Exercise Echocardiography of Left Ventricular Diastolic Function in Healthy Subjects: Insights From the RIGHT-NET
Francesco Ferrara, MD, PhD,
Andreina Carbone, MD,
Luna Gargani, MD, PhD,
Rossana Castaldo, PhD,
Paola Argiento, MD, PhD,
Gergely Agoston, MD,
Rodolfo Citro, MD, PhD,
Anna D'Agostino, PhD,
Antonello D’Andrea, MD, PhD,
Michele D'Alto, MD, PhD,
Monica Franzese, PhD,
Stefano Ghio, MD,
Ekkehard Grünig, MD, PhD,
Marco Guazzi, MD, PhD,
Jarosław D. Kasprzak, MD,
Graziella Lacava, MD,
Giuseppe Limongelli, MD, PhD,
Alberto Marra, MD, PhD,
Matteo Mazzola, MD,
Emanuela Passaro, MSc,
Nicola Riccardo Pugliese, MD, PhD,
Salvatore Rega, MD,
Valeria Visco, MD,
Olga Vriz, MD, PhD,
Karina Wierzbowska-Drabik, MD,
Antonio Cittadini, MD, PhD,
Eduardo Bossone, MD, PhD,
Robert Naeije, MD, PhD
Affiliations
Francesco Ferrara, MD, PhD
Cardio-Thoracic-Vascular Department, University Hospital “San Giovanni Di Dio E Ruggi D'Aragona,” Salerno, Italy
Andreina Carbone, MD
Cardiology Unit, University of Campania Luigi Vanvitelli, Naples, Italy; Department of Public Health, University of Naples Federico II, Naples, Italy
Luna Gargani, MD, PhD
Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, University of Pisa, Pisa, Italy
Rossana Castaldo, PhD
IRCCS Synlab SDN, Naples, Italy
Paola Argiento, MD, PhD
Department of Cardiology, Monaldi Hospital–Naples, Italy
Gergely Agoston, MD
Institute of Family Medicine, University of Szeged, Szeged, Hungary
Rodolfo Citro, MD, PhD
Cardio-Thoracic-Vascular Department, University Hospital “San Giovanni Di Dio E Ruggi D'Aragona,” Salerno, Italy; Department of Vascular Pathophysiology, IRCCS Neuromed, Pozzilli, Isernia, Italy
Anna D'Agostino, PhD
IRCCS Synlab SDN, Naples, Italy
Antonello D’Andrea, MD, PhD
Department of Cardiology, Umberto I Hospital Nocera Inferiore, Nocera Inferiore, Italy
Michele D'Alto, MD, PhD
Department of Cardiology, Monaldi Hospital–Naples, Italy
Monica Franzese, PhD
IRCCS Synlab SDN, Naples, Italy
Stefano Ghio, MD
Division of Cardiology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
Ekkehard Grünig, MD, PhD
Center of Pulmonary Hypertension, Thoraxklinik Heidelberg at Heidelberg University Hospital, Heidelberg, Germany
Marco Guazzi, MD, PhD
University of Milano School of Medicine, Department of Biological Sciences, Milano, Italy; San Paolo Hospital, Cardiology Division, Milano, Italy
Jarosław D. Kasprzak, MD
Department of Cardiology, Bieganski Hospital, Medical University of Lodz, Lodz, Poland
Graziella Lacava, MD
Anesthesia and Intensive Care, University Hospital ''San Giovanni di Dio e Ruggi d'Aragona,'' Salerno, Italy
Giuseppe Limongelli, MD, PhD
Inherited and Heart Disease Unit, Monaldi Hospital, A.O. Colli (University of Campania 'Luigi Vanvitelli'), Naples, Italy
Alberto Marra, MD, PhD
Department of Translational Medical Sciences, University of Naples “Federico II,” Naples, Italy
Matteo Mazzola, MD
Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, University of Pisa, Pisa, Italy
Emanuela Passaro, MSc
IRCCS Synlab SDN, Naples, Italy
Nicola Riccardo Pugliese, MD, PhD
Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
Salvatore Rega, MD
Department of Public Health, University of Naples Federico II, Naples, Italy
Valeria Visco, MD
Department of Medicine, Surgery and Dentistry ''Scuola Medica Salernitana,'' University of Salerno, Baronissi, Italy
Olga Vriz, MD, PhD
Presidio Ospedaliero di San Daniele e Tolmezzo, Gemona Del Friuli, Italy
Karina Wierzbowska-Drabik, MD
Department of Internal Diseases and Clinical Pharmacology, Bieganski Hospital, Medical University of Lodz, Lodz, Poland
Antonio Cittadini, MD, PhD
Department of Translational Medical Sciences, University of Naples “Federico II,” Naples, Italy
Eduardo Bossone, MD, PhD
Department of Public Health, University of Naples Federico II, Naples, Italy; Corresponding author: Prof Eduardo Bossone, Department of Public Health, University of Naples “Federico II,” Via Pansini, 5, 80131, Naples, Italy. Tel.: +1(832) 943-8510.
