With improvement of the public health environment, rheumatic valvular disease has been declining in the developed world. However, valvular heart diseases have not shown any trend of decreasing, whereas the number of degenerative valvular diseases is increasing. Among the population aged 75 years and over, 12.5% have degenerative valvular disease and 33.9% have valvular aortic stenosis.1,2 Surgical aortic valve replacement (SAVR) remains the gold standard treatment for symptomatic severe aortic stenosis (AS). With appropriate patient selection, SAVR was reported to be associated with a low operative mortality rate.3–5 However, at least 30% of patients with severe AS deteriorated to SAVR because of multiple comorbidities, old age, and poor pulmonary or heart function.6,7 For octogenarians and nonagenarians, SAVR 1-year mortality rate was 13% with high morbidity and prolonged intensive care and hospitalization. The risk can be as high as 25% with comorbid conditions.8–10 Hence, there should be some less invasive alternatives for those who are at risk. Transcatheter aortic valve implantation (TAVI) has been developed in the past decade.8,11,12 According to the currently published results of the Placement of Aortic Transcatheter Valve trial (PARTNER-II), the outcomes between conservative treatment (including medication and percutaneous transluminal balloon aortic valvuloplasty) and TAVI were compared; all had severe AS and were not candidates for SAVR. According to the PARTNER II results, the 1-year mortality rates for conservative treatment and TAVI were 49.7% and 30.7%, respectively.12 In this study, we pioneer the use of the TAVI procedure for treatments in severe symptomatic AS in Taiwan. The acute and short-term results have been delivered in our previously published article.13 The mid-term efficacy and safety were further evaluated with 1-year follow-up, and the acute and mid-term results were also compared to evaluate the applicability and durability of this device.
2.1. Patient selection
Between May 2010 and October 2010, 10 patients received TAVI at our hospital. This trial was approved by the Ethics Committee of Taipei Veterans General Hospital. Informed consent was obtained from all patients. All potential candidates for TAVI were evaluated by a multidisciplinary team that was composed of interventional cardiologists and cardiac surgeons. Patients who were considered to be eligible for TAVI underwent a systematic workup protocol that included Doppler echocardiography, coronary angiography, aortoiliofemoral angiography, and computed tomography. Depending on the size, disease, and degree of calcification of iliofemoral arteries, the patients were selected for treatment by either the transfemoral (TF) approach or the transapical approach (TA). The TF approach was the treatment of choice. The Edwards Sapien valve (Edwards LifeSciences, Irvine, Calif) was used in all cases. The 23 mm valve was implanted if the transesophageal echocardiographic (TEE) measurement of the aortic annulus was between 18 mm and 21 mm, and the 26 mm valve was implanted if the aortic annulus measured between 22 mm and 25 mm. Patients' comorbidities and the related surgical risks were defined with logistic EuroSCORE. The inclusion and exclusion criteria were described as follows.
2.2. Inclusion criteria
Patients who met the following criteria were included: severe and symptomatic AS with aortic valve area (AVA) <1 cm2, mean pressure gradient >40 mmHg, NYHA functional class was above class II, the aortic valve annulus diameter was between 18 mm and 25 mm on echocardiography, the distance between the coronary sinus and annulus was >1 cm, the patients were ≤80 years old, and the patients had a high surgical risk with a logistic EuroSCORE >20%. Each patient was declined by at least two surgeons for surgical aortic valve replacement.
2.3. Exclusion criteria
Patients with bicuspid or non-calcified aortic valve are not suitable for TAVI. Those with an intracardiac tumor, thrombus, or other conditions that require open heart surgery other than aortic stenosis, e.g., untreated coronary arterial disease requiring surgical revascularization, are also excluded. The left ventricular ejection fraction (LVEF) cannot be <20%. The annulus diameter (echo data) should be between 18 mm and 25 mm. The patient should be under a relatively stable condition. Therefore, those with the following conditions were also excluded: acute myocardial infarction within 1 month, acute pulmonary embolism, stoke, or transient ischemic attack (TIA) within 1 month, life expectancy <12 months, or little hope for a meaningful lifestyle. The access route should also be considered; patients with iliofemoral disease, insufficient femoral artery diameter, or aortic dissection were all excluded from the TF approach.
2.4. TAVI procedure
The TAVI procedure was completed in a standard cardiac catheterization room. Under general anesthesia and a sterile environment, the patient was under full monitor, including a cerebral oximeter and transesophageal echocardiography. For the patients who received the TF approach, bilateral femoral arteries were cut down. The brain protection embolic filter (Filter Wire EZ Embolic Protection System, Boston Scientific, USA) was placed via one side of the femoral artery. Then, the standard balloon valvular dilatation was performed. The valve stent was then launched via the other side of the femoral artery. After confirming the annulus site under C-arm fluorometry, the Sapien valve stent was deployed with rapid ventricular pacing. Balloon dilatation was performed again to fit the valve.
