Peripartum cardiomyopathy (PPCM) is an uncommon disease of pregnancy, occurring in about 1 in 2000 live births, and is characterized by the development of heart failure, due to left ventricular systolic dysfunction. It is associated with high rates of maternal and neonatal mortality. Cardiac disease is the leading cause of maternal death in the UK: PPCM accounts for about 17% of these. Clinical findings of decompensated heart failure (HF) are often masked by the normal physiological changes seen in pregnancy making the diagnosis challenging. A high index of suspicion is essential—prompting referral for echocardiogram, which is crucial for diagnosis. Favourable prognosis is dependent on the early initiation of HF medications. Although full recovery occurs in around half of cases, left ventricular systolic dysfunction persists in a significant proportion of patients with PPCM and the risk of recurrence in subsequent pregnancies is high. The pathophysiology of PPCM is under intense research. We present four patients with PPCM and a review of the literature. Owing to the diagnostic challenge of PPCM and decompensated HF in pregnant mothers and its high mortality rate without treatment, prompt investigation and referral are key to improving maternal survival. Cardiac disease is the leading cause of maternal death in the UK . PeriparWe present a series of four women who presented with PPCM in our centre, of which two died. Their clinical presentations were variable and, so, represented an important diagnostic challenge.A 26-year-old woman gave birth by spontaneous vaginal delivery at 41 weeks to her third child. She presented to hospital 6 months later with dyspnoea, light-headedness, and palpitations. ECG on admission showed sinus tachycardia, left axis deviation, and T-wave changes . Chest XUnfortunately, her postoperative period was complicated by acute ischaemia of the left lower limb requiring above knee amputation and a prolonged period of renal replacement therapy. Her cardiac function improved over a period of two months and the BiVAD was successfully explanted. She had, remarkably, good cardiac function after explant. She remains well to date on beta-blocker and ACE-inhibitor.A 25-year-old primiparous woman with a history of insulin-dependent diabetes mellitus presented at 34 weeks' gestation with preeclampsia, for which she was given steroids. Emergency Caesarean section was undertaken at 35 weeks for preeclamptic toxaemia, following which she was discharged home on day 4. She was readmitted 2 days later with dyspnoea and orthopnoea. Initial differential diagnoses were panic attack and pulmonary thromboembolism. The diagnosis of decompensated HF was only made following a chest X-ray showing pulmonary oedema.She was intubated and transferred to the National Heart Failure Unit. She was supported by an intra-aortic balloon pump, which was successfully weaned after 5 days. Her follow up echocardiogram showed good ventricular functions. She remains well to date on beta-blocker, ACE-inhibitor, and aldosterone antagonist. She also had a trial of bromocriptine for three months.A 31-year-old primiparous woman presented a 17 weeks' gestation with dyspnoea, which had worsened by 22-week review. At 29 weeks, she represented with a 3-week history of palpitations, tachycardia, and worsening dyspnoea and was discharged home following a normal ECG. She subsequently deteriorated, with further worsening dyspnoea, and was treated at primary care with antibiotics, steroids, and inhalers. She was, again, readmitted at 32 + 6 weeks with dyspnoea at rest and tachycardia.Cardiomyopathy was diagnosed, she had an emergency Caesarean section and delivered a live baby, and then she was transferred to a cardiac unit. Cardiac function further deteriorated, and she died in the postnatal period.A 35-year-old woman, with one previous pregnancy, gave birth by elective Caesarean section at 39 weeks to a live male. She had previously collapsed at home at 28 weeks' gestation. She died in the postnatal period, and cardiomyopathy was demonstrated at postmortem.Peripartum cardiomyopathy (PPCM) is a rare condition, with an incidence estimated to be around 1 in 2000 live births, and is associated with high rates of maternal and neonatal morbidity and mortality .It is characterized by the deterioration of left ventricular systolic function towards the end of pregnancy, or in the postnatal period in the absence of another cause for heart failure . RecurreThe aetiology of PPCM is currently unclear, though this is currently the subject of much promising research, which may pave the way for novel approaches to treatment, which will be discussed later. It may well be that some cases are hitherto undiagnosed cardiomyopathies that only become overt in pregnancy; it is important that it is borne in mind that cardiac disease may come to the fore during gestation and in the peripartum period.Diagnosis is mainly based on clinical suspicion and echocardiogram. However, a problem lies in that many of the signs and symptoms of normal pregnancy are indistinguishable from heart failure, and the condition may be missed completely or misdiagnosed. Electrocardiogram (ECG) may be relatively unremarkable , and cheThe Centre for Maternal and Child Enquiries has thus suggested that “women in late pregnancy or within 6 months of delivery with symptoms of breathlessness, or oedema, or orthopnoea and the signs of tachypnoea and tachycardia may have PPCM, and investigation with a chest X-ray and echocardiogram are indicated” .There are recognised risk factors for PPCM, which provide us with a tool to identify those who are at risk of developing the condition. Obesity, smoking, excessive alcohol consumption, and malnutrition are all potentially modifiable risk factors for the disease, and education about these risk factors should inform all patients' antenatal period regardless of any particular suspicion of PPCM. Any previous personal or family history of heart disease should alert clinicians to a high-risk pregnancy.Several recommendations for alterations to service provision in order to improve maternal outcomes were made by the “Saving Mothers' Lives” report . PrepregThe exact management strategy for PPCM depends on the individual clinical case but is essentially based on the stability of the patient. Acute heart failure and stable heart failure are managed quite differently. Acute heart failure in the peripartum period is managed  in just Management strategies for those with stable heart failure in PPCM  are dictMore than 50% of women recover without complication, with left ventricular systolic function at rest returning to normal . The risRecent genome-wide and family studies have shown a possible basis for the aetiology of PPCM and may present a novel screening tool for at risk populations. It has been shown to show some concordance in families, though this may simply be a first manifestation of familial dilated cardiomyopathy . A genomIt has been shown in mice that a product of protein cleavage causes impairment of cardiac myocyte function resulting in PPCM due to its antiangiogenic and proapoptotic properties. This effect was successfully abrogated in these mice by administration of bromocriptine and by inhibiting prolactin secretion and may hold therapeutic promise in humans .α, IFN-Υ, IL-6, and CRP have been shown to be higher in PPCM than in healthy controls [Inflammatory markers including TNF-controls , though Antibodies directed against cardiac tissue have been found in PPCM patients , 10, thoDue to its rarity, variability in presentation, and potential for mortality, PPCM should be considered in women that present with features consistent with left ventricular failure, though it should be borne in mind that this can mimic the normal physiological changes of pregnancy. And when it does occur, careful cardiac followup is essential.


Chronic heart failure is an important cause for morbidity and mortality in adults with congenital heart disease (ACHD). While NT-proBNP is an established biomarker for heart failure of non-congenital origin, its value in ACHD has limitations. Asymmetrical dimethylarginine (ADMA) correlates with disease severity and independently predicts adverse clinical events in heart failure of non-congenital origin. Its role in ACHD has not been investigated.In 102 patients ADMA and NT-proBNP were measured and related to NYHA class, systemic ventricular function and parameters of cardiopulmonary exercise testing.In contrast to NT-proBNP ADMA differentiated between NYHA classes I-III. Both, ADMA and NT-proBNP showed a good correlation with parameters of cardiopulmonary exercise testing with comparable receiver-operating characteristic curves for identifying patients with severely limited cardiopulmonary exercise capacity.ADMA seems to be a better biomarker than NT-proBNP for the assessment of NYHA class and as a good as NT-proBNP for the estimation of maximum exercise capacity in adults with congenital heart disease. Its use in clinical routine should be evaluated. Chronic heart failure is an important cause for morbidity and mortality in adults with congenital heart disease (ACHD) The patients were recruited during a routine outpatient visit at the Adult Congenital Heart Disease Clinic of the Hannover Medical School. All patients in whom a venous blood sampling was feasible were eligible for this study. The study was approved by the local Ethics Committee of Hannover Medical School, Germany. All patients gave written informed consent.A clinical workup including medical history, physical examination, 12-lead electrocardiography, transthoracic echocardiography and cardiopulmonary exercise testing was performed.The severity of the congenital heart defect was graded according to complexity as proposed by recent guidelines Blood samples for measurement of plasma ADMA and NT-proBNP, and routine chemistry were drawn. Blood samples were immediately cooled on ice, centrifuged at 1,500 g and 4°C for 10 min. Supernatants were stored in 1 ml aliquots at −80°C until further use.Plasma concentrations of ADMA were measured applying a liquid chromatography-mass spectrometry method described elsewhere All other measurements were done with routine laboratory tests using certified assay methods.A standard 2D-Doppler transthoracic echocardiogram was performed according to the recommendations for the assessment of ventricular function and valvular heart disease issued by the American Society of Echocardiography 2), and carbon dioxide production (VCO2), were measured continuously by a breath-by-breath method. Subjects breathed through a fitted mask and a hot-wire anemometer  measuring inspired and expired flow continuously.Cardiopulmonary exercise studies were performed on a bicycle in sitting position, starting with 25 W, increasing further 25 W every 2 min. All patients exercised to the end of their tolerance. A 12-lead ECG was recorded throughout the exercise test to determine heart rate and increase in heart rate. Systolic blood pressure and increase in systolic blood pressure, as well as work rate (W/kg) were measured. Ventilation, oxygen uptake  <20 ml/min/kg, ventilatory equivalent for carbon dioxide (EQCO2)>34, ventilatory equivalent for oxygen (EQO2)>34, oxygen pulse for female <9 ml/heartbeat, for male <12 ml/heartbeat. For further analysis a group of patients that was severely affected was defined. These patients had a peakVO2<20 ml/min/kg or an EQCO2>34 or a combination of both. Univariate logistic regression analysis was performed. Parameters with a p value<0.1 were included into a multivariate logistic regression analysis. Receiver-operating characteristic curves (ROC curve) for these parameters were drawn and the areas under the curves calculated.For the parameters of cardiopulmonary exercise testing cut off values representing patients with limitations of their cardiopulmonary exercise capacity were defined: peak oxygen uptake  of patients with NYHA IV these were also excluded. Hence, the final analysis is based on 94 patients. Renal function assessed by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation ADMA did not reach a statistically significant difference in patients with severe ventricular dysfunction (0.50±0.14 µmol/l) compared to patients with moderate dysfunction  and normal ventricular function . NT-proBNP was elevated in severe ventricular dysfunction compared to moderately impaired ventricular function  and normal ventricular function  and also between the later two (p = 0.037).ADMA differentiated between NYHA classes: NYHA I (0.44±0.06 µmol/l) to NYHA II , and NYHA III  and between NYHA II and III (p = 0.02). Figure 12 was significantly higher in patients in NYHA I (28.8±7.6 ml/min/kg) vs. patients in NYHA II  and patients in NYHA III  and also in comparison between NYHA II and NYHA III (p = 0.001). When grouped according to ventricular function patients with a normal function had a significantly higher peak VO2 (28.5±7.6 ml/min/kg) compared to patients with a moderate  or severe impairment of their ventricular function . There was no significant difference between the later two (p = 0.879).Peak VO2 (p = 0.004), EQCO2 (p = 0.002) and EQO2 (p = 0.005). There was not a statistically significant difference for oxygen pulse (p = 0.088) (ADMA was elevated in patients with limited cardiopulmonary exercise capacity compared to their peers. Significant differences were observed for peak VO= 0.088) Table 4.2<20 ml/min/kg or an EQCO2>34 or a combination of both) revealed four parameters with a p value<0.1: age, ADMA, cystatin C and NT-proBNP  Nitric oxide (NO) is involved in the modulation of all regulatory steps of excitation-contraction coupling in the heart A limitation of this study is its cross-sectional design. To allow predictions about the prognostic value of elevated ADMA levels a longitudinal study is needed. This would be of great interest since previous studies suggest that NT-proBNP is not helpful in predicting clinical course of heart failure in ACHD


