Abstract
Objectives
To evaluate the impact of left ventricular (LV) chamber size on procedural and hospital outcomes of patients undergoing aortic valvuloplasty.
Background
Balloon aortic valvuloplasty (BAV) is used as an integral step during transcatheter aortic valve implantation. Patients with small, thickened ventricles are thought to have more complications during and following BAV.
Methods
Retrospective study of consecutive patients with severe, symptomatic calcific aortic stenosis who underwent retrograde BAV at Massachusetts General Hospital. We compared patients with left ventricular end-diastolic diameters (LVEDD) <4.0 cm (n = 31) to those with LVEDD ≥4.0 cm (n = 78). Baseline and procedural characteristics as well as clinical outcomes were compared. Multivariate logistic regression was used for the adjusted analysis.
Results
Patients with smaller LV chamber size were mostly women (80.7% vs. 19.4%, P < 0.01) and had a smaller body surface area (BSA), (1.61 ± 0.20 m2 vs. 1.79 ± 0.25 m2, P < 0.01). Patients with smaller LV chamber size had higher ejection fractions and thicker ventricles. Otherwise, baseline characteristics were similar. The intraprocedural composite of death, cardiopulmonary arrest, intubation, hemodynamic collapse, and tamponade was higher for patients with LVEDD < 4.0 cm (32.3% v. 11.5%, P = 0.01). Adjusting for age, gender, BSA, LV pressure, and New York Heart Association class, LVEDD < 4.0 cm remained an independent predictor of procedural (OR 5.1, 95% CI 1.4– 18.2) and in-hospital complications (OR 3.8, 95% CI 1.2–11.6).
Conclusions
Compared to patients undergoing BAV with LVEDD ≥4.0 cm, those with smaller LV chambers had worse procedural and in-hospital outcomes.
Keywords: aortic valve stenosis, left ventricular hypertrophy, hypertrophic obstructive cardiomyopathy, subaortic stenosis
INTRODUCTION
With the advent of transcatheter aortic valve implantation, balloon aortic valvuloplasty (BAV) is being used more frequently to bridge patients to valve replacement and as an integral step in the procedure for transcatheter aortic valve replacement (TAVR). The immediate adverse outcomes of BAV are not trivial and range from 2 to 20% for major procedural complications [1–3] and from 3 to 9.4% for procedural and in-hospital mortality [3–7].
Patients with aortic stenosis develop secondary left ventricular (LV) hypertrophy in response to the chronic pressure overload, which can lead to a significant intracavitary gradient [8,9]. The development of a dynamic outflow track gradient after aortic valve replacement has been reported [10]. In patients undergoing BAV, authors have anecdotally reported that patients with thickened, small, left ventricular chambers have greater risk for procedural complications [11,12], presumably due to unmasking of a dynamic obstructive gradient as the aortic stenosis is relieved [9].
We evaluated whether small LV chamber size was associated with a greater risk of intraprocedural and in-hospital complications.
METHODS
Study Population
This is a retrospective cohort study of patients with severe, symptomatic calcific aortic stenosis (aortic valve area (AVA) < 1.0 cm2 and elevated mean valve gradients >40 mm Hg determined by echocardiography) undergoing nonemergent retrograde percutaneous BAV at Massachusetts General Hospital between December 22, 2004, and December 15, 2008. Patients who were in cardiogenic shock and those requiring mechanical ventilatory support prior to the procedure were excluded. We also excluded patients with bicuspid aortic valves, a prior BAV, moderate, or severe aortic regurgitation, history of hypertrophic cardiomyopathy (asymmetric septal hypertrophy on echocardiogram with a clinical diagnosis), and those with severe peripheral vascular disease that precluded retrograde BAV. These patients in the study period underwent BAV prior to the availability of TAVR at our hospital.
Preprocedural transthoracic echocardiograms were obtained routinely in all patients. Intracardiac left ventricular end diastolic diameter (LVEDD) was measured from the proximal septum to the posterior wall by standardized techniques using m-mode echocardiography in the parasternal long axis view. Patients were categorized into those with LVEDD ≥ 4.0 cm and <4.0 cm and compared by clinical, procedural, and hemodynamic characteristics and outcomes. LVEDD of 4.0 cm was chosen because it was the upper limit of the lowest 25th percentile of LVEDD measurements in our patient population.
Patient data were obtained through review of hospital records, echocardiography, and catheterization laboratory database. Patients were designated as having hypertension or dyslipidemia if they were given that diagnosis by their physician or were taking blood pressure or lipid lowering agents. Coronary artery disease was defined as having a documented diagnosis or history of coronary revascularization.
Procedure
Standard right and left-sided heart catheterizations were performed. Cardiac outputs were measured using the thermodilation technique. In the presence of left to right shunting or significant tricuspid regurgitation, cardiac outputs were measured according to the Fick method using assumed O2 consumption. Simultaneous transaortic valve gradients were measured routinely in all patients using a 6F double lumen pigtail catheter. AVA was calculated according to the Gorlin formula. Echocardiographic evaluations of AVA were also performed and were similar to catheter measurements. BAV was performed retrograde from the common femoral artery (12F) using standard technique [13]. The balloon catheter diameter was selected for a diameter equal to or less than the aortic annulus diameter determined by echocardiography. All patients received intravenous heparin to achieve an activated clotting time ≥250 sec prior to BAV. Rapid ventricular pacing was not used for all patients at our center, and was used only at the discretion of the operator. It was performed equally in patients with small LV chambers and those with LVEDD >4.0 cm (58.1% vs. 57.7%, P = 0.97). Right and left-sided heart catheterization was performed at the end of the procedure in every patient. Post-BAV AVA, aortic valve gradient, and cardiac output were obtained by catheterization and were compared to those obtained at baseline.
