Regional Contractile Function Research Articles

#2887 ASSESSMENT OF EXTRA-BONE CALCIFICATION IN PATIENTS UNDERGOING PROGRAMMED HEMODIALYSIS

Abstract Background and Aims Chronic kidney disease is associated with the accumulation of so-called medium molecules in the blood, in particular parathyroid hormone, and the formation of secondary hyperparathyroidism with a tendency to extra-bone calcification. The most vulnerable organ in relation to calcification is the vascular wall. The ail of the study to study the features of vascular wall remodeling in patients with chronic kidney disease who are being treated with programmed hemodialysis. Method The study included 86 patients with CKD C5 (mean age 47.44±5.04 years) who had been on programmed hemodialysis for at least 6 months. All patients underwent examination, including multislice spiral computed tomography (MSCT) with an assessment of the calcium content in the coronary arteries (Agatston index), ultrasound examination of the carotid arteries with determination of the thickness of the intima-media complex, the degree of endothelium-dependent vasodilation in a sample with 5-minute compression of the brachial artery and determination of changes in the diameter of the brachial artery. The data obtained (presented in the form of an arithmetic mean and its standard error) were compared with normal values typical for a healthy population. Results There was an accumulation of calcium in the coronary vessels with an average Agatstone index of 146.83 ± 13.26 units. Also, during MSCT, calcifications were found in the aortic wall in 86 out of 57 patients. The intima-media complex in patients with CKD was significantly increased and averaged 1.21±0.06mm. The degree of endothelium-dependent vasodilation in patients with CKD was reduced and amounted to 5.48± 0.03% of the initial diameter of the brachial artery. Correlation analysis revealed significant positive associations of average strength between the value of the Agatson index, the thickness of the intima-media complex of the carotid arteries and the concentration of parathyroid hormone in peripheral blood (g = +0.58,P<0.05 with the Agatson index and P = 0.42, P<0.05 with the thickness of the intima-media complex), as well as a significant negative relationship between the product of the concentration of calcium and phosphorus in peripheral blood and the degree of endothelium-dependent vasodilation (g = -0.49, P<0.05). Conclusion In patients with CKD, against the background of programmed hemodialysis, there is a remodeling of the heart with an increase in the size of the heart cavities and LV myocardial mass, a violation of regional and general LV contractile function, LV diastolic dysfunction and an increase in pressure in the pulmonary artery system. The introduction of sevelamer hydrochloride into the therapy regimen is associated with the prevention of the progression of cardiac remodeling. Calcification of the aortic valve progresses, regardless of the therapy used. Vascular remodeling in patients with CKD on the background of programmed hemodialysis is manifested by an increase in the thickness of the intima-media complex of the carotid arteries and a violation of endothelium-dependent vasodilation in favor of paradoxical vasoconstriction. Against the background of calcium carbonate therapy, structural disorders of the vascular wall progress. The introduction of sevelamer phosphate binder into the therapy regimen allows to prevent the progression and improve the functional state of endothelial function.

PO-02-206 A MECHANISM FOR PACING-INDUCED REGIONAL CONTRACTILE DYSFUNCTION MEDIATED BY RELEASED CATECHOLAMINES

We have previously shown that non-excitatory epicardial stimulation (NES) increases measures of cardiac function mediated by local release of norepinephrine. In this further investigation we focused on the effects of NES on the local myocardial contractile pattern. Farm pigs were anesthetized and instrumented with a LV high-fidelity pressure/volume conductance transducer, thoracic aortic pressure transducer, left atrial (LA)/ LV epicardial electrodes, and sonomicrometer segment length (SL) gauges placed proximal (lateral base) and distal (posterior mid LV) to the LV stimulation site. During constant LA pacing, LV pulses (0.8ms, 2-3x threshold volts) were applied during the absolute refractory period before and after β-receptor blockade (BB, metoprolol). Regional contractile function was analyzed by constructing LVP vs. SL loops in a beat-by-beat fashion thus allowing characterization of local cardiac function in relation to LV pressure over the entire cardiac cycle. NES resulted in a local contractile dysfunction characterized by an early shortening, subsequent lengthening, and re-shortening pattern during the cardiac cycle in the SL gauge proximal (middle tracing), but not remote to the stimulation site (bottom tracing). The onset of early lengthening in the proximal SL coincided with peak pressure generation, followed by re-shortening as LV pressure fell. The LVP vs. SL loop was markedly altered. This contractile effect rapidly waned within 10-15 seconds after cessation of electrical stimulation and was abolished by BB. The NES induced dysfunction developed within an average of 5-10 seconds of stimulation onset and was accompanied by increases in several global indices of cardiac function (dP/dt, peak LVP, early aortic valve opening) which were also abrogated by B-blockade. These findings demonstrate that pacing elicits local catecholamine release that may cause dyssynergy and mimic the regional pacing-induced contractile dysfunction seen at pacing sites in man.

