Transcatheter Aortic Valve Implantation in Low-Risk Tricuspid or Bicuspid Aortic Stenosis: The NOTION-2 Trial.

BACKGROUND AND AIMS: Transcatheter aortic valve implantation (TAVI) has become the first choice to treat older patients with severe symptomatic aortic stenosis (AS). This study aimed to compare TAVI with surgery in low-risk patients ≤ 75 years of age, including both tricuspid and bicuspid AS. METHODS: The NOTION-2 trial enrolled and 1:1 randomized low-risk patients aged ≤ 75 years with severe symptomatic AS to TAVI or surgery. The primary endpoint was a composite of all-cause mortality, stroke or rehospitalization (related to the procedure, valve or heart failure) at 12 months. RESULTS: A total of 370 patients were enrolled with a mean age of 71.1 years and a median Society of Thoracic Surgeons risk score of 1.1%. A total of 100 patients had bicuspid AS. The 1-year incidence of the primary endpoint was 10.2% in the TAVI group and 7.1% in the surgery group (absolute risk difference 3.1%; 95% confidence interval [CI], -2.7% to 8.8%; hazard ratio (HR) 1.4, 95% CI: 0.7 to 2.9; p=0.3). Patients with TAVI, when compared to surgery, had lower risk of major bleeding and new-onset atrial fibrillation and higher risk of non-disabling stroke, permanent pacemaker implantation and moderate-or-greater paravalvular regurgitation. The risk of the primary composite endpoint was 8.7% and 8.3% in patients with tricuspid AS (HR 1.0, 95% CI: 0.5 to 2.3) and 14.3% and 3.9% in patients with bicuspid AS (HR 3.8, 95% CI: 0.8 to 18.5) treated with TAVI or surgery, respectively (P for interaction=0.1). CONCLUSIONS: Among low-risk patients aged ≤ 75 years with severe symptomatic AS, the rate of the composite of death, stroke, or rehospitalization at one year was similar between TAVI and surgery. TAVI outcomes in young bicuspid AS patients warrant caution and should be further investigated. (NOTION-2, ClinicalTrials.gov, NCT02825134).

Transcatheter and surgical aortic valve replacement in patients with left ventricular dysfunction.

BACKGROUND: Patients with severe aortic stenosis and left ventricular systolic dysfunction have a poor prognosis, and this may result in inferior survival also after aortic valve replacement. The outcomes of transcatheter and surgical aortic valve replacement were investigated in this comparative analysis. METHODS: The retrospective nationwide FinnValve registry included data on patients who underwent transcatheter or surgical aortic valve replacement with a bioprosthesis for severe aortic stenosis. Propensity score matching was performed to adjust the outcomes for baseline covariates of patients with reduced (≤ 50%) left ventricular ejection fraction. RESULTS: Within the unselected, consecutive 6463 patients included in the registry, the prevalence of reduced ejection fraction was 20.8% (876 patients) in the surgical cohort and 27.7% (452 patients) in the transcatheter cohort. Reduced left ventricular ejection fraction was associated with decreased survival (adjusted hazards ratio 1.215, 95%CI 1.067-1.385) after a mean follow-up of 3.6 years. Among 255 propensity score matched pairs, 30-day mortality was 3.1% after transcatheter and 7.8% after surgical intervention (p = 0.038). One-year and 4-year survival were 87.5% and 65.9% after transcatheter intervention and 83.9% and 69.6% after surgical intervention (restricted mean survival time ratio, 1.002, 95%CI 0.929-1.080, p = 0.964), respectively. CONCLUSIONS: Reduced left ventricular ejection fraction was associated with increased morbidity and mortality after surgical and transcatheter aortic valve replacement. Thirty-day mortality was higher after surgery, but intermediate-term survival was comparable to transcatheter intervention. Trial registration The FinnValve registry ClinicalTrials.gov Identifier: NCT03385915.

Comparison between Fluorescence Imaging and Elemental Analysis to Determine Biodistribution of Inorganic Nanoparticles with Strong Light Absorption.

