Understanding arrhythmias and their treatment is not always easy. The current straightforward approach with catheter ablation and device therapy is an amazing achievement, but does not make management of underlying or other cardiac disease and pharmacological therapy unnecessary. The goal of this paper is to describe how much of the knowledge of the 1980s and early 1990s can and should still be applied in the modern treatment of patients with arrhythmias. After an introduction, this review will focus on paroxysmal atrial fibrillation and a prototype of ‘idiopathic’ ventricular arrhythmias, two diseases with a striking similarity, and will discuss the arrhythmogenesis. The ECG continues to play an important role in diagnostics. Both diseases are associated with a structurally normal heart; the autonomic nervous system plays an important role in triggering arrhythmias at both the atrial and ventricular level. Recently, some concerns were expressed on the recent developments in arrhythmia management in general, and on the way clinical electrophysiology is evolving in particular . This isUnderstanding the genesis of arrhythmias (arrhythmogenesis) was not considered to be too difficult some 40 years ago, in the era before the advent of clinical electrophysiology with its ablation and implantable defibrillators. We only had the electrocardiogram at our disposal. Normal impulse generation in the sinus node and conduction through the specialised conduction tissue in the heart leads to electromechanical coupling, and the heart pumps the blood through the blood vessels. A calcium-mediated action potential governs normal impulse formation in the sinus node and in the atrioventricular (AV) node, while all other myocardial tissue is dependent on a sodium-channel mediated action potential. When this nice mechanism is disturbed, arrhythmias are encountered as the consequence of abnormal impulse generation or conduction, mainly due to re-entry . AutomatThe widespread and well-taught pharmacological antiarrhythmic treatment at that time was only seldom subjected to randomised clinical trials . You didIt was more or less at this moment that new options were added to our therapeutic arsenal. Class Ic drugs proved to be dangerous, at least for patients with ischaemic heart disease , but forThe insights into cardiac anatomy and functioning improved considerably. On the one hand, a growing basic knowledge, based on experimental animal studies, the development of molecular cardiology, and the fast evolution in genetics, improved our understanding of cardiomyopathies and diseases associated with arrhythmias , 18. On Antiarrhythmic treatment finally entered or re-entered the phase of randomised trials, often with disappointing results, so that over the last three decades only a few of the active antiarrhythmic drugs that were developed and investigated  were actually put on the market, and then not always in all countries. This really did not help to improve the care of patients when catheter ablation or device therapy were unsuccessful, so, for instance with an incomplete effect of AF ablation or inappropriate shocks from implanted defibrillators. The real progress was not in the niche corner of a new antiarrhythmic, but rather with the advanced understanding of when and how to prescribe or avoid flecainide or amiodarone, with or without a beta-blocker, and how to treat background pathology and heart failure , 21.ECG interpretation remains important. This is not only the case for the 12-lead ECG, but also for Holter analysis, which lost much of its glory at the ventricular level after the CAST , as a matter of fact, without good reason . Its useImaging has evolved, with advanced body surface mapping, and processing of echocardiography and magnetic resonance. However, the real mechanism behind the arrhythmia is still not clarified. Moreover, the noninvasive technologies are not really assisting the general cardiologist, who has to make the first therapeutic decisions and also decide whether to transfer the patient to the electrophysiologist. His computer screen will finally display scars, barriers, rotors and wave fronts.AF is present in more than 20% of the population at a certain moment . Other aPulmonary veins are structures coated by muscular sleeves, which are remnants of the primitive heart, drawn into the lung tissue when the lungs are shaped during our early life. It is therefore not surprising that these muscular sleeves show spontaneous pacemaker activity, or that they form an electrical continuum with the adjacent atrium. Pulmonary vein isolation (PVI) has indeed become the cornerstone of effective interventional AF therapy . The preLarger atria will more easily sustain AF than smaller ones, allowing multiple wavelets to re-enter . The impThe physiology of the autonomic innervation of the heart is intriguing. Bradycardia and tachycardia promote their own automaticity, not necessarily related to the ANS . The sinSudden cardiac death is very often the end result of an interaction of the three factors in the triangle of Coumel . Risk stThis review will now focus on a particular condition in the normal heart, first described by Gallavardin, and also well studied by Coumel, namely extrasystoles originating in the outflow tract. When occurring as tachycardia, it was called ‘tachycardie en salves’, and more recently ‘repetitive monomorphic tachycardia’ .This variant of ventricular extrasystoles or tachycardia is almost ubiquitous, with a typical left bundle branch morphology and inferior axis . The reaWhether these extrasystoles are due to abnormal calcium currents or not, or to delayed activity with afterdepolarisation or enhanced automaticity is important when we are looking for a medical therapy . AdenosiRight ventricular outflow tract arrhythmias are considered benign , indicating that the myocardium is considered to be healthy . This meAbnormalities on magnetic resonance and echocardiography are only seldom detected, and with the present technology can be considered anecdotal. Nevertheless, it is hypothesised that many athletes seen with outflow tract tachycardia have developed fibrosis over time, making re-entry possible . This fiNeurohumoral factors play an important role in the occurrence of arrhythmias and in the development of symptoms. Extrasystoles appear typically at a certain heart rate, and disappear at higher frequencies. A close relation was detected between the heart rate and duration of ventricular runs, and even with the coupling interval of the first extrasystole . ExercisThe ESC guidelines give no real clues for reliable drug therapy, but there is agreement that medical therapy is disappointing . Beta-blIt is concluded that for the daily, clinical, but also for the advanced interventional management of patients a consideration of the classical three mechanisms of arrhythmogenesis remains useful. Both electrocardiography and imaging Fig.  remain iFurther, the parallelism of arrhythmogenesis in atrial and ventricular arrhythmias as described in this selective review is striking. Attempts to prevent atrial and ventricular overloading, and fibrosis (if possible) are of the highest importance. Beta-blockers remain safer than other antiarrhythmic drugs and may prevent benign arrhythmias from becoming malignant.Finally, clinical electrophysiology provides us with important tools to improve this conventional approach. More refined mapping is necessary, and devices are magnificent recorders. We will need electrophysiology specialists who know a lot about the basics and other areas of cardiology to make progress.


Clinical data: Increase in size of the left atrium known since 8 years ofage, when she was labeled as carrier of idiopathic left ventricular restrictivesyndrome. Since then, there was a progressive increase of this cavity with theappearance of fatigue to the efforts and atrial fibrillation five months ago, reversedin the occasion with electric shock and amiodarone. Despite a high dose of this drug,400 mg/day, heart rate remained elevated, around 100 bpm, having developed thyroiddysfunction with TSH elevation and hormone diminution. The arrhythmia reappeared twomonths later and led to new clinical research.Physical Exam: eupneic, acyanotic, normal pulses, HR = 96 bpm, BP = 100x70 mmHg.Venous impulses in the neck. In the precordium, there were no impulses, normal heartsounds, no audible murmurs. Third sound sometimes inconstant. Clean lungs. Abdomenunchanged.Chest X-ray: normal cardiac area with a clear increase of the leftatrium in a double atrial contour and a more prominent pulmonary vascular weave inthe upper fields (r fields .Electrocardiogram: atrial flutter and right bundle branch conductiondisorder with rr1 morphology in V1. AQRS = +70º AT = + 110º.Echocardiogram: exclusive increase of the left atrium. Ao = 28, LA = 53,RV = 22, LV = 40, septum = 8, posterior wall = 10, LVEF = 68%, SPRV = 53 mmHg.Enlarged superior vena cava without ventricular dyskinesias (kinesias .Magnetic nuclear resonance: no fibrosis in late enhancement.Cardiac catheterization: showed signs of restriction to left ventricularfilling with discrete pulmonary hypertension. LA = 12, RV = 35/10, PA = 35/20-28,Wedge = 20, LV = 80/5-18, Ao = 80/50-64, CO = 3.1 l/m, PVR = 2.58 W, SVR = 16.75 WAngiography clearly emphasized the left atrial emptying delay, right ventricularhypertrophy, and the left ventricular endocardial smooth wall (oth wall .Endomyocardial biopsy of the RV septum: Five fragments of the rightventricle myocardium with elastic consistency and brownish, measuring 4x3x1 mm,showed moderate and diffuse hypertrophy in cardiomyocytes, moderate and focalinterstitial myocardial fibrosis, absence of inflammatory infiltrate, absence ofamyloid protein deposition by the Red Congo histochemical method, negativehistochemical investigation of glycogen and neutral mucopolysaccharides, and acidsby the periodic acid method of Schiff, with and without diastase.Clinical diagnosis: idiopathic restrictive syndrome with isolatedincrease of the left atrium size with atrial flutter and pulmonary hypertension, inaddition to hypothyroidism due to the use of high dose of amiodarone.Clinical reasoning: In an initially asymptomatic patient with an evenslight increase in the left atrium, without other commemorative ones, the diagnosisof restrictive left ventricle syndrome becomes imperative. The progressive increaseof this cavity further accentuates this diagnosis, even more with the advent ofpulmonary congestive symptoms expressed by dyspnea, physical fatigue and enlargementof the pulmonary vascular network, in addition to the appearance of atrial flutter.Restrictive syndromes are classified into myocardial, non-infiltrative idiopathic,infiltrative amyloidosis type, sarcoidosis, Gaucher and Huler disease; storagediseases such as hemochromatosis, Fabry disease and glycogen storage. We can alsomention the endomyocardial ones with fibrosis, eosinophilic syndrome, the carcinoid,those by irradiation, of malignant tumors and by anthracycline toxicity.Differential diagnosis: symptoms of fatigue, atrial size increase,pulmonary arterial hypertension and ventricular diastolic dysfunction, assure thediagnosis of restrictive syndrome. Therefore, the cause should immediately be soughtfrom those exposed above, through diagnostic imaging, allied to cardiac biopsy.Treatment depends on the cause, corticosteroids on sarcoidosis, chelation onhemochromatosis.Conduct: having found mild pulmonary arterial hypertension, there was anindication for the use of metoprolol 100 mg/day adrenergic beta-blocker in order toimprove the ventricular filling and to decrease the heart rate after the obligatorysuspension of amiodarone. Atrial flutter ablation was also indicated to improveventricular filling and to prevent the left atrial enlargement. Routine clinicalfollow-up aims to preserve the current condition in order to postpone cardiactransplantation.Comments: The main characteristic of the restrictive syndrome isdiastolic filling difficulty, with normal ventricular volume and more rigidventricular walls despite normal thickness, and also with preservation of systolicfunction. Therefore, it provokes proportional increase of the left atrium,congestion and pulmonary arterial hypertension. Therapeutic options are rare andineffective and cardiac transplantation should be considered in advancedphases.2 Left atrial septum decompression by atriosseptostomyhas been considered in order to reduce congestion and pulmonary hypertension,allowing to postpose the indication for transplantation.2 It is the least common cardiomyopathy of all types.The genetic spectrum points to mutations in sarcomeric genes in half of thecases.1 Evolutionarily,sudden death occurs in 80%, heart failure in 15%, infective endocarditis in 5%,predominantly below 20 years of age.


