Incidence, predictors and clinical impact of permanent pacemaker insertion in women following transcatheter aortic valve implantation: Insights from a prospective multinational registry.

OBJECTIVES: To describe the incidence, predictors, and clinical impact of permanent pacemaker insertion (PPI) following transcatheter aortic valve replacement (TAVR) in women. BACKGROUND: Data on pacemaker insertion complicating TAVR in women are scarce. METHODS: The Women's International Transcatheter Aortic Valve implantation (WIN-TAVI) is a prospective registry evaluating the safety and efficacy of TAVR in women. We included patients without preprocedural pacemakers and divided them into two groups: (1) PPI and (2) no-PPI. We identified PPI predictors using logistic regression and studied its clinical impact on the Valve Academic Research Consortium (VARC)-2 efficacy and safety endpoints. RESULTS: Out of 1019 patients, 922 were included in the analysis. Post-TAVR PPI occurred in 132 (14.3%) patients. Clinical and procedural characteristics were similar in both groups. Pre-existing right bundle branch block (RBBB) was associated with a high risk of post-TAVR PPI (OR 3.62, 95% CI 1.85-7.06, p < 0.001), while implantation of balloon-expandable prosthesis was associated with a lower risk (OR 0.47, 95% CI 0.30-0.74, p < 0.001). Post-TAVR PPI prolonged in-hospital stay by a median of 2 days (11 [9-16] days in PPI vs. 9 [7-14] days in no-PPI, p = 0.005), yet risks of VARC-2 efficacy and safety endpoints at 1 year were similar in both groups (adj HR 0.95, 95% CI 0.60-1.52, p = 0.84 and adj HR 1.22, 95% CI 0.83-1.79, p = 0.31, respectively). CONCLUSION: Pacemaker implantation following TAVR is frequent among women and is associated with pre-existing RBBB and valve type. PPI prolongs hospital stay, albeit without any significant impact on 1-year outcomes.

Prevalence, predictors, and outcomes of patient prosthesis mismatch in women undergoing TAVI for severe aortic stenosis: Insights from the WIN-TAVI registry.

OBJECTIVE: To evaluate the incidence, predictors and outcomes of female patients with patient-prosthesis mismatch (PPM) following transcatheter aortic valve intervention (TAVI) for severe aortic stenosis (AS). BACKGROUND: Female AS TAVI recipients have a significantly lower mortality than surgical aortic valve replacement (SAVR) recipients, which could be attributed to the potentially lower PPM rates. TAVI has been associated with lower rates of PPM compared to SAVR. PPM in females post TAVI has not been investigated to date. METHODS: The WIN-TAVI (Women's INternational Transcatheter Aortic Valve Implantation) registry is a multicenter registry of women undergoing TAVR for severe symptomatic AS. Two hundred and fifty patients with detailed periprocedural and follow-up echocardiographic investigations were included in the WIN-TAVI echocardiographic sub-study. PPM was defined as per European guidelines stratified by the presence of obesity. RESULTS: The incidence of PPM in our population was 32.8%. Patients with PPM had significantly higher BMI (27.4 ± 6.1 vs. 25.2 ± 5.0, p = .002), smaller sized valves implanted (percentage of TAVI ≤23 mm 61% vs. 29.2%, PPM vs. no PPM, p < .001) and were more often treated with balloon expandable valves (48.3 vs. 32.5%, p < .001) rather than self expanding ones (26.3 vs. 52.8%, <.001). BMI (OR = 1.08; 95%CI 1.02-1.14, p = .011) and valve size ≤23 mm (OR = 3.00 95%CI 1.14-7.94, p = .027) were the only independent predictors of PPM. There was no significant interaction between valve size and valve type (p = .203). No significant differences were observed in 1-year mortality or major adverse cardiovascular events. CONCLUSIONS: PPM in females undergoing TAVI occurs in one third of patients. BMI and valve size ≤23 mm are independent predictors. Larger registries are required to determine the impact of PPM on future clinical outcomes.

Feasibility and Outcomes of Transcatheter Aortic Valve Implantation Using the Left Axillary Artery as Primary Access Site.

