Regional myocardial function in healthy adults: assessment through tissue Doppler echocardiography

OBJECTIVE: To characterize left ventricular regional myocardial function through tissue Doppler echocardiography in healthy adults and to assess the influence of aging in this function. METHODS: In 45 healthy volunteers divided in two groups (< 45 and > 45 years old) we assessed longitudinal and radial regional function (velocities, times intervals and velocity-time integrals). Data were compared in each group and between groups. RESULTS: Systolic function: a) longitudinal: higher velocities and integrals in lateral and inferior walls and in basal segments, with a trend to reduction of these parameters with aging; b) radial: higher basal velocities, no significant change with aging. Diastolic function: a) longitudinal: higher velocities in lateral and inferior walls and in basal segments. With aging e and e/a velocities and integrals decreased, a increased and older individuals showed lower percentage of segments with e/a >1; b) radial: aging was associated with lower e and higher a velocities. CONCLUSION: 1) Tissue Doppler echocardiography detects physiological differences between regional myocardial function of different ventricular segments, in velocities, times intervals and integrals, with physiological heterogeneity and asynchrony; 2) Many of these data are age dependent; 3) Our data contribute to define normal values, and may become useful when compared with data from populations with heart diseases.

Real-time imaging of regional myocardial function using fast-SENC.

A technique for fast imaging of regional myocardial function using a spiral acquisition in combination with strain-encoded (SENC) magnetic resonance imaging (MRI) is presented in this paper. This technique, which is termed fast-SENC, enables scan durations as short as a single heartbeat. A reduced field of view (FOV) without foldover artifacts was achieved by localized SENC, which selectively excited the region around the heart. The two images required for SENC imaging (low- and high-tuning) were acquired in an interleaved fashion throughout the cardiac cycle to further shorten the scan time. Regional circumferential contraction and longitudinal shortening of both the left ventricle (LV) and right ventricle (RV) were examined in long- and short-axis views, respectively. The in vivo results obtained from five human subjects and five infarcted dogs are presented. The results of the fast-SENC technique in a single heartbeat acquisition were comparable to those obtained by conventional SENC in a long acquisition time. Therefore, fast-SENC may prove useful for imaging during stress or arrhythmia.

Sustained Ventricular Tachycardia Is Associated with Regional Myocardial Sympathetic Denervation Assessed with (123)I-Metaiodobenzylguanidine in Chronic Chagas Cardiomyopathy

Cardiac sympathetic denervation and ventricular arrhythmia are frequently observed in chronic Chagas cardiomyopathy (CCC). This study quantitatively evaluated the association between cardiac sympathetic denervation and sustained ventricular tachycardia (SVT) in patients with CCC. Methods: We prospectively investigated patients with CCC and left ventricular ejection fraction (LVEF) greater than 35% with SVT (SVT group: n = 5 15; mean age +/- SD, 61 +/- 8 y; LVEF, 51% +/- 8%) and patients without SVT (non-SVT group: n = 11; mean age +/- SD, 55 +/- 10 y; LVEF, 57% +/- 10%). Patients underwent myocardial scintigraphy with (123)I-metaiodobenzylguanidine ((123)I-MIBG) for the evaluation of sympathetic innervation and resting perfusion with (99m)Tc-methoxyisobutylisonitrile ((99m)Tc-MIBI) for the evaluation of myocardial viability. A visual semiquantitative score was attributed for regional uptake of each radiotracer using a 17-segment left ventricular segmentation model (0, normal; 4, absence of uptake). A mismatch defect was defined as occurring in segments with a 99mTc-MIBI uptake score of 0 or 1 and a (123)I-MIBG score of 2 or more. Results: Compared with the non-SVT group, the SVT group had a similar (99m)Tc-MIBI summed score (6.9 +/- 7.5 vs. 4.4 +/- 5.2, respectively, P = 0.69) but a higher (123)I-MIBG summed score (10.9 +/- 7.8 vs. 22.4 +/- 9.5, respectively, P = 0.007) and a higher number of mismatch defects per patient (2.0 +/- 2.2 vs. 7.1 +/- 2.0, respectively, P < 0.0001). The presence of more than 3 mismatch defects was strongly associated with the presence of SVT (93% sensitivity, 82% specificity; P = 0.0002). Conclusion: In CCC, the amount of sympathetically denervated viable myocardium is associated with the occurrence of SVT. Myocardial sympathetic denervation may participate in triggering malignant ventricular arrhythmia in CCC patients with relatively well-preserved ventricular function.

