In vivo cardiovascular magnetic resonance diffusion tensor imaging shows evidence of abnormal myocardial laminar orientations and mobility in hypertrophic cardiomyopathy

Background

Cardiac diffusion tensor imaging (cDTI) measures the magnitudes and directions of intramyocardial water diffusion. Assuming the cross-myocyte components to be constrained by the laminar microstructures of myocardium, we hypothesized that cDTI at two cardiac phases might identify any abnormalities of laminar orientation and mobility in hypertrophic cardiomyopathy (HCM).

Methods

We performed cDTI in vivo at 3 Tesla at end-systole and late diastole in 11 healthy controls and 11 patients with HCM, as well as late gadolinium enhancement (LGE) for detection of regional fibrosis.

Results

Voxel-wise analysis of diffusion tensors relative to left ventricular coordinates showed expected transmural changes of myocardial helix-angle, with no significant differences between phases or between HCM and control groups. In controls, the angle of the second eigenvector of diffusion (E2A) relative to the local wall tangent plane was larger in systole than diastole, in accord with previously reported changes of laminar orientation. HCM hearts showed higher than normal global E2A in systole (63.9° vs 56.4° controls, p = 0.026) and markedly raised E2A in diastole (46.8° vs 24.0° controls, p < 0.001). In hypertrophic regions, E2A retained a high, systole-like angulation even in diastole, independent of LGE, while regions of normal wall thickness did not (LGE present 57.8°, p = 0.0028, LGE absent 54.8°, p = 0.0022 vs normal thickness 38.1°).

Conclusions

In healthy controls, the angles of cross-myocyte components of diffusion were consistent with previously reported transmural orientations of laminar microstructures and their changes with contraction. In HCM, especially in hypertrophic regions, they were consistent with hypercontraction in systole and failure of relaxation in diastole. Further investigation of this finding is required as previously postulated effects of strain might be a confounding factor.

Electronic supplementary material

The online version of this article (doi:10.1186/s12968-014-0087-8) contains supplementary material, which is available to authorized users.     

Early manifestation of alteration in cardiac function in dystrophin deficient mdx mouse using 3D CMR tagging

Background

Duchenne muscular dystrophy (DMD) is caused by the absence of the cytoskeletal protein, dystrophin. In DMD patients, dilated cardiomyopathy leading to heart failure may occur during adolescence. However, early cardiac dysfunction is frequently undetected due to physical inactivity and generalized debilitation. The objective of this study is to determine the time course of cardiac functional alterations in mdx mouse, a mouse model of DMD, by evaluating regional ventricular function with CMR tagging.

Methods

In vivo myocardial function was evaluated by 3D CMR tagging in mdx mice at early (2 months), middle (7 months) and late (10 months) stages of disease development. Global cardiac function, regional myocardial wall strains, and ventricular torsion were quantified. Myocardial lesions were assessed with Masson''s trichrome staining.

Results

Global contractile indexes were similar between mdx and C57BL/6 mice in each age group. Histology analysis showed that young mdx mice were free of myocardial lesions. Interstitial fibrosis was present in 7 month mdx mice, with further development into patches or transmural lesions at 10 months of age. As a result, 10 month mdx mice showed significantly reduced regional strain and torsion. However, young mdx mice showed an unexpected increase in regional strain and torsion, while 7 month mdx mice displayed similar regional ventricular function as the controls.

Conclusion

Despite normal global ventricular function, CMR tagging detected a biphasic change in myocardial wall strain and torsion, with an initial increase at young age followed by progressive decrease at older ages. These results suggest that CMR tagging can provide more sensitive measures of functional alterations than global functional indexes in dystrophin-related cardiomyopathies.     

Clinical experience of strain imaging using DENSE for detecting infarcted cardiac segments

Background

We hypothesised that myocardial deformation determined with magnetic resonance imaging (MRI) will detect myocardial scar.

