MRM 2012, Coolen et al. MRM 2014). It is argued here that when full coverage of the left ventricle myocardium (LVM) is needed, such techniques benefit from applying phase encoding in the slice direction as opposed to using a multi-slice approach.MRI cardiac T2-mapping visualizes edema and has been used for tissue characterization in settings such as myocarditis and ischemia. Clinically it is typically performed via spin-echo based techniques, but preclinically, the high heart rates of rats and mice make such approaches sensitive to motion. Successful implementations instead employ T2-preparation followed by a segmented gradient-echo readout . The acquisition time was ∼6 min. 30 s. per echo-time. T2 maps were calculated via the method described by Pei et al. MRM 2015. Regions-of-Interests (ROIs) were manually placed in the LVM and in the back muscle. ROI-level T2s were calculated as the harmonic mean of pixel-level T2s.All work was approved by the local ethical committee. At day 0, 14 rats  were subjected to sham operation . Scanning was performed at days 1, 4, and 8, under Isoflurane anaesthesia on a Bruker BioSpec 4.7T scanner equipped with a 72 mm quadrature coil. T2-preparation module: non-selective 90°-180°-90° excitation pulses with four echo times . Readout module: 3D gradient echo with phase encoding in the slice direction, FOV 40 × 40 mmT2 appeared homogeneous both in the LVM and in the back muscle Figure . LVM T2 et al. MRM 2014). When multi-slice imaging cannot be interleaved, as is the case for sequences relying on global T2 preparation, employing a phase encoding gradient in the slice direction is inherently a more efficient signal sampling strategy . The signal-to-noise ratio (SNR) is increased by a factor √N for a given acquisition time, where N is the number of slices. Alternatively, for a fixed SNR, a potential reduction in acquisition time by a factor N can be reached. In the present study a standard volume coil was used. Further improvements in SNR or reductions in acquisition times can be obtained by combining the proposed imaging sequence with surface coils and imaging acceleration techniques.Precise T2-maps covering the full LVM were generated in sham operated rats with a signal acquisition technique earlier not used in this setting. T2 remained constant in the LV for eight days contrasting a previous report in healthy mice (Coolen


The patient was a 26-year-old male, from the town of Medina, Minas Gerais state, comingfrom the city of Barueri, São Paulo state, hospitalized due to dyspnea andedema .At the age of 24 years , he was referred to InCor complaining of dyspneaon heavy exertion for 2 months. Before that, he never had any cardiovascular symptom,and, after beginning specific medication, his clinical findings improved. The patientdenied other cardiovascular symptoms, diabetes mellitus, arterial hypertension,dyslipidemia, smoking. He reported using illicit drugs (amphetamines and marijuana) andabusive alcohol consumption on weekends (20 beer cans). He reported prophylaxis forrheumatic fever with monthly use of benzathine penicillin from the age of 12 years to 17years.The clinical and laboratory assessments prior to referral revealed cardiopathy withventricular dilatation.His serology for Chagas disease was negative, and coronary angiography was normal. Theechocardiogram revealed left ventricular systolic and diastolic diameters of 60 mm and44 mm, respectively, and left ventricular ejection fraction of 51%. 2; heart rate, 60 bpm; blood pressure, 116/70 mm Hg;and normal pulmonary auscultation. Cardiac auscultation revealed the presence of thirdcardiac sound and systolic murmur (++/6+) over the mitral area, apex beat palpated onthe precordium , displaced 2 cm from the left midclavicularline, with extension of 2 digital pulps. The examination of the abdomen and lower limbswas normal, and there was no jugular venous distention.The physical examination on July 18, 2011, showed: weight, 99.7 kg; height, 1.70 m; bodymass index, 31.14 kg/m1 and V2 (The electrocardiogram (ECG) on July 14, 2011, revealed atrial flutter with high-degreeatrioventricular block, mean heart rate of 40 bpm, QRS duration of 100 ms,SÂQRS -30º, probable antero-superior divisional block (ASDB) and finalconduction disorder (rsr') on V1 and V2 .His chest X-ray showed pulmonary fields and hila, aorta and cardiac area within thenormal range. 3; creatinine, 1.3 mg/dL; sodium, 137 mEq/L;potassium, 4.7 mEq/L; total cholesterol, 189 mg/dL; HDL-C, 45 mg/dL; LDL-C, 117 mg/dL;triglycerides, 136 mg/dL; AST, 28 U/L; ALT, 44 U/L; TSH, 1.38 UI/mL; free T4, 1.03ng/dL; TP(INR), 1.2; APTT(rel), 1.01; normal urinalysis; negative serology for Chagasdisease.The laboratory tests  revealed: hemoglobin, 17.9 g/dL; red blood cellcount, 51%; leukocytes, 7640/mmThe following drugs were prescribed: daily acetylsalicylic acid 300 mg, carvedilol 12.5mg, losartan 25 mg, spironolactone 25 mg, and furosemide 40 mg. The new echocardiogram (Sept 2011) revealed left ventricular dimensions of 53x40 mm,ejection fraction of 48%, septal thickness and posterior wall of 11 mm, left atrialdiameter of 34 mm, and diffuse left ventricular hypokinesia .The 24-hour Holter showed persistent atrial fibrillation, with mean heart rate of 62 bpm,longest pause of 3.2s, 330 ventricular extrasystoles (14 VE/h), 1 paired extrasystoleand 1 ventricular tachycardia with 3 beats.Acetylsalicylic acid was replaced with warfarin, and electric cardioversion was programed3 weeks after effective anticoagulation.The first cardioversion was performed on December 13, 2011, with relapse of atrialfibrillation minutes after, and very low heart rate. The transesophageal echocardiogram  revealed: aorta, 44 mm; leftatrium, 47 mm; ventricular septum and posterior wall, 11 mm; left ventricle(systole/diastole), 56/49 mm; ejection fraction, 27%; biatrial and biventricularenlargement, with moderate mitral and marked tricuspid valve regurgitation; aorticectasia and no intracavitary thrombus Figure .New electric cardioversion was performed on the following day , withatrial fibrillation recurrence few minutes later. On April 19, 2013, the patient sought urgent medical care, reporting worsening of thedyspnea in the previous 4 months, with progression to occurrence at rest, orthopnea,abdominal volume enlargement and lower limb edema. In addition, he reported dry cough inthe preceding week and marked worsening of dyspnea in the past two days.The physical examination revealed: dyspnea; heart rate, 100 bpm; blood pressure, 100/80mm Hg. The pulmonary auscultation evidenced rales on the bases. The cardiac auscultationrevealed irregular heart rhythm, systolic murmur (+++/6+) over the mitral and tricuspidareas. The liver was palpated 3 cm from the right costal margin, and there was lowerlimb edema (++++/4+). µg/kg/min, were administered.The cough was attributed to heart failure (HF) because there was neither fever, norleukocytosis nor images suggesting pneumonia on chest X-ray, which showed globalcardiomegaly and a rectified middle arch . IntraveThe laboratory tests  evidenceNew electric cardioversion was indicated, as was a new transesophageal echocardiogram torule intracavitary thrombi out.The cough worsened, then with purulent sputum, and the association of tazobactam,piperacillin and azithromycin was introduced.On April 26, 2013, the echocardiogram showed biatrial and biventricular enlargement,marked left ventricular and moderate right ventricular dysfunction, moderate mitral andmarked tricuspid regurgitation, and no intracavitary thrombus  Figure .Right after the exam, the patient had a decrease in his consciousness level and arterialhypotension, requiring orotracheal intubation for respiratory support and increaseddoses of vasoactive amines. On April 26, 2013, he had hyperthermia (38.6°C). Vancomycin was introduced, and the newchest X-ray was unaltered .Despite the administration of increasing doses of vasoactive amines, on April 27, 2013,the patient had shock and cardiac arrest, which was reversed. On the afternoon of thatsame day, he had hypotension and bradycardia, and an irreversible asystolic cardiacarrest.The patient was a 26-year-old male, reporting prophylaxis for rheumatic fever fromthe age of 12 years to 17 years, who, at the age of 24 years, developed dyspnea onheavy exertion, which improved with medication. However, after two years, dyspneaworsening and edema occurred . The clinical and laboratory assessments before the referral revealed cardiopathy withventricular dilatation. The echocardiogram evidenced left ventricular systolic anddiastolic diameters of 60 mm and 44 mm, respectively, and ejection fraction of 51%.His serology for Chagas disease was negative, and his coronary angiography, normal.On physical examination, a third cardiac sound and a systolic murmur (++/6+) overthe mitral area were heard. The ECG showed atrial flutter, atrioventricular blockwith probable ASDB, and heart rate of 40 bpm. 1 Therefore, other etiologies ofdilated cardiomyopathy (DCMP) had to be considered for this case. Over the following two years, the cardiopathy with ventricular dilatation evolved.Because the patient had a history of prophylaxis for rheumatic fever, rheumaticcardiopathy was considered as a possible etiology. However, the progressive andrapid course of our patient's illness is not commonly seen in patients withoutvalvular damage consequent upon the acute event of rheumatic fever. The previousechocardiogram revealed left ventricular systolic and diastolic diameters of 60 mmand 44 mm, respectively, and ejection fraction of 51%. In September 2011, thepatient showed: left ventricular dimensions of 53x40 mm; ejection fraction of 48%;septal and posterior wall thickness of 11 mm; left atrial diameter of 34 mm; anddiffuse left ventricular hypokinesia without valvular damage.2Approximately one in every three cases of congestive HF originates fromDCMP.3 In addition to leftventricular or biventricular dilatation, it is characterized by contractiledysfunction, which results in congestive HF. Patients with DCMP have an increase inmyocardial mass and in interstitial collagen,4 known as remodeling myocardial, which eventually leads toHF. Reversing that process to reduce morbidity and mortality remains a majorchallenge in health care practice.5Our patient had echocardiographic changes compatible with DCMP and clinical findingsof HF. On December 4, 2012, the transesophageal echocardiogram showed: aorta, 44 mm;left atrium, 47 mm; interventricular septum and posterior wall, 11 mm; leftventricle (systole/diastole), 56/49 mm; ejection fraction, 27%; biatrial andbiventricular enlargement; and moderate mitral and marked tricuspid valvularregurgitation. On April 19, 2013, the patient sought medical care complaining ofdyspnea worsening