Leanne Jeffriess

Effects of exercise intervention on myocardial function in type 2 diabetes

Objective: To identify the effects of a 1-year exercise intervention on myocardial dysfunction in patients with type 2 diabetes mellitus (T2DM). Design: Randomised controlled trial, the Diabetes Lifestyle Intervention Study. Setting: University hospital. Patients: 223 T2DM patients without occult coronary artery disease, aged 18–75 were randomised to an exercise training group (n = 111) or a usual care group (n = 112). Complete follow-up data were available in 176 (88 exercise, 88 usual care). Interventions: Exercise training consisted of gym, followed by telephone-monitored home-based exercise training. Main outcome measures: Tissue Doppler-derived myocardial velocities, strain-rate and strain, body composition, glycated haemoglobin (HbA1c), maximum oxygen consumption (VO2max) and physical activity. Results: Overall changes in myocardial function were not different between groups despite improvements in waist circumference, fat mass, blood glucose, HbA1c, insulin sensitivity, VO2max and 6-minute walk distance in the intervention group (p<0.05). The latter also spent significantly more time in vigorous activity (p<0.05). A post-hoc analysis revealed that intervention patients who spent more time in both moderate and vigorous activity showed a significant improvement in myocardial tissue velocity (p<0.01), HbA1c (p = 0.03) and VO2max (p = 0.03) compared to controls. Myocardial strain rate (p = 0.03) and HbA1c improved in intervention patients with the greatest increase in moderate activity (p = 0.03). Conclusions: In patients with T2DM, current exercise recommendations led to an improvement in metabolic function, but failed to improve myocardial function in the overall group. Patients with greater increases in both moderate and vigorous activity showed improvements in myocardial function, glycaemic control and cardiorespiratory fitness. Trial registration number: ACTRN12607000060448.

Assessment of Myocardial Viability at Dobutamine Echocardiography by Deformation Analysis Using Tissue Velocity and Speckle-Tracking

OBJECTIVES Comparison of myocardial tissue-velocity imaging (TVI) and speckle-tracking echocardiography (STE) for prediction of viability at dobutamine echocardiography (DbE). BACKGROUND Use of TVI-based strain imaging during DbE may facilitate the prediction of myocardial viability but has technical limitations. STE overcomes these but requires evaluation for prediction of viability. METHODS We studied 55 patients with ischemic heart disease and left ventricular systolic dysfunction (left ventricular ejection fraction <0.45) who were undergoing DbE for assessment of myocardial viability and who subsequently underwent myocardial revascularization. TVI was used to measure longitudinal end-systolic strain (longS) and peak systolic strain rate (SR) at rest and at low-dose dobutamine (LDD). Longitudinal, radial, and circumferential strain and strain rate were measured with STE. Segmental functional recovery was defined by improved wall-motion score on side-by-side comparison of echocardiographic images before and 9 months after revascularization and areas under the receiver operator characteristic curves were used to compare methods. RESULTS Of the 375 segments with abnormal resting function, 154 (41%) showed functional recovery. Only circumferential resting and low-dose STE strain and low-dose longitudinal strain and SR predicted functional recovery independent of wall-motion analysis. Among different strain parameters, only TVI-based longitudinal end-systolic strain and peak systolic SR at LDD had incremental value over wall-motion analysis (areas under the receiver operator characteristic curves of 0.79, 0.79, and 0.74, respectively). STE measurements of strain and SR identified viability only in the anterior circulation, whereas TVI strain and SR accurately identified viability in both anterior and posterior circulations. CONCLUSIONS Combination of TVI or STE methods with DbE can predict viability, with TVI strain and SR at LDD being the most accurate. TVI measures can predict viability in both anterior and posterior circulations, but STE measurements predict viability only in the anterior circulation.