As for the TA approach, the embolic protection filter was also placed first via the femoral artery. Then a mini-thoracotomy was performed. The apex was identified, and the standard “box suture” was applied. A guide wire and a sheath were inserted. Balloon valvuloplasty was performed first. Then the Edwards Sapien valve stent was deployed via the sheath over the apex, under rapid ventricular pacing and C-arm fluorometry.
2.5. Outcome evaluation
The efficacy and safety of the TAVI procedure was evaluated immediately postoperative, at 30 days, and at 1 year. Clinical and echocardiographic data were obtained prior to discharge and then monthly.
Patients' demographic data and early procedural outcomes (first 24 hours) were mentioned in our previous article in Acta Cardiologica Sinica13. Among the 10 patients enrolled, the average age was 81.5 years. The mean logistic EuroSCORE was 28.3 ± 7.9. None of the patients had received surgical coronary revascularization, whereas one patient had received surgical mitral valve replacement > 10 years ago. There was no patient with conduction disturbance or a pacemaker preoperatively. The mean LVEF was 61 ± 9%. The mean aortic pressure gradient was 48 ± 16 mmHg. The mean AVA was 0.61 ± 0.19. The procedural success rate reached 100%. There was no periprocedural death, valve embolization, malposition, stroke, or coronary artery obstruction. One acute myocardial infarction developed in the TA group within the first 24 hours, which resulted in right ventricle rupture on postoperative Day 3. No additional endovascular intervention was performed. There was no reported severe aortic regurgitation (>Grade II/IV), major access site and all-cause vascular complication, acute renal failure, new onset aortic regurgitation, or atrial fibrillation. Six transient left bundle branch block (LBBB) developed right after TAVI but resolved within 1 week.
3.1. Short-term outcomes (2–30 days)
No major access site complication developed during this period (Table 1). One patient with chronic renal failure developed acute renal failure, which required long-term hemodialysis. One patient (10%) developed pneumonia and ended up with septic shock on postoperative Day 29. It was the only mortality case within the period. No cerebral vascular events were reported. One patient developed right ventricle (RV) rupture in the TA group. It was suspected that postoperative acute myocardial infarction (AMI) on postoperative Day 3 was the cause. Cardiac tamponade then developed and the patient was sent to the operation room for immediate surgery. The patient recovered without any significant events after RV repair and was discharged on postoperative Day 21.
3.2. Echocardiographic findings
The acute echocardiographic findings are as follows13: at discharge, the mean AVA was 1.42 cm2, mean aortic pressure gradient (MPG) was 11 mmHg, and mean PPG was 18 mmHg (Figs. 1 and 2). At 1-year follow-up, they became 1.2 cm2, 13.2 mmHg, and 10.6 mmHg, respectively. The MPG decreased to 23%, and the PPG decreased to 20% at the 3-month follow-up, but then mildly increased to 28% and 23% at 1-year follow up (p = 0.104), respectively. The AVA increased to 251% from the baseline at the 3-month follow-up but mildly decreased to 197% at 1-year follow-up (p = 0.002). Thirty percent of the patients had moderate to severe AR preoperatively. At discharge, 50% of the patients were free from paravalvular AR. At 3-month follow-up, 70% of the patients had trivial or no AR, and the results remained the same throughout the rest of the year. No patient had AR >2+.
3.3. Mid-term (30 day–1 year) mortality and major morbidity
The all-cause 30-day mortality was 10%, whereas the all-cause 1-year mortality was 20% (Table 2). There was zero cardiovascular mortality at 30-day and 1-year follow-up. No ischemic stroke developed during 1-month follow-up. One patient developed hemorrhagic stroke with brainstem failure, which led to mortality on postoperative Day 173. There was no severe paravalvular AR, conduction disturbance, and myocardial infarction between the 1-month and 1-year follow-up.
SAVR used to be the only effective treatment for severe symptomatic AS. For patients with high surgical risks, balloon aortic valvuloplasty was an alternative option for symptomatic relief, although the long-term durability was not satisfactory and the procedure-related mobility and mortality was too high.10 TAVI was introduced and Cribier and colleagues began applying it to clinical practice in 2002.14 Recently, it was proven that TAVI has a similar 1-year mortality rate as SAVR, but with less bleeding complications in patients who were evaluated to be of relatively high risk for surgery.15 It was reported that the TF approach had a better outcome than the TA approach. Generally speaking, TA patients had higher risks because of the selection bias associated with the delivery approach. The patients selected for the TA approach had a higher incidence for multiple comorbidities and worse vessel conditions.9,16 Webb et al12 reported a reduction in mortality to <4% in the TF cohort. In our study group, the two mortality cases were both treated via the TA approach. According to other single-center studies, 32–52% of the TAVI patients required the TA approach.11,12,17 However, in our study, 60% of the patients received TAVI via the TA approach. Due to the relatively small size of femoral arteries in the Asian population, there is a higher proportion of patients who cannot accommodate the 22/24 French catheter for the 23/26 mm valve. Thus, reducing the catheter profile may definitely increase the number of TF cases.