To evaluate the diagnostic performance of different mathematical models and different b-value ranges of diffusion-weighted imaging (DWI) in peripheral zone prostate cancer (PZ PCa) detection.2) were included. The mean signal intensities of the regions of interest (ROIs) placed in benign PZs and cancerous tissues on DWI images were fitted using mono-exponential, bi-exponential, stretched-exponential, and kurtosis models. The b-values were divided into four ranges: 0–1000, 0–2000, 0–3200, and 0–4500 s/mm2, grouped as A, B, C, and D, respectively. ADC, <D>, D*, f, DDC, α, Dapp, and Kapp were estimated for each group. The adjusted coefficient of determination (R2) was calculated to measure goodness-of-fit. Receiver operating characteristic curve analysis was performed to evaluate the diagnostic performance of the parameters.Fifty-six patients with histologically proven PZ PCa who underwent DWI-magnetic resonance imaging (MRI) using 21 b-values (0–4500 s/mmp = 0.980) and were significantly higher than those in groups A and B . The AUCs of ADC and Kapp in groups B and C were similar (p = 0.07 and p = 0.954), and were significantly higher than the other parameters . The AUCs of ADC in group D was slightly higher than Kapp (p = 0.002), and both were significantly higher than the other parameters .All parameters except D* showed significant differences between cancerous tissues and benign PZs in each group. The area under the curve values (AUCs) of ADC were comparable in groups C and D (2) models is an optimal parameter for PZ PCa detection.ADC derived from conventional mono-exponential high b-value (3200 s/mm Magnetic resonance imaging (MRI) is considered the best imaging technique for the detection, staging and surveillance of prostate cancer (PCa) because of its ability to provide functional and anatomic information –3. DiffuIn traditional diffusion theory, a mono-exponential model, based on the assumption of homogeneous Gaussian diffusion, has been adopted for diffusion analysis in most clinical studies , 6. Howe2[2[2; the effect of an ultrahigh b-value (up to 4500 s/mm2) remains unclear.The choice of an appropriate b-value is another crucial aspect of DWI that affects PCa detection efficiency. The appropriate b-value is essential for calculating precise diffusion parameters to aid PCa diagnosis , 15. Nev2, 16, 17.2[2. An earlIn this study, we aimed to address the influence of the range of b-values on the discriminatory value of the diffusion parameters of four different mathematical models  and to determine the optimal parameter and its optimal b-value range for PCa detection.This prospective study was approved by the Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Institutional Review Board; written informed consent was obtained from each patient prior to examination. Between May 2014 and March 2015, patients with clinically suspected PCa due to either a rising or elevated prostate-specific antigen (PSA) level and/or palpable prostatic nodule, with no prior therapy, were recruited to this study. Initially, 166 consecutive patients were identified. Patients were excluded if a) they had histological confirmation of no cancer (n = 43); b) they had no histological confirmation of cancer (n = 51); c) the images were of poor quality due to susceptibility artifact or movement (n = 4); or d) the cancerous focus was located in the transition zone (n = 12). After these exclusions, 56 patients remained.2; and matrix, 320×256. Transversal T1-weighted images were acquired with the following parameters: TR, 446 ms; TE, 8.1 ms; slice thickness, 5 mm; inter-slice gap, 0 mm; FOV, 360×360 mm2; and matrix, 320×224.All examinations were performed on a 3.0 T GE 750 discovery system MRI scanner  with a 32–element torso phased-array coil. An endorectal coil was not used. The entire prostate gland and seminal vesicles were imaged in axial, sagittal and coronal slices, using a T2-weighted fast-recovery fast spin echo sequence with the following parameters TR range/TE range, 3322-3849/108-118 ms; slice thickness, 3 mm; inter-slice gap, 0 mm; FOV, 180×180 mm2; matrix, 128×96, reconstruction matrix size 256 × 256; bandwidth, 250 Hz/pixel; acceleration factor of 2; and 21 b values (number of excitations) 0 (1), 20 (1), 50 (1), 80 (1), 100 (1), 150 (1), 200 (1), 400 (2), 600 (2), 800 (2), 1000 (4), 1200 (4), 1500 (4), 1800 (4), 2000 (6), 2400 (6), 2800 (6), 3200 (8), 3600 (8), 4000 (10), and 4500 (10) s/mm2. The DWI parameter was optimized to ensure a sufficient SNR at the maximum b-values up to 4500mm/s2. The total acquisition time was 10 minutes and 20 seconds. An additional 5mm section thickness axial T2-weighted image was scanned to match the DWI to provide anatomical information.Axial DWI was acquired using a single-shot echo-planar imaging pulse sequence with the following parameters: TR, 2500 ms; TE, 84.1 ms; slice thickness, 5 mm; inter-slice gap, 0 mm; FOV, 400×280 mmAfter the MRI examination, all patients underwent transrectal ultrasound (TRUS)-guided biopsies. All the biopsies were performed by a single urologist with more than 20 years of experience using an ultrasound system  equipped with a 5.1 MHz endocavitary probe, with a spring-loaded biopsy gun with an 18 gauge core biopsy needle. To match biopsy sextants and MR images, the PZ of the prostate was divided into six regions in MRI, which corresponded to the TRUS-guided biopsy , and two core biopsies per region were obtained. Cores were individually labeled according to their location with respect to the biopsy scheme. Each specimen was histologically analyzed as cancerous or noncancerous by an experienced pathologist (with > 15 years of experience).et al. and Li et al.[2. The SNR was defined as the ratio between the average signal intensity of ROIs and the mean of the standard deviation (SD) of the signals in the bilateral internal obturator muscles[MRI assessment was performed according to the methods used by Rosenkrantz Li et al., 19, andLi et al.. The sizr muscles.:All analyses in the current study were performed on an ROI level , 21. We Mono-exponential modelBi-exponential modelStretched exponential modelDiffusion kurtosis imaging0 is the signal intensity at b = 0 s/mm2. ADC is the diffusion coefficient of the mono-exponential model. <D>, D*, and f are the diffusion parameters of the bi-exponential model: f is the perfusion fraction, <D> is the pure molecular diffusion, and D* is the pseudo-diffusion coefficient. DDC is the diffusion coefficient of the stretched exponential model, and α is the water diffusion heterogeneity index between 0 and 1. Dapp is the diffusion coefficient of the kurtosis model, and Kapp is the kurtosis.Where S(b) is the signal intensity at a particular b-value, and S2, grouped as A, B, C, and D, respectively.To validate the dependence of the models on b-values, the b-values were divided into four different ranges: 0–1000, 0–2000, 0–3200, and 0–4500 s/mm2) for the groups were calculated among different models using Eqs . One. One2) fapp, and Kapp were estimated in the benign PZs and cancerous tissues. The parameters were calculated using all the b-values in groups A, B, C, and D. Normal distribution was assessed using the Kolmogorov-Smirnov test; if the data presented a normal distribution, an independent t-test was performed to compare the differences in parameters between benign PZs and cancerous tissues. For non-normally distributed variables, the Mann-Whitney U test was used. Next, receiver operating characteristic curve (ROC) analysis was performed, and the area under the curve (AUC) was calculated to evaluate and compare the diagnostic accuracy of the parameters in distinguishing cancerous tissues from benign PZs. The diagnostic performance was expressed as the AUC. Differences in AUCs were assessed using the method of DeLong et al[ADC, <D>, D*, f, DDC, α, Dong et al.2 was calculated with Matlab . The statistical analysis was performed using SPSS software . The ROC analysis was performed using MedCalc version 13.0.0.0 for Windows . For all the significance level was set at p< 0.05.The adjusted R2was between 8.784 and 64.118. The mean (±SD) ROI