Determinants of tissue Doppler measures of regional diastolic function during dobutamine stress echocardiography

Background Diastolic dysfunction induced by ischemia may alter transmitral blood flow, but this reflects global ventricular function, and pseudonormalization may occur with increased preload. Tissue Doppler may assess regional diastolic function and is relatively load-independent, but limited data exist regarding its application to stress testing. We sought to examine the stress response of regional diastolic parameters to dobutomine echocardiography (DbE). Methods Sixty-three patients underwent study with DbE: 20 with low probability of coronary artery disease (CAD) and 43 with CAD who underwent angiography. A standard DbE protocol was used, and segments were categorized as ischemic, scar, or normal. Color tissue Doppler was acquired at baseline and peak stress, and waveforms in the basal and mid segments were used to measure early filling (Em), late filling (Am), and E deceleration time. Significant CAD was defined by stenoses >50% vessel diameter. Results Diastolic parameters had limited feasibility because of merging of Em and Am waves at high heart rates and limited reproducibility. Nonetheless, compared with normal segments, segments subtended with significant stenoses showed a lower Em velocity at rest (6.2 +/- 2.6 cm/s vs 4.8 +/- 2.2 cm/s, P < .0001) and peak (7.5 +/- 4.2 cm/s vs 5.1 +/- 3.6 cm/s, P < .0001), Abnormal segments also showed a shorter E deceleration time (51 +/- 27 ms vs 41 +/- 27 ms, P = .0001) at base and peak. No changes were documented in Am. The same pattern was seen with segments identified as ischemic with wall motion score. However, in the absence of ischemia, segments of patients with left ventricular hypertrophy showed a lower Em velocity, with blunted Em responses to stress. Conclusion Regional diastolic function is sensitive to ischemia. However, a number of practical limitations limit the applicability of diastolic parameters for the quantification of stress echocardiography.

Automated regional myocardial displacement for facilitating the interpretation of dobutamine echocardiography

Quantification of stress echocardiography may overcome the training requirements and subjective nature of visual wall motion score (WMS) assessment, but quantitative approaches may be difficult to apply and require significant time for image processing. The integral of long-axis myocardial velocity is displacement, which may be represented as a color map over the left ventricular myocardium. This study was designed to explore the feasibility and accuracy of measuring long-axis myocardial displacement, derived from tissue Doppler, for the detection of coronary artery disease (CAD) during dobutamine stress echocardiography (DBE). One hundred thirty patients underwent standard DBE, including 30 patients at low risk of CAD, 30 patients with normal coronary angiography (both groups studied to define normal ranges of displacement), and 70 patients who underwent coronary angiography in whom the accuracy of normal ranges was tested. Regional myocardial displacement was obtained by analysis of color tissue Doppler apical images acquired at peak stress. Displacement was compared with WMS, and with the presence of CAD by angiography. The analysis time was 3.2 +/- 1.5 minutes per patient. Segmental displacement was correlated with wall motion (normal 7.4 +/- 3.2 mm, ischemia 5.8 +/- 4.2 mm, viability 4.6 +/- 3.0 mm, scar 4.5 +/- 3.5 mm, p <0.001). Reversal of normal base-apex displacement was an insensitive (19%) but specific (90%) marker of CAD. The sum of displacements within each vascular territory had a sensitivity and specificity of 89% and 79%, respectively, for prediction of significant CAD, compared with 86% and 78%, respectively, for WMS (p = NS). The displacements in the basal segments had a sensitivity and specificity of 83% and 78%, respectively (p = NS). Regional myocardial displacement during DBE is feasible and offers a fast and accurate method for the diagnosis of CAD. (C),2002 by Excerpta Medica, Inc.

Obesity Preserves Myocardial Function During Blockade of the Glycolytic Pathway

Background: Obesity is defined by excessive accumulation of body fat relative to lean tissue. Studies during the last few years indicate that cardiac function in obese animals may be preserved, increased or diminished. Objective: Study the energy balance of the myocardium with the hypothesis that the increase in fatty acid oxidation and reduced glucose leads to cardiac dysfunction in obesity. Methods: 30-day-old male Wistar rats were fed standard and hypercaloric diet for 30 weeks. Cardiac function and morphology were assessed. In this paper was viewed the general characteristics and comorbities associated to obesity. The structure cardiac was determined by weights of the heart and left ventricle (LV). Myocardial function was evaluated by studying isolated papillary muscles from the LV, under the baseline condition and after inotropic and lusitropic maneuvers: myocardial stiffness; postrest contraction; increase in extracellular Ca2+ concentration; change in heart rate and inhibitor of glycolytic pathway. Results: Compared with control group, the obese rats had increased body fat and co-morbities associated with obesity. Functional assessment after blocking iodoacetate shows no difference in the linear regression of DT, however, the RT showed a statistically significant difference in behavior between the control and the obese group, most notable being the slope in group C. Conclusion: The energy imbalance on obesity did not cause cardiac dysfunction. On the contrary, the prioritization of fatty acids utilization provides protection to cardiac muscle during the inhibition of glycolysis, suggesting that this pathway is fewer used by obese cardiac muscle.

