Transcatheter Aortic Valve Replacement (TAVR): A Clinician’s Perspective Aortic Stenosis: Natural and Unnatural (Treated) History

Fig. 6.1

The natural history of aortic stenosis (AS) is depicted. Following a long asymptomatic period during which survival is nearly normal, mortality rises sharply with the onset of the classic symptoms of angina, syncope, and heart failure (Taken with permission from Ross and Braunwald and modified from [8])

In many years since the publication of these classic data, some aspects of AS have remained the same, while others have changed. Constant in the natural history is the poor prognosis once symptoms develop unless durable relief of outflow obstruction can be achieved [11]. Relief is afforded only by aortic valve replacement. Balloon valvotomy offers palliation but does not alter mortality [11, 12]. A second constant of AS is its progressive nature. Once considered to be a “degenerative” disease, it is now clear that AS is an inflammatory process much akin to atherosclerosis [13]. Inflammation in turn leads to progressive calcification and narrowing of the valve orifice. Not surprisingly, statin therapy, so successful in the treatment of coronary artery disease, was investigated as possibly effective in retarding the progression of AS. While the concept that calcification of the aortic valve in AS can be slowed or reversed is an important therapeutic target, statins failed to achieve the goal of reducing progression of AS [14–16]. Thus, there continues to be no effective medical therapy for AS.

On the other hand two major changes in AS that have occurred over the past 40 years are its usual etiology and consequently the age at onset. The etiologies of AS of the patients comprising the data from 40 years ago were primarily rheumatic heart disease and/or congenital AS. Today calcific atherosclerotic disease is the major cause of AS in developed countries, producing severe disease and thus symptom onset in patients in their 60s, 70s, and 80s as opposed to 40s and 50s [17]. With advancing age comes a host of comorbidities that increase the risk of standard AVR therapy. In turn the older age of AS patients often presents physician and patient with a therapeutic dilemma. Symptomatic AS remains a lethal disease but the usual cure, surgical AVR, may pose too high a risk to perform safely.

Standard Indications for Surgical AVR

The AHA/ACC Guidelines for the Management of Patients with Valvular Heart Disease list only 3 class 1 (general agreement that the procedure is useful and effective) indications for AVR [18]. These are (1) symptomatic severe AS, (2) severe AS with LV dysfunction, and (3) severe AS in a patient undergoing another cardiac operation. Other less certain indications for AVR in asymptomatic patients include a 2a (most would recommend) indication for patients with moderate AS undergoing another cardiac operation [19] and several 2b (may be beneficial) indications: (1) an abnormal response to exercise [20, 21], (2) a heavily calcified valve or proof of rapid progression from frequent observations of valve area over time [22], and (3) very severe AS with an AVA of <0.6 cm [23]. In the past severe left ventricular hypertrophy has also been considered an indication for AVR in asymptomatic patients with severe AS.

These indications for AVR assume that the operation will take place in an otherwise relatively healthy individual. However, as noted above, the typical AS patient today is often aged, and with age comes multiple extra-valvular comorbidities that affect the risk of AVR. This risk can be estimated using a variety of risk calculators based upon the results of thousands of previous operations. One of the most widely used of such instruments is that sponsored by the Society of Thoracic Surgeons (STS). Figure 6.2 demonstrates how collectively adding risk factors affects total operative STS-predicted risk of mortality and morbidity [24]. Even extensive cardiac problems including repeat cardiac surgery, the additional presence of coronary artery disease, and left ventricular dysfunction do not increase the risk of surgical AVR to the point of inoperability. However, when advanced noncardiac disease is added to the mix, surgical mortality increases dramatically such that risk of surgery outweighs its benefit.

Fig. 6.2

Mortality for aortic valve replacement for AS as assessed by STS (see above) risk calculator is shown as various cardiac and noncardiac comorbidities accrue (Taken from Carabello [24])

TAVR

For the practicing clinician considering a patient for AVR, the following clinical scenario may be of particular benefit through the decision-making process:

