Abbate, Antonio

Billingsley, Hayley E.

Canada, Justin M.

Carbone, Salvatore

Celi, Francesco S.

Dixon, Dave L.

Kadariya, Dinesh

Markley, Roshi

Medina de Chazal, Horacio

Paudel, Bishal

Potere, Nicola

Rotelli, Brando

Trankle, Cory R.

Van Tassell, Benjamin W.

English

VCU Scholars Compass

Virginia Commonwealth University VCU Scholars Compass Internal Medicine Publications Dept. of Internal Medicine 2019 Unsaturated Fatty Acids to Improve Cardiorespiratory Fitness in Patients With Obesity and HFpEF Salvatore Carbone Virginia Commonwealth University, salvatore.carbone@vcuhealth.org Hayley E. Billingsley Virginia Commonwealth University Justin M. Canada Virginia Commonwealth University Dinesh Kadariya Virginia Commonwealth University Horacio Medina de Chazal Virginia Commonwealth University See next page for additional authors Follow this and additional works at: https://scholarscompass.vcu.edu/intmed_pubs  Part of the Medicine and Health Sciences Commons  © 2019 The Authors. This is an open access article under the CC by NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/) Downloaded from https://scholarscompass.vcu.edu/intmed_pubs/137 This Article is brought to you for free and open access by the Dept. of Internal Medicine at VCU Scholars Compass. It has been accepted for inclusion in Internal Medicine Publications by an authorized administrator of VCU Scholars Compass. For more information, please contact libcompass@vcu.edu. Authors Salvatore Carbone, Hayley E. Billingsley, Justin M. Canada, Dinesh Kadariya, Horacio Medina de Chazal, Brando Rotelli, Nicola Potere, Bishal Paudel, Roshi Markley, Dave L. Dixon, Cory R. Trankle, Benjamin W. Van Tassell, Francesco S. Celi, and Antonio Abbate This article is available at VCU Scholars Compass: https://scholarscompass.vcu.edu/intmed_pubs/137 LettersUnsaturated Fatty Acidsto ImproveCardiorespiratoryFitness in Patients WithObesity and HFpEFThe UFA-Preserved Pilot StudyHeart failure with preserved ejection fraction(HFpEF) and obesity are 2 common and often coex-isting conditions that reduce cardiorespiratory fitness(CRF) (1,2).Intake of unsaturated fatty acids (UFAs), whichconsist of monounsaturated fatty acids (MUFAs) andpolyunsaturated fatty acids (PUFAs), has recentlybeen associated with favorable CRF, body composi-tion, and cardiac diastolic function in patients withobesity and HFpEF (3). A high UFA diet also pre-vented weight gain and cardiac diastolic dysfunction(3) in a mouse model of Western diet-induced cardiacdysfunction (4), despite similar total caloric and totalfats intake. However, the feasibility of a dietaryintervention aimed at increasing daily UFA intake in aprospective trial is required in this population to testits potential efficacy in a large randomized controlledtrial.We hypothesized that a 12-week dietary interven-tion aimed at increasing UFA consumption wasfeasible in patients with obesity and HFpEF, andwould result in increased consumption of UFAs at12 weeks (primary endpoint), as assessed by bothdietary recall and biomarkers. To test this hypothesis,we performed a proof-of-concept trial and enrolled 9patients with obesity, symptomatic HFpEF (i.e.,dyspnea, fatigue), and reduced CRF (<80% of pre-dicted) measured with maximal cardiopulmonaryexercise testing, in a single-arm dietary intervention.All study participants provided written consent(NCT03310099).Dietary intervention consisted of an individual-ized, in-person meeting with a dietitian at baselineand every 4 weeks thereafter, with a weekly tele-phone call to support dietary adherence. Dietaryintervention was aimed at consuming a recom-mended daily amount (or more, without upper limitfor consumption) of UFA-rich foods: extra-virginolive oil (54 g), canola oil (54 g), unsalted orlightly salted mixed dry tree nuts (walnuts, hazel-nuts, almonds, pecans), and peanuts (28 g), withoutproviding recommendations on