Time-efficient three-dimensional transmural scar assessment provides relevant substrate characterization for ventricular tachycardia features and long-term recurrences in ischemic cardiomyopathy.

Delayed gadolinium-enhanced cardiac magnetic resonance (LGE-CMR) imaging requires novel and time-efficient approaches to characterize the myocardial substrate associated with ventricular arrhythmia in patients with ischemic cardiomyopathy. Using a translational approach in pigs and patients with established myocardial infarction, we tested and validated a novel 3D methodology to assess ventricular scar using custom transmural criteria and a semiautomatic approach to obtain transmural scar maps in ventricular models reconstructed from both 3D-acquired and 3D-upsampled-2D-acquired LGE-CMR images. The results showed that 3D-upsampled models from 2D LGE-CMR images provided a time-efficient alternative to 3D-acquired sequences to assess the myocardial substrate associated with ischemic cardiomyopathy. Scar assessment from 2D-LGE-CMR sequences using 3D-upsampled models was superior to conventional 2D assessment to identify scar sizes associated with the cycle length of spontaneous ventricular tachycardia episodes and long-term ventricular tachycardia recurrences after catheter ablation. This novel methodology may represent an efficient approach in clinical practice after manual or automatic segmentation of myocardial borders in a small number of conventional 2D LGE-CMR slices and automatic scar detection.

Comprehensive assessment of myocardial remodeling in ischemic heart disease by synchrotron propagation based X-ray phase contrast imaging.

Cardiovascular research is in an ongoing quest for a superior imaging method to integrate gross-anatomical information with microanatomy, combined with quantifiable parameters of cardiac structure. In recent years, synchrotron radiation-based X-ray Phase Contrast Imaging (X-PCI) has been extensively used to characterize soft tissue in detail. The objective was to use X-PCI to comprehensively quantify ischemic remodeling of different myocardial structures, from cell to organ level, in a rat model of myocardial infarction. Myocardial infarction-induced remodeling was recreated in a well-established rodent model. Ex vivo rodent hearts were imaged by propagation based X-PCI using two configurations resulting in 5.8 µm and 0.65 µm effective pixel size images. The acquired datasets were used for a comprehensive assessment of macrostructural changes including the whole heart and vascular tree morphology, and quantification of left ventricular myocardial thickness, mass, volume, and organization. On the meso-scale, tissue characteristics were explored and compared with histopathological methods, while microstructural changes were quantified by segmentation of cardiomyocytes and calculation of cross-sectional areas. Propagation based X-PCI provides detailed visualization and quantification of morphological changes on whole organ, tissue, vascular as well as individual cellular level of the ex vivo heart, with a single, non-destructive 3D imaging modality.

Clinical characteristics and outcomes of patients with severe left ventricular dysfunction undergoing cardiac MRI viability assessment prior to revascularization.

Coronary artery bypass grafting improves survival in patients with ischemic cardiomyopathy, however, these patients are at high risk for morbidity and mortality. The role of viability testing to guide revascularization in these patients is unclear. Cardiac magnetic resonance imaging (CMR) has not been studied adequately in this population despite being considered a reference standard for infarct imaging. We performed a multicenter retrospective analysis of patients (n = 154) with severe left ventricular systolic dysfunction [ejection fraction (EF) < 35%] on CMR who underwent CMR viability assessment prior to consideration for revascularization. Using the AHA16-segment model, percent total myocardial viability was determined depending on the degree of transmural scar thickness. Patients with or without revascularization had similar clinical characteristics and were prescribed similar medical therapy. Overall, 43% of patients (n = 66) experienced an adverse event during the median 3 years follow up. For the composite outcome (death, myocardial infarction, heart failure hospitalization, stroke, ventricular tachycardia) patients receiving revascularization were less likely to experience an adverse event compared to those without revascularization (HR 0.53, 95% CI 0.33-0.86, p = 0.01). Patients with > 50% viability on CMR had a 47% reduction in composite events when undergoing revascularization opposed to medical therapy alone (HR 0.53, p = 0.02) whereas patients with a viability < 50% were 2.7 times more likely to experience an adverse event (p = 0.01). CMR viability assessment may be an important tool in the shared decision-making process when considering revascularization options in patients with severe ischemic cardiomyopathy.