Black porous silicon nanoparticles (BPSi NPs) are known as highly efficient infrared light absorbers that are well-suitable for photothermal therapy (PTT) and photoacoustic imaging (PAI). PTT and PAI require a sufficient number of effectively light-absorbing NPs to be accumulated in tumor after intravenous administration. Herein, biodistribution of PEGylated BPSi NPs with different sizes (i.e., 140, 200, and 300 nm in diameter) is investigated after intravenous administration in mice. BPSi NPs were conjugated with fluorescent dyes Cy5.5 and Cy7.5 to track them in vitro and in vivo, respectively. Optical imaging with an in vivo imaging system (IVIS) was found to be an inadequate technique to assess the biodistribution of the dye-labeled BPSi NPs in vivo because the intrinsic strong absorbance of the BPSi NPs interfered fluorescence detection. This challenge was resolved via the use of inductively coupled plasma optical emission spectrometry to analyze ex vivo the silicon content in different tissues and tumors. The results indicated that most of the polyethylene glycol-coated BPSi NPs were found to accumulate in the liver and spleen after intravenous injection. The smallest 140 nm particles accumulated the most in tumors at an amount of 9.5 ± 3.4% of the injected dose (concentration of 0.18 ± 0.08 mg/mL), the amount known to produce sufficient heat for cancer PTT. Furthermore, the findings from the present study also suggest that techniques other than optical imaging should be considered to study the organ biodistribution of NPs with strong light absorbance properties.

Patient-Prosthesis Mismatch Worsens Long-Term Survival: Insights From the FinnValve Registry.

BACKGROUND: The impact of patient-prosthesis mismatch (PPM) on long-term outcome after surgical aortic valve replacement (SAVR) is controversial. We sought to investigate the incidence of PPM and its impact on survival and reinterventions in a Finnish nationwide cohort. METHODS: In the context of the nationwide FinnValve registry, we identified 4097 patients who underwent SAVR with a stented bioprosthesis with or without myocardial revascularization. The indexed effective orifice areas (EOAs) of surgical bioprostheses were calculated using literature-derived EOAs. PPM was graded as moderate (EOA 0.65-0.85 cm2/m2) or severe (EOA ≤0.65 cm2/m2). RESULTS: The incidence of PPM was 46.0%. PPM was moderate in 38.8% (n = 1579) patients and severe in 7.2% (n = 297) patients. Time-trend analysis showed that the proportion of PPM decreased significantly from 74% in 2009 to 18% in 2017 (P < .01). Severe PPM was associated with increased 5-year all-cause mortality (adjusted hazard ratio [HR], 1.72; 95% confidence interval [CI], 1.07-2.76; P = .02). Severe PPM was not associated with an increased risk of repeat AVR (adjusted HR, 5.90; 95% CI, 0.95-36.5; P = .06). In a subanalysis of patients greater than or equal to 70 years of age, in comparison with no PPM, any PPM (adjusted HR, 1.23; 95% CI, 1.05-1.45; P = .01) and severe PPM (HR, 1.53; 95% CI, 1.17-2.00; P < 0.01) were associated with increased risk of 5-year mortality. CONCLUSIONS: Severe PPM after SAVR had a negative impact on survival. This study demonstrated that the effects of PPM should not be overlooked in elderly undergoing SAVR.

Impact of paravalvular regurgitation on the mid-term outcome after transcatheter and surgical aortic valve replacement.

OBJECTIVES: The aim of this study was to evaluate the incidence and prognostic impact of paravalvular regurgitation (PVR) on the outcome after transcatheter (TAVR) and surgical aortic valve replacement (SAVR) for aortic stenosis. METHODS: The nationwide FinnValve registry included data on 6463 consecutive patients who underwent TAVR (n = 2130) or SAVR (n = 4333) with a bioprosthesis for the treatment of aortic stenosis during 2008-2017. The impact of PVR at discharge after TAVR and SAVR on 4-year mortality was herein investigated. RESULTS: The rate of mild PVR was 21.7% after TAVR and 5.2% after SAVR. The rate of moderate-to-severe PVR was 3.7% after TAVR and 0.7% after SAVR. After TAVR, 4-year survival was 69.0% in patients with none-to-trace PVR, 54.2% with mild PVR [adjusted hazard ratio (HR) 1.64, 95% confidence interval (CI) 1.35-1.99] and 48.9% with moderate-to-severe PVR (adjusted HR 1.61, 95% CI 1.10-2.35). Freedom from PVR-related reinterventions was 100% for none-to-mild PVR and 95.2% for moderate-to-severe PVR. After SAVR, mild PVR (4-year survival 78.9%; adjusted HR 1.29, 95% CI 0.93-1.78) and moderate-to-severe PVR (4-year survival 67.8%; adjusted HR 1.36, 95% CI 0.72-2.58) were associated with worse 4-year survival compared to none-to-trace PVR (4-year survival 83.7%), but the difference did not reach statistical significance in multivariable analysis. Freedom from PVR-related reinterventions was 99.5% for none-to-trace PVR patients, 97.9% for mild PVR patients and 77.0% for moderate-to-severe PVR patients. CONCLUSIONS: This multicentre study showed that both mild and moderate-to-severe PVR were independent predictors of worse survival after TAVR. Mild and moderate-to-severe PVR are not frequent after SAVR, but tend to decrease survival also in these patients. CLINICAL TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT03385915.