in the last 4 months, with progression to dyspnea at rest,orthopnea, increased abdominal volume and lower limb edema. The physical examinationrevealed congestive HF with pulmonary congestion, hepatomegaly, edema and bilateralatrioventricular valvular regurgitation.Dilated cardiomyopathy is a progressive primary myocardial disease of unknown cause,characterized by a reduction in left ventricular or biventricularcontractility.6 Althoughmany cases lack an evident cause, DCMP either has a family origin or results frommyocardial lesions produced by several known or unknown toxic, metabolic orinfectious agents. It can be a late consequence of acute viral myocarditis, possiblypartially mediated by immune mechanisms. It can occur at any age, being most oftenclinically apparent in the third or fourth decade of life. Reversible forms of DCMPmay be found in cases of alcohol abuse, pregnancy, thyroid disease, cocaine use, anduncontrolled chronic tachycardia.3The distribution of the DCMP causes is as follows: idiopathic, 50% of the cases;secondary to myocarditis, 9%; secondary to ischemic heart disease, 7%; consequent toinfiltrative disease (amyloidosis and sarcoidosis), 5%; peripartum cardiomyopathy,4%; secondary to systemic arterial hypertension, 4%; associated with humanimmunodeficiency virus (HIV) infection, 4%; post-connective tissue disease, 3%;substance abuse, 3%; doxorubicin use, 1%; and the other 10% comprise Chagas disease,Lyme disease, genetic causes, left ventricular non-compaction, andtachycardia-mediated cardiopathy.Currently, DCMP accounts for around 10,000 deaths and 46,000 hospitalizations peryear in the United States. In addition, DCMP is the major indication for cardiactransplantation.7Rheumatic fever remains the major cause of acquired cardiopathy in many regions, suchas South America, Africa and India. It is frequently asymptomatic, especiallyrheumatic myocarditis. The most common clinical manifestations are arthritis andfever. Rheumatic fever and acute rheumatic myocarditis are under-represented inmedical literature because they are rare in the United States and Europe.8 Leftventricular dilatation and HF have been mainly observed in patients with severevalvular heart disease. Although myocarditis is a common postmortem examinationfinding, the major cause of left ventricular dilatation and HF seems to be severemitral regurgitation with or without aortic regurgitation.9 The ECG findings can include any degree of heartblock, such as atrioventricular dissociation. The chest X-ray can show cardiomegaly.The echocardiography allows assessing the intensity of the valvular lesion,pericardial effusion, ventricular and atrial dilatation, and ventriculardysfunction.10 Therefore,rheumatic fever does not seem to be the most likely cause for this cardiopathy withdilatation and rapid and progressive aggravation. In addition, the clinical andimage findings in this case are not those of rheumatic cardiopathy.Although the first episode of acute rheumatic fever can lead to persistent valvularlesions, rheumatic cardiopathy most often results from cumulative valvular damageattributed to recurring acute rheumatic fever episodes, which can even be silent . This makes its identification challenging. Rheumatic cardiopathyalmost always affects the left-sided heart valves. Direct damage of right-sidedheart valves is rare; they are usually affected as a result of the malfunction ofthe left-sided valves. In addition, narrowing of the mitral valve can develop, withblood flow obstruction, due to fusion of the leaflets or reduction in their mobilitydue to calcification.11 The clinicalmanifestations of cardiac sarcoidosis depend on the location and extension of thegranulomatous inflammation. Other cardiac manifestations comprise conductiondisorders, ventricular and supraventricular arrhythmias, pericarditis and valvulardysfunction. In addition, the involvement of papillary muscles can lead to acutesymptoms like those of hypertrophic cardiomyopathy with asymmetric septalhypertrophy, caused, however, by edema and not by hypertrophy of myocytes. Thelikelihood of heart disease caused by sarcoidosis should be considered for a healthyyoung or middle-aged individual with cardiac symptoms or a patient with knownsarcoidosis who develop arrhythmias, conduction disorder or HF. That is an importantetiology for our case, who had rapid and progressive worsening, arrhythmia,ventricular dilatation and clinical findings of HF, with no family history ofgenetic disease, and normal results of the other tests for heart disease.13Sarcoidosis, another cause of cardiopathy with dilatation, can be considered in thiscase. Sarcoidosis is a granulomatous, non-caseous, heterogeneous disorder of unknownetiology, which can affect any organ. The heart involvement can be isolated orprecede that of other organs (such as lung), or even occur simultaneously withthat.Diagnostic hypothesis: Heart failure secondary to cardiopathy due tosarcoidosis.The heart weighed 680g and showed dilatation of the four chambers . The epiThe other organs revealed signs of chronic passive pulmonary and liver congestion dueto congestive HF with terminal shock. In addition, there were thromboembolism of thesmall branches of the pulmonary bases, alveolar hemorrhage, serous ascites (3200 mL)and pericardial effusion (120 mL). Other signs of terminal heart failure includedfocal acute tubular necrosis, edema of renal tubular cells and cerebral edema. Anatomopathological diagnosis: Arrhythmogenic right ventricularcardiomyopathy (arrhythmogenic right ventricular dysplasia), congestive heartfailure and morphological signs of terminal shock.Cause of death: Cardiogenic shock 14The entity initially described as arrhythmogenic right ventricular "dysplasia" iscurrently known as arrhythmogenic right ventricular cardiomyopathy (ARVC), accordingto the European Society of Cardiology's position statement oncardiomyopathies.Its diagnosis is based on major and minor criteria, which comprise clinical,electrophysiological, hemodynamic and anatomopathological findings. In the case here described, the diagnosis of ARVC was not clinically established.From the anatomopathological viewpoint, however, both the gross and microscopicfindings are typical, with adipose infiltration, and focal fibrosis andinflammation. Usually, the right ventricular involvement predominates, with littleor no left ventricular involvement. In addition, global cardiomegaly is not usuallyfound.Phenotypic overlapping  might have hindered establishing the diagnosis during the patient'shospitalization.15 The diagnosisof ARVC requires the association of two major criteria, or one major criterion andtwo minor criteria, or even four minor criteria.The diagnostic criteria for ARVC established by a task force and published in 1994were divided into major and minor. Those criteria include the presence of global andsegment structural changes of the right ventricle, histological and ECG changes,arrhythmias and genetic factors. In 2010, a review of those criteria was publishedto help to identify ARVC and to diagnose it in the patients' familymembers.16In the case here reported, in vivo endomyocardial biopsy was not performed, but ARVCwas morphologically confirmed on postmortem examination, with the typical finding ofmyocardial areas of fibrofatty replacement in the right ventricular wall and ofthickened arteries in the ventricular septum (previously described in thisdisease).17Left ventricular involvement in ARVC has been reported in a study of 42 hearts frompostmortem examination or from receptors of heart transplantation. That study hasreported that approximately 50% of the specimens had gross involvement of the leftventricle, while 75% evidenced histological involvement. In addition to fibrofattyreplacement in the myocardium in the sub-epicardial or middle-mural region, therewas dilatation of that chamber in all cases with grossly evident disease, which wasmarked in 25% of them.18 Postmortem studies have reported evidence of apoptosis in thatcardiomyopathy.19 Inaddition, that same mechanism has been detected in biopsies (in vivo).20The ARVC consists in fibrofatty replacement in the myocardium. Myocardial atrophy isprogressive and absent at birth. The myocardial process results from the death ofcardiomyocytes beginning at birth.18The fibrofatty replacement occurs gradually from the epicardium towards theendocardium, becoming transmural. Consequently, there is weakening of the rightventricular free wall, causing dilatation and aneurysms, characteristically locatedbetween the inferior, apical and infundibular walls, forming the triangle ofdysplasia.18In addition to weakening the wall, those changes in association with the inflammatoryfactor hinder and delay the intraventricular electrical conduction, resulting inlate potentials, epsilon wave and right bundle-branch block. Therefore, aventricular arrhythmia can install due to reentry phenomenon.21 The first says the disease has a genetic component, andthat the disorder in myocardial development begins in the intrauterine period.Two pathogenetic theories have been described.22 have evidencedtwo types of inheritance for the ARVC phenotype. The first type is autosomaldominant inheritance with variable penetrance, while the second is represented byrecessive forms associated with skin diseases. Ten genetic loci have been detected,but only five genes with mutations. The first ARVC-related gene was found in theNaxos disease, a rare recessive syndrome related to a mutation in the desmosomalprotein called plakoglobin. That syndrome, however, has been characterized as thevariant 2 of ARVC. The first form of autosomal dominant mutation in that variant wasfound in the gene that decodes the cardiac ryanodine receptor (RyR2), the receptorthat accounts for calcium homeostasis and coordinates the excitation-contractionmechanism of cardiomyocytes. The mutations change the calcium-channel closingmechanism, and, thus, a high sympathetic stimulation via emotional or physicalstress can increase excessively intracellular calcium, leading to severearrhythmias. In addition to ARVC, mutations in the gene that decodes RyR2 can causetwo other diseases: catecholaminergic polymorphic ventricular tachycardia andfamilial polymorphic ventricular tachycardia. The discovery of ARVC variant 2 isconsidered essential to unveil the pathogeneses of ARVC. Another recent discovery bythe research team of Rampazzo22has been in ARVC variant 1: the mutation of the genes that decode TGF-beta3. Thiscytokine stimulates the proliferation of mesenchymal cells. Invitro experiments have shown that the mutations in the genes thatencode TGF-beta3 can cause myocardial fibrosis.Genetic studies21could explain left ventricular involvement and atrial rhythm disorders. The viraletiology has been suspected in a study23 with detection of viral genome in the myocardium of somepatients with ARVC. Such theory, however, has been refuted in anotherstudy24 that advocatesthat the viruses are innocent bystanders, and that tissue degradation favors viralcolonization.In addition, a theory speculates whether ARVC results from a previous infection. The theory considers a viral etiology that could beaggravated by an auto-immune reaction. The auto-immune or viral reaction couldexplain the inflammatory phenomenon, which would not occur due to only apoptosis ofcardiomyocytes. That theory18Adipose infiltration by itself does not characterize ARVC, because some hearts have acertain amount of fat in the anterior and apical walls of the right ventricle and donot show degenerative changes in cardiomyocytes. Thus, to establish the diagnosis ofARVC one must identify the fibrous tissue replacement pattern associated withmyocardial degeneration.25 during physicalexercise, there is a subgroup, in which our patient is included, with biventricularfailure, unfavorable outcome and indication for heart transplantation. Although ARVC is clinically recognized as a cause of cardiac sudden death in theyoung26Cardiac magnetic resonance is useful to identify ARVC morphologically, and even toestablish its prognosis.Section editor: Alfredo José Mansur(ajmansur@incor.usp.br)Associated editors: Desidério Favarato(dclfavarato@incor.usp.br)anpvera@incor.usp.br)Vera Demarchi Aiello (


