Echocardiographic assessment of right ventricular coupling predicts cardiopulmonary fitness in cardiac transthyretin amyloidosis

Katharina Knoll (München)1, P. Fuchs (München)1, F. Altunkas (München)1, A. Erben (München)1, C. Lennerz (München)1, W. Hengstenberg (München)2, H. Schunkert (München)1, S. Groß (Greifswald)3, T. Trenkwalder (München)1

1Deutsches Herzzentrum München Klinik für Herz- und Kreislauferkrankungen München, Deutschland; 2Fachinternistische Gemeinschaftspraxis Am Harras München, Deutschland; 3Universitätsmedizin Greifswald Klinik und Poliklinik für Innere Medizin B Greifswald, Deutschland

 

Background
Cardiac wild-type transthyretin amyloidosis (wtATTR) is a restrictive cardiomyopathy characterized by amyloid infiltration in the myocardial interstitium, leading to exercise intolerance and symptoms of heart failure. Cardiopulmonary exercise testing (CPET) is the gold standard for assessment of functional capacity and cardiopulmonary fitness in heart failure. Several CPET variables have been associated with disease severity and prognosis, such as aerobic capacity (peak oxygen uptake or peakVO2) or ventilatory efficiency (VE/VCO2) in patients with cardiac amyloidosis. However, CPET is not broadly available due to logistic constraints (time consuming, special equipment and training necessary). Thus, alternative variables associated with CPET outcomes for routine everyday assessment are warranted.

Aim
In a prospective all-comer single centre study, we aimed to assess routine echocardiographic, laboratory and clinical parameters and their correlation to CPET parameters in patients with cardiac wtATTR.

Methods
Between 2020 and 2022, 96 patients with cardiac wtATTR were prospectively assessed through a comprehensive clinical evaluation including clinical assessment, laboratory analysis, echocardiography, 6MWT, CPET and the Minnesota living with heart failure questionnaire (LHFQ).

Results
The study population consisted of solely male patients, with an average age of 76±14 years, significant left ventricular hypertrophy (mean ± SD, intraventricular septum 19.2±2.8 mm), preserved ejection fraction (51±8 %), impaired right ventricular function with reduced TAPSE (14.8±4.3 mm) and increased systolic pulmonary artery pressures  (39±15 mmHg), impaired global longitudinal strain (GLS -10.5±3.6), increased cardiac markers (TroponinT 50.5±24.7 ng/l; NTproBNP 3284±2996 ng/l) and preserved renal function (GFR 64±20ml/min). CPET testing was safely performed in all patients. Mean pVO2 was 16.2 ml/kg/min with a range of 8.2 to 34.7 ml/kg/min. Pathological blood pressure response was very common in patients with cardiac wtATTR (62% of patients) as well as chronotropic insufficiency (23% of patients). In order to identify clinical, laboratory or imaging variables correlating with peak aerobic capacity on CPET we first performed an univariable correlation analysis (table 1). The variables significantly correlating with pVO2 were then used in a second, multivariable linear regression (table 1). For the multivariable regression, variables were selected for their clinical relevance to avoid collinearity in certain echocardiographic variables. Interestingly, in the multivariable model, only TAPSE/sPAP remained significant for predicting pVO2, a parameter that estimates the right ventricular to pulmonary arterial coupling.

Discussion
In conclusion, TAPSE/sPAP ratio was the most promising predictor of peak VO2 assessed by CPET, while ejection fraction or measures of left ventricular hypertrophy were not associated with exercise capacity in wtATTR patients. Our results highlight the importance of assessment of right ventricular coupling in cardiac wtATTR, possibly allowing an approximation of cardiopulmonary fitness as measured by CPET.




Table 1: Uni- and multivariable analysis

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