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Continuous, Non-Invasive Measurement of the Heart: First Published As 10.1136/Hrt.2009.177113 on 22 October 2009 Diabetes, lipids and metabolism Continuous, non-invasive measurement of the Heart: first published as 10.1136/hrt.2009.177113 on 22 October 2009. Downloaded from haemodynamic response to submaximal exercise in patients with diabetes mellitus: evidence of impaired cardiac reserve and peripheral vascular response D Joshi,1 A Shiwalkar,1 M R Cross,2 S K Sharma,3 A Vachhani,1 C Dutt1 1 Torrent Research Centre, ABSTRACT adaptation to record continuous and dynamic Village Bhat, Gandhinagar, 2 Background: Reduced exercise capacity in diabetics has change in the exercising muscle. Assessing cardiac Gujarat, India; Veeda Clinical function during exercise poses a special challenge as Research, Old Convent of Notre been attributed to limitations in cardiac function and Dame, Derriford, Plymouth, UK; microvascular dysfunction leading to impaired oxygen conventional echocardiographic measures includ- 3 Veeda Clinical Research, supply and nutritive perfusion to exercising muscles. ing strain analysis, can only be done at rest or at Ambawadi Ahmedabad, Gujarat, Objective: To study changes in cardiac function and the end of exercise. Therefore dynamic response to India microvascular utilisation during exercise in diabetic exercise, which is a function of continuous adjust- Correspondence to: individuals compared to age-matched controls. ment of pre-load (Frank-Starling) and after-load as Dr Chaitanya Dutt, Torrent Methods: Diabetics with glycosylated haemoglobin well as direct cardiac adrenergic influence, designed Research Center, PO Bhat, (HbA1c) ,8 (n = 31), diabetics with HbA1c >8 (n = 38) to optimise the inotropic and chronotropic District of Gandhinagar 382428, responses, cannot be captured by these methods. Gujarat, India; cdutt@ and age-matched non-diabetic controls (n = 32) per- torrentpharma.com formed exercise at 50 W for 10 minutes followed by Impedance cardiography (ICG) has been vali- recovery, with continuous monitoring of cardiac function dated to gather ambulatory physiological record- Accepted 29 September 2009 by impedance cardiography and regional flow and oxygen ings and was adapted to monitor cardiac function saturation by laser Doppler and white light spectroscopy. online during exercise.12 For monitoring regional Results: In the diabetics, cardiac reserve during exercise microcirculation this was combined with another and cardiac overshoot during recovery are significantly method where laser Doppler shift caused by the reduced because of reduction in capacity to increase movement of erythrocytes in the detected laser stroke volume. Regional flow to the exercising muscle is light is used to determine arteriolar flow. With the reduced and there is also disproportionately greater same probe, white light is introduced into the desaturation of the regional flow. Abnormalities in cardiac tissue and oxygen saturation of haemoglobin was function and regional perfusion are related to the severity determined from light absorbed by the haemoglo- http://heart.bmj.com/ of diabetes. bin in mixed capillary venous blood at a prede- 3 Conclusion: Cardiac response to exercise is attenuated termined depth from the skin. This study was significantly in diabetic individuals. Simultaneously, there therefore aimed at investigating the sequential is impairment in the regional distribution. These changes changes during mild exercise and recovery in could be the harbinger of reduced exercise capacity in cardiac function and regional microcirculation of diabetics. exercising muscle in diabetes by a method which allows continuous dynamic monitoring, in order to capture early cardiac and vascular correlates, which on September 30, 2021 by guest. Protected copyright. Clinical studies have shown that limitation in could ultimately progress to impaired exercise tolerance. Submaximal exercise is more relevant exercise capacity is a strong predictor of cardiovas- as it is equivalent to the 6-minute walk test, used cular and all-cause mortality in diabetic patients to evaluate exercise capacity in patients with with heart failure. Underlying pathophysiology is marked left ventricular (LV) dysfunction.4 In multifactorial and involves alterations in ventricu- contrast, maximum oxygen consumption lar-vascular coupling consisting of cardiac changes (VO max) may be compromised because of on the one hand and compromised distribution at 2 reduced patient motivation, poor peripheral blood the regional microvasculature on the other. If such flow and impaired skeletal muscle metabolism changes can be detected early (stage A) in those with early development of acidosis, besides limita- who are at risk of progressing to heart failure, it tion in cardiac output, correlates only modestly may help