Mid-term outcomes of Sapien 3 versus Perimount Magna Ease for treatment of severe aortic stenosis.

BACKGROUND: There is limited information on the longer-term outcome after transcatheter aortic valve replacement (TAVR) with new-generation prostheses compared to surgical aortic valve replacement (SAVR). The aim of this study was to compare the mid-term outcomes after TAVR with Sapien 3 and SAVR with Perimount Magna Ease bioprostheses for severe aortic stenosis. METHODS: In a retrospective study, we included patients who underwent transfemoral TAVR with Sapien 3 or SAVR with Perimount Magna Ease bioprosthesis between January 2008 and October 2017 from the nationwide FinnValve registry. Propensity score matching was performed to adjust for differences in the baseline characteristics. The Kaplan-Meir method was used to estimate late mortality. RESULTS: A total of 2000 patients were included (689 in the TAVR cohort and 1311 in the SAVR cohort). Propensity score matching resulted in 308 pairs (STS score, TAVR 3.5 ± 2.2% vs. SAVR 3.5 ± 2.8%, p = 0.918). In-hospital mortality was 3.6% after SAVR and 1.3% after TAVR (p = 0.092). Stroke, acute kidney injury, bleeding and atrial fibrillation were significantly more frequent after SAVR, but higher rate of vascular complications was observed after TAVR. The cumulative incidence of permanent pacemaker implantation at 4 years was 13.9% in the TAVR group and 6.9% in the SAVR group (p = 0.0004). At 4-years, all-cause mortality was 20.6% for SAVR and 25.9% for TAVR (p = 0.910). Four-year rates of coronary revascularization, prosthetic valve endocarditis and repeat aortic valve intervention were similar between matched cohorts. CONCLUSIONS: The Sapien 3 bioprosthesis achieves comparable midterm outcomes to a surgical bioprosthesis with proven durability such as the Perimount Magna Ease. However, the Sapien 3 bioprosthesis was associated with better early outcome. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03385915 .

Favorable outcome of cancer patients undergoing transcatheter aortic valve replacement.

AIM: The aim of this study was to assess the outcome of transcatheter aortic valve replacement (TAVR) in patients with cancer. METHODS: This is a retrospective study from the nationwide FinnValve registry on 2130 consecutive patients who underwent TAVR for severe AS from January 2008 to October 2017. RESULTS: In this cohort, 417 patients (19.6%) had history of cancer and 113 (5.3%) had an active malignancy at the time of TAVR. Patients with any malignancy had similar late mortality than patients without any malignancy (at 7 years, 65.1% vs. 59.3%, adjusted HR 1.105, 95%CI 0.892-1.369). At 7 years, cancer-related mortality was 22.5% among patients with preoperative cancer, and 11.0% in those without preoperative cancer (p < 0.0001). Among cancer patients, 18 died of the same disease (at 7 years, mortality 12.5%). Active malignancy was not associated with increased risk of all-cause mortality (adjusted HR 1.100, 95%CI 0.757-1.599). However, patients with blood malignancies had a significantly increased risk of mortality (at 4-year, 53.5% vs. 35.4%, adjusted HR 2.029, 95%CI 1.328-3.098). CONCLUSIONS: This analysis showed that, when properly selected by the heart team and oncologists, most cancer patients undergoing TAVR can achieve a good survival and eventually die of other diseases. Blood malignancies seem to carry a poor prognosis in these patients. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03385915; https://clinicaltrials.gov/ct2/show/NCT03385915.

Trifecta Versus Perimount Magna Ease Aortic Valve Prostheses.

