TRI-SCORE and benefit of intervention in patients with severe tricuspid regurgitation.

BACKGROUND AND AIMS: Benefit of tricuspid regurgitation (TR) correction and timing of intervention are unclear. This study aimed to compare survival rates after surgical or transcatheter intervention to conservative management according to a TR clinical stage as assessed using the TRI-SCORE. METHODS: A total of 2,413 patients with severe isolated functional TR were enrolled in TRIGISTRY (1217 conservatively managed, 551 isolated tricuspid valve surgery, and 645 transcatheter valve repair). The primary endpoint was survival at 2 years. RESULTS: The TRI-SCORE was low (≤3) in 32%, intermediate (4-5) in 33%, and high (≥6) in 35%. A successful correction was achieved in 97% and 65% of patients in the surgical and transcatheter groups, respectively. Survival rates decreased with the TRI-SCORE in the three treatment groups (all P < .0001). In the low TRI-SCORE category, survival rates were higher in the surgical and transcatheter groups than in the conservative management group (93%, 87%, and 79%, respectively, P = .0002). In the intermediate category, no significant difference between groups was observed overall (80%, 71%, and 71%, respectively, P = .13) but benefit of the intervention became significant when the analysis was restricted to patients with successful correction (80%, 81%, and 71%, respectively, P = .009). In the high TRI-SCORE category, survival was not different to conservative management in the surgical and successful repair group (61% and 68% vs 58%, P = .26 and P = .18 respectively). CONCLUSIONS: Survival progressively decreased with the TRI-SCORE irrespective of treatment modality. Compared to conservative management, an early and successful surgical or transcatheter intervention improved 2-year survival in patients at low and, to a lower extent, intermediate TRI-SCORE, while no benefit was observed in the high TRI-SCORE category.

Unveiling Cardiac Amyloidosis, its Characteristics, and Outcomes Among Patients With MR Undergoing Transcatheter Edge-to-Edge MV Repair.

BACKGROUND: Mitral regurgitation (MR) and cardiac amyloidosis (CA) both primarily affect older patients. Data on coexistence and prognostic implications of MR and CA are currently lacking. OBJECTIVES: This study sought to identify the prevalence, clinical characteristics, and outcomes of MR CA compared with lone MR. METHODS: Consecutive patients undergoing transcatheter edge-to-edge repair (TEER) for MR at 2 sites were screened for concomitant CA using a multiparametric approach including core laboratory 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid bone scintigraphy and echocardiography and immunoglobulin light chain assessment. Transthyretin CA (ATTR) was diagnosed by 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (Perugini grade 1: early infiltration; grades 2/3: clinical CA) and the absence of monoclonal protein, and light chain (AL) CA via tissue biopsy. All-cause mortality and hospitalization for heart failure (HHF) served as the endpoints. RESULTS: A total of 120 patients (age 76.9 ± 8.1 years, 55.8% male) were recruited. Clinical CA was diagnosed in 14 patients (11.7%; 12 ATTR, 1 AL, and 1 combined ATTR/AL) and early amyloid infiltration in 9 patients (7.5%). Independent predictors of MR CA were increased posterior wall thickness and the presence of a left anterior fascicular block on electrocardiography. Procedural success and periprocedural complications of TEER were similar in MR CA and lone MR (P for all = NS). After a median of 1.7 years, 25.8% had experienced death and/or HHF. MR CA had worse outcomes compared with lone MR (HR: 2.2; 95% CI: 1.0-4.7; P = 0.034), driven by a 2.5-fold higher risk for HHF (HR: 2.5; 95% CI: 1.1-5.9), but comparable mortality (HR: 1.6; 95% CI: 0.4-6.1). CONCLUSIONS: Dual pathology of MR CA is common in elderly patients with MR undergoing TEER and has worse postinterventional outcomes compared with lone MR.

Reverse Remodeling Following Valve Replacement in Coexisting Aortic Stenosis and Transthyretin Cardiac Amyloidosis.

