Secondary valve regurgitation in patients with heart failure with preserved ejection fraction, heart failure with mid-range ejection fraction, and heart failure with reduced ejection fraction

Abstract

Secondary mitral regurgitation and secondary tricuspid regurgitation due to heart failure (HF) remain challenging in almost every aspect: increasing prevalence, poor prognosis, notoriously elusive in diagnosis, and complexity of therapeutic management. Recently, defined HF subgroups according to three ejection fraction (EF) ranges (reduced, mid-range, and preserved) have stimulated a structured understanding of the HF syndrome but the role of secondary valve regurgitation (SVR) across the spectrum of EF remains undefined. This review expands this structured understanding by consolidating the underlying phenotype of myocardial impairment with each type of SVR. Specifically, the current understanding, epidemiological considerations, impact, public health burden, mechanisms, and treatment options of SVR are discussed separately for each lesion across the HF spectrum. Furthermore, this review identifies important gaps in knowledge, future directions for research, and provides potential solutions for diagnosis and treatment. Mastering the challenge of SVR requires a multidisciplinary collaborative effort, both, in clinical practice and scientific approach to optimize patient outcomes.

Keywords: HFmrEF; HFpEF; HFrEF; Heart failure; Secondary mitral regurgitation; Secondary tricuspid regurgitation.

Take home figure

Mechanism of secondary valve regurgitation across the heart failure spectrum. Whereas there are distinct characteristics of secondary mitral regurgitation mechanism according to the heart failure phenotype (ventricular vs. atrial secondary mitral regurgitation) mechanisms and prevalence of secondary tricuspid regurgitation are similar across the heart failure spectrum. The mechanisms of secondary tricuspid regurgitation in heart failure patients is complex and often multifactorial and appears to be similar across all heart failure subgroups characterized by right atrial and right ventricular dilatation and increased pulmonary pressures.

Figure 1

Pathophysiologic mechanisms of secondary mitral regurgitation. Distortion of the atrial annular unit feature the development of secondary mitral regurgitation in heart failure with preserved ejection fraction characterized by increased filling pressures, left atrial dilatation and subsequent mitral valve annular dilatation, and decreased annular contraction. In contrast, distortion of the ventricular annular unit promote the development of secondary mitral regurgitation in heart failure with reduced ejection fraction characterized by increased filling pressures, leaflet restriction, dyssynchrony, and left ventricular dilatation with subsequent mitral valve annular dilatation. Notably, distortion of the atrial annular unit and ventricular annular unit coexist with presumably the largest overlap in heart failure with mid-range ejection fraction secondary mitral regurgitation.

Figure 2

Stages of functional tricuspid regurgitation. Regardless of the underlying heart failure phenotype, increased left ventricular filling pressures will lead to increase pressures in the pulmonary circulation with effects on the right ventricle and tricuspid annulus as well as the right atrium that induce secondary tricuspid regurgitation (Phase I). Progressive right ventricular and atrial dilatation as well as annular remodelling will further increase secondary tricuspid regurgitation (Phase II). Progressive volume overload might lead to irreversible alteration of right ventricular and atrial as well as annular structure representing the late, often irreversible, phase of secondary tricuspid regurgitation (Phase III). Adapted from Ref.

Figure 3

Theoretical plot of secondary valve regurgitation severity across the entire heart failure spectrum (at any ejection fraction). Regurgitant volume is plotted against left ventricular total stroke volume, the black line roughly separates haemodynamic significant secondary valve regurgitation (red area, top) from haemodynamic non-severe secondary valve regurgitation (green area, bottom) by assuming a regurgitant fraction cut-off of 50%. There is an area of uncertainty attributable to methodological measurement variability and the different heart failure background risk across the ejection fraction spectrum depicted in yellow. Using a regurgitant volume vs. total left ventricular stroke volume plot has the advantage that it can be uniformly used across the entire heart failure spectrum where ejection fractions and left ventricular volumes are different.

Figure 4

Current and proposed treatment concepts for secondary mitral regurgitation according to heart failure subtype and haemodynamic significance. Guideline-directed medical therapy is the first-line treatment in heart failure with reduced ejection fraction and heart failure with mid-range ejection fraction. Medical therapy for heart failure with preserved ejection fraction relates to controlling risk factors as well as rhythm and rate with atrial fibrillation. Treatment of heart failure with reduced ejection fraction on top of guideline-directed medical therapy and cardiac resynchronization depends on the competing heart failure background risk and secondary valve regurgitation severity. Patients with very severe secondary valve regurgitation but relatively mild myocardial impairment are expected to derive benefits from transcatheter repair, whereas patients with severe myocardial impairment and relatively non-severe secondary mitral regurgitation are not expected to derive immediate benefits and should be evaluated for circulatory support and transplantation without delay. In heart failure with mid-range ejection fraction, transcatheter therapy is expected to improve outcome but rather a perspective than an established therapy which needs to be addressed by controlled trials. Regular follow-up in specialized heart failure and valve clinics is key as secondary valve regurgitation can progress (multicolour arrow, bottom) necessitating regular readjustments of therapeutic strategies.