Multicenter experience with valve-in-valve transcatheter aortic valve replacement compared with primary, native valve transcatheter aortic valve replacement.

BACKGROUND: Valve-in-valve (ViV) transcatheter aortic valve replacement (TAVR) offers an alternative to reoperative surgical aortic valve replacement. The short- and intermediate-term outcomes after ViV TAVR in the real world are not entirely clear. PATIENTS AND METHODS: A multicenter, retrospective analysis of a consecutive series of 121 ViV TAVR patients and 2200 patients undergoing primary native valve TAVR from 2012 to 2017 at six medical centers. The main outcome measures were in-hospital mortality, 30-day mortality, stroke, myocardial infarction, acute kidney injury, and pacemaker implantation. RESULTS: ViV patients were more likely male, younger, prior coronary artery bypass graft, "hostile chest," and urgent. 30% of the patients had Society of Thoracic Surgeons risk score <4%, 36.3% were 4%-8% and 33.8% were >8%. In both groups many patients had concomitant coronary artery disease. Median time to prosthetic failure was 9.6 years (interquartile range: 5.5-13.5 years). 82% of failed surgical valves were size 21, 23, or 25 mm. Access was 91% femoral. After ViV, 87% had none or trivial aortic regurgitation. Mean gradients were <20 mmHg in 54.6%, 20-29 mmHg in 30.6%, 30-39 mmHg in 8.3% and ≥40 mmHg in 5.87%. Median length of stay was 4 days. In-hospital mortality was 0%. 30-day mortality was 0% in ViV and 3.7% in native TAVR. There was no difference in in-hospital mortality, postprocedure myocardial infarction, stroke, or acute kidney injury. CONCLUSION: Compared to native TAVR, ViV TAVR has similar peri-procedural morbidity with relatively high postprocedure mean gradients. A multidisciplinary approach will help ensure patients receive the ideal therapy in the setting of structural bioprosthetic valve degeneration.

Twelve or 30 months of dual antiplatelet therapy after drug-eluting stents.

BACKGROUND: Dual antiplatelet therapy is recommended after coronary stenting to prevent thrombotic complications, yet the benefits and risks of treatment beyond 1 year are uncertain. METHODS: Patients were enrolled after they had undergone a coronary stent procedure in which a drug-eluting stent was placed. After 12 months of treatment with a thienopyridine drug (clopidogrel or prasugrel) and aspirin, patients were randomly assigned to continue receiving thienopyridine treatment or to receive placebo for another 18 months; all patients continued receiving aspirin. The coprimary efficacy end points were stent thrombosis and major adverse cardiovascular and cerebrovascular events (a composite of death, myocardial infarction, or stroke) during the period from 12 to 30 months. The primary safety end point was moderate or severe bleeding. RESULTS: A total of 9961 patients were randomly assigned to continue thienopyridine treatment or to receive placebo. Continued treatment with thienopyridine, as compared with placebo, reduced the rates of stent thrombosis (0.4% vs. 1.4%; hazard ratio, 0.29 [95% confidence interval {CI}, 0.17 to 0.48]; P<0.001) and major adverse cardiovascular and cerebrovascular events (4.3% vs. 5.9%; hazard ratio, 0.71 [95% CI, 0.59 to 0.85]; P<0.001). The rate of myocardial infarction was lower with thienopyridine treatment than with placebo (2.1% vs. 4.1%; hazard ratio, 0.47; P<0.001). The rate of death from any cause was 2.0% in the group that continued thienopyridine therapy and 1.5% in the placebo group (hazard ratio, 1.36 [95% CI, 1.00 to 1.85]; P=0.05). The rate of moderate or severe bleeding was increased with continued thienopyridine treatment (2.5% vs. 1.6%, P=0.001). An elevated risk of stent thrombosis and myocardial infarction was observed in both groups during the 3 months after discontinuation of thienopyridine treatment. CONCLUSIONS: Dual antiplatelet therapy beyond 1 year after placement of a drug-eluting stent, as compared with aspirin therapy alone, significantly reduced the risks of stent thrombosis and major adverse cardiovascular and cerebrovascular events but was associated with an increased risk of bleeding. (Funded by a consortium of eight device and drug manufacturers and others; DAPT ClinicalTrials.gov number, NCT00977938.).

