The review, led by a team from Henan Chest Hospital in Zhengzhou, China, synthesizes evidence from three research fields that have advanced rapidly but largely in isolation: transcatheter tricuspid valve intervention, risk stratification for right ventricular failure after left ventricular assist device implantation, and mechanical support of the failing right heart. The authors contend that clinicians managing the same organ apply inconsistent and sometimes contradictory logic depending on which door the patient enters, and they propose a unified, right-ventricle-first framework built on three principles: assess the unit rather than the valve, stage the ventricle rather than the regurgitation, and time the intervention before, not after, a prognostic threshold is crossed.

The physiological argument begins with the right ventricle’s distinctive architecture. Built for a low-impedance pulmonary circulation, its thin free wall and crescentic geometry eject large volumes efficiently against low pressure but cope poorly with acute increases in afterload. The relationship between the ventricle and its load is captured by the concept of ventriculo-arterial coupling, the ratio of end-systolic to arterial elastance. Under rising afterload the right ventricle first preserves coupling by raising contractility, a process called homeometric adaptation. As that reserve is exhausted, it dilates to maintain stroke volume, the transition that marks the onset of uncoupling and clinical failure. The bedside surrogate for this coupling, the ratio of tricuspid annular plane systolic excursion to pulmonary artery systolic pressure, known as TAPSE/PASP, independently predicts mortality across pulmonary hypertension and the full heart failure spectrum.

Complicating matters further is the phenomenon of ventricular interdependence. The right and left ventricles are mechanically coupled through the shared interventricular septum and the common pericardium, so the loading state of one alters the geometry and function of the other. Acute right ventricular overload displaces the septum leftward and impairs left ventricular filling, which explains why right ventricular failure produces a low-output state even when left ventricular contractility is preserved. This interdependence creates one of the central paradoxes of mechanical support: unloading the left ventricle can compromise the right. Left ventricular decompression by an assist device increases venous return to the right ventricle and shifts the septum away from it, reducing the septal contribution to right ventricular ejection on which the failing ventricle disproportionately depends.

The clinical consequences are substantial. In the standardized STS INTERMACS registry experience, early right ventricular failure affected about a quarter of left ventricular assist device recipients, and a persistent late phenotype remained evident at twelve months in a smaller but prognostically important subset. Late right ventricular failure is an under-recognized driver of readmission, worsening functional status, and death in patients otherwise doing well on left-sided support. Once the right ventricle uncouples and the tricuspid annulus dilates, regurgitation and elevated right atrial pressure are transmitted backward into the systemic venous circulation. Elevated central venous pressure, not low cardiac output, is the principal driver of worsening renal function in decompensated heart failure, and the same congestion injures the liver and gut, producing the multi-organ dysfunction that makes late intervention futile. The cascade is self-reinforcing: right ventricular dysfunction begets annular dilatation and tricuspid regurgitation, which increase volume load and further dilate the ventricle, while congestion degrades the very organs whose function decides whether any intervention can still succeed.

Against this backdrop, the arrival of transcatheter tricuspid intervention has transformed the treatment landscape. For decades the tricuspid valve was the forgotten valve, and its neglect was rational in a narrow sense because isolated tricuspid surgery carried very high operative mortality, much of it attributable to the very right heart failure and end-organ congestion that late referral had allowed to develop. Transcatheter edge-to-edge repair and, more recently, transcatheter tricuspid valve replacement have shown that severe regurgitation can be reduced safely in patients once considered untreatable. The pivotal TRILUMINATE randomized trial of edge-to-edge repair produced a large and durable reduction in regurgitation and a significant improvement in quality of life, meeting a hierarchical composite primary endpoint with a win ratio of 1.48, but it did not reduce all-cause mortality within the trial’s follow-up. The TRISCEND II trial of transcatheter replacement confirmed that regurgitation could be reduced to mild or less in the large majority of patients and met its hierarchical composite endpoint with a win ratio of 2.02, yet the individual components of mortality and heart failure hospitalization were not on their own significantly reduced.

The most striking development is the TRIC-I-HF trial, an investigator-initiated, open-label study that enrolled 360 patients with severe tricuspid regurgitation and overt right-sided heart failure at 29 high-volume German centers. The cohort was high-risk and congested, with a mean age of approximately 80 years and roughly three-quarters in New York Heart Association class III or IV. Both hierarchical primary endpoints were met: at one year the win ratio for the ranked composite of death, heart failure hospitalization and quality of life was 2.42, and through three years freedom from all-cause death or heart failure hospitalization was 52.4 percent versus 21.0 percent, a hazard ratio of 0.40. This is the first adequately powered randomized strategy trial to demonstrate reduction in hard clinical events with tricuspid repair. Several caveats apply, however: the trial was open-label, mortality was a secondary endpoint not adjusted for multiplicity, a high crossover rate of 43.7 percent by three years biases intention-to-treat estimates toward the null, and crucially, patients were neither stratified nor randomized by right ventricular stage, so the trial establishes event benefit in a selected high-risk cohort without testing whether that benefit depends on ventricular stage or reserve.

