Tricuspid Regurgitation and Right Heart Failure: "It all Begins and Ends With the RV"

Wayne Batchelor, MD, MHS; Abbas Emaminia, MD

Disclosures

JACC Heart Fail. 2020;8(8):637-639. 

The real voyage of discovery consists of not in seeking new landscapes but in having new eyes
—V.L.G.E. Marcel Proust [1]

The right ventricle (RV) and tricuspid valve (TV) are inextricably linked, both anatomically and functionally. Tricuspid regurgitation (TR) is a common sequela of right ventricular systolic dysfunction, which in turn begets more TR due to progressive annular dilation, portending a worse outcome in heart failure patients.[2] Although TR may result from an intrinsic structural abnormality of the valve (i.e., primary TR), the majority of cases (~80%) are due to annular dilation and leaflet tethering resulting from RV dysfunction (secondary TR). In the past, high operative mortality rendered stand-alone surgery for TR a rarity, resulting in the gross undertreatment of this condition. However, recently, both surgical and percutaneous TV repair techniques show greater promise and could prove to be transformational. Ultimately, the success of any TV repair procedure will rest on the appropriate selection of patients, repair technique, and timing of intervention. Therefore, predictive models that effectively stratify the risks for these patients and better elucidate the long-term relationships among TR, progressive RV remodeling, and prognosis are needed to assist in the complex decision making involved in contemporary and future treatment algorithms.

In this issue of JACC: Heart Failure, Dietz et al.[3] provide further insight into the relationship between right heart failure (RHF) and long-term survival in patients with concomitant TR. Identifying 1,311 patients from the Leiden University Medical Center echocardiographic database who were treated from June 1995 to September 2016, the authors divided subjects into 1 of 4 previously established stages of RHF: stage 1, patients at risk of RHF without RV dysfunction or symptoms (tricuspid annular plane systolic excursion [TAPSE] ≥17 mm, New York Heart Association [NYHA] functional class I); stage 2, patients with asymptomatic RV systolic dysfunction (TAPSE <17 mm, NYHA functional class I); stage 3, patients with established RV dysfunction and prior or current symptoms (TAPSE <17 mm, NYHA functional classes II to III, and no peripheral edema with the use of diuretics); and stage 4, patients with RV dysfunction and refractory RHF symptoms at rest (TAPSE <17mm, NYHA functional class IV, peripheral edema despite diuretics).[4] Patients were followed for 5 years with a median follow-up of 34 months. The baseline characteristics of the study cohort was consistent with that typically noted for patients with HF; median age was 71 years and hypertension (81%), coronary artery disease (40%), atrial fibrillation (50%), and pacemaker/defibrillators (37%) were prevalent. Left ventricular systolic function was only mildly diminished overall (mean LVEF of 44%), and concomitant aortic stenosis and mitral regurgitation were also quite prevalent (25% and 29%, respectively). Not surprisingly, advanced (stage 4) RHF correlated with older age, more severe TR, and multiple comorbidities (including diabetes mellitus, chronic obstructive pulmonary disease, and impaired renal function). Stage 4 RHF patients also had comparatively more LV and RV dilation, larger right and left atria, lower LVEF, higher RV systolic pressures, and more tricuspid leaflet tenting height and area. Long-term mortality was high (46% at 34 months; 54% at 5 years) and varied according to the stage of RHF, from 20% for stage 1 to 61% for stage 4. With 602 deaths, this study provided a unique opportunity to evaluate the influence of an array of demographic, clinical, and echocardiographic variables on long-term mortality. Although there were more than 20 univariate predictors of mortality, only age, coronary artery disease, renal function, LVEF, RVSP, and RHF stage emerged as independent predictors. This is an important finding, as this is the first study that highlights the fact that the clinical stage of RHF, itself, is an important prognosticator in patients with concomitant TR and RHF. Since this model included multiple variables that reflected the state of the RV, one would expect it to have better content validity than previously established risk predictive models derived from patients with LVHF, such as the MAGICC (Meta-Analysis Global Group in Chronic Heart Failure) score.[5] Still, similar to MAGICC, it would have helped to have this new predictive model validated in other clinical datasets of RHF with TR.

The methods for measuring RV systolic function and TR severity in this study merit discussion. Echocardiographic techniques were practical and reproducible. To measure RV systolic function and grade stages of RHF, the investigators used TAPSE, an echocardiographic parameter that is easy to ascertain in most patients. However, TAPSE, alone, does not adequately reflect global RV function and may be influenced by tricuspid valve regurgitant volume, thereby potentially masking reduced RV function. The study also reported RV fractional area change, which better correlates with cardiac magnetic resonance measurements of global RV function, but requires complete visualization of the RV, a task not always feasible. More sophisticated global assessments of RV function using 2-dimensional RV global longitudinal strain may provide better prognostication. The severity of TR was defined by qualitative, semiquantitative, and quantitative methods and only patients with moderate to severe TR were included. Tricuspid valve tenting height and area, RV systolic pressure, and right atrial area were also measured. However, in the multivariate model, RV systolic pressure was the only echocardiographic parameter that emerged as an independent predictor of mortality. The finding that TR severity itself was not an independent predictor probably relates to the fact that, by definition, all patients in the study had at least moderate TR. This might have reduced the overall discriminative ability of this parameter in the model. Prior studies in patients with heart failure with reduced ejection fraction have shown that TR severity, itself, is an important predictor of mortality.[6]

So, what are the key "take home messages" from this study? First, these patients tended to present late in the course of RHF; and the majority (83%) were already in the most advanced stages (stage 3 or 4) at the time of study inception. This implies that there exists opportunity for earlier diagnosis and treatment of TR to potentially avoid adverse RV remodeling and progression of RHF. Second, with approximately one-half of patients surviving 3 years, the mortality associated with RHF and TR was high. This survival rate is worse than that recently reported for all forms of LV heart failure, including patients with preserved, mid-range, or reduced LVEF.[7] The third important finding from this study is that long-term survival favored patients who underwent TV surgery. Across all stages of RHF, survival favored patients who underwent TV surgery compared to those who were treated medically. Although prone to selection bias, this observation lends credence to reports of undertreatment of TR and the potential for properly selected patients to garner prognostic benefit from TV repair. Taken together, these 3 observations provide impetus for clinical trials that identify candidates for whom novel TV repair techniques may be beneficial.

The authors are to be commended for completing a large-scale, comprehensive, and timely evaluation of RHF with concomitant TR. This work suggests that, when it comes to prognosis and disease progression, it all appears to begin and end with the RV. Armed with this information, clinicians now face the important task of developing effective treatment algorithms that focus on earlier recognition and intervention before the "point of no return," after which it may be too late to alter the path to refractory RHF.

Comments

3090D553-9492-4563-8681-AD288FA52ACE

processing....