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

Author

Elisabetta Salvioni, Ugo Corrà, Massimo Piepoli, Sara Rovai, Michele Correale, Stefania Paolillo, Mario Pasquali, Damiano Magrì, Giuseppe Vitale, Laura Fusini, Massimo Mapelli, Carlo Vignati, Rocco Lagioia, Rosa Raimondo, Gianfranco Sinagra, Federico Boggio, Lorenzo Cangiano, Giovanna Gallo, Alessandra Magini, Mauro Contini, Pietro Palermo, Anna Apostolo, Beatrice Pezzuto, Alice Bonomi, Angela B. Scardovi, Pasquale Perrone Filardi, Giuseppe Limongelli, Marco Metra, Domenico Scrutinio, Michele Emdin, Lucrezia Piccioli, Carlo Lombardi, Gaia Cattadori, Gianfranco Parati, Sergio Caravita, Federica Re, Mariantonietta Cicoira, Maria Frigerio, Francesco Clemenza, Maurizio Bussotti, Elisa Battaia, Marco Guazzi, Francesco Bandera, Roberto Badagliacca, Andrea Di Lenarda, Giuseppe Pacileo, Claudio Passino, Susanna Sciomer, Giuseppe Ambrosio, Piergiuseppe Agostoni, and MECKI score research group

Subjects
Cardiopulmonary exercise test, Prognosis, Ventilation efficiency, Heart failure, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

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.

Published
2020
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2. Pick Your Threshold

Author

Elisabetta Salvioni, Massimo Mapelli, Alice Bonomi, Damiano Magrì, Massimo Piepoli, Maria Frigerio, Stefania Paolillo, Ugo Corrà, Rosa Raimondo, Rocco Lagioia, Roberto Badagliacca, Pasquale Perrone Filardi, Michele Senni, Michele Correale, Mariantonietta Cicoira, Enrico Perna, Marco Metra, Marco Guazzi, Giuseppe Limongelli, Gianfranco Sinagra, Gianfranco Parati, Gaia Cattadori, Francesco Bandera, Maurizio Bussotti, Federica Re, Carlo Vignati, Carlo Lombardi, Angela B. Scardovi, Susanna Sciomer, Andrea Passantino, Michele Emdin, Claudio Passino, Caterina Santolamazza, Davide Girola, Denise Zaffalon, Fabiana De Martino, Piergiuseppe Agostoni, Stefania Farina, Beatrice Pezzuto, Anna Apostolo, Pietro Palermo, Mauro Contini, Paola Gugliandolo, Irene Mattavelli, Michele Della Rocca, Giovanna Gallo, Federica Moscucci, Anita Iorio, Geza Halasz, Bruno Capelli, Simone Binno, Giuseppe Pacileo, Fabio Valente, Rossella Vastarella, Cosimo Carriere, Marco Masè, Marco Cittar, Andrea Di Lenarda, Sergio Caravita, Elena Viganò, Giovanni Marchese, Roberto Ricci, Luca Arcari, Domenico Scrutinio, Elisa Battaia, Michele Moretti, Maria Vittoria Matassini, Matilda Shkoza, Roland Herberg, Antonio Cittadini, Andrea Salzano, Alberto Marra, Eluisa Lafranca, and Giuseppe Vitale

Subjects
Pulmonary and Respiratory Medicine, Cardiology and Cardiovascular Medicine, Critical Care and Intensive Care Medicine
Published
2022
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3. Does moderate hyperkalemia influence survival in HF? Insights from the MECKI score data base