BACKGROUND: Recent surgical bovine pericardial prostheses are widely used despite limited data on their long-term durability. METHODS: This is a comparative analysis of the outcome of the Trifecta (Abbott, Abbott Park, IL) and Perimount Magna Ease (Edwards, Lifesciences Corp, Irvine, CA) bioprostheses from the FinnValve registry, a Finnish nationwide database including patients with aortic stenosis who underwent transcatheter or surgical aortic valve replacement with a bioprosthesis between 2008 and 2017. RESULTS: Overall 2216 patients (mean age, 74.1 ± 6.7 years; age <65 years, 8.9%; mean follow-up, 3.8 ± 2.1 years) received the Trifecta (851 patients) or the Perimount Magna Ease (1365 patients) bioprostheses. The rates of late mortality and prosthetic valve endocarditis were comparable in the study cohorts. At 7 years the Trifecta cohort had a significantly higher risk of repeat aortic valve replacement for structural valve failure (3.3% vs 0%; adjusted subdistribution hazard ratio, 2.224; 95% confidence interval, 1.044-4.737), repeat aortic valve replacement for any cause (3.6% vs 0.4%; adjusted subdistribution hazard ratio, 3.210; 95% confidence interval, 1.286-8.013), and repeat aortic valve replacement and/or prosthetic valve endocarditis (4.1% vs 0.9%; adjusted subdistribution hazard ratio, 3.210; 95% confidence interval, 1.286-8.013) compared with the Perimount Magna Ease cohort. Among 772 propensity score-matched pairs, at 7 years the Trifecta cohort had a higher risk of repeat aortic valve replacement for structural valve failure (5.7% vs 0%, P = .009). CONCLUSIONS: The Trifecta aortic bioprosthesis is associated with a higher occurrence of repeat aortic valve replacement for structural valve failure compared with the Perimount Magna Ease bioprosthesis. Further comparative studies with echocardiographic data on structural valve deterioration and longer follow-up are needed to confirm these findings.

Transcatheter and Surgical Aortic Valve Replacement in Patients With Recent Acute Heart Failure.

BACKGROUND: Patients with severe aortic stenosis and heart failure have poor prognosis, and their outcomes may be suboptimal even after transcatheter (TAVR) and surgical aortic valve replacement (SAVR). METHODS: This is an analysis of the nationwide FinnValve registry, which included patients who underwent primary TAVR or SAVR with a bioprothesis for aortic stenosis. We evaluated the outcome of patients with acute heart failure (AHF) within 60 days prior to TAVR or SAVR. RESULTS: The prevalence of recent AHF was 11.4% (484 of 4241 patients) in the SAVR cohort and 11.3% (210 of 1855 patients) in the TAVR cohort. In the SAVR cohort, AHF was associated with lower 30-day survival (91.3% vs 97.0%; adjusted odds ratio 1.801, 95% confidence interval [CI] 1.125-2.882) and 5-year survival (64.0% vs 81.2%; adjusted hazard ratio 1.482, 95% CI 1.207-1.821). SAVR patients with AHF had higher risk of major bleeding, need of mechanical circulatory support, acute kidney injury, prolonged hospital stay, and composite end-point (30-day mortality, stroke and/or acute kidney injury). Patients with AHF had a trend toward lower 30-day survival (crude rates 95.2% vs 97.9%; adjusted odds ratio 2.028, 95% CI 0.908-4.529) as well as significantly lower 5-year survival (crude rates 45.3% vs 58.5%; adjusted hazard ratio 1.530, 95% CI 1.185-1.976) also after TAVR. AHF increased the risk of acute kidney injury, prolonged hospital stay, and composite end-point after TAVR. CONCLUSIONS: Recent AHF is associated with increased risk of mortality and morbidity after SAVR and TAVR. These findings suggest that aortic stenosis patients should be referred for invasive treatment before the development of clinically evident heart failure.

Percutaneous coronary angioplasty versus coronary artery bypass grafting in the treatment of unprotected left main stenosis: updated 5-year outcomes from the randomised, non-inferiority NOBLE trial.