Cardiorespiratory Fitness Is Related to Physical Inactivity, Metabolic Risk Factors, and Atherosclerotic Burden in Glucose-Intolerant Renal Transplant Recipients

The mechanisms of reduced cardiorespiratory fitness (CF) in renal transplant recipients (RTR) have not been studied closely. This study evaluated the relationships between CF and specific cardiovascular risk factors (metabolic syndrome [MS], physical inactivity, myocardial ischemia, and atherosclerotic burden) in glucose-intolerant RTR. Data were recorded on 71 glucose-intolerant RTR (mean age 55 yr; 55% male; median transplant duration 5.7 yr). MS was defined using National Cholesterol Education Programme Adult Treatment Panel III criteria. Resting and exercise stress echocardiography were performed, and myocardial ischemia was identified by new or worsening wall motion abnormalities. Cardiorespiratory fitness was determined using peak oxygen uptake (VO(2)) by expired gas analysis. Atherosclerotic burden was assessed by carotid intima-media thickness (IMT). Mean peak VO(2) was 19 +/- 7 ml/kg per min and was significantly lower than predicted peak VO(2) (29 +/- 6 ml/kg per min; P < 0.001). Patients with MS (63%) had reduced CF (17 +/- 6 versus 22 +/- 8 ml/kg per min; P = 0.001) and were more likely to be physically inactive (76 versus 48%; P = 0.02). CF was reduced in 14 patients with myocardial ischemia (15 +/- 3 versus 20 +/- 7 ml/kg per min; P = 0.05). CF was positively correlated with male gender, height, and physical activity and inversely correlated with number of MS risk factors and IMT (adjusted R(2) = 0.66). Carotid IMT added incremental value to clinical variables in determining VO(2) (adjusted R(2) = 0.65 versus 0.63; P = 0.04). Reduced CF is associated with physical inactivity, MS, and atherosclerotic burden in glucose-intolerant RTR. Further studies should address whether increasing exercise and modifying MS risk factors improve CF in RTR.

Cardiac contributions to exercise training responses in patients with chronic heart failure: a strain imaging study.

The improvement of exercise capacity due to exercise training in heart failure has been associated with peripheral adaptation, but the contribution of cardiac responses is less clear. We sought the extent to which the improvement of functional capacity in patients undergoing exercise training for heart failure was related to myocardial performance. Thirty‐seven patients (35 men, age 64 ± 11) with symptomatic heart failure and left ventricular ejection fraction ≤35% (29 ± 9%) were studied during a 16‐week exercise training program. LV function was assessed by resting and exercise 2D‐echocardiography, tissue Doppler derived myocardial strain, and strain rate. Peak oxygen consumption (VO2) and LV function were measured at baseline and follow‐up, and the contribution of LV function at baseline and its response to training to the change of each parameter was sought. Baseline peak VO2 (12.4 ± 4.6) increased by 9% at 8 weeks (13.5 ± 4.2, P = 0.26), and by 21% at 16 weeks (15.0 ± 4.9, P < 0.001). Although there were no overall changes in myocardial parameters in this study, change in peak VO2 at 16 weeks was significantly correlated with baseline strain (r = 0.51, P = 0.003) and the improvement of strain at 8 weeks (r = 0.44, P = 0.01), independent of baseline functional capacity and clinical variables. Thus, change in peak VO2 following 16 weeks exercise training is related to myocardial function at baseline.

A new technique for assessing arterial pressure wave forms and central pressure with tissue Doppler

BackgroundNon-invasive assessment of arterial pressure wave forms using applanation tonometry of the radial or carotid arteries can be technically challenging and has not found wide clinical application. 2D imaging of the common carotid arteries is routinely used and we sought to determine whether arterial waveform measurements could be derived from tissue Doppler imaging (TDI) of the carotid artery.MethodsWe studied 91 subjects (52 men, age 52 ± 14 years) with and without cardiovascular disease. Tonometry was performed on the carotid artery simultaneously with pulsed wave Doppler of the LVOT and acquired digitally. Longitudinal 2D images of the common carotid artery with and without TDI were also acquired digitally and both TDI and tonometry were calibrated using mean and diastolic cuff pressure and analysed off line.ResultsCorrelation between central pressure by TDI and tonometry was excellent for maximum pressure (r = 0.97, p < 0.0001). The mean differences between central pressures derived by TDI and tonometry were minimal (systolic 5.36 ± 5.5 mmHg; diastolic 1.2 ± 1.2 mmHg).ConclusionImaging of the common carotid artery motion with tissue Doppler may permit acquisition of a waveform analogous to that from tonometry. This method may simplify estimation of central arterial pressure and calculation of total arterial compliance.