From previous reports, TAVI allowed treatments for up to 76% of the patients who were previously declined for SAVR.16,17 In our study, the 30-day mortality was 10% (pneumonia with septic shock on postoperative Day 26) and the 1-year mortality was 20% (hemorrhagic stroke with brainstem failure in the 6th month postoperatively). No patient died from cardiovascular complications. In the recently published results of the PARTNER II trial, the 30-day mortality was 5%, whereas the 1-year mortality was 30.7%.2 The cardiovascular 30-day and 1-year mortality in our hospital were both 0%, whereas they were 4.5% and 19.6%, respectively, in the PARTNER II trial. There was one major hemorrhagic stroke in our study, which was not procedural-related.
TAVI has a high procedural success rate of 93.8%.9 Some patients may need multiple valve implantation or conversion to SAVR, due to immediate procedural complications, such as valve embolization, migration, leakage, aortic dissection, or aorta rupture.2,9,18 In our trial, the immediate procedural success rate was 100%. No patient needed reintervention for aortic valve replacement. However, there was one case of AMI on postoperative Day 1, resulting in RV rupture. Emergent reopening of the chest was done for RV repair. The patient was discharged on postoperative Day 21 without major morbidities.
The heart failure symptoms were greatly reduced after TAVI. The average NYHA function class was decreased to Class II after 1-month follow-up. The biomarker for heart failure, NT-proBNP, was also decreased. There was a 56% decline at the 1-month follow-up and 62% at the 1-year follow-up. The mean increase in AVA was 251% on postoperative Day 30, whereas it was 250% in the PARTNER trial. Moreover, the MPG decreased 80.0% in 1-month follow-up, whereas that of the PARTNER trial was 75.1%.2
Vascular complication was also a major consideration. The total vascular complication rate was approximately 12%.19,20 The access-related vascular complication accounted for 72.7% of all vascular complications, especially in the TF group. Major vascular complications may be a prognostic factor of the 30-day mortality of the TA group. However, it was reported that the approach site complication does not affect the 30-day and 1-year mortality of the TF group. There was no distal embolization, femoral artery pseudoaneurysm formation, femoral-iliac artery dissection or rupture, or aortic dissection or rupture. Although one patient from the TF group was accessed by external iliac artery cut-down, due to a relatively small femoral artery diameter, there was no vascular complication. We believe that with careful access site evaluation, patient selection for the TF approach and matured technique, arterial complications, such as local dissection, distal embolization, and major bleeding, can be minimized. The improvement of the device and reduction of the catheter profile may also be beneficial.
Atrioventricular block was another usual complication for TAVI. About 4–7% patients needed a new pacemaker for irreversible atrioventricular block.2,12 In our patient group, six (60%) developed transient LBBB immediately after TAVI. Five of them resolved within 24 M hours, and only one patient had LBBB for 6 days. There was no new-onset atrial fibrillation, advanced atrioventricular block, or RBBB at 3 months. No patient required a permanent pacemaker implantation.
This study showed zero incidence of new-onset moderate to severe paravalvular AR in the patients receiving TAVI. The results were superior to other international clinical trials. The reported new-onset paravalvular AR rate exceeded 10–22% at both the 30-day follow-up and the 1-year follow-up.2,21,22 Aortic regurgitation happened frequently after both SAVR and TAVI. Most of the cases were minor leaks without hemodynamic consequences. Severe AR (>2/4) may lead to LV remodeling and hemolytic anemia and may lead to reintervention.18,22–24 After TAVI, significant AR may be related to prosthesis/annulus discongruence, malpositioning, or severe calcified cusps of the native valve or bicuspid valve.25 The exclusion of bicuspid aortic valve in our trial, detailed evaluation and planning, as well as experienced surgeons, may contribute to the low incidence of paravalvular AR.
Among our patients, 80% had variable degrees of pulmonary diseases. The 30-day mortality was attributed to a pulmonary complication, revealing that the lung condition might be a main predictor for prolonged hospitalization and morbidity. The pulmonary complication mainly resulted from general anesthesia. The morbidity and mortality rate will decrease largely if local anesthetic TAVI becomes applicable with the improvement of device and modification of technique.
The bovine bioprosthetic valve stent performed well within the 1-year follow-up period. There was no valve dysfunction detected during 1-year follow-up. However, it is revealed that the increased AVA after the procedure went down slightly at 1 year (p = 0.002). The transvalvular pressure gradient decrease after TAVI seemed to rebound at 1-year follow up, although the data was statistically insignificant (p = 0.104). The long term durability of the valve should be examined and followed up by further study.
TAVI patients have the potential of being promoted to the high-risk AS patients, who are not suitable for surgery. Our study presented results similar to the international multi-center trial data. However, this is a single-center clinical trial. Further randomized trials with a longer follow-up period and a larger sample size should be carried out for more accurate results of the safety and efficacy of TAVI.
In conclusion, this new technique and the device require greater caution and needs more practice to accumulate sufficient experience. The studied patients were very fragile due to old age and multiple comorbidities. Our results are similar to findings of multi-center trials. Further studies should be carried out on long-term durability and applicability.
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