Study Endpoints
The primary endpoint of the study was the composite of in-hospital major adverse cardiovascular events comprised of hospital death, myocardial infarction, stroke, tamponade, and cardiac arrest requiring cardiopulmonary resuscitation. Secondary endpoints included the individual components of the primary endpoint in addition to intraprocedural hypotension requiring intravenous vasopressors, intraprocedural endotracheal intubation, and the composite of all intraprocedural adverse events. Myocardial infarction was defined as an increase of creatinine kinase ≥ 3 times the upper limit of normal measured within 24-hr postprocedure or any new pathological q-wave on electrocardiogram. Acute kidney injury was defined as a 0.5 mg dl−1 or greater increase in creatinine over baseline within 48 hr [14].
All patients were routinely assessed for vascular complications, including retroperitoneal bleeding, pseudoaneurysm, arterial to venous fistula, arterial dissection, and access site major bleeding (hemoglobin decrease of ≥5 g dl−1 or any access bleeding requiring transfusion).
Glomerular filtration rate was estimated using the modification of diet in renal disease equation. LV mass was calculated by the formula 1.05 ([LVIDD + PWTD + IVSTD]3 - [LVIDD]3) grams where LVIDD is left ventricular internal dimension-diastole, PWTD is posterior wall thickness at end diastole and IVSTD is intraventricular septal thickness at end-diastole, described previously [15]. Indexed values were calculated by dividing a variable by body surface area (BSA).
Statistical Analysis
Categorical variables were compared by chi-square analysis, or Fisher’s exact test where appropriate. Continuous variables were compared by Student’s t test. Linear regression was used to compare continuous variables, and variance was evaluated by the F test. Confounding and effect modification were evaluated using the Mantel–Haenszel method. Multivariate logistic regression was performed for the composite of in-hospital and intraprocedural complications. The clinical and hemodynamic factors were evaluated for their relative risk of association with the composite outcome. Factors that were different between the two groups or associated with the composite outcome in the unadjusted comparisons to a significance level of P < 0.1 were included in the adjusted model. The odds ratios derived from the logistic regression are reported as relative risks given the small number of events. Model fit was evaluated using likelihood ratio testing. Analyses were performed using Intercooled STATA version 9.2 (Statacorp, College Station, TX).
RESULTS
A total of 126 patients who underwent retrograde BAV were evaluated of whom 109 patients met study criteria, and 17 were excluded. Of those included, 31 patients (28%) had LVEDD <4.0 cm and 78 patients (72%) had LVEDD >4.0 cm. There was a normal distribution of LVEDD. The mean LVEDD was 4.6 cm and the 25th and 75th percentiles were 4.0 and 5.1, respectively (Fig. 1).
Fig. 1.
Distribution of patients by left end diastolic diameter. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
Baseline demographic and clinical characteristics are shown in Table I.
TABLE I.
Baseline Demographic and Clinical Characteristics
| LVEDD < 4.0 cm (n = 31) |
LVEDD ≥ 4.0 cm (n= 78) |
||||
|---|---|---|---|---|---|
| Characteristic | N | Mean ± SD or (%) | N | Mean ± SD or (%) | P value |
| Baseline clinical characteristics | |||||
| Women | 25 | (80.7) | 15 | (19.4) | 0.00 |
| Age (years) | 84.5 ±8.1 | 81.74 ± 7.6 | 0.01 | ||
| Body Mass Index (kg m−2) | 23.4 ± 3.5 | 25.90 ± 5.7 | 0.03 | ||
| Body surface area (m2) | 1.6 ± 0.1 | 1.8 ± 0.1 | <0.01 | ||
| Race | |||||
| White | 25 | (80.7) | 70 | (89.7) | 0.20 |
| Non-White | 6 | (19.4) | 8 | (10.3) | 0.20 |
| Diabetes mellitus | 10 | (32.3) | 26 | (33.3) | 0.91 |
| Diabetes therapy | |||||
| Oral medication | 6 | (20.0) | 9 | (12.0) | 0.10 |
| Insulin | 19 | (60.0) | 22 | (28.0) | 0.10 |
| Diet | 6 | (20.0) | 47 | (60.0) | 0.10 |
| Hypertension | 24 | (77.4) | 62 | (79.5) | 0.81 |
| Dyslipidemia | 23 | (74.2) | 66 | (84.4) | 0.22 |
| Tobacco use | |||||
| Any previous | 13 | (41.9) | 42 | (53.3) | 0.54 |
| Current | 2 | (6.5) | 3 | (3.9) | 0.54 |
| Coronary artery disease | 15 | (48.4) | 47 | (60.3) | 0.26 |
| Three-vessel coronary artery disease | 2 | (6.5) | 13 | (16.7) | 0.16 |
| Previous myocardial infarction | 7 | (22.6) | 22 | (28.2) | 0.55 |
| Previous PCI | 4 | (12.9) | 15 | (19.2) | 0.43 |
| Previous CABG | 6 | (19.4) | 17 | (21.8) | 0.78 |
| Previous stroke | 8 | (25.8) | 36 | (46.2) | 0.05 |
| Family history of coronary disease | 1 | (3.2) | 4 | (5.1) | 0.67 |
| Previous heart failure | 19 | (61.3) | 60 | (76.9) | 0.10 |
| Chronic obstructive pulmonary disease | 9 | (29.0) | 29 | (37.2) | 0.42 |
| Peripheral vascular disease | 8 | (25.8) | 21 | (26.9) | 0.91 |
| GFR < 60 mL min−1/1.73 m2 | 19 | (61.3) | 53 | (67.5) | 0.54 |
| Atrial fibrillation | 8 | (25.8) | 29 | (37.2) | 0.26 |
| Clinical presentation | 0 | ||||
| Heart failure | 21 | (67.7) | 62 | (79.5) | 0.20 |
| NYHA classa | 0 | ||||
| I | 2 | (6.5) | 2 | (2.6) | 0.33 |
| II | 3 | (9.7) | 4 | (5.1) | 0.38 |
| III | 12 | (38.7) | 37 | (47.4) | 0.41 |
| IV | 14 | (45.2) | 35 | (44.9) | 0.98 |
| Any angina pectoris at presentation | 7 | (22.6) | 10 | (12.8) | 0.21 |
| Scheduling type | 0 | ||||
| Elective | 6 | (19.4) | 17 | (21.8) | 0.61 |
| Urgent | 23 | (74.2) | 59 | (75.6) | |
| Emergent | 2 | (6.5) | 2 | (2.6) | |
| EuroSCORE (additive) | 11.3 ± 0.6 | 12.2 ± 0.3 | 0.21 | ||
| EuroSCORE (logistic) | 28.8 ± 0.1 | 35.7 ±0.1 | 0.12 | ||
Data is presented as number and percentages or as means ± standard deviation. *PCI = percutaneous coronary intervention; CABG = Coronary artery bypass grafting; GFR = glomerular filtration rate; NYHA = New York Heart Association heart failure class.