BACKGROUND: Dual pathology of severe aortic stenosis (AS) and transthyretin cardiac amyloidosis (ATTR) is increasingly recognized. Evolution of symptoms, biomarkers, and myocardial mechanics in AS-ATTR following valve replacement is unknown. We aimed to characterize reverse remodeling in AS-ATTR and compared with lone AS. METHODS: Consecutive patients referred for transcatheter aortic valve replacement (TAVR) underwent ATTR screening by blinded 99mTc-DPD bone scintigraphy (Perugini Grade-0 negative, 1-3 increasingly positive) before intervention. ATTR was diagnosed by DPD and absence of monoclonal protein. Reverse remodeling was assessed by comprehensive evaluation before TAVR and at 1 year. RESULTS: One hundred twenty patients (81.8±6.3 years, 51.7% male, 95 lone AS, 25 AS-ATTR) with complete follow-up were studied. At 12 months (interquartile range, 7-17) after TAVR, both groups experienced significant symptomatic improvement by New York Heart Association functional class (both P<0.001). Yet, AS-ATTR remained more symptomatic (New York Heart Association ≥III: 36.0% versus 13.8; P=0.01) with higher residual NT-proBNP (N-terminal pro-brain natriuretic peptide) levels (P<0.001). Remodeling by echocardiography showed left ventricular mass regression only for lone AS (P=0.002) but not AS-ATTR (P=0.5). Global longitudinal strains improved similarly in both groups. Conversely, improvement of regional longitudinal strain showed a base-to-apex gradient in AS-ATTR, whereas all but apical segments improved in lone AS. This led to the development of an apical sparing pattern in AS-ATTR only after TAVR. CONCLUSIONS: Patterns of reverse remodeling differ from lone AS to AS-ATTR, with both groups experiencing symptomatic improvement by TAVR. After AS treatment, AS-ATTR transfers into a lone ATTR cardiomyopathy phenotype.

Malnutrition outweighs the effect of the obesity paradox.

BACKGROUND: High body mass index (BMI) is paradoxically associated with better outcome in patients with heart failure (HF). The effects of malnutrition on this phenomenon across the whole spectrum of HF have not yet been studied. METHODS: In this observational study, patients were classified by guideline diagnostic criteria to one of three heart failure subtypes: reduced (HFrEF), mildy reduced (HFmrEF), and preserved ejection fraction (HFpEF). Data were retrieved from the Viennese-community healthcare provider network between 2010 and 2020. The relationship between BMI, nutritional status reflected by the prognostic nutritional index (PNI), and survival was assessed. Patients were classified by the presence (PNI < 45) or absence (PNI ≥ 45) of malnutrition. RESULTS: Of the 11 995 patients enrolled, 6916 (58%) were classified as HFpEF, 2809 (23%) HFmrEF, and 2270 HFrEF (19%). Median age was 70 years (IQR 61-77), and 67% of patients were men. During a median follow-up time of 44 months (IQR 19-76), 3718 (31%) of patients died. After adjustment for potential confounders, BMI per IQR increase was independently associated with better survival (adj. hazard ratio [HR]: 0.91 [CI 0.86-0.97], P = 0.005), this association remained significant after additional adjustment for HF type (adj. HR: 0.92 [CI 0.86-0.98], P = 0.011). PNI was available in 10 005 patients and lowest in HFrEF patients. PNI was independently associated with improved survival (adj. HR: 0.96 [CI 0.95-0.97], P < 0.001); additional adjustment for HF type yielded similar results (adj. HR: 0.96 [CI 0.96-0.97], P < 0.001). Although obese patients experienced a 30% risk reduction, malnutrition at least doubled the risk for death with 1.8- to 2.5-fold higher hazards for patients with poor nutritional status compared with normal weight well-nourished patients. CONCLUSIONS: The obesity paradox seems to be an inherent characteristic of HF regardless of phenotype and nutritional status. Yet malnutrition significantly changes trajectory of outcome with regard to BMI alone: obese patients with malnutrition have a considerably worse outcome compared with their well-nourished counterparts, outweighing protective effects of high BMI alone. In this context, routine recommendation towards weight loss in patients with obesity and HF should generally be made with caution and focus should be shifted on nutritional status.

Principal Morphomic and Functional Components of Secondary Mitral Regurgitation.

OBJECTIVES: The aim of this work was to identify the key morphological and functional features in secondary mitral regurgitation (sMR) and their prognostic impact on outcome. BACKGROUND: Secondary sMR in patients with heart failure and reduced ejection fraction typically results from distortion of the underlying cardiac architecture. The morphological components which may account for the clinical impact of sMR have not been systematically assessed or correlated with clinical outcomes. METHODS: Morphomic and functional network profiling were performed on a cohort of patients with stable heart failure optimized on guideline-based medical therapy. Principal component (PC) analysis and subsequent cluster analysis were used to condense the morphomic and functional data first into PCs with varimax rotation (PCVmax) and second into homogeneous clusters. Clusters and PCs were tested for their correlations with clinical outcomes. RESULTS: Morphomic and functional data from 383 patients were profiled and subsequently condensed into PCs. PCVmax 1 describes high loadings of left atrial morphological information, and PCVmax 2 describes high loadings of left ventricular (LV) topology. Based on these components, 4 homogeneous clusters were derived. sMR was most prominent in clusters 3 and 4, with the morphological difference being left ventricular size (median end-diastolic volume 188 mL [interquartile range: 160 mL-224 mL] vs 315 mL [264 mL-408 mL]; P < 0.001). Clusters were associated with mortality (P < 0.001), but sMR remained independently associated with mortality after adjusting for the clusters (adjusted HR: 1.42; 95% CI: 1.14-1.77; P < 0.01). The detrimental association of sMR with mortality was mainly driven by cluster 3 (HR: 2.18; 95% CI: 1.32-3.60; P = 0.002), the "small LV cavity" phenotype. CONCLUSIONS: These results challenge the current perceptions that sMR in heart failure with reduced ejection fraction results exclusively from global or local LV remodeling and are suggestive of a potential role of the left atrial component. The association of sMR with mortality cannot be purely attributed to cardiac morphology alone, supporting other complementary key aspects of mitral valve closure consistent with the force balance theory. Unsupervised clustering supports the association of sMR with mortality predominantly driven by the small LV cavity phenotype, as previously suggested by a conceptional framework and termed disproportionate sMR.

