Current Results of Balloon Aortic Valvuloplasty in High-Risk Patients

The initial interest in the late 1980s in balloon aortic valvuloplasty (BAV) for adults with calcific aortic stenosis (AS) was subsequently tempered by multiple studies demonstrating high rates of restenosis and lack of a favorable impact on long-term survival.^1–3 Currently, few centers have continued to perform BAV regularly, and the number of operators trained in performing BAV has dramatically fallen. With the development of percutaneous valve replacement therapies, there has been a resurgence in BAV.^4,5 A technically-successful BAV is required for delivery of the catheter-mounted valve conduit in all of the percutaneous aortic valves currently being developed and investigated. It is likely that the initial population studied for percutaneous aortic valve replacement will be those at high risk for surgical valve replacement due to comorbid conditions. These patients would be expected to be quite similar to those who have been previously treated as nonsurgical-option BAV candidates. A thorough, contemporary description of the outcomes of such a patient group undergoing BAV would be an important step toward understanding some of the technical and clinical obstacles to percutaneous aortic valve replacement. In this report, we describe our experience with a contemporary series of patients undergoing BAV who were deemed unsuitable surgical candidates. Methods From January 2000 to January 2006, 80 consecutive patients with severe symptomatic AS who were declined surgery due to high-risk features underwent BAV at Good Samaritan Hospital in Los Angeles, California. Patients were referred for BAV for palliation of heart failure symptoms, treatment of cardiogenic shock and as a bridge to noncardiac surgery. Clinical features deemed to be responsible for high surgical risk included advanced age, cardiogenic shock, severe left ventricular dysfunction, severe lung disease and underlying malignancy. Eighty patients underwent 104 BAV procedures and were followed for a mean of 3 ± 2 years. Thirteen patients underwent 2 BAV procedures, 2 patients underwent 3 BAV procedures and 1 patient underwent 5 BAV procedures. Patients included in the study were greater than or equal to 60 years of age, had clinical symptoms secondary to severe AS, and had an aortic valve area of less than or equal to 1.0 cm² and/or a mean transaortic gradient greater than or equal to 30 mmHg by cardiac catheterization. Patients with more than moderate aortic regurgitation were excluded. Data collection. Patients were identified from the Good Samaritan Hospital Cardiac Catheterization database. Hemodynamic and procedural results were obtained from review of the cardiac catheterization reports and hospital records. In-hospital clinical events were determined from review of the medical records. Mortality data were obtained through the National Social Security Death Index (www.ssdi.rootsweb.com). Cardiogenic shock was defined as cardiac index 2, pulmonary capillary wedge pressure > 20 mmHg and/or requiring pressor support. The EuroSCORE was calculated using an online calculator (wwww.euroscore.org), as described by Nashef et al.⁶Procedural details. BAV was performed according to standard techniques via the retrograde femoral approach in all patients. An 8 Fr sheath was initially placed in the right femoral artery. Prior to BAV, a 7 Fr Swan-Ganz catheter (Edwards Life Sciences, Irvine, California) was advanced to the pulmonary capillary wedge position and measurements were recorded at the right atrium, right ventricle and pulmonary artery. Cardiac output was measured by the thermodilution method. The aortic valve was crossed using a 0.038 inch straight guidewire and either a pigtail or an Amplatz Left 1 catheter. Simultaneous left ventricular and aortic pressures were measured and the aortic valve area was calculated using the Gorlin Equation. A 0.038 inch wire with a large-radius distal curve was exchanged into the left ventricle. After anticoagulation with 5,000–7,000 units of heparin, the 8 Fr sheath within the right femoral artery was removed, and BAV was done in a sheathless manner over the 0.38 inch wire using 20–25 mm balloons (Z-Med, Numed Inc.). Full balloon expansion within the aortic valve plane was required before progressively larger balloon sizes were used, and the mean balloon size was 20 ± 2.0 (Table 3). One to three inflations were performed until the transaortic gradient was reduced to 1/3 of baseline and the mean number of inflations was 2 ± 1 (Table 3). The gradient across the aortic valve area was then reassessed and the final aortic valve area calculated using the Gorlin Equation. A 9 or 10 Fr sheath was placed within the femoral artery and the sheath was removed following the procedure when the activated clotting time (ACT) was Statistical analysis. Categorical data are expressed as numbers and percentages, and continuous values are expressed as mean ± standard deviation. A Kaplan-Meier curve was constructed to evaluate cumulative survival rates for the entire cohort of patients. Cox proportional hazards regression was used to assess whether potential patient characteristics and variables were