Among the patients without known disease undergoing invasive angiography, nearly 40% do not have coronary artery disease (CAD) [1]. A possible underlying etiology for such patients is ischemic heart disease associated with coronary microvascular dysfunction (CMD). Despite intense interest and recent advancements, reliable diagnosis of CMD on the basis of first-pass perfusion (FPP) cardiac MRI is an ongoing challenge. We hypothesized that high-resolution systolic FPP imaging can detect diffuse vasodilator-induced subendocardial defects and transmural perfusion gradients (TPGs) consistent with CMD in a swine model of diet-induced diabetes with no obstructive CAD. To this end, we optimized and tested a recently introduced high-resolution FPP method capable of imaging all myocardial slices at the end-systolic phase.2). Retrospective end-systolic self-gating was performed automatically  and compressed sensing combined with apodization was used to generate dark-rim-minimized images. TPG analysis was performed according to the established approach [4].Yucatan mini-pigs  were fed either a high-fat high-sugar diet (n = 4 "HFHS" group) or a normal chow diet (n = 4 "control" group) for 20 weeks. Compared to controls, the HFHS pigs were obese (68 ± 8 kg vs 45 ± 7), and had abnormally elevated fasting glucose (177 ± 19 mg/dL vs 94 ± 12) and insulin levels, indicating early-stage type-2 diabetes and expected to have CMD based on previous studies [2]. Obstructive CAD was ruled out in all pigs using invasive angiography on the day of the MRI study, consistent with their normal serum lipid levels. There was no difference between baseline arterial systolic blood pressure between the two groups, suggesting absence of hypertension in the HFHS group. Adenosine stress/rest FPP data was acquired using a recently introduced T1-weighted steady-state ungated FLASH sequence [3] with optimized slice-interleaved radial sampling (acquired in-plane resolution: 1.2 × 1.2 mmRepresentative myocardial perfusion images for a HFHS pig are shown in Fig We demonstrated that subendocardial ischemia and stress-induced TPGs can be visually detected in the absence of obstructive CAD using an optimized FPP approach. The combination of high isotropic in-plane resolution, end-systolic imaging of all slices, and dark-rim-minimized reconstruction enables reliable detection of subendocardial defects. Our results suggest that this methodology may be a promising approach for accurate diagnosis of CMD in clinical settings.


Patients with repaired tetralogy of Fallot (rTOF) have impairments in cardiac mechanics (strain and dyssynchrony). However, the relationship between cardiac strain, dyssynchrony, and cardiac function (measured by ejection fraction) in patients with rTOF has not been explored comprehensively in a large population. We hypothesized that measures of cardiac mechanics are associated with cardiac function in patients with rTOF.A database search identified patients with rTOF at a single institution who underwent cardiac MRI from May 2005 to March 2012. Left and right ventricular (LV and RV) ejection fraction (EF) were quantified from the MRI and used as measures of cardiac function. Seven parameters of cardiac mechanics were computed using a custom feature-tracking algorithm: LV, RV and inter-ventricular dyssynchrony, as well as LV and RV peak circumferential and longitudinal strains. Dyssynchrony measures and peak circumferential strains were quantified from a stack of short-axis images covering both ventricles, and peak longitudinal strains were quantified from a long-axis four-chamber view. All measures of dyssynchrony were reported as positive numbers, with larger values representing more dyssynchrony. Peak circumferential and longitudinal strains were reported as absolute percentage. A linear regression model was used to determine the correlation between measures of cardiac mechanics and ventricular function.153 patients with rTOF  were included. LV circumferential strain was strongly correlated with LV EF  and moderately with RV EF  . Similarly, RV circumferential strain correlated with RV EF  and LV EF  . Both LV and RV longitudinal strains were moderately correlated with LV and RV EF  may indicate unfavorable ventricular-ventricular interaction. The weak association between ventricular dyssynchrony and cardiac function suggests that dyssynchrony and dysfunction may occur independently in patients with rTOF.


Quantitative myocardial perfusion imaging requires correct measurement of arterial Gd concentration as the input function (AIF). An underestimation of AIF Gd concentration will lead to overestimation of myocardial blood flow (MBF). One source of this underestimation is the T2* effect due to high Gd concentration in the AIF measurement. Despite the short echo time (0.65 ms) used in the dual sequence approach specifically designed to avoid T2* loss, we have found significant loss remains at peak concentrations 5-10 mmol/l). To correct this signal loss in the AIF, a conventional dual sequence AIF acquisition [0 mmol/l.2, 8 mm slice thickness, 3 SAX slices, interleaved parallel acceleration R = 3, acquired matrix 192 × 111, ¾ partial Fourier, temporal resolution 53 ms. Pixel-wise MBF maps were computed inline using a two compartment model. All patient studies were approved by local IRB with written consent. Imaging experiments were performed on a 3T clinical MRI system . The administered Gd dose (Gadavist) was 0.075 mmol/kg (FLASH) with an infusion rate of 2 ml/s.To validate the hypothesis that T2* effect in the perfusion AIF measurement is not negligible, the AIF acquisition was modified to acquire two echoes at different echo times. Parallel imaging (R = 2) was used to maintain a short imaging duration and is applied to reconstruct two images corresponding to two echo times. These two images were combined to correct for T2* effect by utilizing exponential decay and a novel adaptive algorithm to avoid corruption of the low intensity baseline periods. The T2* corrected image were converted into the Gd concentration and input for the MBF estimation. MBF maps with or without T2* AIF correction were computed for N = 8 stress/rest perfusion studies using our standard saturation recovery dual-sequence imaging protocols with FLASH readout: for AIF, echo times 0.65/1.65 ms, flip angle, interleaved parallel acceleration R = 2, acquired matrix 64 × 36; for myocardial perfusion imaging, 14° flip angle, FOV 360 × 270 mmAn example of rest/stress perfusion studies Figure  plots thWe validated the hypothesis that T2* effects in the perfusion AIF measurement can lead to significant overestimation of quantitative myocardial flow estimates.


Myocarditis presenting as isolated acute chest pain with elevated troponins but normal systolic function by echocardiogram is rare in previously healthy children. Diagnosis is challenging in this situation with significant drawbacks even for the gold standard endomyocardial biopsy. Our study aim is to evaluate the diagnostic role of cardiac MRI in comparison with echocardiography in these patients.All children who underwent cardiac MRI (CMR) for evaluation of sudden acute chest pain with elevated troponins from April 2010 to May 2015 at our institution were included in the study and their findings were compared to age-matched controls with normal CMR. Echocardiographic parameters of left ventricular (LV) function included: subjective assessment, fractional shortening (FS%), ejection fraction (EF%) and speckle-tracking-derived strain from vector velocity imaging . CMR parameters included: LVEF%, T2 imaging, late gadolinium enhancement (LGE), and tissue-tracking-derived global peak longitudinal, radial and circumferential strain.Group I included 9 subjects compared with 10 controls in group II. There were 8 males (89%) in group I vs. 7 males (70%) in group II (p=0.6). All 9 subjects had LGE consistent with myocarditis: 8 in left ventricle and 1 in right ventricle. Troponin level ranged from 2.5 - 22.9 ng/ml and did not correlate with the extent of myocardial LGE involvement. EKG was concerning for ST segment elevation in 5 and abnormal Q waves in 1 subject. Qualitative echocardiographic function was normal in all children in both groups, while 2 subjects had decreased function by CMR. Mean echo FS% was not different between groups (36 ± 5 % vs. 35 ± 4 %) while MRI LVEF% had a trend to be lower in subjects . MRI derived strain parameters were lower in subjects compared to controls for global peak longitudinal , circumferential  and radial strains  respectively. Echocardiography derived strain parameters also were lower in subjects compared to controls for global peak longitudinal , circumferential  and radial strains  respectively. Follow-up MRI in 4 patients had persistent LGE findings at 1.0 - 2.1 years.In previously asymptomatic children, myocarditis can present with symptoms of acute chest pain suspicious for coronary ischemia. CMR is a non-invasive, radiation-free diagnostic test of immense diagnostic utility in these situations where clinical picture, EKG and echocardiogram are insufficient to make the diagnosis. In addition to LGE, strain imaging may also aid in diagnosis. Long term studies are needed to assess prognostic significance of these CMR findings.


