TAVI -part 2

Transcatheter aortic valve replacement (TAVR) techniques are rapidly evolving, and results of published trials suggest that TAVR is emerging as the standard of care in certain patient subsets, and a viable alternative to surgery in others.

Comparison to medical therapy in inoperable patients — Evidence of a benefit of TAVR compared to standard medical care was provided by the PARTNER multicenter trial (cohort B) [. The investigators randomly assigned 358 patients with aortic stenosis who were not considered surgical candidates to either standard therapy including balloon aortic valvotomy or TAVR with an Edwards SAPIEN valve via transfemoral approach. The two treatment groups were similar, although the logistic EuroSCORE was slightly lower in the TAVR group (mean 26.4 versus 30.4).

The following findings were noted:

• At one year, the mortality rate was reduced with TAVR compared to medical therapy including balloon aortic valvotomy (30.7 versus 50.7 percent). The rate of the composite end point of death or repeat hospitalization was also reduced with TAVR (42.5 versus 71.6 percent).
• At two years, the mortality rate was 43.4 percent with TAVR compared to 68 percent for medical therapy.
• Among survivors at one and two years, functional class was better with TAVR versus medical therapy (75 versus 42 percent in NYHA functional class I or II at one year).
• The stroke rate was significantly higher in the TAVR group than in the medical therapy group at 30 days (6.7 versus 1.7 percent) and at two years (13.8 versus 5.5 percent).
• In the medical therapy group, balloon aortic valvotomy was performed in 82.3 percent at one year and in 85.3 percent at two years. Moderate or severe transvalvular aortic regurgitation was observed in 16.9 percent at 30 days and 15.2 percent at one year.
• In the TAVR group, moderate or severe paravalvular aortic regurgitation was identified in 11.8 percent at 30 days and in 10.5 percent at one year. Moderate or severe transvalvular aortic regurgitation was observed in 1.3 percent at 30 days and 4.2 percent at one year.
• Of note, TAVR improved survival in patients with an STS score of <15 percent but not in those with an STS score ≥15 percent.

Comparison to surgical therapy — The 699 patients in cohort A of the PARTNER trial were randomly assigned to undergo either TAVR (by transfemoral or transapical approach) or surgical aortic valve replacement . The following findings were noted:

• Mortality rates in the TAVR and surgical group were similar at 30 days (3.4 and 6.5 percent, p = 0.07), one year (24.3 and 26.8 percent), and two years (33.9 and 35.0 percent).
• Combined strokes or transient ischemic attacks were more frequent after TAVR than after surgical aortic valve replacement at 30 days (5.5 versus 2.4 percent, p = 0.04) and at one year (8.7 versus 4.3 percent, p = 0.04) with a borderline significant difference at two years (11.2 versus 6.5 percent, p = 0.05).
• More patients undergoing TAVR reported symptom improvement at 30 days, but at one year symptom improvement was similar in the two groups.
• Differences in other 30-day adverse event rates were also observed:
• TAVR was associated with more frequent major vascular complications (11.0 versus 3.2 percent).

• Surgical aortic valve replacement was associated with more frequent major bleeding (19.5 versus 9.3 percent) and new-onset atrial fibrillation (16.0 versus 8.6 percent).

• Moderate or severe paravalvular aortic regurgitation was more frequent after TAVR than after surgery at 30 days, one and two years (6.9 versus 0.9 percent at two years). The presence of paravalvular aortic regurgitation was associated with increased late mortality as discussed below.

Observational data

Early outcomes

For retrograde approach — Early outcomes were reported following retrograde replacement of the Edwards SAPIEN valve between November 2007 and January 2009 in 463 patients (mean age 82 years) with high estimated surgical risk (mean logistic EuroSCORE 26)

The following findings were noted:

• Procedural success was 95 percent.
• Procedural outcomes included conversion to open aortic valve replacement surgery in 1.7 percent, valve-in-valve replacement (a SAPIEN valve placed within a SAPIEN valve) due to malposition or moderate/severe aortic regurgitation after placement of the first SAPIEN valve in 0.6 percent, greater than moderate (2+) aortic regurgitation in 1.6 percent, coronary obstruction in 0.7 percent, and transfusion was required in 9.9 percent.

Major complications at 30 days included death (6.3 percent), stroke (2.4 percent), renal failure requiring dialysis (1.3 percent), and heart block resulting in permanent pacemaker implantation (6.7 percent). Vascular complications included access-related complications (17.9 percent), aortic dissection (1.9 percent), and non-access-related complications (1.1 percent).

In an echocardiographic study of 88 patients undergoing retrograde Cribier-Edwards or Edwards SAPIEN valve implantation, the mean transaortic valve gradient fell from a preprocedure baseline of 39±14 mmHg to 9±3 mmHg one day after the procedure and was 11±4 two years later .

