Cedric Delhaye

Postprocedural Aortic Regurgitation in Balloon-Expandable and Self-Expandable Transcatheter Aortic Valve Replacement Procedures Analysis of Predictors and Impact on Long-Term Mortality: Insights From the FRANCE2 Registry

Background— Significant postprocedural aortic regurgitation (AR) is observed in 10% to 20% of cases after transcatheter aortic valve replacement (TAVR). The prognostic value and the predictors of such a complication in balloon-expandable (BE) and self-expandable (SE) TAVR remain unclear. Methods and Results— TAVR was performed in 3195 consecutive patients at 34 hospitals. Postprocedural transthoracic echocardiography was performed in 2769 (92%) patients of the eligible population, and these patients constituted the study group. Median follow-up was 306 days (Q1–Q3=178–490). BE and SE devices were implanted in 67.6% (n=1872) and 32.4% (n=897). Delivery was femoral (75.3%) or nonfemoral (24.7%). A postprocedural AR≥grade 2 was observed in 15.8% and was more frequent in SE (21.5%) than in BE-TAVR (13.0%, P=0.0001). Extensive multivariable analysis confirmed that the use of a SE device was one of the most powerful independent predictors of postprocedural AR≥grade 2. For BE-TAVR, 8 independent predictors of postprocedural AR≥grade 2 were identified including femoral delivery (P=0.04), larger aortic annulus (P=0.0004), and smaller prosthesis diameter (P=0.0001). For SE-TAVR, 2 independent predictors were identified including femoral delivery(P=0.0001). Aortic annulus and prosthesis diameter were not predictors of postprocedural AR for SE-TAVR. A postprocedural AR≥grade 2, but not a postprocedural AR=grade 1, was a strong independent predictor of 1-year mortality for BE (hazard ratio=2.50; P=0.0001) and SE-TAVR (hazard ratio=2.11; P=0.0001). Although postprocedural AR≥grade 2 was well tolerated in patients with AR≥grade 2 at baseline (1-year mortality=7%), it was associated with a very high mortality in other subgroups: renal failure (43%), AR<grade 2 at baseline (31%), low transaortic gradient (35%), or nonfemoral delivery (45%). Conclusions— Postprocedural AR≥grade 2 was observed in 15.8% of successful TAVR and was the strongest independent predictor of 1-year mortality. The use of the SE device was a powerful independent predictor of postprocedural AR≥grade 2.Background— Significant postprocedural aortic regurgitation (AR) is observed in 10% to 20% of cases after transcatheter aortic valve replacement (TAVR). The prognostic value and the predictors of such a complication in balloon-expandable (BE) and self-expandable (SE) TAVR remain unclear. Methods and Results— TAVR was performed in 3195 consecutive patients at 34 hospitals. Postprocedural transthoracic echocardiography was performed in 2769 (92%) patients of the eligible population, and these patients constituted the study group. Median follow-up was 306 days (Q1–Q3=178–490). BE and SE devices were implanted in 67.6% (n=1872) and 32.4% (n=897). Delivery was femoral (75.3%) or nonfemoral (24.7%). A postprocedural AR≥grade 2 was observed in 15.8% and was more frequent in SE (21.5%) than in BE-TAVR (13.0%, P =0.0001). Extensive multivariable analysis confirmed that the use of a SE device was one of the most powerful independent predictors of postprocedural AR≥grade 2. For BE-TAVR, 8 independent predictors of postprocedural AR≥grade 2 were identified including femoral delivery ( P =0.04), larger aortic annulus ( P =0.0004), and smaller prosthesis diameter ( P =0.0001). For SE-TAVR, 2 independent predictors were identified including femoral delivery( P =0.0001). Aortic annulus and prosthesis diameter were not predictors of postprocedural AR for SE-TAVR. A postprocedural AR≥grade 2, but not a postprocedural AR=grade 1, was a strong independent predictor of 1-year mortality for BE (hazard ratio=2.50; P =0.0001) and SE-TAVR (hazard ratio=2.11; P =0.0001). Although postprocedural AR≥grade 2 was well tolerated in patients with AR≥grade 2 at baseline (1-year mortality=7%), it was associated with a very high mortality in other subgroups: renal failure (43%), AR<grade 2 at baseline (31%), low transaortic gradient (35%), or nonfemoral delivery (45%). Conclusions— Postprocedural AR≥grade 2 was observed in 15.8% of successful TAVR and was the strongest independent predictor of 1-year mortality. The use of the SE device was a powerful independent predictor of postprocedural AR≥grade 2. # CLINICAL PERSPECTIVE {#article-title-26}