Many genes have been confirmed to be involved in this disease. An ideal system with which to uncover disease mechanisms would be one that can measure the changes in a wide range of cardiac activities associated with mutations in specific, diversely functional cardiac genes. Such a system needs a genetically manipulable model organism that allows Drosophila melanogaster as our model organism and developed for it a dual en-face/Doppler optical coherence tomography (OCT) instrument capable of recording multiple aspects of heart activity, including heart contraction cycle dynamics, ostia dynamics, heartbeat rate and rhythm, speed of heart wall movement and light reflectivity of cardiomyocytes in situ. We applied this OCT instrument to a model of Tropomyosin-associated DCM established in adult Drosophila. We show that DCM pre-exists in the larval stage and is accompanied by an arrhythmia previously unidentified in this model. We also detect reduced mobility and light reflectivity of cardiomyocytes in mutants.With a simple heart, a transparent body surface at larval stages and available genetic tools we chose Drosophila.These results demonstrate the capability of our OCT instrument to characterize in detail cardiac activity in genetic models for heart disease in  Dilated cardiomyopathy (DCM) is a progressive pathological cardiac condition characterized by an enlarged heart with impaired contractility, defects that often lead to heart failure. To date a wide range of genes, from those involved in mechanobiochemical signaling to components of the contractile architecture, have been confirmed to cause DCM when defective Drosophila melanogaster, is an ideal model for this experimental approach. It has an open circulatory system, a cardiovascular organ called the dorsal vessel driving hemolymph flow around the body in vivo. Despite the obvious morphological differences between the Drosophila and vertebrate hearts there is a remarkable degree of conservation between the two, not only in the characteristic rhythmic cardiomyocyte contraction, but also in the genetic networks that regulate early heart development Drosophila and vertebrate hearts mutations in homologous genes cause DCM-like phenotypes Drosophila provide the ability to knockdown more than 90% of the genome using RNAi specifically targeted to the dorsal vessel The fruitfly, Drosophila-based heart model is an imaging technique that can accurately record cardiac dynamics. Several approaches have been reported. In the embryo cardiac dynamics can be recorded in situ using fluorescence microscopy combined with cardiac specific expression of GFP Drosophila larvae Drosophilaen-face image oriented as in conventional microscopy, could provide further functional information.Key to the potential of this en-face orientation, of the Drosophila larval heart. In the Doppler regime, movement of the heart wall is measured. We demonstrate the utility of this instrument in recording larval heart dynamics by applying it to the analysis of a mutation in the Drosophila muscle specific Tropomyosin gene previously shown to cause a DCM phenotype in the adult fly heart in situ. In combination with the genetic tools available in Drosophila, this instrument provides an excellent platform for future detailed study of the molecular mechanisms of DCM and arrhythmia.Here we describe an OCT instrument which can operate in two regimes. In the imaging regime, the system can acquire OCT images, with either cross sectional or en-face OCT  imaged in this work, the dominant form of contraction was a peristaltic wave of caudal origin   , indicat1118w and 3TM2 larvae exhibited chamber shortening contractions , heart pausing increased to ∼26% (n = 27) in 3TM2 mutants .The reduced light reflectivity in the Our data reaffirms that, predominantly, heart contraction takes the form of a peristaltic wave of posterior origin. In embryos DrosophilaDrosophila and human in tropomyosin-associated arrhythmia in DCM suggests a conserved disease mechanism between species. Thus our OCT instrument provides a powerful tool for further investigation of the molecular mechanisms of the DCM coupled arrhythmia.Arrhythmias occur in one third of the patients suffering from DCM associated with mutation in the α-tropomyosin gene Drosophila requires the following attributes. It must be capable of imaging the heart in the intact animal, to do so it must be capable of penetrating the overlying cuticle and be capable of imaging at depth. Ideally orthogonal images of the heart should be acquired so that the full length of the organ can be observed. In addition, as the Drosophila larval heart beats between 3.5 and 4 times a second The ideal instrument for recording cardiac dynamics in OCT has several of these attributes. It is a label-less imaging technique that generates an image from interference between an internal reference beam and light reflected by the target. It is capable of imaging at depth through the cuticle.Drosophila heart have produced cross-sectional images to depict the dynamics of heart diameter, and therefore heart rate, in real time en-face oriented images of the Drosophila heart at the required frame rate, -OCT that can, in principle, achieve high speeds of frame acquisition by using resonant scanners en-face images at up to 5 Hz rate, slightly faster than mean heart rate in Drosophila larvae.Previous studies that applied OCT to imaging of the adult Although the 5 Hz acquisition rate has largely improved our capability of following the heart rate, we are still missing important parts of the heart wall motion during each beat. To address this deficiency, we complemented the information acquired during the imaging process with that acquired during Doppler signal recording. In this regime, the heart wall motion is recorded in real time. This technique exploits the fact that a moving light-scattering object imposes a Doppler shift to the frequency of the scattered light that is proportional to the velocity of the movement of the object. In our instrument a Doppler shift was produced when the distance between fixed detecting focal point and heart wall changes due to the contraction/relaxation movement of the latter. The wavelength of the SLD light source, together with the speed of movement of the heart wall, place the Doppler frequency within the audio range; hence our instrument performs like a stethoscope and the Doppler signal may be plotted as a sound signal using Audicity software. A typical heartbeat audio recording from a control larva is shown in the supplement material , and theen-face imaging/Doppler signal recording OCT system is shown in Drosophila larval heart). Two telescopes conveniently alter the diameter of the beam in order to match the aperture of different elements in the probing path and convey a probing beam of around 8 mm in diameter through the microscope objective MO's pupil plane. The two transverse scanners, SX and SY, are separated here using a telescope in order to project a flat wave-front on the target under high numerical aperture (NA). Lenses L1, L2 and L4 have a focal length of 7.5 cm, while lens L3 has a focal length of 3 cm. The MO is a scan lens  specially designed by ThorLabs to prevent image degradation and distortion during scanning. Hence, a lateral resolution better than 4.3 µm in the en-face OCT images is obtained (determined by imaging a USAF test target). To maintain this lateral resolution throughout the whole depth of the specimen, tracking of coherence gate and focus position (dynamic focus) has been implemented by simultaneously adjusting the two arms of the interferometer via the computer driven translation stages TS1 and TS2.A schematic diagram of the dual en-face  and the frame scanning is much slower . The frame grabber in en-face image, in the plane  is generated at constant depth. The next en-face image at a new depth is then generated by moving the translation stage, TS1, in the reference arm of the interferometer and repeating the  scan. En-face images with a size of 1.5 : 1 in width over height in this report are obtained using suitable amplitudes for the voltages applied to the X and Y-galvoscanners.Light back-scattered by the specimen passes a second time through the object arm, guided via the first directional coupler towards the second single mode directional coupler where it interferes with that coming from the reference arm. Both output fibers from the second coupler are connected to two pin photo-detectors, PD1 and PD2, in a balanced photo-detection unit constructed using a differential amplifier, DA. The OCT signal is rectified and low pass filtered in the demodulator DMOD. A computer-driven translation stage, TS1, is used to alter the reference path length to select different depths for C-scans while acquiring stacks of C-scans as well as scanning the depth in the B-scan acquisition mode. The scanning procedure is similar to that used in any confocal microscope, where the fast scanning is To switch the system to the audio (stethoscope) regime, the scanning of the beam across the specimen is interrupted using switches SWX and SWY. Hence, the recorded interferometric signal, low-pass filtered by the DMOD block, is exclusively due to projection of movement of the heart wall along the axial direction of the objective lens.1118w and Tropomyosin II mutant 3TM2 stocks were obtained from the Bloomington Drosophila Stock Centre  and raised on standard fly food at 25°C. The 1118w is control strain carrying a mutation in the w (white) gene which affects the production of red pigment in the adult eye but has no known effect on heart morphology or physiology.The Drosophila larvae need to be immobilized. There are a number of techniques which can be used to achieve this rd instar larvae were immobilized by adhering them, ventral side down, to double-sided sticky tape on a glass slide. This method is simple, fast and easy. However, care must be taken not to overstretch the larvae, as the heart is suspended via alary muscles anchored to the body wall To image heart activity, http://audacity.sourceforge.net/).The axial plane at which the heart exhibited its widest diameter was chosen for imaging. The photodetected optical signal was finally converted into images by means of a custom Bitflow SDK based software operating on a Raven BitFlow dual stage frame grabber. Individual stacks of over 100 frames per larva were recorded. After imaging, the system was switched to the stethoscope Doppler OCT regime for audio recording. Immediately after switching, the specimen carrying stage was slightly readjusted till the position where the highest pitch or frequency of the Doppler signals was detected. Then the Doppler signal in that position in each heart was acquired via the audio card of the computer and plotted using Audacity software (http://rsbweb.nih.gov/ij/). Among the recorded total frames in each animal, the frame showing the greatest distance was chosen to represent the end of heart diastolic caliber (EDC). The frame with the least distance was chosen to represent the end of systolic caliber (ESC). Heart shortening fraction was calculated by [(EDC − ESC)/EDC] ×100%. Data recorded at 2 Hz and 5 Hz were pulled and used in this shortening fraction analysis.The heart chamber size, the distance between the two sides of heart walls in the heart image frames at the sagittal plane was measured with Image J Click here for additional data file.Movie S1Drosophila larva. The speed of the movie is 5 frames / sec.Heart beat in a wild type (5.23 MB AVI)Click here for additional data file.Movie S2The speed of the movie is 5 frames/ sec. Cardiac chamber-shortening contraction in a Tropomyosin mutant larva.(6.51 MB AVI)Click here for additional data file.Movie S3Cardiac pausing in a Tropomyosin mutant larva. The speed of the movie is 5 frames / sec.(5.09 MB AVI)Click here for additional data file.