Author

Federica Toto, Elisabetta Salvioni, Damiano Magrì, Susanna Sciomer, Massimo Piepoli, Roberto Badagliacca, Arianna Galotta, Nikita Baracchini, Stefania Paolillo, Ugo Corrà, Rosa Raimondo, Rocco Lagioia, Pasquale Perrone Filardi, Annamaria Iorio, Michele Senni, Michele Correale, Mariantonietta Cicoira, Enrico Perna, Marco Metra, Marco Guazzi, Giuseppe Limongelli, Gianfranco Sinagra, Gianfranco Parati, Gaia Cattadori, Francesco Bandera, Maurizio Bussotti, Massimo Mapelli, Manlio Cipriani, Alice Bonomi, Gonçalo Cunha, Federica Re, Carlo Vignati, Andrea Garascia, Carlo Lombardi, Angela B. Scardovi, Andrea Passantino, Michele Emdin, Claudio Passino, Caterina Santolamazza, Davide Girola, Denise Zaffalon, Dario Vizza, Fabiana De Martino, Piergiuseppe Agostoni, Toto, Federica, Salvioni, Elisabetta, Magrì, Damiano, Sciomer, Susanna, Piepoli, Massimo, Badagliacca, Roberto, Galotta, Arianna, Baracchini, Nikita, Paolillo, Stefania, Corrà, Ugo, Raimondo, Rosa, Lagioia, Rocco, Filardi, Pasquale Perrone, Iorio, Annamaria, Senni, Michele, Correale, Michele, Cicoira, Mariantonietta, Perna, Enrico, Metra, Marco, Guazzi, Marco, Limongelli, Giuseppe, Sinagra, Gianfranco, Parati, Gianfranco, Cattadori, Gaia, Bandera, Francesco, Bussotti, Maurizio, Mapelli, Massimo, Cipriani, Manlio, Bonomi, Alice, Cunha, Gonçalo, Re, Federica, Vignati, Carlo, Garascia, Andrea, Lombardi, Carlo, Scardovi, Angela B, Passantino, Andrea, Emdin, Michele, Passino, Claudio, Santolamazza, Caterina, Girola, Davide, Zaffalon, Denise, Vizza, Dario, De Martino, Fabiana, Agostoni, Piergiuseppe, Toto, F., Salvioni, E., Magri, D., Sciomer, S., Piepoli, M., Badagliacca, R., Galotta, A., Baracchini, N., Paolillo, S., Corra, U., Raimondo, R., Lagioia, R., Filardi, P. P., Iorio, A., Senni, M., Correale, M., Cicoira, M., Perna, E., Metra, M., Guazzi, M., Limongelli, G., Sinagra, G., Parati, G., Cattadori, G., Bandera, F., Bussotti, M., Mapelli, M., Cipriani, M., Bonomi, A., Cunha, G., Re, F., Vignati, C., Garascia, A., Lombardi, C., Scardovi, A. B., Passantino, A., Emdin, M., Passino, C., Santolamazza, C., Girola, D., Zaffalon, D., Vizza, D., De Martino, F., and Agostoni, P.

Subjects
Renin angiotensin aldosterone system inhibitor, Prognosi, Heart failure, Hyperkalemia, Prognosis, Settore MED/11 - Malattie dell'Apparato Cardiovascolare, Cardiology and Cardiovascular Medicine
Abstract

Background: The prognostic role of moderate hyperkalemia in reduced ejection fraction (HFrEF) patients is still controversial. Despite this, it affects the use of renin–angiotensin–aldosterone system inhibitors (RAASi) with therapy down-titration or discontinuation. Objectives: Aim of the study was to assess the prognostic impact of moderate hyperkalemia in chronic HFrEF optimally treated patients. Methods and results: We retrospectively analyzed MECKI (Metabolic Exercise test data combined with Cardiac and Kidney Indexes) database, with median follow-up of 4.2 [IQR 1.9–7.5] years. Data on K+ levels were available in 7087 cases. Patients with K+ plasma level ≥ 5.6 mEq/L and < 4 mEq/L were excluded. Remaining patients were categorized into normal >4 and < 5 mEq/L (n = 4826, 68%) and moderately high ≥5.0 and ≤ 5.5 mEq/L (n = 496, 7%) K+. Then patients were matched by propensity score in 484 couplets of patients. MECKI score value was 7% [IQR 3.1–14.1%] and 7.3% [IQR 3.4–15%] (p = 0.678) in patients with normal and moderately high K+ values while cardiovascular mortality events at two years follow-up were 41 (4.2%) and 33 (3.4%) (p = 0.333) in each group respectively. Conclusions: Moderate hyperkalemia does not influence patients' outcome in a large cohort of ambulatory HFrEF patients.

Published
2023

4. Pick Your Threshold: A Comparison Among Different Methods of Anaerobic Threshold Evaluation in Heart Failure Prognostic Assessment

Author

Elisabetta, Salvioni, Massimo, Mapelli, Alice, Bonomi, Damiano, Magrì, Massimo, Piepoli, Maria, Frigerio, Stefania, Paolillo, Ugo, Corrà, Rosa, Raimondo, Rocco, Lagioia, Roberto, Badagliacca, Pasquale Perrone, Filardi, Michele, Senni, Michele, Correale, Mariantonietta, Cicoira, Enrico, Perna, Marco, Metra, Marco, Guazzi, Giuseppe, Limongelli, Gianfranco, Sinagra, Gianfranco, Parati, Gaia, Cattadori, Francesco, Bandera, Maurizio, Bussotti, Federica, Re, Carlo, Vignati, Carlo, Lombardi, Angela B, Scardovi, Susanna, Sciomer, Andrea, Passantino, Michele, Emdin, Claudio, Passino, Caterina, Santolamazza, Davide, Girola, Denise, Zaffalon, Fabiana, De Martino, Piergiuseppe, Agostoni, Giuseppe, Vitale, Salvioni, Elisabetta, Mapelli, Massimo, Bonomi, Alice, Magrì, Damiano, Piepoli, Massimo, Frigerio, Maria, Paolillo, Stefania, Corrà, Ugo, Raimondo, Rosa, Lagioia, Rocco, Badagliacca, Roberto, Filardi, Pasquale Perrone, Senni, Michele, Correale, Michele, Cicoira, Mariantonietta, Perna, Enrico, Metra, Marco, Guazzi, Marco, Limongelli, Giuseppe, Sinagra, Gianfranco, Parati, Gianfranco, Cattadori, Gaia, Bandera, Francesco, Bussotti, Maurizio, Re, Federica, Vignati, Carlo, Lombardi, Carlo, Scardovi, Angela B, Sciomer, Susanna, Marra, Alberto, Passantino, Andrea, Emdin, Michele, Passino, Claudio, Santolamazza, Caterina, Girola, Davide, Zaffalon, Denise, De Martino, Fabiana, and Agostoni, Piergiuseppe

