Conflicting results have been reported about the prognostic impact of left bundle branch block (LBBB) after transcatheter aortic valve implantation (TAVI). The aim of this study was to evaluate the impact of LBBB after TAVI on left ventricular (LV) function and remodeling and on 1-year outcomes. Of 101 TAVI patients, 9 were excluded. All complications were evaluated according to the Valve Academic Research Consortium 2 definition. Of 92 patients, 34 developed LBBB without more advanced myocardial damage or inflammation biomarkers in comparison with patients without LBBB. The only predictor of new LBBB was larger baseline LV end-diastolic volume. LBBB plus advanced atrioventricular block was strongly correlated with permanent pacemaker implantation (p <0.0001). Patients with LBBB had a higher rate of permanent pacemaker implantation at 30 days (59% vs 19%, p <0.0001) and less recovery of LV systolic function and a trend toward a lower rate of LV reverse remodeling at 1 year. The development of acute kidney injury and the logistic European System for Cardiac Operative Risk Evaluation score were associated with poor outcomes (all-cause mortality and heart failure) (hazard ratio 6.86, 95% confidence interval 2.51 to 18.74, p <0.0001, and hazard ratio 1.04, 95% confidence interval 1.01 to 1.08, p = 0.021, respectively), but not LBBB. In conclusion, after TAVI, 37% of patients developed new LBBB without more advanced myocardial damage or inflammation biomarkers. LBBB was associated with a higher rate of permanent pacemaker implantation, which negatively affected the recovery of LV systolic function. The development of acute kidney injury, rather than LBBB, increases the 1-year risk for mortality and hospitalization for heart failure.
Transcatheter aortic valve implantation (TAVI) has been established as a therapeutic option for patients with aortic stenosis considered to be at high or prohibitive surgical risk. The occurrence of new-onset left bundle branch block (LBBB) is 1 of the most frequent complications after TAVI, and its occurrence may attenuate subsequent improvement in left ventricular (LV) systolic function. Conflicting results have been reported about the prognostic impact of LBBB after TAVI. The aim of this study was therefore to determine the incidence, the determinants, and the impact on LV function and remodeling and on 1-year clinical outcomes of new and persistent LBBB in patients who underwent TAVI with a self-expandable valve (CoreValve; Medtronic, Inc., Minneapolis, Minnesota).
Methods
A total of 101 consecutive patients with symptomatic aortic stenosis, with valve areas <1 cm 2 , considered not suitable for or at very high risk for surgical aortic valve replacement, underwent TAVI with self-expandable valves at our center. Eligibility for TAVI was established on the consensus of a local multidisciplinary team, including clinical cardiologists, cardiac surgeons, and cardiac anesthesiologists. Of 101 patients, 9 patients were excluded: 3 who died within 24 hours (1 from cardiac tamponade, 1 from a life-threatening arrhythmia, and 1 from failure of TAVI); 3 who died within 7 days, precluding the evaluation of persistent LBBB on electrocardiography (1 from stroke, 1 from lung failure, and 1 from refractory cardiogenic shock); 1 patient with previous pacemaker implantation; and 2 patients with previous LBBB. The final study population consisted of 92 patients. The decision on whether to revascularize a coronary vessel with an obstructive coronary lesion (70% diameter stenosis, visual estimation) before TAVI depended on the criteria of the physician responsible for the patient and the TAVI team. Details on the TAVI procedure are provided elsewhere. Data were prospectively collected in a dedicated database. The study protocol was in accordance with the institutional ethics committee, and all patients gave informed written consent. Periprocedural events were defined according to the Valve Academic Research Consortium 2 criteria.
Electrocardiographic records were obtained from all patients at baseline, immediately after the procedure, and daily until hospital discharge. Electrocardiographic tracings were analyzed by 2 experienced cardiologists (RV and AM). The diagnosis of intraventricular conduction abnormalities was based on current recommendations. Permanent pacemaker implantation (PPI) was indicated if third-degree or advanced second-degree atrioventricular block (AVB) was found at any anatomic level that was not expected to resolve after the intervention and for sinus node dysfunction with documented symptomatic bradycardia, in agreement with current guidelines. New-onset LBBB was defined as any new LBBB occurring during the hospitalization period after the TAVI procedure that persisted at hospital discharge.
LV volumes and the LV ejection fraction (LVEF) were calculated using the modified biplane Simpson’s rule algorithm. A reduction in LV end-systolic volume (ESV) of >15% at 6-month follow-up compared with baseline echocardiography was considered reverse LV remodeling.