BACKGROUND: Percutaneous coronary intervention (PCI) is increasingly used in revascularisation of patients with left main coronary artery disease in place of the standard treatment, coronary artery bypass grafting (CABG). The NOBLE trial aimed to evaluate whether PCI was non-inferior to CABG in the treatment of left main coronary artery disease and reported outcomes after a median follow-up of 3·1 years. We now report updated 5-year outcomes of the trial. METHODS: The prospective, randomised, open-label, non-inferiority NOBLE trial was done at 36 hospitals in nine northern European countries. Patients with left main coronary artery disease requiring revascularisation were enrolled and randomly assigned (1:1) to receive PCI or CABG. The primary endpoint was major adverse cardiac or cerebrovascular events (MACCE), a composite of all-cause mortality, non-procedural myocardial infarction, repeat revascularisation, and stroke. Non-inferiority of PCI to CABG was defined as the upper limit of the 95% CI of the hazard ratio (HR) not exceeding 1·35 after 275 MACCE had occurred. Secondary endpoints included all-cause mortality, non-procedural myocardial infarction, and repeat revascularisation. Outcomes were analysed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT01496651. FINDINGS: Between Dec 9, 2008, and Jan 21, 2015, 1201 patients were enrolled and allocated to PCI (n=598) or CABG (n=603), with 17 subsequently lost to early follow-up. 592 patients in each group were included in this analysis. At a median of 4·9 years of follow-up, the predefined number of events was reached for adequate power to assess the primary endpoint. Kaplan-Meier 5-year estimates of MACCE were 28% (165 events) for PCI and 19% (110 events) for CABG (HR 1·58 [95% CI 1·24-2·01]); the HR exceeded the limit for non-inferiority of PCI compared to CABG. CABG was found to be superior to PCI for the primary composite endpoint (p=0·0002). All-cause mortality was estimated in 9% after PCI versus 9% after CABG (HR 1·08 [95% CI 0·74-1·59]; p=0·68); non-procedural myocardial infarction was estimated in 8% after PCI versus 3% after CABG (HR 2·99 [95% CI 1·66-5·39]; p=0·0002); and repeat revascularisation was estimated in 17% after PCI versus 10% after CABG (HR 1·73 [95% CI 1·25-2·40]; p=0·0009). INTERPRETATION: In revascularisation of left main coronary artery disease, PCI was associated with an inferior clinical outcome at 5 years compared with CABG. Mortality was similar after the two procedures but patients treated with PCI had higher rates of non-procedural myocardial infarction and repeat revascularisation. FUNDING: Biosensors.

Usefulness of Post-coronary Dilation to Prevent Recurrent Myocardial Infarction in Patients Treated With Percutaneous Coronary Intervention for Acute Coronary Syndrome (from the BASE ACS Trial).

Stent underexpansion is associated with worse outcome after stent implantation. Whether post-dilation (PD) improves outcome in patients with acute coronary syndrome (ACS) remains unclear. We performed post hoc analysis of outcome in patients from the BASE ACS (A prospective randomized comparison of titanium-nitride-oxide-coated bioactive stents with everolimus-eluting stents in acute coronary syndrome) trial who underwent PD versus those who did not. The BASE ACS trial randomized 827 patients (1:1) with ACS to receive either titanium-nitride-oxide-coated bioactive stents or everolimus-eluting stents. The primary end point was major adverse cardiac events (MACE): a composite of cardiac death, nonfatal myocardial infarction (MI), or ischemia-driven target lesion revascularization. Follow-up was planned at 12 months and yearly thereafter for up to 7 years. Of 827 patients enrolled in the BASE ACS trial, 357 (43.2%) underwent PD. Median follow-up duration was 5 years. Patients who underwent PD had less frequent nonfatal MI events at long-term follow-up, compared with those who did not (4.5% vs 8.5%, respectively, p = 0.02). The rates of MACE (15.7% vs 15.1%, respectively, p = 0.81), and the other endpoints, were not significantly different (p >0.5 for all). The results were consistent in propensity score-matched analysis (270 pairs). In patients treated with bioactive stents, those who underwent PD had a trend for a fewer nonfatal MI events (p = 0.076). Comparably, in patients treated with everolimus-eluting stents, MACE and all the individual end points were comparable (p >0.5 for all). In conclusion, patients treated with early percutaneous coronary intervention for ACS who underwent PD had less frequent nonfatal MI events at long-term follow-up, compared with those who did not; MACE rates were not significantly different.

Long-term clinical outcome of elderly patients with acute coronary syndrome treated with early percutaneous coronary intervention: Insights from the BASE ACS randomized controlled trial: Bioactive versus everolimus-eluting stents in elderly patients.

BACKGROUND: The BASE ACS trial demonstrated an outcome of titanium-nitride-oxide-coated bioactive stents (BAS) that was non-inferior to everolimus-eluting stents (EES) in patients presenting with acute coronary syndrome (ACS). We performed a post hoc analysis of elderly versus non-elderly patients from the BASE ACS trial. METHODS: We randomized 827 patients (1:1) presenting with ACS to receive either BAS or EES. The primary endpoint was major adverse cardiac events (MACE): a composite of cardiac death, non-fatal myocardial infarction (MI), or ischemia-driven target lesion revascularization (TLR). Follow-up was planned at 12months and yearly thereafter for up to 7years. Elderly age was defined as ≥65years. RESULTS: Of the 827 patients enrolled in the BASE ACS trial, 360 (43.5%) were elderly. Mean follow-up duration was 4.2±1.9years. MACE was more frequent in elderly versus younger patients (19.7% versus 12.0%, respectively, p=0.002), probably driven by more frequent cardiac death and non-fatal MI events (5.3% versus 1.5%, and 9.7% versus 4.5%, p=0.002 and p=0.003, respectively). The rates of ischemia-driven TLR were comparable (p>0.05). In propensity score-matched analysis (215 pairs), only cardiac death was more frequent in elderly patients (6% versus 1.4%, respectively, p=0.01). Diabetes independently predicted both MACE and cardiac death in elderly patients. CONCLUSIONS: Elderly patients treated with stent implantation for ACS had worse long-term clinical outcome, compared with younger ones, mainly due to a higher death rate.