Computational Analysis of Cardiac Contractile Function.

Heart failure results in the high incidence and mortality all over the world. Mechanical properties of myocardium are critical determinants of cardiac function, with regional variations in myocardial contractility demonstrated within infarcted ventricles. Quantitative assessment of cardiac contractile function is therefore critical to identify myocardial infarction for the early diagnosis and therapeutic intervention. Current advancement of cardiac functional assessments is in pace with the development of imaging techniques. The methods tailored to advanced imaging have been widely used in cardiac magnetic resonance, echocardiography, and optical microscopy. In this review, we introduce fundamental concepts and applications of representative methods for each imaging modality used in both fundamental research and clinical investigations. All these methods have been designed or developed to quantify time-dependent 2-dimensional (2D) or 3D cardiac mechanics, holding great potential to unravel global or regional myocardial deformation and contractile function from end-systole to end-diastole. Computational methods to assess cardiac contractile function provide a quantitative insight into the analysis of myocardial mechanics during cardiac development, injury, and remodeling.

Regional analysis of inflammation and contractile function in reperfused acute myocardial infarction by in vivo 19F cardiovascular magnetic resonance in pigs

Inflammatory cell infiltration is central to healing after acute myocardial infarction (AMI). The relation of regional inflammation to edema, infarct size (IS), microvascular obstruction (MVO), intramyocardial hemorrhage (IMH), and regional and global LV function is not clear. Here we noninvasively characterized regional inflammation and contractile function in reperfused AMI in pigs using fluorine (19F) cardiovascular magnetic resonance (CMR). Adult anesthetized pigs underwent left anterior descending coronary artery instrumentation with either 90 min occlusion (n = 17) or without occlusion (sham, n = 5). After 3 days, in surviving animals a perfluorooctyl bromide nanoemulsion was infused intravenously to label monocytes/macrophages. At day 6, in vivo 1H-CMR was performed with cine, T2 and T2* weighted imaging, T2 and T1 mapping, perfusion and late gadolinium enhancement followed by 19F-CMR. Pigs were sacrificed for subsequent ex vivo scans and histology. Edema extent was 35 ± 8% and IS was 22 ± 6% of LV mass. Six of ten surviving AMI animals displayed both MVO and IMH (3.3 ± 1.6% and 1.9 ± 0.8% of LV mass). The 19F signal, reflecting the presence and density of monocytes/macrophages, was consistently smaller than edema volume or IS and not apparent in remote areas. The 19F signal-to-noise ratio (SNR) > 8 in the infarct border zone was associated with impaired remote systolic wall thickening. A whole heart value of 19F integral (19F SNR × milliliter) > 200 was related to initial LV remodeling independently of edema, IS, MVO, and IMH. Thus, 19F-CMR quantitatively characterizes regional inflammation after AMI and its relation to edema, IS, MVO, IMH and regional and global LV function and remodeling.

USE OF DOBUTAMINE STRESS ECHOCARDIOGRAPHY TO ASSESS MYOCARDIAL VIABILITY BEFORE PCI IN TOTAL OCCLUSION OF CORONARY ARTERY IN A TERTIARY CARE CENTRE

Dobutamine stress echocardiography has significant advantages in our country due to its wide availability, portability, low cost and safety.This study was conducted with the aim to assess myocardial viability by Dobutamine Stress Echocardiography (DSE) before PCI in total occlusion of coronary artery.This study confirms that a biphasic response to dobutamine is highly predictive of postoperative recovery of regional contractile function (100% at 6th week follow-up). This studies provide evidence that, at low doses, inotropic stimulation with P- receptor agonists will result in an increase in LV function in areas of viable myocardium but not in areas of myocardial necrosis.