Patients with small LV chambers were more likely to be older, female and with smaller body habitus. Other than a significantly lower prevalence of previous stroke, baseline clinical characteristics between the groups were similar. Estimated morbidity and mortality by logistic and additive EuroScores were not statistically different.
Patients with smaller LVEDD had notable differences in LV size and function (Table II). They had significantly thicker ventricles and, indexed for BSA, higher LV masses than those with LVEDD ≥ 4.0 cm. The ratio of LVEDD to diastolic intraventricular septal diameter was significantly lower in this group, consistent with the finding that these patients had relatively small, thick walled hearts, compared to those with LVEDD ≥ 4.0 cm (Fig. 2). Overall there was a weak, but significant, association between smaller LVEDD and thicker myocardial septal diameter (r2 = 0.17, F test, P < 0.01).
TABLE II.
Pre and Postpercutaneous Aortic Balloon Valvuloplasty (BAV) Hemodynamics
| Cardiac parameter | LVEDD < 4.0 cm (n = 31) |
LVEDD ≥ 4.0 cm (n= 78) |
P value |
|---|---|---|---|
| Echocardiographic | |||
| Ejection fraction | 65.2 ± 2.9 | 46.5 ±2.1 | <0.01 |
| LV septal thickness (diastole)a | 1.4 ± 2.6 | 1.2 ± 2.1 | <0.01 |
| Left ventricular hypertrophy (septal or posterior wall thickness > 1.1 cm) | 27 (88.0%) | 58 (73.9%) | 0.15 |
| LVEDDb | 35.6 ± 3.5 | 49.6 ± 6.6 | <0.01 |
| LVEDD index | 22.3 ± 2.6 | 28.1 ± 4.5 | <0.01 |
| LV mass (g) | 236.4 ± 78.5 | 306.5 ± 82.9 | <0.01 |
| LV mass index | 172.7 ± 46.2 | 147.0 ± 46.7 | 0.01 |
| Ratio of LVEDD to intraventricular septum | 2.6 ± 0.6 | 4.1 ± 1.0 | <0.01 |
| Pre-BAV pressures (mm Hg) | |||
| Aortic systolic | 128.0 ± 4.8 | 121.8 ± 2.7 | 0.23 |
| Aortic mean | 82.8 ± 3.1 | 80.9 ±1.6 | 0.55 |
| Left ventricular systolic | 184.7 ± 5.2 | 171.7 ± 3.1 | 0.03 |
| Left ventricular end-diastolic | 19.2 ± 1.7 | 20.6 ±1.0 | 0.47 |
| Post-BAV pressures (mm Hg) | |||
| Aortic systolic | 146.1 ± 34.5 | 138.9 ± 27.7 | 0.27 |
| Aortic mean | 91.9 ± 21.1 | 88.8 ± 18.3 | 0.45 |
| Left ventricular systolic | 175.1 ± 36.1 | 163.1 ± 28.1 | 0.07 |
| Left ventricular end-diastolic | 15.7 ±7.3 | 20.2 ± 9.4 | 0.02 |
| Pre- and post-BAV assessment | |||
| Cardiac index (pre) | 2.2 ± 0.6 | 2.4 ± 0.7 | 0.42 |
| Cardiac index (post) | 2.3 ± 0.7 | 2.4 ± 0.7 | 0.42 |
| Mean gradient (pre) (mm Hg) | 51.1 ± 2.9 | 45.86 ± 1.75 | 0.12 |
| Mean gradient (post) (mm Hg) | 31.2 ± 2.0 | 27.8 ± 1.3 | 0.18 |
| AVAc (pre) (cm2) | 0.6 ± 0.0 | 0.7 ± 0.0 | 0.01 |
| AVA index (pre) (cm2) | 0.34 ± 0.02 | 0.37 ± 0.01 | 0.20 |
| AVA (post) (cm2) | 0.7 ±0.1 | 1.0 ± 0.0 | 0.00 |
| AVA index (post) (cm2) | 0.47 ± 0.03 | 0.56 ± 0.02 | 0.01 |
| Δ AVA (% change) | 39.1 ± 5.4 | 56.3 ± 5.8 | 0.10 |
Data is presented as percentages or as means ± standard deviation. PBAV = Percutaneous balloon aortic valvuloplasty.