Strain analysis using feature tracking cardiac magnetic resonance (FT-CMR) in the assessment of myocardial viability in chronic ischemic patients.

The purpose of this study is to test the capability of a commercially available feature tracking-cardiac magnetic resonance (FT-CMR) strain analysis software module in differentiating between viable and non-viable myocardium in chronic ischemic patients. Thirty chronic ischemic patients and 10 healthy volunteers were enrolled. Cine images were used for peak circumferential and radial strains quantification using dedicated FT-CMR software. Global strain was compared between patients and controls. In patients, segmental strain was compared in viable and non-viable myocardium determined by late gadolinium enhancement (LGE); and in segments with wall abnormalities. Among 480 myocardial segments analyzed in patients, 76 segments were non-viable on LGE. The mean left ventricular ejection fraction (LVEF) of the patients (87% males, mean age 55 ± 12 years) was 40 ± 12% vs. 61 ± 5% for the controls (80% males, mean age 39 ± 11 years). Peak global circumferential strain (GCS) and global radial strain (GRS) were significantly impaired in patients compared to controls (-13.89 ± 4.12% vs. -19.84 ± 1.47%), p < 0.001 and (23.11 ± 6.59% vs. 31.72 ± 5.52%), p = 0.001. Segmental circumferential strain (SCS) and segmental radial strain (SRS) were significantly impaired in non-viable compared to viable segments (-9.47 ± 7.26% vs. -14.72 ± 7.5%), p < 0.001 and (15.67 ± 12.11% vs. 24.51 ± 16.22%), p < 0.001. Cut-off points of -9.36% for the SCS (AUC = 0.7, 95% CI = 0.63-0.77) and 19.5% for the SRS (AUC = 0.67, 95%CI = 0.61-0.73) were attained above which the segment is considered viable.SCS was able to discriminate between normokinetic, hypokinetic and akinetic segments (mean = 27.6 ± 17.13%, 18.66 ± 12.88% and 15.24 ± 10.70% respectively, p < 0.001). Circumferential and radial segmental strain analysis by FT-CMR was able to discriminate between viable and non-viable segments of the myocardium defined by LGE and between normokinetic, hypokinetic and akinetic segments, using routinely acquired cine images, and thus can provide a more objective metric for risk stratification in chronic ischemic patients.

Quantification of extracellular volume fraction by cardiac computed tomography for noninvasive assessment of myocardial fibrosis in hemodialysis patients.

Extent of myocardial fibrosis in hemodialysis patients has been associated with poor prognosis. Myocardial extracellular volume (ECV) quantification using contrast enhanced cardiac computed tomography (CT) is a novel method to determine extent of myocardial fibrosis. Cardiac CT-based myocardial ECV in hemodialysis patients with those of propensity-matched non-hemodialysis control subjects were compared. Twenty hemodialysis patients (mean age, 67.4 ± 9.6 years; 80% male) and 20 propensity-matched non-hemodialysis controls (mean age, 66.3 ± 9.1 years; 85% male) who underwent comprehensive cardiac CT consisted of calcium scoring, coronary CT angiography, stress perfusion CT and delayed enhancement CT were evaluated. Myocardial ECV was significantly greater in the hemodialysis group than in the control group (33.8 ± 4.7% versus 26.6 ± 2.9%; P < 0.0001). In the hemodialysis group, modest correlation was evident between myocardial ECV and left atrial volume index (r = 0.54; P = 0.01), while there was no correlation between myocardial ECV and other cardiac parameters including left ventricular mass index and severity of myocardial ischemia. Cardiac CT-based myocardial ECV may offer a potential imaging biomarker for myocardial fibrosis in HD patients.

Clinical assessment of adenosine stress and rest cardiac magnetic resonance T1 mapping for detecting ischemic and infarcted myocardium.

Cardiac magnetic resonance (CMR) spin-lattice relaxation time (T1) may be influenced by pathologic conditions due to changes in myocardial water content. We aimed to validate the principle and investigate T1 mapping at rest and adenosine stress to differentiate ischemic and infarcted myocardium from controls. Patients with suspected coronary artery disease who underwent CMR were prospectively recruited. Native rest and adenosine stress T1 maps were obtained using standard modified Look-Locker Inversion-Recovery technique. Among 181 patients included, T1 values were measured from three groups. In the control group, 72 patients showed myocardium with a T1 profile of 1,039 ± 75 ms at rest and a significant increase during stress (4.79 ± 3.14%, p < 0.001). While the ischemic (51 patients) and infarcted (58 patients) groups showed elevated resting T1 compared to controls (1,040 ± 90 ms for ischemic; 1,239 ± 121 ms for infarcted, p < 0.001), neither of which presented significant T1 reactivity (1.38 ± 3.02% for ischemic; 1.55 ± 5.25% for infarcted). We concluded that adenosine stress and rest T1 mapping may be useful to differentiate normal, ischemic and infarcted myocardium.