Clinical profile, prognostic implication, and response to treatment of pulmonary hypertension in patients with severe aortic stenosis.

The incidence, correlates, and prognostic implications of pulmonary hypertension (PH) are unclear in patients with severe aortic stenosis (AS). We studied 509 patients with severe AS evaluated for transcatheter aortic valve implantation (TAVI). Patients were divided into groups based on pulmonary artery systolic pressure (PASP): group I, 161 (31.6%) with PASP <40 mm Hg; group II, 175 (34.3%) with PASP 40 to 59 mm Hg; and group III, 173 (33.9%) with PASP ≥ 60 mm Hg. Group III patients were more symptomatic and had higher creatinine levels and higher left ventricular end-diastolic pressure. Transpulmonary gradient was >12 mm Hg in 17 patients (10.5%), 31 patients (17.7%), and 80 patients (46.2%) in groups I through III, respectively. In a median follow-up of 202 days (73 to 446) mortality rates were 35 (21.7%), 69 (39.3%), and 85 (49.1%) in groups I through III, respectively (p <0.001). Immediately after TAVI, in patients with PASP >40 mm Hg there was significant decrease in PASP (63.1 ± 16.2 to 48.8 ± 12.4 mm Hg, p <0.0001), which remained at 1 year (50.1 ± 13.1 mm Hg, p = 0.04). After surgical aortic valve replacement there was a significant immediate decrease in PASP (66.1 ± 16.3 to 44.7 ± 14.2 mm Hg, p <0.0001), which persisted at 3 to 12 months (44.8 ± 20.1 mm Hg, p <0.001). In patients who underwent balloon aortic valvuloplasty, PASP decreased immediately after the procedure (63.2 ± 14.8 to 51.8 ± 17.1 mm Hg, p <0.0001), yet at 3 to 12 months pressure returned to baseline levels (57.4 ± 17.0 mm Hg, p = 0.29). In conclusion, patients with severe AS have a high prevalence of PH, and in patients with severe AS increased PASP is associated with increased mortality. Surgical aortic valve replacement and TAVI are effective treatments for these patients and result in a significant PASP decrease.

Correlates and Causes of Death in Patients With Severe Symptomatic Aortic Stenosis Who Are Not Eligible to Participate in a Clinical Trial of Transcatheter Aortic Valve Implantation

Background— Transcatheter aortic valve implantation is currently being evaluated in patients with severe aortic stenosis who are considered high-risk surgical candidates. This study aimed to detect incidences, causes, and correlates of mortality in patients ineligible to participate in transcatheter aortic valve implantation studies. Methods and Results— From April 2007 to July 2009, a cohort of 362 patients with severe aortic stenosis were screened and did not meet the inclusion/exclusion criteria necessary to participate in a transcatheter aortic valve implantation trial. These patients were classified into 2 groups: group 1 (medical): 274 (75.7%): 97 (35.4%) treated medically and 177 (64.6%) treated with balloon aortic valvuloplasty; and group 2 (surgical): 88 (24.3%). The medical/balloon aortic valvuloplasty group had significantly higher clinical risk compared with the surgical group, with significantly higher Society of Thoracic Surgeons score (12.8±7.0 versus 8.5±5.1; P<0.001) and logistic European System for Cardiac Operative Risk Evaluation (EuroSCORE) (42.4±22.8 versus 24.4±18.1; P<0.001). The medical/balloon aortic valvuloplasty group had a higher New York Heart Association functional class, incidence of renal failure, and lower ejection fraction. During median follow-up of 377.5 days, mortality in the medical/balloon aortic valvuloplasty group was 102 (37.2%), and during median follow-up of 386 days, mortality in the surgical group was 19 (21.5%). Multivariable adjustment analysis identified renal failure (hazard ratio [HR]: 5.60), New York Heart Association class IV (HR: 5.88), and aortic systolic pressure (HR: 0.99) as independent correlates for mortality in the medical group, whereas renal failure (HR: 7.45), Society of Thoracic Surgeons score (STS; HR: 1.09) and logistic EuroSCORE (HR: 1.45) were correlates of mortality in the in the surgical group. Conclusion— Patients with severe symptomatic aortic stenosis not included in transcatheter aortic valve implantation trials do poorly and have extremely high mortality rates, especially in nonsurgical groups, and loss of quality of life in surgical groups.