LV = left ventricular.
LVEDD = left ventricular end diastolic diameter.
AVA = aortic valve area.
Fig. 2.
Ratio of left ventricular diameter to interventricular septal diameter at end diastole, comparing patients with LVEDD < 4 to those with LVEDD ≥ 4. LVEDD = left ventricular end diastolic diameter; IVD = interventricular septal diameter. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
Those with smaller LV chambers had higher ejection fractions (65.2% vs. 46.5%, P < 0.01), but similar New York Heart Association (NYHA) class and rates of clinically apparent heart failure.
Pre and post-BAV hemodynamics are shown in Table II. Pre and postprocedural LV systolic pressures were higher in the group with LVEDD < 4.0 cm, but other parameters were similar. Aortic valve gradient, cardiac index, and aortic valve area index were similar. Both groups had similar rates of successful BAV (defined as an increase in AVA by at least 25%), (70.9% vs. 74.4%, P = 0.72). There were no differences in procedural characteristics (combined coronary and valvular procedure, number of balloon inflations, maximum balloon size, and use of rapid ventricular pacing, data not shown).
There was a trend towards more severe bleeding among patients with small LV chambers. The composite of vascular complications was also higher among patients with small LV chambers. These patients also had a significantly higher need for intraprocedural vasopressors and cardiopulmonary resuscitation (Fig. 3). The mean LVEDD of patients requiring vasopressors was significantly smaller than those who did not require vasopressors (4.1 ± 7.1 vs. 4.7 ± 8. 7, P = 0.01), and the baseline ejection fraction was higher, although this did not reach statistical significance (56.1 ± 18.2 vs. 51.1 ± 20.2, P = 0.33). Patients with small LV chamber size had a significantly higher rate of adverse clinical events. The primary endpoint of composite in-hospital events (death, cardiopulmonary arrest, myocardial infarction, tamponade) events was twice as high among those with LVEDD > 4.0 cm (32.3% vs. 15.4%, P = 0.04). The rate of intraprocedural complications was also significantly higher in patients with smaller LVEDD (Table III).
Fig. 3.
Comparison of intraprocedural complications by left ventricular end diastolic diameter (LVEDD). LVEDD = left ventricular end diastolic diameter. *P < 0.05. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
TABLE III.
Intraprocedural and Hospital Outcomes
| LVEDD < 4.0 cm (n = 31) |
LVEDD ≥ 4.0 cm (n= 78) |
||||
|---|---|---|---|---|---|
| Clinical outcome | N | (%) | N | (%) | P value |
| Access site | |||||
| Pseudoaneurysm | 2 | (6.7) | 3 | (3.9) | 0.53 |
| Severe bleeding | 5 | (16.7) | 4 | (5.1) | 0.05 |
| Arteriovenous fistula | 0 | (0.0) | 1 | (1.3) | 0.53 |
| Composite vascular complications | 6 | (20.0) | 6 | (7.7) | 0.07 |
| Intraprocedural | |||||
| Intubation | 3 | (9.7) | 3 | (3.9) | 0.23 |
| Vasopressors (any) | 10 | (32.3) | 7 | (9.1) | <0.01 |
| Transient during procedure | 8 | (25.0) | 4 | (5.4) | <0.01 |
| Continued postprocedure | 4 | (12.5) | 3 | (4.1) | 0.14 |
| Cardiopulmonary resuscitation | 5 | (16.1) | 4 | (5.1) | 0.06 |
| Death (procedural) | 1 | (3.2) | 0 | (0.0) | 0.11 |
| Tamponade | 2 | (6.5) | 0 | (0.0) | 0.02 |
| Any procedural complication | 10 | (32.3) | 9 | (11.5) | 0.01 |
| Hospital | |||||
| Acute renal injury | 1 | (3.2) | 7 | (8.9) | 0.30 |
| Myocardial infarction | 3 | (9.7) | 3 | (3.9) | 0.30 |
| In-hospital mortality | 3 | (9.7) | 5 | (6.4) | 0.56 |
| Composite (death, cardiopulmonary arrest, myocardial infarction, tamponade) | 10 | (32.3) | 12 | (15.4) | 0.04 |
In the multivariate analysis, adjusting for age, gender, BSA, and New York Heart Association class, and pre-BAV left ventricular end diastolic pressure, LVEDD <4.0 cm remained an independent predictor of any procedural complication, and the composite of death, myocardial infarction, tamponade, and cardio-pulmonary arrest (Table IV). There were no documented strokes in this study population. The ratio of LVEDD to interventricular septal diameter was not a significant predictor for adverse outcomes in the unadjusted or adjusted models and did not significantly change the OR for LVEDD when forced into the model. Age, gender, and BSA were not associated with worse outcomes in the unadjusted or adjusted analyses. NYHA class was significantly associated with worse in-hospital outcomes.
TABLE IV.