CRAX: A simple cardiovascular risk assessment tool to predict risk of acute myocardial infarction or death.

BACKGROUND: Determining the risk of cardiovascular events is essential to optimize patient management. METHODS AND RESULTS: 5842 individuals underwent SPECT myocardial perfusion imaging (MPI) with 4.4 ± 1.2 years of follow-up. Models (the CRAX tool) were derived to predict the cumulative risk of death and acute myocardial infarction (AMI) at 1, 3, and 5 years using clinical and MPI variables. Predictors of AMI and death included age, number of hospitalizations in the 3 years preceding MPI, and left ventricular ejection fraction (LVEF). Additional predictors of death were the use of pharmacological stress, and global stress total perfusion deficit (sTPD), while transient ischemic dilation (TID), and ischemic total perfusion deficit (iTPD) change were predictive of AMI. CRAX predictions were significantly (P < .001) more accurate than clinical variables or MPI results alone, resulting in a significant net reclassification improvement (NRI, 7.5% for AMI, 14.5% death) compared to clinical variables alone. Accuracy for predicting major adverse cardiac events (MACE, comprising all-cause death, AMI, unstable angina, late revascularization) was comparable to that of AMI or death. CONCLUSIONS: CRAX is a risk assessment tool that predicts the risk of AMI, death, or MACE, and improves prediction compared to clinical variables or MPI results alone.

Comparison of CZT SPECT and conventional SPECT for assessment of contractile function, mechanical synchrony and myocardial scar in patients with heart failure.

AIM: The aim of this study was to compare CZT-SPECT (CZT SPECT) to conventional SPECT (C-SPECT) in the assessment of left ventricular myocardial scar, contractile function, and mechanical synchrony in patients with heart failure (HF). METHODS: Fifty-nine patients with HF who were referred for myocardial perfusion/metabolism imaging were enrolled. All patients underwent resting 99mTc-MIBI gated myocardial perfusion imaging using a CZT SPECT camera and a C-SPECT camera, respectively, and 18F-FDG PET myocardial metabolism imaging within three days. Summed rest score (SRS) and total perfusion defect (TPD) (as indices of perfusion abnormality), left ventricular (LV), end diastolic volume (EDV), end systolic volume (ESV), and ejection fraction (EF) (as indices of LV systolic function), and histogram band width (BW) and standard deviation (SD) (as indices of mechanical synchrony) were analyzed by automated software while the perfusion/metabolism patterns were analyzed visually. RESULTS: There was a good correlation between CZT SPECT and C-SPECT for SRS and TPD. CZT SPECT tended to underestimate SRS and TPD compared to C-SPECT. CZT-SPECT and C-SPECT showed excellent agreement in assessing the perfusion/metabolism pattern though a small proportion of normal segments (6.6%) identified by CZT/PET exhibited mismatch pattern on C-SPECT/PET. CZT SPECT also showed excellent correlation with C-SPECT in measuring EDV, ESV, and EF. Finally, BW and SD measured by CZT SPECT correlated well with C-SPECT but CZT SPECT tended to overestimate BW and SD compared to C-SPECT. CONCLUSION: CZT SPECT provided comparable data to C-SPECT for measuring LV scar, function and synchrony at a considerable reduction in imaging time. CZT SPECT holds a promise for comprehensive evaluation of myocardial performance in patients with HF.

High spatial resolution free-breathing 3D late gadolinium enhancement cardiac magnetic resonance imaging in ischaemic and non-ischaemic cardiomyopathy: quantitative assessment of scar mass and image quality.