Subjects
Heart Failure, Oxygen Consumption, Anaerobic Threshold, Anaerobic threshold, cardiopulmonary exercise test, heart failure, prognosis, Exercise Test, Humans, Settore MED/11 - Malattie dell'Apparato Cardiovascolare, Prognosis
Abstract

Background: In clinical practice, anaerobic threshold (AT) is used to guide training and rehabilitation programs, to define risk of major thoracic or abdominal surgery, and to assess prognosis in heart failure (HF). AT of oxygen uptake (V.O2; V.O2AT) has been reported as an absolute value (V.O2ATabs), as a percentage of predicted peak V.O2 (V.O2AT%peak_pred), or as a percentage of observed peak V.O2 (V.O2AT%peak_obs). A direct comparison of the prognostic power among these different ways to report AT is missing. Research question: What is the prognostic power of these different ways to report AT? Study design and methods: In this observational cohort study, we screened data of 7,746 patients with HF with a history of reduced ejection fraction (< 40%) recruited between 1998 and 2020 and enrolled in the Metabolic Exercise Combined With Cardiac and Kidney Indexes register. All patients underwent a maximum cardiopulmonary exercise test, executed using a ramp protocol on an electronically braked cycle ergometer. Results: This study considered 6,157 patients with HF with identified AT. Follow-up was median, 4.2 years (25th-75th percentiles, 1.9-5.0 years). Both V.O2ATabs (mean ± SD, 823 ± 305 mL/min) and V.O2AT%peak_pred (mean ± SD, 39.6 ± 13.9%), but not V.O2AT%peak_obs (mean ± SD, 69.2 ± 17.7%), well stratified the population regarding prognosis (composite end point: cardiovascular death, urgent heart transplant, or left ventricular assist device). Comparing area under the receiver operating characteristic curve (AUC) values, V.O2ATabs (0.680) and V.O2AT%peak_pred (0.688) performed similarly, whereas V.O2AT%peak_obs (0.538) was significantly weaker (P < .001). Moreover, the V.O2AT%peak_pred AUC value was the only one performing as well as the AUC based on peak V.O2 (0.710), with an even a higher AUC (0.637 vs 0.618, respectively) in the group with severe HF (peak V.O2 < 12 mL/min/kg). Finally, the combination of V.O2AT%peak_pred with peak V.O2 and V. per CO2 production shows the highest prognostic power. Interpretation: In HF, V.O2AT%peak_pred is the best way to report V.O2 at AT in relationship to prognosis, with a prognostic power comparable to that of peak V.O2 and, remarkably, in patients with severe HF.

Published
2022

5. Revisiting a Prognosticating Algorithm from Cardiopulmonary Exercise Testing in Chronic Heart Failure (from the MECKI Score Population)

Author

Ugo Corrà, Massimo Francesco Piepoli, Andrea Giordano, Francesco Doni, Alessandra Magini, Alice Bonomi, Elisabetta Salvioni, Rocco Lagioia, Giuseppe Limongelli, Stefania Paolillo, Damiano Magrì, Pasquale Perrone Filardi, Gianfranco Sinagra, Angela B. Scardovi, Marco Metra, Michele Senni, Domenico Scrutinio, Rosa Raimondo, Michele Emdin, Gaia Cattadori, Gianfranco Parati, Federica Re, Mariantonietta Cicoira, Chiara Minà, Michele Correale, Maria Frigerio, Enrico Perna, Maurizio Bussotti, Elisa Battaia, Marco Guazzi, Francesco Bandera, Roberto Badagliacca, Andrea Di Lenarda, Aldo Maggioni, Claudio Passino, Susanna Sciomer, Giuseppe Pacileo, Massimo Mapelli, Carlo Vignati, Francesco Clemenza, Carlo Lombardi, Piergiuseppe Agostoni, Corrà, Ugo, Piepoli, Massimo Francesco, Giordano, Andrea, Doni, Francesco, Magini, Alessandra, Bonomi, Alice, Salvioni, Elisabetta, Lagioia, Rocco, Limongelli, Giuseppe, Paolillo, Stefania, Magrì, Damiano, Filardi, Pasquale Perrone, Sinagra, Gianfranco, Scardovi, Angela B, Metra, Marco, Senni, Michele, Scrutinio, Domenico, Raimondo, Rosa, Emdin, Michele, Cattadori, Gaia, Parati, Gianfranco, Re, Federica, Cicoira, Mariantonietta, Minà, Chiara, Correale, Michele, Frigerio, Maria, Perna, Enrico, Bussotti, Maurizio, Battaia, Elisa, Guazzi, Marco, Bandera, Francesco, Badagliacca, Roberto, Lenarda, Andrea Di, Maggioni, Aldo, Passino, Claudio, Sciomer, Susanna, Pacileo, Giuseppe, Mapelli, Massimo, Vignati, Carlo, Clemenza, Francesco, Lombardi, Carlo, and Agostoni, Piergiuseppe