Dietary fish oil is antihypertrophic but does not enhance postischemic myocardial function in female mice.

Clinically and experimentally, a case for omega-3 polyunsaturated fatty acid (PUFA) cardioprotection in females has not been clearly established. The goal of this study was to investigate whether dietary omega-3 PUFA supplementation could provide ischemic protection in female mice with an underlying genetic predisposition to cardiac hypertrophy. Mature female transgenic mice (TG) with cardiac-specific overexpression of angiotensinogen that develop normotensive cardiac hypertrophy and littermate wild-type (WT) mice were fed a fish oil-derived diet (FO) or PUFA-matched control diet (CTR) for 4 wk. Myocardial membrane lipids, ex vivo cardiac performance (intraventricular balloon) after global no-flow ischemia and reperfusion (15/30 min), and reperfusion arrhythmia incidence were assessed. FO diet suppressed cardiac growth by 5% and 10% in WT and TG, respectively (P < 0.001). The extent of mechanical recovery [rate-pressure product (RPP) = beats/min x mmHg] of FO-fed WT and TG hearts was similar (50 +/- 7% vs. 45 +/- 12%, 30 min reperfusion), and this was not significantly different from CTR-fed WT or TG. To evaluate whether systemic estrogen was masking a protective effect of the FO diet, the responses of ovariectomized (OVX) WT and TG mice to FO dietary intervention were assessed. The extent of mechanical recovery of FO-fed OVX WT and TG (RPP, 50 +/- 4% vs. 64 +/- 8%) was not enhanced compared with CTR-fed mice (RPP, 60 +/- 11% vs. 80 +/- 8%, P = 0.335). Dietary FO did not suppress the incidence of reperfusion arrhythmias in WT or TG hearts (ovary-intact mice or OVX). Our findings indicate a lack of cardioprotective effect of dietary FO in females, determined by assessment of mechanical and arrhythmic activity postischemia in a murine ex vivo heart model.

Local transient myocardial liposomal gene transfer of inducible nitric oxide synthase does not aggravate myocardial function and fibrosis and leads to moderate neovascularization in chronic myocardial ischemia in pigs.

Microcirculation (2010) 17, 69-78. doi: 10.1111/j.1549-8719.2010.00002.x Abstract Background: This study was designed to explore the effect of transient inducible nitric oxide synthase (iNOS) overexpression via cationic liposome-mediated gene transfer on cardiac function, fibrosis, and microvascular perfusion in a porcine model of chronic ischemia. Methods and Results: Chronic myocardial ischemia was induced using a minimally invasive model in 23 landrace pigs. Upon demonstration of heart failure, 10 animals were treated with liposome-mediated iNOS-gene-transfer by local intramyocardial injection and 13 animals received a sham procedure to serve as control. The efficacy of this iNOS-gene-transfer was demonstrated for up to 7 days by reverse transcriptase-polymerase chain reaction in preliminary studies. Four weeks after iNOS transfer, magnetic resonance imaging showed no effect of iNOS overexpression on cardiac contractility at rest and during dobutamine stress (resting ejection fraction: control 27%, iNOS 26%; P = ns). Late enhancement, infarct size, and the amount of fibrosis were similar between groups. Although perfusion and perfusion reserve in response to adenosine and dobutamine were not significantly modified by iNOS-transfer, both vessel number and diameter were significantly increased in the ischemic area in the iNOS-treated group versus control (point score: control 15.3, iNOS 34.7; P < 0.05). Conclusions: Our findings demonstrate that transient iNOS overexpression does not aggravate cardiac dysfunction or postischemic fibrosis, while potentially contributing to neovascularization in the chronically ischemic heart.

Slaughterhouse blood as a perfusate for studying myocardial function under ischemic conditions

Metabolic studies using the in vitro non-recirculating blood-perfused isolated heart model require large volumes of blood. The present study was designed to determine whether heterologous pig blood collected from a slaughterhouse can be used as perfusate for isolated pig hearts perfused under aerobic and constant reduced flow conditions. Eight isolated working pig hearts perfused for 90 min at a constant flow of 1.5 ml g-1 min-1 with non-recirculated blood diluted with Krebs-Henseleit bicarbonate buffer at a hematocrit of 23% were compared to eight hearts subjected to the same protocol but perfused only with Krebs-Henseleit bicarbonate buffer solution. Hearts were paced at 100 bpm and subjected to aerobic perfusion at 38ºC. Hearts were weighed before perfusion and at the end of the experiment and the results are reported as percent weight gain (mean ± SD). Comparisons between groups were performed by the Student t-test (P<0.05). After 90 min of perfusion with modified Krebs-Henseleit, perfused hearts presented a larger weight gain than blood-perfused hearts (39.34 ± 9.27 vs 23.13 ± 5.42%, P = 0.003). Left ventricular end-diastolic pressure was higher in the modified Krebs-Henseleit-perfused group than in the blood group (2.8 ± 0.4 vs 2.3 ± 0.3 mmHg, respectively, P = 0.01). We conclude that heterologous blood perfusion, by preserving a more physiological myocardial water content, is a better perfusion fluid than modified Krebs-Henseleit solution for quantitative studies of myocardial metabolism and heart function under ischemic conditions.