Alström syndrome (ALMS) is a rare autosomal recessive genetic disorder characterised by progressive endocrine disarray, sensorineural deficit, cardiac, renal, and hepatic abnormalities. Idiopathic infantile dilated cardiomyopathy (CMP) is common, presenting acutely in 45% of individuals and recurs or develops de novo in 65% of adolescents with high rates of morbidity and mortality. Myocardial fibrosis has been demonstrated at post-mortem and on MRI with patchy diffuse late gadolinium enhancement (LE) in an older cohort of ALMS patients. We hypothesise that subclinical diffuse fibrosis in young patients with ALMS precedes any change in conventional parameters of ventricular function or overt scarring on LE.Thirteen patients  from the National Specialist Commissioning Group for Alström Syndrome, Birmingham, UK and matched age and gender controls were prospectively assessed with 2D echocardiography and cardiac MRI (1.5T). Late gadolinium enhancement images were acquired 5-7 minutes after contrast. Myocardial extracellular volume (ECV) was assessed using T1-mapping pre and 15 minutes post gadolinium (0.1mmol/Kg) using a modified look-locker inversion recovery sequence (MOLLI) . Septal myocardial ECV was increased in ALMS compared to controls . Three male older ALMS patients (mean 43 +/- 5 years vs. 27 +/- 10 years) all without a history of infantile CMP, had patchy diffuse LE in non-coronary artery territories with an increased ECV compared to remote "normal" myocardium . There were no differences in mean LV mass, LV ejection fraction or LA volume between ALMS and controls. Increased septal myocardial ECV correlated with a reduction in lateral and septal TDI systolic velocities . NT-BNP was not correlated with septal ECV but was increased in patients with LGE (median 178 pmol/L vs. 44 pmol/L).Patients with ALMS demonstrate a spectrum of myocardial fibrosis, which correlates with reduced longitudinal contractility before changes in conventional markers of LV structure and function. This precedes a clinically significant increase in BNP that appears with overt LE and suggests that increased ECV may be a target for early modification of pharmacological therapy.National Commissioning Group


Background. Severe mitral regurgitation (MR) is common in patients who are undergoing insertion of a left ventricular assist device (LVAD). This study analyzes the outcomes of a transapical approach for edge-to-edge repair of the mitral valve during insertion of a left ventricular assist device in 19 patients with MR. Methods. This retrospective study includes 19 patients who were implanted between March 21, 2011, and August 31, 2011, at the University of Chicago. Clinical data include preoperative ejection fraction, post- and preoperative pulmonary arterial pressures, cardiopulmonary bypass time, post- and preoperative mitral regurgitation severity, endotracheal CO2, and LVAD pulse index. Results. All of the 19 patients had a reduction in mitral regurgitation. Fourteen of the 19 patients had at least a three-point reduction in MR severity. The average postoperative pulmonary arterial pressure (PAP) decreased after the surgical procedure from 44/22 ± 14/5 mmHg to 57/28 ± 9/5 mmHg. Average CPB time was 128 ± 27 minutes. Average length-of-stay (LOS) was 21 ± 10 days. Conclusions. Concomitant MV repair using a transapical approach is advantageous for this small cohort of patients. The surgical procedure is less complex and has a shorter CPB time and LOS, and all of the patients demonstrated significant improvement in postoperative MR and moderate improvement in PAP. As a consequence of left ventricular remodeling, severe mitral regurgitation (MR) is common in patients with end-stage heart failure who are undergoing insertion of a left ventricular assist device (LVAD). This valvular related pathology often develops in the absence of structural mitral valve abnormalities. Instead, regurgitation develops secondary to left ventricular cavity enlargement and/or increased ventricular sphericity with annular dilation . Concomitant mitral valve repair during LVAD insertion increases the complexity of the operation due to the need for additional dissection and incisions in the heart, bicaval cannulation, and prolonged cardiopulmonary bypass times. Edge-to-edge repair, developed by Alfieri and associates, has been shown to be a fast and reliable method of mitral valve repair in appropriate patients , 3. HereThe degree of MR is evaluated preoperatively by echocardiography and angiography. In the operating room, the mitral valve is again assessed preoperatively with transesophageal echocardiography (TEE). After a median sternotomy, preparation is made for initiation of cardiopulmonary bypass requiring only a single right atrial cannula for venous outflow and aortic cannula for arterial inflow. Cardiopulmonary bypass (CPB) is initiated and normothermic conditions are maintained. A left ventricular vent is placed via the right superior pulmonary vein. The heart is lifted out of the chest, exposing the LV apex. The apical coring knife is then utilized approximately 1.5 cm lateral to the left anterior descending artery in the apical dimple. The left ventricle is inspected for thrombus. Apical sutures are then placed with large Teflon felt pledgets in a horizontal mattress fashion . The mitral valve is then accessed through the apical incision. To better expose the mitral valve, a malleable retractor is used to retract the septum and a floppy sucker is passed between the anterior and posterior leaflet of the valve. The midpoint (equidistant from the two commissures) of the free edge of the anterior leaflet is identified, and the posterior leaflet is exposed. The midpoints of P2 and A2 are then sutured together using a 4-0 Prolene mattress suture buttressed with a felt pledget. The suture is placed approximately 5 mm from the free edge of the leaflets. The LVAD is then connected and secured in the standard fashion by passing sutures through the apical connector sewing ring and seating the apical connector in the LV apex. The LVAD is then attached to the apical connector and secured. The LVAD is positioned in the pericardium  or preperitoneal pocket , and the driveline is tunneled and brought out in the right upper quadrant.A partial occlusion clamp is then placed on the ascending aorta and an aortotomy is created. The distal anastomosis is then constructed between the outflow graft and the ascending aorta in an end to side fashion using running 4-0 Prolene suture. The outflow graft is then clamped and the partial occlusion clamp is released. Meticulous hemostasis is assured at the suture line. The outflow graft is then secured to the assist device. After deairing maneuvers, full VAD support is initiated and the patient is weaned from CPB. Transesophageal echo is then used to assess the degree of MR, mitral stenosis (MS), and ventricular function.The study included 19 consecutive patients who underwent LVAD implantation with concomitant transapical edge-to-edge mitral valve repair between March 21, 2011, and August 31, 2011, at the University of Chicago. All data was collected retrospectively, and use of the data is consistent with the regulations of the University of Chicago's Institutional Review Board. Demographic and clinical characteristics are included in Relevant preoperative and postoperative clinical data are included in This report describes an early experience with edge-to-edge mitral valve repair in patients undergoing LVAD implantation. The described technique offers a simple method of correcting MR. Other authors have described using an edge-to-edge repair via a transaortic approach , 5 and vThe transapical approach described here requires only a single atrial cannulation without the need for additional dissection, cardiotomy, or application of a cross-clamp. Given its simplicity, the approach may promote a more aggressive correction of concomitant MR. This method is unlikely to be suitable for all patients. In particular, it is not suitable for patients with complex mitral valve disease. Rather it should be reserved for cases where LV dysfunction is the predominant mechanism of lacking coaptation of the mitral leaflets. Further, in our brief experience, we have repaired the valve both before and after the placement of pledgeted apical sutures, and we have found that placing the pledgets first serves to tent open the ventriculotomy and improves the exposure to the mitral valve.Previous studies have demonstrated that MR improves with LVAD support . Early f


CMR LGE detects myocardial tissue abnormalities in hypertrophic cardiomyopathy (HCM) and aids in risk stratification, predicting in particular heart failure and to a lesser extent, sudden death. However, LGE quantifies only the area of focal fibrosis only, missing diffuse fibrosis and assuming all LGE is the same. We hypothesized that the total left ventricular fibrosis burden, as measured by the mean global myocardial extracellular volume  using 16 segment T1 mapping, would be a superior marker.Fifty-six patients with HCM from a national cardiomyopathy centre were compared to 46 gender matched healthy volunteers. All participants underwent LGE imaging and ECVglobal quantification at 1.5T . LGE was quantified using the full width at half maximum technique. ECV quantification was performed using dynamic contrast equilibrium at 15 minutes following a single bolus of 0.1mmol/kg Dotarem. The T1 was assessed using the ShMOLLI sequence pre contrast and at dynamic equilibrium with hematocrit measurement on the same day. A 16 segment left ventricular model was used to derive the ECVglobal. In addition, LGE+ areas and LGE- segments were separately analyzed. All patients underwent full conventional HCM risk stratification and echocardiography.The ECVglobal was higher in HCM that in healthy volunteers, as was the ECV in LGE+ areas and LGE- segments. (0.32±0.04, 0.27±0.03, 0.47±0.01, 0.30±0.03, overall P<0.0001, Figure ECVglobal has potential to be a better CMR technique than LGE for tissue characterization in HCM.British Heart Foundation


Abuse of anabolic steroids to induce skeletal muscle hypertrophy is widespread amongst recreational bodybuilders, however, the cardiac effects of such drugs have not been systematically documented. The ability of cardiovascular magnetic resonance (CMR) to image the myocardium in any plane and achieve full myocardial coverage renders it the gold standard for assessing LV volumes and mass.We sought to investigate the cardiac effects of anabolic steroid use with CMR hypothesising that significant hypertrophy and distinct LV remodelling would be seen in steroid users relative to non-users.A total of 23 recreational bodybuilders were studied - 15 anabolic steroid users and 8 non-users. CMR was undertaken on a 1.5T Avanto  using breath-hold steady-state free precession cine sequences. Three long-axis images were obtained followed by sequential short axis cines from the AV-groove to the apex. Late gadolinium enhancement (LGE) imaging was performed ~10 min after intravenous Gadovist 0.1 mmol/kg . Indexed LV and RV ventricular volumes, ejection fraction and indexed LV mass were determined using a semi-automated threshold-based algorithm after manual tracing of epicardial and endocardial borders . LV remodelling index was calculated as the ratio of LV-mass to LV end-diastolic volume (LV-EDV).None of the subjects exhibited any late gadolinium enhancement. Mean indexed LV and RV volumes and EF were comparable for the two groups Table . HoweverAnabolic steroid use amongst bodybuilders can induce significant left ventricular hypertrophy. The pattern and severity of remodelling can mimic hypertrophic cardiomyopathy. The use of such drugs should be considered in the differential diagnosis of significant otherwise unexplained left ventricular hypertrophy, particularly in the athletic cohort.This work is supported by the NIHR Cardiovascular Biomedical Research Unit at the Royal Brompton and Harefield NHS Foundation Trust, and Imperial College. Dr Ismail is supported by the British Heart Foundation.