Subjects
Heart Failure, Oxygen Consumption, Adrenergic beta-Antagonists, Exercise Test, Humans, Stroke Volume, HFrEF, Prognosis, Cardiology and Cardiovascular Medicine, Algorithms, Ventricular Function, Left
Abstract

Cardiopulmonary exercise testing is a prognostic tool in heart failure with reduced left ventricular ejection fraction (HFrEF). Prognosticating algorithms have been proposed, but none has been validated. In 2017, a predictive algorithm, based on peak oxygen consumption (VO2), ventilatory response to exercise (ventilation [VE] carbon dioxide production [VCO2], the VE/VCO2 slope), exertional oscillatory ventilation (EOV), and peak respiratory exchange ratio, was recommended, according treatment with β blockers: patients with HFrEF registered in the metabolic exercise test data combined with cardiac and kidney indexes (MECKIs) database were used to validated this algorithm. According to the inclusion/exclusion criteria, 4,683 MECKI patients with HFrEF were enrolled. At 3years follow-up, the end point was cardiovascular death and urgent heart transplantation (cardiovascular events [CV]). CV events occurred in 25% in patients without β blockers, whereas those with β-blockers had 11% (p 10

Published
2022

6. Cardiovascular Death Risk in Recovered Mid-Range Ejection Fraction Heart Failure: Insights From Cardiopulmonary Exercise Test

Author

Magri', Damiano, Massimo, Piepol, Ugo, Corrà, Gallo, Giovanna, Maruotti, Antonello, Carlo, Vignati, Elisabetta, Salvioni, Massimo, Mapelli, Stefania, Paolillo, Pasquale Perrone Filardi, Davide, Girola, Metra, Marco, Angela, B Scardovi, Rocco, Lagioia, Giuseppe, Limongelli, Michele, Senni, Domenico, Scrutinio, Michele, Emdin, Claudio, Passino, Carlo, Lombardi, Gaia, Cattadori, Gianfranco, Parati, Mariantonietta, Cicoira, Michele, Correale, Maria, Frigerio, Francesco, Clemenza, Maurizio, Bussotti, Guazzi, Marco, Badagliacca, Roberto, Sciomer, Susanna, Andrea Di Lenarda, Aldo, Maggioni, Gianfranco, Sinagra, Volpe, Massimo, Piergiuseppe, Agostoni, MECKI score Research Group, Magri, D., Piepoli, M., Corra, U. G. O., Gallo, G., Maruotti, A., Vignati, C., Salvioni, E., Mapelli, M., Paolillo, S., PERRONE FILARDI, P., Girola, D., Metra, M., Scardovi, A. B., Lagioia, R., Limongelli, G., Senni, M., Scrutinio, D., Emdin, M., Passino, C., Lombardi, C., Cattadori, G. A. I. A., Parati, G., Cicoira, M., Correale, M., Frigerio, M., Clemenza, F., Bussotti, M., Guazzi, M., Badagliacca, R., Sciomer, S., DI LENARDA, A., Maggioni, A. L. D. O., Sinagra, G., Volpe, M., Agostoni, P., Magrì, D, Piepoli, M, Corrà, U, Gallo, G, Maruotti, A, Vignati, C, Salvioni, E, Mapelli, M, Paolillo, S, Perrone Filardi, P, Girola, D, Metra, M, Scardovi, A, Lagioia, R, Limongelli, G, Senni, M, Scrutinio, D, Emdin, M, Passino, C, Lombardi, C, Cattadori, G, Parati, G, Cicoira, M, Correale, M, Frigerio, M, Clemenza, F, Bussotti, M, Guazzi, M, Badagliacca, R, Sciomer, S, DI Lenarda, A, Maggioni, A, Sinagra, G, Volpe, M, and Agostoni, P

