Chiew Wong

Alterations of Left Ventricular Myocardial Characteristics Associated With Obesity

Background—Obesity is associated with heart failure, but an effect of weight, independent of comorbidities, on cardiac structure and function is not well established. We sought whether body mass index (BMI) and insulin levels were associated with subclinical myocardial disturbances. Methods and Results—Transthoracic echocardiography, myocardial Doppler-derived systolic (sm) and early diastolic velocity (em), strain and strain rate imaging and tissue characterization with cyclic variation (CVIB), and calibrated integrated backscatter (cIB) were obtained in 109 overweight or obese subjects and 33 referents (BMI <25 kg/m2). BMI correlated with left ventricular (LV) mass and wall thickness (P<0.001). Severely obese subjects (BMI >35) had reduced LV systolic and diastolic function and increased myocardial reflectivity compared with referents, evidenced by lower average long-axis strain, sm, cIB, lower CVIB, and reduced em, whereas LV ejection fraction remained normal. Differences in regional or global strain, sm, and em were identified between the severely obese (BMI >35) and the referent patients (P<0.001). Similar but lesser degrees of reduced function by sm, em, and basal septal strain and increased reflectivity by cIB were present in overweight (BMI, 25 to 29.9) and mildly obese (BMI, 30 to 35) groups (P<0.05). Although tissue Doppler measures were not associated with duration of obesity, they did correlate with fasting insulin levels and reduced exercise capacity. BMI was independently related to average LV strain (&bgr;=0.40, P=0.02), sm (&bgr;=−0.36, P=0.002), and em (&bgr;=−0.41, P<0.001). Conclusions—Overweight subjects without overt heart disease have subclinical changes of LV structure and function even after adjustment for mean arterial pressure, age, gender, and LV mass.

Obesity cardiomyopathy: pathogenesis and pathophysiology.

Obesity is becoming a worldwide phenomenon. Myocardial changes associated with the obese state are increasingly recognized, independent of hypertension, obstructive sleep apnea and coronary artery disease. The existence of a cardiomyopathy of obesity is supported by a range of evidence: epidemiologic study findings, which have shown an association between obesity and heart failure; clinical studies that have confirmed the association of adiposity with left ventricular dysfunction, independent of hypertension, coronary artery disease and other heart disease; and experimental evidence of structural and functional changes in the myocardium in response to increased adiposity. The most important mechanisms in the development of obesity cardiomyopathy are metabolic disturbances (insulin resistance, increased free fatty acid levels, and also increased levels of adipokines), activation of the renin–angiotensin–aldosterone and sympathetic nervous systems, myocardial remodeling, and small-vessel disease (both microangiopathy and endothelial dysfunction). In the first part of this two-part Review, we seek to evaluate the emerging evidence for the existence of a cardiomyopathy of obesity and clarify the responsible mechanisms.

Relationship between myocardial perfusion and dysfunction in diabetic cardiomyopathy: a study of quantitative contrast echocardiography and strain rate imaging

Objective: To use quantitative myocardial contrast echocardiography (MCE) and strain rate imaging (SRI) to assess the role of microvascular disease in subclinical diabetic cardiomyopathy. Methods: Stress MCE and SRI were performed in 48 patients (22 with type II diabetes mellitus (DM) and 26 controls), all with normal left ventricular systolic function and no obstructive coronary disease by quantitative coronary angiography. Real-time MCE was acquired in three apical views at rest and after combined dipyridamole–exercise stress. Myocardial blood flow (MBF) was quantified in the 10 mid- and apical cardiac segments at rest and after stress. Resting peak systolic strain rate (SR) and peak systolic strain (ε) were calculated in the same 10 myocardial segments. Results: The DM and control groups were matched for age, sex and other risk factors, including hypertension. The DM group had higher body mass index and left ventricular mass index. Quantitative SRI analysis was possible in all patients and quantitative MCE in 46 (96%). The mean ε, SR and MBF reserve were all significantly lower in the DM group than in controls, with diabetes the only independent predictor of each parameter. No correlation was seen between MBF and SR (r  =  −0.01, p  =  0.54) or between MBF and ε (r  =  −0.20, p  =  0.20). Conclusions: Quantitative MCE shows that patients with diabetes but no evidence of obstructive coronary artery disease have impaired MBF reserve, but abnormal transmural flow and subclinical longitudinal myocardial dysfunction are not related.