SNRs in cancerous tissues and benign PZs were 27.784±10.245 and 17.035±8.107, respectively. The mean (±SD) ROI sizes in cancerous tissues and benign PZs were 169.780±107.914mm2 and 97.57±22.041mm2, respectively.The final study population comprised 56 PZ PCa patients . The median PSA level in these 56 patients was 26.036 ng/mL . Among the total 336 ROIs, 198 ROIs were evaluated as benign PZs, and 138 ROIs were evaluated as cancerous tissues. The SNR of the ROIs at the highest b-value of 4500 s/mm2 was calculated to test the goodness-of-fit of the models. The mean values and standard deviations of the adjusted R2 are provided in Table 1. The bi-exponential and the stretched-exponential models provided the highest adjusted R2 among the four models in every group. There were no significant differences between the bi-exponential and stretched-exponential models in any of the four groups . The goodness-of-fit of the kurtosis model was slightly less than that of the bi-exponential and the stretched-exponential models in all groups . The mono-exponential provided the worst goodness-of-fit in the four groups. Significant differences were observed between kurtosis and the other three models in all groups . Similarly, the mono-exponential model showed differences from the other three models in all groups . The mean value of the adjusted R2 of the mono-exponential model decreased with increasing b-value. No clear tendency could be established for the bi-exponential, stretched-exponential or kurtosis models .The adjusted RTable 2. The mean values of ADC, <D>, f, DDC, α, and Dapp were found to be significantly lower in cancerous tissues than in benign PZs in each group . Similarly, the Kapp in cancerous tissues was significantly higher than that in benign PZs in each group . We also found a significant difference in D* between cancerous tissues and benign PZs in groups B and C (p< 0.05), but not in groups A and D (p > 0.05). However, the D* showed a large standard deviation in all groups and were significantly higher than those of groups A and B . The AUCs of <D> calculated in groups A, B, and C were significantly higher than in group D . The AUC of <D> in groups A and B showed no significant difference (p = 0.136), and the value of group B was significantly higher than in groups C and D . The AUCs of DDC calculated using groups B, C and D showed no significant difference . The AUCs of DDC calculated using groups B and D were significantly higher than in group A . The AUCs of DDC calculated using groups A and C showed no significant difference (p = 0.102). The AUCs of Kapp calculated using groups B, C, D were significantly higher than in group A ; however, no significant difference was observed among groups B, C, and D .The parameters ADC, <D>, DDC and Kapp were not significantly different (p = 0.204); the AUCs of ADC and Kapp were not significantly different (p = 0.070); the AUC of DDC was slightly higher than the AUC of ADC (p = 0.014); and the AUCs of ADC, DDC and Kapp were significantly higher than those of the other parameters . For the parameters calculated using the b-values of groups B and C, the AUCs of ADC and Kapp were similar , but were significantly higher than those of the other parameters . For the parameters calculated using the b-value of group D, the AUC of ADC was slightly higher than that of Kapp ; the AUCs of ADC and Kapp were significantly higher than those of the other parameters .For the parameters calculated using the b-value of group A, the AUCs of DDC and K2) provided excellent diagnostic performance in PZ PCa detection, such that no extra benefit was obtained from cumbersome non-Gaussian models  and time-consuming over-high b-value (> 3200 s/mm2).Our study demonstrated that for PZ PCa detection, the parameters derived from the bi-exponential, stretched-exponential, and kurtosis models did not reveal significantly superior diagnostic performance relative to conventional ADC. ADC derived from conventional mono-exponential high b-value  than a low b-value (800 s/mm2). However, the highest b-value they used was only 2300 s/mm2. For brain kurtosis imaging, empirical evidence indicates that maximum b-values of 2000 to 3000 s/mm2 are appropriate[2 provided no extra diagnostic value. Therefore, maximum b-values of approximately 2000 s/mm2 may be appropriate for prostate stretched-exponential and kurtosis model imaging. The suggestion of Rosenkrantz et al., that a maximal b-value of 1500–2000 s/mm2 is suitable for body kurtosis imaging, also supports this conclusion[app, the diagnostic value of ADC calculated using a maximum b-value of 3200 s/mm2 was superior to those derived using maximum b-values of 2000 s/mm2 and 1000 s/mm2. The increased maximum b-value provided greater contrast between cancerous and non-cancerous tissues, adding to the diagnostic performance. However, when the b-value was higher than 3200 s/mm2, the rapid decrease in the goodness-of-fit (0.871 to 0.800) may outweigh the extra benefit of ADC.Our study showed that, for PCa detection, the diagnostic performance of DDC and Karameters. Our resarameters, which fpropriate, 28. Howonclusion. In contet al. found that, compared with the mono-exponential, stretched-exponential, and kurtosis models, the parameters of the bi-exponential model demonstrated the worst repeatability and diagnostic performance [2/s), the ROC analysis in our study did not reveal significantly superior performance of the parameters derived from the stretched-exponential and kurtosis models over the conventional ADC for PCa detection, although a higher-quality fit to DWI signal decay was provided. These results are consistent with several previous studies [Non-Gaussian diffusion models have been proposed to describe complicated water diffusion behavior and are believed to provide a more accurate description of the DWI signal decay curves obtained using higher b-values . Our resformance . The poo studies , 32, 33. studies .2 were used in our study, the SNR of the highest images still reached an extremely high level. The following strategies may have played a positive role in increasing SNR. First, we included imaging at a higher field strength (3.0 Tesla). Second, we increased the number of excitations . Third, we used a slice thickness of 5 mm, which is thicker than the 3mm commonly used in clinical settings. Fourth, the resolution we used was 3.125×2.917mm rather than 2.5×2.5mm, which is routinely used in clinical settings. Despite the limitations, we believe our methodical strategies provide sufficient validity for the principal results of our study.There were several limitations in this study. First, this study took the TRUS-guided biopsy as the standard of reference. The use of whole-mount histopathology would improve the accuracy of the agreement between MR images and histopathology. However, it is unreasonable to expect all of our subjects to undergo prostatectomy. Because TRUS-guided biopsy has good specificity but poor sensitivity, a small tumor focus may be missed, resulting in a false-negative diagnosis. In our study, we focused primarily on large tumors, which could partially obviate this problem. Moreover, TRUS-guided biopsy has been the standard of reference in a large number of studies , 35, 36,2) DWI is an optimal choice for clinical routine application in PZ PCa detection. For PCa detection, the diagnostic value of parameters derived from non-mono-exponential diffusion models or higher b-values (> 3200 s /mm2) warrant further multicenter exploration. Furthermore, as highly parameterized non-Gaussian diffusion models have a higher information content than the single-parameter mono-exponential model, they may provide useful information for differentiating PCa from other prostatic lesions and might be promising for monitoring PCa progression or response to therapy, which also needs further evaluation.In conclusion, our study suggested that ADC derived from a conventional mono-exponential model using a high b-value (3200s /mmS1 Data(XLS)Click here for additional data file.S1 Table(DOC)Click here for additional data file.S2 Table(DOC)Click here for additional data file.


