Hemodynamic Comparison And Prognostication Of V122I Versus Wild Type Transthyretin Amyloid Cardiomyopathy

Introduction

Transthyretin amyloid cardiomyopathy (ATTR-CM), in particular V122I disease, is a highly morbid cause of heart failure (HF). There are limited contemporary data on hemodynamic prognostication in ATTR-CM. We aimed to compare hemodynamics and evaluate prognostic significance in patients with V122I and wild type (wt) ATTR-CM.

Hypothesis

We hypothesize that patients with V122I will have more hemodynamic abnormalities and that hemodynamics will have additive prognostic value in ATTR-CM.

Methods

Patients with either V122I or wtATTR-CM who underwent RHC at our center were included. Hemodynamic abnormalities by each group and prognostic relevance by classic cut offs with endpoint of death was assessed. Characteristics for V122I or wtATTR-CM were compared using chi-squared or Fisher's exact tests, or t-tests or Wilcoxon tests. Kaplan-Meier curves and Cox proportional hazard regression models were used to assess relationships with mortality and the composite of mortality or HF hospitalization.

Results

Of 152 patients, 73 (48%) had V122I variant. V122I vs wtATTR patients were younger (72.7 [7.4] v 78.5 [7.3] yrs), more likely Black (94.5 v 17.7%), and NHYA Class III or IV (53.8 v 35.1%), all p<0.05, with no significant difference in National Amyloid Center (NAC) staging. On RHC, V122I patients were more likely to have abnormal filling pressures compared to wtATTR including mRA >8 (61.1% v 43.8%), mPAP >25 (75.0% v 54.8%), PCWP >18 (56.9% v 38.4%), all p<0.05. CI was low in the majority of patients and not different by V122I v wtATTR (CI <2.2: 82.6% v 80.3%, p=0.72, CI <1.8: 56.5% v 53.5%, p=0.72). V122I patients with abnormal mPAP, PCWP, and CI had significantly lower survival when compared to V122I patients with normal parameters and wtATTR patients with normal and abnormal parameters (Figure). Hemodynamics independently predicted risk on top of NAC stage 3 disease (p<0.05 for all parameters, Table).

Conclusion

The majority of patients with ATTR-CM have abnormal hemodynamics, with greater derangement in V122I disease. In patients with abnormal hemodynamics, V122I patients had poorer survival compared to wtATTR. Hemodynamics are independently predictive of adverse outcomes on top of classification in the most severe prognostic stage. In the era of non-invasive diagnosis for ATTR-CM, our findings highlight the ongoing role for hemodynamic investigation in patients with ATTR-CM.