Multivariate Analysis: Odds Ratio for any Procedural Complication (Procedural Death, Intubation, Cardiopulmonary Arrest, Vasopressor Use, Tamponade), and In-Hospital Death, Myocardial Infarction, Tamponade, or Cardiopulmonary Arrest
| Any procedural complication |
In-hospital death, myocardial infarction, tamponade, or cardiopulmonary arrest |
|||||||
|---|---|---|---|---|---|---|---|---|
| Unadjusted OR (95% CI) |
P value | Adjusted OR (95% CI) |
P value | Unadjusted OR (95% CI) |
P value | Adjusted OR (95% CI) |
P value | |
| LVEDDa < 4.0 cm | 3.7 (1.3, 10.2) | 0.01 | 5.1 (1. 4, 18.2) | 0.01 | 2.6 (1.0, 6.9) | 0.05 | 3.8 (1.2, 11.6) | 0.03 |
| Body surface area | 0.6 (0.1, 4.2) | 0.57 | 1.0 (0.1, 23.4) | 0.98 | 0.8 (0.1, 5.1) | 0.81 | 0.7 (0.1, 9.6) | 0.87 |
| Female gender | 1.6 (0.6, 4.4) | 0.37 | 0.9 (0.2, 4.3) | 0.87 | 1.3 (0.5, 3.1) | 0.59 | 0.7 (0.2, 2.6) | 0.79 |
| Age | 1.0 (0.9, 1.1) | 0.85 | 1.0 (0.9, 1.1) | 0.89 | 1.0 (1.0, 1.1) | 0.88 | 1.0 (0.93, 1.1) | 0.70 |
| NYHAb Class | 1.9 (0.9, 4.2) | 0.11 | 1.9 (0.8, 4.7) | 0.12 | 2.9 (1.2, 6.8) | 0.02 | 2.6 (1.2, 5.9) | 0.02 |
| LVEDPc | 1.1 (1.0, 1.1) | 0.02 | 1.1 (1.0, 1.1) | 0.03 | 1.1 (1.0, 1.1) | <0.01 | 1.1 (1.0, 1.1) | 0.01 |
LVEDD = left ventricular end diastolic diameter.
NYHA = New York heart association.
LVEDP = left ventricular end diastolic pressure, prior to valvuloplasty.
DISCUSSION
Our study demonstrates that patients with smaller left ventricular chamber dimensions, defined as an LVEDD of <4.0 cm, are more likely to experience significant adverse intraprocedural and in-hospital outcomes following BAV. These patients are more likely female, older and with smaller BSA. Nevertheless, multivariate analysis identified the LVEDD as an independent predictor of BAV outcome, adjusting for these baseline differences. The significantly increased incidence of intraprocedural events (cardiac arrest, tamponade, and shock) are important since BAV is an integral step used during TAVR and isolated BAV procedures are being used more frequently as bridging therapy in patients being evaluated for more definitive valve implantation.
Patients with severe aortic stenosis, significant left ventricular hypertrophy, and smaller left ventricular cavities have been reported to develop abnormal intracavitary gradients following surgical aortic valve replacement [10]. The same may occur in patients with significant hypertensive LV hypertrophy without other diagnoses [8,12]. Concomitant aortic valve stenosis and hypertrophic cardiomyopathy [16,17] or subvalvular stenosis [18] have also been reported. In a consecutive study of 53 patients undergoing surgical aortic valve replacement, 13 patients developed an increased intracavitary gradient ranging from 10 to 184 mm Hg, of whom six suffered postoperative hemodynamic compromise. Importantly, the postoperative in-hospital mortality was 38% compared to 12% among patients without increased intracavitary gradients. None of these patients were thought to have an underlying diagnosis of hypertrophic cardiomyopathy. LVEDD was significantly smaller in the former [10]. Patients at risk for developing increased intracavitary gradients following ventricular unloading had smaller LVEDD [10,19], higher mean transvalvular pressure gradient and increased septal wall thickness [20,21]. Increased in-hospital mortality following surgical aortic valve replacement in these patients has been reported by several authors [10,20,21].
One purported cause for worse clinical outcomes among patients with small LVEDD is the development of an obstructive intracavitary gradient [9,10,17,21]. In our study, the finding that a significant number of these patients developed profound hypotension immediately following successful BAV despite normal ejection fractions, bolsters this hypothesis. In contrast to hypertrophic cardiomyopathy in which asymmetric septal thickening can cause significant mitral regurgitation, the ventricular hypertrophy in aortic stenosis can cause a significant intracavitary gradient, without systolic anterior motion of the mitral valve leaflet or increases in pulmonary capillary wedge pressure [20]. Although we did not specifically assess patients for post-BAV intracavitary gradients, we did find that the left ventricular systolic pressures were higher and the diastolic pressures were lower in patients with small LV chambers compared to patients with larger sized ventricles; a finding that is consistent with an increased intracavitary gradient.
The observation that patients with smaller LVEDD and higher ejection fractions are more likely to develop hypotension following their BAV therefore suggests the presence of impaired LV filling in the context of an increased intracavitary gradient. Small, thickened left ventricles would more likely manifest diastolic dysfunction and as a result, these patients would be more susceptible to becoming hypotensive in response to low filling pressures.
The abnormal intracavitary gradients that develop following aortic valvuloplasty may also be attributable to impaired relaxation of dysfunctional myocardium. Patients with aortic stenosis and underlying hypertrophic cardiomyopathy have been reported [16,17]. It may be difficult to distinguish hypertrophy due to chronic LV pressure loading or hypertrophy due to familial hypertrophic cardiomyopathy with typical concentric left ventricular thickening [22]. Both hypertensive and genetic hypertrophic cardiomyopathies have evidence of abnormal myocardium with impaired relaxation [23,24] and both types can lead to the development of significant intracavitary gradients [25].