Standard versus atrial fibrillation-specific management strategy (SAFETY) to reduce recurrent admission and prolong survival: pragmatic, multicentre, randomised controlled trial

BACKGROUND Patients are increasingly being admitted with chronic atrial fibrillation, and disease-specific management might reduce recurrent admissions and prolong survival. However, evidence is scant to support the application of this therapeutic approach. We aimed to assess SAFETY--a management strategy that is specific to atrial fibrillation. METHODS We did a pragmatic, multicentre, randomised controlled trial in patients admitted with chronic, non-valvular atrial fibrillation (but not heart failure). Patients were recruited from three tertiary referral hospitals in Australia. 335 participants were randomly assigned by computer-generated schedule (stratified for rhythm or rate control) to either standard management (n=167) or the SAFETY intervention (n=168). Standard management consisted of routine primary care and hospital outpatient follow-up. The SAFETY intervention comprised a home visit and Holter monitoring 7-14 days after discharge by a cardiac nurse with prolonged follow-up and multidisciplinary support as needed. Clinical reviews were undertaken at 12 and 24 months (minimum follow-up). Coprimary outcomes were death or unplanned readmission (both all-cause), measured as event-free survival and the proportion of actual versus maximum days alive and out of hospital. Analyses were done on an intention-to-treat basis. The trial is registered with the Australian New Zealand Clinical Trials Registry (ANZCTRN 12610000221055). FINDINGS During median follow-up of 905 days (IQR 773-1050), 49 people died and 987 unplanned admissions were recorded (totalling 5530 days in hospital). 127 (76%) patients assigned to the SAFETY intervention died or had an unplanned readmission (median event-free survival 183 days [IQR 116-409]) and 137 (82%) people allocated standard management achieved a coprimary outcome (199 days [116-249]; hazard ratio 0·97, 95% CI 0·76-1·23; p=0·851). Patients assigned to the SAFETY intervention had 99·5% maximum event-free days (95% CI 99·3-99·7), equating to a median of 900 (IQR 767-1025) of 937 maximum days alive and out of hospital. By comparison, those allocated to standard management had 99·2% (95% CI 98·8-99·4) maximum event-free days, equating to a median of 860 (IQR 752-1047) of 937 maximum days alive and out of hospital (effect size 0·22, 95% CI 0·21-0·23; p=0·039). INTERPRETATION A post-discharge management programme specific to atrial fibrillation was associated with proportionately more days alive and out of hospital (but not prolonged event-free survival) relative to standard management. Disease-specific management is a possible strategy to improve poor health outcomes in patients admitted with chronic atrial fibrillation. FUNDING National Health and Medical Research Council of Australia.

Obesity cardiomyopathy: diagnosis and therapeutic implications

Obesity is associated with an increased risk of heart failure. Apparently healthy obese individuals can, however, exhibit subclinical left ventricular dysfunction. The use of myocardial imaging techniques to detect this subclinical change could have important management implications with respect to initiating prophylactic therapy. In this Review, we evaluate possible pharmacologic and nonpharmacologic strategies for treating obesity cardiomyopathy in the context of currently understood mechanisms, including myocardial remodeling and small vessel disease, and more speculative mechanisms such as insulin resistance, and activation of the renin–angiotensin–aldosterone and sympathetic nervous systems.

Use of Body Weight and Insulin Resistance to Select Obese Patients for Echocardiographic Assessment of Subclinical Left Ventricular Dysfunction

Obesity is associated with heart failure. Recognition of subclinical left ventricular (LV) dysfunction may permit the initiation of therapy to prevent the development of heart failure. In this study of anthropometric, biochemical, and echocardiographic measurements in 295 healthy overweight subjects, we sought to investigate the effect of insulin resistance and severity of obesity on LV function and to establish a strategy for detection of LV dysfunction using metabolic and echocardiographic measurements. Correlates of subclinical dysfunction (defined from myocardial deformation in a matched group of 98 slim controls) were sought, and receiver operator characteristic curves for clinical and laboratory parameters were performed to identify optimal cutoffs to permit an effective diagnostic strategy. Subclinical impairment of LV function (average strain<18%) was present in 124 subjects (42%), and 52% of severely obese patients (body mass index [BMI]>35 kg/m2). Independent correlates of strain were BMI (beta=-0.25, p<0.0001), fasting insulin (beta=-0.22, p<0.001), and age (beta=-0.18, p<0.003). In patients with a BMI<35 kg/m2, subclinical impairment was uncommon in the absence of hyperinsulinemia. Using a BMI<35 kg/m2 and an insulin level<13 mIU/L to select patients for further testing allowed echocardiography to be avoided in 35% of subjects in whom the prevalence of LV dysfunction was low. In conclusion, obesity and insulin resistance are important contributors to LV dysfunction, a deleterious effect of hyperinsulinemia on LV performance is particularly seen in overweight and moderately obese subjects, and the combination of BMI, fasting insulin, and echocardiography appears optimal for efficient identification of subclinical LV dysfunction in overweight and obese subjects.

Impact of a nurse‐led home and clinic‐based secondary prevention programme to prevent progressive cardiac dysfunction in high‐risk individuals: the Nurse‐led Intervention for Less Chronic Heart Failure (NIL‐CHF) randomized controlled study

The aim of this study was to determine the effectiveness of a long‐term, nurse‐led, multidisciplinary programme of home/clinic visits in preventing progressive cardiac dysfunction in individuals at risk of developing de novo chronic heart failure (CHF).

Does weight reduction in obese subjects improve subclinical myocardial-vascular function?