ESC Working Group on Myocardial Function Position Paper: how to study the right ventricle in experimental models

The right ventricle has become an increasing focus in cardiovascular research. In this position paper, we give a brief overview of the specific pathophysiological features of the right ventricle, with particular emphasis on functional and molecular modifications as well as therapeutic strategies in chronic overload, highlighting the differences from the left ventricle. Importantly, we put together recommendations on promising topics of research in the field, experimental study design, and functional evaluation of the right ventricle in experimental models, from non-invasive methodologies to haemodynamic evaluation and ex vivo set-ups.

Targeting myocardial remodelling to develop novel therapies for heart failure: a position paper from the Working Group on Myocardial Function of the European Society of Cardiology

The failing heart is characterized by complex tissue remodelling involving increased cardiomyocyte death, and impairment of sarcomere function, metabolic activity, endothelial and vascular function, together with increased inflammation and interstitial fibrosis. For years, therapeutic approaches for heart failure (HF) relied on vasodilators and diuretics which relieve cardiac workload and HF symptoms. The introduction in the clinic of drugs interfering with beta-adrenergic and angiotensin signalling have ameliorated survival by interfering with the intimate mechanism of cardiac compensation. Current therapy, though, still has a limited capacity to restore muscle function fully, and the development of novel therapeutic targets is still an important medical need. Recent progress in understanding the molecular basis of myocardial dysfunction in HF is paving the way for development of new treatments capable of restoring muscle function and targeting specific pathological subsets of LV dysfunction. These include potentiating cardiomyocyte contractility, increasing cardiomyocyte survival and adaptive hypertrophy, increasing oxygen and nutrition supply by sustaining vessel formation, and reducing ventricular stiffness by favourable extracellular matrix remodelling. Here, we consider drugs such as omecamtiv mecarbil, nitroxyl donors, cyclosporin A, SERCA2a (sarcoplasmic/endoplasmic Ca(2 +) ATPase 2a), neuregulin, and bromocriptine, all of which are currently in clinical trials as potential HF therapies, and discuss novel molecular targets with potential therapeutic impact that are in the pre-clinical phases of investigation. Finally, we consider conceptual changes in basic science approaches to improve their translation into successful clinical applications.

Direct effects of colchicine on myocardial function - Studies in hypertrophied and failing spontaneously hypertensive rats

The aging spontaneously hypertensive rat (SHR) is a model in which the transition from chronic stable left ventricular hypertrophy to overt heart failure can be observed. Although the mechanisms for impaired function in hypertrophied and failing cardiac muscle from the SHR have been studied, none accounts fully for the myocardial contractile abnormalities. The cardiac cytoskeleton has been implicated as a possible cause for myocardial dysfunction. If an increase in microtubules contributes to dysfunction, then myocardial microtubule disruption by colchicine should promote an improvement in cardiac performance. We studied the active and passive properties of isolated left ventricular papillary muscles from 18- to 24-month-old SHR with evidence of heart failure (SHR-F, n=6), age-matched SHR without heart failure (SHR-NF, n=6), and age-matched normotensive Wistar-Kyoto rats (WKY, n=5). Mechanical parameters were analyzed before and up to 90 minutes after the addition of colchicine (10(-5), 10(-4), and 10(-3) mol/L). In the baseline state, active tension (AT) developed by papillary muscles from the WKY group was greater than for SHR-NF and SHR-F groups (WKY 5.69+/-1.47 g/mm(2) [mean+/-SD], SHR-NF 3.41+/-1.05, SHR-F 2.87+/-0.26; SHR-NF and SHR-F P<0.05 versus WKY rats). The passive stiffness was greater in SHR-F than in the WKY and SHR-NF groups (central segment exponential stiffness constant, K-cs: SHR-F 70+/-25, SHR-NF 44+/-17, WKY 41+/-13 [mean+/-SD]; SHR-F P<0.05 versus; SHR-NF and WKY rats). AT did not improve after 10, 20, and 30 minutes of exposure to colchicine (10(-5), 10(-4), and 10(-3) mol/L) in any group. In the SHR-F group, AT and passive stiffness did not change after 30 to 90 minutes of colchicine exposure (10(-4) mol/L). In summary, the data in this study fail to demonstrate improvement of intrinsic muscle function in SHR with heart failure after colchicine. Thus, in the SHR there is no evidence that colchicine-induced cardiac microtubular depolymerization affects the active or passive properties of hypertrophied or failing left ventricular myocardium.