Isolated noncompaction of the left ventricle (LV) is a rare disorder, classified as a primary genetic cardiomyopathy by the American Heart Association. The European Society of Cardiology Working Group on Myocardial and Pericardial Diseases classified LV noncompaction as an unclassified cardiomyopathy. LV noncompaction cardiomyopathy characterized by the following features: 1) an altered myocardial wall with prominent trabeculae and deep intertrabecular recesses resulting in thickened myocardium with two layers, consisting of compacted and noncompacted myocardium and 2) continuity between the left ventricular cavity and the deep intertrabecular recesses, which are filled with blood from the ventricular cavity, without evidence of communication with the epicardial coronary artery system. Features of LV noncompaction can overlap with dilated cardiomyopathy, hypertrophic cardiomyopathy , and restrictive cardiomyopathy. The phenotypic expression can vary considerably within the same family. The LV noncompaction can rarely occur as a transient phenomenon during myocarditis.We present the case of a 23-year-old patient, admitted to our Department for cardiac evaluation because of ECG changes and cardiac enlargement revealed at thoracic radiography. She had a history of chronic toxoplasmosis. An echocardiography was performed revealing left ventricular enlargement with severe systolic and diastolic dysfunction, diffuse hypokinesia and signs of isolated left ventricular non-compaction. Under these circumstances, we have considered the presence of isolated left ventricular non-compaction. A cardiac Magnetic Resonance Imaging was performed and it sustained the diagnosis. The alternative cause of isolated left ventricular noncompaction  was considered improbable. The left ventricular (LV) isolated non-compaction is characterized by embryonic myocardium morphology due to an arrest in the compaction process during the first trimester, and it is a very rare cardiomyopathy. Clinical manifestations are non-specific, ranging from asymptomatic patients to acute congestive heart failure. The diagnosis is based on cardiac imaging using echocardiography and magnetic resonance imaging.A healthy 23-year-old woman presented to hospital for cardiac workup after she had been referred to a cardiologist by a general practitioner, after detecting changes on electrocardiogram (ECG), consisting of negative T waves and cardiac enlargement on thoracic radiography. She was asymptomatic at presentation and without any familial cardiac history. She had a history of chronic toxoplasmosis  for which she was taking antibiotic treatment. The clinical examination showed pallor of skin and mucous membrane, maculo-papular non-itching rash on the forearms and thighs. There were also mobile axillary enlarged (2 cm) lymph nodes not tender or painful with moderate hard consistency, hepatosplenomegaly, blood pressure (BP) of 110/60 mmHg, heart rate (HR) of 70 b/min, regularly and apexian systolic murmur grade III/VI radiating to the axilla. Laboratory tests showed a discrete inflammatory syndrome (elevated erythrocyte sedimentation rate and C-reactive protein level), IgG antibodies to Toxoplasma in serum . Figure 1) showed poor r wave progression in V1-V3 leads and negative T waves in DI, DII, aVF, and V4-V6 leads and thoracic radiography  showed an increased cardio-thoracic index.Initial ECG  was performed revealing left ventricular enlargement with severe systolic and diastolic dysfunction , diffuse hypokinesia and trabeculation suggesting isolated left ventricular non-compaction.An echocardiogram  was performed and it confirmed dilated cardiomyopathy with excessively prominent trabeculations in left lateral wall and ventricular apex, severe alteration of left ventricular function with diffuse hypokinesia.A cardiac Magnetic Resonance Imaging (MRI)  presence of multiple trabeculae – especially in the apex and the left ventricular free wall; b) multiple deep recesses, between trabeculae, communicating with ventricular cavity (demonstrated by color Doppler imaging); c) a two-layer structure of the myocardium with non-compact increased layer (ratio between non-compact and compact layer suggested as >2.0) [3]. A cause for dilated cardiomyopathy is known to be infectious myocarditis. The toxoplasma infection has a worldwide distribution and the primary infection is, in most cases, asymptomatic. The involvement of the myocardium is rare in immune-competent hosts and a development of secondary dilated cardiomyopathy has not yet been described. Several cases of toxoplasma myocarditis were published in the past. In 1954, Paulley et al [7], concluded that myocardial toxoplasmosis should be considered in all obscure cases of myocarditis and unexplained cardiac hypertrophy. In 1967, Arturo Arribada and Edgardo Escobar [8] concluded in a small study that cardiac failure might be due to a late complication of the toxoplasmic infection of heart and it is important that the proper diagnosis is made as early as possible. Despite these early reports we have not found any recent published cases of toxoplasma myocarditis in immune-competent host.It is also known that left ventricular dilation, hypertrophy and systolic left ventricular dysfunction can present trabeculae and increased left ventricular bands. This is an apparent non-compaction and it can be difficult to differentiate by imagistic examination, even by using the proposed criteria , there is no specific treatment in noncompaction cardiomyopathy. We have been closely monitoring her condition with clinical examination, ECG and echocardiography and, so far, there have been no changes; currently she remains asymptomatic and she is treated with a beta blocker, an angiotensin-converting enzyme inhibitor, an oral anticoagulant and an implantable cardioverter-defibrillator were proposed for primary prevention of sudden cardiac death.As in previous reported cases [


In the present article, the Authors spread their clinical understanding of genetics and biology of heart failure directly from the bedside investigation of biological systems dynamics through an original diagnostic method with the simple use of the stethoscope, i.e., assessing the splenic arrhythmia , today's growing epidemic, is the first cause of death in world-wide. Despite all the current researches, there are still many open questions, such as the well-localized origin of initial endothelial dysfunction and the relationship between genetic causes and environmental risk factors (about 300!) in atherogenesis. For example, not all patients with intense hyper-dyslipidemia are atherosclerotic, and there are individuals suffering of acute myocardial infarction (AMI), in spite of absent dyslipidemia and type 2 DM.On the other hand, one wonders why a large number of patients with hyperinsulinemia-insulin-resistance, hypertension, hyper dyslipidemia live to old age without getting CVD. On the contrary, even without environmental risk factors for atherosclerosis (ATS), in several patients we can see the onset of AMI and stroke. Notoriously, CVD occurs even in individuals without common risk factors, while the CVD may be absent in smoking subjects with impaired blood counts and hypertension.The pathogenesis of ATS in the first decade of life and the reasons why the ATS arises in well-localized area and evolves differently, both in the single patient, from artery to artery and from patient to patient, are till now unknown and not yet clinically explored.We propose that a subject clinically health could be at inherited real risk (IRR) of ATS  aspecific, new-born pathological endoarteriolar blocking devices (EBDs)   through the “Auscultatory Percussion of the Stomach” . Interestingly, such a reflex is smaller, less than 1 cm, if there is IRR of disease (Stagnaro and Caramel, QBS tools are not only useful for diagnostic purposes, but also for therapeutic advices, because they are able to measure the microcirculatory activity before and after each preventive therapy's treatment, in order to understand the effectiveness of remedies.One of the authors has recently discover a new class of treatments for preventive purposes termed “type B” or “blue” therapy (Stagnaro and Caramel,


Cardiovascular magnetic resonance (CMR) studies in patients with pacemakers or implantable cardioverter/defibrillators (ICD) are increasingly required in daily clinical practice. Therefore, in the last years the manufacturers developed not only MR-conditional pacemakers, but also MR-conditional ICDs. However, the clinical experience regarding the feasibility and limitations of MR studies of the heart in patients with ICDs is still limited. In particular, there are hardly any CMR studies in the same patients performed prior to and post ICD implantation allowing a one-to-one comparison of the obtained CMR images. This is the first presentation of a CMR study in a patient with the world’s first and so far only MR-conditional ICD. In our case, a major problem related to the presence of the MR conditional ICD was an image artifact caused by the device’s generator which hampered the visualization of the midventricular and apical anterior and antero-lateral segments in all sequences performed. Considering previous studies, right chest implantation of the ICD could probably have helped in this setting and may be preferred in future ICD implantations. Our case report nicely illustrates the real clinical need for specially designed implantable devices that ensure safe and high-quality imaging in patients in whom serial CMR is required. Becker muscular dystrophy is an inherited, recessive, X-linked dystrophin deficiency disease with similar, but more benign clinical picture compared to Duchenne muscular dystrophy. Cardiac involvement with dilated cardiomyopathy and ventricular arrhythmias are frequent findings. In muscular dystrophy patients with cardiac involvement, imaging by cardiovascular magnetic resonance (CMR) - in addition to current standard of care (monitoring by ECG and echocardiography) - brings several advantages: By providing accurate and reproducible measurements for left ventricular (LV) volumes and function as well as by visualizing the characteristic non-ischemic pattern of late gadolinium enhancement (LGE) in the infero-lateral wall, CMR represents a sensitive tool for early diagnosis, monitoring of disease progression and response to treatment . ConventA 26-year-old male patient with Becker muscular dystrophy and secondary dilated cardiomyopathy received an MR-conditional ICD  for primary prevention of sudden cardiac death. Screening by echocardiography and CMR had revealed cardiac involvement already three years ago and etiology was confirmed by endomyocardial biopsy with immunohistochemical proof of myocardial dystrophin deficiency at that time. The patient was still ambulatory, presenting moderate muscle weakness with difficulties in climbing stairs and mild to moderate exertional dyspnea. Before ICD implantation, he underwent regular follow-up echocardiography and CMR studies (every year) as a participant in an ongoing research project on patients with muscular dystrophy.2, LV end systolic volume (LVESV) = 95 mL/m2) with severely impaired systolic function (LV-EF = 35%) due to diffuse hypokinesia, highly pronounced in the inferior and lateral free wall  showed sinus rhythm, normal duration QRS with left anterior fascicular block and deep lateral Q waves. Transthoracic echocardiography showed a dilated LV with severely impaired systolic function (LV ejection fraction (LV-EF) = 35% by Simpson’s method) due to hypo-/akinesia predominantly in the left ventricular free wall. Repeated ambulatory ECG monitoring showed frequent non-sustained ventricular tachycardia episodes. For further characterization of LV function and morphology, additional CMR studies were performed on a 1.5-T scanner . In the last study prior to ICD implantation, functional analysis by SSFP-cine sequences showed a dilated LV (LV end diastolic volume (LVEDV) = 146 mL/mThis year, the patient presented again for cardiac follow-up and underwent his first follow-up CMR study six months after ICD implantation (as part of the study protocol). There were no changes in physical examination, ECG and echocardiography findings. No sustained arrhythmic events, nor ICD therapy were recorded since implantation. Before performing CMR, device interrogation was performed and both ICD as well as pacemaker functions were switched off. Scanning was performed on the same scanner as the initial study with the same imaging protocol. Only the specific absorption rate (SAR) was