Luis Miguel Benitez

Timing, Predictive Factors, and Prognostic Value of Cerebrovascular Events in a Large Cohort of Patients Undergoing Transcatheter Aortic Valve Implantation

Background— The objective of this study was to evaluate the timing, predictive factors, and prognostic value of cerebrovascular events (CVEs) after transcatheter aortic valve implantation. Methods and Results— The study included 1061 consecutive patients who underwent transcatheter aortic valve implantation with a balloon-expandable (64%) or self-expandable (36%) valve. CVEs were classified as acute (⩽24 hours), subacute (1–30 days), or late (>30 days). CVEs occurred in 54 patients (5.1%; stroke, 4.2%) within 30 days after transcatheter aortic valve implantation (acute in 54% of cases). The predictors of acute CVEs were balloon postdilation of the valve prosthesis (odds ratio, 2.46; 95% confidence interval,1.07–5.67) and valve dislodgment/embolization (odds ratio, 4.36; 95% CI, 1.21–15.69); new-onset atrial fibrillation (odds ratio, 2.76; 95% CI, 1.11–6.83) was a predictor of subacute CVEs. Late CVEs occurred in 35 patients (3.3%; stroke, 2.1%) at a median follow-up of 12 months (3–23 months). The predictors of late CVEs were chronic atrial fibrillation (2.84; 95% CI, 1.46–5.53), peripheral vascular disease (hazard ratio, 2.02; 95% CI, 1.02–3.97), and prior cerebrovascular disease (hazard ratio, 2.04; 95% CI, 1.01–4.15). Major stroke was associated with 30-day (odds ratio, 7.43; 95% CI, 2.45–22.53) and late (hazard ratio, 1.75; 95% CI, 1.01–3.04) mortality. Conclusions— In a large cohort of patients undergoing transcatheter aortic valve implantation, the rates of acute and subacute CVEs were 2.7% and 2.4%, respectively. While balloon postdilation and valve dislodgment/embolization were the predictors of acute CVEs, new-onset atrial fibrillation determined a higher risk for subacute events. Late events were determined mainly by a history of chronic atrial fibrillation and peripheral and cerebrovascular disease. The occurrence of major stroke was associated with increased early and late mortality. These results provide important insights for the implementation of preventive measures for CVEs after transcatheter aortic valve implantation.