Animal models have demonstrated a recovery in systolic strain following reperfusion of acutely ischemic myocardium, however this has not been shown in clinical practice.We aimed to determine whether there was long term improvement of regional strain in acutely ischemic myocardium following primary coronary intervention using cardiac magnetic resonance imaging (CMR)We studied 16 patients with acute ST elevation myocardial infarction (STEMI) who had received successful primary coronary intervention (PCI) to the culprit coronary artery. CMR was performed on a 1.5T Philips Achieva system  within 7 days of PCI and again at 1 year. We used segmentation of T2-weighted spectrally-selective inversion recovery (SPIR) imaging to detect the ischemic area-at-risk and delayed enhancement inversion recovery imaging to measure infarct size and transmural thickness. Complementary spatial modulation of magnetization (CSPAMM) tagging with harmonic phase analysis (HARP) was used to measure peak midwall systolic strain at baseline and follow-up. Each section was divided according to the American Heart Association classification providing a total of 96 myocardial segments for analysis at each visit.2=0.01, NS).All patients showed acute myocardial edema within the reperfused territory and a variable transmural extent of enhancing necrosis. Mean myocardial salvage, given as the proportion of viable myocardium within the ischemic area-at-risk, was 62±21% at baseline. The mean infarct area at baseline was 20±10.2% and 14±5.7% at 1 year follow-up. In total 45 segments showed enhancing necrosis and the peak systolic midwall circumferential strain (Ecc) improved between baseline and follow-up . In the remaining non-infarcted 45 segments there was no change in Ecc . The mean radial transmural extent of necrosis showed no correlation with ΔEcc (rThese findings demonstrate a long-term improvement in systolic function in acutely ischemic reperfused myocardium.


Fabry disease (FD) is a rare lysosomal storage disorder also affecting the heart. The aims of this study were to determine the frequency of cardiac troponin I (cTNI) elevation, a sensitive parameter reflecting myocardial damage, in a smaller cohort of FD-patients, and to analyze whether persistent cTNI can be a suitable biomarker to assess cardiac dysfunction in FD.cTNI values were determined at least twice per year in 14 FD-patients  regularly followed-up in our centre. The data were related to other parameters of heart function including cardiac magnetic resonance imaging (cMRI).3) in cardiomyocytes.Three patients (21%) without specific vascular risk factors other than FD had persistent cTNI-elevations . cMRI disclosed late gadolinium enhancement (LGE) in all three individuals with cTNI values ≥0.01, while none of the 11 patients with cTNI <0.01 showed a pathological enhancement (p<0.01). Two subjects with increased cTNI-values underwent coronary angiography, excluding relevant stenoses. A myocardial biopsy performed in one during this procedure demonstrated substantial accumulation of globotriaosylceramide (GbContinuous cTNI elevation seems to occur in a substantial proportion of patients with FD. The high accordance with LGE, reflecting cardiac dysfunction, suggests that cTNI-elevation can be a useful laboratory parameter for assessing myocardial damage in FD. Fabry disease (FD) is a rare X-linked disorder affecting hemizygous males and heterozygous females. Deficiency of the lysosomal enzyme alpha-galactosidase A (α-GAL-A) results in accumulation of glycosphingolipids with terminal alpha-galactosyl residues in various organs and tissues, in particular in the central and peripheral nervous system, vessels and kidneys. Approximately 60% of patients with FD have cardiac involvement such as ventricular hypertrophy, valvular heart disease, conduction defects, or coronary artery disease Cardiac troponin I (cTNI) is a laboratory parameter well known to reflect acute and chronic cardiac muscular damage 3, values >0.5 ng/ml were interpreted as increased) were determined in all patients. The definite diagnosis of FD had been confirmed by molecular genetic analysis demonstrating a heterozygous or hemizygous mutation in the α-GAL-A-gene The study cohort included 14 patients with FD treated and followed-up in our centre . Specific parameters such as enzyme activity (α-GAL-A reference range 33.2–109 nmol MU/h/mg protein) and levels of Lyso-globotriaosylceramide in serum (Lyso-GbAge at last follow-up ranged from 21–80 years (median 50 years). 7 subjects received enzyme replacement therapy with recombinant alpha galactosidase A. In all patients the routine follow-up protocol encompassed laboratory testing including cTNI determination at least twice per year, assessment of the patient’s overall condition and his neurological, cardiac, and nephrological status. Magnetic Resonance Imaging (MRI) of the brain and the heart was done annually.The study protocol was reviewed by the ethical committee of the medical faculty of the Justus Liebig University Giessen. To use routine clinical data the ethical board recommend obtaining patient’s written informed consent from each participant if possible. In 13 patients a written consent was obtained, one patient could not be contacted any longer. The ethical board approved the conduction of the analysis.cTNI, was measured by the ADVIA Centaur® TnI-Ultra immunoassay . A cTNI cut-off level of ≥0.01 ng/ml was considered as relevant elevation. Furthermore, brain natriuretic peptide (BNP) was determined in all patients. Values >37 pg/ml were considered as abnormal.In all patients, a routine electrocardiogram (ECG), a Holter-ECG and a cardiac ultrasound were performed. Arrhythmia was diagnosed if one of the following symptoms was detected in Holter-ECG: persistent or intermittent atrial fibrillation or flatter, sustained tachycardia (heart rate ≥100/minute for more than 30 seconds), non-sustained tachycardia (heart rate ≥100/minute for less than 30 seconds in at least 3 subsequent heart cycles), incomplete bundle branch block (QRS-duration: 100–119 ms) or complete bundle branch block (QRS-duration ≥120 ms).Cardiac MRI findings were analyzed by an experienced radiologist blinded from any clinical data. The following parameters were systematically assessed: left ventricular ejection fraction (LVEF), left ventricular (LV) hypertrophy, right ventricular (RV) hypertrophy, left ventricular posterior wall thickness measured during diastole (LVPWd), interventricular septum thickness during diastole (IVSd), LV mass index, and late gadolinium enhancement (LGE). The LGE technique  was applied to detect changes in tissue integrity in the left ventricle. Short-axis views at the basal, mid, and apical segments were used for the semiquantitative assessment of the appearance of gadolinium enhancement in every left ventricular segment indicating the occurrence of intramyocardial fibrosis.Glomerular filtration rate (eGFR) was calculated according to the simplified MDRD equation: eGFR  = 186×(serum creatinine)−1.154×(age) −0.203×0.742 ×1.212 (if black) A thorough neurological examination was performed in all patients at least twice per year. Small fibre dysfunction was assessed by quantitative sensory testing. Affection status of the brain supplying arteries was determined by measuring intima-media thickness in the common carotid artery by means of transcranial Doppler sonography. In addition, all patients underwent a brain MRI for assessment of white matter lesions.Data are presented as median values and range. cTNI levels were related to the nephrological data and various cardiac and cardiac MRI parameters obtained at last follow-up examination. Cardiac MRI and other parameters were compared between patients with cTNI values ≥0.01 ng/ml and those with normal values (<0.01 ng/ml).3 in cardiomyocytes . All three subjects with cTNI elevation had proteinuria and albuminuria, while eGFRs were not relevantly reduced (53.4–88.7 ml/min/1.73 m2).During follow-up, in the patients with continuously increased cTNI-values, serial echocardiographic examinations revealed no significant changes of cardiac wall thickness (data not shown).The main findings of this study were that approximately 20% of patients in this FD cohort had continuously increased cTNI values, and that cTNI elevation was highly correlated with pathologic LGE in the cardiac MRI.3 has been demonstrated in various structures of the heart including cardiomyocytes, cells of the conduction system, fibroblasts and endothelium cells within all types of vessels In FD it is assumed that the cardiac pathology is mainly related to progressive cardiac hypertrophy 3 storage appears to be the most likely cause of persistent cTNI elevation. This assumption is also supported by the marked accumulation of Gb3 in cardiomyocytes as observed in the myocardial biopsy of patient two (In two of our patients with elevated cTNI values, coronary macroangiopathy could be ruled out by angiography, performed to clarify cTNI elevation. Persistent cTNI elevation secondary to small vessel stenosis also seems unlikely, because no clinical signs and no electrocardiographic abnormalities characteristic of myocardial ischemia were detected. Furthermore, distribution of LGE within the myocardial wall does not support the hypothesis of an ischemic mechanism in these subjects. Therefore, a direct damage of cardiomyocytes by abnormal Gbient two .Since cTNI elevation is usually considered highly specific for myocardial damage, this finding often prompts further examinations such as coronary angiography. Therefore, the observation of increased cTNI-values in FD patients without coronary artery disease is of clinical relevance, since it may help to avoid nonessential invasive procedures However, when interpreting our results, potential causes for cTNI elevation other than cardiac pathology needs to be taken into account. Elevated cTNI values not related to myocardial damage have been described in patients with critical illness, sepsis, stroke, and seizures Further, it has been shown that renal insufficiency can result in elevated cTNI values Late gadolinium enhancement in cMRI is a valid and sensitive method for visualizing myocardial interstitial abnormalities in FD 3, is a biomarker considered to be closely related to disease severity 3 levels, but due to the small patient sample and since Gb3 values were not determined systematically in all our patients, we were not able to relate reliably cTNI levels to results of mutational analysis and lyso-Gb3 values.Recently, a correlation between genotype, phenotype and clinical severity in FD has been emphasized Notably, all 3 FD subjects with cTNI elevations received ERT. Since these patients started ERT before first cTNI determination, it is not clear whether their cTNI values increased during or remained elevated despite ERT. However, the impact of a continuous cTNI release from cardiomyocytes under ERT deserves particular attention, since it can be speculated that ERT in its current form is not sufficient to avoid ongoing cardiac damage in such patients 3 deposition in myocytes. Further studies with larger numbers of patients are required to determine whether cTNI is a valid surrogate marker of cardiac involvement in FD.In summary, continuous cTNI release seems not to be infrequent in FD, and occurred in this study cohort exclusively in subjects with evidence of cardiac involvement. In FD, a persistent cTNI elevation appears to be primarily related to direct cardiac muscular injury by Gb