Fractional flow reserve versus angiography for guidance of PCI in patients with multivessel coronary artery disease (FAME): 5-year follow-up of a randomised controlled trial.

BACKGROUND: In the Fractional Flow Reserve Versus Angiography for Multivessel Evaluation (FAME) study, fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) improved outcome compared with angiography-guided PCI for up to 2 years of follow-up. The aim in this study was to investigate whether the favourable clinical outcome with the FFR-guided PCI in the FAME study persisted over a 5-year follow-up. METHODS: The FAME study was a multicentre trial done in Belgium, Denmark, Germany, the Netherlands, Sweden, the UK, and the USA. Patients (aged ≥ 18 years) with multivessel coronary artery disease were randomly assigned to undergo angiography-guided PCI or FFR-guided PCI. Before randomisation, stenoses requiring PCI were identified on the angiogram. Patients allocated to angiography-guided PCI had revascularisation of all identified stenoses. Patients allocated to FFR-guided PCI had FFR measurements of all stenotic arteries and PCI was done only if FFR was 0·80 or less. No one was masked to treatment assignment. The primary endpoint was major adverse cardiac events at 1 year, and the data for the 5-year follow-up are reported here. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00267774. FINDINGS: After 5 years, major adverse cardiac events occurred in 31% of patients (154 of 496) in the angiography-guided group versus 28% (143 of 509 patients) in the FFR-guided group (relative risk 0·91, 95% CI 0·75-1·10; p=0·31). The number of stents placed per patient was significantly higher in the angiography-guided group than in the FFR-guided group (mean 2·7 [SD 1·2] vs 1·9 [1·3], p<0·0001). INTERPRETATION: The results confirm the long-term safety of FFR-guided PCI in patients with multivessel disease. A strategy of FFR-guided PCI resulted in a significant decrease of major adverse cardiac events for up to 2 years after the index procedure. From 2 years to 5 years, the risks for both groups developed similarly. This clinical outcome in the FFR-guided group was achieved with a lower number of stented arteries and less resource use. These results indicate that FFR guidance of multivessel PCI should be the standard of care in most patients. FUNDING: St Jude Medical, Friends of the Heart Foundation, and Medtronic.

Fractional flow reserve versus angiography for guiding percutaneous coronary intervention.

BACKGROUND: In patients with multivessel coronary artery disease who are undergoing percutaneous coronary intervention (PCI), coronary angiography is the standard method for guiding the placement of the stent. It is unclear whether routine measurement of fractional flow reserve (FFR; the ratio of maximal blood flow in a stenotic artery to normal maximal flow), in addition to angiography, improves outcomes. METHODS: In 20 medical centers in the United States and Europe, we randomly assigned 1005 patients with multivessel coronary artery disease to undergo PCI with implantation of drug-eluting stents guided by angiography alone or guided by FFR measurements in addition to angiography. Before randomization, lesions requiring PCI were identified on the basis of their angiographic appearance. Patients assigned to angiography-guided PCI underwent stenting of all indicated lesions, whereas those assigned to FFR-guided PCI underwent stenting of indicated lesions only if the FFR was 0.80 or less. The primary end point was the rate of death, nonfatal myocardial infarction, and repeat revascularization at 1 year. RESULTS: The mean (+/-SD) number of indicated lesions per patient was 2.7+/-0.9 in the angiography group and 2.8+/-1.0 in the FFR group (P=0.34). The number of stents used per patient was 2.7+/-1.2 and 1.9+/-1.3, respectively (P<0.001). The 1-year event rate was 18.3% (91 patients) in the angiography group and 13.2% (67 patients) in the FFR group (P=0.02). Seventy-eight percent of the patients in the angiography group were free from angina at 1 year, as compared with 81% of patients in the FFR group (P=0.20). CONCLUSIONS: Routine measurement of FFR in patients with multivessel coronary artery disease who are undergoing PCI with drug-eluting stents significantly reduces the rate of the composite end point of death, nonfatal myocardial infarction, and repeat revascularization at 1 year. (ClinicalTrials.gov number, NCT00267774.)