slow down progression by more aggres- with this test.5 sive management of the problem. Though there is fair body of evidence on the mechanism underlying the decline in exercise STUDY PROTOCOL tolerance and despite the recognition of its prog- Subjects nostic significance, monitoring microvascular The investigation conforms to the principles out- changes underlying altered skeletal muscle exercise lined in the Declaration of Helsinki.6 The study capacity and mapping them dynamically against was approved by the institutional review board of cardiac response capacity has not been attempted. Torrent Research Centre and Veeda Clinical This paper is freely available online under the BMJ Journals Monitoring of regional alterations in the micro- Research (Ahmedabad, India). After signing the unlocked scheme, see http:// circulation in patients is restricted by the invasive written informed consent, 127 subjects were heart.bmj.com/info/unlocked.dtl character of methodology and limitations to its screened. The inclusion criteria were subjects with 36 Heart 2010;96:36–41. doi:10.1136/hrt.2009.177113 Diabetes, lipids and metabolism confirmed diabetes as ascertained by history, clinical examina- Response during recovery was measured as AUC of the data Heart: first published as 10.1136/hrt.2009.177113 on 22 October 2009. Downloaded from tion and laboratory investigations, who had no history of points recorded during the recovery phase. Subjects who breathlessness on exertion or limitation in exercise capacity, and completed the exercise phase of 10 minutes were included for age-matched controls who were non-diabetic. Subjects with analysis on exercise data (table 1). For analysis on recovery data, arrhythmia, significant peripheral vascular disease, retinopathy, only those who completed exercise followed by 15 minutes of insulin dependence and those with blood pressure (BP) .180/ recovery were included (28 diabetics with HbA1c,8, 35 100 mm Hg, were excluded from the study. One-hundred and diabetics with HbA1c >8 and 32 age-matched normal controls). one subjects were included in the study and all completed the To calculate oxygen debt for each subject, the value of mean exercise protocol. Data from diabetics with glycosylated SO2 at resting supine baseline, multiplied by the same period of haemoglobin (HbA1c) ,8 (n = 31), diabetics with HbA1c >8 time—that is, 15 minutes, was subtracted from AUC over (n = 38) and age-matched normal controls (n = 32) were 15 minutes of recovery.7 AUC has been calculated using included in the analysis. WinNonlin (Version-5.2). Experimental procedure Statistical analysis At Veeda Clinical Research, after their breakfast subjects had a Data are expressed as mean (SD) and graphically represented as brief physical examination, blood samples were collected for mean (SEM). Statistical analysis has been performed using SAS (Version-9.1). Demographic data have been tested to see estimation of HbA1c, vascular cell adhesion molecule (VCAM), N-terminal brain natriuretic propeptide (NTProBNP) and urine differences among three groups using ANOVA followed by samples for creatinine and microalbumin estimation. Oxygen to post-hoc Dunnett t tests (two-sided). Repeatability was See (O2C, LEA Medizintechnik, Germany) probe LF3 incorpor- determined by a two-sided paired t test on AUC values (derived ating Doppler (830 nm) and near infra-red light spectrum (500– from percentage change during exercise from sitting baseline) of 850 nm), which allows measurement at skeletal muscle post- the O2C parameters, SO2 and flow and ICG parameter, CO. capillary venular site, was placed on the belly of the Proportions of concomitant medications were subjected to gastrocnemious on one leg. ICG (Bioz, Cardiodynamics, USA) Fisher’s exact test. CO, SV, time for downward inflection, and and electrocardiogram (ECG-Mac5000, GE Healthcare, Germany) AUC or AOC of percentage change from baseline, during probes were placed on the chest and BP cuff on the arm. exercise and for recovery period, was compared between groups After calibration, continuous measurements were obtained at by the one-sided unpaired t test. In the absence of normality, baseline in the resting supine position for 10 minutes followed data were subjected to the non-parametric Wilcoxon test. by the upright position for 10 minutes and then acclimatisation Percentage change in systolic time interval over time, of normal, on the bicycle ergometer (eBike, GE Healthcare, Germany) for diabetics with HbA1c ,8 and diabetics with HbA1c >8, were 10 minutes. Exercise was for a duration of 10 minutes, at a compared by repeated measures analysis of variance constant load of 50 W, on the electrically braked ergometer, (RMANOVA). Statistical significance was defined as p value (0.05. varying rpm to maintain the constant load, which is equivalent
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