We sought to determine the relative impact of myocardial scar and viability on post-infarct left ventricular (LV) remodeling in medically-treated patients with LV dysfunction. Forty patients with chronic ischemic heart disease (age 64±9, EF 40±11%) underwent rest-redistribution Tl201 SPECT (scar = 50% transmural extent), A global index of scarring for each patient (CMR scar score) was calculated as the sum of transmural extent scores in all segts. LV end diastolic volumes (LVEDV) and LV end systolic volumes (LVESV) were measured by real-time threedimensional echo at baseline and median of 12 months follow-up. There was a significant positive correlation between change in LVEDV with number of scar segts by all three imaging techniques (LVEDV: SPECT scar, r = 0.62, p 15%) was predicted bySPECTscars(AUC= 0.79),DbEscars(AUC= 0.76),CMR scars (AUC= 0.70), and CMR scar score (AUC 0.72). There were no significant differences between any of the ROC curves (Z score <0.74). Number of SPECT scars (p = 0.002), DbE scars (p = 0.01), CMR scars (p = 0.004), and CMR scar score (p = 0.03) were independent predictors of LVEDV. The extent of scar tissue can predict global LV remodeling irrespective of cardiac imaging technique but myocardial viability may not be protective against LV remodeling in medically-treated patients.Transmural extent of infarction (TME) may be an important determinant of functional recovery and remodeling. Recent animal data suggest that strain rate imaging (SRI) maybe able to identify subendocardial ischemia.We compared SRI and cyclic variation of integrated backscatter (CVIB) for predicting TME in the quantitative assessment of regional subepicardial function. Forty-nine (n = 49) postmyocardial infarct patients (61±10 years, EF 41±10%) underwent tissue Doppler echocardiography (TDE) and contrast enhanced magnetic resonance imaging (CMR). A15 mm×2mm sampling volume (tracked to wall motion) was placed over the long axis subepicardial region of each segment during TDE offline analysis to measure peak longitudinal systolic strain rate (SR), peak longitudinal systolic strain (PS), and CVIB. Findingswere compared with TME classified into two categories of scar thickness by CMR: Non-transmural (TME≤50%), and transmural (TME > 50%). Of 213 segments identified with resting wall motion abnormalities, 145 segments showed delayed hyperenhancement on CMR. SR, PS and CVIB were similar with no significant differences between transmural and non-transmural infarcts regardless of the echo modality.Revascularization (RVS) of scar segts does not lead to recovery of left ventricular (LV) function, but its effect on post-infarct remodeling is unclear. We examined the impact of RVS on regional remodeling in different transmural extents of scar (TME). Dobutamine echo (DbE) and contrast enhanced magnetic resonance imaging (ce- MRI) were performed in 72 pts post MI (age 63±10, EF 49±12%). Pts were selected for RVS (n = 31) or medical treatment (n = 41). Segts were classified as scar if there were no contractile reserve during lowdose DbE.TMEwas measured by ce-MRI; a cutoff of 75% was used to differentiate transmural (TM) from non-transmural (NT) scars. Regional end systolic (ESV) and end diastolic volumes (EDV) were measured at baseline and 12 months follow up.Of 218 segts identified as scar on DbE, 164wereNTand 54 were TM on ce-MRI. Revascularization was performed to 62 NT and 11 TM segts. In the RVS group, there was reverse remodeling with significant reduction in LV volumes in NT (ESV, 6.8±3.2 ml versus 5.8±3.7 ml, p = 0.002; EDV, 10.9±4.9 ml versus 9.8±5.6 ml, p = 0.02), but no significant change in volumes in TM (ESV, 6.9±3.7 ml versus 5.4±2.1 ml, p = 0.09; EDV, 10.2±4.4 ml versus 9.4±4.3 ml, p = 0.5). In the medically treated group, there were no changes in LV volumes in both NT (ESV, 12.0±11.9 ml versus 12.7±13.8 ml, p = 0.3; EDV, 12.5±7.8 ml versus 12.6±9.7 ml, p = 0.8) and TM (ESV, 8.0±3.8 ml versus 7.9±4.6 ml, p = 0.8; EDV, 10.3±4.8 ml versus 10.4±5.4 ml, p = 0.9). Despite absence of contractile reserve on DbE, NT benefit from coronary revascularization with regional reverse LV remodeling.Left ventricular (LV) volumes have important prognostic implications in patients with chronic ischemic heart disease. We sought to examine the accuracy and reproducibility of real-time 3D echo (RT-3DE) compared to TI-201 single photon emission computed tomography (SPECT) and cardiac magnetic resonance imaging (MRI). Thirty (n = 30) patients (age 62±9 years, 23 men) with chronic ischemic heart disease underwent LV volume assessment with RT-3DE, SPECT, and MRI. Ano vel semi-automated border detection algorithmwas used by RT-3DE. End diastolic volumes (EDV) and end systolic volumes (ESV) measured by RT3DE and SPECT were compared to MRI as the standard of reference. RT-3DE and SPECT volumes showed excellent correlation with MRI (Table). Both RT- 3DE and SPECT underestimated LV volumes compared to MRI (ESV, SPECT 74±58 ml versus RT-3DE 95±48 ml versus MRI 96±54 ml); (EDV, SPECT 121±61 ml versus RT-3DE 169±61 ml versus MRI 179±56 ml). The degree of ESV underestimation with RT-3DE was not significant.