Natural Course of Nonsevere Secondary Tricuspid Regurgitation.

BACKGROUND: Secondary tricuspid regurgitation (sTR) is frequent in patients with heart failure with reduced ejection fraction and is associated with adverse outcomes despite guideline-directed therapy. However, little is known about the natural course of nonsevere sTR and its relation to cardiac remodeling and outcomes. The aims of this study were therefore to investigate the natural course of sTR progression using quantitative measurements, to assess the prognostic impact on long-term mortality, and to identify risk factors associated with progressive sTR. METHODS: A total of 216 patients with heart failure with reduced ejection fraction receiving guideline-directed therapy were included in this long-term observational study. Progression of sTR was quantitatively defined as an increase of 0.2 cm2 in effective regurgitant orifice area or 15 mL in regurgitant volume, with transition to at least moderate sTR. Kaplan-Meier and Cox regression analyses were applied to assess survival during a 5-year follow-up period. RESULTS: Among patients with nonsevere sTR at baseline, 62 (29%) experienced sTR progression. Progressive sTR was accompanied by larger left and right atrial volumes (P = .02 and P < .02, respectively) and a higher prevalence of atrial fibrillation (P < .04). During a median follow-up period of 60 months (interquartile range, 37-60 months), 82 patients died. Progression of sTR conveyed a higher risk for long-term mortality (hazard ratio, 1.77; 95% CI, 1.1-2.83; P < .02), even after multivariate adjustment for bootstrap-selected (adjusted hazard ratio, 1.70; 95% CI, 1.06-2.74; P < .03) and clinical confounder (adjusted hazard ratio, 1.80; 95% CI, 1.07-3.05; P < .03) models. CONCLUSIONS: The incidence of progressive sTR despite guideline-directed therapy is associated with adverse cardiac and valvular remodeling as well as a significantly higher long-term mortality. Biatrial enlargement as well as atrial fibrillation are associated with the development of subsequent progressive sTR and may help identify patients at risk for sTR progression, potentially creating a window of opportunity for closer follow-up and newly arising minimally invasive transcatheter repair therapies.

A Unifying Concept for the Quantitative Assessment of Secondary Mitral Regurgitation.

BACKGROUND: Diverging guideline definitions for the quantitative assessment of severe secondary mitral regurgitation (sMR) reflect the lacking link of the sMR spectrum to mortality and has introduced a source of uncertainty and continuing debate. OBJECTIVES: The current study aimed to define improved risk-thresholds specifically tailored to the complex nature of sMR that provide a unifying solution to the ongoing guideline-controversy. METHODS: This study enrolled 423 heart failure patients under guideline-directed medical therapy and assessed sMR by effective regurgitant orifice area (EROA), regurgitant volume (RegVol), and regurgitant fraction (RegFrac). RESULTS: Measures of sMR severity were consistently associated with 5-year mortality with a hazard ratio of 1.42 for a 1-SD increase (95% confidence interval [CI]: 1.25 to 1.63; p < 0.001) for EROA, 1.37 (95% CI: 1.20 to 1.56; p < 0.001) for RegVol, and 1.50 (95% CI: 1.30 to 1.73; p < 0.001) for RegFrac. Results remained statistically significant after bootstrap- or clinical confounder-based adjustment. Spline-curve analyses showed a linearly increasing risk enabling the ability to stratify into low-risk (EROA <20 mm2 and RegVol <30 ml), intermediate-risk (EROA 20 to 29 mm2 and RegVol 30 to 44 ml), and high-risk (EROA ≥30 mm2 and RegVol ≥45 ml) groups. In the intermediate-risk group, a RegFrac ≥50% as indicator for hemodynamic severe sMR was associated with poor outcome (p = 0.017). A unifying concept based on combined assessment of the EROA, the RegVol, and the RegFrac showed a significantly better discrimination compared with the currently established algorithms. CONCLUSIONS: Risk-based thresholds tailored to the pathophysiological concept of sMR provide a unifying solution to the ongoing guideline controversy. An algorithm based on the combined assessment of the unifying cutoffs for EROA, RegVol, and RegFrac improves risk prediction compared with currently established grading.