BACKGROUND: The femoral artery is generally used as primary access for transcatheter aortic valve implantation. However, peripheral artery disease often precludes femoral access. The purpose of this study was to describe clinical outcome of transcatheter aortic valve implantation using the left axillary artery (LAA) as primary access site. METHODS: From December 2008 until June 2016, data on all consecutive patients treated with a Medtronic device through the LAA at our hospital were registered, and outcome was prospectively collected according to the updated Valve Academic Research Consortium-2 criteria. Mortality check was performed nationally. RESULTS: In total, 362 patients were included (median age 80 years [range, 76 to 84]; logistic European System for Cardiac Operative Risk Evaluation 17% ± 12%). Successful axillary access was achieved in 99%. Medtronic CoreValve (86%) and Evolut R (14% [Medtronic, Minneapolis, MN]) were implanted. Major vascular complications occurred in 5% of patients, 1% was LAA related. Life-threatening bleeding and major bleeding were observed in 2% and 10%, respectively. Additional complications were new left bundle branch blood (30%), new permanent pacemaker (11%), and stroke (1%). There were 6 procedural deaths (2%) and 19 deaths (5%) within 30 days. One-year mortality rate was 19%. CONCLUSIONS: This is the first study reporting outcome after transcatheter aortic valve implantation using the LAA as default access. We conclude that it is highly feasible and safe with low rates of major vascular complications, bleeding, and stroke.

Rationale and design of POPular-TAVI: antiPlatelet therapy fOr Patients undergoing Transcatheter Aortic Valve Implantation.

BACKGROUND: Despite improving experience and techniques, ischemic and bleeding complications after transcatheter aortic valve implantation (TAVI) remain prevalent and impair survival. Current guidelines recommend the temporary addition of clopidogrel in the initial period after TAVI to prevent thromboembolic events. However, explorative studies suggest that this is associated with a higher rate of major bleeding without a decrease in thromboembolic complications. METHODS: The POPular TAVI trial is a prospective randomized, controlled, open-label multicenter clinical trial to test the hypothesis that monotherapy with aspirin or oral anticoagulation (OAC) after TAVI is safer than the addition of clopidogrel for 3 months, without compromising clinical benefit. This trial encompasses 2 cohorts: cohort A, patients are randomized 1:1 to aspirin vs aspirin + clopidogrel, and cohort B, patients on OAC therapy are randomized 1:1 to OAC vs OAC + clopidogrel. Primary outcome is freedom from non-procedure-related bleeding at 1 year. Secondary net-clinical benefit outcome is freedom from the composite of cardiovascular death, non-procedural-related bleeding, myocardial infarction, or stroke at 1 year. The primary outcome is analyzed for superiority, whereas the secondary outcome is analyzed for noninferiority. Recruitment began in February 2014, and the trial will continue until a total of 1,000 patients (684 expected in cohort A and 316 in cohort B) are included and followed up for 1 year. SUMMARY: The POPular TAVI trial (NCT02247128) is the first large randomized controlled trial to test if monotherapy with aspirin or OAC vs additional clopidogrel after TAVI reduces bleeding with a favorable net-clinical benefit.

Surgical aortic valve replacement in patients older than 75 years: is there really a quality of life benefit?

BACKGROUND: To evaluate the results of elective isolated surgical aortic valve replacement (SAVR) on quality of life (QoL) in patients > 75 years. METHODS: 138 patients operated between January 2008 and December 2011 were included. The EuroQOL questionnaire (EQ-5D, EQ-VAS) was completed preoperatively, and 1- and 2-years postoperatively. The logistic EuroSCORE was used for risk stratification, the Corpus Christi Heart project criteria to assess physical activity. RESULTS: Mean age was 79.5 ± 2.8 years, mean risk 9.7 ± 5.4, hospital mortality 2.8 %. For 115 patients (83.3 %) the preoperative QoL information was complete. Fifty patients were classified as sedentary. In the first postoperative year 13 patients died, mostly sedentary patients (p = 0.046) with a low EQ-5D (p = 0.017). There was no QoL information on 32 survivors, mostly sedentary patients (p = 0.001). The 70 patients with QoL information showed an increased QoL (NS). Two years postoperatively, 16 patients died, significantly more sedentary patients (p = 0.015) with a low EQ-5D (p = 0.006). For 42 survivors, there was no QoL information; these were mostly sedentary patients (p = 0.021). The 57 patients with 2-year QoL information had an increased EQ-5D (NS) and EQ-VAS (p = 0.024). CONCLUSIONS: QoL increases after SAVR. However, the patients lost to follow-up were mostly sedentary or had a low preoperative QoL, which can lead to biased results.

Prolonged anticoagulation therapy adjunctive to aspirin after successful fibrinolysis: from early reduction in reocclusion to improved long-term clinical outcome.