Congenital heart block (CHB) is a rare disorder that may be associated with a high morbidity and even mortality, with a risk of death both in utero and during infancy. Women with serum titres of anti-Ro and/or anti-La antibodies carry a risk of CHB of 1–5% in their offspring, with a recurrence risk of approximately 20%. We present a case of a 36-year-old female with a pregnancy complicated by congenital heart block. Autoimmune profiling at booking showed she was positive for lupus anticoagulant and anti-Ro antibodies. A fetal echocardiogram at 21 + 3 showed complete heart block. She was monitored throughout the remainder of her pregnancy with serial growth scans, cardiovascular profiling, and BPP scoring. She had a normal vaginal delivery at term to a female infant. Congenital heart block (CHB) is a rare disorder with an incidence of 1 in 22,000 live births [Mrs. N is a 36-year-old with G 4 P3 booked at 7-week gestation and viability and EDD of 10/3/10 confirmed by ultrasound scan. She had a history of Sjogren's Syndrome and postpartum DVT and was positive for lupus anticoagulant and anti-Ro antibodies. This pregnancy was managed in the multidisciplinary joint Obstetric and Haematology Clinic and Low Molecular Weight Heparin (LMWH) was commenced at presentation.An anomaly scan at 20 weeks was unremarkable and a fetal echocardiogram confirmed a structurally normal heart with a normal PR interval  24 hours later with mild tightening. A BPP during the latent phase of labour was reassuring. Labour established later the same day, progressing rapidly to a spontaneous vaginal delivery of a female infant weighing 3.02 kg with Apgars of 9 at 1 and 5 minutes. She was transferred to SCBU for assessment and observation. An ECG confirmed complete heart block, and an echocardiogram reaffirmed good cardiac function despite a ventricular rate of 55 bpm. She established demand feeding over the next 48–72 hours without compromise and was discharged home with mum within the week. Although she remains under review, at the time of Mrs. N's postnatal review in the JOHC her daughter was thriving and had not required cardiac pacing. actively transferred across the placenta. These are thought to bind to specific cells within the fetal conducting system, resulting in inflammation, scarring, and/or fibrosis. With this in mind Saxena et al. (2015) [At approximately 12 weeks of gestation maternal IgG antibodies against Ro and La intracellular ribonuclear protein are. (2015)  showed aWhilst CHB is the main cardiac manifestation in infants exposed to anti-Ro/La antibodies other pathologies  also occur .Mortality from heart disease unfortunately remains high with the majority of deaths occurring in utero or early infancy  secondarWhilst fluorinated steroids, like dexamethasone, can cross the placenta and may treat first or second degree heart block, they have no benefit in third degree heart block which is considered complete and irreversible . A seconBased on the assumption that treatment for identified heart block in utero may be effective if it can reduce a generalized inflammatory insult and lower the titre of maternal autoantibodies, several prenatal therapeutic protocols have been utilized. All women at risk with antibodies present should be closely followed during the pregnancy with serial echocardiograms, specifically looking for the earliest signs of conduction system disease such as PR interval prolongation by Doppler (see later discussion). If complete heart block is recently diagnosed (within three weeks of onset), a therapeutic course of dexamethasone 4 mg orally once a day may be tried.Prenatal dexamethasone may have a role in preventing late onset cardiomyopathy, which frequently requires pacing; however, this viewpoint is far from universal . By contIt has hitherto been suggested that all women at risk of fetal cardiac disease because of a previous history and/or high positive antibodies should be followed up with serial echocardiograms specifically looking for any prolongation in the PR interval. Nevertheless it has subsequently been established that the onset of CHB is far from predictable and measurement of the mechanical PR interval lacks sensitivity (44%) and/or specificity (88%). Whilst it may be useful in diagnosis, it has no role in prediction or prognosis. However, the electrical PR interval (whilst not available at the time of this case) is proving to be more useful .In our patient, Mrs. N, the changes in the degree of heart block was sudden and unpredictable. However, regular/frequent surveillance permitted prompt recognition which was then amenable to steroid therapy; despite this no benefit was achieved as therapy did not reverse the heart block. This agrees with outcome data from larger data sets. Prenatal dexamethasone would appear to have a role in the prevention of cardiomyopathy necessitating frequent cardiac pacing.umbilical venous pulsation is only scored when noted to be at the atrial rate;intermittent holosystolic tricuspid and/or mitral regurgitation is normal in CHB and therefore not scored;diastolic AV valve regurgitation is low, common, and not scored;small effusion can be seen secondary to inflammation and should therefore be scored.For those infants that survive pregnancy the main dilemma is then how to deliver. Continuous CTG is not possible and there is concern that the fetal heart in heart block does not have the capacity to withstand the demands of labour. The BPP is a 10-point fetal assessment tool first described by Manning et al.  in 1980. Excellent cardiac function was maintained throughout pregnancy (CVP score 10/10) and vaginal delivery, at term, of a female infant, was achieved.With the advances in the ultrasound technology the prenatal diagnosis of autoimmune CHB has become standard care in most institutions. Fetal echocardiogram with measurement of the mechanical PR interval would not predict but will allow earlier diagnosis of heart block and/or the possibility of very early treatment, which may be able to reverse the disease .On the other hand electrical PR reproducibility, sensitivity, and specificity are superior, which, if available, would be the diagnostic tool of choice to use in any trial to investigate both the natural history and therapy of conduction abnormalities in Ro/La pregnancies.What really made a difference is that this case was the consistently reassuring high CVP score through cardiothoracic ratio, atrioventricular valve regurgitation fraction shortening, absence of hydrops, and normal fetal umbilical Doppler.


Takostsubo (stress) cardiomyopathy (TC) is a clinical syndrome featuring transient left ventricular dysfunction and wall-motion abnormalities, usually following emotional or physical stress. The diagnosis of TC depends on fulfillment of multiple clinical criteria. Although the pathogenesis has not been firmly established, myocardial cathecholamine toxicity is thought to represent a primary mechanism.The vast majority of patients with TC survive. However, a rare cause of death in TC is myocardial rupture. All documented cases of rupture have followed known, recently diagnosed or suspected TC. However, in this report we propose that an initial diagnosis of TC with myocardial rupture can be made by autopsy when supported by a compelling clinical history and appropriate histologic changes in the myocardium.An 82 year-old female underwent elective craniotomy for a recently discovered craniopharyngioma. The surgery was uneventful; the initial postoperative course featured diabetes insipidus and delirium. With no prior warning, on the third postoperative day she was found unresponsive in bed. Two prolonged cardiopulmonary resuscitations were successful, however, during a third arrest maneuvers were stopped at the request of the family. An autopsy was conducted which revealed hemopericardium due to cardiac rupture. Coronary artery atherosclerosis, valve disease, and renal and extra-renal pheochromocytoma were absent. Microscopy of the myocardium showed a recent, localized, transmural myocardial infarction and diffuse changes  typical of cathecholamine cardiomyopathy. The findings were considered compatible with TC with secondary myocardial rupture.An initial diagnosis of TC with myocardial rupture can be reasonably made by autopsy in the context of an appropriate clinical history and the presence of the characteristic microscopic features of cathecholamine excess in the myocardium. Takostsubo (stress) cardiomyopathy (TC) is a well-recognized clinical syndrome featuring transient left ventricular dysfunction and wall-motion abnormalities, usually following emotional or physical stress . ElderlyAn 82 year old white female underwent elective craniotomy for resection of a recently discovered craniopharyngioma that had presented as diplopia. Her medical history included mild dyslipidemia, hypothyroidism and osteoporosis. Preoperative evaluation revealed an active lifestyle with no history of cardiac symptoms. A baseline ECG showed a left bundle branch block; no previous ECG was available for comparison. An endocrinological profile was carried out one week before surgery. The serum prolactin was elevated at 60 ng/mL . The following were normal: serum IGF-1 64 ng/mL (33–185), serum TSH 1.86 mIU/L (0.3-4.2), FSH/LH ratio 4/0.8, serum cortisol 385 nmol/mol creatinine (289–35105). The serum sodium was 140 mmol/L (135–145). Other preoperative baseline laboratory values were normal.The surgery was uneventful. Intravenous hydrocortisone was begun according to post-craniotomy protocol. The initial postoperative course featured diabetes insipidus and delirium. The sodium level rose to 148 accompanied by diuresis reaching 1 L per hour. Desmopressin was commenced; the sodium leveled descended to 139 on the second postoperative day. Of note, neither cardiac arrhythmia nor hemodynamic instability was documented.On the third postoperative day she was found unresponsive in bed with agonal breathing. Prolonged cardiopulmonary resuscitation following standard ACLS protocol was promptly started. The patient was stabilized; an emergency head CT scan was performed which showed a small subdural hematoma. Then, approximately ninety minutes after the first episode, a second cardiac arrest occurred in the form of sudden pulseless ventricular tachycardia. The initial cardiac shock provided successful defibrillation. Point-of-care cardiac ultrasound showed a small pericardial effusion (less than 1 cm), normal left ventricular function, and a dilated and diffusely hypokinetic right ventricle. Shortly thereafter, sudden bradycardia with loss of cardiac output developed. During the following third resuscitation attempt cardiac massage and an external pacemaker resulted in no return of cardiac output. At this point the family requested that all maneuvers be stopped. Permission was granted to perform an autopsy.A complete autopsy was performed. Hemopericardium (approximately one liter) was present. The heart weighed 360 g  [Microscopic examination of sections from the rupture site showed epicardial hemorrhage and contraction band necrosis with heavy polymorphonuclear leukocyte infiltrates typical of a recent acute myocardial infarction, approximately 48–72 h  Fig. 1b1b. The uThe pathogenesis of TC is considered to involve neurogenically mediated coronary microvascular spasm and direct myocyte injury due to cathecholamine excess , 2. EvidDescriptions of myocardial cathecholamine toxicity include the following: in an autopsy study of 26 patients with pheochromocytoma Van Vliet et al. found evidence of “active catecholamine myocarditis” in 58% of cases. “Disseminated focal lesions”, found in the myocardium of all four heart chambers, were associated with diffuse myocardial edema and were characterised by focal myocardial fiber degeneration and necrosis with “foci of inflammatory cells that were predominately histiocytes but also included plasma cells and occasionally polymorphonuclear leukocytes”. Lesions most often occurred around small blood vessels . WittsteThe differential diagnosis of the autopsy findings in our case includes “acute myocardial infarction-like syndrome with normal coronary arteries”, viral or post-viral cardiomyopathy, and a toxic or hypersensitivity drug reaction . AlthougCardiac rupture following TC is uncommon, with at least sixteen well-documented cases reported –8. (TempGiven the above observations, there appear to be circumstances in which the diagnosis of TC can reasonably be made post mortem. This is pertinent as a recent study found that TC is associated with significant morbidity and mortality: 7.1% of patients admitted to hospital suffer a major cardiac or cerebrovascular event within 30 days, the death rate from all causes is 5.6% per patient year, and the rate of major cardiac and cerebrovascular events is 9.9% per patient year . PatientWe conclude, based on the findings in this case, that although TC is classically defined by clinical criteria it can be diagnosed at autopsy, as it has features that can be assessed by traditional pathologic evaluation, including distinctive diffuse mononuclear cell infiltrates, and the rare but well described occurrence of myocardial infarction with rupture. The clinical features of our case are those of a typical TC patient, and these, in correlation with the macroscopic and microscopic features of the heart, allow for a reasonably confident diagnosis of TC. However, it is important to note that our case represents a single preliminary observation. To confirm that autopsy diagnosis of TC is indeed feasible will require further reports of additional well documented cases.Lastly, it is important to note the considerable value to the family and treating physicians of establishing by autopsy the cause of this upsetting sudden and unforeseen death.