Subjects
medicine.medical_specialty, Multivariate analysis, Settore MED/11 - Malattie dell'Apparato Cardiovascolare, Heart failure, 030204 cardiovascular system & hematology, Cardiovascular death, heart failure, mecki score, cardiopulmonary exercise test, prognosis, 03 medical and health sciences, 0302 clinical medicine, MECKI score, Internal medicine, Cardiopulmonary exercise test, Cause of Death, medicine, Humans, 030212 general & internal medicine, Ejection fraction, End point, business.industry, VO2 max, Cardiopulmonary exercise testing, Stroke Volume, medicine.disease, Cardiology, Exercise Test, Cardiology and Cardiovascular Medicine, business, prognosi
Abstract

Background Heart failure with midrange ejection fraction (HFmrEF) represents a heterogeneous category where phenotype, as well as prognostic assessment, remains debated. The present study explores a specific HFmrEF subset, namely those who recovered from a reduced EF (rec-HFmrEF) and, particularly, it focuses on the possible additive prognostic role of cardiopulmonary exercise testing. Methods and Results We analyzed data from 4535 patients with HFrEF and 1176 patients with rec-HFmrEF from the Metabolic Exercise combined with Cardiac and Kidney Indexes database. The end point was cardiovascular death at 5 years. The median follow-up was 1343 days (25th–75th range 627–2403 days). Cardiovascular death occurred in 552 HFrEF and 61 rec-HFmrEF patients. The multivariate analysis confirmed an independent role of the MECKI score's variables in HFrEF (C-index = 0.744) whereas, in the rec-HFmrEF group, only age and peak oxygen uptake (pVO2) remained associated to the end point (C-index = 0.745). A peak oxygen uptake of ≤55% of predicted and a ventilatory efficiency of ≥31 resulted as the most accurate cut-off values in the outcome prediction. Conclusions: Present data support the cardiopulmonary exercise test and, particularly, the peak oxygen uptake, as a useful tool in the rec-HFmrEF prognostic assessment. A peak VO2 of ≤55% predicted and ventilatory efficiency of ≥31 might help to identify a high-risk rec-HFmrEF subgroup.

Published
2020

7. Long-term prognostic role of diabetes mellitus and glycemic control in heart failure patients with reduced ejection fraction: Insights from the MECKI Score database

Author

Stefania, Paolillo, Elisabetta, Salvioni, Pasquale, Perrone Filardi, Alice, Bonomi, Gianfranco, Sinagra, Piero, Gentile, Paola, Gargiulo, Alessandra, Scoccia, Nicola, Cosentino, Paola, Gugliandolo, Roberto, Badagliacca, Rocco, Lagioia, Michele, Correale, Maria, Frigerio, Enrico, Perna, Massimo, Piepoli, Federica, Re, Rosa, Raimondo, Chiara, Minà, Francesco, Clemenza, Maurizio, Bussotti, Giuseppe, Limongelli, Rita, Gravino, Andrea, Passantino, Damiano, Magrì, Gianfranco, Parati, Sergio, Caravita, Angela B, Scardovi, Luca, Arcari, Carlo, Vignati, Massimo, Mapelli, Gaia, Cattadori, Carlo, Cavaliere, Ugo, Corrà, Piergiuseppe, Agostoni, Paolillo, S, Salvioni, E, Perrone Filardi, P, Bonomi, A, Sinagra, G, Gentile, P, Gargiulo, P, Scoccia, A, Cosentino, N, Gugliandolo, P, Badagliacca, R, Lagioia, R, Correale, M, Frigerio, M, Perna, E, Piepoli, M, Re, F, Raimondo, R, Minà, C, Clemenza, F, Bussotti, M, Limongelli, G, Gravino, R, Passantino, A, Magrì, D, Parati, G, Caravita, S, Scardovi, Ab, Arcari, L, Vignati, C, Mapelli, M, Cattadori, G, Cavaliere, C, Corrà, U, Agostoni, P, Paolillo, S., Salvioni, E., Perrone Filardi, P., Bonomi, A., Sinagra, G., Gentile, P., Gargiulo, P., Scoccia, A., Cosentino, N., Gugliandolo, P., Badagliacca, R., Lagioia, R., Correale, M., Frigerio, M., Perna, E., Piepoli, M., Re, F., Raimondo, R., Mina, C., Clemenza, F., Bussotti, M., Limongelli, G., Gravino, R., Passantino, A., Magri, D., Parati, G., Caravita, S., Scardovi, A. B., Arcari, L., Vignati, C., Mapelli, M., Cattadori, G., Cavaliere, C., Corra, U., and Agostoni, P.