restricted to 2.0 W/kg. The patient was closely monitored (ECG and pulse-oximetry) during the whole stay in the MR environment. During the scan, the patient was completely asymptomatic and no arrhythmic events were recorded. Image quality was limited compared to the previous study without an ICD due to substantial susceptibility/banding artefacts associated with the ICD generator on the left hemithorax Figures  and 2. NTo the best of our knowledge, this is the first presentation of MR of the heart in a patient with the world’s first and so far only MR-conditional ICD. In our case, a major problem related to the presence of the MR conditional ICD was an image artifact caused by the device’s generator which hampered the visualization of the midventricular and apical anterior and antero-lateral segments in all sequences performed. Considering previous studies, right chest implantation of the ICD could probably have helped in this setting and may be preferred in future ICD implantations . In the Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.CMR: Cardiovascular magnetic resonance; ICD: Implantable cardioverter/defibrillator; LGE: Late gadolinium enhancement; LV: Left ventricle; LVEDV: Left ventricular end diastolic volume; LVESV: Left ventricular end systolic volume; SAR: Specific absorption rate.The authors declare that they have no competing interests.AF planned the scan protocol, assisted in image acquisition and interpretation, and helped to draft the manuscript. AY provided cardiology supervision during scanning, reviewed device interrogations, assisted in image acquisition and interpretation, and drafted the manuscript. AL and SR assisted with preparing the patient and planning as well as performing the scan protocol. US provided additional supervision and critically reviewed the manuscript. All authors read and approved the final manuscript.Movies 1A-C.Click here for file


To determine the association of carotid atherosclerosis and right ventricular diastolic dysfunction (DD) among treated hypertensive Nigerian patients.This was a single center cross-sectional study performed at the Cardiology Clinic of LAUTECH Teaching Hospital, Ogbomoso, Nigeria between January and December 2012. The study included 122 hypertensive Nigerians . Patients’ clinical, demographic, and echocardiographic parameters were obtained. Diastolic dysfunction was assessed with the trans-tricuspid Doppler flow.P = 0.049) and interventricular septal thickness in diastole  were significantly higher and tricuspid annular pulmonary systolic excursion  was significantly lower in patients with right ventricular DD than in those with normal diastolic function. Carotid intima media thickness measurements were correlated with early trans-tricuspid Doppler flow and early transtricuspid diastolic flow/late right atrial transtricupsid diastolic flow ratio.Patients with DD were significantly older than those with normal diastolic function. Mean and maximum carotid intima media thickness measurements were significantly higher among patients with right ventricular DD than in those with normal diastolic function. Mean systolic blood pressure (148.3 ± 31.9 vs 128.0 ± 2.8 mm Hg, Right ventricular DD in hypertensive patients was significantly correlated with increased carotid atherosclerosis. Carotid intima media thickness measurements may therefore be a surrogate marker for DD in hypertensive subjects. Systemic hypertension has been shown to be associated with right ventricular abnormalities in both morphology and function. Right ventricular diastolic dysfunction (DD) may be an early indicator of hypertensive heart disease accompanying left ventricular DD (1-3). It can be diagnosed by various means including the ratio of early and late trans-tricuspid Doppler inflow velocities and tissue Doppler velocities.Atherosclerosis is the underlying factor for many cases of cardiovascular morbidity and mortality (4). A useful surrogate marker for carotid atherosclerosis is carotid intima media thickness (5). This parameter reflects the severity of thickening/atherosclerosis of the major arteries and is directly linked with the severity of hypertension and target organ damage associated with hypertension . DD is a typical part of the cardiovascular risk spectrum with increased risk for accelerating progressive cardiac dysfunction (6). However, it is still not known whether carotid intima media thickness, which has been shown to correlate with many conventional cardiovascular risk factors, is associated with right ventricular DD, especially among Africans (7). This study aims to determine the association between right ventricular DD and carotid intima media thickness in a sample of Nigerian hypertensive patients.This was a single center cross-sectional study performed at the Cardiology Clinic of LAUTECH Teaching Hospital, Ogbomoso, Nigeria. One hundred and twenty two hypertensive patients were consecutively recruited for this study. The study was conducted between January and December 2012. We obtained clinical and demographic parameters, including age, sex, weight, height, and body mass index.The study included hypertensive participants who were on treatment and had been diagnosed according to the standardized criteria (8). Hypertension was defined as persistent elevated sitting blood pressure >140/90 mm Hg (the patients had to be sitting for at least five minutes). At the time of the study some participants had normal blood pressure due to the applied therapy. All participants underwent echocardiography according to the recommendation of the American Society of Echocardiography (9). We excluded those who had been diagnosed with diabetes mellitus, chronic kidney disease, liver disease, were pregnant, were on statin treatment or refused to give their consent to participate in the study.Echocardiography and B Mode Carotid Doppler were performed using General Electric Ultrasound Machine (LOGIQPro 6) with 3.5MHz and 9 MHz probes, respectively. The parameters obtained in the echocardiography included posterior wall thickness in diastole (PWTd), interventricular septal thickness in diastole (IVSd), left ventricular end diastolic dimension (LVDD), left ventricular end systolic dimension (LVSD), and right ventricular dimension (RVD). Left ventricular mass and left ventricular mass index were calculated using the Devereux modified ASE cube formula (6). Right ventricular diastolic function was assessed using the trans-tricuspid Doppler flow velocity. The early (E wave) and late (A wave) trans-tricuspid wave velocity were determined by putting the Doppler sampling volume at the ventricular end of the tricuspid valve. Right ventricular diastolic dysfunction was defined as Tricuspid E/A ratio <1. The right ventricular dimension was taken in the left parasternal long axis in the mid-ventricular section.The carotid intima media thickness was measured in common carotid artery, with the participant lying down, neck extended and head slightly turned in the direction opposite to the carotid artery being examined. A 10-mm longitudinal section located at a distance of 1-2 cm from the bifurcation was studied and measurements were performed in the distal walls along an axis perpendicular to the artery, to establish two lines: the intima-media interface and the media-adventitia interface. Six measurements were obtained in each carotid artery, and the average mean and maximum values were recorded .t test and χ2 test. Pearson correlation statistics was done to show the association between indices of carotid atherosclerosis and that of right ventricular diastolic function. P < 0.05 was set as the significance level. The study conforms to the Protocol of Helsinki and ethical approval was obtained from the institutional ethics research committee. Written and informed consent was obtained from all participants.Statistical analysis was done using the SPSS 18.0 . Quantitative data are presented as means ± standard deviation and qualitative data as frequency and percentages. Group comparison was done using P = 0.049).The mean age of the study participants was 57.3 ± 14.7 years (Table 1). Of 122 patients, 45 were women (36.9%). About half of the study participants had their blood pressure controlled, ie had blood pressure ≤140/90 mm Hg. Fifty-eight patients (47.5%) had evidence of right ventricular DD. The mean systolic blood pressure of patients with right ventricular DD was significantly higher than of patients with normal right ventricular diastolic function . Patients with right ventricular DD had significantly higher mean systolic blood pressure, interventricular septal thickness in the diastole , and posterior wall thickness in the diastole  than patients with normal diastolic function. Patients with normal diastolic function had significantly higher tricuspid annular pulmonary systolic excursion (TAPSE), an indicator of right ventricular systolic function  (Table 2).The mean and maximum carotid intima media thickness measurements were significantly higher in participants with right ventricular DD than in those with normal diastolic function (Table 2). Participants with right ventricular diastolic dysfunction were significantly older than those with normal right ventricular diastolic function  (Table 3). Other right ventricular parameters such as TA, pulmonary systolic velocities, pressure gradient, right ventricular internal diastolic dimension, and TAPSE were not significantly correlated with the carotid intima media thickness measurements. The exception was that the peak pulmonary arterial systolic velocities correlated significantly with mean carotid intima media thickness in the left carotid artery and the pulmonary pressure gradient significantly correlated with the mean carotid intima media thickness in the right carotid artery (Table 3).Our study found that right ventricular DD in hypertensive patients was significantly correlated with increased carotid atherosclerosis. Systemic hypertension has been associated with many long term complications including systolic and diastolic heart failure, stroke, and myocardial infarction (10-12). Diastolic dysfunction associated with hypertension, especially of the left ventricle, has been linked with increasing mortality and morbidity . Diastolic heart failure (or heart failure with preserved ejection fraction) has been reported to have a higher risk and worse prognosis than heart failure with reduced ejection fraction . There is evidence that systemic hypertension is often followed by similar affectation of the right ventricle as well as the left ventricle in function and in morphology (1).Carotid atherosclerosis, reflected by the carotid intima media thickness is additional evidence of increasing predisposition to complications due to stroke and myocardial infarction. This study provides an additional set of information linking carotid atherosclerosis with right ventricular DD among treated hypertensive Nigerians. We noted that all carotid intima media thickness measurements were correlated with the early trans-tricuspid right ventricular filling pressures and also with the ratio of the early and late right ventricular diastolic inflow velocity. This study also revealed that carotid intima media thickness measurements were significantly higher in patients with right ventricular DD than in those with normal right ventricular diastolic function. In addition, mean interventricular septal thickness which is the shared part with the left ventricle was significantly greater than the posterior wall in hypertensive patients with right ventricular DD than in those with normal diastolic function. We postulate that the impact of an additional insult from the right ventricular DD on the interventricular septum might be responsible for this. These two groups were similar in body mass index distribution and the impact of obesity is therefore almost excluded. Hypertensive patients in this study with right ventricular DD had significantly higher mean carotid intima media thickness measurements than hypertensive patients with normal right ventricular diastolic function as evaluated by the trans-tricuspid E/A ratio. Hypertensive patients with right ventricular diastolic dysfunction were significantly older than hypertensive subjects with normal right ventricular diastolic function.Plausible explanations for the apparent involvement of the right ventricle in systemic hypertension are suggested. However, many of them are not well elucidated. The mechanisms of ventricular interaction are unknown but may relate to restriction of ventricular filling by the pericardium (16), although most