We hypothesize that lysosomal storage of sphingolipids in the heart as occurring in Fabry disease does not reflect in higher cardiac lipid concentrations detectable by 1H-MRS in 30 patients  with genetically proven Fabry disease and in 30 healthy controls. The study protocol combined 1H-MRS with cardiac cine imaging and LGE MRI in a single examination.Myocardial lipid content was quantified in vivo by p = 0.225). Left ventricular (LV) mass was significantly higher in patients suffering from Fabry disease compared to controls (p = 0.019). Comparison of patients without signs of myocardial fibrosis in MRI  to patients with signs of fibrosis  revealed similar myocardial lipid content in both groups (p > 0.05), while the latter showed a trend towards elevated LV mass (p = 0.076).Myocardial lipid content was not significantly elevated in Fabry disease , could hold the highest potential for the final assessment of early and late myocardial changes in Fabry disease.This study demonstrates the potential of lipid metabolic investigation embedded in a comprehensive examination of cardiac morphology and function in Fabry disease. There was no evidence that lysosomal storage of sphingolipids influences cardiac lipid content as measured by  Fo. Fo3 voxtra Fig. , the quaups Fig. .Fig. 1Il1H-MRS data. In both types of spectra, post-processing was applied with a Hanning apodization of 300 ms and automatic frequency shift correction. Determination of integral values for the resonance signals was supported by prior knowledge. The water signal was set to a ∂-value of 4.7 ppm, which caused protons in methylene (CH2) groups to appear at 1.3 ppm, as well as protons in methyl (CH3) groups at 0.9 ppm ; mean ± SE 0.92 ± 0.36 % in LGEneg.) .Within the patients cohort the comparison of mean lipid/water ratio in LGE negative and LGE positive Fabry patients revealed similar myocardial lipid content in both subgroups  Fig. , showingn = 10) patients, we observed a trend towards LV mass increase in LGE positive (n = 20) Fabry patients (mean LV mass of 173.6 ± 68.9 g in LGEpos. vs. 130.8 ± 54.2 g in LGEneg. patients) . LV function (expressed as EF) was similar in LGE positive and LGE negative Fabry patients  (p = 0.188).Compared to LGE negative (ts) Fig.  without With progress of the disease, almost all male Fabry patients develop symptoms of cardiac insufficiency due to pathological alteration of cardiac morphology and function . IncreasAccordingly, 20 of our 30 patients presented LGE in the inferolateral parts of the left ventricular wall, corresponding with the typical localization of fibrosis in Fabry cardiomyopathy. One might argue that myocardial lipid acquisition and, respectively, voxel placement should be chosen in a position typical for LGE, improving the likelihood of acquiring even higher pathological lipid values. Taking into account that patients suffering from Fabry disease develop a global left ventricular hypertrophy in late stages of the disease and ubiquitous deposition of sphingolipids in the myocardium of patients suffering from cardiac Fabry disease is described in literature, we assume a change of lipid concentration spread over the whole myocardium. There is an appealing advantage of voxel placement in the interventricular septum: there is only a minor or even zero risk to acquire false positive results deriving from lipid contamination of the voxel by epicardial fat , 31–36.Because of the coexistence of advanced renal disease in Fabry patients, which sometimes precludes the use of a contrast agent, retention parameters  were collected from all patients. Furthermore most of the patients had normal blood pressure values. Only one female presented with an elevated blood pressure of 178/88 mmHg. Possible explanations might be the patient suffering from Fabry cardiomyopathy , or her advanced obesity (BMI 37.7).2) and methyl (CH3) groups do not represent the total myocardial lipid content, we limited our measurements to these two peaks in accordance with previous studies  with a lipid/water resonance ratio > 3 %), which raises the question of potential gender effects. The average cardiac lipid content found in our Fabry cohort is not in line with former study results by Thompson et al. postulating elevated cardiac lipid content in a relatively small cohort of n = 4 Fabry patients [Our results show no significant difference between myocardial lipid content in Fabry patients and healthy controls , indicating a prolonged disease history. On the other hand, the potential of ERT to affect myocardial lipid content has not been addressed in literature. Secondly, the published cohort gender proportion is imbalanced towards females . Consequently, a necessary consideration includes the lack of correlation of loss of myocardial function and fibrosis with myocardial hypertrophy among females as opposed to males , an assup = 0.076). When evaluating LGE positive and negative subgroups within the Fabry cohort, no correlation between the presence of LGE  and septal lipid concentration measured by 1H-MRS was observed. Our results suggest that there are at least two different underlying pathomechanisms in Fabry cardiomyopathy. Time line development of fibrosis and elevated myocardial lipid content occurring in some individuals seems unpredictable at this time, possibly due to differences in underlying pathomechanisms.The subgroup evaluation of LGE positive and LGE negative patients within the Fabry cohort revealed a trend towards elevated LV mass in LGE positive patients  could hold the highest potential for the final assessment of early and late myocardial changes, including the potential role of lipid accumulation in cardiac Fabry disease.Most studies concerning ERT in Fabry disease demonstrate a decelerated development of disease after early ERT onset. Therefore early detection of myocardial changes is from utmost importance. Including the results of Sado et al., who suggested myocardial Tolvement , a compr1H-MRS) and ex vivo triglyceride measurements [Due to the known risks of myocardial biopsy, we did not perform comparative invasive triglyceride measurements. Previously published data by O´Connor et al. demonstrated a remarkably high correlation coefficient between in vivo , especially when using short echo times . Particustration .2 vs. 22.4 kg/m2 in controls; p = 0.079). We cannot exclude any influence of the BMI on lipid levels within our patients. Moreover, the gender proportion of the patient cohort is imbalanced towards females .Furthermore, mean age comparison between patients and controls is not fully congruent. More importantly, in the light of the knowledge that BMI correlates with myocardial lipid content , the meaOwing to the x-linked inheritance of Fabry disease, a separate evaluation of both genders will be necessary in future studies. Due to the sample size this was not feasible in the present study. Therefore, further larger studies will be needed to elucidate possible gender aspects.1H-MRS. Therefore the potential of 1H-MRS as a tool for early diagnosis of cardiac involvement and for optimization of ERT onset as leading therapy in Fabry disease remains questionable and needs to be further evaluated. In future native T1 mapping might be a superior comparator to validate actual changes in the myocardium. Finally, the authors share the opinion that a comprehensive cardiac examination including three subsections , could hold the highest potential for the final assessment of early and late myocardial changes in Fabry disease.The present study demonstrates the potential of lipid metabolic investigation embedded in a comprehensive examination of cardiac morphology and function in Fabry disease. There was no evidence that lysosomal storage of sphingolipids influences cardiac lipid content as measured by


Population based studies showed an association of early repolarization in the electrocardiogram (ECG) and a higher rate of sudden cardiac death presumably due to ventricular fibrillation. The triggers for ventricular fibrillation in patients with early repolarization are not fully understood.We describe the case of a young patient with a survived ventricular fibrillation arrest while asleep followed by multiple episodes of recurrent ventricular fibrillation. The admission ECG showed an early repolarization pattern with substantial J-point elevation in most of the ECG-leads. After initiation of a hypothermia protocol, the patient developed an electrical storm with multiple ventricular fibrillation episodes requiring multiple cardioversions. Intravenous isoproterenol infusion successfully suppressed the malignant arrhythmia.Hypothermia appears proarrhythmic in patients with early repolarization and may trigger ventricular fibrillation. This knowledge is particularly important when initiating temperature management protocols in patients after a survived cardiac arrest. During the acute phase of an early repolarization associated electrical storm, isoproterenol is the most effective treatment suppressing the ventricular fibrillation-inducing premature ventricular complexes at higher heart rates. Population based studies showed an association of early repolarization (ER) in the electrocardiogram (ECG) and a higher rate of sudden cardiac death presumably due to ventricular fibrillation (VF) , 2. The A 31-year-old man suffered an out-of-hospital cardiac arrest during the night while asleep. His girlfriend started CPR immediately. Upon arrival of the emergency medical team, the patient was found in VF and defibrillation could restore spontaneous circulation. He had no significant past medical history and was taking no medications. Family’s medical history revealed that the patient’s sister had implanted a pacemaker due to sick-sinus syndrome, at the age of 22 years. Plasma electrolyte levels, including potassium and calcium, were within normal ranges. Toxicological screening was negative. The ECG at presentation showed sinus rhythm and an ER pattern with substantial J-point elevation in most of the ECG-leads with notching of the terminal part of the QRS complex in the lateral leads and slurring in the inferior leads Fig. . The patER is common, occurring in 1% to 5% of the general population [Historically ER was considered benign. Population based studies by Tikkanen et al.  then shoWith regard to risk stratification, Antzelevitch et al  describeDifferent triggers leading to an electrical storm can be discussed. Recent reports point to an association between ER and the development of VF in the setting of hypothermia –10. CurrThe finding of an LAD originating from the right sinus of Valsalva is extremely rare (0.03%) . In geneDifferent therapeutic management options for electrical storms in ERS patients can be discussed. For the acute phase, beta-blockers, verapamil and lidocaine/mexiletine are generally ineffective, while amiodarone may be partially effective (3/10 patients) . The mosIntensive care physicians should be aware of hypothermia as a possible trigger of electrical storm in patients with ERS. This knowledge is particularly important when initiating temperature management protocols in patients after a survived cardiac arrest. During the acute phase of an electrical storm, isoproterenol is the most effective treatment suppressing the VF-inducing PVCs at higher heart rates. For the long-term management, both catheter ablation of the PVC triggers and quinidine have been used successfully to reduce or even prevent recurrent VF episodes.


