Log in to MyACC
Echo Phenotype and Prognosis in Transthyretin Cardiac Amyloidosis
Study Questions:
What are the structural and functional echocardiographic phenotypes across the spectrum of wild-type (wtATTR-CM) and hereditary (hATTR-CM) transthyretin cardiomyopathy, and the echocardiographic features predicting prognosis?
Methods:
The study cohort was comprised of 1,240 patients with ATTR-CM (mean age 77.5 ± 6.7 years) who underwent prospective evaluations including full echocardiographic assessment and survival between 2000 and 2019, comprising 766 (62%) with wtATTR-CM and 474 with hATTR-CM, of whom 314 had the V122I variant (of whom 272 or ~87% were black) and 127 the T60A variant. The study authors performed multivariable Cox proportional hazards analysis with the selected variables initially in the overall population and then this repeated in the population in which patients with severe aortic stenosis (AS) were omitted and in the two genotypic subgroups wtATTR-CM and V122I-hATTR-CM. Fifteen echocardiographic parameters and heart rate were explored in the univariate Cox regression analysis. Eleven echocardiographic variables and heart rate were entered into a multivariable Cox proportional hazards analysis.
Results:
Median patient survival from diagnosis by Kaplan–Meier analysis was 58 months in patients with wtATTR-CM compared to 36 months among patients with V122I-hATTR-CM and >60 months in T60A-hATTR-CM. At diagnosis, patients with V122I-hATTR-CM had the most severe degree of systolic and diastolic dysfunction across all echocardiographic parameters and patients with T60A-hATTR-CM the least; patients with wtATTR-CM had intermediate features. Stroke volume index (hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.95–0.99; p = 0.004), right atrial area index (HR, 1.05; 95% CI, 1.01–1.10; p = 0.016), longitudinal strain (HR, 1.08; 95% CI, 1.04–1.12; p < 0.001), and E/e’ (HR, 2.46; 95% CI, 1.29–4.72; p = 0.007) were all independently associated with mortality (p < 0.05 for all). Severe AS was also independently associated with prognosis, conferring a significantly shorter median survival of 22 months (95% CI, 7.94–36.06) versus 53 months (95% CI, 49.27–56.74; p = 0.001). Also, patients who underwent transcatheter aortic valve replacement had significantly longer survival than patients who did not receive any intervention, but this was in very small patient numbers and potentially affected by selection biases.
Conclusions:
The authors concluded that three distinct genotypes present with varying degrees of severity. Echocardiography indicates a complex pathophysiology in which both systolic and diastolic function are independently associated with mortality. The presence of severe AS was independently associated with significantly reduced patient survival.
Perspective:
This is an important study of a large cohort, which suggests that TTR cardiac amyloid is not merely a condition dominated by diastolic dysfunction but a complex pathophysiological model where both left ventricular systolic and diastolic function, right ventricular function, and atrial function are all independently associated with prognosis. The next step would be to determine the natural history of these distinct phenotypes including the impact of new therapies, such as tafamidis, on the trajectory of these different phenotypes.
Clinical Topics: Arrhythmias and Clinical EP, Cardiac Surgery, Geriatric Cardiology, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Valvular Heart Disease, Atrial Fibrillation/Supraventricular Arrhythmias, Aortic Surgery, Cardiac Surgery and Arrhythmias, Cardiac Surgery and Heart Failure, Cardiac Surgery and VHD, Acute Heart Failure, Interventions and Imaging, Interventions and Structural Heart Disease, Echocardiography/Ultrasound
Keywords: Amyloidosis, Aortic Valve Stenosis, Atrial Fibrillation, Atrial Function, Cardiomyopathies, Diastole, Diagnostic Imaging, Echocardiography, Genotype, Geriatrics, Heart Failure, Heart Rate, Phenotype, Stroke Volume, Systole, Transcatheter Aortic Valve Replacement, Ventricular Function
< Back to Listings