Relation of Proton Pump Inhibitor Use After Percutaneous Coronary Intervention With Drug-Eluting Stents to Outcomes

Recent evidence has shown that clopidogrel and proton pump inhibitors (PPIs) are metabolized by the same pathway and that patients taking both drugs have greater levels of platelet reactivity and more adverse outcomes than patients taking only clopidogrel. We sought to examine the effect of a PPI at discharge from the hospital after percutaneous coronary intervention with drug-eluting stents on the incidence of major adverse cardiac events (MACE) at 1 year. We compared 502 patients who were not prescribed a PPI at discharge and 318 patients who were prescribed a PPI. All patients were taking clopidogrel. We followed patients for 1 year with regard to MACE, including death, Q-wave myocardial infarction, target vessel revascularization, and stent thrombosis. We performed multivariate Cox regression to adjust for confounding variables, including compliance with clopidogrel, to assess the effect of a PPI at discharge on the 1-year outcomes. The baseline characteristics of patients discharged with a PPI were similar to those of patients discharged without a PPI. Univariate survival analysis of the outcomes showed a greater rate of MACE (13.8% vs 8.0%, p = 0.008) and overall mortality (4.7% vs 1.8%, p = 0.02) in the PPI group. After multivariate analysis, the adjusted MACE hazard ratio for PPI at discharge was 1.8 (95% confidence interval 1.1 to 2.7, p = 0.01). In conclusion, in patients undergoing percutaneous coronary intervention with drug-eluting stents and receiving clopidogrel, the prescription of a PPI at discharge was associated with a greater rate of MACE at 1 year.

Hypothermia Therapy: Neurological and Cardiac Benefits

Due to its protective effect on the brain and the myocardium, hypothermia therapy (HT) has been extensively studied in cardiac arrest patients with coma as well as in patients presenting with acute myocardial infarction (MI). In the setting of cardiac arrest, randomized studies have shown that HT decreases mortality and improves neurological outcomes. Subsequent guidelines have therefore recommended cooling (32°C to 34°C) for 12 to 24 h in unconscious adult patients with spontaneous circulation after out-of-hospital cardiac arrest due to ventricular fibrillation. Observational studies have also confirmed the feasibility of this therapy in clinical practice and support its early application in patients with nonventricular fibrillation cardiac arrest and in post-resuscitation circulatory shock. In patients with acute MI, available clinical evidence does not yet support HT as the standard of care, because no study to date has shown a clear net benefit in such a cohort. After a brief review of the mechanisms of action for HT, we provide a review of the clinical evidence, cooling techniques, and potential adverse effects associated with HT in the setting of post-cardiac arrest patient and acute MI.