Subjects
Diabetes mellitu, Diabetes mellitus, Glycated hemoglobin, Humans, Stroke Volume, Heart failure, Prognosis, Settore MED/11 - Malattie dell'Apparato Cardiovascolare, Glycemic Control, diabetes mellitus, glycated hemoglobin, heart failure, prognosis, glycemic control, humans, kidney, stroke volume, Kidney
Abstract

Background: The prognostic role of diabetes mellitus (DM) in heart failure (HF) patients is undefined, since DM is outweighed by several DM-related variables when confounders are considered. We determined the prognostic role of DM, treatment, and glycemic control in a real-life HF population. Methods: 3927 HF patients included in the Metabolic Exercise Cardiac Kidney Index (MECKI) score database were evaluated with a median follow-up of 3.66 years (IQR 1.70–6.67). Data analysis considered survival between DM (n = 897) vs. non-DM (n = 3030) patients, and, in diabetics, between insulin (n = 304), oral antidiabetics (n = 479), and dietary only (n = 88) treatments. The role of glycemic control was evaluated grouping DM patients according to glycated hemoglobin (HbA1c): 8% (n = 149). All analyses were performed also adjusting for ejection fraction, renal function, hemoglobin, sodium, exercise peak oxygen uptake, and ventilation/carbon dioxide relationship slope. Study primary endpoint was the composite of cardiovascular death, urgent heart transplantation, or left ventricular assist device implantation. Secondary endpoints were cardiovascular and all causes death. Results: For all endpoints, upon adjustment for confounders, DM status and insulin treatment or dietary regimen were not significantly associated with adverse long-term prognosis compared to non-DM and oral antidiabetic treated patients, respectively. A worse prognosis was observed in HbA1c >8% patients (Log-Rank p < 0.001), even after correction for confounding factors. All results were replicated by hazard ratio analysis. Conclusion: In HF patients, DM, insulin treatment and dietary regimen are not adverse outcome predictors. The only condition related to long-term prognosis, considering potential confounders, is poor glycemic control.

Published
2020

8. Deceptive meaning of oxygen uptake measured at the anaerobic threshold in patients with systolic heart failure and atrial fibrillation

Author

Damiano, Magrì, Piergiuseppe, Agostoni, Ugo, Corrà, Claudio, Passino, Domenico, Scrutinio, Pasquale, Perrone-Filardi, Michele, Correale, Gaia, Cattadori, Marco, Metra, Davide, Girola, Massimo F, Piepoli, AnnaMaria, Iorio, Michele, Emdin, Rosa, Raimondo, Federica, Re, Mariantonietta, Cicoira, Romualdo, Belardinelli, Marco, Guazzi, Giuseppe, Limongelli, Francesco, Clemenza, Gianfranco, Parati, Maria, Frigerio, Matteo, Casenghi, Angela B, Scardovi, Alessandro, Ferraironi, Andrea, Di Lenarda, Maurizio, Bussotti, Anna, Apostolo, Stefania, Paolillo, Rocco, La Gioia, Paola, Gargiulo, Pietro, Palermo, Chiara, Minà, Stefania, Farina, Elisa, Battaia, Antonello, Maruotti, Giuseppe, Pacileo, Mauro, Contini, Fabrizio, Oliva, Roberto, Ricci, Gianfranco, Sinagra, Corrado, Vassanelli, Magrì, D, Agostoni, P, Corrà, U, Passino, C, Scrutinio, D, Perrone Filardi, P, Correale, M, Cattadori, G, Metra, M, Girola, D, Piepoli, M, Iorio, A, Emdin, M, Raimondo, R, Re, F, Cicoira, M, Belardinelli, R, Guazzi, M, Limongelli, G, Clemenza, F, Parati, G, Frigerio, M, Casenghi, M, Scardovi, A, Ferraironi, A, Di Lenarda, A, Bussotti, M, Apostolo, A, Paolillo, S, La Gioia, R, Gargiulo, P, Palermo, P, Minà, C, Farina, S, Battaia, E, Maruotti, A, Pacileo, G, Contini, M, Oliva, F, Ricci, R, Sinagra, G, Magrì, Damiano, Agostoni, Piergiuseppe, Corrà, Ugo, Passino, Claudio, Scrutinio, Domenico, Perrone Filardi, Pasquale, Correale, Michele, Cattadori, Gaia, Metra, Marco, Girola, Davide, Piepoli, Massimo F., Iorio, Annamaria, Emdin, Michele, Raimondo, Rosa, Re, Federica, Cicoira, Mariantonietta, Belardinelli, Romualdo, Guazzi, Marco, Limongelli, Giuseppe, Clemenza, Francesco, Parati, Gianfranco, Frigerio, Maria, Casenghi, Matteo, Scardovi, Angela B., Ferraironi, Alessandro, DI LENARDA, Andrea, Bussotti, Maurizio, Apostolo, Anna, Paolillo, Stefania, La Gioia, Rocco, Gargiulo, Paola, Palermo, Pietro, Minà, Chiara, Farina, Stefania, Battaia, Elisa, Maruotti, Antonello, Pacileo, Giuseppe, Contini, Mauro, Oliva, Fabrizio, Ricci, Roberto, Sinagra, Gianfranco, PERRONE FILARDI, Pasquale, Piepoli, Massimo F, Scardovi, Angela B, Di Lenarda, Andrea, Magri', D, Corra', U, PERRONE FILARDI, P, Correal, M, Piepoli, Mf, Iorio, Am, Raimonod, R, Cicoria, M, Scardovi, Ab, DI LENARDA, A, LA GIOIA, R, Mina', C, and Sinagra, G.