The risk of BAV is not insignificant—there was one intraprocedural death in our study, and the overall rate of periprocedural death, myocardial infarction, respiratory, and cardiac arrest was 15.3%, which is similar to that reported in other studies [2,3]. Patients undergoing BAV are frequently older with significant comorbidities [26–28] which inevitably increase the morbidity and mortality of the procedure. Nevertheless, balloon aortic valvuloplasty continues to have a valuable role in the treatment scheme of high-risk patients with severe calcific aortic stenosis (AS). With advent of transcatheter aortic valve implantation, BAV as primary and adjunctive therapy has experienced a major revival [29,30,31]. New techniques have improved the overall safety of BAV, such as rapid ventricular pacing [32], the use of echocardiography for precise balloon sizing [2], peri-procedural percutaneous coronary interventions to reduce ischemic burden [33] and other approaches to avoid vascular complications [34]. In patients with smaller LV chambers, we strongly recommend that patients have adequate preload at the time of BAV and that operators consider responding to hemodynamic compromise after balloon inflation in such patients with fluid resuscitation.
Limitations
For this retrospective study, we cannot fully account for baseline differences, selection biases and different treatment strategies between patients with small versus normal LVEDD. However, the clinical and procedural variables that were recorded were relatively similar between the two groups. Another important limitation is that we did not measure intracavitary gradients routinely, so we would be unable to determine whether the adverse outcomes were due specifically to an obstructive intracavitary gradient. Nevertheless, the adverse outcomes may not merely be due to an obstructive gradient, but may be related to impaired relaxation and myocardial dysfunction, with which a small LVEDD is associated. The patients with small LVEDD also had smaller post-BAV AVA, which has been associated with worse clinical outcomes [35]. When evaluated by multivariate analysis, however, small LVEDD remained a significant predictor of intraprocedural complications while post-AVA did not.
CONCLUSIONS
Patients with small left ventricular chambers (LVEDD < 4.0 cm) have significantly worse intra-procedural and in-hospital outcomes following BAV. Our findings are consistent with the surgical literature suggesting greater morbidity for such patients following aortic valve replacement. It is well accepted that NYHA class, cardiogenic shock and depressed left ventricular function at the time of BAV are associated with adverse in-hospital and long-term outcomes [35–37]. Our findings reaffirm the caveat that patients with small LV chambers undergoing BAV have worse outcomes. As further transcatheter aortic valve technologies develop, LV size should inform decisions about patient selection and help operators to better prevent (such as ensuring a patient has adequate preload) and respond to hemodynamic decompensation.
ACKNOWLEDGEMENTS
Special thanks to Dr. Jesus Herrero-Garibi, Dr. Eugene Pomerantsev, and Dr. David McCarty who contributed significantly to the collection of data for this study.
Grant sponsor: National Center for Research Resources (NCRR); grant number: KL2 RR025015
Footnotes
Conflict of interest: Nothing to report.
REFERENCES
- 1.Eltchaninoff H, Cribier A, Tron C, Anselme F, Koning R, Soyer R, Letac B. Balloon aortic valvuloplasty in elderly patients at high risk for surgery, or inoperable. Immediate and mid-term results. Eur Heart J. 1995;16:1079–1084. doi: 10.1093/oxfordjournals.eurheartj.a061050. [DOI] [PubMed] [Google Scholar]
- 2.Sack S, Kahlert P, Khandanpour S, Naber C, Philipp S, Möhlenkamp S, Sievers B, Kälsch H, Erbel R. Revival of an old method with new techniques: Balloon aortic valvuloplasty of the calcified aortic stenosis in the elderly. Clin Res Cardiol. 2008;97:288–297. doi: 10.1007/s00392-008-0650-0. [DOI] [PubMed] [Google Scholar]
- 3.McKay RG. The mansfield scientific aortic valvuloplasty registry: Overview of acute hemodynamic results and procedural complications. J Am Coll Cardiol. 1991;17:485–491. doi: 10.1016/s0735-1097(10)80120-2. [DOI] [PubMed] [Google Scholar]
- 4.Block P, Palacios I. Clinical and hemodynamic follow-up after percutaneous aortic valvuloplasty in the elderly. Am J Cardiol. 1988;62:760–763. doi: 10.1016/0002-9149(88)91218-0. [DOI] [PubMed] [Google Scholar]
- 5.Agarwal A, Kini AS, Attanti S, Lee PC, Ashtiani R, Steinheimer AM, Moreno PR, Sharma SK. Results of repeat balloon valvuloplasty for treatment of aortic stenosis in patients aged 59 to 104 years. Am J Cardiol. 2005;95:43–47. doi: 10.1016/j.amjcard.2004.08.061. [DOI] [PubMed] [Google Scholar]
