Transcatheter aortic valve implantation (TAVI) is rapidly evolving in Germany. Especially severe reduced left ventricular ejection fraction (LVEF) is known as a prominent risk factor for adverse outcome in open heart surgery. Thus, the data of the prospective multicenter German Transcatheter Aortic Valve Interventions Registry were analyzed for outcomes in patients with severe depressed LVEF. Data of 1,432 patients were consecutively collected after transcatheter aortic valve implantation. Patients were divided into 2 groups (A: LVEF ≤30%, n = 169, age 79.9 ± 6.7 years, logES 34.2 ± 17.8%; B: LVEF >30%, n = 1,263, age 82.0 ± 6.1 years, logES 18.9 ± 12.0%), and procedural success rates, New York Heart Association classification, and quality of life were compared at 30 days and 1 year, respectively. Technical success was achieved in 95.9% (A) and 97.6% (B). Survival and the New York Heart Association classification at 30 days demonstrated an excellent outcome in both groups. There was a significant improvement according to the self-assessment in health condition (0 to 100 scale) with a much larger gain in group A (28 vs 19 patients, p <0.0001). Nevertheless, low cardiac output syndrome (12.3% vs 5.9%, p <0.01) and resuscitation (10.4% vs 5.6%, p <0.05) were more frequently seen in group A, contributing to a higher mortality at 30 days (14.3% vs 7.2%) and 1 year (33.7% vs 18.1%, p <0.001). In conclusion, this real-world registry demonstrated a comparably high success rate for patients with severe reduced LVEF and an early improvement in functional status as demonstrated by substantial benefit, despite a doubled postprocedural mortality.
Severe aortic valvular stenosis (AS) with signs of congestive heart failure is well known to have a rather poor prognosis. Accordingly, the guidelines clearly recommend surgical aortic valve replacement (SAVR) in patients with severe AS presenting with left ventricular ejection fraction (LVEF) <50% as a class I indication. But over the last 3 decades, there was an ongoing discussion if SAVR remains a true treatment option when LVEF has decreased <30%. This is reflected by that many patients with AS and left ventricular dysfunction are frequently withheld from surgery. Despite an elevated perioperative mortality in such patients, SAVR has repeatedly been proved to be beneficial compared with medical treatment. As a further risk stratification tool, dobutamine stress is widely adopted to distinguish between left ventricular dysfunction with and without contractile reserve. Especially in the latter group, SAVR has been associated with a marked increased perioperative mortality. Accordingly, the level of evidence for SAVR in AS remains shifted down to class IIa/C for patients with left ventricular dysfunction and remaining contractile reserve and to class IIb/C in patients without contractile reserve, respectively. Meanwhile, transcatheter aortic valve implantation (TAVI) is established as an alternative treatment to SAVR in patients considered at high surgical risk. Because of its lower invasiveness (sparing cardiopulmonary bypass, hypothermia, and ischemic reperfusion), TAVI may be an appealing new therapeutic option for patients in advanced heart failure.
Methods
Registry data of 1,432 patients who underwent TAVI between 2009 and 2010 were analyzed. The indication for TAVI was at the discretion of the data-supplying center. Typically patients were included for TAVI with an aortic valve area (AVA) <1 cm 2 or indexed AVA <0.6 cm 2 /m 2 . Patients were separated into 2 groups with an LVEF ≤30% (group A) and >30% (group B) before TAVI. Patients without data about the LVEF before TAVI were excluded from the data analysis. Clinical, Doppler echocardiographic, operative, and outcome data were collected prospectively at each participating center. After inclusion into the German TAVI registry, the follow-up was performed by specifically trained members of the TAVI registry in Ludwigshafen, using a standardized phone interview protocol. The study protocol was performed in accordance with the institutional ethics committees of each participating center, and all patients gave written informed consent for data entry into the German TAVI registry.
