Beyond the Valve: Right Heart Dysfunction, Cardiorenal Interactions, and Prognosis in Low-Flow, Low-Gradient Aortic Stenosis

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J INVASIVE CARDIOL 2026. doi:10.25270/jic/26.00140. Epub July 23, 2026.
 

Low-flow, low-gradient (LFLG) aortic stenosis (AS) represents one of the most complex and diagnostically challenging phenotypes of valvular heart disease. The discordance between a small calculated aortic valve area and a relatively low transvalvular gradient obscures the true severity of valve obstruction, often reflecting a complex interplay among impaired ventricular performance, altered loading conditions, and systemic comorbidities. Consequently, establishing the diagnosis requires meticulous integration of echocardiographic findings, hemodynamic assessment, computed tomography calcium scoring, and stress imaging, complemented by careful clinical judgment to distinguish true severe from pseudo-severe disease. Beyond its diagnostic complexity, LFLG AS carries important prognostic implications.^1-3 Patients with LFLG AS experience higher mortality than those with high-gradient severe AS despite deriving substantial benefit from transcatheter aortic valve replacement (TAVR). Yet even after successful valve intervention, excess mortality persists, suggesting that outcomes are influenced by factors extending beyond the stenotic valve itself. Myocardial dysfunction, right ventricular (RV) impairment, pulmonary vascular disease, and chronic kidney disease (CKD) frequently coexist and may substantially influence both survival and recovery after valve replacement.

It is within this context that Kim et al present an important and thought-provoking investigation examining the relationship between CKD, right-sided extravalvular damage, and survival in patients with LFLG AS undergoing TAVR.⁴ In this retrospective study of 402 patients, the investigators evaluated associations between CKD severity, right-sided cardiac abnormalities—including pulmonary hypertension, significant tricuspid regurgitation (TR), and RV dysfunction—and post-TAVR mortality. Several findings merit particular attention. First, advanced CKD, especially end-stage renal disease (ESRD), was independently associated with right-sided extravalvular damage. Second, both advanced CKD and right-sided extravalvular damage were associated with worse survival after TAVR.  Finally, among patients with paradoxical LFLG AS, the coexistence of advanced CKD and right-sided extravalvular damage was associated with a substantially greater risk of death than either condition alone, suggesting a synergistic interaction that was not observed in the classical LFLG phenotype.

At first glance, these observations may appear unsurprising. CKD has long been recognized as a powerful predictor of adverse outcomes after TAVR,⁵ and a growing body of evidence has demonstrated that RV dysfunction, RV dilation, and significant TR are associated with increased mortality following TAVR.^1,6-9 However, the novelty of the present study lies not in confirming the importance of either factor individually, but rather in highlighting the prognostic combination of both factors, specifically in paradoxical LFLG AS. Kim et al shift attention from isolated risk markers toward a broader cardiorenal-right heart phenotype that may represent a particularly advanced stage of disease.

These observations align closely with the evolving understanding of AS as a progressive disorder of cardiac damage rather than a disease confined to the valve leaflets.^1,6 The staging framework proposed by Généreux et al demonstrated that prognosis deteriorates as pathological changes extend beyond the left ventricle to involve the left atrium, pulmonary circulation, tricuspid valve, and eventually the right ventricle.⁶ Importantly, this classification was derived from analyses of the PARTNER 2 and PARTNER 3 trials, which enrolled predominantly high-gradient severe AS populations and did not include patients with paradoxical LFLG AS. As a result, the applicability of this staging framework to paradoxical LFLG AS has remained less well defined. The findings of Kim et al provide important insights into the prognostic significance of extracardiac and right-sided cardiac damage in a population that was not represented in the cohorts from which the contemporary cardiac damage staging framework was derived.

Kim et al further extend this concept by highlighting the important contribution of renal dysfunction. Their findings suggest that cardiorenal interactions may serve as markers of advanced disease, identifying patients in whom the systemic effects of longstanding hemodynamic stress have become clinically dominant. The relationship between right-sided cardiac dysfunction and CKD is biologically plausible. Progressive right-sided heart failure may impair renal perfusion while increasing renal venous congestion, creating a self-perpetuating cycle of worsening cardiac and renal function. Impaired right ventricle–pulmonary artery coupling has likewise been associated with acute kidney injury, worsening long-term renal function, and adverse clinical outcomes following TAVR, further underscoring the close interrelationship between right-heart performance and renal physiology in severe AS.¹⁰ Conversely, CKD promotes volume overload, neurohormonal activation, systemic inflammation, vascular calcification, and myocardial fibrosis. Whether advanced CKD simply represents a marker of frailty and multisystem illness rather than an independent mediator of adverse outcomes remains unclear.

Another notable finding in the present study is the differential prognostic significance of CKD and right-sided cardiac damage in classical vs paradoxical LFLG AS. In classical LFLG AS, mortality appeared predominantly associated with CKD regardless of right-sided damage. In contrast, among patients with paradoxical LFLG AS, the combination of advanced CKD and right-sided extravalvular damage identified a subgroup with particularly poor survival post TAVR. Although these findings should be interpreted cautiously given the relatively small numbers of patients with advanced CKD, they raise important questions regarding the underlying pathophysiology of paradoxical LFLG AS.

Traditionally, paradoxical LFLG AS has been viewed as a phenotype driven by concentric remodeling and diastolic dysfunction that results in low stroke volume despite preserved ejection fraction.¹ The findings reported by Kim et al suggest a more complex phenotype in which progression to pulmonary vascular, RV, and renal dysfunction may contribute significantly to poor post-TAVR outcomes. Importantly, RV dysfunction rarely occurs in isolation and is often accompanied by pulmonary hypertension and significant TR, underscoring the importance of comprehensive right-heart phenotyping. These findings suggest that assessment of RV function, pulmonary hemodynamics, and renal dysfunction may provide incremental prognostic information beyond traditional measures of stenosis severity, particularly in patients with paradoxical LFLG AS. Whether incorporation of these factors into contemporary risk stratification models can improve prognostication and clinical decision-making remains uncertain, but the study highlights the potential value of a more comprehensive cardiorenal-right heart assessment in this population.

Ultimately, the study by Kim et al reinforces the growing recognition that LFLG AS is not solely a disease of the aortic valve but rather a complex syndrome involving cardiac, pulmonary vascular, and renal dysfunction. The coexistence of advanced CKD and right-sided cardiac damage may identify a particularly high-risk phenotype, the outcomes of which are influenced by disease processes extending beyond the stenotic valve itself. As TAVR continues to move earlier in the disease course, an important unanswered question is whether intervention before the development of irreversible RV dysfunction, pulmonary vascular remodeling, and advanced cardiorenal syndrome could alter the natural history of LFLG AS. Future studies should determine whether integrating right-heart and renal phenotyping into patient selection and the timing of intervention can improve outcomes beyond conventional measures of valve severity alone.

Neda Dianati-Maleki, MD, MSc; Puja B. Parikh, MD, MPH

From the Department of Medicine, Stony Brook Renaissance School of Medicine, Stony Brook, New York.

Disclosures: Dr Parikh is a consultant for Medtronic and has received institutional research support from Edwards Lifesciences and Abbott. Dr Dianati-Maleki reports no financial relationships or conflicts of interest regarding the content herein.

Address for correspondence: Puja B. Parikh, MD, MPH, FACC, FAHA, FSCAI, Division of Cardiovascular Medicine, Stony Brook Medicine, Health Sciences Center T16-080, Stony Brook, NY 11794, USA. Email: puja.parikh@stonybrookmedicine.edu