studies have assessed only the effect of right ventricular volume expansion on left ventricular function (17) rather than vice versa. Other explanations include enhanced sympathetic tone, increased delivery of blood borne vasoconstrictor substances, or abnormal local release of vasoactive factors acting on both the greater and the lesser circulation (18).Tricuspid annular pulmonary systolic excursion is a relative good estimate of right ventricular systolic function (19). Although both were within the normal limits, we noted that the right ventricular systolic function of patients with DD was significantly worse than of patients with normal diastolic function. This may be a consequence of associated progressive decline in right ventricular systolic function with increasing right ventricular DD in association with carotid atherosclerosis, which this study was not able to detect. This may be a new finding; we believe that tissue Doppler and right ventricular fractional area change may be a better instrument to delineate right ventricular function.This study therefore confirms the results of other studies that have shown that right ventricular diastolic dysfunction is a marker of adverse effects as it parallel blood pressure driven left ventricular diastolic remodeling (20). The relationship between left ventricular DD and carotid stiffness or atherosclerosis has been better described among Caucasians (21-23). However, because of the systemic nature of most of the pathogenetic linkages associated with left ventricular DD, there is ample evidence that right ventricle is equally affected in hypertension. Hypertensive patients with DD had a higher risk of carotid atherosclerosis and consequently increased cardiovascular risk as revealed by a significantly higher mean carotid intima media thickness, which is a surrogate marker of cardiovascular burden. Apart from this, left ventricular mass and wall chamber dimensions were significantly higher among those with increased atherosclerosis, which further points to a seemingly higher cardiovascular burden.This study has some limitations. It is a hospital based study and the result cannot be directly extrapolated to the general population. The trans-tricuspid Doppler flow, which was used as a measure of DD can be affected by preload and its impact could not be assessed. Also, this was a cross-sectional study and therefore it cannot investigate causal relations between carotid atherosclerosis and right ventricular DD. A well designed prospective study will be necessary in that regard. Furthermore, our Center does not have tissue Doppler, which could have possibly revealed more patients with right ventricular diastolic dysfunction.In conclusion, this study revealed that right ventricular DD in hypertensive patients was significantly correlated with carotid atherosclerosis. Further studies are necessary to reveal the timing and other determinants of biventricular diastolic involvement in hypertensive patients.


The pathophysiology of myocardial injury and repair in patients with ST‐elevation myocardial infarction is incompletely understood. We investigated the relationships among culprit artery microvascular resistance, myocardial salvage, and ventricular function.2‐weighted‐ and late gadolinium–enhanced cardiac magnetic resonance delineated the ischemic area at risk and infarct size, respectively. Myocardial salvage was calculated by subtracting infarct size from area at risk. Univariable and multivariable models were constructed to determine the impact of IMR on cardiac magnetic resonance–derived surrogate outcomes. The median (interquartile range) IMR was 28 (17–42) mm Hg/s. The median (interquartile range) area at risk was 32% (24%–41%) of left ventricular mass, and the myocardial salvage index was 21% (11%–43%). IMR was a significant multivariable predictor of early myocardial salvage, with a multiplicative effect of 0.87  per 20% increase in IMR; P<0.001. In patients with anterior myocardial infarction, IMR was a multivariable predictor of early and late myocardial salvage, with multiplicative effects of 0.82  and 0.92 , respectively. IMR also predicted the presence and extent of microvascular obstruction and myocardial hemorrhage.The index of microvascular resistance (IMR) was measured by means of a pressure‐ and temperature‐sensitive coronary guidewire in 108 patients with ST‐elevation myocardial infarction  at the end of primary percutaneous coronary intervention. Paired cardiac MRI (cardiac magnetic resonance) scans were performed early  and late  after myocardial infarction. TJ Am Heart Assoc. 2012;1:e002246 doi: 10.1161/JAHA.112.002246)(Microvascular resistance measured during primary percutaneous coronary intervention significantly predicts myocardial salvage, infarct characteristics, and left ventricular ejection fraction in patients with ST‐elevation myocardial infarction.  Standard clinical methods for assessing the efficacy of reperfusion, such as the electrocardiogram5 and angiographic perfusion grade,6 are indirect and have limited diagnostic accuracy for culprit artery microvascular function. Microvascular damage revealed noninvasively by contrast‐enhanced cardiac magnetic resonance (CMR) imaging is an independent predictor of prognosis after acute myocardial infarction (MI).3 However, because of issues around feasibility and cost, CMR is not normally performed early after MI. When CMR is available, it is usually performed up to 7 days after hospital admission in medically stabilized patients. Therefore, a direct quantitative measure of microvascular function during primary PCI would be an important advance for very early risk stratification in routine clinical practice.Ex vivo studies in experimental animals have suggested that maintained microvascular patency in ischemic myocardium limits infarct size.11 including in patients with ST‐elevation MI (STEMI).11 IMR measured at the end of primary PCI is an independent predictor of left ventricular ejection fraction as measured by echocardiography10 or CMR11 3 months after PCI. These observations suggest that IMR can be used to study the pathophysiology of microvascular function in STEMI and that IMR could have utility for very early prognostication.The index of microvascular resistance (IMR) is a simple coronary guidewire–based method for assessing coronary microvascular function,2‐weighted CMR,16 we aimed to investigate the ability of acutely measured IMR to predict subsequent myocardial salvage and left ventricular remodeling in a cohort of patients with STEMI. Our first hypothesis was that microvascular resistance measured by IMR after culprit artery reperfusion is a determinant of subsequent myocardial salvage. Our second hypothesis was that IMR is a predictor of left ventricular function during follow‐up. Our final hypothesis was that IMR would predict the occurrence and severity of infarct characteristics, such as myocardial hemorrhage and microvascular obstruction, which have prognostic importance.3Given that myocardial salvage can be measured with T17 Exclusion criteria represented standard contraindications to CMR, including an estimated glomerular filtration rate <30 mL/min per 1.73 m2. The project was approved by the West of Scotland Research Ethics Committee.Consecutive acute STEMI patients undergoing primary PCI at a regional cardiac center were screened. The inclusion criteria were an indication for primary PCI for acute STEMI due to a history of symptoms consistent with acute myocardial ischemia and with supporting changes on the electrocardiogram .17 Aspiration thrombectomy, direct stenting, antithrombotic drugs, and other therapies were administered according to clinical judgment.Acute STEMI management followed contemporary guidelines.11 Hyperemia was induced by 140 μ/kg per minute of intravenous adenosine preceded by a 2‐mL intracoronary bolus of 200 μg nitrate. The mean aortic and distal coronary pressures were recorded during maximal hyperemia. Previous studies in patients with stable coronary disease have established that IMR is repeatable and independent of hemodynamic variations, including heart rate, blood pressure, and myocardial contractility.9 In our study, the repeatability of IMR was assessed by duplicate measurements 5 minutes apart in a subset of 12 consecutive patients.A coronary pressure‐ and temperature‐sensitive guidewire  was used as the primary guidewire. The guidewire was calibrated outside the body, equalized with aortic pressure at the ostium of the guide catheter, and then advanced to the distal third of the culprit artery. IMR is defined as the distal coronary pressure multiplied by the mean transit time of a 3‐mL bolus of saline at room temperature during maximal coronary hyperemia, measured simultaneously .2‐weighted CMR,19 and delayed‐enhancement phase‐sensitive inversion‐recovery pulse sequences.20 The bright‐blood T2‐weighted ACUT2E method (Acquisition for Cardiac Unified T2 Edema)19 incorporates elements of the bright‐blood2007 and turbo spin‐echo methods.22 Typical imaging parameters were as follows: acquisition time 7 to 12 seconds, matrix 192×192, flip angle 180°, echo time 1.69 ms, and bandwidth 789 Hz/pixel. Twenty‐nine coherent spin echoes (echo train length) were obtained per heartbeat, and the time interval (echo spacing) between the 180° inversion pulses was 3.4 ms. Data were acquired every second RR interval. The voxel size was 1.9×1.9×6 mm3. Microvascular obstruction was defined as a central dark zone on early delayed‐enhancement imaging 1, 3, 5, and 7 minutes after contrast injection and within an area of late gadolinium enhancement (LGE). MI was imaged by using a segmented phase‐sensitive inversion‐recovery turbo fast low‐angle shot18 radiofrequency pulse sequence 15 minutes after intravenous injection of 0.10 mmol/kg gadoterate meglumine . Typical imaging parameters were as follows: matrix 192×256, flip angle 25°, echo time 3.36 ms, bandwidth 130 Hz/pixel, echo spacing 8.7 ms, and trigger pulse 2. The voxel size was 1.8×1.3×8 mm3.CMR was performed approximately 2 days after MI and 3 months after MI on a Siemens MAGNETOM Avanto  1.5‐Tesla scanner with a 12‐element phased‐array cardiac surface coil. The imaging protocol included cine MRI with steady‐state free precession, edema imaging with bright‐blood T23 These cardiologists have considerable CMR experience in patients with acute MI, including protocols with bright‐blood T2‐weighted CMR. A third CMR trained‐cardiologist (N.T.) provided an independent opinion when disagreement occurred, and agreement was established by consensus. All of the cardiologists were blinded to the PCI and IMR results. Left ventricular dimensions, volumes, and ejection fractions were quantified with computer‐assisted planimetry.The images were analyzed on a Siemens workstation by 2 cardiologists  with 3 and 5 years’ CMR experience, respectively.Reference ranges used in the laboratory were 105 to 215 g for left ventricular mass in men, 70 to 170 g for left ventricular mass in women, 77 to 195 mL for left ventricular end‐diastolic volume in men, 52 to 141 mL for left ventricular end‐diastolic volume in women, 19 to 72 mL for left ventricular end‐systolic volume in men, and 13 to 51 mL for left ventricular end‐systolic volume in women.19 The jeopardized area at risk on each axial image was defined as the percentage of left ventricular area delineated by the hyperintense zone on T2‐weighted images.19Quantitative assessments were performed by 2 independent observers, and their results were averaged. The approach to image analysis, including interobserver agreement, has been reported previously.19 Infarct regions with evidence of microvascular obstruction were included within the infarct area. Microvascular obstruction was classified as relevant  or nonrelevant (dots or nil) and also was expressed as a percentage of total left ventricular mass.The presence of acute infarction was established with CMR on the basis of abnormalities in cine wall motion, rest first‐pass myocardial perfusion, and LGE imaging. In addition, supporting changes on the electrocardiogram and coronary angiogram were required. Acute infarction was considered present only if LGE was confirmed on both the short‐ and long‐axis acquisitions. The myocardial mass of LGE (in grams) was quantified by a semiautomatic detection method that used a signal intensity threshold of >2 standard deviations (SDs) above a remote reference region.12 The myocardial salvage index was calculated by dividing the myocardial salvage area by the initial area at risk.Myocardial salvage was calculated by subtraction