Methods

Displacement Encoding with Stimulated Echoes (DENSE) was used to calculate left ventricular strain in 125 patients (29 women and 96 men) with suspected coronary artery disease. The patients also underwent cine imaging and late gadolinium enhancement. 57 patients had a scar area >1 % in at least one segment, 23 were considered free from coronary artery disease (control group) and 45 had pathological findings but no scar (mixed group). Peak strain was calculated in eight combinations: radial and circumferential strain in transmural, subendocardial and epicardial layers derived from short axis acquisition, and transmural longitudinal and radial strain derived from long axis acquisitions. In addition, the difference between strain in affected segments and reference segments, “differential strain”, from the control group was analysed.

Results

In receiver-operator-characteristic analysis for the detection of 50 % transmurality, circumferential strain performed best with area-under-curve (AUC) of 0.94. Using a cut-off value of -17 %, sensitivity was 95 % at a specificity of 80 %. AUC did not further improve with differential strain. There were significant differences between the control group and global strain circumferential direction (-17 % versus -12 %) and in the longitudinal direction (-13 % versus -10 %). Interobserver and scan-rescan reproducibility was high with an intraclass correlation coefficient (ICC) >0.93.

Conclusions

DENSE-derived circumferential strain may be used for the detection of myocardial segments with >50 % scar area. The repeatability of strain is satisfactory. DENSE-derived global strain agrees with other global measures of left ventricular ejection fraction.     

Antithrombin attenuates myocardial dysfunction and reverses systemic fluid accumulation following burn and smoke inhalation injury: a randomized,controlled, experimental study

Introduction

We hypothesized that maintaining physiological plasma levels of antithrombin attenuates myocardial dysfunction and inflammation as well as vascular leakage associated with burn and smoke inhalation injury. Therefore, the present prospective, randomized experiment was conducted using an established ovine model.

Methods

Following 40% of total body surface area, third degree flame burn and 4 × 12 breaths of cold cotton smoke, chronically instrumented sheep were randomly assigned to receive an intravenous infusion of 6 IU/kg/h recombinant human antithrombin (rhAT) or normal saline (control group; n = 6 each). In addition, six sheep were designated as sham animals (not injured, continuous infusion of vehicle). During the 48 h study period the animals were awake, mechanically ventilated and fluid resuscitated according to standard formulas.

Results

Compared to the sham group, myocardial contractility was severely impaired in control animals, as suggested by lower stroke volume and left ventricular stroke work indexes. As a compensatory mechanism, heart rate increased, thereby increasing myocardial oxygen consumption. In parallel, myocardial inflammation was induced via nitric oxide production, neutrophil accumulation (myeloperoxidase activity) and activation of the p38-mitogen-activated protein kinase pathway resulting in cytokine release (tumor necrosis factor-alpha, interleukin-6) in control vs. sham animals. rhAT-treatment significantly attenuated these inflammatory changes leading to a myocardial contractility and myocardial oxygen consumption comparable to sham animals. In control animals, systemic fluid accumulation progressively increased over time resulting in a cumulative positive fluid balance of about 4,000 ml at the end of the study period. Contrarily, in rhAT-treated animals there was only an initial fluid accumulation until 24 h that was reversed back to the level of sham animals during the second day.

Conclusions

Based on these findings, the supplementation of rhAT may represent a valuable therapeutic approach for cardiovascular dysfunction and inflammation after burn and smoke inhalation injury.     

A quantitative comparison of regional myocardial motion in mice,rabbits and humans using in-vivo phase contrast CMR

Background

Genetically manipulated animals like mice or rabbits play an important role in the exploration of human cardiovascular diseases. It is therefore important to identify animal models that closely mimic physiological and pathological human cardiac function.

Methods

In-vivo phase contrast cardiovascular magnetic resonance (CMR) was used to measure regional three-directional left ventricular myocardial motion with high temporal resolution in mice (N=18), rabbits (N=8), and humans (N=20). Radial, long-axis, and rotational myocardial velocities were acquired in left ventricular basal, mid-ventricular, and apical short-axis locations.

