Author + information
- Published online April 1, 2019.
- Mackram F. Eleid, MD∗ ()
- ↵∗Address for correspondence:
Dr. Mackram F. Eleid, Department of Cardiovascular Medicine, Mayo Clinic, 200 1st Street SW, Rochester, Minnesota 55905.
- aortic stenosis
- recovery of right ventricular function
- right ventricular function
- transcatheter aortic valve replacement
Aortic valve replacement is considered to be a life-saving treatment for patients with isolated severe symptomatic aortic stenosis. The development of transcatheter aortic valve replacement (TAVR) in the last decade has led to dramatic changes in the treatment of this condition. Patients at intermediate or higher risk for surgical aortic valve replacement now routinely undergo TAVR instead of open heart surgery, benefitting not only from elimination of aortic valve obstruction but also from the minimally invasive nature of the procedure. Despite remarkable advances achieved with TAVR, some patients, particularly those with multiple comorbidities in addition to aortic stenosis, may not derive benefit from the procedure, as evidenced by the 23.7% one-year mortality after TAVR reported from the Transcatheter Valve Therapies Registry (1). A major challenge is the identification of patients unlikely to benefit from this readily available transcatheter therapy. Several predictors of poor 1-year survival after TAVR have been identified, including a Society for Thoracic Surgery (STS) risk score >15%, severe chronic lung disease, end-stage renal disease, advanced liver disease (Child-Pugh class B or C), severe tricuspid regurgitation, nontransfemoral access, and low stroke volume index (1,2). However, the prognostic importance of right ventricular (RV) dysfunction in this population has not been well studied.
RV dysfunction typically develops as a result of chronic pressure and/or volume overload due to varying factors such as left heart disease, chronic lung disease, pulmonary hypertension, sleep-disordered breathing, and chronic arrhythmias. Although historically termed “the forgotten ventricle,” RV size and function are well-recognized predictors of adverse outcome after cardiac surgery. Although not included in the STS risk score, RV dysfunction is often a reason for classification of high surgical risk by cardiac surgeons due to the risk of hemodynamic deterioration upon discontinuation of cardiopulmonary bypass. The relationship between RV function and outcome after TAVR, however, is less clear, and formed the basis for the investigation by Asami et al. (3) in this issue of iJACC. Well-validated 2-dimensional and Doppler echocardiographic measurements of RV function were systematically used in this single-center study to define RV dysfunction, including fractional area change, tricuspid annular plane systolic excursion, and tissue Doppler assessment of RV lateral wall systolic velocity.
Of 1,116 patients in the study, 325 (29.1%) met the definition for RV dysfunction (3). Patients with RV dysfunction undergoing TAVR as expected had a higher STS risk score with greater prevalence of comorbidities, including reduced left ventricular (LV) ejection fraction, previous myocardial infarction, previous cardiac surgery, renal dysfunction, and concomitant mitral and tricuspid regurgitation (nearly one-third had moderate or greater mitral or tricuspid regurgitation). Accordingly, N-terminal pro–B-type natriuretic peptide levels were twice as high in patients with RV dysfunction versus those without RV dysfunction. Not surprisingly, patients with RV dysfunction had lower aortic valve mean gradient, smaller aortic valve area (likely due to lower forward stroke volume), and higher estimated pulmonary artery pressure compared with patients with preserved RV function. Although the majority of relevant comorbidities were available for review, no data were provided on heart failure medication use or markers of frailty, a well-recognized determinant of procedural risk and long-term outcome.
Procedural characteristics (i.e., access route, transcatheter valve type) and acute complications (stroke, paravalvular leak, pacemaker, and major bleeding) were similar in patients with and without RV dysfunction, with the exception of the use of general anesthesia being more common in patients with RV dysfunction (3). Afterwards, RV dysfunction patients were more likely to develop acute kidney injury and had longer hospital length of stay. Major adverse cardiovascular events, including myocardial infarction, were more common at 1 year in patients with RV dysfunction. A striking difference in 1-year mortality was observed between patients with RV dysfunction and those with normal RV function (26.2% vs. 11.1%), and this difference in mortality emerged as early as 30 days’ post-procedure (30-day mortality: 9.9% vs. 2.7%). After multivariable analysis, including major relevant risk factors, RV dysfunction was the strongest predictor of 1-year cardiovascular mortality after TAVR (hazard ratio: 2.51; 95% confidence interval: 1.64 to 3.86).