caloric intake. Inpatients who could not consume the recommendedfoods for personal and/or cultural preferences, thefollowing foods were recommended: unsalted mixedseeds (28 g), Hass avocado (50 g), and fatty fish(salmon, tuna, trout, mackerel, sardines) (170 g). Weprovided $100 of financial support to purchase therecommended UFA-rich foods at baseline and 12-week visits, as well as $50 at 4- and 8-week visits.At each visit, a standardized 5-pass, 24-h dietaryrecall (3) was administered by a dietitian and non-fasting plasma UFA (oleic acid [MUFA], a-linolenicacid, and linoleic acid [PUFA]) levels were measured(Salveo Diagnostics Inc., Henrico, Virginia). We alsomeasured exercise time, peak oxygen consumption(VO2) and peak oxygen (O2) pulse at baseline andat 12 weeks using a metabolic cart interfacedwith a treadmill using a conservative rampingprotocol. Physical activity was assessed usingthe International Physical Activity Questionnaire-short version (IPAQ) to calculate the cumulativemetabolic equivalent of task-minutes per week(MET-min/week). The Shapiro-Wilk test was used toassess deviation from a Gaussian distribution withpaired Student’s t-tests and Pearson’s rank testwith mean  SD used to examine changes betweenbaseline and 12 weeks for normally distributedvariables. Wilcoxon’s test and Spearman’s rank testwith median and interquartile ranges were used tocompare abnormally distributed variables, respec-tively. Statistical analysis was performed using SPSSversion 24.0 (IBM, Armonk, New York).Of 9 patients (6 African American) enrolled, 5 werewomen; mean age was 54  5 years. All patients hadarterial hypertension, and 5 had type 2 diabetes mel-litus. Baseline left ventricular EF, N-terminal pro–brain natriuretic peptide, E/e0 ratio, and left atrialvolumewere 584%, 29 pg/ml (range 17.5 to 54 pg/ml),8.7  2.9, and 57.9  29.7 ml/m2, respectively. Base-line peak VO2 was 16.3  5.9 ml/kg1/min1 or 53  12%of predicted according to age, sex, height, and idealbody weight. Baseline exercise time and O2 pulseJ A C C : B A S I C T O T R A N S L A T I O N A L S C I E N C E V O L . 4 , N O . 4 , 2 0 1 9ª 2 0 1 9 T H E A U T H O R S . P U B L I S H E D B Y E L S E V I E R O N B E H A L F O F T H E A M E R I C A NC O L L E G E O F C A R D I O L O G Y F O U N D A T I O N . T H I S I S A N O P E N A C C E S S A R T I C L E U N D E RT H E C C B Y - N C - N D L I C E N S E ( h t t p : / / c r e a t i v e c o mm o n s . o r g / l i c e n s e s / b y - n c - n d / 4 . 0 / ) .I S S N 2 4 5 2 - 3 0 2 Xwere 10.7  3.2 min and 12.8  4.8 ml/beat,respectively.After 12 weeks, patients reported a significant in-crease in the proportion of daily calories derived fromdietary UFAs and demonstrated an increase in plasmaUFA biomarkers (Figure 1A). In addition to increasedUFA consumption, we observed a significant increasein proportion of calories from total fat consumption(p ¼ 0.007), but not a proportion of calories fromsaturated fatty acids, protein, total calories and mil-ligrams of sodium intake (all p > 0.05). We found asignificant reduction in the proportion of caloriesfrom total carbohydrates (p ¼ 0.011) and fructose (p ¼0.02).Baseline plasma UFAs, MUFAs, and PUFAs werepositively associated with peak VO2 (R ¼ þ0.79; p ¼0.036; R ¼ þ0.75; p ¼ 0.052; R ¼ þ0.79; p ¼ 0.036,respectively) and O2 pulse (R ¼ þ0.86; p ¼ 0.014;R ¼ þ0.89; p ¼ 0.007; R ¼ þ0.86; p ¼ 0.014, respec-tively). After 12 weeks of UFA supplementation, weobserved a significant improvement in exercise timeand O2 pulse (Figure 1B) with a trend toward a sig-nificant increase in peak VO2 (p ¼ 0.069), withoutsignificant changes in the respiratory exchange ratio(1.09  0.09 to 1.07  0.11; p ¼ 0.44), body mass index(40.0 to 40.2 kg/m2; p ¼ 0.21) or IPAQ-estimatedphysical activity (1,155 to 1,030 MET-min/wk; p ¼0.67). Changes in peak VO2 tended to associate withchanges in plasma UFAs (R ¼ þ0.71; p ¼ 0.071),MUFAs (R ¼ þ0.75; p ¼ 0.052), and PUFAs (R ¼ þ0.71;p ¼ 0.071), although the associations did not reachstatistical significance (p < 0.05).Although limited by the small sample size andsingle-arm intervention, for the first time, we showedthat a dietary intervention aimed at increasing UFAconsumption was feasible and had the potential toimprove CRF in patients with severe obesity andHFpEF. Larger randomized controlled trials to testthe efficacy of UFA supplementation on CRF andclinical outcomes, as well as understanding themechanisms through which UFAs may exert thesebeneficial effects are clearly warranted. Finally, un-derstanding whether the improvements in CRFinduced by increased UFA consumption result fromimprovement in cardiac function or noncardiac fac-tors, such as favorable changes in body composition(5), remains a critical question to investigate in futurestudies.*Salvatore Carbone, PhDHayley E. Billingsley, RDJustin M. Canada, PhDDinesh Kadariya, MDHoracio Medina de Chazal, MDBrando Rotelli, BANicola Potere, MDBishal Paudel, BSRoshi Markley, MDFIGURE 1 Dietary and Plasma Level of UFAs, MUFAs, and PUFAsBApeakVO2ExerciseTimeO 2pulse0.02.55.07.510.012.515.017.520.022.525.027.530.0%changefrombasel ineto12week sp=0.069 p=0.024p=0.049(A) Dietary and plasma level of unsaturated fatty acids (UFAs) (monounsaturated fatty acids [MUFAs], polyunsaturated fatty acids [PUFA]) and (B) changes in peakoxygen consumption (VO2), exercise time, and O2 pulse.Letters J A C C : B A S I C T O T R A N S L A T I O N A L S C I E N C E V O L . 4 , N O . 4 , 2 0 1 9A U G U S T 2 0 1 9 : 5 6 3 – 5564Dave L. Dixon, PharmDCory R. Trankle, MDBenjamin W. Van Tassell, PharmDFrancesco S. Celi, MD, MHScAntonio Abbate, MD, PhD*VCU Pauley Heart CenterVirginia Commonwealth UniversityWest Hospital5th Floor, Room 529b1200 East Broad StreetP.O. Box 980204Richmond, Virginia 23298E-mail: salvatore.carbone@vcuhealth.orghttps://doi.org/10.1016/j.jacbts.2019.04.001Please note: The study was supported by the VCU Department of InternalMedicine Pilot Project Grant Program 2017 and by the VCU Pauley Heart CenterPilot Project Grant Program 2017. All authors have reported that they have norelationships relevant to the contents of this paper to disclose.All authors attest they are in compliance with human studies committees andanimal welfare regulations of the authors’ institutions and Food and DrugAdministration guidelines, including patient consent where appropriate. Formore information, visit the JACC: Basic to Translational Science authorinstructions page.REF ER ENCES1. Carbone S, Canada JM, Buckley LF, et al. Obesity contributes to exerciseintolerance in heart failure with preserved ejection fraction. J Am Coll Cardiol2016;68:2487–8.2. Obokata M, Reddy YNV, Pislaru SV, Melenovsky V, Borlaug BA. Evidencesupporting the existence of a distinct obese phenotype of heart failure withpreserved ejection fraction. Circulation 2017;136:6–19.3. Carbone S, Canada JM, Buckley LF, et al. Dietary fat, sugar consumption,and cardiorespiratory fitness in patients with heart failure with preservedejection fraction. J Am Coll Cardiol Basic Transl Sci 2017;2:513–25.4. Carbone S, Mauro AG, Mezzaroma E, et al. A high-sugar and high-fat diet im-pairs cardiac systolic and diastolic function in mice. Int J Cardiol 2015;198:66–9.5. Del Buono MG, Arena R, Borlaug BA, et al. Exercise intolerance in patientswith heart failure. JACC State-of-the-Art Review. J Am Coll Cardiol 2019;73:2209–25.J A C C : B A S I C T O T R A N S L A T I O N A L S C I E N C E V O L . 4 , N O . 4 , 2 0 1 9 LettersA U G U S T 2 0 1 9 : 5 6 3 – 5565

Unsaturated Fatty Acids to Improve Cardiorespiratory Fitness in Patients With Obesity and HFpEF

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Unsaturated Fatty Acids to Improve Cardiorespiratory Fitness in Patients With Obesity and HFpEF

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