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ESC Heart Fail. 2020 Jan 1. doi: 10.1002/ehf2.12582. [Epub ahead of print]

Gender and age normalization and ventilation efficiency during exercise in heart failure with reduced ejection fraction.

Author information

1
Centro Cardiologico Monzino, IRCCS, Via Parea 4, Milan, 20138, Italy.
2
Cardiology Department, Istituti Clinici Scientifici Maugeri, IRCCS, Veruno Institute, Veruno, Italy.
3
UOC Cardiologia, G da Saliceto Hospital, Piacenza, Italy.
4
Università degli Studi di Padova, Padova, Italy.
5
Department of Cardiology, University of Foggia, Foggia, Italy.
6
Department of Advanced Biomedical Sciences, Federico II University of Naples, Naples, Italy.
7
Dipartimento di medicina e scienze dell'invecchiamento, Università G. D'Annunzio, Chieti, Italy.
8
Department of Clinical and Molecular Medicine, Azienda Ospedaliera Sant'Andrea, "Sapienza" Università degli Studi di Roma, Roma, Italy.
9
Cardiovascular Rehabilitation Unit, Buccheri La Ferla Fatebenefratelli Hospital, Palermo, Italy.
10
Department of Clinical Sciences and Community Health, Cardiovascular Section, University of Milano, Milano, Italy.
11
Division of Cardiology, "S. Maugeri" Foundation, IRCCS, Institute of Cassano Murge, Bari, Italy.
12
Fondazione Salvatore Maugeri, IRCCS, Istituto Scientifico di Tradate, Tradate, Italy.
13
Cardiovascular Department, Ospedali Riuniti and University of Trieste, Trieste, Italy.
14
Cardiology Division, Santo Spirito Hospital, Roma, Italy.
15
Cardiologia SUN, Ospedale Monaldi (Azienda dei Colli), Seconda Università di Napoli, Napoli, Italy.
16
Cardiology, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, Brescia, Italy.
17
Fondazione Gabriele Monasterio, CNR-Regione Toscana, Pisa, Italy.
18
Life Science Institute, Scuola Superiore Sant'Anna, Pisa, Italy.
19
Unità Operativa Cardiologia Riabilitativa, Multimedica IRCCS, Milano, Italy.
20
Department of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy.
21
Department of Cardiovascular, Neural and Metabolic Sciences, San Luca Hospital, Istituto Auxologico Italiano, Milan, Italy.
22
Cardiology Division, Cardiac Arrhythmia Center and Cardiomyopathies Unit, San Camillo-Forlanini Hospital, Roma, Italy.
23
Section of Cardiology, Department of Medicine, University of Verona, Verona, Italy.
24
Dipartimento Cardiologico "A. De Gasperis", Ospedale Cà Granda-A.O. Niguarda, Milano, Italy.
25
Department for the Treatment and Study of Cardiothoracic Diseases and Cardiothoracic Transplantation, IRCCS-ISMETT, Palermo, Italy.
26
Cardiac Rehabilitation Unit, Fondazione Salvatore Maugeri, IRCCS, Scientific Institute of Milan, Milan, Italy.
27
Department of Cardiology, S. Chiara Hospital, Trento, Italy.
28
Cardiology University Department, Heart Failure Unit and Cardiopulmonary Laboratory, IRCCS Policlinico San Donato, San Donato Milanese, Italy.
29
Dipartimento di Scienze Cardiovascolari, Respiratorie, Nefrologiche, Anestesiologiche e Geriatriche, "Sapienza", Rome University, Rome, Italy.
30
Cardiovascular Center, Health Authority no. 1, University of Trieste, Trieste, Italy.
31
Division of Cardiology, University of Perugia School of Medicine, Perugia, Italy.

Abstract

AIMS:

Ventilation vs. carbon dioxide production (VE/VCO2 ) is among the strongest cardiopulmonary exercise testing prognostic parameters in heart failure (HF). It is usually reported as an absolute value. The current definition of normal VE/VCO2 slope values is inadequate, since it was built from small groups of subjects with a particularly limited number of women and elderly. We aimed to define VE/VCO2 slope prediction formulas in a sizable population and to test whether the prognostic power of VE/VCO2 slope in HF was different if expressed as a percentage of the predicted value or as an absolute value.

METHODS AND RESULTS:

We calculated the linear regressions between age and VE/VCO2 slope in 1136 healthy subjects (68% male, age 44.9 ± 14.5, range 13-83 years). We then applied age-adjusted and sex-adjusted formulas to predict VE/VCO2 slope to HF patients included in the metabolic exercise test data combined with cardiac and kidney indexes score database, which counts 6112 patients (82% male, age 61.4 ± 12.8, left ventricular ejection fraction 33.2 ± 10.5%, peakVO2 14.8 ± 4.9, mL/min/kg, VE/VCO2 slope 32.7 ± 7.7) from 24 HF centres. Finally, we evaluated whether the use of absolute values vs. percentages of predicted VE/VCO2 affected HF prognosis prediction (composite of cardiovascular mortality + urgent transplant or left ventricular assist device). We did so in the entire cardiac and kidney indexes score population and separately in HF patients with severe (peakVO2 < 14 mL/min/kg, n = 2919, 61.1 events/1000 pts/year) or moderate (peakVO2 ≥ 14 mL/min/kg, n = 3183, 19.9 events/1000 pts/year) HF. In the healthy population, we obtained the following equations: female, VE/VCO2 = 0.052 × Age + 23.808 (r = 0.192); male, VE/VCO2 = 0.095 × Age + 20.227 (r = 0.371) (P = 0.007). We applied these formulas to calculate the percentages of predicted VE/VCO2 values. The 2-year survival prognostic power of VE/VCO2 slope was strong, and it was similar if expressed as absolute value or as a percentage of predicted value (AUCs 0.686 and 0.690, respectively). In contrast, in severe HF patients, AUCs significantly differed between absolute values (0.637) and percentages of predicted values (0.650, P = 0.0026). Moreover, VE/VCO2 slope expressed as a percentage of predicted value allowed to reclassify 6.6% of peakVO2 < 14 mL/min/kg patients (net reclassification improvement = 0.066, P = 0.0015).

CONCLUSIONS:

The percentage of predicted VE/VCO2 slope value strengthens the prognostic power of VE/VCO2 in severe HF patients, and it should be preferred over the absolute value for HF prognostication. Furthermore, the widespread use of VE/VCO2 slope expressed as percentage of predicted value can improve our ability to identify HF patients at high risk, which is a goal of utmost clinical relevance.

KEYWORDS:

Cardiopulmonary exercise test; Heart failure; Prognosis; Ventilation efficiency

PMID:
31893579
DOI:
10.1002/ehf2.12582
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