Permanent Pacemaker Implantation After Transcatheter Aortic Valve Implantation

Background— Very few data exist on the clinical impact of permanent pacemaker implantation (PPI) after transcatheter aortic valve implantation. The objective of this study was to assess the impact of PPI after transcatheter aortic valve implantation on late outcomes in a large cohort of patients. Methods and Results— A total of 1556 consecutive patients without prior PPI undergoing transcatheter aortic valve implantation were included. Of them, 239 patients (15.4%) required a PPI within the first 30 days after transcatheter aortic valve implantation. At a mean follow-up of 22±17 months, no association was observed between the need for 30-day PPI and all-cause mortality (hazard ratio, 0.98; 95% confidence interval, 0.74–1.30; P=0.871), cardiovascular mortality (hazard ratio, 0.81; 95% confidence interval, 0.56–1.17; P=0.270), and all-cause mortality or rehospitalization for heart failure (hazard ratio, 1.00; 95% confidence interval, 0.77–1.30; P=0.980). A lower rate of unexpected (sudden or unknown) death was observed in patients with PPI (hazard ratio, 0.31; 95% confidence interval, 0.11–0.85; P=0.023). Patients with new PPI showed a poorer evolution of left ventricular ejection fraction over time (P=0.017), and new PPI was an independent predictor of left ventricular ejection fraction decrease at the 6- to 12-month follow-up (estimated coefficient, −2.26; 95% confidence interval, −4.07 to −0.44; P=0.013; R2=0.121). Conclusions— The need for PPI was a frequent complication of transcatheter aortic valve implantation, but it was not associated with any increase in overall or cardiovascular death or rehospitalization for heart failure after a mean follow-up of ≈2 years. Indeed, 30-day PPI was a protective factor for the occurrence of unexpected (sudden or unknown) death. However, new PPI did have a negative effect on left ventricular function over time.Background— Very few data exist on the clinical impact of permanent pacemaker implantation (PPI) after transcatheter aortic valve implantation. The objective of this study was to assess the impact of PPI after transcatheter aortic valve implantation on late outcomes in a large cohort of patients. Methods and Results— A total of 1556 consecutive patients without prior PPI undergoing transcatheter aortic valve implantation were included. Of them, 239 patients (15.4%) required a PPI within the first 30 days after transcatheter aortic valve implantation. At a mean follow-up of 22±17 months, no association was observed between the need for 30-day PPI and all-cause mortality (hazard ratio, 0.98; 95% confidence interval, 0.74–1.30; P =0.871), cardiovascular mortality (hazard ratio, 0.81; 95% confidence interval, 0.56–1.17; P =0.270), and all-cause mortality or rehospitalization for heart failure (hazard ratio, 1.00; 95% confidence interval, 0.77–1.30; P =0.980). A lower rate of unexpected (sudden or unknown) death was observed in patients with PPI (hazard ratio, 0.31; 95% confidence interval, 0.11–0.85; P =0.023). Patients with new PPI showed a poorer evolution of left ventricular ejection fraction over time ( P =0.017), and new PPI was an independent predictor of left ventricular ejection fraction decrease at the 6- to 12-month follow-up (estimated coefficient, −2.26; 95% confidence interval, −4.07 to −0.44; P =0.013; R 2=0.121). Conclusions— The need for PPI was a frequent complication of transcatheter aortic valve implantation, but it was not associated with any increase in overall or cardiovascular death or rehospitalization for heart failure after a mean follow-up of ≈2 years. Indeed, 30-day PPI was a protective factor for the occurrence of unexpected (sudden or unknown) death. However, new PPI did have a negative effect on left ventricular function over time. # CLINICAL PERSPECTIVE {#article-title-43}

Permanent Pacemaker Implantation After Transcatheter Aortic Valve Implantation Impact on Late Clinical Outcomes and Left Ventricular Function

Background— Very few data exist on the clinical impact of permanent pacemaker implantation (PPI) after transcatheter aortic valve implantation. The objective of this study was to assess the impact of PPI after transcatheter aortic valve implantation on late outcomes in a large cohort of patients. Methods and Results— A total of 1556 consecutive patients without prior PPI undergoing transcatheter aortic valve implantation were included. Of them, 239 patients (15.4%) required a PPI within the first 30 days after transcatheter aortic valve implantation. At a mean follow-up of 22±17 months, no association was observed between the need for 30-day PPI and all-cause mortality (hazard ratio, 0.98; 95% confidence interval, 0.74–1.30; P=0.871), cardiovascular mortality (hazard ratio, 0.81; 95% confidence interval, 0.56–1.17; P=0.270), and all-cause mortality or rehospitalization for heart failure (hazard ratio, 1.00; 95% confidence interval, 0.77–1.30; P=0.980). A lower rate of unexpected (sudden or unknown) death was observed in patients with PPI (hazard ratio, 0.31; 95% confidence interval, 0.11–0.85; P=0.023). Patients with new PPI showed a poorer evolution of left ventricular ejection fraction over time (P=0.017), and new PPI was an independent predictor of left ventricular ejection fraction decrease at the 6- to 12-month follow-up (estimated coefficient, −2.26; 95% confidence interval, −4.07 to −0.44; P=0.013; R2=0.121). Conclusions— The need for PPI was a frequent complication of transcatheter aortic valve implantation, but it was not associated with any increase in overall or cardiovascular death or rehospitalization for heart failure after a mean follow-up of ≈2 years. Indeed, 30-day PPI was a protective factor for the occurrence of unexpected (sudden or unknown) death. However, new PPI did have a negative effect on left ventricular function over time.Background— Very few data exist on the clinical impact of permanent pacemaker implantation (PPI) after transcatheter aortic valve implantation. The objective of this study was to assess the impact of PPI after transcatheter aortic valve implantation on late outcomes in a large cohort of patients. Methods and Results— A total of 1556 consecutive patients without prior PPI undergoing transcatheter aortic valve implantation were included. Of them, 239 patients (15.4%) required a PPI within the first 30 days after transcatheter aortic valve implantation. At a mean follow-up of 22±17 months, no association was observed between the need for 30-day PPI and all-cause mortality (hazard ratio, 0.98; 95% confidence interval, 0.74–1.30; P =0.871), cardiovascular mortality (hazard ratio, 0.81; 95% confidence interval, 0.56–1.17; P =0.270), and all-cause mortality or rehospitalization for heart failure (hazard ratio, 1.00; 95% confidence interval, 0.77–1.30; P =0.980). A lower rate of unexpected (sudden or unknown) death was observed in patients with PPI (hazard ratio, 0.31; 95% confidence interval, 0.11–0.85; P =0.023). Patients with new PPI showed a poorer evolution of left ventricular ejection fraction over time ( P =0.017), and new PPI was an independent predictor of left ventricular ejection fraction decrease at the 6- to 12-month follow-up (estimated coefficient, −2.26; 95% confidence interval, −4.07 to −0.44; P =0.013; R 2=0.121). Conclusions— The need for PPI was a frequent complication of transcatheter aortic valve implantation, but it was not associated with any increase in overall or cardiovascular death or rehospitalization for heart failure after a mean follow-up of ≈2 years. Indeed, 30-day PPI was a protective factor for the occurrence of unexpected (sudden or unknown) death. However, new PPI did have a negative effect on left ventricular function over time. # CLINICAL PERSPECTIVE {#article-title-43}