- 6.Reeder G, Nishimura R, Holmes DJ. Patient age and results of balloon aortic valvuloplasty: The mansfield scientific registry experience. The mansfield scientific aortic valvuloplasty registry investigators. J Am Coll Cardiol. 1991;17:909–913. doi: 10.1016/0735-1097(91)90873-8. [DOI] [PubMed] [Google Scholar]
- 7.Kastrup J, Wennevold A, Thuesen L, Nielsen T, Kassis E, Fritz-Hansen P, Thayssen P. Short- and long-term survival after aortic balloon valvuloplasty for calcified aortic stenosis in 137 elderly patients. Dan Med Bull. 1994;41:362–365. [PubMed] [Google Scholar]
- 8.Hess OM, Schneider J, Turina M, Carroll JD, Rothlin M, Krayenbuehl HP. Asymmetric septal hypertrophy in patients with aortic stenosis: An adaptive mechanism or a coexistence of hypertrophic cardiomyopathy? J Am Coll Cardiol. 1983;1:783–789. doi: 10.1016/s0735-1097(83)80191-0. [DOI] [PubMed] [Google Scholar]
- 9.Panza JA, Maron BJ. Valvular aortic stenosis and asymmetric septal hypertrophy: Diagnostic considerations and clinical and therapeutic implications. Eur Heart J. 1988;9(Suppl E):71–76. doi: 10.1093/eurheartj/9.suppl_e.71. [DOI] [PubMed] [Google Scholar]
- 10.Aurigemma G, Battista S, Orsinelli D, Sweeney A, Pape L, Cuenoud H. Abnormal left ventricular intracavitary flow acceleration in patients undergoing aortic valve replacement for aortic stenosis. A marker for high postoperative morbidity and mortality. Circulation. 1992;86:926–936. doi: 10.1161/01.cir.86.3.926. [DOI] [PubMed] [Google Scholar]
- 11.Rodriguez A, Kleiman N, Minor S, Zoghbi W, West M, DeFelice C, Samuels D, Cashion R, Pickett J, Lewis J. Factors influencing the outcome of balloon aortic valvuloplasty in the elderly. Am Heart J. 1990;120:373–380. doi: 10.1016/0002-8703(90)90082-9. [DOI] [PubMed] [Google Scholar]
- 12.Suh WM, Witzke CF, Palacios IF. Suicide left ventricle following transcatheter aortic valve implantation. Catheter Cardiovasc Interv. 2010;76:616–620. doi: 10.1002/ccd.22609. [DOI] [PubMed] [Google Scholar]
- 13.Letac B, Cribier A, Koning R, Lefebvre E. Aortic stenosis in elderly patients aged 80 or older. Treatment by percutaneous balloon valvuloplasty in a series of 92 cases. Circulation. 1989;80:1514–1520. doi: 10.1161/01.cir.80.6.1514. [DOI] [PubMed] [Google Scholar]
- 14.Waikar SS, Bonventre JV. Creatinine kinetics and the definition of acute kidney injury. J Am Soc Nephrol. 2009;20:672–679. doi: 10.1681/ASN.2008070669. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Troy BL, Pombo J, Rackley CE. Measurement of left ventricular wall thickness and mass by echocardiography. Circulation. 1972;45:602–611. doi: 10.1161/01.cir.45.3.602. [DOI] [PubMed] [Google Scholar]
- 16.Feizi O, Farrer Brown G, Emanuel R. Familial study of hypertrophic cardiomyopathy and congenital aortic valve disease. Am J Cardiol. 1978;41:956–964. doi: 10.1016/0002-9149(78)90740-3. [DOI] [PubMed] [Google Scholar]
- 17.Brown PS, Jr, Roberts CS, McIntosh CL, Roberts WC, Clark RE. Combined obstructive hypertrophic cardiomyopathy and stenotic congenitally bicuspid aortic valve. Am J Cardiol. 1990;66:1273–1275. doi: 10.1016/0002-9149(90)91120-u. [DOI] [PubMed] [Google Scholar]
- 18.Harrison EE, Sbar SS, Martin H, Pupello DF. Coexisting right and left hypertrophic subvalvular stenosis and fixed left ventricular outflow obstruction due to aortic valve stenosis. Am J Cardiol. 1977;40:133–136. doi: 10.1016/0002-9149(77)90111-4. [DOI] [PubMed] [Google Scholar]
- 19.Wiseth R, Skjaerpe T, Hatle L. Rapid systolic intraventricular velocities after valve replacement for aortic stenosis. Am J Cardiol. 1993;71:944–948. doi: 10.1016/0002-9149(93)90911-u. [DOI] [PubMed] [Google Scholar]
- 20.Bartunek J, Sys SU, Rodrigues AC, van Schuerbeeck E, Mortier L, de Bruyne B. Abnormal systolic intraventricular flow velocities after valve replacement for aortic tenosis. Mechanisms, predictive factors, and prognostic significance. Circulation. 1996;93:712–719. doi: 10.1161/01.cir.93.4.712. [DOI] [PubMed] [Google Scholar]
- 21.Orsinelli DA, Aurigemma GP, Battista S, Krendel S, Gaasch WH. Left ventricular hypertrophy and mortality after aortic valve replacement for aortic stenosis. A high risk subgroup identified by preoperative relative wall thickness. J Am Coll Cardiol. 1993;22:1679–1683. doi: 10.1016/0735-1097(93)90595-r. [DOI] [PubMed] [Google Scholar]
- 22.Karam R, Lever HM, Healy BP. Hypertensive hypertrophic cardiomyopathy or hypertrophic cardiomyopathy with hypertension? A study of 78 patients. J Am Coll Cardiol. 1989;13:580–584. doi: 10.1016/0735-1097(89)90596-2. [DOI] [PubMed] [Google Scholar]
- 23.Kunkel B, Schneider M. Myocardial structure and left ventricular function in hypertrophic and dilative cardiomyopathy and aortic valve disease. Z Kardiol. 1987;76(Suppl 3):9–13. [PubMed] [Google Scholar]
- 24.Iwakami M, Numano F. Regional wall motion abnormalities during early diastole in patients with hypertensive left ventricular hypertrophy: A doppler tissue echocardiographic study. J Med Dent Sci. 2001;48:45–49. [PubMed] [Google Scholar]