Percutaneous coronary angioplasty versus coronary artery bypass grafting in treatment of unprotected left main stenosis (NOBLE): a prospective, randomised, open-label, non-inferiority trial.

BACKGROUND: Coronary artery bypass grafting (CABG) is the standard treatment for revascularisation in patients with left main coronary artery disease, but use of percutaneous coronary intervention (PCI) for this indication is increasing. We aimed to compare PCI and CABG for treatment of left main coronary artery disease. METHODS: In this prospective, randomised, open-label, non-inferiority trial, patients with left main coronary artery disease were enrolled in 36 centres in northern Europe and randomised 1:1 to treatment with PCI or CABG. Eligible patients had stable angina pectoris, unstable angina pectoris, or non-ST-elevation myocardial infarction. Exclusion criteria were ST-elevation myocardial infarction within 24 h, being considered too high risk for CABG or PCI, or expected survival of less than 1 year. The primary endpoint was major adverse cardiac or cerebrovascular events (MACCE), a composite of all-cause mortality, non-procedural myocardial infarction, any repeat coronary revascularisation, and stroke. Non-inferiority of PCI to CABG required the lower end of the 95% CI not to exceed a hazard ratio (HR) of 1·35 after up to 5 years of follow-up. The intention-to-treat principle was used in the analysis if not specified otherwise. This trial is registered with ClinicalTrials.gov identifier, number NCT01496651. FINDINGS: Between Dec 9, 2008, and Jan 21, 2015, 1201 patients were randomly assigned, 598 to PCI and 603 to CABG, and 592 in each group entered analysis by intention to treat. Kaplan-Meier 5 year estimates of MACCE were 29% for PCI (121 events) and 19% for CABG (81 events), HR 1·48 (95% CI 1·11-1·96), exceeding the limit for non-inferiority, and CABG was significantly better than PCI (p=0·0066). As-treated estimates were 28% versus 19% (1·55, 1·18-2·04, p=0·0015). Comparing PCI with CABG, 5 year estimates were 12% versus 9% (1·07, 0·67-1·72, p=0·77) for all-cause mortality, 7% versus 2% (2·88, 1·40-5·90, p=0·0040) for non-procedural myocardial infarction, 16% versus 10% (1·50, 1·04-2·17, p=0·032) for any revascularisation, and 5% versus 2% (2·25, 0·93-5·48, p=0·073) for stroke. INTERPRETATION: The findings of this study suggest that CABG might be better than PCI for treatment of left main stem coronary artery disease. FUNDING: Biosensors, Aarhus University Hospital, and participating sites.

Efficacy and safety of the Lotus Valve System for treatment of patients with severe aortic valve stenosis and intermediate surgical risk: Results from the Nordic Lotus-TAVR registry.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) has become an established therapeutic option for patients with symptomatic, severe aortic valve stenosis (AS) who are ineligible or at high risk for conventional valvular surgery. In Northwestern Europe, the TAVR technology is also increasingly used to treat patients with an intermediate risk profile. METHODS AND RESULTS: The study was designed as an independent Nordic multicenter registry of intermediate risk patients treated with the Lotus Valve System (Boston Scientific, MA, USA; N=154). Valve Academic Research Consortium (VARC)-defined device success was obtained in 97.4%. A Lotus Valve was successfully implanted in all patients. There was no valve migration, embolization, ectopic valve deployment, or TAV-in-TAV deployment. The VARC-defined combined safety rate at 30days was 92.2%, with a mortality rate of 1.9% and stroke rate of 3.2%. The clinical efficacy rate after 30days was 91.6% - only one patient had moderate aortic regurgitation. When considering only those patients in the late experience group (N=79), the combined safety and clinical efficacy rates were 93.7% and 92.4%, respectively. The pacemaker implantation rate was 27.9% - this rate was 12.8% in case of a combined implantation depth <4mm and a device/annulus ratio<1.05. CONCLUSIONS: The present study demonstrates the efficacy and safety of the repositionable, retrievable Lotus Valve System in intermediate risk patients with AS. The VARC-defined device success rate was 97.4% with a 30-day patient safety and clinical efficacy rate of more than 90%. Less than moderate aortic regurgitation was obtained in 99.4% of patients.

