balloon and call-to-balloon times in primary PCI. METHODS We performed a prospective evaluation of a new system of paramedic electrocardiogram diagnosis of STEMI and subsequent direct ambulance admission to the cardiac catheterization laboratory for primary PCI. Door-to-balloon and call-to-balloon times were recorded for all patients. Direct admissions were compared with admissions via the emergency room of the interventional center and of 2 referring hospitals. All times are quoted as medians. RESULTS Five hundred and seventy-seven patients (70% male, age 63 +/- 13 years) underwent primary PCI between April 2005 and May 2007. After February 2006, 172 (44%) of 387 patients were admitted directly from the ambulance to the catheterization laboratory. Directly admitted patients had significantly reduced door-to-balloon (58 vs 105 minutes, P < .001) and call-to-balloon times (105 vs 143 minutes, P < .001). The 90-minute target for door-to-balloon time was achieved in 94% of direct admissions compared to 29% of patients referred from the emergency room. CONCLUSIONS Direct admission of patients with suspected STEMI from the ambulance service to the catheterization laboratory significantly reduces time to treatment in primary PCI and allows the 90-minute door-to-balloon time target to be reliably achieved.

Assessment of valve haemodynamics, reverse ventricular remodelling and myocardial fibrosis following transcatheter aortic valve implantation compared to surgical aortic valve replacement: a cardiovascular magnetic resonance study

Objective To compare the effects of transcatheter aortic valve implantation (TAVI) and surgical aortic valve replacement (SAVR) on aortic valve haemodynamics, ventricular reverse remodelling and myocardial fibrosis (MF) by cardiovascular magnetic resonance (CMR) imaging. Design A 1.5 T CMR scan was performed preoperatively and 6 months postoperatively. Setting University hospitals of Leeds and Leicester, UK. Patients 50 (25 TAVI, 25 SAVR; age 77±8 years) high-risk severe symptomatic aortic stenosis (AS) patients. Main outcome measures Valve haemodynamics, ventricular volumes, ejection fraction (EF), mass and MF. Results Patients were matched for gender and AS severity but not for age (80±6 vs 73±7 years, p=0.001) or EuroSCORE (22±14 vs 7±3, p<0.001). Aortic valve mean pressure gradient decreased to a greater degree post-TAVI compared to SAVR (21±8 mm Hg vs 35±13 mm Hg, p=0.017). Aortic regurgitation reduced by 8% in both groups, only reaching statistical significance for TAVI (p=0.003). TAVI and SAVR improved (p<0.05) left ventricular (LV) end-systolic volumes (46±18 ml/m2 vs 41±17 ml/m2; 44±22 ml/m2 vs32±6 ml/m2) and mass (83±20 g/m2 vs 65±15 g/m2; 74±11 g/m2 vs 59±8 g/m2). SAVR reduced end-diastolic volumes (92±19 ml/m2 vs 74±12 ml/m2, p<0.001) and TAVI increased EF (52±12% vs 56±10%, p=0.01). MF reduced post-TAVI (10.9±6% vs 8.5±5%, p=0.03) but not post-SAVR (4.2±2% vs 4.1±2%, p=0.98). Myocardial scar (p≤0.01) and baseline ventricular volumes (p<0.001) were the major predictors of reverse remodelling. Conclusions TAVI was comparable to SAVR at LV reverse remodelling and superior at reducing the valvular pressure gradient and MF. Future work should assess the prognostic importance of reverse remodelling and fibrosis post-TAVI to aid patient selection.