BACKGROUND: Long-term addition of antithrombotics (clopidogrel, anticoagulants) to aspirin has improved outcome after acute coronary syndromes. Data on the impact after fibrinolysis are scarce. In Antithrombotics in the Prevention of Reocclusion In COronary Thrombolysis-2 (APRICOT-2), adjunctive moderate-intensity coumarin (median international normalized ratio 2.6) conferred a marked reduction in 3-month reocclusion and ischemic events. Given the association between reocclusion and long-term outcome, we performed long-term clinical follow-up. METHODS: Patients with thrombolysis in myocardial infarction (TIMI) 3 flow <48 hours after fibrinolysis for ST-elevation myocardial infarction were randomized to aspirin plus coumarin, with prolonged heparinization until the target international normalized ratio (2-3) was reached, or aspirin with standard heparinization. Three-month follow-up angiography (reocclusion rates 15% vs 28%) and long-term clinical follow-up (median 7.3 years, interquartile range 5.9-8.6 years) were performed. RESULTS: Patients randomized to adjunctive anticoagulation (n = 123) received coumarin for a median of 280 days (113-387 days). Survival was 94% versus 88% in patients on aspirin alone (n = 128, P = .12). Infarct-free survival was 86% versus 71% (P = .01). Thrombolysis in myocardial infarction bleeding was 4% in both groups. Patients with reocclusion had impaired survival: 80% versus 94% (P < .01). In a multivariable model without reocclusion, combination therapy independently predicted survival (hazard ratio [HR] 0.36, 95% confidence interval [CI] 0.13-1.00) and infarct-free survival (HR 0.51, 95% CI 0.28-0.95). When adjusted for reocclusion, combination therapy did not predict outcome. Reocclusion independently predicted death (HR 2.56, 95% CI 1.02-6.43) and reinfarction. CONCLUSIONS: Moderate-intensity oral anticoagulation added to aspirin improved 8-year clinical outcome after successful fibrinolysis. The beneficial effect was largely attributed to a reduction in reocclusion, which independently predicted death and reinfarction. This study provides a mechanistic rationale for prolonged adjunctive anticoagulation after fibrinolysis.

The smoker's paradox after successful fibrinolysis: reduced risk of reocclusion but no improved long-term cardiac outcome.

BACKGROUND: In smokers treated with fibrinolysis for ST-elevation myocardial infarction (STEMI) a paradoxical beneficial short-term outcome has been reported. This was attributed to favorable clinical and angiographic baseline variables and a better response to fibrinolysis. During follow-up infarct artery reocclusion is an important prognosticator. We studied the effects of smoking on reocclusion and long-term cardiac outcome after successful fibrinolysis. METHODS: In the Antithrombotics in the Prevention of Reocclusion In COronary Thrombolysis trials (APRICOT-1 and -2) 499 STEMI patients with an open infarct artery <48 h after fibrinolysis received randomized antithrombotic treatment until 3-month follow-up angiography. Five-year clinical follow-up was complete. RESULTS: Current smokers (317 patients, 64%) had favorable clinical (age 54 vs. 60 years, P < 0.01) and angiographic (single vessel disease 61% vs. 49%, P = 0.02) baseline characteristics. Reocclusion rates were 21% (67/317) in smokers versus 32% (59/182) in non-smokers (P < 0.01). Five-year infarct-free cardiac survival did not differ: 82% vs. 85%. Reocclusion (HR 2.41, 95%CI 1.05-5.56, P = 0.04) independently predicted cardiac mortality. Smoking was independently associated with a reduced risk of reocclusion (OR 0.58, 95%CI 0.37-0.91, P = 0.02), but not with improved 5-year cardiac outcome (HR 1.34, 95%CI 0.79-2.25, P = ns). CONCLUSIONS: After successful fibrinolysis, smoking is independently associated with a more than 40% reduced risk of reocclusion, which is an independent predictor of adverse outcome. However, even with more favorable baseline characteristics smokers did not have improved 5-year cardiac outcome in this low-risk population.

Sustained coronary patency after fibrinolytic therapy as independent predictor of 10-year cardiac survival Observations from the Antithrombotics in the Prevention of Reocclusion in COronary Thrombolysis (APRICOT) trial.