Across the quartiles of FT3, decreased percentage of segments with LGE and perfusion/metabolism abnormalities were found. As for FT4 and TSH levels, no significant distribution trend of myocardial injuries could be detected. In logistic analysis, FT3 was independently associated with the presence of LGE , perfusion abnormalities  and metabolism abnormalities . After a median follow-up of 46 months, LGE-positive and FT3 < 2.77 pg/mL was identified as the strongest predictor of cardiac events . Low FT3 level is associated with myocardial fibrosis and perfusion/metabolism abnormalities in patients with IDCM. The combination of FT3 level and LGE provides useful information for assessing the prognosis of IDCM.Thyroid dysfunction is associated with poor prognosis in heart failure, but theories of mechanisms are mainly based on animal experiments, not on human level. We aimed to explore the relation between thyroid function and myocardial injuries in idiopathic dilated cardiomyopathy (IDCM) using cardiac magnetic resonance imaging (MRI), single-photon emission computed tomography (SPECT) and positron emission tomography (PET). Myocardial fibrosis was detected by late gadolinium enhancement (LGE) MRI, and myocardial perfusion/metabolism was evaluated by  With a growing body of evidence125in vitro11Animal experiments have demonstrated that THs have complex effects on myocytes, matrix, vascular growth, and ventricular function through genomic or non-genomic mechanisms7899mTc-MIBI single-photon emission computed tomography (SPECT) perfusion imaging and 18F-FDG positron emission tomography (PET) metabolic imaging enables the detection of ischemic and necrotic myocardiumClinically, application of cardiac magnetic resonance imaging (MRI) and radionuclide tests has become frequent in DCM patients for etiological diagnosis and risk stratification. Late gadolinium enhanced (LGE) MRI provides useful noninvasive evaluation of myocardial fibrosis. The presence of LGE has also been indicated as a predictor for long-term mortality1699mTc-MIBI myocardial perfusion SPECT imaging and 18F-FDG myocardial metabolic PET imaging were undertaken by all patients within an interval of 3–7 days.We conducted a prospective observational study of 71 IDCM patients who were admitted to Fuwai Hospital  from January 2010 to October 2011. This subgroup belongs to a cohort study of 458 IDCM patients previously reportedThyroid status was evaluated when HF symptoms could be controlled under regular oral medication before they were discharged, rather than in the acute phase. The median duration between hospital admission and thyroid function test was 10 days. Twelve-hour-fasting blood samples were drawn and the serum levels of TH and TSH were measured using radioimmunoassay  in the Nuclear Medicine Department of Fuwai Hospital. The reference intervals of TH and TSH in our laboratory are as follows: TSH = 0.55–4.78 mIU/L; FT3 = 1.79–4.09 pg/mL; FT4 = 0.8–1.88 ng/dL; TT3 = 0.65–1.91 ng/mL; TT4 = 4.29–12.47 ug/dL. Distribution trend of myocardial injuries was explored across FT3 quartiles. In Cox survival analysis and Kaplan-Meier plot, we used the median value of FT3 (2.77) as cut-off for two reasons: first, we did comparison of segments and logistic analysis based on FT3 quartiles, so as sequential procedure, the prognosis analysis was also performed with previous cutoff; second, with only 71 IDCM patients, the strength of our current study is the complete information of cardiac MRI and radionuclide tests, while the small population limited the use of ROC curve to choose an accurate cutoff value, and this question might be further explored in a large population.99mTc-MIBI and 18F-FDG uptake were scored using a 4-grade system . Segments were divided into four groups with different patterns of perfusion/ metabolism: normal perfusion/metabolism, perfusion/metabolism mismatch, mild-to-moderate perfusion/metabolism match, and severe perfusion/metabolism match. Representative examples of LGE-positive and perfusion/metabolism abnormality images can be found in Detailed information about the procedures and assessment of cardiac MRI and SPECT/PET imaging can be found in Follow-up started at inception with thyroid function testing. We contacted patients by phone every six months according to our follow-up schedule. Patients’ medical records would be examined if they were re-admitted into hospital. Median duration of follow-up was 36 months (1 to 58 months). Endpoints of the study were cardiac death and all-cause death. Cardiac death was defined by the occurrence of sudden death without an autopsy, cardiac arrest, or death attributable to significant arrhythmia, progressive heart failure. All-cause deaths were considered as all deaths from any natural cause. Patients lost to follow-up were censored upon last contact with them.2 test. Cochran-Armitage trend test was used to explore the distribution trend of myocardial injuries across FT3 quartiles. To adjust for the traditional risk factors, multivariable logistic regression analysis was performed while evaluating the relationship between LGE, myocardial perfusion/metabolic parameters and thyroid hormone levels. Cox proportional hazards model was used to estimate hazard ratio (HR). Kaplan-Meier analysis was used to study cumulative survival of different groups. A P-value less than 0.05 was considered statistically significant.Statistical analysis was assessed with SPSS statistical package for Windows 18.0. All continuous variables are presented as means ± SD and analysis of variance was used to compare means across multiple groups. Non-continuous and categorical variables are presented as frequencies or percentages and were compared using the χWith the semi-quantitative 17-segments model, a total of 1207 segments were analyzed in the present study and detailed distribution of the segment types and percentages are shown in We also compared FT4 and TSH levels shown in . No signTo establish the relationship between thyroid hormones, LGE and perfusion/metabolism abnormalities at patient level, univariate and multivariate logistic analyses were used to detect potential bias and adjust for traditional risk factors . We applDuring follow-up, there were 23 cumulative deaths, of which 19 were determined as cardiac. Kaplan-Meier plot is shown in 99mTc-MIBI SPECT/18F-FDG PET imaging in patients with IDCM. The results indicated a significantly decreasing trend of myocardial fibrosis and perfusion/metabolism abnormalities across the quartiles of FT3. After adjusting for conventional risk factors, low FT3 level was still independently associated with the presence of LGE, perfusion abnormalities and metabolism abnormalities. In survival analysis, the combination of LGE-positive and FT3 < 2.77 pg/mL was identified as the strongest predictor of all-cause death. The present study confirmed and extended previous knowledge about the effects of thyroid hormone levels on IDCM.Our study explored the relationship between thyroid status and myocardial injury evaluated by cardiac MRI and et al. first reported that TH-induced myocardial hypertrophy could be distinguished by decreased biosynthesis of type I collagen at the level of mRNA and protein. An in vitro experiment by Chen WJ et al. demonstrated that hypothyroidism can lead to increased abundance of mRNA for pro-α1(I) collagen and T3-dependent repression was through thyroid hormone receptor (TR) β1One of the major findings in our study was the significantly decreasing trend of LGE-positive segments across FT3 quartiles. Histological basis for LGE in DCM is myocardial replacement fibrosis, which refers to reparative microscopic scarring that follows myocyte deathIn an UK cohort of 472 non-ischemic DCM patients, those with LGE exhibited a greater degree of left ventricular dilatation and systolic impairment and were re-classified into higher risk for all-cause mortality22in vitroin vitro through a PDGF-Akt-dependent signalAnother interesting finding in our study is that low FT3 level contributed to impaired myocardial blood flow. Regional myocardial ischemia in IDCM has been determined from some studies24et al. found that estimates of cardiac work are more severely suppressed than those of oxidative metabolism, suggesting decreased myocardial efficiency in hypothyroidism. This is pertinent to our previous animal studies suggesting the hypothyroid heart is inefficientIn the present study, patients with low FT3 level tended to be at higher risk of myocardial metabolic abnormalities. Bengel FM and colleagues reported that cardiac oxygen consumption was reduced in patients with hypothyroidism and the reduction was associated with reduced contractilityAlthough no significant association was found between other thyroid parameters and myocardial injuries, patients with TSH below the reference range should be noted. In this subclinical hyperthyroid group, the percentage of LGE-positive segments was significantly lower. This finding corresponds to an interesting result of our previous study in which the prevalence of atrial fibrillation was unexpectedly lower in the subclinical hyperthyroid group than in other thyroid statesDespite the encouraging findings, our study has some limitations. The first one is that multiple thyroid tests were only available in 25% of the initially evaluated patients, so the present study could not resolve the ambiguity due to a transient change of thyroid status which is frequent in exacerbated HF. Second, thyroid function profiles were evaluated according to serum TH level rather than myocardial tissue level. As mentioned before, myocardial T3 could be down-regulated by the induced DIO3 in HF, which is independent from changes of serum TH level. Finally, because of the limited population in our study, the role of TH levels and myocardial injuries in IDCM survival needs to be further evaluated in a large population. However, strengths of the present study include the well-characterized IDCM cohort, complete information of cardiac MRI and radionuclide tests, and the exclusion of drug administration that might affect thyroid profile.99mTc-MIBI SPECT/18F-FDG PET imaging, the present study confirmed and extended previous knowledge based on animal experiments about the effects of thyroid hormone levels on IDCM, providing physicians with more comprehensive information with implications for TH therapeutic efficiency in HF.We found a clear relationship between FT3 level and myocardial injuries detected by semi-quantitative evaluation of myocardial fibrosis and ischemic/viable myocardium. Combining cardiac MRI and How to cite this article: Wang, W. et al. Free Triiodothyronine Level Correlates with Myocardial Injury and Prognosis in Idiopathic Dilated Cardiomyopathy: Evidence from Cardiac MRI and SPECT/PET Imaging. Sci. Rep.6, 39811; doi: 10.1038/srep39811 (2016).Publisher's note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.