Pharmacodynamic effect and clinical efficacy of clopidogrel and prasugrel with or without a proton-pump inhibitor: an analysis of two randomised trials.

BACKGROUND: Proton-pump inhibitors (PPIs) are often prescribed in combination with thienopyridines. Conflicting data exist as to whether PPIs diminish the efficacy of clopidogrel. We assessed the association between PPI use, measures of platelet function, and clinical outcomes for patients treated with clopidogrel or prasugrel. METHODS: In the PRINCIPLE-TIMI 44 trial, the primary outcome was inhibition of platelet aggregation at 6 h assessed by light-transmission aggregometry. In the TRITON-TIMI 38 trial, the primary endpoint was the composite of cardiovascular death, myocardial infarction, or stroke. In both studies, PPI use was at physician's discretion. We used a multivariable Cox model with propensity score to assess the association of PPI use with clinical outcomes. FINDINGS: In the PRINCIPLE-TIMI 44 trial, 201 patients undergoing elective percutaneous coronary intervention were randomly assigned to prasugrel (n=102) or high-dose clopidogrel (n=99). Mean inhibition of platelet aggregation was significantly lower for patients on a PPI than for those not on a PPI at 6 h after a 600 mg clopidogrel loading dose (23.2+/-19.5% vs 35.2+/-20.9%, p=0.02), whereas a more modest difference was seen with and without a PPI after a 60 mg loading dose of prasugrel (69.6+/-13.5% vs 76.7+/-12.4%, p=0.054). In the TRITON-TIMI 38 trial, 13,608 patients with an acute coronary syndrome were randomly assigned to prasugrel (n=6813) or clopidogrel (n=6795). In this study, 33% (n=4529) of patients were on a PPI at randomisation. No association existed between PPI use and risk of the primary endpoint for patients treated with clopidogrel (adjusted hazard ratio [HR] 0.94, 95% CI 0.80-1.11) or prasugrel (1.00, 0.84-1.20). INTERPRETATION: The current findings do not support the need to avoid concomitant use of PPIs, when clinically indicated, in patients receiving clopidogrel or prasugrel. FUNDING: Daiichi Sankyo Company Limited and Eli Lilly and Company sponsored the trials. This analysis had no funding.

Serious renal dysfunction after percutaneous coronary interventions can be predicted.

BACKGROUND: A prediction rule for determining the post-percutaneous coronary intervention (PCI) risk of developing contrast-induced nephropathy (> or = 25% or > or = 0.5 mg/dL increase in creatinine) has been reported. However, little work has been done on predicting pre-PCI patient-specific risk for developing more serious renal dysfunction (SRD; new dialysis, > or = 2.0 mg/dL absolute increase in creatinine, or a > or = 50% increase in creatinine). We hypothesized that preprocedural patient characteristics could be used to predict the risk of post-PCI SRD. METHODS: Data were prospectively collected on a consecutive series of 11141 patients undergoing PCI without dialysis in northern New England from 2003 to 2005. Multivariate logistic regression model was used to identify the combination of patient characteristics most predictive of developing post-PCI SRD. The ability of the model to discriminate was quantified using a bootstrap validated C-Index (area under the receiver operating characteristic [ROC] curve). Its calibration was tested with a Hosmer-Lemeshow statistic. The model was validated on PCI procedures in 2006. RESULTS: Serious renal dysfunction occurred in 0.74% of patients (83/11141) with an associated inhospital mortality of 19.3% versus 0.9% in those without SRD. The model discriminated well between patients who did and did not develop SRD after PCI (ROC 0.87, 95% CI 0.82-0.91). Preprocedural creatinine (37%), congestive heart failure (24%), and diabetes (15%) accounted for 76% of the predictive ability of the model. The other factors contributed 24%: urgent and emergent priority (10%), preprocedural intra-aortic balloon pump use (8%), age > or = 80 years (5%), and female sex (1%). Validation of the model was successful with ROC: 0.84 (95% CI 0.80-0.89). CONCLUSIONS: Although infrequent, the occurrence of SRD after PCI is associated with a very high inhospital mortality. We developed and validated a robust clinical prediction rule to determine which patients are at high risk for SRD. Use of this model may help physicians perform targeted interventions to reduce this risk.