Transcutaneous Aortic Valve Implantation Using the Left Carotid Access: Feasibility and Early Clinical Outcomes

BACKGROUND In some patients, transfemoral, transaxillary, or transapical aortic valve implantation is not possible. Thus, carotid artery access may represent a safe alternative to those accesses, and even offers certain advantages. In this article, we describe aortic valve implantation using the left carotid arterial approach and report our initial experience. METHODS Using a self-expandable nitinol based device (CoreValve ReValving system, Medtronic Ltd, Luxembourg), we exposed the left carotid artery through a small incision. Arterial puncture and initial 6F sheath introduction were achieved through a contraincision. The same implantation technique as for transaxillary implantation was used. Progressive artery dilatation was achieved using sheaths of increasing diameter. Rapid ventricular pacing was used to reduce cardiac output while performing a routine aortic balloon valvuloplasty. Only then, an 18F sheath was inserted into the carotid artery and pushed down into the ascending aorta. The patients were monitored using cerebral oxymetry to assess cerebral perfusion. RESULTS Twelve consecutive patients, at high surgical risk, were implanted and studied prospectively. Transfemoral and subclavian catheterization were considered unfeasible or at risk of severe complications. Carotid arterial injury did not occur in any patient. A transient ischemic attack occurred in 1 patient, contralateral to the carotid access. There were no deaths in either intraprocedural or during the 30-day follow-up period. CONCLUSIONS This initial experience suggests that left carotid transarterial aortic valve implantation, in selected high-risk patients, is feasible and safe with satisfactory short-term outcomes.

Stent thrombosis in 2008: definition, predictors, prognosis and treatment.

Stent thrombosis remains a major pitfall of stent implantation in contemporary percutaneous coronary intervention, leading to high rates of death and nonfatal myocardial infarction (MI). Recently, the emergence of drug-eluting stents (DES) has raised concerns regarding the occurrence of late and very late stent thrombosis. Last year, a standardized definition of stent thrombosis was established to provide consistency in the reporting of this complication and to enable accurate and reliable data to be described for both types of stents: bare metal and drug eluting. Subsequent to the publication of this new definition, many updated data have been reported in the literature. On the other hand, antiplatelet therapy response variability is a recent concept and its real place in the pathogenesis of stent thrombosis is yet to be determined. In this article, we review the definition of and predictors for stent thrombosis focusing on DES use and variability in response to antiplatelet therapy, prognosis and treatment.

Von Willebrand Factor Multimers during Transcatheter Aortic-Valve Replacement

BACKGROUND Postprocedural aortic regurgitation occurs in 10 to 20% of patients undergoing transcatheter aortic-valve replacement (TAVR) for aortic stenosis. We hypothesized that assessment of defects in high-molecular-weight (HMW) multimers of von Willebrand factor or point-of-care assessment of hemostasis could be used to monitor aortic regurgitation during TAVR. METHODS We enrolled 183 patients undergoing TAVR. Patients with aortic regurgitation after the initial implantation, as identified by means of transesophageal echocardiography, underwent additional balloon dilation to correct aortic regurgitation. HMW multimers and the closure time with adenosine diphosphate (CT-ADP), a point-of-care measure of hemostasis, were assessed at baseline and 5 minutes after each step of the procedure. Mortality was evaluated at 1 year. A second cohort (201 patients) was studied to validate the use of CT-ADP in order to identify patients with aortic regurgitation. RESULTS After the initial implantation, HMW multimers normalized in patients without aortic regurgitation (137 patients). Among the 46 patients with aortic regurgitation, normalization occurred in 20 patients in whom additional balloon dilation was successful but did not occur in the 26 patients with persistent aortic regurgitation. A similar sequence of changes was observed with CT-ADP. A CT-ADP value of more than 180 seconds had sensitivity, specificity, and negative predictive value of 92.3%, 92.4%, and 98.6%, respectively, for aortic regurgitation, with similar results in the validation cohort. Multivariable analyses showed that the values for HMW multimers and CT-ADP at the end of TAVR were each associated with mortality at 1 year. CONCLUSIONS The presence of HMW-multimer defects and a high value for a point-of-care hemostatic test, the CT-ADP, were each predictive of the presence of aortic regurgitation after TAVR and were associated with higher mortality 1 year after the procedure. (Funded by Lille 2 University and others; ClinicalTrials.gov number, NCT02628509.).

Transcarotid Transcatheter Aortic Valve Replacement: Feasibility and Safety.