BACKGROUND: Whether late coronary patency after myocardial infarction has prognostic impact independent of left ventricular function remains a matter of debate. Reocclusion rates in the first year after fibrinolysis vary between 20% and 30%. Of all reocclusions, about 30% present as clinical reinfarction, associated with a 2-fold-increased risk of mortality. The clinical impact of reocclusion that presents without reinfarction has not been studied; but an association has been demonstrated with impaired contractile recovery of left ventricular function, the strongest prognosticator of long-term outcome. We therefore studied the impact of 3-month coronary patency after successful fibrinolysis on 10-year cardiac survival. METHODS: In the APRICOT-1 trial, 248 ST-elevation myocardial infarction patients with an open infarct artery 24 hours after fibrinolysis had 3-month repeated angiography. Ten-year clinical follow-up was complete in 99.6%. RESULTS: The reocclusion rate was 29% (71/248). Of these reocclusions, 24% presented as clinical reinfarction (17/71). Cardiac survival at 10 years was 73% in patients with a reoccluded infarct artery and 88% in patients with sustained patency (P < .01). This difference was also present in patients in whom reocclusion was only detected as a result of systematic repeated angiography, that is, in the absence of reinfarction or ischemic symptoms between angiograms (70% vs 86%, P < .03). Multivariable analysis identified sustained patency at 3-month angiography as independent predictor of 10-year cardiac survival (hazard ratio 2.10, 95% CI 1.10-4.02) together with left ventricular ejection fraction. CONCLUSIONS: Sustained infarct artery patency in the first 3 months after successful fibrinolysis is a strong predictor of 10-year cardiac survival, independent of left ventricular function. Notably, this also holds true when reocclusion occurs without signs of clinical reinfarction or recurrent ischemia. Therefore, future preventive strategies should also focus on "clinically silent" reocclusions. Additional studies on better antithrombotic regimens and the combination with a routine invasive strategy early after successful fibrinolysis are warranted.

Lack of concordance between a rapid bedside and conventional laboratory method of cardiac troponin testing: impact on risk stratification of patients suspected of acute coronary syndrome.

OBJECTIVES: This study was designed to test the usefulness of a bedside assay as compared to a laboratory method of troponin testing to predict adverse cardiac outcome of chest pain patients. METHODS: We studied 358 ER visits of patients suspected of a non ST-elevation acute coronary syndrome. cTnI (Immulite, DPC) on a lab analyser and cTnT (Cardiac Reader, Roche) at bedside were measured at baseline. The between-assay level of concordance, reporting turnaround times and clinical outcomes during 180 days of follow-up were assessed. Death and myocardial infarction were then evaluated according to troponin result, either concordant negative, discordant or concordant positive. RESULTS: Discordance occurred in 11.4% (41/358) of cases. The proportion of patients with a positive cTnI and negative cTnT result (8.9%) versus the reverse (2.5%) differed significantly (p<0.001). The median time gained using the rapid test was 72 min. The rate of death and/or MI was 25% (10/40) among patients with discordant results as compared to 7.5% (17/228) with a concordant negative result (p<0.001). All patients from the discordant group with an event had a positive cTnI result, while cTnT was negative. CONCLUSION: Patients with a discordant reading were at high risk of adverse cardiac outcome, which was only identified by the laboratory cTnI assay. Markedly, the use of the rapid assay saved time at the expense of clinical sensitivity.

High-grade infarct-related stenosis after successful thrombolysis: strong predictor of reocclusion, but not of clinical reinfarction.

BACKGROUND: After successful thrombolysis, a high-grade stenosis at 24-hour angiography is strongly predictive of reocclusion and is often believed to result in high reinfarction rates. However, routine angioplasty did not reduce death or reinfarction in past trials. Systematic angiographic follow-up shows that reocclusion often occurs without clinical reinfarction. This study investigates whether the increased risk for reocclusion associated with a high-grade lesion translates into impaired clinical outcome. METHODS: In the ischemia-guided Antithrombotics in the Prevention of Reocclusion in COronary Thrombolysis (APRICOT-1) trial, 240 patients with ST-elevation MI who had an open infarct artery 24 hours after thrombolysis had 3-month repeat angiography to assess reocclusion, with clinical follow-up at 3 months and 3 years. RESULTS: On the basis of the optimal discriminative stenosis severity, the reocclusion rate was 40% (47/118) in patients with a high-grade residual stenosis and 16% (20/122) in patients with a low-medium-grade lesion (risk ratio [RR], 2.43; 95% CI, 1.54-3.84; P <.01). Three-month death and reinfarction rates did not differ: 6% (7/118) versus 9% (11/122; RR, 0.66; 95% CI, 0.26-1.64; P = not significant). Systematic angiographic follow-up revealed that reocclusion of a high-grade lesion occurred in the absence of clinical reinfarction in 85% (40/47) of patients, as compared with 45% (9/20) in patients with a low-medium-grade stenosis (RR, 1.89; 95% CI, 1.15-3.12; P <.01). Despite an independent association with reocclusion, a high-grade stenosis was not predictive of either short- or long-term death and reinfarction. CONCLUSIONS: After successful thrombolysis and adopting an ischemia-guided revascularization strategy, patients with a high-grade stenosis experience death/reinfarction rates similar to that of patients with a low-medium-grade lesion. This is true despite a 2- to 3-fold higher risk for reocclusion. The finding that reocclusion of a high-grade lesion often occurs without clinical reinfarction explains the absence of a relationship between a severe stenosis and death/reinfarction. Appreciation of these observations may contribute to an optimal design of a future randomized trial to re-evaluate the impact of a routine invasive strategy.