Biomarker and imaging responses to spironolactone in subclinical diabetic cardiomyopathy

BACKGROUND Subclinical diabetic cardiomyopathy (DCM) is frequent in asymptomatic subjects with type 2 diabetes (T2DM). We sought the response of functional and fibrosis markers to therapy in a trial of aldosterone antagonism for treatment of DCM. METHODS Biochemical, anthropometric, and echocardiographic data were measured in 225 subjects with T2DM. Myocardial function was evaluated with standard echocardiography and myocardial deformation; ischaemia was excluded by exercise echocardiography. Calibrated integrated backscatter and post-contrast T1 mapping from cardiac magnetic resonance imaging were used to assess myocardial structure. Amino-terminal propeptides of pro-collagen type I (PINP) and III (PIIINP), the carboxy-terminal propeptide of pro-collagen type I (PICP) and transforming growth factor beta-1 were measured from peripheral blood or urine to assess myocardial collagen turnover. RESULTS Diastolic dysfunction was identified in 81 individuals, of whom 49 (25 male, age 60 ± 10 years) were randomized to spironolactone 25 mg/day or placebo therapy for 6 months. Groups were well-matched at baseline. Spironolactone therapy was associated with improvements in diastolic filling profile (Δpeak E wave velocity -4 ± 15 vs. 9 ± 10 ms, P = 0.001; ΔE/A ratio -0.1 ± 0.3 vs. 0.2 ± 0.2, P < 0.001) and cIB values (-21.2 ± 4.5 dB vs. -18.0 ± 5.2 dB, P = 0.026; ΔcIB -5.1 ± 6.8 vs. -1.3 ± 5.2, P = 0.030). ΔcIB was independently associated with spironolactone therapy (β = 0.320, P = 0.026) but not Δblood pressure. With intervention, pro-collagen biomarkers (ΔPINP P = 0.92, ΔPICP P = 0.25, ΔPIIINP P = 0.52, and ΔTGF-β1 P = 0.71) and T1 values (P = 0.54) remained similar between groups. CONCLUSIONS Spironolactone-induced changes in myocardial structure and diastolic properties in DCM are small, and are unassociated with changes in collagen biomarkers or T1 values.

Cardiac and vascular structure and function parameters do not improve with alternate nightly home hemodialysis: An interventional cohort study

BackgroundNightly extended hours hemodialysis may improve left ventricular hypertrophy and function and endothelial function but presents problems of sustainability and increased cost. The effect of alternate nightly home hemodialysis (NHD) on cardiovascular structure and function is not known.MethodsSixty-three patients on standard hemodialysis (SHD: 3.5-6 hours/session, 3-5 sessions weekly) converted to NHD (6-10 hours/session overnight for 3-5 sessions weekly). 2Dimensional transthoracic echocardiography and ultrasound measures of brachial artery reactivity (BAR), carotid intima-media thickness (CIMT), total arterial compliance (TAC) and augmentation index (AIX) were performed post dialysis at baseline and 18-24 months following conversion to NHD. In 37 patients, indices of oxidative stress: plasma malonyldialdehyde (MDA) and anti-oxidant enzymes: catalase (CAT), glutathione peroxidase (GPX) and superoxide dismutase (SOD) activity and total antioxidant status (TAS) were measured at baseline, 3 and 6 months.ResultsLeft ventricular mass index (LVMI) remained stable. Despite significant derangement at baseline, there were no changes in diastolic function measures, CIMT, BAR and TAC. AIX increased. Conversion to NHD improved bone mineral metabolism parameters and blood pressure control. Interdialytic weight gains increased. No definite improvements in measures of oxidative stress were demonstrated.ConclusionsDespite improvement in uremic toxin levels and some cardiovascular risk factors, conversion to an alternate nightly NHD regimen did not improve cardiovascular structure and function. Continuing suboptimal control of uremic toxins and interdialytic weight gains may be a possible explanation. This study adds to the increasing uncertainty about the nature of improvement in cardiovascular parameters with conversion to intensive hemodialysis regimens. Future randomized controlled trials will be important to determine whether increases in dialysis session duration, frequency or both are most beneficial for improving cardiovascular disease whilst minimizing costs and the impact of dialysis on quality of life.