of percent infarct size from percent area at risk.2‐weighted CMR was defined as a confluent dark zone with a mean signal intensity <2 SDs of the mean signal intensity of the surrounding affected brighter area.23 Hemorrhage was expressed as a percentage of total left ventricular mass.Myocardial hemorrhage revealed by bright‐blood T24 and corrected TIMI frame count25 were used to grade culprit artery flow at initial angiography and at the end of the PCI. The TIMI myocardial perfusion grade was used to assess myocardial perfusion.26All angiograms were analyzed by 2 interventional cardiologists independent of the CMR analyses. The Thrombolysis In Myocardial Infarction (TIMI) flow classificationr) to describe correlations between log IMR and CMR parameters. Normal distributions were achieved where necessary by logarithmic transformation. All tests were 2 tailed, with a significance level of 0.05.The primary end point was myocardial salvage index. The sample size estimate was based on the adjusted effect (multiple regression) for the relationship between IMR measured acutely and myocardial salvage index as revealed by contrast‐enhanced CMR, after adjustment for prespecified known prognostic clinical confounders. In multiple‐regression models for myocardial salvage index, 80 subjects would provide ≥80% power to detect a correlation of 0.3 with a type 1 error rate of 0.05. With allowance for occasional problems with data acquisition, the projected sample size was ≥100 subjects. All subjects with available data were used in models fitted for CMR parameters at initial and follow‐up scans. Normality was assessed by using the Shapiro‐Wilk test. Means and SDs were used to summarize normally distributed data, geometric means and SDs to describe skewed data, percentages to summarize distributions, and Pearson coefficients  for CMR parameters measured independently by 2 observers in 20 randomly selected patients. Univariable and multivariable regression models were constructed to determine the prognostic significance of IMR with CMR parameters: myocardial salvage index, infarct size, microvascular obstruction, hemorrhage, area at risk, and left ventricular ejection fraction and volumes. Further subgroup analysis explored patients with and without a culprit left anterior descending coronary artery at initial angiography and patients with and without an occluded culprit coronary artery. We used a backward variable selection process with the cut point of 0.1 to select variables for the final multivariable models. IMR was specified in each multivariable model, but because renal function and serum troponin are not available at the time of primary PCI when IMR is measured, these variables were not included. Multivariable models adjusted for variables in stepwise selection models. For all baseline CMR outcomes, adjustment was made for the following variables: previous MI, sex, pain‐to‐balloon time, door‐to‐balloon time, thrombectomy, catheterization laboratory pulse pressure, TIMI flow, corrected TIMI frame count, and percent of ST elevation still present after PCI. For all follow‐up CMR outcomes, we adjusted for baseline value of the CMR parameter, age, door‐to‐balloon time, glycoprotein IIb/IIIa, TIMI flow, and percent of ST elevation still present after PCI.Between‐group comparisons of continuous variables used Student P values. All statistical analyses were performed in SAS .IMR associations were described by an effect estimate (either additive or multiplicative) on the continuous CMR parameters per 20% increase in IMR, with 95% confidence intervals (CIs) and P=0.1). IMR was measured at the end of primary PCI in all patients. Intravenous adenosine was well tolerated in all patients, and there were no adverse events. All patients were alive after 3 months’ follow‐up.One hundred eight patients with acute STEMI treated by primary PCI were enrolled between October 1, 2009, and July 8, 2010 . Forty‐sr=0.99, P<0.001), with a mean difference between IMR measurements of 0.01 . The median (interquartile range) IMR in all patients was 28 (17–42) mm Hg/s, with a range of 9 to 149 mm Hg/s. IMR correlated with time from symptom onset to coronary reperfusion . The median (interquartile range) arterial pressure measured simultaneously with IMR was 79.5 (69.5–97.0) mm Hg. Arterial pressure and IMR were not correlated .Repeated IMR measurements obtained by 4 different operators in 12 STEMI patients were highly correlated (The 2‐weighted CMR was 32% (24%–41%) of left ventricular mass, and the myocardial salvage index was 21% (11%–43%) (P<0.001).One hundred eight patients underwent CMR an average of 2 days after primary PCI. Ninety‐six patients (89%) returned for a follow‐up scan ≍3 months later . The bas11%–43%) . The areThe patients were divided into quartiles according to IMR. With higher values of IMR, the area at risk and initial infarct size increased and left ventricular ejection fraction decreasedP=0.006. IMR correlated positively with the presence of microvascular obstruction  and with myocardial hemorrhage  and negatively with myocardial salvage index .. Median r=−0.27, P=0.009) and positively with left ventricular end‐systolic volume .At 3 months, IMR correlated negatively with left ventricular ejection fraction (P<0.001 for both comparisons).IMR was a univariable predictor of area at risk and early infarct size, myocardial salvage, microvascular obstruction, hemorrhage, and left ventricular ejection fraction. IMR was a univariable predictor of infarct size and left ventricular ejection fraction at 3 months . At 2 daIn a comparison of patients with anterior and nonanterior infarctions , IMR wasIn a comparison of patients with an occluded culprit artery (TIMI flow grade 0/1) at initial presentation to those with a patent culprit artery (TIMI flow grade 2/3) , IMR wasMultivariable models with left ventricular end‐diastolic and end‐systolic volumes at 3 months showed no association with IMR after adjustment for initial volumes , and 7.Our results indicate that after primary PCI for STEMI, microvascular resistance assessed by IMR is a significant predictor of myocardial salvage. Second, microvascular resistance was associated significantly with left ventricular ejection fraction in all patients initially and in patients with anterior MI after 3 months’ follow‐up. Finally, in addition to predicting myocardial salvage, microvascular resistance was a significant predictor of several infarct characteristics, including infarct size, microvascular obstruction, and myocardial hemorrhage. Importantly, IMR provided additive predictive value to established measures of coronary/myocardial reperfusion, including time to reperfusion, coronary flow grades, and electrocardiogram changes. IMR adds early prognostic information at the key time of emergency reperfusion therapy when CMR is not possible, and, potentially, IMR represents a measurable therapeutic target after coronary reperfusion in STEMI.4 Independent of other early predictors of myocardial salvage, such as time to reperfusion and initial infarct size, our findings suggest that microvascular function influences the balance between recovery of viable injured tissue and progressive infarction. The pathophysiology of microvascular injury in STEMI is complex and encompasses embolization of proximal thrombus and in situ microvascular thrombosis, as well as extravascular pathologies such as edema and hemorrhage.27 We also have demonstrated for the first time that microvascular resistance shortly after coronary reperfusion is associated with subsequent evidence of myocardial hemorrhage as revealed by CMR, consistent with the notion that hemorrhage is an adverse complication of more severe MI.Because microvascular resistance significantly predicted initial myocardial salvage, we conclude that microvascular patency is a key pathophysiological determinant of the injury/repair response in the infarcted human heart. This observation is a new insight into the pathophysiology of MI and is consistent with previous experimental observations in large animal models.10 who found that IMR predicted left ventricular wall motion score at 3 months after MI in 28 STEMI patients, as well as our own data in a prior study of a separate cohort of patients in whom CMR was used to assess ventricular function.11 Our present study confirms these observations in a much larger cohort but also demonstrates that microvascular resistance predicts infarct characteristics, including initial microvascular obstruction and infarct size, especially in patients with anterior MI or an occluded artery.Our study extends the results of Fearon et al,3Intuitively, it makes sense that IMR did not predict final left ventricular ejection fraction in all patients because its predictive value is most likely to be discriminative in patients with large infarctions. For example, a small MI might have little impact on systolic function  even if microvascular injury is pronounced within distribution of the culprit artery. One other explanation could be that because the sample size is relatively small, there might have been insufficient power to detect a true inverse association between IMR and ejection fraction. We also found that IMR was more closely associated with infarct size than with microvascular injury . Because IMR was performed before CMR, we cannot say whether infarct burden is a determinant of microvascular dysfunction or vice versa. However, IMR also correlated with the extent of microvascular obstruction and hemorrhage, which points to the pathological importance of the extent and not just the presence of these abnormalities.9 We found that IMR was highly repeatable when measured twice 5 minutes apart at the end of primary PCI.The accuracy and precision of IMR has been established in patients with stable coronary artery disease, but its performance in STEMI has not been fully explored.2‐weighted CMR.23 In the current study, IMR was nearly 2‐fold higher in patients with myocardial hemorrhage than in patients without hemorrhage. Myocardial hemorrhage could represent an unintended consequence of evidence‐based antithrombotic and antiplatelet therapies, a manifestation of more severe MI (as suggested by our data), or both. Our other main finding is that early myocardial salvage is a significant predictor of subsequent changes in left ventricular function. This result complements the cohort study by Dall'Armellina et al,15 who performed serial CMR scans in 30 STEMI patients over 6 months of follow‐up and found that regression in infarct size during follow‐up predicted the recovery in wall motion. Taken together, both studies indicate that the propensity for improvement in the initial extent of injury  is a determinant of future changes in left ventricular systolic function. On the basis of our findings, microvascular patency might permit recovery of salvageable myocardium, whereas microvascular injury might predispose to limited salvage and impaired systolic function in the longer term.We have shown that IMR is predictive of myocardial hemorrhage as revealed by bright‐blood T6 Results from preliminary therapeutic trials during primary PCI for STEMI support the notion that microvascular injury is a therapeutic target.30Our results raise the possibility that microvascular injury might be a measurable therapeutic target after coronary reperfusion in STEMI. For this to be the case, IMR should identify patients who might benefit from a specific treatment. Ideally, the treatment should be given at the time of primary PCI, leading to a measurable reduction in IMR or an improvement in prognostically important surrogate measures of microvascular injury.2 values. We could have used a larger signal intensity difference between remote and affected myocardium on LGE CMR to delineate infarct area, but we believe that the main conclusions in our analysis remain valid. Although IMR a multivariable predictor of left ventricular volumes after 3 months, this was not the case after adjustment for volumes measured early after MI. The predictive value of IMR for adverse remodeling needs further prospective study in a larger cohort.Microvascular patency is only one of several characteristics that influence myocardial salvage and systolic function after MI, and our multivariable models account for only part of this variability, as reflected by the RMicrovascular function is a determinant of myocardial salvage in patients with reperfused STEMI and predicts changes in left ventricular function and remodeling. IMR seems to be most informative in patients with an anterior MI or occluded culprit artery.