PURPOSE: To compare breath-hold (BH) with navigated free-breathing (FB) 3D late gadolinium enhancement cardiac MRI (LGE-CMR) MATERIALS AND METHODS: Fifty-one patients were retrospectively included (34 ischaemic cardiomyopathy, 14 non-ischaemic cardiomyopathy, three discarded). BH and FB 3D phase sensitive inversion recovery sequences were performed at 3T. FB datasets were reformatted into normal resolution (FB-NR, 1.46x1.46x10mm) and high resolution (FB-HR, isotropic 0.91-mm voxels). Scar mass, scar edge sharpness (SES), SNR and CNR were compared using paired-samples t-test, Pearson correlation and Bland-Altman analysis. RESULTS: Scar mass was similar in BH and FB-NR (mean ± SD: 15.5±18.0 g vs. 15.5±16.9 g, p=0.997), with good correlation (r=0.953), and no bias (mean difference ± SD: 0.00±5.47 g). FB-NR significantly overestimated scar mass compared with FB-HR (15.5±16.9 g vs 14.4±15.6 g; p=0.007). FB-NR and FB-HR correlated well (r=0.988), but Bland-Altman demonstrated systematic bias (1.15±2.84 g). SES was similar in BH and FB-NR (p=0.947), but significantly higher in FB-HR than FB-NR (p<0.01). SNR and CNR were lower in BH than FB-NR (p<0.01), and lower in FB-HR than FB-NR (p<0.01). CONCLUSION: Navigated free-breathing 3D LGE-CMR allows reliable scar mass quantification comparable to breath-hold. During free-breathing, spatial resolution can be increased resulting in improved sharpness and reduced scar mass. KEY POINTS: • Navigated free-breathing 3D late gadolinium enhancement is reliable for myocardial scar quantification. • High-resolution 3D late gadolinium enhancement increases scar sharpness • Ischaemic and non-ischaemic cardiomyopathy patients can be imaged using free-breathing LGE CMR.

Intravascular Ultrasound-Derived Virtual Fractional Flow Reserve for the Assessment of Myocardial Ischemia.

BACKGROUND: Fractional flow reserve (FFR) is widely used for the assessment of myocardial ischemia. Intravascular ultrasound (IVUS) is an intracoronary imaging method that provides information about lumen and vessel morphology. Previous studies on the expanded use of IVUS to identify functional ischemia have noted an association between anatomy and physiology, but IVUS-derived minimum lumen area (MLA) has a weak-moderate correlation with myocardial ischemia compared with FFR. We developed a method to calculate FFR using IVUS-derived anatomical information for the assessment of myocardial ischemia. The aims of this study were to investigate the relationship between wire-based FFR and IVUS-derived FFR (IVUS-FFR) and to compare the usefulness of IVUS-FFR and IVUS-derived MLA for functional assessment.Methods and Results:We retrospectively analyzed 50 lesions in 48 patients with coronary stenosis who underwent IVUS and FFR simultaneously. IVUS-FFR was calculated using our original algorithm and fluid dynamics. Mean percent diameter stenosis determined on quantitative coronary angiography and on FFR was 56.4±10.7 and 0.69±0.08, respectively. IVUS-FFR had a stronger linear correlation with FFR (R=0.78, P<0.001; root mean square error, 0.057 FFR units) than with IVUS-derived MLA (R=0.43, P=0.002). CONCLUSIONS: IVUS-FFR may be a more valuable method to identify myocardial ischemia, compared with IVUS-derived MLA.

Epidemiology of ischemic heart disease in HIV.

PURPOSE OF REVIEW: The purpose of this review is to summarize and synthesize recent data on the risk of ischemic heart disease (IHD) in HIV-infected individuals. RECENT FINDINGS: Recent studies in the field demonstrate an increasing impact of cardiovascular disease (CVD) on morbidity and mortality in HIV relative to AIDS-related diagnoses. Studies continue to support an approximately 1.5 to two-fold increased risk of IHD conferred by HIV, with specific risk varying by sex and virologic/immunologic status. Risk factors include both traditional CVD risk factors and novel, HIV-specific factors including inflammation and immune activation. Specific antiretroviral therapy (ART) drugs may increase CVD risk, yet the net effect of ART with viral suppression is beneficial with regard to CVD risk. Management of cardiovascular risk and prevention of CVD is complex, because current general population strategies target traditional CVD risk factors only. Extensive investigation is being directed at developing tailored CVD risk prediction algorithms and interventions to reduce CVD risk in HIV. SUMMARY: Increased IHD risk is a significant clinical and public health challenge in HIV. The development and application of HIV-specific interventions to manage CVD risk factors and reduce CVD risk will improve the long-term health of this ageing population.