Follow-up was carried out by clinical outpatient visits at 1, 6, and 12 months and yearly thereafter. The median follow-up period was 360 days (range 10 to 410), and no patient was lost to follow-up. All clinical events were defined according to the Valve Academic Research Consortium 2 criteria, and any death was recorded and further classified as of cardiovascular or noncardiovascular origin. Rehospitalizations for all causes and heart failure (HF) were recorded during the follow-up period. Complete 2-dimensional echocardiographic examinations were performed at baseline, after TAVI procedures, and at 1-, 6-, and 12-month follow-up. For patients who died, the last echocardiogram available was considered.
Qualitative variables were compared using chi-square or Fisher’s exact tests as appropriate and are expressed as percentages. Continuous variables were compared using 2-sided Student’s t tests or Wilcoxon’s rank sum tests, depending on the variable distribution, and are expressed as mean ± SD or as median (interquartile range [IQR]). Relations between new LBBB plus advanced AVB and PPI were tested using Spearman’s correlation. The independent predictors of new LBBB were evaluated using multivariate logistic regression analysis. Analysis of variance with Tukey’s post hoc test was used to analyze repeated measures of aortic valve area, LV end-diastolic volume (EDV), LV ESV, and the LVEF over time between groups. A Cox proportional-hazards regression model was used to identify independent predictors of mortality from any cause and hospitalization for HF at 1 year. Event-free survival was estimated using the Kaplan-Meier method. The log-rank test was used to compare mortality from any cause and hospitalization for HF between patients with and without new LBBB after TAVI procedures. The results were considered significant at p <0.05. All tests were 2 sided. Analyses were performed using SPSS version 19 (IBM Corporation, Somers, New York).
Results
The baseline clinical characteristics of the patients, stratified by the occurrence of new LBBB, are listed in Table 1 . Among 92 patients, 34 (37%) developed new LBBB, and the remaining 58 did not. The clinical characteristic of the 2 groups were well matched, without significant differences ( Table 1 ). There were no significant differences between the groups with respect to echocardiographic parameters, but larger baseline LV EDVs were found in patients with LBBB ( Table 2 ). Vascular access was obtained through the subclavian artery in 3 patients and the common femoral artery in the remaining patients. No differences were observed in terms of the amount of iodinated contrast agent used (121.7 ± 57 vs 127.3 ± 60 ml, p = 0.682), procedure-related fluoroscopy time (15.4 ± 6.5 vs 14.2 ± 5.8 min, p = 0.374), number of rapid pacing runs (1.21 ± 0.43 vs 1.15 ± 0.36, p = 0.474), and distribution of CoreValve sizes (23 mm: 0 [0%] vs 1 [1.7%], p = 0.441; 26 mm: 13 [38%] vs 22 [38%], p = 0.977; 29 mm: 21 [62%] vs 34 [59%], p = 0.767; 31 mm: 0 [0%] vs 1 [1.7%], p = 0.441) between patients with and those without LBBB. After TAVI procedures, between patients with and those without LBBB, no significant difference was observed regarding the rate of low implantation (26.5% vs 19%, p = 0.399), defined as a distance >8 mm between the lower edge of the noncoronary cusp and the lower edge of the self-expandable valve frame, regarding the increase in cardiac troponin I level as a marker of myocardial damage (median 1.64 μg/L [IQR 0.97 to 4.30] vs 1.92 μg/L [IQR 0.99 to 4.58], p = 0.910), as well as the peak of white cell count as a marker of myocardial inflammation (median 10.4 × 10 9 /L [IQR 8.98 to 13.30] vs 11 × 10 9 /L [IQR 9.38 to 15.90], p = 0.398) ( Supplementary Figure S1 ).