In the assessment of left ventricular stroke volume in cine magnetic resonance, drawing the endocardial contours in short axis slices are difficult at the 1 or 2 most basal slices due to systolic movement of the base towards the apex. The forward flow in the ascending aorta can be quantified using phase contrast velocity mapping. This study investigated which basal slices should be included in the assessment of left ventricular stroke volume, compared with those of phase contrast velocity mapping.In 46 patients with various type of heart disease, multi slice breath-hold cine imaging of short axis views covering the entire left ventricle were obtained using 1.5 Tesla clinical scanner with 32-channel coil. The cases with mitral regurgitation were excluded. The endocardial contours in short axis views were drawn semi-automatically from left ventricular apex to 3 different basal slices, trace A; circular left ventricular endocardial contours in both end-diastole and end-systole, trace B; uninterrupted endocardial contour in end-diastole and interrupted endocardial contour by left ventricular outflow tract in end-systole, and trace C; interrupted endocardial contours with left ventricular outflow tract even in end-diastole. The most basal segment with muscle less than half of the circumference was excluded for analysis. The measured stroke volumes were compared with those of obtained by phase contrast velocity mapping in the ascending aorta.The total short axis slices included in the analysis were 6.7±1.6, 7.7±1.6, and 8.7±1.6 in trace A, B, and C, respectively. The stroke volume by cine imaging were 49±13 ml, 58±14 ml, and 65±15 ml in trace A, B, and C, respectively. The forward flow in the ascending aorta was 66±18 ml by phase contrast mapping, which showed good agreement only with trace C (p<0.001).The basal short axis slice with interrupted endocardial contour by outflow tract should be included for tracing in the assessment of left ventricular chamber size and ejection fraction.None.


Plasma fibulin-1 levels have been associated with N-terminal pro–B-type natriuretic peptide levels and left atrial size and shown to be predictive of mortality in patients with diabetes. The mechanisms behind these connections are not fully understood but are probably related to its roles as an extracellular matrix protein in cardiovascular tissues.P=0.004). Likewise, reduced longitudinal systolic LV function  and increased LV filling pressures was systolic velocity of the mitral annulus observed with increasing plasma fibulin-1 concentrations .One hundred twenty-five patients with severe aortic stenosis who were scheduled for aortic valve replacement (AVR) were evaluated with preoperative echocardiography and their plasma fibulin-1 levels were determined with ELISA. The cohort was followed for a median of 4 years after AVR. Increased restrictive left ventricular (LV) filling pattern was observed with increased plasma fibulin-1 levels (2% versus 29% versus 24% in low, middle, and high plasma fibulin-1 tertile groups, In patients with symptomatic severe aortic stenosis undergoing AVR, plasma fibulin-1 is associated with restrictive filling of the LV, decreased longitudinal systolic function of the LV, and increased LV filling pressures.http://www.clinicaltrial.gov with Identifier: NCT00294775URL:  A restrictive LV filling pattern assessed by echocardiography may identify patients with increased myocardial stiffness. Because LV filling pattern, however, also is affected by loading conditions and LV relaxation, increased myocardial stiffness may be present despite a nonrestrictive filling pattern.The cardiac consequences of aortic valve stenosis (AS) are characterized by chronic left ventricular (LV) pressure overload leading to LV hypertrophy and myocardial fibrosis, with both increasing myocardial stiffness. The consequence of increased myocardial stiffness is diastolic dysfunction, increased LV filling pressures, left atrial (LA) dilatation, shortness of breath, and increased risk of atrial fibrillation (AF).6 During development, it is expressed in endocardial cushions, cardiac valves, and myocardium.9 In adults, it is also a prominent ECM component of cardiac valves, heart muscle, and blood vessels.10 We recently demonstrated an association between plasma fibulin-1 levels and the presence of cardiovascular disease and showed that it is predictive for all-cause and cardiovascular mortality in patients with diabetes.5 Fibulin-1 is upregulated in cardiomyopathy,11 and fibulin-1 blood levels are positively associated with plasma N-terminal pro–B-type natriuretic peptide (NT-proBNP) levels and LA size.6 In the present investigation, we evaluated the hypothesis that plasma fibulin-1 may be associated with LV diastolic impairment and increased LV filling pressures, which result in a poorer postoperative outcome in patients with AS.Fibulin-1 is an extracellular matrix (ECM) and blood protein emerging as a biomarker in several cardiovascular diseases.http://ClinicalTrials.gov Identifier: NCT00294775) and was approved by the local ethical committee, and all patients gave written informed consent. The study design and effect of candesartan on regression of LV hypertrophy have previously been published.12 In brief, patients aged >18 years with symptomatic severe AS  scheduled for AVR at Odense University Hospital, Odense, Denmark, during February 2006 to April 2008 were enrolled. Patients with LV ejection fraction <40%, serum creatinine >220 μmol/L, previous aortic valve surgery, planned additional valve repair/replacement, infective endocarditis, predominant aortic valve regurgitation, or ongoing treatment with an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker were excluded. All patients undergoing AVR were enrolled in this study and divided among 3 groups according to fibulin-1 tertile.The present investigation is a substudy of a prospective single-center, randomized study to evaluate the effect of candesartan compared with conventional treatment on reverse remodeling in consecutive patients undergoing aortic valve replacement (AVR) for symptomatic AS. The study was registered with the National Board of Health and the Danish Data Protection Agency  the day before surgery and were repeated 12 months after AVR. Echocardiograms were digitally stored and later analyzed in a blinded manner for all clinical data, survival data, and fibulin-1 levels. Aortic valve area was estimated with quantitative Doppler using the continuity equation. Peak flow velocity across the valve was determined in the window where the highest velocity could be recorded using continuous-wave Doppler with the cursor as parallel as possible with the flow across the valve. Peak transvalvular gradient was estimated using the modified Bernoulli equation. Finally, the peak systolic flow velocity in the outflow tract was estimated with pulsed-wave Doppler.3 − [LV internal diameter]3)+0.6 g. Diastolic LV wall thickness and dimensions were estimated from the average of 3 consecutive frozen 2-dimensional images obtained in the parasternal long axis.14 In men and women, LV mass index (LVMi) >116 g/m2 and >100 g/m2, respectively, was considered indicative of LV hypertrophy.15 Relative wall thickness was calculated using the formula 2×posterior wall thickness/LV internal diameter in diastole.16As a measure of LV hypertrophy, LV mass was estimated according to the joint recommendations of the American Society of Echocardiography and European Association of Echocardiography using the Devereux formula: 0.8× was used as a noninvasive marker of LV filling pressures.15 from the apical 4- and 2-chamber views. Measurements were obtained in end-systole from the frame preceding mitral valve opening, and the volume was indexed for body surface area.LA volume was assessed using the area–length method19 NT-proBNP and creatinine levels were analyzed with a Modular Analytics P device .Blood samples were collected immediately after the echocardiogram, after the subject had been resting recumbent for at least 30 minutes. Samples were collected in EDTA-containing tubes. The tubes were then centrifuged, and plasma samples were stored at −80°C for later analysis. A sandwich immunoassay for fibulin-1 was used for measuring fibulin-1 levels.20 Episodes of AF occurring within 30 days of AVR were considered to be postoperative AF and were not recorded as an end point.Patients were examined 1, 3, 6, 9, and 12 months after AVR and underwent a 12-lead resting ECG for 2 minutes in the supine position. In addition, a 24-hour Holter electrocardiographic recording was performed 3 months after surgery, and a 48-hour Holter was performed at 12 months. These recordings were performed with a Reynolds Medical Tracker 3 and a Pathfinder 700  for analysis. All ECGs were interpreted by the same experienced cardiologist, who was blinded to treatment allocation and fibulin-1 levels. An episode of irregular heart rhythm with no definite p waves and with a duration >30 seconds was considered to be AF according to guidelines.Patients with known AF before AVR were excluded in analyses estimating the association of fibulin-1 with the development of AF.21All patients had coronary angiography performed before AVR and underwent a thorough clinical examination on the day before AVR. Arteriosclerosis was defined as previous history of cerebral stroke, aortic disease, peripheral arterial disease, or coronary heart disease or if arteriosclerosis was present on the preoperative coronary angiogram. In addition operative risk was estimated using the European System for Cardiac Operative Risk Evaluation (EuroSCORE).By July 2011, data on outcomes were collected from the Danish Personnel Register  and from discharge notes available in the Danish admission registry. In case of ambiguous information, local hospitals were contacted and detailed patient charts were reviewed.The main end point for this study was cardiovascular mortality; the secondary end point was AF.22 This DAG program was used to identify sets of confounders that together fully adjust for confounding in multivariable modeling.23 Several of these sets of confounders were identified . The set containing age, history of diabetes, AS severity, and LVMi was used for multivariable analysis.Data are presented as mean±SD or number and percentages. Differences between groups were tested by ANOVA; categorical variables were tested by Fisher exact test. Due to a nongaussian distribution, NT-proBNP was logarithm transformed. The association of fibulin-1 with arteriosclerosis and restrictive filling was tested by multivariate ANOVA. Mortality and event rates were calculated using the product–limit method and plotted according to the Kaplan–Meier method; death rates were compared using the log-rank test. Further estimation of risk was performed using Cox proportional hazard models. In addition to hazard ratios, adjusted hazard ratios for 1 SD were calculated, dividing the variable by the SD of the measure. We used DAGitty, a web-based application based on the directed acyclic graph theory, to model the causal relationship between fibulin-1 and cardiovascular mortality and any confounders.The assumptions  were tested and found to be valid.P value <0.05 was considered significant. STATA/SE 9.0  software was used for statistical analysis.A P=0.01). There was a trend toward an increased EuroSCORE result in patients with increased plasma fibulin-1 levels .r=0.18, P=0.042; data not shown). Creatinine levels were, however, similar between groups   patients with no difference between groups ; complet P=0.22) . Table 22, respectively; P=0.07). Plasma fibulin-1 correlated positively with indices of LV hypertrophy . The presence of LV hypertrophy was, however, not significantly different between groups . Increased plasma fibulin-1 levels were associated with increased occurrence of LV restrictive filling, elevated filling pressures, and increased LA volume index . In addition, plasma fibulin-1 levels were associated with reduced longitudinal systolic LV function measured as s′sep . Plasma fibulin-1 was increased in patients with LV restrictive filling independent of the presence of arteriosclerosis .A trend toward decreased aortic valve area was seen in patients with increased plasma fibulin-1 levels   at 12 months after surgery. Although ejection fraction at 12 months after AVR was similar between groups, s′sep remained reduced in patients with increased preoperative fibulin-1 levels .LVMi regression during follow-up was not significantly different between groups (−14±25 versus −20±36 versus −31±42 g/m P=0.15) , althougTwenty-nine patients developed AF during the first postoperative year: 7 in the first group, 9 in the second group, and 13 in the third group. In a univariable Cox regression model, plasma fibulin-1, LA volume index, age, plasma NT-proBNP, and LVMi were associated with the development of AF. After adjustment for age and LAVi, only plasma fibulin-1 remained significantly associated with AF development .The mean follow-up duration after AVR in the total cohort was 3.8±1.5 years (median 4.0 years). Survival status was available for all patients. Overall, there were 29 deaths: 8 in the first tertile, 8 in the second tertile, and 13 in the third tertile. The cause of 4 deaths was not a cardiac condition , and 25 patients had a cardiac cause of death .P=0.04, Overall mortality and cardiac mortality were significantly increased in patients with increased plasma fibulin-1 levels  is only seen in the presence of a stiff myocardium and elevated filling pressures, as opposed to impaired relaxation pattern with a long deceleration time, which is predominant among patients with arterial stiffness. The observed association between plasma fibulin-1 and restrictive LV filling pattern is therefore compatible with the idea that plasma fibulin-1 directly reflects the degree of myocardial stiffness. Decreased LV compliance and increased LA pressures will eventually dilate the LA, increasing the risk of AF. In line with this notion, we find that plasma fibulin-1 levels predict AF when adjusted for LA size, suggesting an effect not merely related to changes in hemodynamic parameters. Interestingly, novel findings of Garcia et al31 recently demonstrated that fibulin-1 levels are significantly altered in atrial tissue of patients with AF, although decreased levels were observed in diseased tissue. It is known that atrial fibrosis is associated with AF independent of filling hemodynamics32; it is possible that fibulin-1 plays a central role in the development of aberrant ECM in the atrial tissue of individuals with AF. Weidemann and colleagues recently demonstrated an association between increased fibrosis assessed by MRI and reduced longitudinal systolic function measured with tissue Doppler in AS.3 It is therefore intriguing that we observed reduced s′ velocities in patients with increased fibulin-1 levels, compatible with the idea that plasma fibulin-1 could reflect myocardial fibrosis.As stated earlier, our previous study established a link between plasma fibulin-1 and LA dilatation and plasma NT-proBNP concentrations in diabetic patients. We suggested that these associations could be secondary to increased arterial stiffness, because we observed increased arterial fibulin-1 concentrations in the arterial ECM in individuals with type 2 diabetes and because there was a correlation between plasma fibulin-1 and carotid compliance.Our sample size is relatively small, with few events, which makes our models unstable because confounding may be present; the small sample size does not allow control for potential confounders. Larger studies are therefore warranted. The entry criterion for the study was symptomatic AS referred for AVR. Future studies should also include asymptomatic patients to clarify whether our findings apply to a general population with AS.17LV structure was assessed by echocardiography, and no histologic examinations were performed; thus, we can only speculate on the degree of myocardial and valvular pathologic conditions. No direct hemodynamic measurements of LV end-diastolic or LA pressure were performed. However, E/e′ is accepted as a well-validated surrogate in a wide range of patients with cardiac disease including AS.The present study demonstrates that preoperative plasma fibulin-1 levels in patients with AS are associated with restrictive filling of the LV, decreased longitudinal systolic function of the LV, and increased LV filling pressures. Moreover, plasma fibulin-1 levels are associated with AF and long-term postoperative mortality when adjusted for other factors in these patients. Thus, plasma fibulin-1 may be a new candidate marker to be used in clinical settings and research investigations to assess myocardial stiffness.