The anticoagulant therapy with bivalirudin to assist in the performance of percutaneous coronary intervention in patients with heparin-induced thrombocytopenia (ATBAT) study: main results.

Up to 5% of patients given heparin develop heparin-induced thrombocytopenia (HIT). These patients may need anticoagulation for acute coronary syndromes (ACS) or percutaneous coronary intervention (PCI), a clinical challenge given the limited alternatives. In a prospective, open-label study, we evaluated the safety and efficacy of bivalirudin in patients with HIT or HIT with thrombotic syndrome (HITTS) undergoing PCI. Patients aged 18 years were enrolled in 24 centers in 2 countries. Bivalirudin was given 5 minutes before PCI (1 mg/kg bolus; 2.5 mg/kg/hour infusion for 4 hours [high-dose group] or 0.75 mg/kg bolus; 1.75 mg/kg/hour infusion [low-dose group]). Clinical and hematological measures were assessed within 24 hours after starting bivalirudin, just before PCI, just before sheath removal, and 48 hours after treatment or at discharge, whichever occurred first. The primary endpoint was major bleeding 48 hours after discontinuation or until discharge, whichever occurred first. From July 1999 to February 2003, 52 patients were recruited. Procedural success (TIMI grade 3 flow and < 50% stenosis) was achieved in 98% of patients, and clinical success (absence of death, emergency bypass surgery, or Q-wave infarction) was achieved in 96%. One high-dose patient who underwent elective bypass surgery had major bleeding (1.9%; 95% CI: 0.05 10.65%), and 7 patients had minor bleeding. No patient had significant thrombocytopenia (platelet count < 50 109/L) after treatment. One patient in the low-dose group died from cardiac arrest ~46 hours after uncomplicated PCI. Bivalirudin appeared safe and provided effective anticoagulation during PCI. These data, and extensive experience with bivalirudin in PCI, support its use in high-risk patients with HIT requiring PCI.

How do centres begin the process to prevent contrast-induced acute kidney injury: a report from a new regional collaborative.

OBJECTIVES: This study evaluates the variation in practice patterns associated with contrast-induced acute kidney injury (CI-AKI) and identifies clinical practices that have been associated with a reduction in CI-AKI. Background CI-AKI is recognised as a complication of invasive cardiovascular procedures and is associated with cardiovascular events, prolonged hospitalisation, end-stage renal disease, and all-cause mortality. Reducing the risk of CI-AKI is a patient safety objective set by the National Quality Forum. METHODS: This study prospectively collected quantitative and qualitative data from 10 centres, which participate in the Northern New England Cardiovascular Disease Study Group PCI Registry. Quantitative data were collected from the PCI Registry. Qualitative data were obtained through clinical team meetings to map care processes related to CI-AKI and focus groups to understand attitudes towards CI-AKI prophylaxis. Fixed and random effects modelling were conducted to test the differences across centres. RESULTS: Significant variation in rates of CI-AKI were found across 10 medical centres. Both fixed effects and mixed effects logistic regression demonstrated significant variability across centres, even after adjustment for baseline covariates (p<0.001 for both modelling approaches). Patterns were found in reported processes and clinical leadership that were attributable to centres with lower rates of CI-AKI. These included reducing nil by mouth (NPO) time to 4 h prior to case, and standardising volume administration protocols in combination with administering three to four high doses of N-acetylcysteine (1200 mg) for each patient. CONCLUSIONS: These data suggest that clinical leadership and institution-focused efforts to standardise preventive practices can help reduce the incidence of CI-AKI.

Angiographic versus functional severity of coronary artery stenoses in the FAME study fractional flow reserve versus angiography in multivessel evaluation.