Asami et al. (3) provide important data on the temporal change in RV function and surprisingly found that more than one-half of patients with RV dysfunction experienced improvement in the RV function after TAVR. It is difficult to imagine how such a large number of patients experienced normalization of RV function solely by correcting aortic stenosis; presumably, these were patients with a more advanced degree aortic stenosis. Despite improvement in RV function, their prognosis remained worse than those without RV dysfunction at baseline. Patients who did not recover their RV function after TAVR or developed new-onset RV dysfunction after TAVR had the worst 1-year prognosis. Low LV ejection fraction and atrial fibrillation seemed to be predictors of lack of recovery of RV function. Unfortunately, no data were available on the effect of TAVR on symptoms or exercise capacity in patients with or without RV dysfunction to help understand the relative importance of aortic stenosis to other comorbidities.
The common prevalence of RV dysfunction in patients undergoing TAVR at first glance may be surprising given the remote “upstream” location of the aortic valve to the right ventricle. However, its association with LV dysfunction in patients with aortic stenosis shown in this study (3) is consistent with previous investigations (4). In aortic stenosis, chronic LV pressure overload initially results in LV hypertrophy and fibrosis, followed by a reduction in systolic function in later stages. How are these changes transmitted to the right ventricle? Chronic elevation in LV filling pressures results in pulmonary artery pressure elevation, but this factor alone does not entirely explain the RV dysfunction. Chronic effects on the left ventricle mediated by both local and systemic factors such as angiotensin I and catecholamines also occur in the right ventricle, as seen in systemic hypertension (5). It is plausible that in the earlier stages of severe aortic stenosis (before severe fibrosis and irreversible systolic dysfunction have occurred), acute correction of valvular obstruction may result in a relief of afterload mismatch on the right ventricle similar to that seen in patients with LV dysfunction.
The study by Asami et al. (3) for the most part is concordant with previous yet smaller studies denoting a similar prevalence and increased long-term mortality risk associated with RV enlargement and dysfunction after TAVR (6–8). Compared with several other variables, including post-procedural aortic regurgitation and severe tricuspid regurgitation, RV dysfunction was the strongest predictor of 1-year survival. The compelling data provided in this study suggest that RV dysfunction is a highly prognostic variable for both 30-day and 1-year mortality after TAVR. Despite the wealth of data provided in this latest contribution to the TAVR literature, several questions are raised deserving future study: Which patients with RV dysfunction have a favorable long-term survival? How much symptomatic benefit do patients with RV dysfunction derive from TAVR? What can be done to optimize RV function before and after TAVR? What are the mechanism(s) by which RV function can improve after TAVR? Future studies investigating the natural history and development of RV dysfunction in patients with severe aortic stenosis using parameters employed in this study and others such as RV longitudinal strain and/or magnetic resonance imaging will be helpful to shed light on the pathophysiology of this phenomenon. The striking difference in 1-year survival between patients with and without RV dysfunction supports its incorporation into TAVR risk assessment models. This effort will require that detailed RV imaging be performed on all patients with severe aortic stenosis to facilitate earlier detection of this dilemma, in keeping with the concept of aortic stenosis as a systemic disease, rather than an isolated valvular problem. These ideas lead to a central question that is becoming increasingly important: can we predict individual patient risk and hence optimize timing and patient selection for TAVR to improve long-term outcome? If we do not forget about the right ventricle, then perhaps we can.
↵∗ Editorials published in JACC: Cardiovascular Imaging reflect the views of the authors and do not necessarily represent the views of iJACC or the American College of Cardiology.
Dr. Eleid has reported that he has no relationships relevant to the contents of this paper to disclose.
- 2019 American College of Cardiology Foundation
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