Right ventricular (RV) dysfunction is a complication of pulmonary hypertension and portends a poor prognosis. Pharmacological therapies targeting RV function in pulmonary hypertension may reduce symptoms, improve hemodynamics, and potentially increase survival. We hypothesize that recombinant human angiotensin-converting enzyme 2 (rhACE2) will improve RV function in a pressure overload model.in vivo hemodynamics. Specifically, rhACE2 increased RV ejection fraction and decreased RV end diastolic pressure and diastolic time constant (p<0.05). In addition, rhACE2 decreased RV hypertrophy as measured by RV/LV+S ratio (p<0.05). There were no significant negative effects of rhACE2 administration on LV function. rhACE2 had no significant effect on fibrosis as measured by trichrome staining and collagen1α1 expression. In pulmonary artery banded mice, rhACE2 increased Mas receptor expression and normalized connexin 37 expression.rhACE2 administered at 1.8 mg/kg/day improved RV systolic and diastolic function in pulmonary artery banded mice as measured by In a mouse RV load-stress model of early heart failure, rhACE2 diminished RV hypertrophy and improved RV systolic and diastolic function in association with a marker of intercellular communication. rhACE2 may be a novel treatment for RV failure. Pulmonary hypertension (PH) is a broad term describing any elevation in mean pulmonary artery pressure greater than 25 mmHg at rest as determined by right heart catheterization. PH is caused by a variety of diseases including pulmonary arterial hypertension (PAH), PH secondary to left-sided heart disease, PH associated with lung disease and/or hypoxia, and PH resulting from chronic thrombotic/embolic disease Pharmacological approaches limiting angiotensin II (Ang II) bioactivity (angiotensin-converting enzyme inhibitors and angiotensin receptor blockers) are the cornerstone of management of left ventricular (LV) dysfunction; however, there is no convincing evidence for use of these therapies in RV failure Although the literature supports a beneficial role for ACE2 in LV function, the effects of ACE2 specifically on RV function have not been examined. Importantly, the response of the RV to stress should not be extrapolated from left heart experiments. The function, structure, and embryology of the right and left ventricles are unique. The RV is smaller, crescent shaped, thin-walled, and has a much lower afterload than the LV In preliminary studies, we demonstrated that ACE2 improves pulmonary vascular disease in a transgenic mouse model of PH, and now wish to study the effects of ACE2 on RV load-stress responses. We hypothesized that ACE2 would prevent RV hypertrophy and prevent hemodynamic dysfunction during RV load-stress. In order to study pharmaceutical effects of ACE2 on RV dysfunction in isolation, we administered rhACE2 to pulmonary artery banded (PAB) mice via osmotic pumps for two weeks. In this PAB model of early heart failure, we assessed structural, hemodynamic, and molecular effects of rhACE2 on the RV.PAB resulted in significant RV hypertrophy as measured by RV/LV+Septum (LV+S) ratio that was attenuated with rhACE2 administration . rhACE2 The effects of 14 days of PAB or control with or without rhACE2 exposure on RV hemodynamics were studied . There win vivo hemodynamics , nor did it decrease afterload in our PAB model (the pulmonary vasculature is dilated at baseline). Consequently, RV improvement with ACE2 administration is likely secondary to improved contractility. There was significant increase in EF and stroke volume, and there was a trend towards increased dPdt  with ACE2. Other studies have linked ACE2 with contractility; profound contractile dysfunction occurs after ACE2 gene inactivation in the mouse heart We evaluated molecular effects of ACE2 on the RV by measuring Mas receptor and connexin expression levels. Review of the literature suggests that ACE2 may improve LV cardiac function through Ang-(1-7) activity at the Mas receptor rhACE2 had minimal effect in control animals on echocardiography and catheterization . Our study did not examine the underlying mechanisms by which ACE2 may have affected normal RV function, but changes in normal LV function have been observed by other investigators with ACE2 In human PAH patients, ACE2 may provide therapeutic effects in both the RV and lung. Although the PAB model presented in this manuscript cannot evaluate distal pulmonary vascular disease, success in both monocrotaline and transgenic animal models of PAH support ACE2 as an effective pulmonary vascular treatment. For example, researchers have prevented pulmonary vascular disease in a monocrotaline rat model using XNT, a synthetic activator of ACE2 Limitations of this study include lack of cardiac conduction evaluation with electrocardiograms. It has been suggested that ACE2 transgene overexpression can cause heart block, ventricular tachycardia, and sudden death In summary, RV function is a critical determinant of morbidity and mortality in PH This study was carried out in accordance with the National Institutes of Health's Public Health Service Policy of Humane Care and Use of Laboratory Animals and in accordance with the Animal Welfare Act. Vanderbilt University Institutional Animal Care and Use Committee approved all procedures (protocol M/08/083). All experiments were performed using appropriate analgesics and anesthetics, and every effort was made to minimize pain and distress.2, pH 7.5, Apeiron Biologics). Pumps were placed subcutaneously between the scapula using sterile technique. Mice received analgesic after pump insertion with a subcutaneous injection of 5 mg/kg of carprofen. All assessments were obtained by our technician who was blinded to rhACE2 or placebo.Twenty-seven adult male C57BI/6 mice 10 weeks of age (Jackson Laboratory) were anesthetized with 3% isoflurane, administered intraperitoneal etomidate (20–40 mL/kg), and orotracheally intubated. Animals were mechanically ventilated with isoflurane general anesthesia for PAB or sham surgery. A sternal incision was made using sterile technique, the pericardium was removed, and a partially occlusive tantalum clip was placed around the pulmonary artery . The animal was then sutured closed and allowed to recover from anesthesia. Mice received post-operative analgesic with a subcutaneous injection of 5 mg/kg of carprofen. Sham treated animals underwent the same procedure without vascular clip placement. On post-op day 2, mice were separated into control or rhACE2 groups: ACE2.PAB n = 10, ACE2.CON n = 5, CON.PAB n = 7, CON.CON n = 5. The rhACE2 group received rhACE2  at 1.8 mg/kg/day through micro-osmotic pumps (ALZET 1002). The control group received vehicle alone . Echocardiograms were obtained the day prior to sacrifice under isoflurane anesthetic. In the short axis, left and right ventricular end systolic and diastolic diameters and heart rate were recorded in M-mode Two-dimensional echocardiography was performed using Vivo 770© catheter into a surgically exposed heart. Open-chested catheterization was chosen since this method provides better quality pressure-volume loops than the close-chested technique in our hands. Hemodynamics were continuously recorded with a Millar MPVS-300 unit coupled to a Powerlab 8-SP analog-to-digital converter acquired at 1,000 Hz and captured to a Macintosh G4 . After obtaining RV measurements, the catheter was removed and placed into the LV. Mice were sacrificed using a lethal dose of phenobarbital (Schering-Plough). The right and left heart were weighed separately and quick-frozen in liquid nitrogen. Several RV and LV in each group were placed in formalin for histology.Right ventricular systolic pressure (RVSP) was obtained on all but one mouse who died prior to RVSP measurement. Two weeks after receiving rhACE2 or vehicle, mice were anesthetized with 3% isoflurane, administered intraperitoneal etomidate, and orotracheally intubated. Animals were mechanically ventilated with vaporized isoflurane general anesthesia. Mice were positioned supine, ventral side up on a heated operating table. A vertical incision over the abdomen was made and cautery was used to cut the diaphragm and expose the heart. RVSP was directly measured via insertion of a 1.4F Mikro-tip2O2 (10 ml of H2O2+90 ml MetOH). Slides were blocked in 10% powerblock  and 0.4% Triton in PBS and placed in a humid chamber for 15 minutes. ACE2  primary antibody in the presence of 10% powerblock in 0.4% Triton-x 100 in PBS was added 1∶200 at 4°C overnight. Secondary antibody  anti-rabbit Igs, biotinylated goat (mouse/rat-absorbed) was applied and incubated for 20 minutes. Biogenex streptavidin HRP (Innogenex streptavidin enzyme conjugate CJ-1005-25) was added for 20 minutes. Slides were stained with vector NovaRed (SK-4800) and counterstained in Mayers hematoxylin. Hearts were also stained with Masson's trichrome stain and hematoxylin and eosin. Epicardial and endocardial fibrosis was quantified by measuring the width of the three most fibrotic regions per slide. Perivascular fibrosis was measured on the three most fibrotic vessels on each slide. Percentage of collagen per cardiac tissue area was obtained using Nikon NIS-Elements Advanced Research software . Microvessels were defined as vessels which were not main coronary vessels and were identified using immunofluorescence staining for vWF 1∶100 . Microvessels were counted in twenty fields at 400×.Antigen retrieval on cardiac tissue was performed with retrievit-8 . Sections were rinsed in DI water and soaked for 20 minutes in 3% HRNA was obtained using Qiagen RNeasy Mini Kit . First strand cDNA was made using QuantiTect® Reverse Transcription Kit (Qiagen) from 1 µg total RNA. Quantitative real-time PCR was performed using a total reaction volume of 25 µl, containing 5 µl of diluted cDNA, 12.5 µl SYBR Green Supermix  and 0.03 µl of each oligonucleotide primer (250 µM). PCR was carried out in a StepOnePlus Real Time PCR System (Applied Biosystems) using 40 cycles of 95°C for 15 seconds followed by 60°C for 1 minute with a ten minute 95°C initial soak. Each measurement was made in triplicate and expressed relative to the detection of the standard HPRT. PCR was preformed for the primer sets HPRT, collagen1α1, Mas1, and connexin 37 .10 transformed before statistical analyses. A p value <0.05 was considered significant.Statistical tests were two-way ANOVA with post-hoc Bonferroni test performed using GraphPad Prism Plus version 5.0 Software . Expression data was log