Children with obesity have hypertrophic cardiac remodeling. Hypertension is common in pediatric obesity, and may independently contribute to hypertrophy. We hypothesized that both the degree of obesity and ambulatory blood pressure (ABP) would independently associate with measures of hypertrophic cardiac remodeling in children.2.7 (LVMI), myocardial thickness and end-diastolic volume were quantified from a 3D LV model reconstructed from cine balanced steady state free precession images. Categories of remodeling were determined based on cutoff values for LVMI and mass/volume. Principal component analysis was used to define a “hypertrophy score” to study the continuous relationship between concentric hypertrophy and ABP.Children, aged 8–17 years, prospectively underwent cardiovascular magnetic resonance (CMR) and ABP monitoring. Left ventricular (LV) mass indexed to height2.7, p < 0.001), myocardial thickness , mass/volume , and hypertrophy score . Thirty-five percent of obese/overweight children had concentric hypertrophy. Ambulatory hypertension was observed in 26% of the obese/overweight children and none of the controls while masked hypertension was observed in 32% of the obese/overweight children and 16% of the controls. Univariate linear regression showed that BMI z-score, systolic BP , and systolic load correlated with LVMI, thickness, mass/volume and hypertrophy score, while 24 h and nighttime diastolic BP and load also correlated with thickness and mass/volume. Multivariate analysis showed body mass index z-score and systolic blood pressure were both independently associated with left ventricular mass index (β=0.54 [p < 0.001] and 0.22 [p = 0.03]), thickness (β=0.34 [p < 0.001] and 0.26 [p = 0.001]) and hypertrophy score .Seventy-two children were recruited, and 68 of those  completed both CMR and ABP monitoring. Obese/overweight children had increased LVMI (27 ± 4 vs 22 ± 3 g/mIn children, both the degree of obesity and ambulatory blood pressures are independently associated with measures of cardiac hypertrophic remodeling, however the correlations were generally stronger for the degree of obesity. This suggests that interventions targeted at weight loss or obesity-associated co-morbidities including hypertension may be effective in reversing or preventing cardiac remodeling in obese children. Childhood obesity affects 17% of children and adolescents 2–19 years) in the United States –19 years. AlthougMechanisms underlying hypertrophic cardiac remodeling in obese children are not well understood, at least in part because several obesity co-morbidities, particularly high blood pressure (BP), are known to independently cause LV hypertrophy . High syHypertension is commonly diagnosed with a repeated  clinic mThe relationship between ABP and LV hypertrophy in obese children is not well understood. A few studies using ABP monitoring have shown a positive correlation between systolic BP and increased LVMI –15, 20. In addition, all previous studies used echocardiography to assess LV mass and/or thickness. Transthoracic ehocardiography suffers from limited acoustic windows and angle dependency. Cardiovascular magnetic resonance (CMR) imaging overcomes the above limitations, and is therefore the ideal tool for definitively assessing cardiac geometry and remodeling. The objective of this study was to comprehensively evaluate the relationship between obesity, ABP measurements and cardiac remodeling in uncomplicated, asymptomatic children without and with obesity. We hypothesized that ABP measurements and obesity would both independently correlate with CMR derived measures of cardiac remodeling .Children ages 8–17 years were prospectively recruited from the University of Kentucky  and Geisinger Medical Center. Body mass index (BMI) percentiles for age and gender based on the Centers for Disease Control growth charts  were use2 in kg/m2) percentiles. Resting BP was measured manually by auscultation using an appropriately sized cuff after 10 min of rest. Three measurements were taken, and the average of the last two was reported as the clinic BP. The clinic BP was classified into normal, pre-hypertensive or hypertensive based on established reference values for age, height and sex. All children had a normal 12-lead electrocardiogram.Clinical assessment took place at the time of the CMR scan. Height and weight were measured twice using a digital scale and the average values were used to determine age and sex specific BMI  using 6-element chest and 24-element spine coils. Standard elecrocardiogram-gated balanced steady-state free-precession (bSSFP) images were acquired during 10–15 s breath-holds to assess cardiac geometry and remodeling. Two-chamber, four-chamber and a stack of short-axis bSSFP images spanning both ventricles were acquired. 7–11 short-axis images were acquired depending on the size of the heart. Acquisition parameters included 3.16−3.37 ms repetition time, 1.3−1.5 ms echo time, [292−400] x [340−400] mm2.7 (LVMI), which has been shown to best predict cardiac risk compared to other methods of normalization [2.7, RVMI) was calculated from the end-diastolic frame assuming a myocardial density of 1.05 g/mL. LV and RV ejection fraction were also derived ((EDV-ESV)/EDVx100%).To assess cardiac geometry and remodeling, both LV and right ventricular (RV) endocardial boundaries were manually delineated on end-diastolic and end-systolic frames of the bSSFP images. LV epicardial boundaries were defined on an end-diastolic frame to quantify LV mass and wall thickness. LV end-diastolic (EDV) and end-systolic (ESV) volumes were computed from reconstructed 3D endocardial surfaces Figure  using a lization . LV myoclization . The ave2.7) and mass/volume ratio (0.69), defined from a previous study [To study the relationship between hypertrophic cardiac remodeling and BP measurements, cutoff values of LVMI . An appropriate cuff based on the subject’s arm circumference was chosen from four available sizes, and placed tightly on the subject’s non-dominant arm. The device would inflate shortly after activation and take two readings within the first 5 min, which a member of the study team used to confirm correct functionality. These initial readings were not included in subsequent analysis. The device was programmed to take a reading every 20–30 min between 7:00 am and 10:00 pm, and every 30–45 min from 10:00 pm to 7:00 am. Daytime and nighttime for each subject were determined by self-reported sleep and wake times from diaries. Subjects were advised to follow ordinary daily activities but avoid vigorous exercise and to relax the arm during the inflation and deflation of the cuff. Measurements were automatically repeated if the device failed to take a reading.Following the CMR scan, ABP monitoring was conducted using a AccuWin Pro, and analyzed according to the American Heart Association (AHA) statement [n = 4) with fewer than 14 daytime readings or fewer than 7 nighttime readings were excluded from analysis. Height- and sex- specific normative reference values from a European cohort provided by the German Working Group on Pediatric Hypertension were used [day-BPnight)/BPdayx100%). A dipping of at least 10% was considered normal [Normal BP: clinic BP <90th percentile, ABP <95th percentile and BP load <25%;Masked hypertension: clinic BP <95th percentile, ABP >95th percentile and BP load ≥25%;Pre-hypertension: clinic BP ≥90th percentile, ABP <95th percentile and BP load ≥25%;Ambulatory or sustained hypertension: both clinic BP and ABP >95th percentile and BP load ≥25%.After 24 h, the device and cuff were removed. Data were downloaded using the manufacturer’s software tatement . Subjectd normal . BP stagd normal  using bop < 0.05. All statistical analyses were performed in R [Continuous variables were reported as mean ± SD. The two-sample student’s t-test was used to compare differences between the obese/overweight and healthy groups. Categorical variables were compared between groups using either Pearson’s Chi-Square or Fisher’s exact tests. Linear regression, with adjustment for age, was used to estimate the differences in measures of cardiac remodeling and ABP parameters between groups. Correlations between BMI z-score, BP parameters and measures of cardiac remodeling were estimated using Pearson’s correlation coefficient. Stepwise linear regression was performed to determine independent predictors for measures of cardiac remodeling. Akaike information criterion (AIC) was used for model selection, i.e. the model with the smallest AIC was selected as the final model by the stepwise regression. Statistical significance level was set to med in R   and 37 healthy weight  children, completed both CMR and ABP monitoring and were included in subsequent analysis. Table 2.7, p < 0.001), mean myocardial thickness  and mass/volume ratio  were significantly larger in obese/overweight children compared to healthy controls . LV and RV EDV and ESV were comparable between the groups. There were no significant differences in LV or RV ejection fractions  had concentric hypertrophy, 1 (3%) had concentric remodeling, 4 (13%) had eccentric hypertrophy, and the remaining 15 (49%) had normal geometry. The hypertrophy score was also higher in the obese/overweight children compared to the healthy weight group  and mean arterial pressure  (Table p = 0.004), while systolic load almost doubled that of the healthy controls (p = 0.001). In addition, obese/overweight children had slightly higher nighttime DBP  and 24 h diastolic load , while 24 h and daytime DBP and daytime and nighttime diastolic load were comparable to healthy controls. Systolic dipping  and diastolic dipping  trended lower in obese/overweight children.Compared to healthy controls, obese/overweight children had elevated clinic SBP .Results of the univariate linear regression between ABP measurements, BMI z-score and measures of cardiac remodeling are reported in Table r = 0.36, p = 0.003; hypertrophy score: r = 0.44, p < 0.001). Mean thickness and mass/volume correlated to all BP and BP load measurements except for daytime DBP. The strongest correlations were also with 24 h SBP . There was also a weak negative correlation between mass/volume and systolic dipping .LVMI and hypertrophy score correlated with all measures of SBP and systolic load, but most strongly with 24 h SBP (LVMI: β coefficients) with the measures of LV remodeling compared to the ABP derived metrics.After adjusting for sex and height, BMI z-score and 24 h SBP were independent predictors of LVMI (β=0.54 and 0.22) and hypertrophy score (β=0.47 and 0.36), while nighttime SBP and BMI z-score were independent predictors of thickness (β=0.26 and 0.34) and mass/volume ratio (β=0.35 and 0.31)  obese/overweight children have LV and RV remodeling, as evidenced by increased LVMI, LV wall thickness, LV mass/volume and RVMI; 35% of obese/overweight children have concentric LV hypertrophy; 2) ambulatory SBP, DBP and BP loads are elevated in obese/overweight children; 26% of obese/overweight children have ambulatory hypertension and 32% have masked hypertension; 3) BMI z-score, systolic BP and BP load correlate with all measures of LV remodeling ; 4) BMI z-score and 24 h SBP independently associate with LVMI and the extent of LV concentric hypertrophy.Hypertension is a common comorbidity in childhood obesity . In multBased on American Heart Association criteria , 26% of 2.7 using echocardiography [Cardiac remodeling, estimated by increased LVMI, wall thickness and the presence of LV hypertrophy defined as LVMI > 51 g/miography , has beeiography , 38, 39.iography . TherefoObesity and hypertension have both been related to cardiac remodeling in children. Although obesity is known to impact LV geometry independent of its associated risk factors such as insulin resistance and inflammatory biomarkers , 38, 40,2.7, probably due to multiple reasons. First, the 51 g/m2.7 threshold was defined using echocardiography, and is not directly applicable to CMR since discrepancies between CMR and echocardiography have been reported [2.7 threshold was defined in adults. Therefore, we used threshold values of LVMI and mass/volume ratio derived from a previous CMR study in healthy children to categorize the different remodeling types [In the current study, to comprehensively evaluate the contribution of obesity and blood pressure to cardiac remodeling in obese children, we used CMR with 3D surface reconstructions to assess LV geometry and remodeling, and defined a continuous variable (the hypertrophy score) to represent the presence of LV hypertrophy. CMR is superior to 2D transthoracic echocardiography for quantification of cardiac geometry and remodeling due to better image quality and inter-observer and inter-test reproducibility , while ereported . Second,Consistent with most previous studies, we found that both BMI z-score and systolic BP (24 h or nighttime) are independently associated with LVMI, thickness, mass/volume and hypertrophy score. Moreover, compared to systolic BP, BMI z-score may be more strongly associated with measures of cardiac remodeling, especially for LVMI. When plotting LVMI against 24 h systolic BP, LVMI for obese/overweight children fit on a different line from healthy weight children. This finding suggests that although LV remodeling is affected by elevated BP to some extent, it may not be the most important contributor. Thus, while antihypertensive treatment may be warranted in children with hypertension, additional interventions targeted at weight loss or pathways involved in other obesity co-morbidities may be necessary to effectively reverse or prevent cardiac remodeling and future cardiovascular risk.In this cross-sectional study, contributions of obesity and ABP to changes in measures of cardiac remodeling could not be investigated. Future studies with longitudinal follow-up are required to address this issue. In addition, most subjects in the current study were white. As racial differences have been shown to affect ABP in children , resultsMultiple statistical tests were performed in the current study, however, we chose not to adjust for multiple testing and to leave it to the reader to interpret the statistical results in the presence of multiple testing. The associations between ABP and cardiac outcomes were investigated using linear models, it is possible that the associations were nonlinear. However, an assessment of the linearity assumption for the continuous variables was performed and all were found to be linear.In children, both the degree of obesity and elevated ambulatory blood pressure are independently associated with increased LVMI and wall thickness as well as the presence of concentric hypertrophy. This suggests that interventions targeted at weight loss or pathways involved in obesity-associated co-morbidities such as hypertension may be effective in reversing or preventing cardiac remodeling and future cardiovascular risk.