Results

Regional analysis revealed different patterns of motion: 1) In humans and rabbits, the apex showed slower radial velocities compared to the base. 2) Significant differences within species were seen in the pattern of long-axis motion. Long-axis velocities during systole were fairly homogeneously distributed in mice, whereas humans showed a dominant component in the lateral wall and rabbits in the base. 3) Rotational velocities and twist showed the most distinct patterns in both temporal evolution and relative contribution of base, mid-ventricle and apex, respectively. Interestingly, a marked difference in rotational behavior during early-systole was found in mice, which exhibited clockwise rotation in all slice locations compared to counter-clockwise rotation in rabbits and humans.

Conclusions

Phase contrast CMR revealed subtle, but significantly different regional myocardial motion patterns in mice, rabbits and humans. This finding has to be considered when investigating myocardial motion pattern in small animal models of heart disease.     

Utility of Cardiac Magnetic Resonance to assess association between admission hyperglycemia and myocardial damage in patients with reperfused ST-Segment Elevation Myocardial Infarction

Aims

to investigate the association between admission hyperglycemia and myocardial damage in patients with ST-segment elevation myocardial infarction (STEMI) using Cardiac Magnetic Resonance (CMR).

Methods

We analyzed 113 patients with STEMI treated with successful primary percutaneous coronary intervention. Admission hyperglycemia was defined as a glucose level ≥ 7.8 mmol/l. Contrast-enhanced CMR was performed between 3 and 7 days after reperfusion to evaluate left ventricular function and perfusion data after injection of gadolinium-DTPA. First-pass images (FP), providing assessment of microvascular obstruction and Late Gadolinium Enhanced images (DE), reflecting the extent of infarction, were investigated and the extent of transmural tissue damage was determined by visual scores.

Results

Patients with a supramedian FP and DE scores more frequently had left anterior descending culprit artery (p = 0.02 and <0.001), multivessel disease (p = 0.02 for both) and hyperglycemia (p < 0.001). Moreover, they were characterized by higher levels of HbA_1c (p = 0.01 and 0.04), peak plasma Creatine Kinase (p < 0.001), left ventricular end-systolic volume (p = 0.005 and <0.001), and lower left ventricular ejection fraction (p = 0.001 and <0.001).In a multivariate model, admission hyperglycemia remains independently associated with increased FP and DE scores.

Conclusion

Our results show the existence of a strong relationship between glucose metabolism impairment and myocardial damage in patients with STEMI. Further studies are needed to show if aggressive glucose control improves myocardial perfusion, which could be assessed using CMR.     

Volumetric motion quantification by 3D tissue phase mapped CMR

Background

The objective of this study was the quantification of myocardial motion from 3D tissue phase mapped (TPM) CMR. Recent work on myocardial motion quantification by TPM has been focussed on multi-slice 2D acquisitions thus excluding motion information from large regions of the left ventricle. Volumetric motion assessment appears an important next step towards the understanding of the volumetric myocardial motion and hence may further improve diagnosis and treatments in patients with myocardial motion abnormalities.

Methods

Volumetric motion quantification of the complete left ventricle was performed in 12 healthy volunteers and two patients applying a black-blood 3D TPM sequence. The resulting motion field was analysed regarding motion pattern differences between apical and basal locations as well as for asynchronous motion pattern between different myocardial segments in one or more slices. Motion quantification included velocity, torsion, rotation angle and strain derived parameters.

Results

All investigated motion quantification parameters could be calculated from the 3D-TPM data. Parameters quantifying hypokinetic or asynchronous motion demonstrated differences between motion impaired and healthy myocardium.

Conclusions

3D-TPM enables the gapless volumetric quantification of motion abnormalities of the left ventricle, which can be applied in future application as additional information to provide a more detailed analysis of the left ventricular function.     

Magnetic susceptibility anisotropy of myocardium imaged by cardiovascular magnetic resonance reflects the anisotropy of myocardial filament α-helix polypeptide bonds

Background

A key component of evaluating myocardial tissue function is the assessment of myofiber organization and structure. Studies suggest that striated muscle fibers are magnetically anisotropic, which, if measurable in the heart, may provide a tool to assess myocardial microstructure and function.