Electromechanical substrate characterization in arrhythmogenic cardiomyopathy using imaging-based patient-specific computer simulations.

AimsArrhythmogenic cardiomyopathy (AC) is an inherited cardiac disease, characterized by life-threatening ventricular arrhythmias and progressive cardiac dysfunction. The aim of this study is to use computer simulations to non-invasively estimate the individual patient’s myocardial tissue substrates underlying regional right ventricular (RV) deformation abnormalities in a cohort of AC mutation carriers. Methods and resultsIn 68 AC mutation carriers and 20 control subjects, regional longitudinal deformation patterns of the RV free wall (RVfw), interventricular septum (IVS), and left ventricular free wall (LVfw) were obtained using speckle-tracking echocardiography. We developed and used a patient-specific parameter estimation protocol based on the multi-scale CircAdapt cardiovascular system model to create virtual AC subjects. Using the individual’s deformation data as model input, this protocol automatically estimated regional RVfw and global IVS and LVfw tissue properties. The computational model was able to reproduce clinically measured regional deformation patterns for all subjects, with highly reproducible parameter estimations. Simulations revealed that regional RVfw heterogeneity of both contractile function and compliance were increased in subjects with clinically advanced disease compared to mutation carriers without clinically established disease (17 ± 13% vs. 8 ± 4%, P = 0.01 and 18 ± 11% vs. 10 ± 7%, P < 0.01, respectively). No significant difference in activation delay was found.ConclusionRegional RV deformation abnormalities in AC mutation carriers were related to reduced regional contractile function and tissue compliance. In clinically advanced disease stages, a characteristic apex-to-base heterogeneity of tissue abnormalities was present in the majority of the subjects, with most pronounced disease in the basal region of the RVfw.

Non-transmural myocardial infarction associated with regional contractile function is an independent predictor of positive outcome: an integrated approach to myocardial viability

BackgroundCardiovascular magnetic resonance permits assessment of irreversible myocardial fibrosis and contractile function in patients with previous myocardial infarction. We aimed to assess the prognostic value of myocardial fibrotic tissue with preserved/restored contractile activity.MethodsIn 730 consecutive myocardial infarction patients (64 ± 11 years), we quantified left ventricular (LV) end-diastolic (EDV) and end-systolic (ESV) volumes, ejection fraction (EF), regional wall motion (WM) (1 normal, 2 hypokinetic, 3 akinetic, 4 dyskinetic), and WM score index (WMSI), and measured the transmural (1–50 and 51–100) and global extent of the infarct scar by late gadolinium enhancement (LGE). Contractile fibrotic (CT-F) segments were identified as those showing WM-1 and WM-2 with LGE ≤ or ≥ 50%.ResultsDuring follow-up (median 2.5, range 1–4.7 years), cardiac events (cardiac death or appropriate implantable defibrillator shocks) occurred in 123 patients (17%). At univariate analysis, age, LVEDV, LVESV, LVEF, WMSI, extent of LGE, segments with transmural extent > 50%, and CT-F segments were associated with cardiac events. At multivariate analysis, age > 65 years, LVEF < 30%, WMSI > 1.7, and dilated LVEDV independently predicted cardiac events, while CT-F tissue was the only independent predictor of better outcome. After adjustment for LVEF < 30% and LVEDV dilatation, the presence of CT-F tissue was associated with good prognosis.ConclusionsIn addition to CMR imaging parameters associated with adverse outcome (severe LV dysfunction, poor WM, and dilated EDV), the presence of fibrotic myocardium showing contractile activity in patients with previous myocardial infarction yields a beneficial effect on patient survival.

Regional myocardial work as determinant of heart failure in left bundle branch block