Mesenchymal Stem Cells Combined with Hepatocyte Growth Factor Therapy for Attenuating Ischaemic Myocardial Fibrosis: Assessment using Multimodal Molecular Imaging.

Clinically, myocardial fibrosis is increasingly being recognized as a new therapeutic target for ischaemic heart diseases. The aim of this study was to investigate whether noninvasive multimodal molecular imaging could be used to dynamically assess whether the combination of bone marrow mesenchymal stem cells (BMSCs) and hepatocyte growth factor (HGF) therapy can synergistically attenuate myocardial fibrosis after myocardial infarction (MI). MI was induced in 28 rats by coronary ligation with subsequent injection of BMSCs/HGF, BMSCs, HGF, or saline into the border zone under echocardiography guidance. The therapeutic procedure and treatment effects were tracked and assessed using bioluminescence imaging (BLI) and cardiac magnetic resonance (MR) imaging. Four weeks after transplantation therapy, cardiac MR imaging demonstrated that BMSC/HGF-treated animals showed better ejection fractions (p < 0.001) and smaller scar sizes (p < 0.001) than those treated with BMSCs or HGF alone. Histopathological and immunohistochemical results showed less collagen deposition, increased microvessel densities and more regenerative cardiomyocytes in the BMSC/HGF-treated animals than in those receiving HGF or BMSCs alone (all p < 0.05). Multimodal molecular imaging allows a specific and timely strategy to be established for dynamically tracking treatment and noninvasively assessing the therapeutic effects. Under echocardiography guidance, intramyocardial injection of transfected HGF with BMSCs can enhance cell survival, improve cardiac function, stimulate angiogenesis, and reduce myocardial fibrosis in a post-MI rat model.

Myocardial Fibrosis Assessment by LGE Is a Powerful Predictor of Ventricular Tachyarrhythmias in Ischemic and Nonischemic LV Dysfunction: A Meta-Analysis.

OBJECTIVES: The authors performed a meta-analysis to evaluate the predictive value of late gadolinium enhancement (LGE) cardiac magnetic resonance for ventricular tachyarrhythmia in ischemic cardiomyopathy (ICM) and nonischemic cardiomyopathy (NICM) patients with ventricular dysfunction. BACKGROUND: The use of LGE to detect myocardial fibrosis and its related arrhythmic substrate is well established. Several recent studies have described the predictive value of LGE for ventricular tachyarrhythmias; however, their validity is limited by small sample size and low number of events. METHODS: MEDLINE and the Cochrane Library electronic databases were systematically searched to identify studies that applied LGE in ICM and NICM patients with ventricular dysfunction and reported arrhythmic clinical outcomes (sudden death, aborted sudden death, ventricular tachycardia, ventricular fibrillation, and appropriate implantable cardioverter-defibrillator [ICD] therapy, including antitachycardia pacing). A meta-analysis was performed to determine pooled odds ratios (ORs) for these arrhythmic events. RESULTS: Nineteen studies that evaluated 2,850 patients with 423 arrhythmic events over a mean/median follow-up of 2.8 years were identified. The composite arrhythmic endpoint was reached in 23.9% of patients with a positive LGE test (annualized event rate of 8.6%) versus 4.9% of patients with a negative LGE test (annualized event rate of 1.7%; p < 0.0001). LGE correlated with arrhythmic events in the different patient groups. In the overall population, the pooled OR was 5.62 (95% confidence interval [CI]: 4.20 to 7.51), with no significant differences between ICM and NICM patients. In a subgroup of 11 studies (1,178 patients) with mean ejection fraction (EF) ≤30%, the pooled OR for the arrhythmic events increased to 9.56 (95% CI: 5.63 to 16.23), with a negative likelihood ratio of 0.13 (95% CI: 0.06 to 0.30). CONCLUSIONS: LGE is a powerful predictor of ventricular arrhythmic risk in patients with ventricular dysfunction, irrespective of ICM and NICM etiology. The prognostic power of LGE is particularly strong in patients with severely depressed EF, which suggests its potential to improve patient selection for ICD implantation.