OBJECTIVES The purpose of this study was to assess the feasibility and safety of transcarotid transcatheter aortic valve replacement (TAVR). BACKGROUND Many candidates for TAVR have challenging vascular anatomy that precludes transfemoral access. Transcarotid arterial access may be an option for such patients. METHODS The French Transcarotid TAVR Registry is a voluntary database that prospectively collected patient demographics, procedural characteristics, and clinical outcomes among patients undergoing transcarotid TAVR. Outcomes are reported according to the updated Valve Academic Research Consortium criteria. RESULTS Among 96 patients undergoing transcarotid TAVR at 3 French sites (2009 to 2013), the mean age and Society of Thoracic Surgeons predicted risk of mortality were 79.4 ± 9.2 years and 7.1 ± 4.1%, respectively. Successful carotid artery access was achieved in all patients. The Medtronic CoreValve (Medtronic, Inc., Minneapolis, Minnesota) (n = 89; 92.7%) and Edwards SAPIEN valves (Edwards Lifesciences, Irvine, California) (n = 7; 7.3%) were used. Procedural complications included: valve embolization (3.1%), requirement for a second valve (3.1%), and tamponade (4.2%). There were no major bleeds or major vascular complications related to the access site. There were 3 (3.1%) procedural deaths and 6 (6.3%) deaths at 30 days. The 1-year mortality rate was 16.7%. There were 3 (3.1%) cases of Valve Academic Research Consortium-defined in-hospital stroke (n = 0) or transient ischemic attack (TIA) (n = 3). None of these patients achieved the criteria for stroke and none manifested new ischemic lesions on cerebral computed tomography or magnetic resonance imaging. At 30 days, a further 3 TIAs were observed, giving an overall stroke/TIA rate of 6.3%. CONCLUSIONS Transcarotid vascular access for TAVR is feasible and is associated with encouraging short- and medium-term clinical outcomes. Prospective studies are required to ascertain if transcarotid TAVR yields equivalent results to other nonfemoral vascular access routes.

Incidence, correlates, and clinical impact of nuisance bleeding after antiplatelet therapy for patients with drug-eluting stents

BACKGROUND Nuisance bleeding (NB) after dual antiplatelet therapy (DAPT) is not well characterized despite its potential to impact patient compliance. We therefore aimed to evaluate the incidence, correlates, and clinical impact of NB after DAPT after drug-eluting stent (DES) implantation. METHODS Included were 2,948 patients with DES implantation who were discharged on DAPT for 12 months. New bleeding classifications were used: alarming bleeding, internal bleeding, and NB. RESULTS After excluding patients with alarming bleeding (9 [0.3%]) and internal bleeding (128 [4.3%]), the 2,811 remaining patients were divided into 2 groups: those with NB (812 [28.9%]) and those without (1,999 [71.1%]). Patients with NB were significantly younger (63.0 +/- 11.4 vs 65.2 +/- 11.6 years, P < .001), were more often white (82.0% vs 69.6%, P < .001), had lower body mass indices (29.2 +/- 6.1 vs 29.8 +/- 6.0 kg/m(2), P = .01), and a lower prevalence of diabetes (25.5% vs 34.8%, P < .001) compared to those without NB. At 1 year, the rate of major adverse cardiac events was higher in the NB group compared to the nonbleeding group (77 [9.4%] vs 134 [6.7%], P = .02). In the NB group, 46 patients (5.7%) stopped 1 or both antiplatelet therapies. Thirty-five (4.3%) discontinued clopidogrel, 16 (2.0%) stopped aspirin, and 5 (0.61%) stopped both as a result of the reported NB. Multivariable analysis detected younger age, lower body mass index, white race, and without diabetes as correlates associated with NB while on clopidogrel therapy. CONCLUSION Nuisance bleeding is common in patients on prolonged DAPT post-DES implantation and can impact compliance. Nuisance bleeding appears to have important clinical implications and, if confirmed in prospective trials, should be added to the safety end points assessing new antiplatelet agents.