Continuous data are presented as mean ± SD, and categorical variables are depicted as percentages and numbers. Categorical variables were compared by means of the chi-square or Fisher’s exact test, and continuous variables using the 2-tailed Wilcoxon rank-sum test. Two-sided p values <0.05 were considered statistically significant. Mortality at 30 days and 1 year was estimated using the Kaplan-Meier method. The vital status of patients already discharged or transferred to a rehabilitation program was verified by standardized follow-up calls performed by the Institute of Myocardial Infarction Research, Ludwigshafen (IHF). Kaplan-Meier curves were calculated for visualizing long-term survival and compared using the log-rank test. Cox proportional hazards regression analysis was performed among established predictors of 30-day and 1-year mortality in patients with LVEF >30% and in patients with LVEF ≤30%. All covariates with a p value of <0.1 were included in the Cox regression model. Stepwise parameter selection was subsequently performed to identify independent predictors for 30-day and 1-year mortality. A covariate was entered in the model or removed from the model if the p value was less than or exceeded the boundary of 0.10. In the final model, all p values <0.05 were considered statistically significant. In Cox regression models, adjustments were made for the potential confounders of age, gender, diabetes, body mass index, frailty, American Society of Anesthesiologists (ASA) 4, ASA 5, chronic obstructive pulmonary disease, 3-vessel coronary artery disease, pulmonary hypertension, peripheral vascular disease, previous cardiac procedures, previous cardiac decompensation <12 months, New York Heart Association (NYHA) class IV, previous balloon valvuloplasty, previous myocardial infarction, concomitant mitral regurgitation ≥II+, renal insufficiency, and low-flow low-gradient AS. Additionally, urgent performance of the TAVI, the TAVI prosthesis type, postprocedural aortic regurgitation (AR), vascular complications, conversion to open heart surgery, and periprocedural stroke and myocardial infarction were considered for analysis. Stepwise regression models for multivariable analysis were used to avoid overfitting in the respective statistical model. All statistical analyses were performed using the SAS statistical package, version 9.2 (SAS Institute, Cary, North Carolina).
Results
Demographic data of all patients with an LVEF ≤30% (group A; n = 169, 11.8%) and of patients with an LVEF >30% (group B; n = 1,263, 88.2%) are listed in Tables 1 and 2 . The logistic EuroSCORE and a preprocedural presence of a cardiogenic shock were approximately twofold higher in group A ( Tables 1 and 2 ). Thus, congestive heart failure classified by the NYHA was significantly more shifted toward NYHA classes III and IV in patients of group A ( Figure 1 ), whereas the distribution of symptoms classified by the Canadian Cardiovascular Society (CCS) was comparable between both groups (p = 0.09). The higher operative risk in patients of group A was substantiated by the distribution into various classes of the ASA (p <0.0001). There were significantly more patients of group A in ASA classes 4 and 5 ( Figure 2 ).
| Left Ventricular Ejection Fraction | p-value | ||
|---|---|---|---|
| ≤ 30% n=169 | > 30% n=1263 | ||
| Age (years) | 79.9 ± 6.7 | 82.0 ± 6.1 | <0.001 |
| men | 99 (58.7%) | 506 (39.8 %) | <0.0001 |
| Weight (kg) | 73.0 ± 19 (27 ± 9) | 73.0 ± 21 (27 ± 10) | 0.75 (<0.05) |
| log EUROscore (%) | 34 ± 18 | 19 ± 12 | <0.0001 |
| Pulmonary hypertension | 124 (75.6 %) | 817 (65.1 %) | <0.01 |
| Systolic PA pressure | 49.4 ± 16.8 | 44.8 ± 33.0 | <0.001 |
| Coronary artery disease | 128 (64.7 %) | 729 (57.8 %) | <0.0001 |
| Percutaneous coronary intervention | 67 (40.6 %) | 426 (33.8 %) | 0.08 |
| Previous myocardial infarction | 48 (28.7 %) | 179 (14.2 %) | <0.0001 |
| Previous heart surgery | 54 (32.3 %) | 264 (20.9 %) | <0.001 |
| Previous coronary bypass | 51 (30.5 %) | 216 (17.1 %) | <0.05 |
| Previous valve operation | 4 (2.4 %) | 46 (3.6 %) | 0.07 |
| Atrial fibrillation | 37 (22.3 %) | 319 (25.3 %) | 0.35 |
| Previous pace maker/ ICD | 25 / 11 (15.1 % / 11 %) | 156 / 10 (12.4 % / 0.8 %) | 0.33 / <0.0001 |
| peripheral vascular disease | 48 (28.7 %) | 257 (20.4 %) | <0.05 |
| COPD | 45 (26.9 %) | 298 (23.6 %) | 0.34 |
| Neurological disease | 26 (15.6 %) | 166 (13.2 %) | 0.37 |