Blood Transfusion and the Risk of Acute Kidney Injury After Transcatheter Aortic Valve Implantation

Background—Blood transfusion is associated with acute kidney injury (AKI) after transcatheter aortic valve implantation (TAVI). We sought to elucidate in more detail the relation between blood transfusion and AKI and its effects on short- and long-term mortality. Methods and Results—Nine hundred ninety-five patients with aortic stenosis underwent TAVI with the Medtronic CoreValve or the Edwards Valve in 7 centers. AKI was defined by the Valve Academic Research Consortium (absolute increase in serum creatinine ≥0.3 mg/dL [≥26.4 &mgr;mol/L] or ≥50% increase <72 hours). Logistic and Cox regression was used for predictor and survival analysis. AKI occurred in 20.7% (n=206). The number of units of blood transfusion <24 hours was the strongest predictor of AKI (≥5 units, OR, 4.81 [1.45–15.95], 3–4 units, OR, 3.05 [1.24–7.53], 1–2 units, OR, 1.47 [0.98–2.22]) followed by peripheral vascular disease (OR, 1.48 [1.05–2.10]), history of heart failure (OR, 1.43 [1.01–2.03]), leucocyte count <72 hours after TAVI (OR, 1.05 [1.02–1.09]) and European System for Cardiac Operative Risk Evaluation (EuroSCORE; OR, 1.02 [1.00–1.03]). Potential triggers of blood transfusion such as baseline anemia, bleeding-vascular complications, and perioperative blood loss were not identified as predictors. AKI and life-threatening bleeding were independent predictors of 30-day mortality (OR, 3.15 [1.56–6.38], OR, 6.65 [2.28–19.44], respectively), whereas transfusion (≥3 units), baseline anemia, and AKI predicted mortality beyond 30 days. Conclusions—AKI occurred in 21% of the patients after TAVI. The number of blood transfusions but not the indication of transfusion predicted AKI. AKI was a predictor of both short- and long-term mortality, whereas blood transfusion predicted long-term mortality. These findings indicate that outcome of TAVI may be improved by more restrictive use of blood transfusions.

Incidence, Timing, and Predictors of Valve Hemodynamic Deterioration After Transcatheter Aortic Valve Replacement: Multicenter Registry.