related to mortality. A hazard ratio > 1 corresponds to a greater risk of death. A p-value of Patient characteristics. The mean age of the study group was 81 ± 10 years, and 23% were greater than or equal to 90 years of age. Women accounted for 55%, 91% had a history of hypertensive and 88% had a history of hypercholesterolemia (Table 1). Presenting symptoms consisted mainly of refractory congestive heart failure (95%). Angina was present in 29% of patients, and syncope in 21%. Among those with congestive heart failure, 60% were classified as NYHA Class IV. Cardiogenic shock was present in 20% of patients on arrival to the cardiac catheterization laboratory. By echocardiography, the ejection fraction was 30% in 38% of the study group. Comorbid conditions are listed in Table 2. Chronic renal insufficiency (defined as a glomerular filtration rate Indications for BAV. The main indication for BAV was critical AS in patients at high risk for surgical mortality. Ninety-seven of the 104 procedures (93%) were therefore classified as Class IIb indication by American College of Cardiology/American Heart Association guidelines.⁷ Five patients underwent BAV as a bridge to noncardiac surgery, also a Class IIb indication. Two patients required BAV before hip surgery, 2 patients before vascular surgery and 1 patient before a radical nephrectomy. Five patients underwent BAV as a bridge to surgical aortic valve replacement, currently a Class IIa indication. Twenty-one patients (20%) were in cardiogenic shock at the time of BAV, including 2 who were pregnant at the time of the procedure. Procedural results. There was a significant decrease in peak and mean transaortic valve gradient from 57 ± 21 to 31 ± 15 mmHg and from 51 ± 18 to 23 ± 12 mmHg, respectively, following BAV (p 2 (p p 2 respectively; p = NS. Procedural complications. There were no procedural deaths and no patients developed severe aortic regurgitation following BAV. One patient (1%) developed a stroke during the procedure, and there were no cases of left ventricular perforation. There were 9 (9%) total vascular complications, including 3 (3%) hematomas, 2 (2%) pseudoaneurysms and 3 (3%) patients required a blood transfusion. One patient (1%) underwent surgical repair for a pseudoaneurysm. Outcome data. During a mean follow-up period of 88.95 person-years (PY), there were 50 deaths. The median survival time from the first BAV procedure was 378 days (95% CI: 226 to 664). In-hospital and 30-day mortality rates were 6% and 12%, respectively. One-, two- and three-year mortality rates were 44%, 62% and 71%, respectively. The Kaplan-Meier survival curve is shown in Figure 1. Clinical variables that showed the strongest trend toward an increased risk of mortality were: (1) need for ventilator support and pressor support (OR 1.66, 95% CI 0.88–3.11; p = 0.12), and (2) chronic renal insufficiency (OR 1.47, 95% CI 0.75–2.87; p = 0.27). Patients receiving hemodialysis (n = 13, 13%) had a significantly higher 30-day mortality compared to those not receiving hemodialysis, 40% vs. 12%, respectively; p = 0.01. Multiple BAV procedures. Seventeen patients (21%) underwent repeat BAV procedures with a mean time between procedures of 9 months. There was 1 in-hospital death in this subgroup, and 3 other patients died within 6 months of the index procedure. Of the 2 patients who underwent 3 BAV procedures, 1 died within 6 months. One patient underwent 5 BAV procedures and survived for approximately 4 years after the initial procedure. There were 39 deaths during 69.5 PY of follow up with a single BAV, or 39/69.5 = 0.561 deaths per PY. There were 11 deaths during 19.5 PY of follow up with multiple BAV, or 11/19.5 = 0.564 deaths per PY. Patients who underwent multiple BAV procedures had similar mortality to patients with a single procedure, suggesting that repeat procedures may be a viable option for patients awaiting more definitive treatment such as surgical or percutaneous valve replacement. Discussion Surgical aortic valve replacement for symptomatic AS is the only accepted treatment option with a long-term mortality benefit. However, surgery can have an operative mortality of up to 50% in high-risk patients.⁸ BAV has therefore evolved into a palliative procedure for patients with high operative risk, and is now used in selective centers as a temporizing measure to improve the quality of life and stabilize patients for either definitive aortic valve replacement or noncardiac surgery. In addition, it remains unclear if there is a survival advantage in older patients and octogenarians undergoing aortic valve replacement. In the future, BAV may be more widely used during percutaneous valve replacement therapies. Our current series found similar short- and long-term survival rates to prior studies (Table 4). Procedural mortality in our series was 0%, which compares favorably to larger series such as the NHLBI aortic valvuloplasty registry 9 (3%), and the Mansfield registry (5%).¹⁰ Lieberman et al reported a 3-year survival rate of 18% in 165 patients after single BAV.¹¹ Aggarwal et al reported a 3-year survival rate of 28% in patients who underwent multiple BAV procedures, which was better than previous studies.