End-diastolic (EDV) and end-systolic (ESV) volumes, ejection fraction (LVEF), and regional wall motion and thickening (17-segment model) were assessed using Cedars-Sinai QGS Software. Concordance between single- and dual-isotope acquisitions was tested using Lin’s concordance correlation coefficient (CCC) and Bland–Altman plots.The Amsterdam-gated dynamic cardiac phantom  was successively filled with a solution of 123I and 99mTc) for EDV, ESV, LVEF, or segmental wall motion and thickening. Myocardial volumes using single-  and dual-isotope (reconstructed using both 123I and 99mTc energy windows) acquisitions were, respectively, the following: EDV (mL) 88 ± 27 vs. 89 ± 27 vs. 92 ± 29 vs. 90 ± 26 for DNM 530c (p = NS) and 82 ± 20 vs. 83 ± 22 vs. 79 ± 19 vs. 77 ± 20 for DSPECT (p = NS); ESV (mL) 40 ± 1 vs. 41 ± 2 vs. 41 ± 2 vs. 42 ± 1 for DNM 530c (p = NS) and 37 ± 5 vs. 37 ± 1 vs. 35 ± 3 vs. 34 ± 2 for DSPECT (p = NS); LVEF (%) 52 ± 14 vs. 51 ± 13 vs. 53 ± 13 vs. 51 ± 13 for DNM 530c (p = NS) and 52 ± 16 vs. 54 ± 13 vs. 54 ± 14 vs. 54 ± 13 for DSPECT (p = NS); regional motion (mm) 6.72 ± 2.82 vs. 6.58 ± 2.52 vs. 6.86 ± 2.99 vs. 6.59 ± 2.76 for DNM 530c (p = NS) and 6.79 ± 3.17 vs. 6.81 ± 2.75 vs. 6.71 ± 2.50 vs. 6.62 ± 2.74 for DSPECT (p = NS). The type of camera significantly impacted only on ESV (p < 0.001).There was no significant difference between single- or simultaneous dual-isotope acquisition (123I or 99mTc) and acquisition types . With simultaneous dual-isotope acquisitions, the presence of 123I did not impact on LVEF assessment within the 99mTc energy window for either CZT camera.The new CZT cameras yielded similar results for the assessment of LVEF and regional motion using different energy windows ( Gaten-making . In addianalogue  that refanalogue . Previoufarction –8. Due tfarction , 11.123I-mIBG and a 99mTc-labelled perfusion tracer. Bellevre et al. [123I-mIBG uptake in patients with heart failure using dual-isotope imaging with a CZT camera (DSPECT) and combined 99mTc-tetrofosmin injection to localise the heart within the thorax.The new cadmium–zinc–telluride (CZT) detectors offer higher photon sensitivity and dramatically increased spatial energy resolution compared with standard cameras. The advanced technical capabilities of these dedicated cardiac cameras enable combined assessment of myocardial innervation and perfusion within a single imaging session, using a dual injection of 99mTc photopeak during a 123I/99mTc dual-isotope acquisition, further compromising the accuracy of ventricular function assessment using gated SPECT with 99mTc-labelled tracer. This situation remains however to be investigated.Despite their increased energy resolution, the scatter fraction remains high with CZT cameras  . Moreove123I/99mTc) acquisition on the assessment of global and regional left ventricular function in the 99mTc photopeak using two commercially available CZT cameras, Discovery NM 530c  and DSPECT .The aim of this study was to evaluate the impact of simultaneous dual-isotope  simulating the myocardial wall. The cardiac phantom stroke volume was controlled by a programmable adjustable pumping system, and an ECG-triggered signal was produced at a constant heart rate. Four datasets  were acquired using three different ejection fractions  on each camera (DNM 530c and DSPECT) with the following parameters: 10-min acquisition and 70-bpm contraction rate. EDV, ESV, LVEF, and regional wall thickening and motion (17-segment model) were assessed using Quantitative Gated SPECT software . The acquisition parameters were as follows: 70 × 70 matrix for the DNM 530c system and 64 × 64 for the DSPECT with a total of 120 projections recorded by each block in the heart area defined on a short prescan acquisition [99mTc and 159 keV (−5 + 10 %) for 123I, for each acquisition.We used the Amsterdam gated (Agate) dynamic phantom  as a reference for volume and LVEF measurements . This phuisition . The eneWe successively used (i) a DNM 530c equipped with a multiple pinhole collimator and 19 stationary CZT detectors that simultaneously image 19 cardiac views, each detector being composed of four 5-mm-thick elements of 32 × 32 pixels (pixel size 2.46 × 2.46 mm)  and (ii)123I vs. 99mTc), and the interaction between camera type and isotope. Continuous mean values were compared using the Wilcoxon signed-rank test or Mann–Whitney U test when appropriate. Relationship between DNM 530c and DSPECT results were assessed using Pearson’s (r) correlation coefficient, Bland–Altman limit-of-agreement, and Lin’s concordance correlation coefficient (CCC), a measure of both precision and bias [r, r being Pearson’s correlation coefficient. The values of r and CCC were characterised using the Landis and Koch scale  [p value <0.05 was considered statistically significant.Values are presented as mean ± SD. A linear model analysis evaluated the effect of camera, acquisition type , isotope  . A p valStatistical analyses were performed using R software  except the linear model analysis performed using JMP 11 .The mean values of overall cardiac volumes (EDV and ESV), LVEF, and regional wall motion and thickening using single- and dual-isotope acquisitions with DNM 530c and DSPECT are shown in Table p < 0.0001) whereas EDV, LVEF, and segmental wall motion were similar for the two cameras.Linear model analysis demonstrated that the type of camera but not the acquisition mode  impacted on volume measurements. Post hoc Mann–Whitney test showed that this impact was only observed for the ESV measurements  and CCC were similar, also indicating that no systematic bias was present (C.b > 0.97) between the two cameras and the acquisition mode.Lin’s concordance correlation coefficient and Bland–Altman plots .Our results demonstrated the feasibility of LVEF evaluation using gated perfusion SPECT with CZT cameras. On simultaneous dual radionuclide acquisitions, the 123I-mIBG uptake, requiring a dual-isotope protocol to localise the heart [123I-mIBG assessment have an ischemic cardiomyopathy with heart failure . In thiOur results demonstrated that DNM 530c provided higher systolic volumes compared to the DSPECT camera. This camera effect on volume assessment is likely related to spatial resolution. Imbert et al.  reported99mTc acquisition, dual 123I/99mTc acquisition did not compromise the assessment of ventricular function using the 99mTc photopeak. In some patients with severe heart failure, the sole use of 123I-mIBG SPECT can lead to suboptimal localisation of the heart because of the CZT camera’s narrow field-of-view, particularly when cardiac mIBG uptake is very low and the left ventricle is dilated. A dual-isotope protocol acquisition using both perfusion and innervation tracers provides a clear perfusion image and a perfect registration that allows the definition of the heart contours and thus an accurate measurement of 123I-mIBG uptake [Our results also demonstrated that, in comparison with single 99mTc-sestamibi/123I-BMIPP imaging was proposed for assessing rest perfusion and fatty acid metabolism at the same time in patients with recent myocardial infarction [201Tl and 123I-mIBG is well documented on conventional Anger cameras, using the triple-energy window [123I-mIBG and 99mTc-labelled tracers enables the evaluation of innervation-flow mismatch and may provide valuable information to target the trigger zone in the setting of ventricular arrhythmia [123I-mIBG and 99mTc-tetrofosmin myocardial SPECT demonstrated a relevant association between innervation derangement (123I-mIBG) and myocardial synchronicity (99mTc-tetrofosmin).In the clinical setting, simultaneous dual-radionuclide acquisition provides perfectly registered functional images leading to a reduced imaging time. In cardiac SPECT, several dual-radionuclide imaging protocols have been proposed. Simultaneous farction . The duay window  for scatrhythmia , 26. In rhythmia , 27 usin99mTc and 123I from projection data, taking into account the tailing effect to correct the scatter and crosstalk in 99mTc–123I dual imaging. In the present study, we did not apply any tailing effect correction and observed no significant impact on ventricular function assessment.Despite a significant increase in energy resolution and sensitivity, the scatter fraction with the CZT camera is still high, evaluated up to 30 vs. 34 % with conventional Anger cameras . Due to 123I and 99mTc concentration was set to 1:2, which is representative of the low 123I-mIBG myocardial uptake, observed in severe heart failure. Under these specific conditions, the absence of scatter and crosstalk correction using the DNM 530c did not affect ventricular function assessment using 99mTc acquisitions. In severe heart failure, 123I-mIBG myocardial uptake is low and we assumed that the crosstalk and scatter of 123I in the 99mTc photopeak had no consequences.All reconstructions were performed using the vendor’s workstation and available software for both cameras. Routinely, scatter and crosstalk correction is not performed on the DNM 530c camera. Image data from DSPECT were corrected for scatter and crosstalk but not for the tailing effect. In our study, the ratio between Due to the design of the phantom, EDV and ESV were not predetermined. The phantom was filled under static equilibrium conditions at atmospheric pressure to provide a reproducible ejection fraction. Based on this equilibrium, ejection fraction was imposed by injecting a stroke volume into the ventricular cavity , 22. As 99mTc window, even with the DNM 530c. At best, the demonstration could be made by comparing the results obtained with and without scatter and crosstalk corrections. However, the aim of our study was to compare the results obtained with the two CZT cameras using the dedicated commercially available software to mimic routine clinical conditions.As we used only commercially available software, scatter and crosstalk were corrected with DSPECT but not with DNM 530c. However, our results displayed no critical differences between the single-isotope and dual-isotope 123I and 99mTc acquisitions) and simultaneous dual-isotope (123I and 99mTc) acquisitions. Further studies are needed to evaluate perfusion match and mismatch using 123I-mIBG and 99mTc-labelled tracers.In this phantom study, the two CZT cameras (DNM 530c and DSPECT) provided similar results for ventricular function assessment  with single- (separate