Methods

To determine whether this weak anisotropy is observable and spatially quantifiable with cardiovascular magnetic resonance (CMR), both gradient-echo and diffusion-weighted data were collected from intact mouse heart specimens at 9.4 Tesla. Susceptibility anisotropy was experimentally calculated using a voxelwise analysis of myocardial tissue susceptibility as a function of myofiber angle. A myocardial tissue simulation was developed to evaluate the role of the known diamagnetic anisotropy of the peptide bond in the observed susceptibility contrast.

Results

The CMR data revealed that myocardial tissue fibers that were parallel and perpendicular to the magnetic field direction appeared relatively paramagnetic and diamagnetic, respectively. A linear relationship was found between the magnetic susceptibility of the myocardial tissue and the squared sine of the myofiber angle with respect to the field direction. The multi-filament model simulation yielded susceptibility anisotropy values that reflected those found in the experimental data, and were consistent that this anisotropy decreased as the echo time increased.

Conclusions

Though other sources of susceptibility anisotropy in myocardium may exist, the arrangement of peptide bonds in the myofilaments is a significant, and likely the most dominant source of susceptibility anisotropy. This anisotropy can be further exploited to probe the integrity and organization of myofibers in both healthy and diseased heart tissue.     

Respiratory muscle endurance is limited by lower ventilatory efficiency in post-myocardial infarction patients

Background

Reduced respiratory muscle endurance (RME) contributes to increased dyspnea upon exertion in patients with cardiovascular disease.

Objective

The objective was to characterize ventilatory and metabolic responses during RME tests in post-myocardial infarction patients without respiratory muscle weakness.

Method

Twenty-nine subjects were allocated into three groups: recent myocardial infarction group (RG, n=9), less-recent myocardial infarction group (LRG, n=10), and control group (CG, n=10). They underwent two RME tests (incremental and constant pressure) with ventilatory and metabolic analyses. One-way ANOVA and repeated measures one-way ANOVA, both with Tukey post-hoc, were used between groups and within subjects, respectively.

Results

Patients from the RG and LRG presented lower metabolic equivalent and ventilatory efficiency than the CG on the second (50± 06, 50± 5 vs. 42± 4) and third part (50± 11, 51± 10 vs. 43± 3) of the constant pressure RME test and lower metabolic equivalent during the incremental pressure RME test. Additionally, at the peak of the incremental RME test, RG patients had lower oxygen uptake than the CG.

Conclusions

Post-myocardial infarction patients present lower ventilatory efficiency during respiratory muscle endurance tests, which appears to explain their inferior performance in these tests even in the presence of lower pressure overload and lower metabolic equivalent.     

Prevalence of scarred and dysfunctional myocardium in patients with heart failure of ischaemic origin: A cardiovascular magnetic resonance study

Background

Cardiovascular magnetic resonance (CMR) with late gadolinium enhancement (LGE) can provide unique data on the transmural extent of scar/viability. We assessed the prevalence of dysfunctional myocardium, including partial thickness scar, which could contribute to left ventricular contractile dysfunction in patients with heart failure and ischaemic heart disease who denied angina symptoms.

Methods

We invited patients with ischaemic heart disease and a left ventricular ejection fraction < 50% by echocardiography to have LGE CMR. Myocardial contractility and transmural extent of scar were assessed using a 17-segment model.

Results

The median age of the 193 patients enrolled was 70 (interquartile range: 63-76) years and 167 (87%) were men. Of 3281 myocardial segments assessed, 1759 (54%) were dysfunctional, of which 581 (33%) showed no scar, 623 (35%) had scar affecting ≤50% of wall thickness and 555 (32%) had scar affecting > 50% of wall thickness. Of 1522 segments with normal contractile function, only 98 (6%) had evidence of scar on CMR. Overall, 182 (94%) patients had ≥1 and 107 (55%) patients had ≥5 segments with contractile dysfunction that had no scar or ≤50% transmural scar suggesting viability.

Conclusions

In this cohort of patients with left ventricular systolic dysfunction and ischaemic heart disease, about half of all segments had contractile dysfunction but only one third of these had > 50% of the wall thickness affected by scar, suggesting that most dysfunctional segments could improve in response to an appropriate intervention.     

Does intra-aortic balloon support for myocardial infarction with cardiogenic shock improve outcome?