Similar results were found in a multicenter study of retrograde implantation of a self-expanding stent valve (CoreValve) in 646 patients (mean age 81) with a mean logistic EuroSCORE of 23 :

• Procedure success was 97 percent and the mean transaortic valve gradient decreased from 49 to 3 mmHg.
• Procedural outcomes included death in 1.5 percent, conversion to open aortic valve replacement surgery in 0.5 percent, and implantation of a second valve (including valve-in-valve) in 2.6 percent. Paravalvular regurgitation was common but usually mild and not more than moderate.

At 30 days, mortality was 8 percent, heart block was treated with permanent pacemaker implantation in 9.3 percent, myocardial infarction occurred in 0.6 percent, and stroke occurred in 1.9 percent.

For transapical approach — The following early outcomes were reported following transapical implantation of the Edwards SAPIEN valve in 575 patients (mean age 81 years) with logistic EuroSCORE of 29

The valve prosthesis was implanted successfully in 93 percent with a 3.5 percent rate of conversion to open surgery. The early incidence of greater than moderate (2+) aortic regurgitation was 2.3 percent.

• At 30 days, major complications included death (10.3 percent), stroke (2.6 percent), major vascular complication (2.4 percent), myocardial infarction (0.7 percent), need for dialysis (7.1 percent), pacemaker implantation (7.3 percent), and bleeding requiring reoperation (2.1 percent).
• Outcomes for 100 patients undergoing transapical aortic valve implantation (mean age 83, mean logistic EuroSCORE 29) were comparable to those for 100 propensity-matched controls undergoing conventional aortic valve replacement (mean age 82, mean EuroSCORE 30) . Transapical aortic valve implantation was successful in 97 patients, and three patients required conversion to open surgery. There were no strokes in the transapical group and two strokes in the conventional group. The mortality rates for the transapical and conventional surgery groups were similar: 10 and 15 percent at 30 days and 27 and 31 percent at one year.

In a Canadian multicenter study of 339 adults with severe AS and high surgical risk, the Edwards Sapien valve was implanted by either the retrograde transfemoral approach or the antegrade transapical approach. The procedural success rate was 93 percent. Mortality at 30 days was 10.4 percent (9.5 percent for transfemoral and 11.3 for transapical approach). At one year, mortality was 25 and 22 percent in those treated with the transfemoral versus transapical approach. Predictors of cumulative late mortality were sepsis, need for hemodynamic support, pulmonary hypertension, chronic obstructive pulmonary disease, and chronic kidney disease. Compared to the rest of the cohort, outcomes were no different in adults with a heavily calcified proximal aorta (porcelain aorta) and those with frailty, conditions that were postulated to indicate higher risk .

A valve-in-valve procedure involves catheter-based valve implantation inside an already implanted bioprosthetic valve. This approach may provide an alternative to replacement of a degenerated surgically-implanted valve, or a means of salvaging suboptimal implantation of a catheter-based valve during the initial implantation procedure.

Preliminary reports have demonstrated the feasibility of transcatheter placement of a prosthetic valve within a degenerated bioprosthetic valve. As an example, valve-in-valve implantation was performed on 24 high-risk patients with aortic (n = 10), mitral (n = 7), pulmonary (n = 6), or tricuspid (n = 1) failed (stenotic and/or regurgitant) bioprostheses . Implantation was unsuccessful for one (mitral) case. There were no deaths during the procedure. There was one stroke and one death in 30 days; the death was related to attempted transseptal mitral positioning. The NYHA functional class improved from 88 percent in class III or IV at baseline to 88 percent in class I or II at last follow-up.

Valve-in-valve implantation has been used to salvage suboptimal initial transcatheter aortic valve implantation and significant paravalvular aortic regurgitation . In a series using Edwards SAPIEN valves, valve-in-valve implantation was performed in 0.6 percent of 463 retrograde procedures and 3.3 percent of 575 transapical antegrade procedures. In a series of 646 retrograde CoreValve procedures, moderate to severe aortic regurgitation during the implantation procedure was treated with balloon re-dilatation (in 21.2 percent of procedures) and/or valve-in-valve placement (in 2.6 percent) . None of the 628 patients with successful CoreValve implantation had greater than moderate aortic regurgitation.

One and two year outcomes — Longer term outcomes are illustrated by the following reports from multicenter registries:

One year outcomes were reported for 1038 patients from 32 centers in the European Edwards SAPIEN registry . Patients treated with the transapical approach (n = 575) have greater frequency of comorbidities and higher logistic EuroSCORE (29 versus 25.8 percent) compared to those treated with the transfemoral approach.

• One year mortality rates were 27.9 and 18.9 percent for transapical and transfemoral patients, respectively.
• Multivariable analysis identified logistic EuroSCORE, renal disease, liver disease, and smoking as the variables with the highest hazard ratios for one year mortality.

Early and two-year outcomes were reported for a multicenter cohort of 126 patients with symptomatic severe aortic stenosis who received the CoreValve between 2006 and 2008 . The mean logistic EuroSCORE was 23 percent. The cohort was retrospectively classified into moderate surgical risk (54 patients), high-risk operable (51 patients), and high-risk inoperable (21 patients) groups.