The pathophysiology of paradoxical low-gradient (LG) severe aortic stenosis (SAS) remains controversial. As low transvalvular flow has been implicated, we sought to investigate the impact of left ventricular outflow tract (LVOT) ellipticity on the estimation of the LV stroke volume, the calculation of the aortic valve area (AVA) by use of the continuity equation and on AS severity grading.2/m2) and preserved LV ejection fraction, including 120 patients with severe high gradient (HG) AS and 70 with severe paradoxical LG-AS. AS severity, LV volumes and LVOT ellipticity were assessed by 2D-Doppler echocardiography and cardiac magnetic resonance (CMR).We studied 190 consecutive patients  with SAS (indexed AVA < 0.6 cmp < 0.01). Accordingly, the LVOT area measured by planimetry was larger than by 2D-echocardiography, assuming a circular orifice . Inputting the elliptical LVOT area into the continuity equation resulted in a 29% increase in the indexed AVA (from 0.41 ± 0.09 cm2 to 0.54 ± 0.10 cm2). Accordingly, 30 (43%) patients with severe paradoxical LG-SAS were reclassified as having moderate AS. Similar results were obtained when considering 3D-echo for direct planimetry of the LVOT in a subset of 75 patients.The LVOT exhibited an elliptical shape on CMR images, with a shorter anterior-posterior than median-lateral diameter (2.2 ± 0.2 vs 2.8 ± 0.3 cm, Our results confirm that the LVOT is elliptical in shape and that taking this parameter into account in the calculation of the AVA results in reclassification of 43% of patients with severe paradoxical LG-AS into moderate AS. Several recent retrospective studies have indicated that in elderly patients, and particularly in elderly women, severe aortic stenosis (AS) is frequently associated with lower than expected mean transvalvular gradients, even in the presence of preserved left ventricular (LV) ejection fraction (EF) –3. The t2/m2) and truly severe AS (with HG and AVAi < 0.6 cm2/m2). We further hypothesized that use of the continuity equation to calculate the AVA could explain why some patients transiently pass through a stage of severe paradoxical LG-AS during their disease progression [There is considerable debate as to the mechanisms underlying severe paradoxical LG-AS , 4–11. Bgression . There agression . Second,gression –20. DepeThe present study was designed to test the impact of LVOT ellipticity on the Doppler-echocardiographic estimation of LV stroke volume, AVA and AS severity grading, using cardiac magnetic resonance (CMR) as a reference standard. LVOT ellipticity was measured by direct planimetry of the aortic annulus using cardiovascular magnetic resonance (CMR). LVOT ellipcity was also measured by using transthoracic 3D-echocardiography in the subset of patient in whom 3D-volumetric datasets centered on the LVOT were available.st, 2005 and February 30th, 2015. To be selected, patients needed to display a preserved LVEF (≥50%) and to have undergone CMR as part of their initial clinical workup. Patients with more than mild aortic regurgitation or more than trivial mitral regurgitation were not considered for inclusion.Since January 2000, all patients with valvular heart disease referred to our Institution are enrolled into the prospective SALVARE (SAint-Luc VAlve Registry) registry. Baseline demographics, clinical features, as well as echocardiographic and CMR data are collected and stored in an electronic database. Subsequent clinical, echocardiographic and CMR data are regularly updated. From the registry database, we retrospectively selected all patients with native severe aortic stenosis who were included between May1Echocardiographic data were obtained by use of commercially available ultrasound systems. All patients underwent a comprehensive examination, including 3-dimensional echocardiography when available. All tests were conducted by experienced sonographers. Images were analysed off-line using the XCelera software .For assessment of AS, multiple transducer positions were systematically used to record peak aortic jet velocities . The LVO2/m2 and was further stratified into subgroups with high and paradoxically low transvalvular gradients, respectively in the presence of a mean transvalvular gradient ≥ and < 40 mmHg. Patients with severe paradoxical LG-AS were further stratified into subgroups with low flow and normal flow, respectively in the presence of an indexed stroke volume ≤ 35 or > 35 mL/m2 [Severe AS was defined as an indexed AVA < 0.6 cmThree-dimensional echocardiographic datasets centered on the LVOT were available in a subset of 75 patients and analyzed using a QLab workstation . After proper reorientation of the imaging plane, the true short axis of the LVOT was identified just below the aortic annulus. The LVOT area was then measured in midsystole by direct planimetry of the LVOT. Minimal and maximal diameters were also measured at the same level, to calculate the ellipticity index.CMR imaging was performed on a 1.5 T or 3 T magnet  using a five-element cardiac synergy coil for signal reception . After lBy combining hemodynamic echocardiographic data and LVOT area measured on CMR images, the fused indexed AVA was calculated introducing the CMR-derived LVOT area in the continuity equation.χ2 or the Fisher exact test. Correlation between CMR and echo data was evaluated by linear regression. Agreement between the two methods was assessed by Bland-Altman analysis. Intra- and interobserver variability for 2D-echocardiography, 3D-echocardiography and CMR data were assessed in a subgroup of 25 randomly selected patients by use of the intraclass correlation coefficient (ICC) and the Bland Altman method. All tests were two-sided and a p value of < 0.05 was considered indicative of a statistically significant difference.All analyses were performed using the SPSS v19.0 . Continuous variables were expressed as mean ± 1 SD when normally distributed and as median and range when non-normally distributed. Normality was assessed by use of the the Kolmogorov Smirnov test. Continuous variables were compared among groups using ANOVA when normally distributed or else using the Kruskall-Wallis test. Individual differences among groups were compared post-hoc using Tukey-Kramers test for normally distributed data with equal variances, the Games-Howell test for normally distributed data with unequal variances and the Mann-Whitney U tests (with Bonferroni correction for multiple comparisons) for non-normally distributed data. Categorical variables were expressed as counts and percentages. Categorical variables of patients in different groups were compared using n = 43) or more than mild aortic regurgitation or trivial mitral regurgitation (n = 40). The final study population thus consisted of 190 patients; of which 120 displayed a mean transaortic pressure gradient > 40 mmHg (HG-SAS) and 70 had a mean transaortic pressure gradient ≤ 40 mmHg . Patients with severe paradoxical LG-AS were further stratified into groups with normal  and low  transvalvular flow, using the previously described cut-off value of 35 mL/m2 [Among the 273 subjects who met the inclusion criteria, 83 patients were subsequently excluded because of incomplete or poor quality echocardiographic images n = 3 or moreAre summarized in Tables p < 0.001), yielding an averaged ellipticity index of 1.28 ± 0.08. Although the anterior-posterior LVOT dimensions by 2D-echocardiography and CMR were quite similar , with a mean bias of 0.1 ± 1.2 mm  with a mean bias of 1.1 ± 0.6 cm2 , with a mean bias of 10 ± 11 mLs/m2. Similarly, the indexed AVA calculated by use of 2D-Doppler echocardiography and the continuity equation was also smaller than the indexed AVA measured using CMR and direct planimetry of the anatomical orifice , with a mean bias of 0.13 ± 0.09 cm2/m2.As shown in Fig. 2) and indexed AVA . As a consequence, the systematic biases seen when assuming a circular LVOT almost completely disappeared . Using the CMR planimetered LVOT area increased the indexed AVA40mmHg from 0.41 ± 0.09 to 0.59 ± 0.11 cm2/m2.Inputting the CMR planimetered LVOT area into the calculation of the LV stroke volume resulted in a 29% increased of the indexed stroke volume (from 42 ± 9 to 54 ± 11 mL/m/2/m2), including 19/120 HG-SAS (16%), 5/25 paradoxical LF-LG-SAS (20%) and 25/45 paradoxical NF-LG-SAS (55%). Accordingly, the concordance between Doppler-echocardiography and CMR increased from 74 to 84%, when defining severe AS as an indexed AVA < 0.6 cm2/m2, and from 84 to 93%, when defining severe AS as either an indexed AVA < 0.6 cm2/m2or a MG > 40 mmHg (p < 0.01).By using the fused indexed AVA, 49 patients with severe AS were reclassified as having moderate AS  with a mean bias of 0.1 ± 0.6 cm2. Inputting the 3D-echo or CMR planimetered LVOT areas into the continuity equation yielded similar indexed stroke volumes  and indexed AVAs . Reclassification of AS severity based on 3D-echo and CMR derived planimetered LVOT areas yielded similar results.To test the ability of 3D-echocardiography to measure the true LVOT area and hence to compensate for the inherent limitations of 2D-echocardiography, we compared the planimetered LVOT areas by 3D-echo and CMR in a subset of 75 patients in who zoomed 3D-echo datasets centered on the LVOT were available. 