BACKGROUND Scarce data exist on the incidence of and factors associated with valve hemodynamic deterioration (VHD) after transcatheter aortic valve replacement (TAVR). OBJECTIVES This study sought to determine the incidence, timing, and predictors of VHD in a large cohort of patients undergoing TAVR. METHODS This multicenter registry included 1,521 patients (48% male; 80 ± 7 years of age) who underwent TAVR. Mean echocardiographic follow-up was 20 ± 13 months (minimum: 6 months). Echocardiographic examinations were performed at discharge, at 6 to 12 months, and yearly thereafter. Annualized changes in mean gradient (mm Hg/year) were calculated by dividing the difference between the mean gradient at last follow-up and the gradient at discharge by the time between examinations. VHD was defined as a ≥10 mm Hg increase in transprosthetic mean gradient during follow-up compared with discharge assessment. RESULTS The overall mean annualized rate of transprosthetic gradient progression during follow-up was 0.30 ± 4.99 mm Hg/year. A total of 68 patients met criteria of VHD (incidence: 4.5% during follow-up). The absence of anticoagulation therapy at hospital discharge (p = 0.002), a valve-in-valve (TAVR in a surgical valve) procedure (p = 0.032), the use of a 23-mm valve (p = 0.016), and a greater body mass index (p = 0.001) were independent predictors of VHD. CONCLUSIONS There was a mild but significant increase in transvalvular gradients over time after TAVR. The lack of anticoagulation therapy, a valve-in-valve procedure, a greater body mass index, and the use of a 23-mm transcatheter valve were associated with higher rates of VHD post-TAVR. Further prospective studies are required to determine whether a specific antithrombotic therapy post-TAVR may reduce the risk of VHD.

Late Cardiac Death in Patients Undergoing Transcatheter Aortic Valve Replacement Incidence and Predictors of Advanced Heart Failure and Sudden Cardiac Death

BACKGROUND Little evidence exists of the burden and predictors of cardiac death after transcatheter aortic valve replacement (TAVR). OBJECTIVES The purpose of this study was to assess the incidence and predictors of cardiac death from advanced heart failure (HF) and sudden cardiac death (SCD) in a large patient cohort undergoing TAVR. METHODS The study included a total of 3,726 patients who underwent TAVR using balloon (57%) or self-expandable (43%) valves. Causes of death were defined according to the Valve Academic Research Consortium-2. RESULTS At a mean follow-up of 22 ± 18 months, 155 patients had died due to advanced HF (15.2% of total deaths, 46.1% of deaths from cardiac causes) and 57 had died due to SCD (5.6% of deaths, 16.9% of cardiac deaths). Baseline comorbidities (chronic obstructive pulmonary disease, atrial fibrillation, left ventricular ejection fraction ≤40%, lower mean transaortic gradient, pulmonary artery systolic pressure >60 mm Hg; p < 0.05 for all) and 2 procedural factors (transapical approach, hazard ratio [HR]: 2.38, 95% confidence interval [CI]: 1.60 to 3.54; p < 0.001; presence of moderate or severe aortic regurgitation after TAVR, HR: 2.79, 95% CI: 1.82 to 4.27; p < 0.001) independently predicted death from advanced HF. Left ventricular ejection fraction ≤40% (HR: 1.93, 95% CI: 1.05 to 3.55; p = 0.033) and new-onset persistent left bundle-branch block following TAVR (HR: 2.26, 95% CI: 1.23 to 4.14; p = 0.009) were independently associated with an increased risk of SCD. Patients with new-onset persistent left bundle-branch block and a QRS duration >160 ms had a greater SCD risk (HR: 4.78, 95% CI: 1.56 to 14.63; p = 0.006). CONCLUSIONS Advanced HF and SCD accounted for two-thirds of cardiac deaths in patients after TAVR. Potentially modifiable or treatable factors leading to increased risk of mortality for HF and SCD were identified. Future studies should determine whether targeting these factors decreases the risk of cardiac death.