| Variables | All (n=92) | New LBBB | p Value | |
|---|---|---|---|---|
| Yes (n=34) | No (n=58) | |||
| Age (years) | 81 ± 6.3 | 81 ± 6.3 | 81 ± 6.4 | 0.874 |
| Logistic EuroSCORE (%) | 20 ± 14 | 18 ± 12 | 21 ± 16 | 0.270 |
| Men | 48 (52%) | 18 (53%) | 30 (52%) | 0.910 |
| Hypertension † | 55 (60%) | 19 (56%) | 36 (62%) | 0.559 |
| Dyslipidemia ‡ | 26 (28%) | 12 (35%) | 14 (24%) | 0.251 |
| Current smokers | 10 (11%) | 5 (15%) | 5 (8.6%) | 0.365 |
| Diabetes mellitus | 28 (30%) | 14 (41%) | 14 (24%) | 0.086 |
| Previous myocardial infarction | 11 (12%) | 5 (15%) | 6 (10%) | 0.534 |
| Previous percutaneous coronary intervention | 30 (33%) | 9 (27%) | 21 (36%) | 0.336 |
| Previous coronary artery bypass grafting | 8 (8.6%) | 5 (15%) | 3 (5.0%) | 0.117 |
| Previous angina pectoris | 26 (28%) | 8 (24%) | 18 (31%) | 0.440 |
| Previous stroke | 5 (5.4%) | 3 (8.8%) | 2 (3.4%) | 0.272 |
| Peripheral artery disease | 9 (9.8%) | 4 (11.8%) | 5 (8.6%) | 0.624 |
| Chronic obstructive pulmonary disease | 17 (18.5%) | 7 (21%) | 10 (17%) | 0.690 |
| Previous chronic kidney disease | 17 (18.5%) | 8 (23.5%) | 9 (15.5%) | 0.339 |
| Creatinine (mg/dl) | 0.89 (0.73-1.13) | 0.86 (0.75-1.19) | 0.90 (0.71-1.11) | 0.766 |
| Cardiac troponin I (μg/L) | 0.04 (0.02-0.15) | 0.04 (0.02-0.20) | 0.04 (0.02-0.10) | 0.636 |
| Creatine kinase-MB isoenzyme (μg/L) | 2.20 (1,10-3.05) | 2.40 (1.60-3.35) | 1.80 (1.00-2.98) | 0.138 |
| White blood cells (*10 9 /L) | 7.23 (5.94-8.82) | 7.66 (6.02-9.03) | 7.10 (5.84-8.58) | 0.561 |
† History of hypertension diagnosed and treated with medication, systolic blood pressure >140 mm Hg or diastolic blood pressure >90 mm Hg on ≥2 occasions, or current use of antihypertensive medication.
‡ History of dyslipidemia diagnosed and/or treated with medication or fasting total cholesterol level >5.0 mmol/L, high density lipoprotein level <1.0 mmol/L, or triglyceride level >2.0 mmol/L.
| Variables | All (n=92) | New LBBB | p Value | |
|---|---|---|---|---|
| Yes (n=34) | No (n=58) | |||
| Left ventricular end diastolic diameter (mm) | 48 ±6.7 | 49 ± 4.6 | 47 ± 7.6 | 0.133 |
| Interventricular septum (mm) | 14 ± 2.1 | 14 ± 1.7 | 15 ± 2.0 | 0.788 |
| Posterior wall (mm) | 12 ± 1.5 | 12 ±1.8 | 12 ±1.4 | 0.609 |
| Left atrium diameter (mm) | 42 ± 4.4 | 43 ±3.1 | 42 ±4.9 | 0.559 |
| Annulus (mm) | 22 ± 1.7 | 22 ± 1.6 | 22 ± 1.7 | 0.866 |
| Sinuses (mm) | 32 ± 3.9 | 32 ±3.8 | 31 ± 3.9 | 0.360 |
| Sinotubular junction (mm) | 32 ± 3.7 | 32 ± 3.5 | 32 ± 3.5 | 0.430 |
| Ascending Aorta (mm) | 35 ±3.5 | 36 ± 2.4 | 35 ± 4.1 | 0.336 |
| Left ventricular end diastolic volume (mL) | 102 ± 45 | 114 ± 46 | 95 ± 43 | <0.0001 |
| Left ventricular end systolic volume (mL) | 57 ± 38 | 64 ± 37 | 52 ± 38 | <0.0001 |
| Left ventricular ejection fraction (%) | 48 ± 13 | 48 ± 12 | 48 ± 15 | 0.818 |
| Left ventricular ejection fraction < 40% | 29 (32%) | 11 (32%) | 18 (31%) | 0.895 |
| Peak aortic gradient (mmHg) | 75 ± 20 | 77 ± 24 | 74 ± 18 | 0.398 |
| Aortic valvular area (cm 2 ) | 0.54 ± 0.15 | 0.55 ± 0.16 | 0.53 ± 0.15 | 0.693 |
| Mitral valve regurgitation grade > 2 | 21 (23%) | 8 (24%) | 13 (22%) | 0.902 |
| Aortic valve regurgitation grade > 2 | 9 (10%) | 6 (18%) | 3 (5%) | 0.052 |
| Pulmonary artery systolic pressure (mmHg) | 30 ± 12 | 30 ± 12 | 30 ± 12 | 0.910 |
| Tricuspid annular plane systolic excursion (mm) | 20 ± 3.9 | 21 ± 3.9 | 20 ± 3.9 | 0.249 |
By multivariate analysis including variables significant on univariate analysis and others known to potentially increase the risk for conduction system disturbances before TAVI (logistic European System for Cardiac Operative Risk Evaluation score, baseline LV EDV, the LVEF, and septal wall thickness) or after TAVI (low implantation, markers of myocardial damage, and markers of inflammation), baseline LV EDV was the only variable associated with the development of new LBBB; only a trend toward a nonsignificant association was found for septal wall thickness (see Table 3 ).