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): The Norwegian Health Association Background Left bundle branch block (LBBB) worsen prognosis in heart failure patients. LBBB may also cause heart failure in otherwise healthy individuals. The mechanical changes induced by LBBB are potential determinants of heart failure in these patients, but their relation to left ventricular (LV) systolic function is incompletely understood. Purpose This study investigates the contribution of regional contractile function to heart failure in patients with LBBB. Methods In 76 patients with LBBB and 11 healthy controls, myocardial strain was measured by speckle-tracking echocardiography and myocardial work by pressure-strain analysis. Patients with ischemic heart disease or myocardial scarring were excluded. LBBB patients were stratified by LV ejection fraction (EF) &amp;gt;50% (EFpreserved), 36-50% (EFmid), and ≤35% (EFlow). 62 LBBB patients subsequently underwent cardiac resynchronization therapy (CRT) implantation and was re-examined at 6 months. Results Septal work was significantly and successively reduced from controls, EFpreserved, EFmid, to EFlow (1977 ± 506, 1025 ± 342, 601 ± 494 and -41 ± 303 mmHg·%, respectively, all p &amp;lt; 0.01) (Figure 1). There was a strong correlation (R = 0.84, p &amp;lt; 0.01) between septal work and LVEF. In contrast, work in the LV lateral wall was preserved in both EFpreserved (2367 ± 459 mmHg·%) and EFmid (2252 ± 449 mmHg·%) vs controls (2062 ± 459 mmHg·%, all NS). In the EFlow group, however, LV lateral wall work was reduced (1473 ± 568 mmHg·%, p &amp;lt; 0.01 vs controls). Thus, lateral wall function was not correlated with LVEF in patients with LVEF &amp;gt;35% (NS). At six month CRT septal work was markedly increased (165 ± 485 vs 1288 ± 523 mmHg·%, p &amp;lt; 0.01) and LV lateral wall work reduced (1730 ± 620 vs 1264 ± 490 mmHg·%, p &amp;lt; 0.01). LVEF increased from 32 ± 8 to 47 ± 10 % (p &amp;lt; 0.01). Conclusions Heart failure in LBBB patients is determined by degree of septal dysfunction. LV lateral wall function, on the other hand, is preserved in the early phase of heart failure and was only reduced in patients with severe heart failure. Further clinical studies should investigate if measuring LV lateral wall function can increase precision in patient selection for CRT. Abstract Figure.

Myocardial stunning and hibernation revisited.

Unlike acute myocardial infarction with reperfusion, in which infarct size is the end point reflecting irreversible injury, myocardial stunning and hibernation result from reversible myocardial ischaemia-reperfusion injury, and contractile dysfunction is the obvious end point. Stunned myocardium is characterized by a disproportionately long-lasting, yet fully reversible, contractile dysfunction that follows brief bouts of myocardial ischaemia. Reperfusion precipitates a burst of reactive oxygen species formation and alterations in excitation-contraction coupling, which interact and cause the contractile dysfunction. Hibernating myocardium is characterized by reduced regional contractile function and blood flow, which both recover after reperfusion or revascularization. Short-term myocardial hibernation is an adaptation of contractile function to the reduced blood flow such that energy and substrate metabolism recover during the ongoing ischaemia. Chronic myocardial hibernation is characterized by severe morphological alterations and altered expression of metabolic and pro-survival proteins. Myocardial stunning is observed clinically and must be recognized but is rarely haemodynamically compromising and does not require treatment. Myocardial hibernation is clinically identified with the use of imaging techniques, and the myocardium recovers after revascularization. Several trials in the past two decades have challenged the superiority of revascularization over medical therapy for symptomatic relief and prognosis in patients with chronic coronary syndromes. A better understanding of the pathophysiology of myocardial stunning and hibernation is important for a more precise indication of revascularization and its consequences. Therefore, this Review summarizes the current knowledge of the pathophysiology of these characteristic reperfusion phenomena and highlights their clinical implications.

Remote ischemic preconditioning ameliorates anthracycline-induced cardiotoxicity and preserves mitochondrial integrity: results from a randomized preclinical trial in pigs