The presence of ischemia-induced microvascular obstruction (MVO) despite successful coronary revascularization, has been associated with poor functional recovery and adverse left ventricular remodeling after acute myocardial infarction (AMI). Additionally, the extent of the infarct gray zone is a strong independent predictor of post-AMI mortality. However, the evolution of gray zone after AMI has not been investigated and its relationship with MVO in terms of risk stratification is unknown.To characterize the evolution of gray zone and determine its correlation with the presence of MVO during infarct healing in patients treated with primary percutaneous coronary intervention (PCI).Patients were enrolled post-PCI and underwent MRI examination on a 1.5T scanner (GE Signa Excite) at day 2, week 4 and month 6 following AMI. Cardiac function  was evaluated using a steady-state-free-precession (SSFP) sequence in cine mode. A T1-weighted IR-GRE sequence was used for delayed-hyperenhancement (DHE) of infarcted myocardium. Infarct core (IC) and gray zone (GZ) volumes were quantified using the full-width-half-maximum technique as previously described; both quantities were expressed as a percentage of myocardial volume. MVO’s were manually traced and included in the infarct core calculation.r = 100*GZ/(GZ+IC) increased in the MVO group at month 6 while it remained stable in the non-MVO group; (d) EF was reduced in the MVO group compared to the non-MVO at all time points (p<0.05). The percent change in GZr (ΔGZr) at week 4 and month 6, relative to day 2 is shown in Figure Ten patients who completed MRI exams at all three time points were included in the study . Figure The increase in infarct gray zone or arrhythmogenic substrate may be one of the possible mechanisms responsible for adverse remodeling and poor clinical prognosis in patients with MVO. Monitoring the early evolution of gray zone in the high-risk patients could also potentially help identify the optimal timing and candidates for placement of implantable cardioverter-defibrillator.


We report a case of a 67-year old male with a recent diagnosis of left ventricular non-compaction (LVNC), initially presenting with symptomatic ventricular ectopy and runs of non-sustained ventricular tachycardia (VT). This ventricular arrhythmia originated in a structurally normal right ventricle (RV) and was successfully localized and ablated with the aid of the three-dimensional mapping and remote magnetic navigation. A 67-year old Caucasian man with a recent diagnosis of left ventricular non-compaction (LVNC) and previous ablation of ventricular extrasystoles (VEs) in the right ventricular outflow tract was transferred as an emergency to our institution for electrophysiological study and further management of multiple episodes of non-sustained VT. He had a two-year history of palpitations on exertion with associated pre-syncopal symptoms and one syncopal episode.The 12-lead ECG on admission showed ventricular bigeminy and telemetry revealed multiple short runs of monomorphic non-sustained ventricular tachycardia (VT) of similar morphology to the VEs, and without haemodynamic compromise . The QRSAt the beginning of the electrophysiological study the patient was in sinus rhythm with monomorphic ventricular bigeminy. A three dimensional map of the RV was acquired using magnetic navigation in conjunction with CARTO 3 RMT   and 2B. Continuous monitoring for 48 hours post-procedure showed no further VEs /VT off any anti-arrhythmic medication.In order to identify if there was any underlying anatomical substrate for the right ventricular origin of the arrhythmia in this case, we reviewed the images from a pre-ablation cardiac magnetic resonance (CMR) scan. The RV free wall at the site of the origin of the arrhythmia close to the tricuspid annulus (as determined from the CARTO merge 2D slices) was carefully reviewed in all views. The appearance of the LV confirmed non-compaction according to the CMR criteria described by Petersen  Figure  and 2D, In this patient with LVNC and VT, the electrophysiological study demonstrated that the VT originated from a structurally normal RV. LVNC is a rare congenital cardiomyopathy with a reported incidence of 0.05% in adults . It can With an abnormal LV, it is expected that the substrate for arrhythmia is located in the LV as a result of abnormal trabeculations creating a substrate for left VT. However, in our patient with LVNC the VT originated from a structurally normal RV. Interestingly, the CMR showed a normal RV and this is regarded as a highly effective imaging modality to distinguish the compacted and non-compacted myocardial layers . HoweverAnother hypothesis could be that the VT originated from the ventricular end of an accessory pathway that has regressed, particularly in view of the fact that the origin of arrhythmia was close to the tricuspid annulus. WPW syndrome has been reported in these patients . HoweverEven though it is possible that the occurrence of these findings is co-incidental, this case emphasises that patients with LVNC have an arrhythmogenic substrate that can extend beyond the LV. This could be secondary to either structural abnormalities that are below the resolution of the currently available imaging modalities or can be the result of microscopic changes such as altered ion channels or signalling pathways.