OBJECTIVES: The purpose of this study was to investigate the relationship between angiographic and functional severity of coronary artery stenoses in the FAME (Fractional Flow Reserve Versus Angiography in Multivessel Evaluation) study. BACKGROUND: It can be difficult to determine on the coronary angiogram which lesions cause ischemia. Revascularization of coronary stenoses that induce ischemia improves a patient's functional status and outcome. For stenoses that do not induce ischemia, however, the benefit of revascularization is less clear. METHODS: In the FAME study, routine measurement of the fractional flow reserve (FFR) was compared with angiography for guiding percutaneous coronary intervention in patients with multivessel coronary artery disease. The use of the FFR in addition to angiography significantly reduced the rate of all major adverse cardiac events at 1 year. Of the 1,414 lesions (509 patients) in the FFR-guided arm of the FAME study, 1,329 were successfully assessed by the FFR and are included in this analysis. RESULTS: Before FFR measurement, these lesions were categorized into 50% to 70% (47% of all lesions), 71% to 90% (39% of all lesions), and 91% to 99% (15% of all lesions) diameter stenosis by visual assessment. In the category 50% to 70% stenosis, 35% were functionally significant (FFR 0.80). In the category 71% to 90% stenosis, 80% were functionally significant and 20% were not. In the category of subtotal stenoses, 96% were functionally significant. Of all 509 patients with angiographically defined multivessel disease, only 235 (46%) had functional multivessel disease (>or=2 coronary arteries with an FFR

Fractional flow reserve versus angiography for guiding percutaneous coronary intervention in patients with multivessel coronary artery disease: 2-year follow-up of the FAME (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation) study.

OBJECTIVES: The purpose of this study was to investigate the 2-year outcome of percutaneous coronary intervention (PCI) guided by fractional flow reserve (FFR) in patients with multivessel coronary artery disease (CAD). BACKGROUND: In patients with multivessel CAD undergoing PCI, coronary angiography is the standard method for guiding stent placement. The FAME (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation) study showed that routine FFR in addition to angiography improves outcomes of PCI at 1 year. It is unknown if these favorable results are maintained at 2 years of follow-up. METHODS: At 20 U.S. and European medical centers, 1,005 patients with multivessel CAD were randomly assigned to PCI with drug-eluting stents guided by angiography alone or guided by FFR measurements. Before randomization, lesions requiring PCI were identified based on their angiographic appearance. Patients randomized to angiography-guided PCI underwent stenting of all indicated lesions, whereas those randomized to FFR-guided PCI underwent stenting of indicated lesions only if the FFR was 0.80, the rate of myocardial infarction was 0.2% and the rate of revascularization was 3.2 % after 2 years. CONCLUSIONS: Routine measurement of FFR in patients with multivessel CAD undergoing PCI with drug-eluting stents significantly reduces mortality and myocardial infarction at 2 years when compared with standard angiography-guided PCI. (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation [FAME]; NCT00267774).

Fluoroscopy-guided femoral artery puncture reduces the risk of PCI-related vascular complications.

BACKGROUND: In previous work by the Northern New England Cardiovascular Study Group, risk factors for vascular access site complications in percutaneous coronary intervention (PCI) were identified and a regional effort to reduce these complications was initiated. As part of this effort we considered making a regional recommendation that location of the femoral head as seen on fluoroscopy (fluoro) be used to help determine the site of femoral artery puncture. Therefore, we assessed the use of fluoro to determine whether it actually reduced the rate of vascular complications and shortened length of stay. METHODS: Data were collected prospectively on 2,651 consecutive PCIs at Eastern Maine Medical Center from 2000 to 2003 including use of fluoro, vascular access site complications (bleeding, pseudoaneurysm formation, hematoma, embolic event or thrombus, A-V fistula), and length of stay. RESULTS: Use of fluoro among eight interventionists was variable: 3 < 20%, 3 35-50%, 2 > 70%. Among all interventions, 48% were performed with fluoro to guide vascular access. The use of fluoro was associated with a significantly lower incidence of pseudoaneurysms (0.3% vs. 1.1%, P = 0.017) and any arterial injury (0.7% vs. 1.9%, P < 0.01). There was no significant difference in bleeding (1.6% vs. 1.8%, P = 0.69). For each physician, there were fewer vascular injuries when fluoro was used. Average length of stay was significantly lower among patients in the fluoro group (2.1 days vs. 2.4, P < 0.01). CONCLUSION: We conclude that using fluoro to guide vascular access leads to lower complication rates and a shorter length of stay. This approach may become our regional standard of care.