Expanded abstract

Citation

Thiele H, Zeymer U, Neumann FJ, Ferenc M, Olbrich HG, Hausleiter J, Richardt G, Hennersdorf M, Empen K, Fuernau G, Desch S, Eitel I, Hambrecht R, Fuhrmann J, Böhm M, Ebelt H, Schneider S, Schuler G, Werdan K; IABP-SHOCK II Trial Investigators: Intraaortic balloon support for myocardial infarction with cardiogenic shock. N Engl J Med 2012, 367:1287-1296.

Background

In the current international guidelines, intra-aortic balloon pump (IABP) counterpulsation is considered a class I treatment for acute myocardial infarction complicated by cardiogenic shock. However, evidence is based mainly on registry data, and there is a paucity of randomized clinical trials.

Methods

Objective

To test the hypothesis that IABP counterpulsation, as compared with the best available medical therapy alone, results in a reduction in mortality among patients with acute myocardial infarction complicated by cardiogenic shock for whom early revascularization is planned.

Design

Randomized, prospective, open-label, multicenter trial.

Setting

Thirty-seven centers in Germany.

Subjects

All adults had acute myocardial infarction complicated by cardiogenic shock and were expected to undergo early revascularization (by means of percutaneous coronary intervention or bypass surgery).

Intervention

After enrollment, 600 patients were randomly assigned to intra-aortic balloon counterpulsation (IABP group, 301 patients) or no IABP counterpulsation (control group, 299 patients).

Outcomes

The primary efficacy endpoint is 30-day all-cause mortality.

Results

At 30 days, 119 patients in the IABP group (39.7%) and 123 patients in the control group (41.3%) had died (relative risk with IABP, 0.96; 95% confidence interval, 0.79 to 1.17; P = 0.69). There were no significant differences in secondary endpoints or in process-of-care measures, including the time to hemodynamic stabilization, the length of stay in the intensive care unit, serum lactate levels, the dose and duration of catecholamine therapy, and renal function.

Conclusions

The use of IABP counterpulsation did not significantly reduce 30-day mortality in patients with acute myocardial infarction complicated by cardiogenic shock for whom an early revascularization strategy was planned.     

Structural and functional cardiac changes in myotonic dystrophy type 1: a cardiovascular magnetic resonance study

Background

Myotonic dystrophy type 1 (MD1) is a neuromuscular disorder with potential involvement of the heart and increased risk of sudden death. Considering the importance of cardiomyopathy as a predictor of prognosis, we aimed to systematically evaluate and describe structural and functional cardiac alterations in patients with MD1.

Methods

Eighty MD1 patients underwent physical examination, electrocardiography (ECG), echocardiography and cardiovascular magnetic resonance (CMR). Blood samples were taken for determination of NT-proBNP plasma levels and CTG repeat length.

Results

Functional and structural abnormalities were detected in 35 patients (44%). Left ventricular systolic dysfunction was found in 20 cases, left ventricular dilatation in 7 patients, and left ventricular hypertrophy in 6 patients. Myocardial fibrosis was seen in 10 patients (12.5%). In general, patients had low left ventricular mass indexes. Right ventricular involvement was uncommon and only seen together with left ventricular abnormalities. Functional or structural cardiac involvement was associated with age (p = 0.04), male gender (p < 0.001) and abnormal ECG (p < 0.001). Disease duration, CTG repeat length, severity of neuromuscular symptoms and NT-proBNP level did not predict the presence of myocardial abnormalities.

Conclusions

CMR can be useful to detect early structural and functional myocardial abnormalities in patients with MD1. Myocardial involvement is strongly associated with conduction abnormalities, but a normal ECG does not exclude myocardial alterations. These findings lend support to the hypothesis that MD1 patients have a complex cardiac phenotype, including both myocardial and conduction system alteration.     

Prediction of global left ventricular functional recovery in patients with heart failure undergoing surgical revascularisation,based on late gadolinium enhancement Cardiovascular Magnetic Resonance

Background

The new gold standard for myocardial viability assessment is late gadolinium enhancement-cardiovascular magnetic resonance (LGE-CMR); this technique has demonstrated that the transmural extent of scar predicts segmental functional recovery. We now asked how the number of viable and number of viable+normal, segments predicted recovery of global left ventricular (LV) function in patients undergoing CABG. Finally, we examined which segmental transmural threshold of scarring best predicted global LV recovery.