• The technical success rate was 83.1 percent. Thirty-day mortality was 15.2 percent without significant differences in the subgroups. Of note, this study started enrollment before other studies  and the lower observed technical success rate as well as higher early mortality rate are likely largely due to learning curve issues.
• At two years, mortality was 38.1 percent with a significantly higher mortality in the combined high-risk groups as compared to the moderate-risk group (45.8 versus 27.8 percent).
• Functional class improved in 80 percent of patients and remained stable at two-year follow-up. The mean aortic valve gradient was unchanged at two-year follow-up (8.5 at 30 days and 9.0 at two years).

The United Kingdom registry reported outcomes of two years for 870 patients undergoing 877 TAVR procedures (with a CoreValve or SAPIEN valve) from 2007 through 2009 . The mean logistic EuroSCORE was 18.5 percent.

• The procedural success rate was 97 percent. Thirty-day mortality was 7.1 percent. The in-hospital stroke risk was 4.1 percent.
• Mortality was 21.4 percent at one year and 26.3 percent at two years. There was no difference in mortality between the CoreValve and SAPIEN groups.
• In a multivariate model, the independent predictors of mortality were left ventricular ejection fraction <30 percent, the presence of moderate to severe aortic regurgitation, and chronic obstructive pulmonary disease.

Risk factors for early and late mortality were identified in a study of 663 patients undergoing TAVR with a CoreValve . Intraprocedural mortality was 0.9 percent. Mortality was 5.4 percent at 30 days and 15 percent at one year. Independent predictors of mortality at 30 days included certain procedural complications (conversion to open heart surgery, cardiac tamponade, major vascular or access site complications) as well as baseline characteristics (left ventricular ejection fraction <40 percent, prior balloon valvuloplasty, and diabetes mellitus). Independent predictors of mortality between 30 days and one year included prior stroke, postprocedural paravalvular leak ≥2+, prior acute pulmonary edema, and chronic kidney disease.



expert consensus document on transcatheter aortic valve replacement
http://www.sciencedirect.com/science/article/pii/S0735109712000022

Comparison of three methods of assessing cardiovascular disability

Class	New York Heart Association functional classification[1]	Canadian Cardiovascular Society functional classification[2]	Specific activity scale[3]
I	Patients with cardiac disease but without resulting limitations of physical activity. Ordinary physical activity does not cause undue fatigue, palpitation, dyspnea, or anginal pain.	Ordinary physical activity, such as walking and climbing stairs, does not cause angina. Angina with strenuous or rapid prolonged exertion at work or recreation.	Patients can perform to completion any activity requiring ≥7 metabolic equivalents, eg, can carry 24 lb up eight steps; do outdoor work (shovel snow, spade soil); do recreational activities (skiing, basketball, squash, handball, jog/walk 5 mph).
II	Patients with cardiac disease resulting in slight limitation of physical activity. They are comfortable at rest. Ordinary physical activity results in fatigue, palpitation, dyspnea, or anginal pain.	Slight limitation of ordinary activity. Walking or climbing stairs rapidly, walking uphill, walking or stair climbing after meals, in cold, in wind, or when under emotional stress, or only during the few hours after awakening. Walking more than two blocks on the level and climbing more than one flight of ordinary stairs at a normal pace and in normal conditions.	Patients can perform to completion any activity requiring ≤5 metabolic equivalents, eg, have sexual intercourse without stopping, garden, rake, weed, roller skate, dance fox trot, walk at 4 mph on level ground, but cannot and do not perform to completion activities requiring ≥7 metabolic equivalents.
III	Patients with cardiac disease resulting in marked limitation of physical activity. They are comfortable at rest. Less than ordinary physical activity causes fatigue, palpitation, dyspnea, or anginal pain.	Marked limitation of ordinary physical activity. Walking one to two blocks on the level and climbing one flight in normal conditions.	Patients can perform to completion any activity requiring ≤2 metabolic equivalents, eg, shower without stopping, strip and make bed, clean windows, walk 2.5 mph, bowl, play golf, dress without stopping, but cannot and do not perform to completion any activities requiring >5 metabolic equivalents.
IV	Patient with cardiac disease resulting in inability to carry on any physical activity without discomfort. Symptoms of cardiac insufficiency or of the anginal syndrome may be present even at rest. If any physical activity is undertaken, discomfort is increased.	Inability to carry on any physical activity without discomfort - anginal syndrome may be present at rest.	Patients cannot or do not perform to completion activities requiring >2 metabolic equivalents. Cannot carry out activities listed above (Specific activity scale III).

References:

1. The Criteria Committee of the New York Heart Association. Nomenclature and Criteria for Diagnosis of Diseases of the Heart and Great Vessels, 9th ed, Little, Brown & Co, Boston, 1994. p.253.
2. Lucien C. Grading of angina pectoris. Circulation 1976; 54:5223.
3. Goldman L, Hashimoto B, et al. Comparative reproducibility and validity of systems for assessing cardiovascular functional class: Advantages of a new specific activity scale. Circulation 1981; 64:1227