Strain analysis is feasible using three-dimensional (3D) echocardiography. This approach provides various parameters based on speckle tracking analysis from one full-volume image of the left ventricle; however, evidence for its volume independence is still lacking.Fifty-eight subjects who were examined by transthoracic echocardiography immediately before and after hemodialysis (HD) were enrolled. Real-time full-volume 3D echocardiographic images were acquired and analyzed using dedicated software. Two-dimensional (2D) longitudinal strain (LS) was also measured for comparison with 3D strain values.P < 0.001); circumferential ; and radial strain  values were significantly decreased after HD. The values of 3D principal strain (PS), a unique parameter of 3D images, were affected by acute preload changes . Twist and torsion values were decreased after HD . The 2D LS values correlated with the 3D LS and PS values.Longitudinal (pre-HD: −24.57 ± 2.51, post-HD: −21.42 ± 2.15, Various parameters representing left ventricular mechanics were easily acquired from 3D echocardiographic images; however, like conventional parameters, they were affected by acute preload changes. Therefore, strain values from 3D echocardiography should be interpreted with caution while considering the preload conditions of the patients. Two-dimensional (2D) echocardiography is the most widely used examination method for left ventricular (LV) dimension and function assessment, and the high frame rate of 2D speckle tracking echocardiography (STE) allows for the precise assessment of myocardial function through the analysis of myocardial deformation. Longitudinal, circumferential and radial movements, which represent dynamic LV changes during a cardiac cycle, can be measured from parasternal and apical echocardiographic windows. However, assumptions about LV geometry were inevitably the limitation of this method .Real-time three-dimensional 3D) echocardiography is better correlated with cardiac MRI than 2D echocardiography in the measurement of LV volumes D echocar. MoreoveRecent studies have shown that 3D strain measurements of the left ventricle using speckle tracking can represent LV mechanical function and can be achieved using several types of vendor-dependent and independent software. Strain assessed by 3D STE can predict the prognosis of patients who have suffered acute myocardial infarction and heart failure , 8. It cPrincipal strain (PS) is a newly introduced parameter in cardiology that can be obtained from 3D echocardiography. This is accomplished by recognizing the direction along which strain occurs  and the entities of actual deformation along the principal direction. It characterizes 3D strain properties, including longitudinal and circumferential strain values as well as torsional shear deformation, and can therefore represent dynamic 3D movements of the left ventricle , 12.Longitudinal and circumferential strain calculated by 2D STE was demonstrated to be affected by acute preload changes caused by normal saline infusion . HoweverWe hypothesized that various kinds of strain values from 3D STE, including PS, twist and torsion, may be influenced by acute volume change. We attempted to test this in a group of patients with end-stage renal disease (ESRD) who underwent periodic hemodialysis (HD) and experienced a subsequent preload reduction.Patients who were regularly undergoing HD at Bucheon St. Mary’s Hospital in Bucheon, South Korea, were recruited. All subjects were enrolled on a prospective basis. Among the 98 patients who were regularly undergoing HD on a periodic basis for at least 1 month prior to enrollment in the institute, 63 patients volunteered. An experienced echocardiographer who was blinded to the study design performed screening echocardiography on all volunteer subjects. Before and after the screening echocardiography, the exclusion criteria were as follows: (i) current acute coronary syndrome; (ii) previous cardiac surgery or device implantation; (iii) current presence or previous history of significant arrhythmia, such as atrial fibrillation; (iv) LV ejection fraction less than 50%; (v) evidence of major valvular heart disease ; and (vi) a poor echocardiographic window that was not appropriate for interpretation.n = 2), arrhythmia detected during echocardiographic examination (n = 1), LV regional wall motion abnormalities (n = 1) and a poor echocardiographic window (n= 1); therefore, 58 subjects were finally enrolled in this analysis.Five patients were excluded after the screening echocardiography due to significant valve dysfunction  equipped with phased array transducers (M5S-D and 4 V–D) was applied for echocardiographic examination. Echocardiograms were performed immediately before and less than 30 min after a single dialysis session.From the M-mode measurements, LV dimension and diastolic LV septal and posterior thickness were determined in the parasternal long-axis view. The 2D data were acquired from the parasternal long-axis and short-axis views and the three standard apical views. For each view, three consecutive cardiac cycles were recorded during quiet respiration. LV mass was determined using the area–length method and was corrected for body surface area. LV volume, ejection fraction and left atrial volume were determined using the modified Simpson’s method from apical 4- and 2-chamber views. Pulsed Doppler echocardiography of transmitral velocities was used to determine the peak E velocity, peak A velocity and the ratio between peak E and A velocities (E/A ratio). LV early diastolic e’ velocity and late diastolic a’ velocity were determined at the septal and lateral portion of the mitral annulus by Doppler tissue imaging and then averaged for evaluation. These measurements were obtained by setting the sample volume at the septal and lateral annulus and then recording at a sweep of 100 mm/s. All examinations were performed according to the recommendations of the American Society of Echocardiography and the European Association of Cardiovascular Imaging .During 3D imaging, to achieve a high frame rate and the highest spatial resolution, the pyramidal scan volume was focused on the LV volume and the data sets were acquired during a single breath hold, taking care to include the whole left ventricle.2D and 3D images were kept in a proprietary format  with Digital Imaging and Communications in Medicine Wrapper. Images were downloaded into a software package  and then exported into ImageArena Software  for analysis, including 2D and 3D strain analyses. The 2D strain data were used to validate the 3D strain data. For this purpose, three apical B-mode sequences  were recorded at an optimal frame rate  and optimal resolution for myocardium while focusing the image on the entire left ventricle; the images were kept in the DICOM format for post-processing. LS was assessed using the speckle tracking method at the endocardial level with Cardiac Performance Analysis software . Global values were then calculated as averages from the segments in each view.Three-dimensional images were analyzed using commercially available vendor-independent software . First, the LV long axis was designated in the three apical views  by the operator. The software distinguished the LV endocardial border and tracked it for an entire cardiac cycle. Last, the curves of PS strain were determined using the standard 16-segment model.The reliability of the 3D measurements was estimated by comparing the 3D global longitudinal strain (LS) parameters with the corresponding parameter measured by 2D analysis from the relevant subjects. Correlations between 3D global PS and 2D global LS were also investigated. We also compared the differences in the 3D data analyzed by vendor-independent  and vendor-dependent  software. Area strain  could not be determined by vendor-independent software, and PS could not be calculated by vendor-dependent software. We directly compared only the values of 3D global longitudinal, circumferential, and radial strain that were acquired from the same 3D echocardiographic images using two different 3D image analysis systems. We also investigated the correlation between PS and AS.To evaluate intra-observer variability in the offline analysis, 20 patients were randomly selected and analyzed by the same operator with at least a 1-week interval between the two analyses. To assess the effect of inter-observer variability, the same 20 subjects were analyzed in a random order at different times using the same software by a second investigator who was blinded to the results from the first investigator.2 and Fisher’s exact tests were applied to assess differences between categorical variables. The correlations between 3D PS, 3D LS and 2D LS were evaluated by Pearson’s correlation coefficient. Linear regression analysis between the values of 2D and 3D strain was performed. The correlation between 3D PA and AS was also evaluated by Pearson’s correlation coefficient and linear regression analysis [All data analyses were performed using the statistical analysis software package R version 3.4.1 . All conanalysis .P-values <0.05 were considered statistically significant.Reliability was evaluated using the intra-class correlation coefficient (ICC) to determine both intra- and inter-observer variability using an R package for the ICC . The int3D STE analysis successfully performed in all 58 patients, but the measurement of LS from 2D STE could not be performed due to poor image quality in one patient pre-HD and two patients post-HD.n = 29). The most common cause of ESRD was diabetes mellitus , the second was hypertension , and the third was chronic glomerulonephritis  . The values of twist and torsion were decreased according to the preload change caused by HD  (Table Table Table Table Table 2D speckle tracking is a useful method for cardiac evaluation. It has been applied in cases of subclinical cardiac dysfunction and for predicting prognosis. 2D echocardiographic images at higher frame rates enable the calculation of strain rate, and thus, it is possible to determine subtle changes in cardiac performance using this technique. However, at least six images should be obtained to measure the global strain and twist values from 2D echocardiography, and one type of strain cannot represent the dynamic cardiac motion. 2D speckle tracking also has limitations in measuring twist because its values are greatly affected by the position of image planes .Real-time 3D echocardiography was first introduced in 1991 . It has Recent advances in cardiovascular imaging techniques have made it possible to measure values of various types of strains from 3D echocardiographic images using the speckle tracking method, which is already widely used and has proven to have clinical importance in 2D imaging . LV 3D sESRD patients who are regularly undergoing HD have been used as a model for acute preload change in several previous studies. These studies showed that LV and atrial strain values were significantly decreased following preload reduction by HD , 24. 