Atrial vs mixed phenotype of secondary tricuspid regurgitation: characterization and outcomes

Background Atrial secondary tricuspid regurgitation(A-STR) is a recognised form of STR related to predominant right atrial(RA) remodeling, in the presence of normal biventricular function. Although specific definition criteria have been proposed by PCR/TVARC, a subset of A-STR patients may present overlapping characteristics with ventricular TR(V-STR), possibly due to the hemodynamic consequences of a long-standing A-STR. This group presents, therefore, a mixed phenotype for which limited data are available and whose prognosis remains poorly understood. The aim of this study was to compare outcomes in patients fulfilling the definition criteria for A-STR phenotype versus those presenting mixed features of both A-STR and V-STR, and to identify the parameters associated with adverse outcomes in these patients. Methods This multicentre study included 347 patients(age73±13 years,61% female) with ≥moderate A-STR. Of these, those who met the majority of A-STR criteria based on a multiparametric approach, except for one criterion typical of V-STR, were categorized as having mixed A-STR phenotype(n=186). The mixed A-STR phenotype group was further subdivided into: type A, with right ventricular (RV) dilatation (n=69); type B, with elevated pulmonary pressure(n=54); and type C, with RV dysfunction(n=63). The primary endpoint was a composite of all-cause mortality and heart failure hospitalisation. Results Patients with a mixed A-STR phenotype were generally more symptomatic than those with pure A-STR phenotype. As expected, the highest RV sphericity index (60±10) was observed in the type A subgroup, while elevated pulmonary pressure (TR gradient 36±8mmHg) was seen in the type B subgroup, and RV free wall strain (16±4%) was lowest in the type C subgroup (Fig1). During a median follow-up of 37(24-108) months, 117(34%) patients reached the endpoint. Compared to A-STR patients, patients with mixed A-STR phenotype had a significantly worse outcome (p=0.011,Fig 2). On multivariable Cox regression analyses (adjusted for age, NYHA class, signs of congestion, renal function, atrial fibrillation, coronary artery disease, left ventricular global longitudinal strain, biatrial myopathy, and TR severity), the mixed A-STR phenotype group was independently associated with worse outcome [HR 1.775 95%CI(1.015-3.104), p=0.044]. Among the subgroups, only the type C of mixed A-STR phenotype showed significantly worse outcome compared to A-STR phenotype [HR 1.871,95%CI(1.035–3.383),p=0.038](Fig2). Conclusion The presence of a mixed A-STR phenotype was associated with significantly worse clinical outcomes, particularly when subtle RV dysfunction, as indicated by free wall strain, was present in conjunction with classical features of A-STR. These findings highlight the importance of close echocardiographic monitoring for an early recognition of subtle RV dysfunction in A-STR patients, in order to improve their risk stratification and clinical management.Baseline characteristics. Event-free survival curve.