Since diabetic cardiomyopathy was first reported four decades ago, substantial information on its pathogenesis and clinical features has accumulated. In the heart, diabetes enhances fatty acid metabolism, suppresses glucose oxidation, and modifies intracellular signaling, leading to impairments in multiple steps of excitation–contraction coupling, inefficient energy production, and increased susceptibility to ischemia/reperfusion injury. Loss of normal microvessels and remodeling of the extracellular matrix are also involved in contractile dysfunction of diabetic hearts. Use of sensitive echocardiographic techniques (tissue Doppler imaging and strain rate imaging) and magnetic resonance spectroscopy enables detection of diabetic cardiomyopathy at an early stage, and a combination of the modalities allows differentiation of this type of cardiomyopathy from other organic heart diseases. Circumstantial evidence to date indicates that diabetic cardiomyopathy is a common but frequently unrecognized pathological process in asymptomatic diabetic patients. However, a strategy for prevention or treatment of diabetic cardiomyopathy to improve its prognosis has not yet been established. Here, we review both basic and clinical studies on diabetic cardiomyopathy and summarize problems remaining to be solved for improving management of this type of cardiomyopathy. The number of patients with diabetes has been increasing worldwide in the past two decade, and these patients are predisposed to serious cardiovascular morbidity and mortality . The impPopulation-based studies have shown that the risk of heart failure is increased two- to threefold by diabetes , 5. The “Diabetic cardiomyopathy” is a concept that was introduced in 1972 by Rubler et al. , who exaInterstitial and perivascular fibrosis is a histological hallmark of diabetic cardiomyopathy , 14, 15,Ins2WT/C96Y) mouse -enkephalin acetate [DADLE] and isoflurane) were also ineffective in limitation of infarct size in diabetic hearts [Diabetes is one of the pathological states that impair intracellular signaling for cardiomyocyte protection. Except for a few studies, previous studies showed that cardioprotection achieved by ischemic preconditioning (IPC) or ischemic postconditioning (IPost) is lost or required extra-cycles of “conditioning” in experimental diabetes Table  141, 14, 182. Mic hearts –163, 169Like animal models of diabetes, diabetic human hearts have defects in cytoprotective mechanisms. Ishihara et al.  showed tMultiple defects in cytoprotective signal pathways have been indicated in diabetic hearts. Our recent studies have shown that Jak2, being upstream of PI3K-Akt signaling, is inhibited by enhanced calcineurin activity and that phosphorylation of GSK-3β by ERK is lost by an endoplasmic reticulum stress-dependent mechanism in a rat model of T2DM , 143. FuATP channel opener and anesthetic agents [There is limited information on whether glycemia control repairs defects in protective signaling in diabetic hearts. Acute hyperglycemia induced by dextrose infusion impaired infarct size limitation by IPC, a mitochondrial Kc agents , 174–178c agents  reportedc agents –190, resCurrently, the best approach to the diagnosis of diabetic cardiomyopathy is detection of functional and structural changes in the LV and exclusion of other heart diseases being responsible for the changes in a diabetic patient. Diagnostic clues of diabetic cardiomyopathy are listed in Table Left ventricular diastolic dysfunction detectable by TDI  at exercise stress may be the earliest sign of diabetes-induced LV dysfunction as discussed in section “31P-MRS and by1H-MRS. As discussed in section “1H-MRS have demonstrated that increase in myocardial triglyceride content  was associated with LV diastolic dysfunction in diabetic patients [A promising novel approach to diagnosis of diabetic myopathy is characterization of metabolic changes in the myocardium by patients , 193. Fupatients  showed tAlthough high prevalence of subclinical myocardial dysfunction has been reported in the early stage of T1DM, clinically relevant heart failure is relatively rare in this type of diabetes. In an observational study, 462 T1DM patients without a previous history of heart disease were followed up, and it found that only 17 patients (3.7 %) developed heart failure during a 12-year follow-up period . The patA number of clinical trials have been conducted to evaluate the impact of glycemic control on the prevention of cardiovascular events in T2DM. However, end-points in the studies were atherosclerotic cardiovascular events and death, leaving non-ischemic heart failure not specifically determined. A recently published meta-analysis including a total of 27,049 subjects in the UKPDS 33 (UK Prospective Diabetes Study 33), ACCORD, ADVANCE, and VADT trials showed that mortality was not affected by intensive glycemic control, with hazard risks of 1.10 for cardiovascular death  and 1.04 for all-cause death (95 % CI: 0.90–1.20) . These fWhether incidence and/or outcome of heart failure differ depending on the type of hypoglycemic agent selected for hyperglycemia control remains unclear. This issue has not been addressed by a prospective randomized clinical trial. In observational cohort studies and retrospective analyses of registered patients, use of metformin is associated with low incidence of heart failure compared with other glycemia control regimens . FurtherIn contrast with metformin, thiazolidinedione (TZD) has been shown to increase incidence of “heart failure” in diabetes compared with sulfonylurea. Unfortunately, it is not clear whether the increase in “heart failure” by TZD indeed reflects worsening of LV function or just retention of fluids –206. In Optimal treatment of heart failure in diabetic patients has not been specifically addressed, and relevant information is limited to effects of diabetes on the efficacy of a heart failure therapy in subgroup analyses of trials. In earlier studies, ACE inhibitor was suggested to be similarly effective in diabetic and non-diabetic patients with heart failure with reduced LVEF , 210 andAccumulating evidence obtained by novel imaging techniques  indicates that these techniques for functional and metabolic analyses of human hearts will make it possible to formulate clinical parameters for diagnosis of diabetic cardiomyopathy. Such diagnostic criteria would facilitate the design of prospective studies to search for optimal therapy for prevention and treatment of this cardiomyopathy. Numerous questions regarding pathogenesis of diabetic cardiomyopathy still remain, but molecular mechanisms of down-regulation of SERCA2a, mitochondrial dysfunction, and defects in cytoprotective signaling appear particularly important issues for designing novel therapies for restoration of contractile function and prevention of progressive heart failure. Novel therapy is in urgent need since even mild diastolic dysfunction in diabetic hearts has been shown to be associated with more than a threefold increase in all-cause mortality .