In Vivo Quantitative Assessment of Myocardial Structure, Function, Perfusion and Viability Using Cardiac Micro-computed Tomography.

The use of Micro-Computed Tomography (MicroCT) for in vivo studies of small animals as models of human disease has risen tremendously due to the fact that MicroCT provides quantitative high-resolution three-dimensional (3D) anatomical data non-destructively and longitudinally. Most importantly, with the development of a novel preclinical iodinated contrast agent called eXIA160, functional and metabolic assessment of the heart became possible. However, prior to the advent of commercial MicroCT scanners equipped with X-ray flat-panel detector technology and easy-to-use cardio-respiratory gating, preclinical studies of cardiovascular disease (CVD) in small animals required a MicroCT technologist with advanced skills, and thus were impractical for widespread implementation. The goal of this work is to provide a practical guide to the use of the high-speed Quantum FX MicroCT system for comprehensive determination of myocardial global and regional function along with assessment of myocardial perfusion, metabolism and viability in healthy mice and in a cardiac ischemia mouse model induced by permanent occlusion of the left anterior descending coronary artery (LAD).

Contractile function assessment by intraventricular balloon alters the ability of regional ischaemia to evoke ventricular fibrillation.

BACKGROUND AND PURPOSE: In drug research using the rat Langendorff heart preparation, it is possible to study left ventricular (LV) contractility using an intraventricular balloon (IVB), and arrhythmogenesis during coronary ligation-induced regional ischaemia. Assessing both concurrently would halve animal requirements. We aimed to test the validity of this approach. EXPERIMENTAL APPROACH: The electrocardiogram (ECG) and LV function (IVB) were recorded during regional ischaemia of different extents in a randomized and blinded study. KEY RESULTS: IVB-induced proarrhythmia was anticipated, but in hearts with an ischaemic zone (IZ) made deliberately small, an inflated IVB reduced ischaemia-induced ventricular fibrillation (VF) incidence as a trend. Repeating studies in hearts with large IZs revealed the effect to be significant. There were no changes in QT interval or other variables that might explain the effect. Insertion of an IVB that was minimally inflated had no effect on any variable compared with 'no IVB' controls. The antiarrhythmic effect of verapamil (a positive control drug) was unaffected by IVB inflation. Removal of an inflated (but not a non-inflated) IVB caused a release of lactate commensurate with reperfusion of an endocardial/subendocardial layer of IVB-induced ischaemia. This was confirmed by intracellular (31) phosphorus ((31) P) nuclear magnetic resonance (NMR) spectroscopy. CONCLUSIONS AND IMPLICATIONS: IVB inflation does not inhibit VF suppression by a standard drug, but it has profound antiarrhythmic effects of its own, likely to be due to inflation-induced localized ischaemia. This means rhythm and contractility cannot be assessed concurrently by this approach, with implications for drug discovery and safety assessment.

Therapeutic Transdifferentiation: A Novel Approach for Ischemic Syndromes.

The technological development of induced pluripotent stem cells (iPSCs) has overcome many of the limitations of adult and embryonic stem cells. We have found that activation of innate immunity signaling is necessary for this process, as it facilitates epigenetic plasticity in cells by a process called transflammation. More recently, we have discovered that transflammation also facilitates the transdifferentiation of cells directly from one somatic cell type to another. This insight may lead to a promising therapeutic pathway that avoids reverting cells all the way back to pluripotency before achieving a cell type of interest. While there is much therapeutic promise to transflammation and transdifferentiation, there is also evidence that transdifferentiation plays a role in some pathological conditions, including atherosclerosis. Ultimately, better understanding of transflammation will facilitate the development of regenerative therapies.

Characterization of an anesthetized dog model of transient cardiac ischemia and rapid pacing: a pilot study for preclinical assessment of the potential for proarrhythmic risk of novel drug candidates.