- 25.Sgreccia A, Morabito G, Gurgo Di Castelmenardo A, Bernardo ML, Petrilli AC, De Leva R, De Marzio P, Nuccio F, Morelli S. Congestive heart failure in hypertensive patients with normal systolic function and dynamic left ventricular outflow obstruction. Minerva Cardioangiol. 2001;49:99–106. [PubMed] [Google Scholar]
- 26.Don CW, Witzke C, Cubeddu RJ, Herrero-Garibi J, Pomerantsev E, Caldera AE, McCarty D, Inglessis I, Palacios IF. Comparison of procedural and in-hospital outcomes of percutaneous balloon aortic valvuloplasty in patients >80 years versus patients < or =80 years. Am J Cardiol. 2010;105:1815–1820. doi: 10.1016/j.amjcard.2010.01.366. [DOI] [PubMed] [Google Scholar]
- 27.Bernard Y, Etievent J, Mourand J, Anguenot T, Schiele F, Guseibat M, Bassand J. Long-term results of percutaneous aortic valvuloplasty compared with aortic valve replacement in patients more than 75 years old. J Am Coll Cardiol. 1992;20:796–801. doi: 10.1016/0735-1097(92)90174-l. [DOI] [PubMed] [Google Scholar]
- 28.Kapadia SR, Goel SS, Svensson L, Roselli E, Savage RM, Wallace L, Sola S, Schoenhagen P, Shishehbor MH, Christofferson R, Halley C, Rodriguez LL, Stewart W, Kalahasti V, Tuzcu EM. Characterization and outcome of patients with severe symptomatic aortic stenosis referred for percutaneous aortic valve replacement. J Thorac Cardiovasc Surg. 2009;137:1430–1435. doi: 10.1016/j.jtcvs.2008.12.030. [DOI] [PubMed] [Google Scholar]
- 29.Moreno PR, Jang IK, Newell JB, Block PC, Palacios IF. The role of percutaneous aortic balloon valvuloplasty in patients with cardiogenic shock and critical aortic stenosis. J Am Coll Cardiol. 1994;23:1071–1075. doi: 10.1016/0735-1097(94)90592-4. [DOI] [PubMed] [Google Scholar]
- 30.Bonow RO, Carabello BA, Chatterjee K, de Leon AC, Jr, Faxon DP, Freed MD, Gaasch WH, Lytle BW, Nishimura RA, O’Gara PT, O’Rourke RA, Otto CM, Shah PM, Shanewise JS. 2008 focused update incorporated into the acc/aha 2006 guidelines for the management of patients with valvular heart disease: A report of the american college of cardiology/american heart association task force on practice guidelines (writing committee to revise the 1998 guidelines for the management of patients with valvular heart disease). Endorsed by the society of cardiovascular anesthesiologists, society for cardiovascular angiography and interventions, and society of thoracic surgeons. J Am Coll Cardiol. 2008;52:e1–e142. doi: 10.1016/j.jacc.2008.05.007. [DOI] [PubMed] [Google Scholar]
- 31.Cribier A, Eltchaninoff H, Bash A, Borenstein N, Tron C, Bauer F, Derumeaux G, Anselme F, Laborde F, Leon MB. Percutaneous transcatheter implantation of an aortic valve prosthesis for calcific aortic stenosis: First human case description. Circulation. 2002;106:3006–3008. doi: 10.1161/01.cir.0000047200.36165.b8. [DOI] [PubMed] [Google Scholar]
- 32.Witzke C, Don CW, Cubeddu RJ, Herrero-Garibi J, Pomerantsev E, Caldera A, McCarty D, Inglessis I, Palacios IF. Impact of rapid ventricular pacing during percutaneous balloon aortic valvuloplasty in patients with critical aortic stenosis: Should we be using it? Catheter Cardiovasc Interv. 2010;75:444–452. doi: 10.1002/ccd.22289. [DOI] [PubMed] [Google Scholar]
- 33.Pedersen W, Klaassen P, Pedersen C, Wilson J, Harris K, Goldenberg I, Poulose A, Mooney M, Henry T, Schwartz R. Comparison of outcomes in high-risk patients>70 years of age with aortic valvuloplasty and percutaneous coronary intervention versus aortic valvuloplasty alone. Am J Cardiol. 2008;101:1309–1314. doi: 10.1016/j.amjcard.2007.12.033. [DOI] [PubMed] [Google Scholar]
- 34.Cubeddu RJ, Jneid H, Don CW, Witzke CF, Cruz-Gonzalez I, Gupta R, Rengifo-Moreno P, Maree AO, Inglessis I, Palacios IF. Retrograde versus antegrade percutaneous aortic balloon valvuloplasty: Immediate, short- and long-term outcome at 2 years. Catheter Cardiovasc Interv. 2009;74:225–231. doi: 10.1002/ccd.22085. [DOI] [PubMed] [Google Scholar]
- 35.Hamid T, Eichhofer J, Clarke B, Mahadevan VS. Aortic balloon valvuloplasty: Is there still a role in high-risk patients in the era of percutaneous aortic valve replacement? J Interv Cardiol. 2010;23:358–361. doi: 10.1111/j.1540-8183.2010.00559.x. [DOI] [PubMed] [Google Scholar]
- 36.Lieberman E, Bashore T, Hermiller J, Wilson J, Pieper K, Keeler G, Pierce C, Kisslo K, Harrison J, Davidson C. Balloon aortic valvuloplasty in adults: Failure of procedure to improve long-term survival. J Am Coll Cardiol. 1995;26:1522–1528. doi: 10.1016/0735-1097(95)00363-0. [DOI] [PubMed] [Google Scholar]
- 37.Elmariah S, Lubitz SA, Shah AM, Miller MA, Kaplish D, Kothari S, Moreno PR, Kini AS, Sharma SK. A novel clinical prediction rule for 30-day mortality following balloon aortic valuloplasty: The crrac the av score. Catheter Cardiovasc Interv. 2011;78:112–118. doi: 10.1002/ccd.22912. [DOI] [PMC free article] [PubMed] [Google Scholar]