In vitro studies showed that BMSCs expressed the elastin protein, which was deposited into the extracellular matrix. Transduced BMSCs were injected into the infarcted myocardium of adult rats. Control groups received either BMSCs transduced with the green fluorescent protein gene or medium alone. Elastin deposition in the infarcted myocardium was associated with preservation of myocardial tissue structural integrity . As a result, infarct scar thickness and diastolic compliance were maintained and infarct expansion was prevented (P < 0.05 versus controls). Over a 9-week period, rats implanted with BMSCs demonstrated better cardiac function than medium controls; however, rats receiving BMSCs overexpressing elastin showed the greatest functional improvement (P < 0.01). Overexpression of elastin in the infarcted heart preserved the elastic structure of the extracellular matrix, which, in turn, preserved diastolic function, prevented ventricular dilation and preserved cardiac function. This cell-based gene therapy provides a new approach to cardiac regeneration.After a myocardial infarction, thinning and expansion of the fibrotic scar contribute to progressive heart failure. The loss of elastin is a major contributor to adverse extracellular matrix remodelling of the infarcted heart, and restoration of the elastic properties of the infarct region can prevent ventricular dysfunction. We implanted cells genetically modified to overexpress elastin to re-establish the elastic properties of the infarcted myocardium and prevent cardiac failure. A full-length human elastin cDNA was cloned, subcloned into an adenoviral vector and then transduced into rat bone marrow stromal cells (BMSCs).  Progressive ventricular remodelling after myocardial infarction (MI) can result in progressive congestive heart failure. After coronary occlusion, the necrosed cardiomyocytes are replaced by fibroblasts and the infarcted myocardium becomes fibrotic scar tissue containing predominantly type III collagen. Because the intraventricular pressure consistently stretches the stiff, non-elastic, infarcted tissue with each contraction, the scar expands and the left ventricular (LV) chamber dilates with time, initiating the spiral of increased ventricular chamber stiffness and decreased cardiac function , 2.The elastic properties of tissues are essential to maintain their structural and biological function. Elastin is a major fibrous protein in the extracellular matrix of organs and tissues that exhibit stretch and recoil, such as vessel walls and articular ligaments . When thRestoration of the elastic properties of the infarct region can prevent progressive cardiac dilation and deterioration of ventricular function following an MI , 10. MyoIn the present study, we transduced primary cultured rat bone marrow stromal cells (BMSCs) with a high-efficiency adenoviral vector to overexpress the full-length elastin gene and found that implantation of autologous BMSCs overexpressing elastin prevented post-MI ventricular remodelling and improved cardiac function. This study provides a new approach to restore the promise of cardiac regeneration by cell transplantation.A full-length human lung elastin cDNA was isolated, compared with sequences in GenBank  at a dilution of 1:200. The cells were then stained with FITC-conjugated phalloidin (Invitrogen) at a dilution of 1:50. The nuclei were counterstained with DAPI , and the cells were visualized by fluorescence microscopy.in vitro and in vivo. Primer pairs were specific for human elastin  or rat elastin . Reverse transcription was carried out at 50°C for 30 min. For PCR, we used 30 cycles at 95°C for 30 sec., 55°C for 1 min. and 72°C for 1 min. The RT-PCR products were visualized on 1% agarose gels using ethidium bromide. GAPDH was amplified as a reference.RT-PCR was performed using the SuperScript III system (Invitrogen) to evaluate human and rat elastin gene expression Guide for the Care and Use of Laboratory Animals .All animal procedures were approved by the Animal Care Committee of the University Health Network, and all animals received humane care in compliance with the 6 cells/rat) was directly injected into the central region (one injection) and border region (one injection in each of two different sites) of the infarct using a 28G needle 7 days after MI. We consider 1 week after ligation the optimal time for cell transplantation as the acute inflammatory response has subsided, but the scar is not yet mature with dense collagen deposition.Adult female Lewis rats were anaesthetized using isoflurane 2%) during mechanical ventilation. The left coronary artery ligation technique was used to induce an MI and generate an infarct scar in the heart % during , 13. Aniin vitro elastin expression in BMSCs transduced with Ad-CMV-elastin, an antibody specific for human tropoelastin was used. Tropoelastin protein was detected by Western blot and quantitated by densitometry, with GAPDH as a loading control.For determination of Left ventricular sections from all groups were collected 9 weeks after cell transplantation. To assess the elastic structure of the tissue, sections were stained using the Verhoeff Van Gieson method and visualized with a Nikon Ti-Eclipse microscope. Three random fields of view were acquired and averaged for the positive pixel area of elastin fibres in the remote, border and infarct regions of each animal using ImageJ software. Elastin fibre–coated blood vessels were identified and digitally removed. Elastin fibre–positive pixel area was measured and expressed as the percentage of total possible pixels.The LV volume was measured using image analysis of pressure-fixed heart specimens, as previously described . Brieflyex vivo as previously described [Tissue birefringence was measured escribed . BrieflyEchocardiographic examinations were performed on treated rats, using an ACUSON Sequoia C256 System  with a 15L8 transducer (13 MHz), prior to ligation, prior to cell transplantation and every 2 weeks for 10 weeks after ligation. LV end-diastolic and end-systolic diameters and areas were measured, and per cent fractional shortening was calculated as previously described .End-point functional assessments were performed using Millar pressure and conductance catheters , as previously described . Real-tiData are presented as mean ± S.E.M. Time course analyses were carried out using two-way ANOVA, comparisons among groups were carried out with one-way ANOVA, and Tukey's multiple comparison test was used to detect data points at which differences between groups reached statistical significance. The P–V relations were compared by analysis of covariance.Rat BMSCs were first transduced with Ad-CMV-GFP to test the transduction efficiency. The cells expressed GFP at detectable levels 2 days after transduction, and the efficiency was approximately 90–95% A. To conOne week after coronary artery ligation, we implanted genetically modified rat BMSCs expressing either human elastin (BMSC-elastin) or GFP (BMSC-G) into the infarcted rat myocardium. Medium without cells served as the control. RT-PCR was used to evaluate human and rat elastin mRNA expression in the infarct and border regions 7 days after injection. The BMSC-elastin group expressed human elastin mRNA, but no human elastin mRNA was detected in the medium control or BMSC-G groups. Expression of the endogenous rat elastin was not significantly altered by the induction of human elastin A. To furAt 9 weeks after implantation, Verhoeff Van Gieson staining for elastic tissues demonstrated that the infarct scar and border region of the control and BMSC-G groups contained few elastin fibres C. In conP < 0.05) and thinner (P < 0.01) scars in the medium control group compared with the BMSC-G group  and BMSC-G  groups, suggesting that elastin overexpression in vivo stabilized the infarct region.Morphological examination of the hearts 9 weeks after cell implantation A reveale-G group B and C. P < 0.001 versus medium control; P < 0.05 versus BMSC-G). This increase in birefringence (retardance) indicates an increase in tissue organization and suggests that elastin overexpression preserved the tissue structural integrity of the infarcted myocardium.The variation in the organization of the extracellular matrix after cell implantation was evaluated by quantification of myocardial birefringence , throughP < 0.01). A significantly greater preservation of fractional shortening was observed in the BMSC-elastin group compared to the BMSC-G group (P < 0.01).Cardiac function was evaluated with echocardiography A prior tP < 0.05) and end-systolic volume (P < 0.05) compared to medium alone .Cardiac function and ventricular volumes were also evaluated using a P–V catheter 9 weeks after cell transplantation A. A shamum alone B and C. P < 0.05; P < 0.05), and dP/dtmin was better preserved in the BMSC-elastin group compared to the other two groups , and best preserved in the BMSC-elastin group .With respect to load-sensitive indices of cardiac function, the BMSC-elastin group had greater ejection fraction than the BMSC-G group (Stem cell therapy of infarcted hearts promised to restore ventricular function by replacing lost cardiomyocytes with functioning contractile elements. However, cell implantation has been shown to improve ventricular function only by paracrine signalling . Cell-baVariations in the human elastin gene from different tissues indicate that there are tissue-specific isoforms of tropoelastin, which may possess different biological properties . We clonin vitro and in vivo studies, we used RT-PCR to evaluate rat endogenous elastin expression and believe that the expression of human elastin did not significantly alter the endogenous elastin gene expression. However, a limitation of our study is that we do not have real-time PCR data to draw a definitive conclusion. We confirmed the presence of more elastic fibres in the infarct scar of the BMSC-elastin group by Verhoeff Van Gieson staining. In addition, these elastin fibres were configured in a wavy pattern, forming an extensive elastin network around the infarcted area. In the medium control and BMSC-G groups, the infarct scars had substantially fewer organized elastin fibres. We speculate that expression of elastin preserved the organized extracellular matrix and prevented adverse matrix modulation. Future studies would be of interest to determine the effects of elastin overexpression on other extracellular molecules, such as collagen.The human lung elastin gene was recombined into an adenoviral vector and successfully expressed in primary cultured rat BMSCs. Matrix modulation with increased elastin deposition in the extracellular matrix was observed in these cell cultures. We injected these genetically modified BMSCs into infarcted rat hearts in the belief that improvements in cardiac function due to cell transplantation could be further enhanced by introducing the full-length elastin gene into the transplanted cells, hence increasing the elasticity of the scar tissue after an MI. We observed elastin mRNA and protein in the rat hearts injected with BMSCs expressing human elastin. In both our Morphometric analysis of the infarct scars revealed that scar expansion and thinning were reduced in the BMSC-elastin group, supporting the observation that matrix disruption was reduced by the expression of elastin in the transplanted cells. Subsequent investigation confirmed the preservation of structure as myocardial birefringence in the scar region of the BMSC-elastin hearts was significantly higher than that of the other two groups, indicating a better aligned and organized extracellular matrix. Linear birefringence results from spatial anisotropy of optical refractive indices in tissue and can be used as a metric of tissue organizational structure , with siTimp3−/− mice was associated with decreased ventricular distensibility, chamber dilation, and systolic and diastolic dysfunction [Timp3 gene reversed these effects and improved the recovery of ventricular function [Matrix modulation plays an important role in maintaining ventricular geometry and function. We have previously shown that the loss of matrix structure and spatial architecture in function  and thatfunction . These cfunction . Enhancifunction .Decreased diastolic distensibility and compliance are important contributors to heart failure. Nearly half of the patients presenting with symptoms of congestive heart failure exhibit a near normal LV systolic function at rest , 31, andP/dtmin, the maximal velocity of ventricular pressure fall during diastole, is a load-dependent index of diastolic compliance. In our study, the BMSC-elastin group had the smallest dP/dtmin value. The EDPVR provides direct load-independent quantitative evidence of chamber stiffness. These data demonstrated that elastin overexpression in transplanted BMSCs significantly prevented the increase in diastolic stiffness seen in the other groups. Preservation of matrix structure and diastolic function may have contributed to the improved systolic function and cardiac performance associated with the transplantation of elastin-transduced BMSCs. Compared with our previous study using the elastin gene fragment [The passive compliance of the ventricular wall is as important to ventricular filling as active myocardial relaxation. Other determinants of diastolic function in addition to myocardial stiffness include wall thickness, chamber geometry and the timing of relaxation. The dfragment , overexpIn the current study, we demonstrated that matrix modulation by gene-enhanced cell transplantation preserved regional elasticity through overexpression of the full-length elastin gene. Elastin overexpression stabilized tissue structure, reduced scar expansion and improved cardiac function, especially LV diastolic function. These observations suggest that increasing the elasticity of the infarct scar will produce significant physiological benefits. The improved ventricular function following implantation of BMSCs transduced with the elastin gene suggests that elastin overexpression may be an important method to improve the results of cell transplantation.