Methods and Results

Fifty patients with reduced LV ejection fraction (EF) referred for CABG were recruited, and 33 included in this analysis. Patients underwent CMR to assess LV function and viability pre-operatively at 6 days and 6 months. Mean LVEF 38% ± 11, which improved to 43% ± 12 after surgery. 21/33 patients improved EF by ≥3% (EF before 38% ± 13, after 47% ± 13), 12/33 did not (EF before 39% ± 6, after 37% ± 8). The only independent predictor for global functional recovery after revascularisation was the number of viable+normal segments: Based on a segmental transmural viability cutoff of <50%, ROC analysis demonstrated ≥10 viable+normal segments predicted ≥3% improvement in LVEF with a sensitivity of 95% and specificity of 75% (AUC = 0.9, p < 0.001). Transmural viability cutoffs of <25 and <75% and a cutoff of ≥4 viable segments were less useful predictors of global LV recovery.

Conclusions

Based on a 50% transmural viability cutoff, patients with ≥10 viable+normal segments improve global LV function post revascularisation, while patients with fewer such segments do not. LGE-CMR is a simple and powerful tool for identifying which patients with impaired LV function will benefit from CABG.

Trial registration

Research Ethics Committee Unique Identifier: NRES:05/Q1603/42. The study is listed on the Current Controlled Trials Registry: ISRCTN41388968.URL: http://www.controlled-trials.com     

Myocardial Fiber Mapping of Rat Hearts,Using Apparent Backscatter,with Histologic Validation

Myocardial fiber architecture is a physiologically important regulator of ejection fraction, strain and pressure development. Apparent ultrasonic backscatter has been shown to be a useful method for recreating the myocardial fiber architecture in human-sized sheep hearts because of the dependence of its amplitude on the relative orientation of a myofiber to the angle of ultrasonic insonification. Thus, the anisotropy of the backscatter signal is linked to and provides information about the fiber orientation. In this study, we sought to determine whether apparent backscatter could be used to measure myofiber orientation in rodent hearts. Fixed adult-rat hearts were imaged intact, and both a transmural cylindrical core and transmural wedge of the left ventricular free wall were imaged. Cylindrical core samples confirmed that backscatter anisotropy could be measured in rat hearts. Ultrasound and histologic analysis of transmural myocardial wedge samples confirmed that the apparent backscatter could be reproducibly mapped to fiber orientation (angle of the fiber relative to the direction of insonification). These data provided a quantitative relationship between the apparent backscatter and fiber angle that was applied to whole-heart images. Myocardial fiber architecture was successfully measured in rat hearts. Quantifying myocardial fiber architecture, using apparent backscatter, provides a number of advantages, including its scalable use from rodents to man, its rapid low-cost acquisition and minimal contraindications. The method outlined in this study provides a method for investigators to begin detailed assessments of how the myocardial fiber architecture changes in preclinical disease models, which can be immediately translated into the clinic.     

Regional assessment of left ventricular torsion by CMR tagging

Purpose

To introduce a standardized method for calculation of left ventricular torsion by CMR tagging and to determine the accuracy of torsion analysis in regions using an analytical model.

Methods

Torsion between base and apex, base and mid, and mid and apex levels was calculated using CSPAMM tagging and Harmonic Phase tracking. The accuracy of torsion analysis on a regional basis (circumferential segments and transmural layers) was analyzed using an analytical model of a deforming cylinder with a displaced axis of rotation (AoR). Regional peak torsion values from twelve healthy volunteers calculated by the described method were compared to literature.

Results

The deviation from the analytical torsion per % AoR-displacement (of the radius) was 0.90 ± 0.44% for the circumferential segments and only 0.05% for the transmural layers. In the subjects, circumferentially, anterolateral torsion was larger than inferior (12.4 ± 3.9° vs. 5.0 ± 3.3°, N.S.). Transmurally, endocardial torsion was smaller than epicardial (7.5 ± 1.3° vs. 8.0 ± 1.5°, p < 0.001).