Abstract Introduction Anthracycline-induced cardiotoxicity (AIC) is a serious adverse effect occurring in a significant proportion of patients. Irreversible mitochondrial damage is a central mechanism of AIC. Despite many efforts, there is a lack of therapies able to prevent AIC. Remote ischemic preconditioning (RIPC) could be a promising therapy to prevent AIC due to the scheduled application of chemotherapy in cancer patients. Purpose To evaluate the cardioprotective efficacy of RIPC in large animal model of AIC. Methods Large-White pigs (n=20) underwent a validated protocol of AIC consisting on five intracoronary doxorubicin injections (0.45 mg/kg), on weeks 0, 2, 4, 6, 8 of the study. Pigs were randomized before the initiation of the study to remote ischemic pre-conditioning (RIPC, 3 cycles of 5 min lower limb ischemia followed by 5 min reperfusion) or sham procedure immediately before doxorubicin injections. An additional group of 10 pigs without any exposure to doxorubicin was carried out as controls. Pigs underwent a comprehensive serial cardiac magnetic resonance (CMR) exam baseline, and on weeks 6, 8, 12, and 16. After 16-week CMR, pigs were sacrificed and tissue samples collected. A second group of 10 pigs (randomized 1:1 for RIPC) underwent the same protocol but were sacrificed 2 weeks after the third doxorubicin dose for early evaluation of tissue changes. Primary endpoint of the study was CMR-based left ventricular ejection fraction on week 16. Results Until week 6 (time of fourth doxorubicin injection), LVEF remained unchanged in both groups. From there on, a progressive decline in LVEF was observed. LVEF depression trajectory was blunted in RIPC animals. Compared to controls, pigs undergoing RIPC before each doxorubicin dose had a significantly higher LVEF at week 16: median (IQR) 45% (27–50%) vs 33% (19–47%) in RIPC and controls respectively, p=0.04. Improvement in LVEF was mainly due to a more preserved contractile function, as evidence by smaller LVESV, and better regional contractile function. After 3 doxorubicin doses, a time where global (LVEF) and regional contractile function was still unchanged, transmission electron microscopy (TEM) showed fragmented mitochondria with remodeled cristae only in control pigs. At the end of the 16 weeks, TEM evaluation in control pigs (as compared to RIPC pigs) showed overt cardiomyocyte's mitochondrial fragmentation with overt structural derangement. At this time, RIPC pigs had significantly less interstitial fibrosis on histology. Conclusions In a translatable large animal model of AIC, RIPC applied immediately before each doxorubicin cycle resulted in a preservation of cardiac contractility with significantly higher long-term LVEF and less cardiac fibrosis. RIPC prevented the deleterious effects of doxorubicin on mitochondria since early stages of AIC. RIPC is a promising intervention to be tested in clinical trials to prevent cardiotoxicity. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): The CNIC is supported by the Instituto de Salud Carlos III (ISCIII), the Ministerio de Ciencia e Innovaciόn and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505)

Remote ischaemic preconditioning ameliorates anthracycline-induced cardiotoxicity and preserves mitochondrial integrity.

AimsAnthracycline-induced cardiotoxicity (AIC) is a serious adverse effect among cancer patients. A central mechanism of AIC is irreversible mitochondrial damage. Despite major efforts, there are currently no effective therapies able to prevent AIC.Methods and resultsForty Large-White pigs were included. In Study 1, 20 pigs were randomized 1:1 to remote ischaemic preconditioning (RIPC, 3 cycles of 5 min leg ischaemia followed by 5 min reperfusion) or no pretreatment. RIPC was performed immediately before each intracoronary doxorubicin injections (0.45 mg/kg) given at Weeks 0, 2, 4, 6, and 8. A group of 10 pigs with no exposure to doxorubicin served as healthy controls. Pigs underwent serial cardiac magnetic resonance (CMR) exams at baseline and at Weeks 6, 8, 12, and 16, being sacrifice after that. In Study 2, 10 new pigs received 3 doxorubicin injections (with/out preceding RIPC) and were sacrificed at week 6. In Study 1, left ventricular ejection fraction (LVEF) depression was blunted animals receiving RIPC before doxorubicin (RIPC-Doxo), which had a significantly higher LVEF at Week 16 than doxorubicin treated pigs that received no pretreatment (Untreated-Doxo) (41.5 ± 9.1% vs. 32.5 ± 8.7%, P = 0.04). It was mainly due to conserved regional contractile function. In Study 2, transmission electron microscopy (TEM) at Week 6 showed fragmented mitochondria with severe morphological abnormalities in Untreated-Doxo pigs, together with upregulation of fission and autophagy proteins. At the end of the 16-week Study 1 protocol, TEM revealed overt mitochondrial fragmentation with structural fragmentation in Untreated-Doxo pigs, whereas interstitial fibrosis was less severe in RIPC+Doxo pigs.ConclusionIn a translatable large-animal model of AIC, RIPC applied immediately before each doxorubicin injection resulted in preserved cardiac contractility with significantly higher long-term LVEF and less cardiac fibrosis. RIPC prevented mitochondrial fragmentation and dysregulated autophagy from AIC early stages. RIPC is a promising intervention for testing in clinical trials in AIC.