Cardiogenic shock is very uncommon in healthy people. The differential diagnosis for patients with acute heart failure in previously healthy hearts includes acute myocardial infarction and myocarditis. However, many drugs can also depress myocardial function. Propofol and fentanyl are frequently used during different medical procedures. The cardiovascular depressive effect of both drugs has been well established, but the development of cardiogenic shock is very rare when these agents are used.After a minor surgical intervention, a 32-year-old Caucasian woman with no significant medical history went into sudden hemodynamic deterioration due to acute heart failure. An urgent echocardiogram showed severe biventricular dysfunction and an estimated left ventricular ejection fraction of 20%. Extracorporeal life support and mechanical ventilation were required. Five days later her ventricular function had fully recovered, which allowed the progressive withdrawal of medical treatment. Prior to her hospital discharge, cardiac MRI showed neither edema nor pathological deposits on the delayed contrast enhancement sequences. At her six-month follow-up examination, the patient was asymptomatic and did not require treatment.Although there are many causes of cardiogenic shock, the presence of abrupt hemodynamic deterioration and the absence of a clear cause could be related to the use of propofol and fentanyl. Cardiogenic shock is the most serious form of presentation of heart failure (HF). The anticipation of hemodynamic deterioration and multiple organ failure in these patients is very important in terms of survival. The outcome for patients with refractory acute cardiogenic shock remains disproportionately poor. Technological advances in recent years have enabled the development of new treatments, such as extracorporeal life support (ELS). ELS is a variation of cardiopulmonary bypass which could improve the outcomes of patients in cardiogenic shock . AlthougWe report the case of a 32-year-old Caucasian woman who experienced sudden, severe hemodynamic deterioration after undergoing a minor surgical procedure. Her medical history was unremarkable except for a vaginal delivery two years before. She underwent surgery to remove a Bartholin cyst, and no infection in the gland was found. The operation was performed while the patient was under sedation and being given an analgesic. Spontaneous breathing was maintained by infusing a propofol bolus 1 mg/kg) and fentanyl 100 μg intravenously. During surgery, the patient remained hemodynamically stable. She has nausea and vomiting in the early post-operative period, which were treated with intravenous ondansetron 4 mg). A few minutes later the patient went into sudden hemodynamic deterioration, with sinus tachycardia (113 regular beats/minute) and hypotension (50/30 mmHg). Pulse oximetry showed that her oxygen saturation level had decreased to 80% despite oxygen supplementation through a face mask (fraction of inspired oxygen 40%). In this clinical situation, we treated her with intravenous dopamine and dobutamine, as well as with mechanical ventilation because of global respiratory failure . The electrocardiogram showed sinus tachycardia. Signs of HF were found on her chest X-ray, and urgent transthoracic echocardiography (TTE) revealed severe biventricular dysfunction with global hypokinesia and a LVEF estimated to be 35%. Coronary angiography showed no coronary lesions, and an intra-aortic balloon pump was inserted for counterpulsation. Repeat TTE revealed a LVEF of 20% with a dilated left ventricle  showing severe left ventricular dysfunction during the acute phase.Click here for fileShort-axis view showing severe left ventricular dysfunction. Transthoracic echocardiography  showing severe left ventricular dysfunction during the acute phase.Click here for fileApical four-chamber view after total recovery of left ventricular function. Transthoracic echocardiography  showing total recovery of left ventricular function before discharge.Click here for fileShort-axis view after total recovery of left ventricular function. Transthoracic echocardiography  showing total recovery of left ventricular function before discharge.Click here for file


Left ventricular non-compaction (LVNC) is a rare congenital disorder characterized by two layered myocardium; trabeculated (non-compacted) and a non-trabeculated (compacted). LVNC is increasingly being recognized due to better imaging technology as a cause for heart failure and sudden cardiac death; however, data on clinical and imaging characteristics remains limited.To investigate the association of clinical presentation and outcomes in LVNC with cardiac phenotype by CMR.Fourteen patients  were retrospectively identified from CMR database between December 2007 and May 2010. CMR imaging included SSFP cine in standard views and late gadolinium enhancement. Quantitative analysis included left and right ventricular function, volumes, mass, LV wall motion score and non-compacted to compacted myocardium (NC/C) ratios in different segments. Number of involved LV segments and regions of maximum NC/C ratio were also recorded.Patient's medical records were reviewed for clinical history including NYHA functional class, ECG, telemetry, Holter/event monitoring and electrophysiology studies.Non-parametric U test, logistic regression analysis and parametric T-test were used to determine statistical significance as appropriate.Seven patients presented with acute heart failure including one in cardiogenic shock. Three patients presented with syncope, one with documented ventricular tachycardia (VT).Mean LVEF was 36.2 ± 22.8% and mean RVEF 31.5 ± 16.7%. LVEF <50% was present in 8 patients (57.1%), RVEF <40% in 7 (50%) and both in 6 (42.8%) patients. Mean NC/C myocardium ratio was 3.7±0.8 with mean of 5.5±3.1 LV segments involved. Patients with LV dysfunction were older, more symptomatic with higher NYHA class, had more myocardial segments involvement with non-compaction, and higher NC/C ratios .There were no deaths over a mean follow-up of 7.0 ± 4.6 months. One patient received a heart transplant for severe refractory heart failure. Five patients received an ICD; 4 with non-sustained VT and 1 with severe LV dysfunction. Patient with AVNRT underwent successful ablation.Patients with LVNC have a spectrum of cardiac phenotypes ranging from normal LV and RV to severe biventricular dysfunction. Clinical presentation and symptoms are associated with degree of non-compaction and ventricular dysfunction.


Type 2 diabetes and the metabolic syndrome are associated with impaired diastolic function and increased heart failure risk. Animal models and autopsy studies of diabetic patients implicate myocardial fibrosis, cardiomyocyte hypertrophy, altered myocardial microvascular structure and advanced glycation end-products (AGEs) in the pathogenesis of diabetic cardiomyopathy. We investigated whether type 2 diabetes and the metabolic syndrome are associated with altered myocardial structure, microvasculature, and expression of AGEs and receptor for AGEs (RAGE) in men with coronary artery disease.We performed histological analysis of left ventricular biopsies from 13 control, 10 diabetic and 23 metabolic syndrome men undergoing coronary artery bypass graft surgery who did not have heart failure or atrial fibrillation, had not received loop diuretic therapy, and did not have evidence of previous myocardial infarction.All three patient groups had similar extent of coronary artery disease and clinical characteristics, apart from differences in metabolic parameters. Diabetic and metabolic syndrome patients had higher pulmonary capillary wedge pressure than controls, and diabetic patients had reduced mitral diastolic peak velocity of the septal mitral annulus (E'), consistent with impaired diastolic function. Neither diabetic nor metabolic syndrome patients had increased myocardial interstitial fibrosis (picrosirius red), or increased immunostaining for collagen I and III, the AGE Nε-(carboxymethyl)lysine, or RAGE. Cardiomyocyte width, capillary length density, diffusion radius, and arteriolar dimensions did not differ between the three patient groups, whereas diabetic and metabolic syndrome patients had reduced perivascular fibrosis.Impaired diastolic function of type 2 diabetic and metabolic syndrome patients was not dependent on increased myocardial fibrosis, cardiomyocyte hypertrophy, alteration of the myocardial microvascular structure, or increased myocardial expression of Nε-(carboxymethyl)lysine or RAGE. These findings suggest that the increased myocardial fibrosis and AGE expression, cardiomyocyte hypertrophy, and altered microvasculature structure described in diabetic heart disease were a consequence, rather than an initiating cause, of cardiac dysfunction. Type 2 diabetes and the metabolic syndrome (MetS) are associated with impaired diastolic function and an increased risk of heart failure ,2. ThereThe present study was undertaken to investigate the association of type 2 diabetes and the MetS with myocardial fibrosis, cardiomyocyte size, capillary length density, diffusion radius, arteriolar dimensions, and myocardial expression of the advanced glycation end-product (AGE) Nε-(carboxymethyl)lysine (CML) and the receptor for AGEs (RAGE). We obtained LV biopsies from patients without heart failure or previous myocardial infarction who were undergoing coronary artery bypass graft surgery. By comparing MetS (pre-diabetic) and diabetic patients with control patients without these conditions, we examined the effects of the insulin-resistant state before diabetes (and anti-diabetes medication) commenced, and the effects of diabetes before heart failure developed. Although we obtained LV biopsies from both men and women, preliminary analysis showed gender-specific differences in myocardial structure ; therefoDetails of the Cardiac Tissue Bank have been previously described . The St.2 were considered to exceed the abdominal circumference threshold for MetS. A patient had diabetes if a history of diabetes was evident from use of glucose-lowering medications and/or insulin or if fasting plasma glucose was ≥ 7 mmol/L [Of the 46 patients, 13 control patients had neither MetS nor diabetes, 10 had type 2 diabetes, and 23 had MetS. MetS was defined according to the International Diabetes Federation . For pat7 mmol/L . Of the Blood Hb and HbA1c, and plasma levels of creatinine were measured as part of the routine pre-surgery workup. All other variables were measured on fasting blood collected on the day of surgery, before induction of anesthesia. Blood Hb and HbA1c, and plasma levels of glucose, insulin, lipids, and creatinine were measured by St. Vincent's Health Pathology using routine clinical methods. Estimated