Conclusion

Variability in the position of the AoR causes a large variability in torsion in circumferential segments. This effect was negligible for global torsion, and torsion calculated in transmural layers. Results were documented for the healthy human heart and are in agreement with data from literature.     

Assessment of myocardial infarction in mice by Late Gadolinium Enhancement MR imaging using an inversion recovery pulse sequence at 9.4T

Purpose

To demonstrate the feasibility of using an inversion recovery pulse sequence and to define the optimal inversion time (TI) to assess myocardial infarction in mice by late gadolinium enhancement (LGE) MRI at 9.4T, and to obtain the maximal contrast between the infarcted and the viable myocardium.

Methods

MRI was performed at 9.4T in mice, two days after induction of myocardial infarction (n = 4). For cardiovascular MR imaging, a segmented magnetization-prepared fast low angle shot (MP-FLASH) sequence was used with varied TIs ranging from 40 to 420 ms following administration of gadolinium-DTPA at 0.6 mmol/kg. Contrast-to-noise (CNR) and signal-to-noise ratio (SNR) were measured and compared for each myocardial region of interest (ROI).

Results

The optimal TI, which corresponded to a minimum SNR in the normal myocardium, was 268 ms ± 27.3. The SNR in the viable myocardium was significantly different from that found in the infarcted myocardium (17.2 ± 2.4 vs 82.1 ± 10.8; p = 0.006) leading to a maximal relative SI (Signal Intensity) between those two areas (344.9 ± 60.4).

Conclusion

Despite the rapid heart rate in mice, our study demonstrates that LGE MRI can be performed at 9.4T using a protocol similar to the one used for clinical MR diagnosis of myocardial infarction.     

First-pass perfusion CMR two days after infarction predicts severity of functional impairment six weeks later in the rat heart

Background

In humans, dynamic contrast CMR of the first pass of a bolus infusion of Gadolinium-based contrast agent has become a standard technique to identify under-perfused regions of the heart and can accurately demonstrate the severity of myocardial infarction. Despite the clinical importance of this method, it has rarely been applied in small animal models of cardiac disease. In order to identify perfusion delays in the infarcted rat heart, here we present a method in which a T₁ weighted MR image has been acquired during each cardiac cycle.

Methods and results

In isolated perfused rat hearts, contrast agent infusion gave uniform signal enhancement throughout the myocardium. Occlusion of the left anterior descending coronary artery significantly reduced the rate of signal enhancement in anterior regions of the heart, demonstrating that the first-pass method was sensitive to perfusion deficits. In vivo measurements of myocardial morphology, function, perfusion and viability were made at 2 and 8 days after infarction. Morphology and function were further assessed using cine-MRI at 42 days. The perfusion delay was larger in rat hearts that went on to develop greater functional impairment, demonstrating that first-pass CMR can be used as an early indicator of infarct severity. First-pass CMR at 2 and 8 days following infarction better predicted outcome than cardiac ejection fraction, end diastolic volume or end systolic volume.

Conclusion

First-pass CMR provides a predictive measure of the severity of myocardial impairment caused by infarction in a rodent model of heart failure.     

To JUPITER and beyond: Statins,inflammation, and primary prevention

Citation

Ridker PM, Danielson E, Fonseca FAH, Genest J, Gotto AM, Kastelein JJP, Koenig W, Libby P, Lorenzatti AJ, MacFadyen JG, Nordestgaard BG, Shepherd J, Willerson JT, Glynn RJ: Rosuvastatin to Prevent Vascular Events in Men and Women with Elevated C-Reactive Protein. NEJM 2008, 359: 2195-2207 [1].

Background

Increased levels of the inflammatory biomarker high-sensitivity C-reactive protein predict cardiovascular events. Since statins lower levels of high-sensitivity C-reactive protein as well as cholesterol, we hypothesized that people with elevated high-sensitivity C-reactive protein levels but without hyperlipidemia might benefit from statin treatment.