Quantification of regional right ventricular strain in healthy rats using 3D spiral cine dense MRI

Statistical data from clinical studies suggests that right ventricular (RV) circumferential strain (Ecc) and longitudinal strain (Ell) are significant biomarkers for many cardiovascular diseases. However, a detailed and regional characterization of these strains in the RV is very limited. In the current study, RV images were obtained with 3D spiral cine DENSE MRI in healthy rats. An algorithm for surface growing was proposed in order to fit irregular topology. Specifically, a new custom plugin for the DENSEanalysis program, called 3D DENSE Plugin for Crescent Organ, was developed for surface reconstruction and precise segmentation of organs with sharp curvature, such as the murine RV. The RV free wall (RVFW) was divided into three longitudinal thirds (i.e., basal, middle, and apical) with each one partitioned into circumferential fourths (i.e., anterior, anteriorlateral, inferiorlateral and inferior). Peak systolic strains were quantified for each segment and comparisons were performed statistically. The inclusion of a new plugin was able to generate global values for Ecc and Ell that are in good agreement with previous findings using MRI. Despite no regional variation found in the peak Ecc, the peak Ell exhibited regional variation at the anterior side of the RV, which is potentially due to differences in biventricular torsion at the RV insertion point and fiber architecture. These results provide fundamental insights into the regional contractile function of the RV in healthy rat and could act as a normative baseline for future studies on regional changes induced by disease or treatment.

Transplantation of Human-induced Pluripotent Stem Cell-derived Cardiomyocytes Is Superior to Somatic Stem Cell Therapy for Restoring Cardiac Function and Oxygen Consumption in a Porcine Model of Myocardial Infarction.

BackgroundSomatic stem cell (SC) therapy can improve cardiac performance following ischemic injury. In this study, we investigated whether induced pluripotent SC-derived cardiomyocytes (iPS-CMs) are more effective than somatic SCs, such as skeletal myoblasts (SM) and mesenchymal (M)SCs, in promoting functional recovery upon transplantation in a porcine model of myocardial infarction.MethodsMyocardial injury was induced by ameroid ring placement in immunosuppressed female mini pigs; after 1 month, epicardial cell transplantation was performed with iPS-CMs (n = 7), SMs (n = 7), and MSCs (n = 7). Control pigs underwent sham operation (n = 8).ResultsCell therapy improved functional recovery 2 months after myocardial infarction, as evidenced by increased ejection fraction (iPS-CM, +7.3% ± 2.2% and SM, +5.8% ± 5.4% vs control, −4.4% ± 3.8%; P < 0.05). The analysis of regional contractile function in the infarcted zone revealed an increase in transverse peak strain (iPS-CM, +4.6% ± 2.2% vs control, −3.8% ± 4.7%; P < 0.05). The C-11 acetate kinetic analysis by positron emission tomography showed that the work-metabolic cardiac energy efficacy increased by the transplantation of iPS-CMs, but was reduced by the other cell types. This was accompanied by decreased myocardial wall stress in the infarcted zone (iPS-CM, −27.6 ± 32.3 Pa and SM, −12.8 ± 27 Pa vs control, +40.5 ± 33.9 Pa; P < 0.05).ConclusionsThe iPS-CM is superior to other somatic cell sources in terms of improving regional contractile function and cardiac bioenergetic efficiency, suggesting greater clinical benefits in severely damaged myocardium.

Regional quantification of myocardial mechanics in rat using 3D cine DENSE cardiovascular magnetic resonance.