Subjects
Male, Time Factors, Digoxin, Anaerobic Threshold, Epidemiology, medicine.medical_treatment, Heart failure, anaerobic threshold, atrial fibrillation, exercise, prognosis, Predictive Value of Test, Kaplan-Meier Estimate, Risk Factors, Atrial Fibrillation, Sinus rhythm, Prospective Studies, Multivariate Analysi, Heart transplantation, Ejection fraction, Cardiology and Cardiovascular Medicine, Atrial fibrillation, Middle Aged, Prognosis, Italy, Area Under Curve, Cardiology, Female, Anaerobic exercise, prognosi, medicine.drug, Human, medicine.medical_specialty, Time Factor, Prognosi, Reproducibility of Result, Oxygen Consumption, Predictive Value of Tests, Internal medicine, Aged, Heart Failure, Systolic, Heart Transplantation, Humans, Multivariate Analysis, Proportional Hazards Models, ROC Curve, Reproducibility of Results, Exercise Test, medicine, business.industry, Risk Factor, medicine.disease, Transplantation, Prospective Studie, Proportional Hazards Model, business, Systolic
Abstract

Background: Oxygen uptake at the anaerobic threshold (VO 2 AT), a submaximal exercise-derived variable, independent of patients' motivation, is a marker of outcome in heart failure (HF). However, previous evidence of VO 2 AT values paradoxically higher in HF patients with permanent atrial fibrillation (AF) than in those with sinus rhythm (SR) raised uncertainties. Design: We tested the prognostic role of VO 2 AT in a large cohort of systolic HF patients, focusing on possible differences between SR and AF. Methods: Altogether 2976 HF patients (2578 with SR and 398 with AF) were prospectively followed. Besides a clinical examination, each patient underwent a maximal cardiopulmonary exercise test (CPET). Results: The follow-up was analysed for up to 1500 days. Cardiovascular death or urgent cardiac transplantation occurred in 303 patients (250 (9.6%) patients with SR and 53 (13.3%) patients with AF, p=0.023). In the entire population, multivariate analysis including peak oxygen uptake (VO 2 ) showed a prognostic capacity (C-index) similar to that obtained including VO 2 AT (0.76 vs 0.72). Also, left ventricular ejection fraction, ventilation vs carbon dioxide production slope, β-blocker and digoxin therapy proved to be significant prognostic indexes. The receiver-operating characteristic (ROC) curves analysis showed that the best predictive VO 2 AT cut-off for the SR group was 11.7 ml/kg/min, while it was 12.8 ml/kg/min for the AF group. Conclusions: VO 2 AT, a submaximal CPET-derived parameter, is reliable for long-term cardiovascular mortality prognostication in stable systolic HF. However, different VO 2 AT cut-off values between SR and AF HF patients should be adopted.

Published
2015

9. Exercise performance is a prognostic indicator in elderly patients with chronic heart failure: application of metabolic exercise cardiac kidney indexes score

Author

Valentina, Carubelli, Marco, Metra, Ugo, Corrà, Damiano, Magrì, Claudio, Passino, Carlo, Lombardi, Domenico, Scrutinio, Michele, Correale, Gaia, Cattadori, Massimo F, Piepoli, Elisabetta, Salvioni, Marta, Giovannardi, Rosa, Raimondo, Mariantonietta, Cicoira, Romualdo, Belardinelli, Marco, Guazzi, Giuseppe, Limongelli, Francesco, Clemenza, Gianfranco, Parati, Angela B, Scardovi, Andrea, Di Lenarda, Maurizio, Bussotti, Rocco, La Gioia, Piergiuseppe, Agostoni, Federica, Re, Carubelli, V., Metra, M., Corra, U., Magri, D., Passino, C., Lombardi, C., Scrutinio, D., Correale, M., Cattadori, G., Piepoli, M. F., Salvioni, E., Giovannardi, M., Raimondo, R., Cicoira, M., Belardinelli, R., Guazzi, M., Limongelli, G., Clemenza, F., Parati, G., Scardovi, A. B., Di Lenarda, A., Bussotti, M., La Gioia, R., Agostoni, P., Carubelli, V, Metra, M, Corrà, U, Magrì, D, Passino, C, Lombardi, C, Scrutinio, D, Correale, M, Cattadori, G, Piepoli, M, Salvioni, E, Giovannardi, M, Raimondo, R, Cicoira, M, Belardinelli, R, Guazzi, M, Limongelli, G, Clemenza, F, Parati, G, Scardovi, A, Di Lenarda, A, Bussotti, M, La Gioia, R, and Agostoni, P

