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Prognostic value of cardiopulmonary exercise testing in patients with transthyretin cardiac amyloidosis

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Abstract

The aim of this study is to evaluate the prognostic value of cardiopulmonary testing (CPET) in a cohort of patients with transthyretin cardiac amyloidosis (ATTR-CA). ATTR-CA is associated with a progressive reduction in functional capacity. The prognostic role of CPET parameters and in particular of normalized peak VO2 (%ppVO2) remains to be thoroughly evaluated. In this study, 75 patients with ATTR-CA underwent cardiological evaluation and CPET in a National Referral Center for cardiac amyloidosis (Careggi University Hospital, Florence). Fifty-seven patients (76%) had wild-type ATTR. Median age was 80 (75–83) years, 68 patients (91%) were men. Peak oxygen consumption (14.1 ± 4.1 ml/kg/min) and %ppVO2 (68.4 ± 18.8%) were blunted. Twenty-seven (36%) patients had an abnormal pressure response to exercise. After a median follow-up of 25 (12–31) months, the composite outcome of death or heart failure hospitalization was registered in 19 (25.3%) patients. At univariate analysis %ppVO2 was a stronger predictor for the composite outcome than peak VO2. %ppVO2 and NT-proBNP remained associated with the composite outcome at multivariate analysis. The optimal predictive threshold for %ppVO2 was 62% (sensitivity: 71%; specificity: 68%; AUC: 0.77, CI 0.65–0.88). Patients with %ppVO2 ≤ 62%and NT-proBNP > 3000 pg had a worse prognosis with 1- and 2-year survival of 69 ± 9% and 50 ± 10%, respectively. CPET is a safe and useful prognostic tool in patients with ATTR-CA. CPET may help to identify patients with advanced disease that may benefit from targeted therapy.

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Abbreviations

HF:

Heart failure

AT:

Anaerobic threshold

ATTR-CA:

Transthyretin cardiac amyloidosis

ATTRwt:

Wild-type transthyretin cardiac amyloidosis

ATTRv:

Hereditary transthyretin cardiac amyloidosis

CPET:

Cardiopulmonary exercise testing

HFpEF:

HF with preserved ejection fraction

LV:

Left ventricle/ventricular

%ppVO2 :

Percentage of predicted peak VO2

SV:

Stroke volume

VO2 :

Oxygen uptake

VCO2 :

Carbon dioxide production

VE/VCO2 slope:

Minute ventilation/carbon dioxide production

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Funding

The authors received no specific funding for this work.

Author information

Author notes

  1. Maria Vittoria Silverii and Alessia Argirò contributed equally as the first authors.

  2. Francesco Fattirolli and Francesco Cappelli equally contributed as the last authors.

Authors and Affiliations

  1. Tuscan Regional Amyloidosis Centre, Careggi University Hospital, Florence, Italy

    Alessia Argirò, Carlo Fumagalli, Mattia Zampieri, Ludovica Guerrieri, Simone Bartolini, Carlotta Mazzoni, Alessia Tomberli, Federico Perfetto & Francesco Cappelli

  2. Cardiomyopathy Unit Largo, Careggi University Hospital, Brambilla 3, 50141, Florence, Italy

    Alessia Argirò, Mattia Zampieri, Alessia Tomberli & Iacopo Olivotto

  3. Geriatric Medicine and UTIG, Azienda Ospedaliera Careggi, Florence, Italy

    Samuele Baldasseroni

  4. Cardiac Rehabilitation Unit, Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy

    Maria Vittoria Silverii, Carlo Fumagalli, Costanza Burgisser & Francesco Fattirolli

  5. Department of Experimental and Clinical Medicine, Division of General Cardiology, University of Florence, Careggi University Hospital, Florence, Italy

    Niccolò Marchionni

  6. Division of Interventional Structural Cardiology, Cardiothoracovascular Department, Careggi University Hospital, Florence, Italy

    Carlo Di Mario

Authors
  1. Maria Vittoria Silverii
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  2. Alessia Argirò
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Contributions

MVS and AA: methodology, investigation, data curation and formal analysis, writing—original draft. SB, CF and MZ: conceptualization, methodology, investigation, data curation and formal analysis, writing—original draft. SB and CM: data curation and formal analysis, writing—original draft. CDM, NM, IO: writing—review and editing. AT, LG and CB: resources and data curation. FF, FC and FP: conceptualization, methodology, writing—review and editing, supervision.

Corresponding author

Correspondence to Mattia Zampieri.

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Silverii, M.V., Argirò, A., Baldasseroni, S. et al. Prognostic value of cardiopulmonary exercise testing in patients with transthyretin cardiac amyloidosis. Intern Emerg Med 18, 585–593 (2023). https://doi.org/10.1007/s11739-022-03125-3

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