Rat models have assumed an increasingly important role in cardiac research. However, a detailed profile of regional cardiac mechanics, such as strains and torsion, is lacking for rats. We hypothesized that healthy rat left ventricles (LVs) exhibit regional differences in cardiac mechanics, which are part of normal function. In this study, images of the LV were obtained with 3D cine displacement encoding with stimulated echoes (DENSE) cardiovascular magnetic resonance in 10 healthy rats. To evaluate regional cardiac mechanics, the LV was divided into basal, mid-ventricular, and apical regions. The myocardium at the mid-LV was further partitioned into four wall segments (i.e. septal, inferior, lateral, and anterior) and three transmural layers (i.e. sub-endocardium, mid-myocardium, and sub-epicardium). The six Lagrangian strain components (i.e. Err , Ecc , Ell , Ecl , Erl , and Ecr ) were computed from the 3D displacement field and averaged within each region of interest. Torsion was quantified using the circumferential-longitudinal shear angle. While peak systolic Ecl differed between the mid-ventricle and apex, the other five components of peak systolic strain were similar across the base, mid-ventricle, and apex. In the mid-LV myocardium, Ecc decreased gradually from the sub-endocardial to the sub-epicardial layer. Ell demonstrated significant differences between the four wall segments, with the largest magnitude in the inferior segment. Err was uniform among the four wall segments. Ecl varied along the transmural direction and among wall segments, whereas Erl differed only among the wall segments. Erc was not associated with significant variations. Torsion also varied along the transmural direction and among wall segments. These results provide fundamental insights into the regional contractile function of healthy rat hearts, and form the foundation for future studies on regional changes induced by disease or treatments.

Magnetic resonance imaging for characterizing myocardial diseases.

The National Institute of Health defined cardiomyopathy as diseases of the heart muscle. These myocardial diseases have different etiology, structure and treatment. This review highlights the key imaging features of different myocardial diseases. It provides information on myocardial structure/orientation, perfusion, function and viability in diseases related to cardiomyopathy. The standard cardiac magnetic resonance imaging (MRI) sequences can reveal insight on left ventricular (LV) mass, volumes and regional contractile function in all types of cardiomyopathy diseases. Contrast enhanced MRI sequences allow visualization of different infarct patterns and sizes. Enhancement of myocardial inflammation and infarct (location, transmurality and pattern) on contrast enhanced MRI have been used to highlight the key differences in myocardial diseases, predict recovery of function and healing. The common feature in many forms of cardiomyopathy is the presence of diffuse-fibrosis. Currently, imaging sequences generating the most interest in cardiomyopathy include myocardial strain analysis, tissue mapping (T1, T2, T2*) and extracellular volume (ECV) estimation techniques. MRI sequences have the potential to decode the etiology by showing various patterns of infarct and diffuse fibrosis in myocarditis, amyloidosis, sarcoidosis, hypertrophic cardiomyopathy due to aortic stenosis, restrictive cardiomyopathy, arrythmogenic right ventricular dysplasia and hypertension. Integrated PET/MRI system may add in the future more information for the diagnosis and progression of cardiomyopathy diseases. With the promise of high spatial/temporal resolution and 3D coverage, MRI will be an indispensible tool in diagnosis and monitoring the benefits of new therapies designed to treat myocardial diseases.

Effect of cellular and extracellular pathology assessed by T1 mapping on regional contractile function in hypertrophic cardiomyopathy

BackgroundRegional contractile dysfunction is a frequent finding in hypertrophic cardiomyopathy (HCM). We aimed to investigate the contribution of different tissue characteristics in HCM to regional contractile dysfunction.MethodsWe prospectively recruited 50 patients with HCM who underwent cardiovascular magnetic resonance (CMR) studies at 3.0 T including cine imaging, T1 mapping and late gadolinium enhancement (LGE) imaging. For each segment of the American Heart Association model segment thickness, native T1, extracellular volume (ECV), presence of LGE and regional strain (by feature tracking and tissue tagging) were assessed. The relationship of segmental function, hypertrophy and tissue characteristics were determined using a mixed effects model, with random intercept for each patient.ResultsIndividually segment thickness, native T1, ECV and the presence of LGE all had significant associations with regional strain. The first multivariable model (segment thickness, LGE and ECV) demonstrated that all strain parameters were associated with segment thickness (P < 0.001 for all) but not ECV. LGE (Beta 2.603, P = 0.024) had a significant association with circumferential strain measured by tissue tagging.In a second multivariable model (segment thickness, LGE and native T1) all strain parameters were associated with both segment thickness (P < 0.001 for all) and native T1 (P < 0.001 for all) but not LGE.ConclusionImpairment of contractile function in HCM is predominantly associated with the degree of hypertrophy and native T1 but not markers of extracellular fibrosis (ECV or LGE). These findings suggest that impairment of contractility in HCM is mediated by mechanisms other than extracellular expansion that include cellular changes in structure and function. The cellular mechanisms leading to increased native T1 and its prognostic significance remain to be established.