| Stroke / TIA | 18 (10.8 %) | 96 (7.6 %) | 0.16 |
| Porcelain aorta | 10 (6.1 %) | 138 (11.0 %) | 0.05 |
| Diabetes mellitus | 72 (43.1 %) | 419 (33.2 %) | <0.05 |
| Chronic renal failure | 111 (65.7 %) | 758 (60.0 %) | 0.16 |
| Glomerular filtration rate (ml/min/1,73m 2 ) | 56 ± 22 | 58 ± 26 | 0.22 |
| Variable | Left Ventricular Ejection Fraction | p-value | |
|---|---|---|---|
| ≤ 30% n=169 | > 30% n=1263 | ||
| Aortic stenosis (grade 1 / 2 / 3 / 4) | 0 / 5.4 / 66.5 / 28.1 % | 0 / 3.8 / 67.4 / 28.8 % | 0.62 |
| mean gradient (mmHg by TTE) | 37.8 ± 21.4 | 50.8 ± 18.3 | <0.0001 |
| low flow and low gradient AS ∗ | 63 (38.7%) | 95 (7.6 %) | <0.0001 |
| aortic surface area (cm 2 ) | 0.72 ± 0.63 | 0.68 ± 0.39 | 0.92 |
| aortic annulus (mm) | 23.86 ± 2.39 | 23.19 ± 2.63 | <0.01 |
| calcification in % (minor / moderate / severe) † | 3.0 / 29.3 / 67.7 % | 5.2 / 28.2 / 66.6 % | 0.48 |
| Left ventricular ejection fraction (%) | 25 ± 5 | 56 ± 12 | <0.0001 |
| previous cardiogenic shock / left heart decompensation | 69 (41.3 %) | 272 (21.6 %) | <0.0001 |
| cardiogenic shock / decompensation <48h | 11/69 (15.9%) | 14/272 (5.1 %) | <0.01 |
| previous myocardial infarction | 48 (28.7 %) | 179 (14.2 %) | <0.0001 |
| previous balloon aortic valvuloplasty | 34 (20.4 %) | 136 (10.8 %) | <0.001 |
| Aortic regurgitation (grade 0/1/2/3/4) | 73.9 % (26.1 / 48.5 / 21.2 / 3.0 / 1.2) | 78.7 % (21.3 / 57.1 / 17.8 / 2.5 / 1.3) | 0.34 |
| Mitral regurgitation (grade 0/1/2/3/4) | 92.7 % (7.3 / 47.0 / 38.4 / 7.3 / 0) | 88.1 % (11.9 / 56.6 / 29.9 / 2.5 / 0.1) | 0.0004 |
| Tricuspid regurgitation (grade 0/1/2/3/4) | 85.0 % (14.8 / 50.0 / 29.0 / 5.6 / 0.6) | 81.7 % (20.0 / 59.0 / 18.9 / 2.0 / 0.2) | 0.0006 |
∗ low flow and low gradient AS defined as mean transvalvular gradient below 40mmHg.
Quality of life assessment by EURO-Qol 5d demonstrated a significantly lower mobility in group A (bed-bound: 15.2% vs 4.7%, p <0.0001), more limited self-caring capacity (unable for dressing and washing without help: 16.1% vs 7.8%, p <0.001), a significantly reduced physical capacity to accomplish general daily work (25.2% vs 14.6%, p <0.01), and a higher level for pain (extreme pain or complaints: 21.3% vs 10.5%, p <0.001) compared with group B. The self-assessment of health condition on a scale from 0 to 100 was significantly worse in patients of group A (p <0.0001; Figure 1 ).
Baseline AVA was similar between both groups, but a “low-flow and low-gradient” AS was more frequently found in group A ( Table 2 ). In addition, a staged aortic balloon valvuloplasty before TAVI was more frequently performed in group A ( Table 2 ). Regarding aortic valve anatomy, there were no relevant differences in size, extent of aortic valvular calcification, prevalence of bicuspid valvular morphology, or preprocedural AR. Femoral access-site diameters and prevalence of relevant kinking were similar in both groups.
Most patients were treated by transfemoral TAVI (group A vs group B: transfemoral 88.8% vs 87.6%, p = 0.66; transapical 7.1% vs 8.8%, p = 0.46; transaortic 0.6% vs 0.7%, p = 0.86; trans-subclavian 3.6% vs 2.9%, p = 0.66). Importantly, TAVI was performed more frequently as an urgent or emergency procedure or even under resuscitation in group A (p <0.01; Figure 2 ). In both groups, TAVI was most frequently performed with the Medtronic CoreValve (A vs B: 84.6% vs 81.0%, p = 0.26), followed by Edwards SAPIEN valves (15.4% vs 18.9%, p = 0.27). Transvalvular hemodynamic data showed very low gradients after TAVI (mean gradient in group A: 6.0 ± 7.1 mm Hg vs 5.9 ± 6.9 mm Hg in group B, p = 0.75). Nevertheless, some degree of postprocedural AR was frequently observed (A vs B: 72.6% vs 68.4%, p = 0.26). It may be important to note that AR was graded as moderate in 23.2% in group A after TAVI compared with 12.3% in group B (p <0.0001). Overall procedural success was high (A vs B: 95.9% vs 97.6%, p = 0.17; procedure abortion 3.6% vs 1.1%, p = 0.05), and the rate of conversion to open heart surgery was low (A vs B: 0.6% vs 1.3%, p = 0.45). In general, the rate of documented severe procedural complications was remarkably low and did not differ between both groups (severe bleeding 0.5%, coronary ischemia 0.9%, prosthesis dysfunction 0.3%, other causes 0.8%). Nevertheless, vascular complications were quite frequently observed (21.7%) but were graded as severe only in 3.5% (A vs B: 2.5% vs 3.7%, p = 0.42).