3D-echo and CMR LVOT areas were similar  of 0.99 with a bias of 0.06 ± 0.46 cmIn almost every patient, the LVOT exhibits an elliptical shape, with a larger transverse than anterior-posterior diameter;Inputting the CMR planimetered LVOT area into the continuity equation increased the indexed stroke volume and the indexed AVA by 29% and significantly reduced the bias between echocardiographic and CMR data;Based on the fused indexed AVAs, 55% of patients with severe paradoxical NF-LG-AS, 20% of patients with severe paradoxical LF-LG-AS and 16% of patients with severe HG-AS were reclassified as having only moderate AS. Use of the fused indexed AVA improved the concordance between Doppler-echocardiography and CMR by an average of 10%.The aim of the present study was to test the impact of LVOT ellipticity on the estimation of LV stroke volume, on the calculation of the AVA by use of continuity equation and on AS severity grading. CMR was used as the reference method for estimation of both LV stroke volume and AVA. Our results can be summarized as follows:Accurate measurement of the LV stroke volume is of paramount importance in the calculation of the AVA by use of the continuity equation . Using 2The present study fully supports these previous findings. Our observations confirm that the LVOT is elliptically shaped and that its minor axis corresponds to that measured by 2D-echocardiography. Our data also indicate that the degree of underestimation of the LVOT area by 2D-echocardiography when assuming a circular orifice is as large as 29%. Since the LVOT area is used to calculate the LV stroke volume, this parameter was proportionately underestimated. Other studies have previously reported similar underestimation of stroke volume by 2D-Doppler echocardiography –29.Because stroke volume is at the numerator in the continuity equation, calculated AVAs should be underestimated as well. Large degrees of underestimation of the AVA by the continuity equation in comparison of the planimetric AVA have been described before,  but were2. Minners et al. demonstrated that using 2D-Doppler echocardiography instead of catheterization to calculate the AVA results in a significant downward and leftward shift of the mean gradient valve area relationship, [2 but rather to an AVA of 0.81 cm2, when using the Gorlin formula, and 0.75 cm2, when using the continuity equation. This 19–25% underestimation of the expected aortic valve area when using 2D-Doppler echocardiography explains why up to 40–45% of patients with a calculated AVA < 1 cm2 present with lower than expected mean transaortic pressure gradients, i.e. with a mean transaortic pressure difference < 40 mmHg and why, at the opposite, very few patients with an aortic valve area > 1 cm2 present with a mean transaortic pressure difference > 40 mmHg (<3%). The present study confirms and extends these observations. In line with previous studies, the proportion of patients presenting with lower than expected mean transaortic pressure gradient was as high as 37%. Based on the mean gradient gradient - AVA relationship, a mean transvalvular gradient of 40 mmHg was found to correspond to an indexed AVA of 0.44 cm2/m2 (AVA40mmHg). Correcting for LVOT ellipticity reduced the proportion of patients presenting with lower than expected mean gradients to 25% and increased the indexed AVA40mmHg to 0.59 cm2/m2.As expected, underestimation of both the stroke volume and the AVA by conventional 2D-Doppler echocardiography had a major impact on the relationship between the AVA and the mean transaortic pressure difference. Gorlin and Gorlin were the first to systematically study this relationship . CompariCorrecting the hemodynamic equations for the LVOT ellipticity also had a profound impact on the classification of AS patients into the different AS subgroups. Indeed, as many as 25% of patients with initially severe AS were reclassified as having moderate AS, including 16% of patients with severe HG-AS, 20% of patients with severe paradoxical LF-LG-AS and 55% of patients with severe paradoxical NF-LG-AS. As a consequence, the concordance between Doppler-echocardiography and CMR improved from 74 to 84%. Similar results were recently reported by other investigators, using either multidetector computed tomography  or CMR .Reclassification of patients with severe paradoxical NF-LG-AS into moderate AS may have important therapeutic implications since previous studies have shown that the survival of these patients was quite similar to that of patients with moderate AS. Their valves have also been shown to contain less calcium than those from patients with severe HG-AS, which further support the contention that they most probably do not exhibit truly severe AS , 34.By contrast, only a minority of patients with severe paradoxical LF-LG-AS were reclassified as having moderate AS when correcting for LVOT ellipticity. Although this could indicate that they suffer from a more severe form of AS, as would be suggested by their worse outcome in some of the previously published series, , 8, 9 onSeveral studies have demonstrated the accuracy of 3D-echocardiography, and particularly 3D-transesophgeal echocardiography to delineate the elliptical shape of the LVOT and to measure its true cross-sectional area , 36. OurOur study has several limitations that should be acknowledged. First, this is an observational study based on the a posteriori selection of patients having undergone CMR as part of their initial workup as well as on the retrospective analysis of the CMR data. Our results thus need to be confirmed in prospective studies. Second, planimetry and continuity equation-based AVAs are not identical. As discussed above, the first measures the anatomic valve area and the second measures the effective orifice area at the level of the vena contracta. In theory, they differ by a factor known as the coefficient of orifice contraction, which compensates for the continuous convergence of fluid streamlines beyond a stenotic orifice. Although fluid dynamics studies have indicated that neglecting this coefficient could lead to a 10–15% underestimation of the true anatomical orifice when using the continuity equation, our date indicate that this is certainly not the only factor to be considered and that underestimation of the LVOT area plays, at least, an equally important role. Finally, planimetry of the LVOT by 3D-echo was only available in 75 patients. The accuracy of this measurement should thus be confirmed in larger cohorts.Our results confirm that the LVOT is elliptically shaped and that failure to take this characteristic into consideration when calculating the LV stroke volume and the AVA results in a 29% underestimation of these parameters as compared to CMR. Consequently, as many as 25% of patients with severe AS are reclassified as having only moderate AS when inputting the correct LVOT area into the continuity equation. This is particularly true in patients with severe paradoxical NF-LG-AS, of whom about 2/3 are reclassified as having only moderate AS.


Delineating the area-at-risk (AAR) is crucial in determining the amount of salvaged myocardium following an acute myocardial infarction (MI). Myocardial parametric mapping (native T1- and T2-mapping) has been promoted as an excellent method to delineate the AAR, and image reproducibility appears to be superior to that for black-blood TSE imaging [We used a canine model of acute MI with variable coronary occlusion times (40-90 min) to create a range of infarct sizes and transmurality (n = 12). We obtained high spatial resolution T1 and T2 maps (0.75 × 0.75 × 6 mm) to reduce the magnitude of partial volume effects in altering T1 and T2 measurements. CMR was performed 2-5 days following MI at 3T (Siemens Verio). The AAR and MI were delineated by pathology using microspheres and TTC staining, respectively. Abnormal regions on MRI were compared to pathology by quantitative measurement of the transmural-extent of the abnormality . T1 and T2 values were measured within the infarcted and salvaged portions of the AAR and in remote myocardium. CMR was also performed in five patients with acute MI for which imaging and analysis were performed similar to that for canines.Analysis of the 60 matched slices in canines demonstrated there was no relationship between the transmural extent of elevated T1 and T2 regions on MRI and that of the AAR delineated by microspheres . Instead, there was a strong correlation with that of infarction by TTC . Of 32 slices with subendocardial MI  confirmed by pathology, 30 (94%) and 30 had T1 and T2 abnormalities that were limited to the subendocardium, respectively (Fig. With high resolution T1 and T2 mapping, no relationship was seen between the transmural extent of T1 and T2 abnormalities and that of the AAR by pathology. Instead there was a strong correlation with the transmural extent of infarction. The use of native T1 and T2 mapping to delineate the AAR is problematic.