4-Year outcome of bioactive stents versus everolimus-eluting stents in acute coronary syndrome.

OBJECTIVES: The BASE-ACS trial demonstrated non-inferiority of titanium-nitride-oxide-coated bioactive stents (BAS), versus everolimus-eluting stents (EES), for major adverse cardiac events (MACE) at 1- and 2-year follow-up, in patients with acute coronary syndrome (ACS). We presented the 4-year outcome of the BASE-ACS trial. DESIGN: We randomized 827 patients with ACS to receive either BAS (417) or EES (410). MACE was a composite of cardiac death, non-fatal myocardial infarction (MI) or ischemia-driven target lesion revascularization (TLR) at 12-month follow-up. Analyses were performed by intention to treat. Follow-up was planned at 12 months, and yearly thereafter for 5 years. RESULTS: Four-year clinical follow-up was completed in 753 (91.1%) patients. At 4 years, BAS were non-inferior to EES for MACE (14.7% versus 17.8%, respectively; p = 0.24 for superiority; p = 0.001 for non-inferiority). Non-fatal MI was less frequent with BAS (5.0% versus 9.2%, respectively; p = 0.025). Cardiac death and ischemia-driven TLR were comparable (2.9% versus 3.5%, and 8.6% versus 9.2%; p = 0.62 and p = 0.80, respectively). Independent predictors of MACE were calcified lesions (HR 1.54, p = 0.021), the number of vessels treated (HR 1.53, p = 0.025), and reference vessel diameter (HR 0.54, p = 0.006). CONCLUSIONS: In patients presenting with ACS, BAS was associated with a clinical outcome non-inferior to EES at 4-year follow-up.

Gender-based analysis of randomized comparison of bioactive versus everolimus-eluting stents in acute coronary syndrome.

AIMS: The randomized comparison of titanium-nitride-oxide-coated bioactive stent with everolimus-eluting stent in acute coronary syndrome (BASE-ACS) trial demonstrated an outcome of the titanium-nitride-oxide coated bioactive stents (BASs) that was statistically noninferior to that of the everolimus-eluting stents (EESs) at 12-month follow-up, in patients presenting with acute coronary syndrome (ACS) who underwent early percutaneous coronary intervention. We performed a post-hoc gender-based analysis of the BASE-ACS trial at 24-month follow-up. METHODS: A total of 827 patients (198 women) with ACS were randomly assigned to receive either BAS or EES. The primary endpoint was a composite of cardiac death, nonfatal myocardial infarction (MI), or ischemia-driven target lesion revascularization. RESULTS: Women were older, and more likely to have diabetes and hypertension compared with men (P < 0.05 for all). Moreover, women had significantly smaller reference vessel diameter and stent diameter (P < 0.05 for all). At 24-month follow-up, the cumulative incidence of the primary endpoint was similar between the two sex subgroups (15.2 versus 11.0%, for women versus men, respectively, P = 0.13). However, the rate of nonfatal MI was significantly higher in women compared with men (8.6 versus 3.8%, respectively, P = 0.007). After propensity score-adjusted analysis, there was a trend toward more nonfatal MI among women (8.6 versus 4.0%, respectively, P = 0.08). Moreover, among male patients, those assigned to BAS had significantly lower nonfatal MI compared with those assigned to EES (P = 0.027). However, among patients assigned to EES, female patients had a significantly higher rate of nonfatal MI compared with men (P = 0.02). CONCLUSION: In the current post-hoc gender-based analysis of the BASE-ACS trial, the 24-month outcome of patients undergoing percutaneous coronary intervention for ACS was slightly worse in women, compared with men, as reflected by a trend toward more nonfatal MI events after propensity score-adjusted analysis.

The effect of bone marrow microenvironment on the functional properties of the therapeutic bone marrow-derived cells in patients with acute myocardial infarction.