¹² Our study population included 20% with cardiogenic shock, which is significantly higher than prior studies. In the study by Aggarwal et al,¹² only 5% were in cardiogenic shock. We attempted to identify patient characteristics and variables that were associated with increased mortality during follow up. While the need for ventilator and pressor support and chronic renal insufficiency showed a trend for increased risk of mortality, they did not reach statistical significance, most likely related to small patient numbers. Few recent studies have addressed procedural complications and short- and long-term outcomes of BAV.12,13 Given that patients are living longer because of advances in cardiovascular care and medical therapy, it would be anticipated that current patients undergoing BAV would be of much higher risk with more advanced age and comorbid conditions compared to the initial studies.¹⁰ Therefore, we feel our study adds to the current literature and complements other recent studies by further characterizing the contemporary outcome of these high-risk patients treated in another tertiary medical center. In an attempt to assess the overall risk of patients in this series, we applied the EuroSCORE as initially described by Nashef et al.^6,14 This scoring system was developed using 13,302 patients and validated in 1,479 patients and provides a simple and objective method to assess risk in patients undergoing cardiac surgery. Our average EuroSCORE was 16.2 ± 5, and 98% had a high-risk score (defined as EuroSCORE > 6). The two largest series describing percutaneous aortic valve replacement were published in 2006.^15,16 Cribier et al treated 36 no-option patients in France with an equine pericardial valve sewn into a balloon-expandable, stainless-steel stent.¹⁵ The average EuroSCORE in this cohort was 12 ± 2, with 27/36 (75%) patients undergoing a successful implant. Webb et al treated 18 similar no-option patients in Canada with the same percutaneous valve and achieved successful device implantation in 14/18 (78%).¹⁶ The average EuroSCORE in this cohort was 11 ± 2. The acuity of the patients presented in our current series is therefore higher than that encountered in the initial trials of percutaneous valve replacement. In recent years, there have been two major advances in the technique of BAV: (1) the use of suture-mediated closure devices to reduce vascular complications, and (2) a novel antegrade transseptal approach using the Inoue balloon. In 2000, Marchant et al described the use of a suture-mediated closure device with deployment of the sutures prior to intervention — the so-called “preclose technique”.¹⁷ This resulted in removal of the sheath immediately following the procedure with excellent hemostasis and no vascular complications in a small series of 4 patients. Solomon et al later evaluated 31 patients using the “preclose technique” and found shorter length of hospital stay and a lower need for blood transfusions compared to patients receiving manual compression.¹⁸ The second major advance in the performance of BAV was described in 2005 by Sakata et al.¹⁹ In this study, the authors used an antegrade transseptal approach with the Inoue balloon in a series of 71 high-risk surgical patients. The acute hemodynamic results of the antegrade approach were compared to a group of similar patients treated with the traditional retrograde approach. The antegrade approach achieved more favorable acute hemodynamic results with a larger increase in aortic valve area compared to the retrograde approach. In addition, the authors found that use of the venous system to accommodate the large valvuloplasty balloons and the stability of the Inoue balloon within the aortic valve annulus were additional benefits of this new technique. All of the patients in the current series were refused surgery because of high-risk features. In the surgical literature, a number of studies have tried to address the issue of why elderly patients with AS are refused surgery. In 1999, Bouma et al published a paper entitled “To operate or not on elderly patients with aortic stenosis: The decision and its consequences”.²⁰ The authors studied 205 consecutive patients with AS without serious comorbidity and found that only 59% were actually offered surgery. Those undergoing surgery had a much higher survival than those treated medically at 3 years, 80% compared with 49%, respectively. More recently, Iung et al evaluated 216 patients with severe, symptomatic AS in the Euro Heart Survey and found that 33% did not receive surgery.²¹ Factors associated with not receiving surgery included older age and left ventricular dysfunction. While a variety of models have been developed to aid clinical decision making in elderly patients with AS, proceeding with surgery remains a complicated and difficult process.²² Given that the long-term survival of patients undergoing BAV in the current series was poor, surgical aortic valve replacement may have been a better option for those patients who could have survived the high operative mortality risk. This remains speculative, however, given that all of the patients in the current series were refused surgery.

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