A comparison of methods for assessing total arterial compliance

There are several methods of assessing total arterial compliance (TAC) based on the two element Windkessel model, which is a ratio of pressure and volume, but the optimal technique is unclear. In this study, three methods of estimating TAC were compared to determine which was the most robust in a large group of patients with and without cardiovascular risk. In all, 320 patients (170 men; age 55±10) were studied; TAC was determined by the pulse-pressure method (PPM), the area method (AM) and the stroke volume/pulse-pressure method (SVPP). We obtained arterial waveforms using radial applanation tonometry, dimensions using two-dimensional echocardiography and flow data by Doppler. Clinical data, risk factors, echo parameters and TAC by all three methods were then compared. TAC (ml mm Hg–1) by the PPM was 1.24±0.51, by the AM 1.84±0.90 and by the SVPP 1.96±0.76 (P<0.0001 between groups). Correlation was good between all methods: PPM/AM r=0.83, PPM/SVPP r=0.94 and AM/SVPP r=0.80 (all P<0.0001). Subgroup analysis showed significant differences between patients with and those without cardiovascular risk for all three methods; TAC–AM and TAC–SVPP values were similar and significantly higher than TAC–PPM. The only significant relationships observed with TAC and echo parameters were in left ventricular (LV) septal thickness (R2=0.07; P<0.0001) and LV mass (R2=0.04; P=0.004). Normal and abnormal values of TAC vary according to method, which should be expressed. Each of the techniques shows good correlation with each other, however, values for TAC–PPM are significantly lower. TAC–PPM and TAC–SVPP are comparable in determining differences between groups with and without cardiovascular risk.

Effect of duration of data averaging interval on reported peak VO2 in patients with heart failure

AIM To describe the effect of the duration of the data averaging interval on the calculated peak oxygen uptake (VO2) reported from a symptom-limited maximal exercise test in patients with heart failure. METHODS Maximal exercise test results from 275 patients diagnosed with stable heart failure due to left ventricular systolic dysfunction (ejection fraction<45%; age: 45-75 years; peak VO2: 8.0-20.0mL/kg/min), were examined. Sampling rates of 10, 20, 30 and 60s were used to calculate peak VO2, which was identified as the highest interval value that occurred during the final minute of exercise or the first interval in immediate recovery. RESULTS Mean peak VO2 (mL/kg/min) across the four sampling periods was as follows: 14.0±3.0 (10s), 13.7±3.0 (20s), 13.5±3.0 (30s) and 13.2±2.9 (60s) and there was a significant reduction with increasing averaging duration (p<0.0001). Peak VO2 was significantly different between the 10s and 60s sampling times (p<0.0001). Peak respiratory exchange ratio (RER) was also significantly different between 10 and 60s sampling rates (p<0.0001). Sub-analyses showed peak VO2 values in those people achieving RER>1.05 to be +0.8±0.7mL/kg/min higher than those who had not achieved RER values>1.05; similar findings, +0.8±0.7mL/kg/min, were seen in those patients achieving RER>1.10 versus those who did not. CONCLUSIONS Sampling rate method has a significant effect on calculated peak VO2 and RER. We suggest that laboratories standardize their sampling rate method to ensure consistency.

Derivation of the distensibility coefficient using tissue Doppler as a marker of arterial function.

To date, the main cardiovascular application of TDI (tissue Doppler imaging) has been in myocardial evaluation. In the present study, we investigated the feasibility and reproducibility of assessing arterial elasticity using the DC (distensibility coefficient) measured by TDI, the correlation of this with the DC obtained by other methods and the DC in patients with various degrees of cardiovascular risk. We studied 450 subjects (256 men; age, 51+/-10 years) with and without risk factors of cardiovascular disease. Arterial displacement was measured from TDI, and B-mode and M-mode images of the common carotid artery in the longitudinal plane, and the DC with each method was compared. Linear regression showed a good correlation between all three methods. The results for TDI and B-mode were comparable [(21+/-10) compared with (21+/-10)x10(-3)/kPa respectively; P=not significant], but there were significant differences between TDI and M-mode [(21+/-10) compared with (31+/-13)x10(-3)/kPa respectively; P<0.0001] and between B-mode and M-mode [(21+/-10) compared with (31+/-13)x10(-3)/kPa respectively; P<0.0001]. Similarly, Bland-Altman analysis showed the least variability in the DC between TDI and B-mode, and there were no significant differences between the average measurements. The TDI DC also had the lowest paired difference for inter-observer variability [(-0.1+/-1.1)x10(-3)/kPa; P=not significant]. In conclusion, the results of the present study suggest that TDI of the carotid arteries is feasible, comparable with B-mode measurements, more robust than M-mode and less variable than the other methods.