Clinical Impact of Aortic Regurgitation After Transcatheter Aortic Valve Replacement : Insights Into the Degree and Acuteness of Presentation

OBJECTIVES The aim of this study was to determine the impact of the degree of residual aortic regurgitation (AR) and acuteness of presentation of AR after transcatheter aortic valve replacement (TAVR) on outcomes. BACKGROUND The degree of residual AR after TAVR leading to excess mortality remains controversial, and little evidence exists on the impact of the acuteness of presentation of AR. METHODS A total of 1,735 patients undergoing TAVR with balloon-expandable or self-expanding valves were included. The presence and degree of AR were evaluated by transthoracic echocardiography; acute AR was defined as an increase in AR severity of ≥1 degree compared with pre-procedural echocardiography. RESULTS Residual AR was classified as mild in 761 patients (43.9%) and moderate to severe in 247 patients (14.2%). The presence of moderate to severe AR was an independent predictor of mortality at a mean follow-up of 21 ± 17 months compared with none to trace (adjusted hazard ratio [HR]: 1.81, 95% confidence interval [CI]: 1.32 to 2.48; p < 0.001) and mild AR (adjusted HR: 1.68, 95% CI: 1.27 to 2.24; p < 0.001) groups. There was no increased risk in patients with mild AR compared with those with none to trace AR (p = 0.393). In patients with moderate to severe AR, acute AR was observed in 161 patients (65%) and chronic AR in 86 patients (35%). Acute moderate to severe AR was independently associated with increased risk of mortality compared with none/trace/mild AR (adjusted HR: 2.37, 95% CI: 1.53 to 3.66; p < 0.001) and chronic moderate to severe AR (adjusted HR: 2.24, 95% CI: 1.17 to 4.30; p = 0.015) [corrected]. No differences in survival rate were observed between patients with chronic moderate to severe and none/trace/mild AR (p > 0.50). CONCLUSIONS AR occurred very frequently after TAVR, but an increased risk of mortality at ∼2-year follow-up was observed only in patients with acute moderate to severe AR.

Advanced chronic kidney disease in patients undergoing transcatheter aortic valve implantation: insights on clinical outcomes and prognostic markers from a large cohort of patients

AIM The aim of this study was to determine the effects of advanced chronic kidney disease (CKD) on early and late outcomes after transcatheter aortic valve implantation (TAVI), and to evaluate the predictive factors of poorer outcomes in such patients. METHODS AND RESULTS This was a multicentre study including a total of 2075 consecutive patients who had undergone TAVI. Patients were grouped according the estimated glomerular filtration rate as follows: CKD stage 1-2 (≥60 mL/min/1.73 m(2); n = 950), stage 3 (30-59 mL/min/1.73 m(2); n = 924), stage 4 (15-29 mL/min/1.73 m(2); n = 134) and stage 5 (<15 mL/min/1.73 m² or dialysis; n = 67). Clinical outcomes were evaluated at 30-days and at follow-up (median of 15 [6-29] months) and defined according to the VARC criteria. Advanced CKD (stage 4-5) was an independent predictor of 30-day major/life-threatening bleeding (P = 0.001) and mortality (P = 0.027), and late overall, cardiovascular and non-cardiovascular mortality (P < 0.01 for all). Pre-existing atrial fibrillation (HR: 2.29, 95% CI: 1.47-3.58, P = 0.001) and dialysis therapy (HR: 1.86, 95% CI: 1.17-2.97, P = 0.009) were the predictors of mortality in advanced CKD patients, with a mortality rate as high as 71% at 1-year follow-up in those patients with these 2 factors. Advanced CKD patients who had survived at 1-year follow-up exhibited both a significant improvement in NYHA class (P < 0.001) and no deterioration in valve hemodynamics (P = NS for changes in mean gradient and valve area over time). CONCLUSIONS Advanced CKD was associated with a higher rate of early and late mortality and bleeding events following TAVI, with AF and dialysis therapy determining a higher risk in these patients. The mortality rate of patients with both factors was unacceptably high and this should be taken into account in the clinical decision-making process in this challenging group of patients.

Clinical outcome following Transcatheter Aortic Valve Implantation in patients with impaired left ventricular systolic function.

