Among a cohort of TAVR patients with low incidence of significant paravalvular aortic regurgitation, we observed that a low heart rate adjusted diastolic delta was independently associated with increased total mortality compared with a high heart rate adjusted diastolic delta. Aortic regurgitation index, diastolic delta, and pulse pressure were not associated with increased total mortality. Thirty day (2%) and 1-year mortality (15.2%) was low in this cohort of veterans from a single center experience.
As heart rate increases, diastole shortens resulting in higher aortic diastolic pressure and LVEDP. This may help to explain the superiority of the heart rate adjusted diastolic delta as an invasive hemodynamic test in capturing the complex interplay of heart rate and blood pressure. In the absence of significant aortic regurgitation, a low heart rate adjusted diastolic delta may reflect central aorta stiffness and/or an increase in LVEDP from diastolic dysfunction. Increased pulse pressure is a marker for central aorta stiffness. In an observational study of 22,576 patients with hypertension and coronary artery disease, increased pulse pressure was independently associated with increased all-cause mortality (nadir pulse pressure 60 mm Hg) . The reference standard for non-invasively assessing central aorta stiffness is the aortic pulse wave velocity . Increased pulse wave velocity has been independently associated with increased mortality among hypertensive patients with normal pulse pressure (mean pulse pressure 59 mm Hg) . Pulse wave velocity may be an important risk factor among those without established atherosclerotic disease, while the pulse pressure becomes important later in the disease process . Interestingly, TAVR may be superior to surgical aortic valve replacement in preserving aortic elasticity . This could possibly be related to TAVR not resulting in mediastinal scar formation or inflammatory changes within the aorta . At the present time, central aorta stiffness has not been viewed as an important prognostic factor among patients with valvular heart disease. How this condition is best diagnosed and treated are important future questions. For example, these patients may require different heart rate and/or blood pressure targets; however, these concepts would need to be prospectively evaluated.
Early procedural complications are captured with 30-day mortality, while the patient’s overall medical condition and frailty are better reflected in 1-year mortality [17, 18]. From the Society of Thoracic Surgeons/American College of Cardiology/Transcatheter Valve Therapies registry (STS/ACC/TVT), procedural success was documented at 92%, 30-day mortality, 4.6%–7.0%, and 1-year mortality, 21.6%–23.7% [19,20,21]. Despite excellent acute procedural success and low early mortality, late mortality remains quite high nationally. Therefore, ongoing attempts to understand and improve long-term survival are important.
In addition to heart rate adjusted diastolic delta, other independent predictors of total mortality included severe pulmonary hypertension (mean ≥ 45 mm Hg), low SVi (<24 cc/m2), and moderate or greater paravalvular aortic regurgitation. The current incidence of significant paravalvular aortic regurgitation is quite low (<5%–6% incidence of moderate to severe paravalvular aortic regurgitation with the Sapien S3 and Evolut R devices) [21,22,23]. In addition to device improvements, optimal valve implantation by avoiding implants within significant calcification in the left ventricular outflow tract may also be a contributing factor. As the incidence of significant paravalvular aortic regurgitation continues to decline, other patient characteristics will become more important in predicting late mortality. In fact, moderate to severe paravalvular aortic regurgitation was marginally significant in this dataset, which is likely a reflection of limited events for this outcome.
Previous studies have documented low echocardiography-derived SVi (<35 cc/m2) as a significant independent predictor of late mortality [24, 25]. By using receiver operator curve analysis, we determined that <24 cc/m2 provided the best prediction of late mortality. This variable carried the strongest hazard ratio for late mortality among our four retained variables. Low flow predominately affects stage D2 aortic stenosis patients. In such patients, careful determination of the stroke volume through cardiac catheterization may be preferential to echocardiography derived valves. In patients with markedly reduced stroke volume, consideration could be given to optimization of flow before proceeding with TAVR. Examples could include multi-vessel coronary revascularization, restoration of sinus rhythm, cardiac resynchronization therapy, and control of systemic and/or pulmonary hypertension. We preferentially obtained the SVi from the pre-operative valve study, which may help to explain the different cut point from previous studies. Resting pulmonary hypertension has been reported in up to one third of patients with symptomatic aortic stenosis; however, this is usually mild in severity (23% with mild, 8.9% with moderate, and 4.8% with severe pulmonary hypertension) . Severe pulmonary hypertension has been associated with late mortality after TAVR [27, 28]. However, some data suggest a gender effect that places women at disproportionate risk from pulmonary hypertension . Our analysis, in 98% men, suggests that severe pulmonary hypertension may be equally hazardous in men.
Although this is a relatively small dataset, it allows for more detailed variables that are not available in the larger STS/ACC/TVT registry . For example, this allowed us to evaluate the prognostic performance of SVi (predominately derived from catheterization) and heart rate adjusted diastolic delta, which is difficult to obtain on a large scale. SVi was considered from multiple sources, although we preferentially utilized values in the following order (derived from thermodilution cardiac output > derived from fick cardiac output > derived from echocardiogram). This could have decreased the precision of this measurement. Although low heart rate adjusted diastolic delta was retained in the multivariate Cox regression analysis, this predictor was only present in eight patients. Moreover, these hemodynamic indices were obtained in patients who underwent general anesthesia and conscious sedation, which could have resulted in measurement variability. It is possible that the prognostic significance of a low heart rate adjusted diastolic delta was related to unrecognized aortic regurgitation. However, from multiple imaging studies, there was no sign of moderate to severe aortic regurgitation in these patients. Cardiac magnetic resonance imaging might be helpful in selecting patients to evaluate for occult aortic regurgitation . This study applies almost exclusively to men; therefore, any conclusions among women must be cautious.