BACKGROUND: Treatment of acute myocardial infarction with stem cell transplantation has achieved beneficial effects in many clinical trials. The bone marrow microenvironment of ST-elevation myocardial infarction (STEMI) patients has never been studied even though myocardial infarction is known to cause an imbalance in the acid-base status of these patients. The aim of this study was to assess if the blood gas levels in the bone marrow of STEMI patients affect the characteristics of the bone marrow cells (BMCs) and, furthermore, do they influence the change in cardiac function after autologous BMC transplantation. The arterial, venous and bone marrow blood gas concentrations were also compared. METHODS: Blood gas analysis of the bone marrow aspirate and peripheral blood was performed for 27 STEMI patients receiving autologous stem cell therapy after percutaneous coronary intervention. Cells from the bone marrow aspirate were further cultured and the bone marrow mesenchymal stem cell (MSC) proliferation rate was determined by MTT assay and the MSC osteogenic differentiation capacity by alkaline phosphatase (ALP) activity assay. All the patients underwent a 2D-echocardiography at baseline and 4 months after STEMI. RESULTS: As expected, the levels of pO(2), pCO(2), base excess and HCO(3) were similar in venous blood and bone marrow. Surprisingly, bone marrow showed significantly lower pH and Na(+) and elevated K(+) levels compared to arterial and venous blood. There was a positive correlation between the bone marrow pCO(2) and HCO(3) levels and MSC osteogenic differentiation capacity. In contrast, bone marrow pCO(2) and HCO(3) levels displayed a negative correlation with the proliferation rate of MSCs. Patients with the HCO(3) level below the median value exhibited a more marked change in LVEF after BMC treatment than patients with HCO(3) level above the median (11.13 ± 8.07% vs. 2.67 ± 11.89%, P = 0.014). CONCLUSIONS: Low bone marrow pCO(2) and HCO(3) levels may represent the optimal environment for BMCs in terms of their efficacy in autologous stem cell therapy in STEMI patients.

Radial versus femoral access for coronary angiography and intervention in patients with acute coronary syndromes (RIVAL): a randomised, parallel group, multicentre trial.

BACKGROUND: Small trials have suggested that radial access for percutaneous coronary intervention (PCI) reduces vascular complications and bleeding compared with femoral access. We aimed to assess whether radial access was superior to femoral access in patients with acute coronary syndromes (ACS) who were undergoing coronary angiography with possible intervention. METHODS: The RadIal Vs femorAL access for coronary intervention (RIVAL) trial was a randomised, parallel group, multicentre trial. Patients with ACS were randomly assigned (1:1) by a 24 h computerised central automated voice response system to radial or femoral artery access. The primary outcome was a composite of death, myocardial infarction, stroke, or non-coronary artery bypass graft (non-CABG)-related major bleeding at 30 days. Key secondary outcomes were death, myocardial infarction, or stroke; and non-CABG-related major bleeding at 30 days. A masked central committee adjudicated the primary outcome, components of the primary outcome, and stent thrombosis. All other outcomes were as reported by the investigators. Patients and investigators were not masked to treatment allocation. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, NCT01014273. FINDINGS: Between June 6, 2006, and Nov 3, 2010, 7021 patients were enrolled from 158 hospitals in 32 countries. 3507 patients were randomly assigned to radial access and 3514 to femoral access. The primary outcome occurred in 128 (3·7%) of 3507 patients in the radial access group compared with 139 (4·0%) of 3514 in the femoral access group (hazard ratio [HR] 0·92, 95% CI 0·72-1·17; p=0·50). Of the six prespecified subgroups, there was a significant interaction for the primary outcome with benefit for radial access in highest tertile volume radial centres (HR 0·49, 95% CI 0·28-0·87; p=0·015) and in patients with ST-segment elevation myocardial infarction (0·60, 0·38-0·94; p=0·026). The rate of death, myocardial infarction, or stroke at 30 days was 112 (3·2%) of 3507 patients in the radial group compared with 114 (3·2%) of 3514 in the femoral group (HR 0·98, 95% CI 0·76-1·28; p=0·90). The rate of non-CABG-related major bleeding at 30 days was 24 (0·7%) of 3507 patients in the radial group compared with 33 (0·9%) of 3514 patients in the femoral group (HR 0·73, 95% CI 0·43-1·23; p=0·23). At 30 days, 42 of 3507 patients in the radial group had large haematoma compared with 106 of 3514 in the femoral group (HR 0·40, 95% CI 0·28-0·57; p<0·0001). Pseudoaneurysm needing closure occurred in seven of 3507 patients in the radial group compared with 23 of 3514 in the femoral group (HR 0·30, 95% CI 0·13-0·71; p=0·006). INTERPRETATION: Radial and femoral approaches are both safe and effective for PCI. However, the lower rate of local vascular complications may be a reason to use the radial approach. FUNDING: Sanofi-Aventis, Population Health Research Institute, and Canadian Network for Trials Internationally (CANNeCTIN), an initiative of the Canadian Institutes of Health Research.