INTRODUCTION: Preclinical proarrhythmic risk assessment of drug candidates is focused predominantly on arrhythmias arising from repolarization abnormalities. However, drug-induced cardiac conduction slowing is associated with significant risk of life-threatening ventricular arrhythmias, particularly in a setting of cardiac ischemia. Therefore, we optimized and characterized an anesthetized dog model to evaluate the potential proarrhythmic risk of drug candidates in ischemic heart disease patients. METHODS: Anesthetized dogs were instrumented with atrial and ventricular epicardial electrodes for pacing and measurement of conduction times, and a balloon occluder and flow probe placed around the left anterior descending coronary artery (LAD) distal to the first branch. Conduction times, ECG intervals and incidence of arrhythmias were assessed serially at the end of each dose infusion (flecainide: 0.32, 0.63, 1.25, 2.5 and 5mg/kg, i.v.; dofetilide:1.25, 2.5, 5, 10 and 20 µg/kg, i.v.; or vehicle; n=6/group) both during normal flow (with and without rapid pacing) and during 5-min LAD occlusion (with and without rapid pacing). Compound X, a development candidate with mild conduction slowing activity, was also evaluated. RESULTS: Flecainide produced pronounced, dose-dependent slowing of conduction that was exacerbated during ischemia and rapid pacing. In addition, ventricular tachycardia (VT) and fibrillation (VF) occurred in 4 of 6 dogs (3 VF @ 0.63 mg/kg; 1VT @ 2.5mg/kg). In contrast, no animals in the vehicle group developed arrhythmias. Dofetilide, a potent IKr blocker that does not slow conduction, prolonged QT interval but did not cause further conduction slowing during ischemia with or without pacing and there were no arrhythmias. Compound X, like flecainide, produced marked conduction slowing and arrhythmias (VT, VF) during ischemia and pacing. DISCUSSION: This model may be useful to more accurately define shifts in safety margins in a setting of ischemia and increased cardiac demand for drugs that slow conduction.

Automated left ventricle segmentation in late gadolinium-enhanced MRI for objective myocardial scar assessment.

PURPOSE: To develop and validate an objective and reproducible left ventricle (LV) segmentation method for late gadolinium enhanced (LGE) magnetic resonance imaging (MRI), which can facilitate accurate myocardial scar assessment. MATERIALS AND METHODS: A cohort of 25 ischemic patients and 25 nonischemic patients were included. A four-step algorithm was proposed: first, the Cine-MRI and LGE-MRI volume were globally registered; second, the registered Cine-MRI contours were fitted to each LGE-MRI slice via the constructed contour image; third, the fitting was optimized in full LGE-MRI stack; finally, the contours were refined by taking into account patient-specific scar patterns. The automated LV segmentation results were compared with that of manual segmentation from two experienced observers. RESULTS: The accuracy of automated segmentation, expressed as the average contour distances to manual segmentation, was 0.82 ± 0.19 pixels, in the same order as interobserver difference between manual results (0.90 ± 0.26 pixels), but with lower variability (0.60 ± 0.37 pixels, P < 0.05). The myocardial scar identification based on automated LV segmentation further demonstrated higher consistency than that of manual segmentation (Pearson correlation 0.97 vs. 0.84). CONCLUSION: An automated LV segmentation method for LGE-MRI was developed, providing high segmentation accuracy and lower interobserver variability compared to fully manual image analysis. The method facilitates objective assessment of myocardial scar.

Prevalence of ischemic heart disease and management of coronary risk in daily clinical practice: results from a Mediterranean cohort of HIV-infected patients.

BACKGROUND: There are conflicting data on the prevalence of coronary events and the quality of the management of modifiable cardiovascular risk factors (CVRF) in HIV-infected patients. METHODS: We performed a retrospective descriptive study to determine the prevalence of coronary events and to evaluate the management of CVRF in a Mediterranean cohort of 3760 HIV-1-infected patients from April 1983 through June 2011. RESULTS: We identified 81 patients with a history of a coronary event (prevalence 2.15%); 83% of them suffered an acute myocardial infarction. At the time of the coronary event, CVRF were highly prevalent (60.5% hypertension, 48% dyslipidemia, and 16% diabetes mellitus). Other CVRF, such as smoking, hypertension, lack of exercise, and body mass index, were not routinely assessed. After the coronary event, a significant decrease in total cholesterol (P = 0.025) and LDL-cholesterol (P = 0.004) was observed. However, the percentage of patients who maintained LDL-cholesterol > 100 mg/dL remained stable (from 46% to 41%, P = 0.103). Patients using protease inhibitors associated with a favorable lipid profile increased over time (P = 0.028). CONCLUSIONS: The prevalence of coronary events in our cohort is low. CVRF prevalence is high and their management is far from optimal. More aggressive interventions should be implemented to diminish cardiovascular risk in HIV-infected patients.