A complicated postprocedural course was more frequently observed in patients of group A. The incidence of low cardiac output was doubled in patients of group A compared with group B ( Figure 3 ) and was more often treated conservatively in 70% versus 66.2% (p <0.01) by IABP in 15% versus 6.7% (p <0.05) or other mechanical support devices in 15% versus 27.0% (p = 0.82), respectively. Likewise, resuscitation was more frequently necessary in group A ( Figure 3 ). In addition, acute kidney failure requiring hemodialysis was documented in 6.7% (A vs B: 10.4% vs 6.2%, p <0.05). With regard to respiratory ventilation, reintubation, tracheostomy, and cerebrovascular or other thromboembolic events, there were no differences between both groups. Postprocedural pacemaker or implantable cardiac defibrillator implantation was necessary in 36.5% after TAVI (A vs B: 31.3% vs 36.8%, p = 0.17) and most frequently performed because of persistent high-degree AV block (21.4%) and new left bundle branch block (14.0%). Because of the much LVEF in group A, ICD implantation was more frequently performed in group A (A vs B: 6.7% vs 0.6%, p <0.0001).
The data set was completed at 30 days for 98.6% (group A) and 99.2% (group B), respectively. The estimated cumulative 30-day mortality was 14.2% (group A) compared with 7.3% (group B, p <0.0001). There were no differences in documented strokes, systemic embolism, myocardial infarction, and severe bleeding between both groups. But the combined end points major adverse cardiac event (death and myocardial infarction) and major adverse cardiac and/or cerebrovascular events (death, myocardial infarction, stroke) until 30 days after TAVI were significantly higher in group A (A vs B: 16.6% vs 8.4%, p <0.001, and 16.6% vs 8.1%, p <0.001, respectively). Nevertheless, there was a significant improvement in functional status according to the NYHA ( Figure 1 ) and CCS (data not shown) in both groups. As opposed to baseline status, NYHA classification was no longer different at 30 days and 1 year after TAVI. In addition, there was no difference in the rate of rehospitalization (A vs B: 6.8% vs 5.3%, p = 0.12) and need for specific care between both groups (care level stage 1 to 3). Quality of life showed a significant improvement as assessed by the EURO-Qol 5d. In fact, the improvement compared with baseline was larger in patients of group A (A vs B: 0.19 ± 0.3 vs 0.05 ± 0.3, p <0.01). The self-assessment of health condition demonstrated a much better score in group A ( Figure 1 ), and there was no longer any difference between both groups with regard to the self-assessment in health condition on a scale from 0 to 100 ( Figure 1 ) as opposed to baseline, and 85.2% of the patients in group A and 83% of group B were independent of any care level (p = 0.6).
Follow-up data were available at 12 months in 93.4% (group A) and 95.2% (group B), respectively. Three were no differences in documented strokes, systemic embolism, myocardial infarction, and severe bleedings between both groups, but the combined end points major adverse cardiac event and major adverse cardiac and/or cerebrovascular events were significantly higher in group A compared with group B (36.1% vs 21.3%, p <0.001, and 36.7% vs 22.4%, p <0.01, respectively). Accordingly, the Kaplan-Meier survival curve showed a higher mortality in group A ( Figure 3 ). Nevertheless, the functional status according to the NYHA ( Figure 1 ) and CCS remained comparably improved in both groups and the rate of rehospitalizations (A vs B: 17.3% vs 22.1%, p = 0.1) and the distribution to any care level program was no longer significantly different between both groups. Most importantly, the quality of life as assessed by EURO-Qol 5d demonstrated a substantially larger benefit in patients of group A (gain: 0.22 ± 0.34) compared with patients of group B (gain: 0.05 ± 0.3, p <0.01). In addition, the self-assessment in health condition demonstrated a stable and similar level in both groups ( Figure 1 ). A further subdivision of group B into patients with an LVEF >30% to ≤40% (group C), LVEF >40% to ≤50% (group D), and LVEF >50% (group E) demonstrated superimposable survival curves for patients in groups D and E, whereas group C showed an intermediate mortality ( Figure 4 ).