3D PS analysis is a method for describing multidimensional deformations. It identifies the directions along which strain develops and the entity of actual contractions, and therefore, it is particularly well suited for biologic tissues with an underlying structure of muscular fibers along which the stress is generated, such as the heart . In thisThree-dimensional PS has proven to be effective in detecting subclinical cardiac abnormalities , 27. AS In this study, twist and torsion calculated using 3D STE were also affected by acute preload changes. LV rotation plays an important role in LV contraction and relaxation. From 2D STE, the difference in the systolic rotation of the myocardium in the apical and basal short-axis planes is referred to as twist and reported in degrees. Data normalized to the distance between the respective image planes are referred to as torsion and reported in degrees/cm . Weiner This study has several strong points compared to other studies investigating changes in the echocardiographic parameters based on preload changes , 24, 28.First, we used newly developed novel strain values for the evaluation of preload reduction. Other strain values, which can be obtained from 2D STE, were also easily and simultaneously calculated during the same cardiac cycle. This benefit made it possible to measure various parameters representing cardiac mechanics more accurately.Second, the software used was newly introduced vendor-independent software for 3D echocardiographic image analysis. There are several types of software for 3D strain evaluation on the market, but they yield different values in the measurement of 3D strain, even within the same patients . Our resThird, 3D strain values could have been acquired from all subjects even though we could not calculate the LS value in 3 subjects due to poor echocardiographic windows. For measurements of acceptable strain values, good-quality real-time 3D echocardiographic images are essential. In addition, a significant learning curve is required even for experienced physicians or echocardiographers.However, there are also several weak points in this study. The major limitation of this study is that it was performed in a single center with a relatively small number of patients, although the number of individuals enrolled in this study was larger than that in other studies , 24, 28.Second, this study only tracked the endocardium and not the entire myocardium. Compared with the epicardium, endocardial shape change is known to be more associated with global shape change; epicardial, endocardial or global volume; and global rotation and global twist parameters .Third, although the heart rate and frame rate were not significantly different between the pre- and post-HD phases, the relatively higher heart rate post-HD due to acute volume reduction might have affected the frame rate of the 3D echocardiographic images and ultimately led to a greater decrease in all LV mechanical parameters. The frame rates of both groups were greater than 25 frames/s in this study. Yodwut et al. previously demonstrated that frame rates greater than 18 frames/s did not affect the strain values . The lowFourth, HD is not a simple process that leads to only acute volume reduction. During HD, activation of the sympathetic nervous system occurs for the invitation and maintenance of compensatory mechanisms to maintain blood pressure, especially mechanisms involving heart rate and peripheral vasoconstriction . The heaFifth, a study that aimed to determine normal reference values of 3D echocardiographic strain showed that there were differences in normal values between different segments, walls and levels of the left ventricle. There is still no accepted reference value of 3D strain, and there are significant inter-vendor differences in the measured values . We usedThis study showed that deformation parameters measured from 3D echocardiographic images using the speckle tracking method are affected by acute preload changes. 3D echocardiography can be used to calculate strain, twist and torsion, which can represent complex LV mechanics, from a single image. However, all parameters representing LV systolic function, including the novel parameter of PS, were affected by acute preload changes. Therefore, the values of strain, twist and torsion acquired from 3D STE should be interpreted with caution and with consideration of the preload status of the patient. The findings of this study are important for patients in critical settings, such as acute heart failure and shock patients, who are experiencing significant volume shifts due to the disease and the treatment. More studies are needed to explore the prognostic value of PS, a novel parameter that reflects actual deformation along the principal direction, especially in ESRD patients who are very susceptible to cardiovascular complications.


Extracorporeal cardiopulmonary resuscitation (E-CPR) is increasingly used as a rescue method in the management of cardiac arrest and provides the opportunity to rapidly induce therapeutic hypothermia. The survival after a cardiac arrest is related to post-arrest cardiac function, and the application of therapeutic hypothermia post-arrest is hypothesized to improve cardiac outcome. The present animal study compares normothermic and hypothermic E-CPR considering resuscitation success, post-arrest left ventricular function and magnitude of myocardial injury.After a 15-min untreated ventricular fibrillation, the pigs (n = 20) were randomized to either normothermic (38 °C) or hypothermic (32–33 °C) E-CPR. Defibrillation terminated ventricular fibrillation after 5 min of E-CPR, and extracorporeal support continued for 2 h, followed by warming, weaning and a stabilization period. Magnetic resonance imaging and left ventricle pressure measurements were used to assess left ventricular function pre-arrest and 5 h post-arrest. Myocardial injury was estimated by serum concentrations of cardiac TroponinT and Aspartate transaminase (ASAT).E-CPR resuscitated all animals and the hypothermic strategy induced therapeutic hypothermia within minutes without impairment of the resuscitation success rate. All animals suffered a severe global systolic left ventricular dysfunction post-arrest with 50–70% reductions in stroke volume, ejection fraction, wall thickening, strain and mitral annular plane systolic excursion. Serum concentrations of cardiac TroponinT and ASAT increased considerably post-arrest. No significant differences were found between the two groups.Two-hour therapeutic hypothermia during E-CPR offers an equal resuscitation success rate, but does not preserve the post-arrest cardiac function nor reduce the magnitude of myocardial injury, compared to normothermic E-CPR.Trial registration FOTS 4611/13 registered 25 October 2012The online version of this article (doi:10.1186/s12967-016-1099-y) contains supplementary material, which is available to authorized users. Survival after cardiac arrest is greatly influenced by early post-arrest cardiac function , 2. HencTo achieve cardiac benefit from HT the importance of early and rapid cooling has been emphasized in experimental studies –14. E-CPA severe cardiac dysfunction following normothermic E-CPR is recently demonstrated in pigs . The preA prospective controlled block-randomized animal study was completed to compare a normothermic  and a hypothermic  E-CPR group.The experimental protocol was approved by the Norwegian National Animal Research Authority and the animal experiments were performed in accordance with the European Convention for the Protection of Vertebrate Animals used for Experimental and Other Scientific Purposes . Detailed information according to the ARRIVE guidelines is presented in Additional file The animal preparation included premedication in the pig enclosure and total intravenous anaesthesia in the operating theatre, mechanical ventilation and a succeeding surgical tracheotomy and placements of intravascular catheters and ECMO-cannulas as recently described . Ringer’After the preparation and a following 30-min stabilization period, baseline cardiac MRI  and haemodynamic measurements of LV function  were obtained. Arterial and mixed venous blood samples were analyzed  and serum concentrations of cardiac Troponin T (cTnT) and Aspartate aminotransferase (ASAT) were measured.After baseline assessments, the pig was connected to a Ringer’s acetate-primed femoro-jugular veno-arterial ECMO circuit  featuring an oxygen/air mixer  to adjust sweep gas oxygen content and sweep gas flow rate. A connected heat-exchanger  enabled animal blood temperature control.After an intravenous injection of 2 mg/kg heparin, an electrical stimulator connected to a right ventricular pacing lead  induced ventricular fibrillation (VF), confirmed by ECG shape and aortic blood pressure drop.After 15 min of untreated VF the animals received either normothermic [pulmonary artery blood temperature 38.0 °C (normothermia in the pig)] or hypothermic (32.0–33.0 °C) E-CPR at maximum ECMO blood flow rate with a 100% oxygen sweep gas set at the same flow rate as the ECMO blood flow rate.HT in the 32-ECPR group was achieved using 20.0 °C priming solution with later adjustments at the heat-exchanger. The heat-exchanger thermostat at 38.0 °C ensured normothermia in the 38-ECPR group.After 5 min of E-CPR 360 Joule monofasic defibrillations  were provided until regain of spontaneous cardiac beating (ROSB) with extracorporeal support continuing at unchanged blood flow rate and temperature target for 120 min. In the 32-ECPR group a 30-min warming period followed, whereas a corresponding 30-min continued run at 38.0 °C was provided in the 38-ECPR group.The mean aortic blood pressure (MAP) target (≥50 mmHg) and pulse-pressure target (≥15 mmHg) after ROSB were met using repeated 10–25 µg adrenaline (epinephrine) intravenously followed by dobutamine infusion if needed .After the 120 + 30-min extracorporal support, with all animals being normothermic, a step-wise separation from ECMO (weaning) was completed during a 60-min period, and the animals were allowed to stabilize after weaning for another 60 min before the post-arrest assessments.At 285 min post-arrest LV function was re-assessed by LV pressure measurements and MRI. Finally, a second arterial and mixed venous blood sample were analyzed and blood samples for cTnT and ASAT measurements were collected, before the pig was euthanized.max), maximum positive and negative first time derivate of LV pressure (dP/dtmax and dP/dtmin), end-diastolic LV pressure (EDP), end-systolic LV pressure (ESP), isovolumetric relaxation constant (tau), and arterial