Subjects
Databases, Factual, medicine.medical_treatment, Adrenergic beta-Antagonists, Adult, Age Factors, Aged, Chronic Disease, Female, Follow-Up Studies, Humans, Male, Middle Aged, Oxygen, Sodium, Exercise Therapy, Heart Failure, Systolic, Kidney, Organ Dysfunction Scores, Stroke Volume, heart failure, Organ Dysfunction Score, middle aged, Clinical endpoint, Medicine, Age Factor, humans, sodium, Heart transplantation, education.field_of_study, Framingham Risk Score, Ejection fraction, exercise therapy, adult, General Medicine, follow-up studies, aged, cardiology and cardiovascular medicine, female, Quartile, Cardiology, cardiopulmonary exercise test, Human, medicine.medical_specialty, age factors, kidney, databases factual, Population, exercise performance, elderly, MECKI score, adrenergic beta-antagonists, chronic disease, male, oxygen, heart failure, systolic, organ dysfunction scores, stroke volume, Follow-Up Studie, Databases, Internal medicine, education, Factual, business.industry, Kidney metabolism, Adrenergic beta-Antagonist, Cardiopulmonary exercise test, Elderly, Exercise performance, Heart failure, Cardiology and Cardiovascular Medicine, medicine.disease, Exercise Performance, Prognostic Indicator, Chronic Heart Failure, systolic, business
Abstract

Background:In patients with chronic heart failure (HF) the Metabolic Exercise Cardiac Kidney Indexes (MECKI) score, is a predictor of cardiovascular death and urgent heart transplantation. We investigated the relationship between age, exercise tolerance and the prognostic value of the MECKI score.Methods and Results:We analyzed data from 3,794 patients with chronic systolic HF. The primary endpoint was a composite of cardiovascular death and urgent heart transplantation. Older patients had higher prevalence of comorbidities and lower exercise performance compared with younger subjects (peak V̇O2, 925 vs. 1,351 L/min; P#x003C;0.0001; V̇E/V̇CO2slope, 33.2 vs. 28.3; P>0.0001). The rate of the primary endpoint was 19% in the highest age quartile and 14% in the lowest quartile. At multivariable analysis, the independent predictors of the primary endpoint were left ventricular ejection fraction (LVEF), eGFR, peak V̇O2, serum Na+and the use of β-blockers in patients aged ≥70 years, and LVEF, eGFR and peak V̇O2in younger subjects. The MECKI risk score increased across age subgroups, but on receiver operating characteristic curve analysis its prognostic power was similar in both patients aged ≥70 and #x003C;70 years.Conclusions:Older patients with HF are a high-risk population with lower exercise performance. The MECKI score increased according to age and maintained its prognostic value also in older patients.

Published
2015

10. Additive prognostic value of cardiopulmonary exercise testing in elderly patients with heart failure.

Author

Angela B. Scardovi, Renata De maria, Andrea Celestini, Silvia Perna, Claudio Coletta, Mauro Feola, Nadia Aspromonte, Gian Luca Rosso, Alessandro Carunchio, Alessandro Ferraironi, Alessandro Pimpinella, and Roberto Ricci

Subjects
*HEART failure, *DISEASES in older people, *EXERCISE tests, *ARRHYTHMIA, *CLINICAL prediction rules, *HEALTH risk assessment, *PROGNOSIS
Abstract

To date, the role of CPET (cardiopulmonary exercise testing) for risk stratification in elderly patients with HF (heart failure) with depressed or preserved ventricular function has not been evaluated. In the present study, we analysed whether CPET is useful in predicting outcome in this population. A total of 220 NYHA (New York Heart Association) class I–III patients with HF ≥70 years of age [median age, 75 years; 23% had NYHA class III; and 59% had preserved ventricular systolic function (left ventricular ejection fraction ≥40%)] performed maximal CPET (peak expiratory exchange ratio >1.00). Median peak oxygen uptake was 11.9 ml·kg−1of body weight·min−1, median V̇E/V̇CO2slope (slope of the minute ventilation/carbon dioxide production ratio) was 33.2 and 45% had an EVR (enhanced ventilatory response) to exercise (V̇E/V̇CO2slope ≥34). During 19 months of follow-up, 94 patients (43%) met the combined end point of death and hospital admission for worsening HF, arrhythmias or acute coronary syndromes. By Cox multivariable analysis, a creatinine clearance of <50 ml/min {HR (hazard ratio), 1.657 [95% CI (confidence interval), 1.055–2.602]} and EVR [HR, 1.965 (95% CI, 1.195–3.231)] were the best predictors of outcome, while ventricular function had no influence on prognosis. In conclusion, in elderly patients with HF, a steeper V̇E/V̇CO2slope provides additional information for risk stratification across the spectrum of ventricular function and identifies a high-risk population, commonly not considered in exercise testing guidelines. [ABSTRACT FROM AUTHOR]

Published
2009
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