glomerular filtration rate (eGFR) was calculated from the Modification of Diet in Renal Disease formula . InsulinDetails of tissue collection and fixation have been previously described . All hisPerivascular fibrosis was calculated as the ratio of the area of perivascular fibrosis to the total vessel area  as determined by planimetry , for artImmunohistochemistry for collagen I and collagen III was performed in frozen sections using mouse monoclonal antibodies ab6308 and ab6310 , respectively. Myocardial total collagen I and collagen III densities were calculated using the positive pixel count algorithm  as the area of collagen staining expressed as a percentage of the total myocardial tissue area, after excluding the pericardium. Immunohistochemistry for CML was performed in paraffin sections using a mouse monoclonal antibody as described by Schalkwijk et al. . ImmunohP < 0.05.The significance of differences between study groups was determined by analysis of variance (ANOVA) for continuous variables and Fisher's exact test for categorical variables. Continuous data were logarithmically transformed when necessary to normalize variances. The Fisher's Protected Least Significant Difference test and the Bonferroni correction were used for multiple comparisons of continuous and categorical variables, respectively. Correlations were estimated using Pearson correlation coefficients. All tests were two-tailed. Differences were considered significant at Patient characteristics are shown in Table Whereas cardiac index was not different between the three patient groups, MetS patients had higher central venous pressure than control patients. Because of the close correlation between central venous pressure and pulmonary capillary wedge pressure , pulmonary capillary wedge pressure data were analyzed with central venous pressure as a covariate, and both MetS and diabetic patients had higher pulmonary capillary wedge pressures than control patients, consistent with impaired diastolic function Figure . Control2) was similar for the different patient groups. Total and interstitial fibrosis were similar for the three patient groups, whereas perivascular fibrosis of MetS and diabetic patients was less than in control patients , with a weaker non-significant correlation with mitral septal E' .Among all patients combined, fasting plasma glucose was positively correlated with the E/E' ratio , with a weaker non-significant inverse correlation with mitral septal E' , but was not correlated with any of the parameters of myocardial structure, microvasculature, or AGE and RAGE expression. Additionally, neither fasting plasma insulin concentrations nor HOMA2-IR was correlated with any parameter of myocardial structure, microvasculature, or AGE and RAGE expression.This study investigated the association of type 2 diabetes and the MetS with myocardial fibrosis (assessed by picrosirius red staining and immunostaining for collagen I and III), cardiomyocyte size, capillary length density, diffusion radius, arteriolar dimensions, and myocardial expression of CML and RAGE. We confirmed the impaired diastolic function of type 2 diabetic and MetS patients , as showOur findings for myocardial fibrosis and CML expression are in agreement with a recent study by van Heerebeek et al.  who studCardiomyocyte size has been reported to be increased ,13,17, nOur finding that RAGE expression was predominantly localized to vascular endothelium and capillaries is in agreement with previous studies , althougOur study highlights possible differences between diabetic humans and animal models of diabetes. In addition to the lack of increased myocardial fibrosis, we found no evidence for the cardiomyocyte and arteriolar hypertrophy and reduced myocardial capillary density reported in animal models of diabetes ,9-11, whMany mechanisms other than increased fibrosis, cardiomyocyte hypertrophy and alteration in myocardial vasculature have been proposed to explain the diastolic dysfunction of diabetes and the MetS. These include alterations in cardiomyocyte metabolism, abnormal calcium homeostasis and contractile mechanisms, oxidative stress, direct glucotoxicity, and inflammation ,22,43,44Our study had a number of limitations. These included a limited sample size because of the need for myocardial biopsies from each patient. However, in a separate study of 11 control, 7 diabetic, and 6 MetS patients with aortic stenosis we similarly found no association of diabetes or the MetS with increased myocardial fibrosis or altered cardiomyocyte width, capillary length density, diffusion radius, or arteriolar dimensions, although, in comparison with the patients in this study, aortic stenosis patients had more interstitial fibrosis, greater cardiomyocyte width, lower capillary length density, and greater diffusion radius (unpublished data). Another limitation was the inherent selection bias caused by the sampling of patients presenting for coronary artery bypass graft surgery. However, in a comparison of aortic stenosis patients with and without coronary artery disease we found no effect of coronary artery disease on myocardial fibrosis, cardiomyocyte width, capillary length density, diffusion radius, or arteriolar dimensions (unpublished data). Patients with coronary artery disease were an important patient group to study because of the high prevalence of coronary artery disease in diabetic patients ,46, and We compared MetS (pre-diabetic) and diabetic patients with patients without these conditions in order to examine the effects of the insulin-resistant state before diabetes (and anti-diabetes medication) commenced, and the effects of diabetes before heart failure developed. We found that the increased LV filling pressures of MetS and type 2 diabetic patients were not dependent on increased myocardial fibrosis or alteration in cardiomyocyte size, capillary length density, diffusion radius, arteriolar dimensions, or myocardial expression of CML and RAGE. Our findings suggest that the increased myocardial fibrosis and CML expression, cardiomyocyte hypertrophy, and altered microvasculature structure previously described in diabetic heart disease were a consequence, rather than an initiating cause, of cardiac dysfunction.AGEs: advanced glycation end-products; ANOVA: analysis of variance; ARB: angiotensin receptor blocker; CML: Nε-(carboxymethyl)lysine; eGFR: estimated glomerular filtration rate calculated using the Modification of Diet in Renal Disease study equation; HOMA: Homeostasis Model Assessment calculator version 2.2; LMWF: low molecular weight fluorophore; LV: left ventricle; MetS: metabolic syndrome; NT-proBNP: amino-terminal-pro-B-type natriuretic peptide; RAGE: receptor for AGEs.The authors declare that they have no competing interests.DJC, JBS, AJJ, DLP, MY, JFK, AEN, CGS, MJB, and DJK participated in the design of the study and acquisition of the data. DJC, JBS, DLP, MJB, and DJK participated in the analysis and interpretation of data. DJC participated in manuscript preparation. JBS, AJJ, DLP, MY, JFK, AEN, CGS, MJB, and DJK participated in review of the manuscript. All authors have read and approved the final manuscript.


Atrial septal defects (ASDs) may escape detection before adulthood, particularly those in unusual locations, which may elude echocardiographic visualisation. CMR is established for the quantification of shunt flow and, if appropriately acquired, can provide clear visualisation of ASDs and adjacent structures to inform decisions regarding intervention. Our objective is to recommend cardiovascular magnetic resonance (CMR) cine acquisition strategies suitable for the visualisation of the less common as well as the common types of ASD.In the CMR Unit of a tertiary referral centre for adults with congenital heart disease we retrospectively reviewed the CMRs of patients with unoperated ASDs over a 3 year period to assess the suitability of cine acquisition strategies for the visualisation of different types of ASD and any associated anomalies of pulmonary venous connection.157 patients with unoperated ASDs had CMR studies in 3 years. If already suspected, we had routinely acquired an ‘atrial stack' of cines, meaning a contiguous stack, 5mm thick, parallel to the routine ventricular short axis (SA) stack, stepping backward from the basal ventricular plane until the superior vena cava was identifiable. This orientation visualized ostium secundum ASDs well (n=117), and was also good for inferior sinus venosus defects (n=2) and unroofed coronary sinus (n=3). In superior sinus venosus defects (n=21), a transaxial cine stack was found to give clearer visualisation of both the defect and any associated anomalous pulmonary vein connection(s) . The transaxial cine orientation was also the more suitable one for atrio-ventricular septal defects  as it depicted insertions of the A-V valve leaflets adjacent to the defect(s).In patients with suspected ASDs, we recommend the acquisition of an atrial SA cine stack and a transaxial cine stack that covers atrial to aortic arch levels. Additional oblique cines aligned with the defect can supplement these, as indicated in the table.None


Changes in left ventricular compliance caused by diffuse fibrosis after MI may result in diastolic dysfunction and left atrial enlargement. We sought to test the hypothesis that left atrial volume is associated with ECV  during the sub-acute phase of infarction and can predict the increase of ECV during the ensuing months of infarct healing. We quantified left atrial volumes serially in patients after ST-elevation myocardial infarction and assessed their relationship with indices of post-MI remodeling including left ventricular dimensions, ECV, and infarct size.Sixty-seven patients underwent gadolinium-enhanced cardiac magnetic resonance (CMR) imaging serially at 2-4 weeks and 6 months after STEMI. Left atrial volumes (LAV) were calculated at the end of ventricular systole (LAVmax), just before atrial contraction (LAVbac), and at the end of ventricular diastole (LAVmin) using the biplane area-length method. Using a segmented, breath-held Look-Locker sequence in 3 short axis slices, T1 measurements were made pre- and post-contrast up to 30 minutes after administration of gadolinium . Regression of myocardial R1 (defined as 1/T1) against R1 of the blood pool was used to determine the gadolinium partition coefficient, which when multiplied by (1-hematocrit/100), to estimate ECV. Total infarct size was measured using a full-width half maximum (FWHM) methodology and was expressed in total grams and %LGE.Patients were predominantly male (83%), with a mean age of 58±11 years, and had a mean LVEF of 53±10% .Dr. Jerosch-Herold is supported in part by a research grant from the National Institutes of Health (R01HL090634-01A1).