| Variables | Univariate analysis | Multivariate analysis | ||||
|---|---|---|---|---|---|---|
| HR | 95% C.I. | p Value | HR | 95% C.I. | p Value | |
| Logistic EuroSCORE (%) | 0.98 | (0.95-1.02) | 0.319 | 0.97 | (0.93-1.01) | 0.151 |
| Left ventricular end diastolic volume (mL) | 1.01 | (0.99-1.02) | 0.067 | 1.01 | (1.00-1.22) | 0.048 |
| Interventricular septum (mm) | 0.84 | (0.67-1.03) | 0.097 | 0.79 | (0.62-1.02) | 0.070 |
| Baseline left ventricular ejection fraction (%) | 1.00 | (0.97-1.03) | 0.844 | – | – | . |
| Peak cardiac troponin I (μg/L) | 0.98 | (0.92-1.05) | 0.577 | – | – | – |
| Peak white blood cells (*10 9 /L) | 0.96 | (0.87-1.05) | 0.348 | – | – | – |
| Low implant | 1.54 | (0.56-4.20) | 0.401 | – | – | – |
Before TAVI procedures, 20 patients (25.3%) underwent percutaneous coronary intervention (n = 10 [30.3%] with LBBB, p = 0.405). After TAVI procedures, major peripheral vascular complications occurred in 20 patients (3 with LBBB); nonfatal stroke occurred in 2 patients (1 with LBBB), 23 patients (4 with LBBB) received blood transfusions, and acute kidney injury (AKI) developed in 13 patients (14%) (3 requiring ultrafiltration), showing increases in creatinine reaching the median value of 0.94 mg/dl (IQR 0.77 to 1.34). Specifically, AKI level 1 was found in 9 patients (9.8%) (4 with LBBB) and AKI levels 2 and 3 in 4 patients (4.3%) (2 with LBBB) ( Supplementary Figure S1 ). After TAVI, no patient developed new Q waves in the inferior or anterior leads on electrocardiography.
After TAVI procedures, a high rate of advanced AVB occurred in patients with LBBB (n = 17) compared with those without LBBB (13 patients, 3 with atrial fibrillation) (50% vs 22.4%, p = 0.006). The development of new LBBB plus advanced AVB (n = 17) was strongly correlated with PPI (p <0.0001), and a higher rate of PPI was found in LBBB compared with patients without LBBB at 30 days (59% vs 19%, p <0.001). One month after TAVI, 2 patients needed PPI, 1 patient with LBBB for complete AVB (LBBB) and 1 patient without LBBB for slow atrial fibrillation. After hospital discharge, throughout 1 year of follow-up outpatient visits, the percentage of right ventricular stimulation by PPI (available in all surviving patients but 1) was high, reaching a median value of 90% (IQR 26% to 99%).
After hospital discharge, throughout 1 year of follow-up (rate 100%), 11 patients died (4 with LBBB): 10 from noncardiac causes and 1 of a cardiac cause (refractory HF) ( Supplementary Table S1 ). Nine patients were hospitalized for HF (2 with LBBB); overall, 6 events (17.6%) (all-cause mortality and HF) occurred in patients with LBBB compared with 14 (24.1%) in those without LBBB (p = 0.466).
Significant improvements in aortic valve area were observed in the 2 groups immediately after TAVI, and aortic valve area remained substantially unchanged without signs of deterioration over time in the 2 groups ( Figure 1 ). In patients without LBBB, LVEFs significantly improved soon after TAVI, and from 1 to 6 months and 6 months to 1 year, no further recovery was observed. In patients with LBBB, no significant recovery of the LVEF was observed early after TAVI, and LVEFs remained unchanged up to 1 month. Afterward, from 1 to 6 months, LVEFs decreased and remained substantially unchanged up to 12 months ( Figure 1 ). Throughout the follow-up period, between the 2 groups, no significant difference in recovery of the LVEF was observed at each time point, except at 6 months. Early after TAVI, reductions in LV EDV and ESV were observed in the 2 groups, which became statistically significant at 6 months, after which LV volumes remained substantially unchanged up to 12 month ( Figure 1 ). Throughout the follow-up period, between the 2 groups, significant differences in LV volumes were observed at each time point. At 6 months, a trend toward a lower rate of reverse LV remodeling was observed in patients with LBBB in comparison with those without LBBB (40.6% vs 60.8%, p = 0.073). Moreover, from baseline to 6 months, recovery of the LVEF was significantly higher in TAVI patients with (n = 44) compared with those without (n = 39) reverse LV remodeling (7.39 ± 9.05% vs −0.46 ± 5.63%, p <0.0001).