elastance (Ea  =  ESP/SV))  mid LV radial wall thickening, mitral annular plane systolic excursion (MAPSE), and peak global systolic LV circumferential strain) together with LV pressure measurements (maximum systolic LV pressure (LVPESP/SV)) , 18. ConThe serum concentration measurements of cTnT and ASAT pre-arrest and 6 h post-arrest were performed by an electro-chemiluminescence immunoassay  and by an UV-test with pyridoxal phosphate activation  using an automated clinical chemistry analyzer  to estimate myocardial injury.Eleven  hearts excised immediate post-mortem were sliced and stained in 1% triphenyl tetrazolium chloride  in phosphate buffer and examined for myocardial infarction , 20.Statistical analyses were made using Graphpad prism 6.04 . Data are reported as mean ± standard deviation if not otherwise stated. The statistical significance level α was set to 0.05 and power 1 −β to 0.80.The study sample size was estimated by a prospective power analysis. The least detectable difference considered as clinically significant between cardiac function variables was 15% of baseline values. Cardiac function variability in range of 5–15% of baseline values in pilot experiments made a calculated sample size of 20 necessary to achieve the desired power.t test (t) was used to compare baseline and post-arrest measurements within each treatment group, and an unpaired two sample t-test (T) was used to compare post-arrest measurements between the two different treatment groups. Alternatively, a two-tailed Mann–Whitney test (MW) of group differences with exact p-value was used for data not normally distributed.A paired two-tailed Student's Animal weight (49.2 ± 2.8 kg), preparation time (122 ± 22 min) and cardiac MRI scan time (63 ± 15 min) were similar in the two groups. Neither activated clotting-time prior to cardiac arrest (330 ± 76 s) nor ECMO circuit priming volume (544 ± 22 ml) differed between the two groups, and the experiment durations were also similar, averaging 762 ± 63 min .One animal in the 38-ECPR group was euthanized after ROSB, and was thus excluded from further analyses, because MAP could not be sustained as dictated by the protocol, due to ECMO venous cannula malfunctioning.At initiation of VF the blood temperature was 38.0 ± 0.2 °C and was maintained at this level in the 38-ECPR group Fig. . In the All animals were successfully defibrillated by a median of 1 shock (range 1–6) with no significant differences between the groups . After ROSB three animals in the 38-ECPR group spontaneously had a second VF, and immediately received a median of 1 (range 1–3) additional defibrillations. No additional defibrillations were needed in the 32-ECPR group .MAP at the time of defibrillation was 54 ± 9 mmHg in the 38-ECPR group and 60 ± 5 mmHg in the 32-ECPR group  ] was 100 µg (0–340 µg) in the 38-ECPR group vs. 183 µg (50–1700 µg) in the 32-ECPR group . The dobutamine requirements differed between the groups [38-ECPR dobutamine [median (range)] = 15.8 mg (0–31.2 mg) vs. 32-ECPR dobutamine = 36.2 mg (10–93.6 mg)] , but the dosages after ECMO weaning to the end of the experiments were not significantly different; four of nine animals in the 38-ECPR group and five of ten in the 32-ECPR group received dobutamine dosages [median (range)] of 2 mg (0.5–2.2) and 2.6 mg (0.01–5 mg), respectively, after weaning .max, dP/dtmin, EDP, EDP/EDV relationship, and tau did not change significantly from baseline values in either group.HR increased similarly post-arrest in both groups Table , limitinMixed venous oxygen saturation dropped considerably and group-similarly post-arrest Table . A smallIn both groups the LV function was severely affected post-arrest Fig. . EF decrConsistent with the reduced SV the strain decreased group-alike; from −17 ± 4 to −5 ± 3%  in the 38-ECPR group and from −18 ± 3 to −7 ± 4%  in the 32-ECPR group . MAPSE in the 38-ECPR group was reduced from 12 ± 1 to 6 ± 1 mm  and likewise in the 32-ECPR group from 12 ± 2 to 6 ± 1 mm  . Correspondingly, the wall thickening in the 38-ECPR group was severely affected by a reduction from 54 ± 11 to 18 ± 7% . A similar reduction from 57 ± 14 to 13 ± 24%  was found in the 32-ECPR group .The serum concentrations of cTnT and ASAT remained minimal after the surgical preparation (38-ECPR cTnT (median (range)) = 13 (10–32) ng/L vs. 32-ECPR cTnT= 16 (7–28) ng/L; 38-ECPR ASAT = 27 (18–33) U/L vs. 32-ECPR ASAT = 28 (18–31)) U/L, but increased considerably post-arrest without significant differences between the groups; 38-ECPR cTnT = 2295 (782–5203) ng/L vs. 32-ECPR cTnT = 2452 (925–5475) ng/L  and 38-ECPR ASAT = 123 (61–1630) U/L vs. 32-ECPR ASAT = 266 (112–969) U/L .The assessment of myocardial infarction by TTC staining post mortem did not demonstrate regional infarctions.In the present controlled animal study comparing hypothermic and normothermic E-CPR considering resuscitation success, post-arrest LV function, and myocardial injury, surprisingly, and contrary to our hypothesis, no beneficial effects of HT during E-CPR could be demonstrated.A better preserved LV function would be desirable in resuscitated patients as post-arrest cardiac function is related to patient survival. In the present study, HT during E-CPR was hypothesized as being beneficial because HT has demonstrated cardioprotective effects in various animal studies with regional myocardial ischaemia (i.e. coronary occlusion) , 22.The best strategy of E-CPR to preserve early post-arrest cardiac function is not known and no guidelines exist to assist clinicians deciding on an E-CPR strategy for patients in refractory cardiac arrest. To date HT is not recommended as a cardioprotective intervention in patients with acute myocardial infarction without associated cardiac arrest , 23. In Correct timing of HT has been emphasized in recent years as HT is claimed to be cardioprotective only if induced either shortly before or at the time point of myocardial reperfusion , 26, 27.Two-hour HT duration was investigated as brief cooling has been sufficient to achieve cardioprotective effects in previous animal studies  and 3-h Compared to our study, rewarming of patients after cardiac arrest is slow (0.3–0.5 °C/h), tailored for neuroprotection . In cardInotropic support is regularly used during VA–ECMO to sustain aortic ejections with a sufficient pulse-pressure to avoid LV distention and failure. The increased dobutamine requirements observed during HT may be related to altered pharmacologic properties of dobutamine with a reduced effect  as suppoIn the present study, the 50–70% reductions in SV, EF, wall thickening, strain and MAPSE were consistent, demonstrating a severe global systolic LV dysfunction post-arrest with uniform impairments in all directions of systolic LV motion, and with no differences between the two treatment groups.min, tau and EDP/EDV relationship was preserved in both groups post-arrest, and neither EDV (preload) nor Ea (afterload) differed between the two groups.The diastolic LV function assessed by dP/dtThe post-arrest LV dysfunction indicated a severe and global myocardial injury as was confirmed by the considerable increase in serum concentrations of cTnT and ASAT in both groups. A global injury without distinguished regional areas was also confirmed by the TTC assessment, as no regional infarctions could be demonstrated, excluding coronary thrombus or embolic complications.The success rate of resuscitation by hypothermic E-CPR was not inferior to the normothermic strategy, and neither LV function nor myocardial injury was exacerbated. E-CPR initiated by a room tempered ECMO may be convenient, as a normothermic ECMO (or a circuitry heating device) will not always be available in clinical emergency settings that may include emergency rooms, ambulance transfers and even pre-hospital use.The clinical scenario of E-CPR differs from a controlled animal experiment as the period of no-flow is usually short (preferably <5 min) and the patient is cannulated at ongoing CPR in a low-flow period of varying duration. In the present study, a healthy pig heart suffered an electrically induced VF and the total ischemic insult was prepared to be substantial and consistent to assure a significant post-arrest cardiac dysfunction and injury that could be compared between the two different treatment groups. The duration of no-flow thus exceeded usual clinical limits, and the low-flow period was bypassed.E-CPR is an effective resuscitation technique for prolonged cardiac arrest that may rapidly induce HT. In the present animal study, 2-h HT during E-CPR offered an equal resuscitation success rate, but did not preserve the post-arrest cardiac function nor reduce the magnitude of myocardial injury, compared to normothermic E-CPR.


Endomyocardial biopsy (EMB) is the current gold standard to monitor patients for heart transplant rejection. Quantification of myocardial T2 relaxation time using cardiac magnetic resonance (CMR) has been shown to have high sensitivity and specificity to detect rejection episodes. In this study, we evaluated the prognostic value of myocardial T2 to predict adverse cardiovascular outcomes during 5-year follow-up after initial CMR.49 cardiac transplant patients  were recruited from a single institution. CMR at 1.5T was performed in all patients, with subsequent quantifications of regional and global myocardial T2. Clinical data was gathered post-CMR over a 5-year period. EMBs were graded according to the International Society of Heart & Lung Transplantation criteria. Rejection episodes were defined by EMB ≥ 2R, new onset heart failure (HF), LV ejection fraction < 40%, or death. Adverse cardiovascular events gathered included coronary artery disease, cardiomyopathies, arrhythmias, and different types of HFs. Multivariable logistic regression and Kaplan-Meier analysis was performed to measure the prognostic value of myocardial T2.Myocardial T2 was found to increase with worsening EMB grade from 53.0 ms  to 59.9 ms . ROC analysis using two groups (EMBs ≤ 1R and ≥ 2R) showed T2 = 55.0 ms to have the highest specificity and sensitivity. In multivariable analysis that considered T2 measures, age, length of surgery, donor ischemic time, and BMI, both peak T2 (p = 0.038) and septal T2 (p = 0.035) were significant predictors of EMB grade ≥ 2R. Kaplan-Meier analysis showed a significant higher probability of developing EMB ≥ 2R, new onset HF, or death with a global T2 ≥ 55 (p = 0.02). Adverse cardiovascular outcomes of systolic HF, acute systolic HF, and chronic diastolic HF had a higher probability of developing in patients with global T2 ≥ 55 .CMR T2 quantification demonstrated prognostic value for all-cause rejection and various types of HFs in cardiac transplant patients. These findings suggest that CMR may be a suitable modality to non-invasively monitor cardiac transplant patients for rejection.