Background: Exercise transthoracic Doppler echocardiography (TTE) is considered suggestive of left ventricular (LV) diastolic dysfunction when the ratio of mitral Doppler E to tissue Doppler e′ waves is >15 with or without a peak tricuspid regurgitation velocity (TRV) >3.4 m/s. However, these measurements may be affected by exercise intensity. The aim of the study was to define the normal limits of LV diastolic function indices during exercise TTE. Methods: One hundred ninety-two healthy adults (47% females, aged 16-76 years) underwent resting and exercise TTE on a semirecumbent cycle ergometer. LV diastolic measurements were acquired at baseline and midlevel exercise (heart rate ≤110 bpm) fusion of E and A waves. TRV was acquired at rest and at peak exercise. The E/e′ ratio was calculated with e′ as the average of septal and lateral measurements. Results: At midlevel exercise, E/e′ increased modestly from 6.3 ± 1.9 to 7.3 ± 2.3 (P < 0.001) as a function of workload and cardiac output (CO), independently of sex and age. The 95th percentile of exercise E/e′ was 11.8. The slope of E/e′/CO was 0.4 ± 1.2/L/min. The slope of TRV/CO was 10.8 ± 11.5 cm/s/L/min. The upper 95% confidence interval of the E/e′/CO and TRV/CO slopes were 0.6/L/min and 13.1 cm/s/L/min, corresponding to an E/e′ of 13.2 and a TRV of 3.4 m/s at a CO of 15 L/min. Conclusions: In healthy adult subjects, E/e′ slightly increased during midlevel exercise. Both E/e′ and TRV are exercise intensity-dependent and would therefore be better expressed as a function of CO for the diagnosis of normal vs abnormal LV diastolic response to exercise. Résumé: Contexte: L’échocardiographie Doppler transthoracique (ETT) à l’effort est considérée comme évoquant une dysfonction diastolique ventriculaire gauche (VG) lorsque le rapport entre l’onde E du Doppler mitral et l’onde e′ du Doppler tissulaire est supérieur à 15 avec ou sans un pic de vitesse de régurgitation tricuspidienne (VRT) supérieur à 3,4 m/s. Cependant, ces mesures peuvent être influencées par l’intensité de l’effort. L’étude visait à définir les limites normales des indices de la fonction diastolique VG pendant l’ETT à l’effort. Méthodologie: Cent quatre-vingt-douze adultes en bonne santé (47 % de femmes; de 16 à 76 ans) ont été soumis à une ETT au repos et à l’effort sur un ergocycle en position semi-allongée. Les mesures diastoliques VG ont été prises au départ et à l’effort modéré (fréquence cardiaque ≤ 110 bpm) en fusion des ondes E et A. La VRT a été mesurée au repos et à l’effort maximal. Le rapport E/e′ a été calculé, la valeur de e′ correspondant à la moyenne des mesures septales et latérales. Résultats: À l’effort modéré, le rapport E/e′ a augmenté modestement, passant de 6,3 ± 1,9 à 7,3 ± 2,3 (p < 0,001) en fonction du travail et du débit cardiaque (DC), indépendamment du sexe et de l’âge. Le 95e percentile du rapport E/e′ à l’effort était de 11,8. La pente du rapport E/e′/DC était de 0,4 ± 1,2/L/min. La pente du rapport VRT/DC était de 10,8 ± 11,5 cm/s/L/min. La limite supérieure de l’intervalle de confiance à 95 % des pentes E/e′/DC et VRT/DC était de 0,6/L/min et de 13,1 cm/s/L/min, respectivement, soit un E/e′ de 13,2 et une VRT de 3,4 m/s à un DC de 15 L/min. Conclusions: Chez des sujets adultes en bonne santé, le rapport E/e′ a légèrement augmenté pendant l’effort modéré. Les valeurs E/e′ et VRT dépendent toutes deux de l’intensité de l’effort et seraient donc mieux exprimées comme une fonction du débit cardiaque pour le diagnostic d’une réponse diastolique VG normale ou anormale à l’effort.