Objectives: To determine the prevalence of impaired left ventricular (LV) systolic function and its impact on the in‐hospital and long‐term outcome in patients who underwent Transcatheter Aortic Valve Implantation (TAVI). Background: Although impaired LV function may be considered a contra‐indication for aortic valve replacement, the hemodynamic characteristics of transcatheter valves may offer procedural and long‐term clinical benefit in such patients. Methods: 230 consecutive patients underwent TAVI with the Medtronic‐CoreValve System. Impaired LV function was defined by a Left Ventricular Ejection Fraction (LVEF) ≤ 35% (European Multicenter Study on Operative Risk Stratification and Long‐term Outcome in patients with Low‐Flow/Low‐Gradient Aortic Stenosis). Study endpoints were selected and defined according to the Valve Academic Research Consortium recommendations. Results: Compared with patients with a LVEF > 35% (n = 197), those with LVEF ≤ 35% (n = 33) were more often male (78.8 % vs. 46.7%, P < 0.001), more symptomatic (NYHA class III or IV, 97.0% vs. 77.2%, P = 0.008) and had a higher prevalence of prior coronary artery disease (63.6% vs. 43.1%, P = 0.029). The Logistic EuroSCORE was 14.8% and 22.8, respectively (P = 0.012). No difference was observed between the two groups in in‐hospital or 30‐day mortality (3.0% vs. 9.6%, P = 0.21), the Combined Safety Endpoint at 30 days (24.2% and 24.4%, P = 0.99) and survival free from readmission at one year (69.2% and 69.7%, P = 0.85). After adjustment, LVEF ≤ 35% was not associated with an increased risk of 30‐day mortality, in‐hospital complications and survival free from readmission at follow‐up. Conclusion: The immediate and long‐term outcome after TAVI did not differ between patients with an impaired and preserved LVEF. LVEF ≤ 35% did not predict adverse immediate and long‐term outcome. These findings suggest that TAVI should not be withheld in selected patients with impaired LV function.

Prevalence, Factors Associated With, and Prognostic Effects of Preoperative Anemia on Short- and Long-Term Mortality in Patients Undergoing Transcatheter Aortic Valve Implantation

Background—There is scant information on the prevalence and factors associated with preoperative anemia in patients undergoing transcatheter aortic valve implantation (TAVI) and whether it is associated with mortality. We sought to determine the prevalence and factors associated with preoperative anemia in addition to the prognostic effects of the various levels of preoperative hemoglobin level on mortality in patients undergoing TAVI. Methods and Results—Ten-center observational study encompassing 1696 patients with aortic stenosis who underwent TAVI was conducted. Anemia was defined by the World Health Organization criteria (hemoglobin <12.0 g/dL in women and <13.0 g/dL in men). The prevalence of preoperative anemia was 57%. Patient-related factors associated with preoperative anemia were (descending order of odds ratio [95% confidence interval]) as follows: anemia-related medication (4.90 [3.08–7.80]), history of heart failure (1.77 [1.43–2.20]), male sex (1.69 [1.32–2.16]), mitral regurgitation grade ≥III (1.61 [1.15–2.25]), history of malignancy (1.44 [1.03–2.09]), and peripheral vascular disease (1.33 [1.04–1.70]). The creatinine clearance was inversely associated with preoperative anemia (odds ratio, 0.92 [0.87–0.97]). In multivariable analyses, preoperative anemia was not associated with 30-day mortality (1.72 [0.96–3.12]; P=0.073) but showed the strongest association with 1-year mortality with a hazard ratio (95% confidence interval) of 2.78 (1.60–4.82) in patients with hemoglobin <10 g/dL. Patients with anemia received ≥1 blood transfusion 2× more often, but the indication of transfusion was unrelated to overt bleeding in 60%. Blood transfusion was associated with mortality at 30 days (odds ratio, 1.25 [95% confidence interval, 1.08–3.67]) and during follow-up (hazard ratio, 1.09 [95% confidence interval, 1.03–1.14]). Conclusions—Preoperative anemia is prevalent in >50% of patients undergoing TAVI. Various baseline factors were related to anemia, which in turn was associated with 1-year mortality. Patients with anemia received more transfusions but mostly for indications unrelated to overt bleeding, whereas transfusion was independently associated with both early and 1-year mortality. These findings indicate that optimization of baseline factors related to preoperative anemia, in addition to more strict criteria of the use of blood products, may improve outcome after TAVI.