Methods

Objective

To investigate whether treatment with rosuvastatin, 20 mg daily, as compared to placebo, would decrease the rate of first major cardiovascular events.

Design

Randomized, double-blind, placebo-controlled, multicenter trial.

Setting

1315 sites in 26 countries.

Subjects

17,802 apparently healthy men and women with low-density lipoprotein (LDL) cholesterol levels of less than 130 mg per deciliter (3.4 mmol per liter) and high-sensitivity C-reactive protein levels of 2.0 mg per liter or higher.

Intervention

Subjects were randomly assigned to rosuvastatin, 20 mg daily, or placebo.

Outcomes

The primary outcome was the occurrence of a first major cardiovascular event, defined as myocardial infarction, stroke, arterial revascularization, hospitalization for unstable angina, or death from cardiovascular causes. Secondary endpoints included the components of the primary end point considered individually as well as death from any cause.

Results

The trial was stopped after a median follow-up of 1.9 years (maximum, 5.0). Rosuvastatin reduced LDL cholesterol levels by 50% and high-sensitivity C-reactive protein levels by 37%. The rates of the primary end point were 0.77 and 1.36 per 100 person-years of follow-up in the rosuvastatin and placebo groups, respectively (hazard ratio for rosuvastatin, 0.56; 95% confidence interval [CI], 0.46 to 0.69; P < 0.00001), with corresponding rates of 0.17 and 0.37 for myocardial infarction (hazard ratio, 0.46; 95% CI, 0.30 to 0.70; P = 0.0002), 0.18 and 0.34 for stroke (hazard ratio, 0.52; 95% CI, 0.34 to 0.79; P = 0.002), 0.41 and 0.77 for revascularization or unstable angina (hazard ratio, 0.53; 95% CI, 0.40 to 0.70; P < 0.00001), 0.45 and 0.85 for the combined end point of myocardial infarction, stroke, or death from cardiovascular causes (hazard ratio, 0.53; 95% CI, 0.40 to 0.69; P < 0.00001), and 1.00 and 1.25 for death from any cause (hazard ratio, 0.80; 95% CI, 0.67 to 0.97; P = 0.02). Consistent effects were observed in all subgroups evaluated. The rosuvastatin group did not have a significant increase in myopathy or cancer but did have a higher incidence of physician-reported diabetes.

Conclusions

In this trial of apparently healthy persons without hyperlipidemia but with elevated high-sensitivity C-reactive protein levels, rosuvastatin significantly reduced the incidence of major cardiovascular events. (ClinicalTrials.gov number, {"type":"clinical-trial","attrs":{"text":"NCT00239681","term_id":"NCT00239681"}}NCT00239681.)     

Using simulation to estimate the cost effectiveness of improving ambulance and thrombolysis response times after myocardial infarction

Objectives

To quantify the health gains and costs associated with improving ambulance and thrombolysis response times for acute myocardial infarction.

Design

A computer simulation model.

Patients/setting

Patients experiencing acute myocardial infarction in England.

Interventions

Improving the ambulance response time to 75% of calls reached within 8 minutes and the hospital arrival to thrombolysis time interval (door‐to‐needle time) to 75% receiving it within 30 minutes and 20 minutes, compared to best estimates of response times in the mid‐1990s.

Main outcome measures

Deaths prevented, life years saved, and discounted cost per life year saved.

Results

Improving the ambulance response to 75% of calls within 8 minutes resulted in an estimate of 5 deaths prevented or 57 life years saved per million population per year, with a discounted incremental cost per life year saved of £8540 over 20 years. The corresponding benefit of improving the door‐to‐needle time to 75% of myocardial infarction patients within 30 minutes was an estimated 2 deaths prevented and 15 life years saved per million population per year, with a discounted incremental cost per life year saved of between £10 150 to £54 230 over 20 years. Little further gain was associated with reaching the 20 minute target. Combining ambulance and thrombolysis targets resulted in 70 life years saved per million population per year.

Conclusions

Improving ambulance response times appears to be cost effective. Reducing door‐to‐needle time will have a smaller effect at an uncertain cost. Further benefits may be gained from reducing the time from onset of symptoms to starting thrombolysis.