Magnetic resonance imaging assessment of cardiac function in a swine model of hibernating myocardium 3 months following bypass surgery

ObjectiveClinical studies demonstrate delayed recovery of hibernating myocardium (HM) following coronary artery bypass graft (CABG) surgery. Cardiac magnetic resonance (CMR) imaging is effective in identifying HM in clinical settings. Our animal model of HM shows partial but incomplete functional recovery 1 month following CABG using echocardiography. This study uses CMR imaging to determine completeness of recovery 3 months post-CABG. MethodsSwine (N = 12) underwent left anterior descending artery (LAD) 1.5-cm constrictor placement creating a territory of HM over 12 weeks. CMR at 12 weeks confirmed hibernation without infarction (N = 12). Off-pump left internal thoracic artery (LITA) to the LAD was performed in 9 animals. Three animals were killed as HM controls. CMR imaging was repeated in revascularized animals before death at 1 (n = 4) or 3 months (n = 5). CMR imaging was performed at baseline and with dobutamine infusion (5 μg/kg/min). ResultsTwelve weeks after constrictor placement, CMR imaging confirmed viability in LAD region and LAD stenosis in all animals. In HM, wall thickening is reduced at baseline but with contractile reserve present during dobutamine infusion. Following revascularization, CMR imaging confirmed patent LITA graft (n = 9). Analysis of baseline regional function shows incomplete recovery of HM following CABG, with reduced contractile reserve at both 1 and 3 months post-CABG. ConclusionsCMR imaging provides accurate spatial resolution of regional contractile function and confirms the presence of HM at 12 weeks following instrumentation of the LAD. Three months following CABG, partial recovery of HM with contractile reserve is present in the single LAD territory.

Intradialytic Cardiac Magnetic Resonance Imaging to Assess Cardiovascular Responses in a Short-Term Trial of Hemodiafiltration and Hemodialysis.

Hemodynamic stress during hemodialysis (HD) results in recurrent segmental ischemic injury (myocardial stunning) that drives cumulative cardiac damage. We performed a fully comprehensive study of the cardiovascular effect of dialysis sessions using intradialytic cardiac magnetic resonance imaging (MRI) to examine the comparative acute effects of standard HD versus hemodiafiltration (HDF) in stable patients. We randomly allocated 12 patients on HD (ages 32-72 years old) to either HD or HDF. Patients were stabilized on a modality for 2 weeks before undergoing serial cardiac MRI assessment during dialysis. Patients then crossed over to the other modality and were rescanned after 2 weeks. Cardiac MRI measurements included cardiac index, stroke volume index, global and regional contractile function (myocardial strain), coronary artery flow, and myocardial perfusion. Patients had mean±SEM ultrafiltration rates of 3.8±2.9 ml/kg per hour during HD and 4.4±2.5 ml/kg per hour during HDF (P=0.29), and both modalities provided a similar degree of cooling. All measures of systolic contractile function fell during HD and HDF, with partial recovery after dialysis. All patients experienced some degree of segmental left ventricular dysfunction, with severity proportional to ultrafiltration rate and BP reduction. Myocardial perfusion decreased significantly during HD and HDF. Treatment modality did not influence any of the cardiovascular responses to dialysis. In conclusion, in this randomized, crossover study, there was no significant difference in the cardiovascular response to HDF or HD with cooled dialysate as assessed with intradialytic MRI.

Chagas’ Disease: Update on Current Diagnosis

Purpose of Review Chagas’ disease has become an emerging health problem due to increased migration. In the present review, we have summarized the usefulness of non-invasive imaging tools for the diagnosis of cardiac involvement in Chagas’ disease, with emphasis on modern technologies. M-mode, bidimensional (2-D), and three-dimensional (3-D) echocardiographies may allow the evaluation of left ventricular (LV) regional and global contractile function, right ventricle (RV) impairment, evidence of aneurysms and thrombi, and assessment of diastolic function in any stage of the disease.

Myocardial Ischemia: Lack of Coronary Blood Flow or Myocardial Oxygen Supply/Demand Imbalance?

Regional myocardial blood flow and contractile function in ischemic myocardium are well matched, and there is no evidence for an oxygen supply/demand imbalance. Thus, myocardial ischemia is lack of coronary blood flow with electric, functional, metabolic, and structural consequences for the myocardium. All therapeutic interventions must aim to improve blood flow to ischemic myocardium as much and as quickly as possible.