The dissociation between symptom benefit and survival benefit admits several non-exclusive explanations, each pointing back to the right ventricle. Follow-up in these trials remains short relative to the slow natural history of congestion-driven organ injury. More fundamentally, tricuspid regurgitation in the heart failure population is frequently the consequence of right ventricular and annular remodeling rather than its cause, so abolishing the regurgitant volume need not reverse the underlying ventricular dysfunction that drives outcome. Patient selection may also have been suboptimal, intervening once right ventricular failure is established in a manner analogous to the late-referral problem of the surgical era. Hypothesis-generating evidence from a multicenter propensity-matched analysis suggests the survival benefit of transcatheter tricuspid intervention is concentrated in patients with mid-range right ventricular function and attenuated in those with advanced dysfunction, precisely the gradient a valve-centric selection strategy would miss. A further mechanistic consideration is that abruptly abolishing severe regurgitation removes a low-pressure pop-off for the failing right ventricle and can precipitate acute decompensation, making knowledge of right ventricular reserve before eliminating the regurgitation particularly important.

At the acute end of the spectrum, the story repeats itself. For years, mechanical support in infarct-related shock accumulated a strikingly negative evidence base, with intra-aortic balloon counterpulsation showing no mortality benefit and randomized trials of veno-arterial extracorporeal membrane oxygenation failing to show a survival benefit from routine early support. The DanGer Shock trial marked a turning point, showing that a microaxial flow pump in the left ventricle reduced 180-day all-cause mortality in STEMI-related shock by an absolute margin of about 13 percent, from 59 percent to 46 percent, albeit with more bleeding, limb ischemia and renal-replacement therapy. Notably, the trial excluded overt right ventricular failure, so its result cannot be extrapolated to dedicated right ventricular support. Meanwhile, registry cohorts of the Impella RP right-sided device report in-hospital mortality near 47 percent, and a large contemporary analysis of temporary percutaneous right ventricular assist devices found they were used in only a small fraction of shock patients and carried in-hospital mortality above 50 percent. These figures are most plausibly explained in part by late deployment into established multi-organ failure rather than by device inadequacy, though unadjusted registry data cannot exclude that such patients were unsalvageable regardless of timing. No randomized trial has yet defined the optimal timing or device for acute right ventricular support.

The review’s authors propose a four-stage crosswalk aligning the SCAI shock stages, the INTERMACS right ventricular failure definitions and contemporary tricuspid regurgitation staging onto a common axis of the right ventricle-tricuspid unit, from compensated coupling through adaptive dilatation and active decompensation to overt failure with exhausted reserve. They deliberately attach no numerical thresholds, because the source cohorts use incompatible measurements and right ventricular indices are load-dependent, and they present treatment triggers as research propositions for stage-stratified trials rather than validated clinical recommendations. The framework is explicitly falsifiable: the staging-primacy claim fails if a randomized trial shows that tricuspid regurgitation reduction improves survival to a similar degree regardless of baseline right ventricular stage, and the timing principle fails if earlier, stage-triggered right ventricular support does not improve outcomes against later support in patients matched on baseline severity. Recent guidelines are moving in this direction, with the 2025 ESC/EACTS valvular guidelines recommending transcatheter tricuspid intervention in high-risk symptomatic severe regurgitation only in the absence of severe right ventricular dysfunction or pre-capillary pulmonary hypertension. Whether treating the right ventricle as an organizing principle rather than an afterthought converts the field’s recurring disappointments into durable survival gains is now a hypothesis that can, at last, be tested directly.

Subject of Research: Right ventricular and tricuspid valve dysfunction in mechanical circulatory support and transcatheter tricuspid intervention

Article Title: The right ventricle as the Achilles' heel: tricuspid regurgitation and right heart failure in the era of mechanical circulatory support

Article References: The right ventricle as the Achilles' heel: tricuspid regurgitation and right heart failure in the era of mechanical circulatory support. (n.d.). https://doi.org/10.3389/fcvm.2026.1946476

Image Credits: AI Generated

DOI: 10.3389/fcvm.2026.1946476

Keywords: right ventricle, tricuspid regurgitation, mechanical circulatory support, left ventricular assist device, cardiogenic shock, transcatheter tricuspid repair, TRIC-I-HF, TRILUMINATE, TRISCEND II, right heart failure, ventriculo-arterial coupling, heart failure