History of Present Illness: An 82-year-old woman is referred for evaluation of a heart murmur that she has known about for many years. Over the past 6 months, she has noted near syncope when she climbs the stairs to her bedroom in her two-story home. Accordingly, she has limited her activity to a bed to chair existence, living in a downstairs bedroom.
Past Medical History: She has a past history of insulin-requiring diabetes which has resulted in peripheral vascular disease, a remote stroke from which she has fully recovered, and moderately severe kidney disease (creatinine 3.5 mg/dl). She suffered a non-ST segment elevation myocardial infarction 6 years ago.
Physical Examination: Blood pressure was 112/67. Heart rate was 72.
Neck: Carotid upstrokes delayed. Estimated central venous pressure: 7 cm H₂O.
Chest: Clear.
Heart: Apical impulse forceful, 5th interspace, midclavicular line; 3/6 late-peaking SEM radiating to the neck.
Extremities: Pedal pulses absent; no edema.
Echocardiography: Severe aortic stenosis; aortic valve area 0.7 cm [2], mean gradient 55 mmHg. Ejection fraction 0.45.
Coronary Angiography: Non-obstructive disease of the left coronary artery; chronic total right coronary occlusion.
STS Mortality Risk Score: 19; risk of morbidity and mortality 41.

The patient presented above represents a common conundrum in the treatment of patients with AS. With advancing age she has also developed extra-cardiac diseases that have added substantially to the risk of a standard AVR. Further, even if she survived surgery, prolonged hospitalization due to complications or discharge to a rehabilitation center to treat her deconditioning and other medical problems might vitiate the potential benefit to surgical AVR. Indeed these negative consequences of AVR in such patients have relegated many such patients to the inevitable downward spiral of untreated AS as shown in Fig. 6.1.

The advent of the transcatheter aortic valve replacement (TAVR) now offers a less invasive approach to aortic valve replacement [11, 25, 26]. Instead of requiring open heart surgery and extracorporeal circulatory support, AVR is provided by deployment of a stented bioprosthesis via catheter manipulation from the arterial tree to the aortic annulus or transapically, through the left ventricle. The two TAVRs available in the USA are the Edwards Sapien valve (available commercially) and the Medtronic’s CoreValve (in clinical trials). The Edwards valve is approved (as of this writing) in the USA for use only from the transfemoral and transapical approach in inoperable and those at very high surgical risk. The valve has also been deployed from other arterial sites in clinical trials here and commercially in Europe where general use was approved several years ago.

Approval in the USA was largely predicated upon the success of the PARTNER trial (Fig. 6.3) [11, 25, 26] that showed a large survival benefit of TAVR over medical therapy. In a second arm of the trial, TAVR proved equal in survival to standard AVR in high risk but operable patients. Initially there appeared to be an increased risk of stroke for TAVR. This risk persisted for 1 year after valve replacement, but stroke rate equalized after 2 years because of increased late risk in the surgical group [26]. Importantly TAVR not only increased survival but also relieved symptoms and enhanced the quality of life.

Fig. 6.3

(a) Death from any cause, (b) cardial death, (c) all cause mortality or hospitalization, (d) all cause mortality or major stroke. Data from the PARTNER trial comparing outcome with TAVR versus “medical therapy” showing striking benefit for TAVR are shown (Taken from Leon et al. [11])

Thus, the clinician treating the AS patient previously thought to be inoperable now has a safer less invasive option that is truly a “game changer.”

Effects of TAVR on Aortic Stenosis Therapy

The availability of TAVR obviously provides a novel effective alternative to surgical AVR for treating AS. However, the effects of TAVR go beyond the procedure itself. It has revived an interest in AS and its therapy. It has been estimated that half of patients with severe AS never receive AVR because they or their physicians think they are too ill or too old for surgery [27, 28]. TAVR has brought many of these previously untreated patients to medical attention. In many cases such patients turn out to be excellent candidates for surgical AVR despite their advanced years because age by itself is only a modest contributor to surgical risk (Fig. 6.2). The net effect is that between TAVR and surgical AVR, many more patients can now benefit from mechanical relief of AS.

Pitfalls to Be Overcome

Access and Delivery

Extensive use of TAVR in Europe and elsewhere gives some insight as to the immediate future of TAVR in the USA. In Europe over 60,000 valves roughly split between the CoreValve and the Edwards Sapien valve have been implanted from the femoral, transaxillary, transfemoral, and transaortic routes. While the Edwards delivery system is through a 24 or 28 F sheath in the USA, smaller delivery systems employing 18 F devices are use in Europe. Obviously the smaller the delivery device that can be used, the easier and more applicable the procedure becomes. Additionally the valve sizes available in the USA include only 23 and 26 mm diameter housings that then must fit into a given patient’s aortic annulus. Larger annuli may prevent the valve from seating properly, leading either to paravalvular aortic regurgitation or valve embolization. Smaller annuli may prevent valve deployment or lead to annular rupture. The technical development of more valve sizes will also increase applicability to more patients.

Only gold members can continue reading. Log In or Register to continue