Objectives. To describe the process of selection of candidates for fetal cardiac intervention (FCI) in fetuses diagnosed with pulmonary atresia-critical stenosis with intact ventricular septum (PA/CS-IVS) and report our own experience with FCI for such disease. Methods. We searched our database for cases of PA/CS-IVS prenatally diagnosed in 2003–2012. Data of 38 fetuses were retrieved and analyzed. FCI were offered to 6 patients (2 refused). In the remaining it was not offered due to the presence of either favourable prognostic echocardiographic markers (n = 20) or poor prognostic indicators (n = 12). Results. The outcome of fetuses with PA/CS-IVS was accurately predicted with multiparametric scoring systems. Pulmonary valvuloplasty was technically successful in all 4 fetuses. The growth of the fetal right heart and hemodynamic parameters showed a Gaussian-like behaviour with an improvement in the first weeks and slow worsening as pregnancy advanced, probably indicating a restenosis. Conclusions. The most likely type of circulation after birth may be predicted in the second trimester of pregnancy by means of combining cardiac dimensions and functional parameters. Fetal pulmonary valvuloplasty in midgestation is technically feasible and in well-selected cases may improve right heart growth, fetal hemodynamics, and postnatal outcome.  Pulmonary atresia-critical stenosis with intact ventricular septum (PA/CS-IVS) is a complex and heterogeneous disease which, depending on the morphology and function of the tricuspid valve (TV), may be associated with underdevelopment of the right ventricle (RV) , 2 or wiCurrent development of fetal echocardiography and interventional cardiac technology makes it possible to offer an intrauterine approach to some cardiac diseases . For PA/The objective of this paper is to describe firstly the process of selection of candidates for FCI in fetuses diagnosed with PA/CS-IVS and secondly report our own experience with FCI for such disease.Our database was queried for cases of PA/CS-IVS prenatally diagnosed in the period October 2003–January 2012 at our tertiary care referral centre. PA was diagnosed by the absence of flow across the pulmonary valve and CS by the presence of thickened and domed pulmonary valve cusps with a pinhole jet of flow, and in both with Doppler evidence of ductal-dependent pulmonary circulation [z-scores for most cardiac dimensions were obtained with the software available [Fetal ultrasound examinations included a detailed extracardiac structural survey and a complete echocardiography, performed following guidelines , 16. Allvailable . The preAll fetuses diagnosed as having PA/CS-IVS routinely undergo an echocardiographic assessment aimed to predict their more likely outcome (BV versus non-BV circulation) and also to evaluate the risk of developing right heart failure.Different criteria for predicting non-BV outcome have been described over time . In our In these cases the decision on whether performing FCI relied upon the assessment of the parameters which are commonly evaluated in fetuses with PA/CS-IVS and marked TR, including cardiac size, severity of TR, venous Doppler, and peripheral edema, as suggested by Huhta . We consμg/kg) is administered intramuscularly to the fetus for paralysis and anesthesia before passage of the cannula. Prior to FCI, the cannula, guidewires, and balloon shafts are premeasured and marked so that positioning within the heart is known from external measurements rather than the ultrasound imaging alone. Under continuous ultrasound guidance, we advanced a 15 cm long 18-gauge cannula and stylet needle through the maternal abdomen into the uterus and from there through the fetal chest wall into the cardiac region of interest. Specifically, the RV is entered at the infundibulum, in the longitudinal view, with the cannula course parallel to the RV outflow tract, making easier thereby crossing the valve with the device , vecuronium 0.2 mg/kg), and fentanyl , reversed , or mixed .z-score < −5) or with RV-dependent coronary circulation, defined following published criteria [Our standard practice is to perform an echocardiogram and cardiac catheterization in the first days of life. Patients with severely small RV , and 5 of them also had a cardiovascular profile score <7. FCI was offered in all 5, and it was accepted in 3. The rest of the fetuses presented with non-severe TR, and in most of them a non-BV outcome was predicted. Only one fetus was considered suitable to FCI at the time of diagnosis and it was accepted. FCI was not offered in 32 fetuses: in 7 cases the parents opted to terminate the pregnancy, and among those surviving the perinatal period their outcome was accurately predicted prenatally. The prenatal diagnosis was confirmed after birth by echocardiographic and angiographic examinations in all patients. Four fetuses underwent pulmonary valvuloplasty, performed at a mean gestational age of 25 weeks. All cases were performed with percutaneous access and were technically successful. The first three cases were diagnosed as having CS-IVS, with a pinhole jet of flow (1 mm) across the PV, while the fourth was diagnosed of PA-IVS. Baseline and follow-up echocardiographic data of the 4 cases as well as their outcome are summarized in Associated with the data shown in Following the initial diagnosis of a dysplastic pulmonary valve at 22 weeks, this fetus developed ascites likely due to restrictive right-to-left interatrial shunting of 1.5 mm, accompanied by cardiomegaly (CTI 58%), mild pericardial effusion, and high velocity TR (3.1 m/s). A forward jet of flow of 2.6 mm was observed immediately after valvuloplasty, with a peak systolic velocity of 0.9 m/s and a holodiastolic pulmonary regurgitation. Color Doppler showed a dominant antegrade filling of the central pulmonary arteries. Initial follow-up scans also showed a slight reduction in the TR velocity (1.5 m/s), an improvement in venous Doppler with antegrade end-diastolic flow in the ductus venosus and a reduction in the amount of ascites. These features were stable throughout the pregnancy, the antegrade jet of flow across the PV reached a maximum diameter of 4.5 mm, the right heart dimensions remained within normal limits, the RV showed normal tripartite appearance with myocardial hypertrophy affecting the trabecular component, but in the last scans before birth TR velocity rose again to 2.8 m/s. Spontaneous preterm delivery of a male weighing 2600 g took place at 35 weeks. Postnatal echocardiography confirmed the prenatal diagnosis. Diagnostic catheterization performed 48 h after birth showed VCCs in the RV and interruption of the circumflex artery. During this procedure the patient became hemodynamically unstable and had an episode of cardiac arrest. Diffuse ischemic lesions were seen in the central nervous system three days later, and the therapeutic support was subsequently withdrawn.Following the initial diagnosis at 21 weeks of CS-IVS with a right coronary to RV fistula, the fetus remained in a stable condition with tripartite normal-sized RV, a small PV, high-velocity holosystolic TR (2 m/s), and absent-reversed diastolic flow in the ductus venosus. Therefore, the patient was not considered initially to be a candidate for FCI. However, a new scan performed at 26 weeks showed the presence of pericardial effusion and ascites. A forward jet of flow of 2.3 mm was observed immediately following valvuloplasty, with a peak systolic velocity of 1.2 m/s, mild protodiastolic pulmonary regurgitation, and mixed filling (antegrade and duct dependent) of the pulmonary artery. This situation remained stable in the initial follow-up scans, but it was not accompanied by changes in venous Doppler, in the severity of TR, in the flow waveform in the fistula, or in the amount of ascites. Right heart dimensions maintained within normal limits and the RV kept its normal tripartite appearance, with myocardial hypertrophy affecting the trabecular component. This leads us to hypothesize that pulmonary valvuloplasty could at least halt the deterioration of the fetus, preventing the progression of right heart failure. With a similar antegrade jet of flow across the pulmonary valve of 2.6 mm and peak systolic velocity of 1.17 m/s, a relative worsening was observed at 33 weeks including small growth of the RV, increasing ascites and reappearance of a small amount of pericardial fluid. It was considered that early delivery would improve the chances of biventricular repair, and after induction of fetal lung maturity, labor was induced at 34 + 2 weeks. Unfortunately, delivery was complicated by intrapartum placental abruption, and despite urgent caesarean section, a severely hypoxemic baby weighing 2000 g was born and died at 24 hours secondary to multisystem organ failure.z-score of the TV fell from −1.8 to −2.7 and the RV/LV ratio decreased from 0.60 to 0.52. This child was delivered by elective caesarian section for a previous caesarian section at 38 weeks, weighing 2630 g. Postnatal echocardiography showed a small tripartite RV, and after a failed pulmonary valvuloplasty, an open valvotomy with placement of a modified right Blalock-Taussig shunt was performed at the age of 2 weeks. This girl has undergone a one and a half ventricle repair and is healthy at 21 months.Following the initial diagnosis at 21 weeks of PA-IVS, this patient was referred to our unit at 24 weeks. Fetal echocardiography showed a tripartite but small RV, which did not reach the apex, with myocardial hypertrophy affecting the trabecular component and biphasic filling followed by holosystolic TR with peak velocity of 1.5 m/s. In such a scenario, a BV outcome was considered highly unlikely and pulmonary valvuloplasty was attempted 3 days later. A forward jet of flow of 2.3 mm was observed immediately after valvuloplasty, with a peak systolic velocity of 1.4 m/s, mild protodiastolic pulmonary regurgitation, and mixed filling (antegrade and duct dependent) of the pulmonary artery. These features remained stable in follow-up scans together with biphasic RV inflow and increased TR, which was of high velocity (2.4 m/s), likely reflecting an improvement in RV filling. However, no significant changes were seen in venous Doppler throughout the pregnancy. The anatomy was favourable with a good-sized RV and TV, increasing thereby the chances for a BV outcome. However, between 32 and 37 weeks the More than 20 years have elapsed since the first description of a FCI , and theRegarding the first point, several predictive models have been described in the last years. In accordance with the policy usually followed postnatally, where the decision regarding the management pathway usually relies upon several cardiovascular parameters which address both the size of the right inflow and outflow tracts and morphological features as well –31, we hIn the setting of severe TR, it is of paramount importance the analysis of surrogate markers of right heart failure. In this sense either morphological parameters such as serous effusions, skin edema, or severe cardiomegaly or hemodynamical markers such as the severity of TR and ductus venosus flow may provide useful information regarding the degree of raised systemic venous pressure , 34. SpeFCI for patients affected with PA/CS-IVS is a challenging procedure given the special anatomy of the right outflow tract and the difficult access to the pulmonary valve. However, it has been shown that pulmonary valvuloplasty in fetal life is technically feasible even in mid-gestation, although it should be acknowledged that the experience with this procedure is still limited to a few number of cases , 14, 35.In conclusion, although we acknowledge that there is still limited experience with fetal pulmonary valvuloplasty and that randomized studies have not been performed (and probably never will), it seems that in selected cases this intervention may improve fetal hemodynamics, right heart growth, and postnatal outcome. Future experience will give us a better knowledge about the prenatal and postnatal outcome of FCI in right cardiac defects.


Obesity is associated with cardiac remodelling with increased left ventricular mass and end-diastolic volume. CMR is a unique technique to evaluate cardiac morphology and function in obese individuals. Among CMR techniques, myocardial tagging allows to quantify myocardial strain and left ventricular rotation along the RR cycle (1). The aim of this preliminary study was to explore the feasibility of left ventricular apical rotation quantification by CMR tagging in obese individuals and exploring possible alteration of myocardial motion pattern.8 healthy controls (18<BMI<25) were imaged using a 3T trio system and 7 obese subjects (BMI>30) without other cardiovascular risk factors and with normal left ventricular ejection fraction were imaged using a 1.5T Espree system . We used an ECG gated, single breath hold balanced SSFP line tagging sequence with LISA, with CSPAMM acquisition scheme (2). The field of view was 340 x340 mm, matrix 256 with 32% phase resolution, bandwidth 850 Hz, slice thickness 7 mm, tag spacing 7 mm, TE 1.28 (TE 1.54 @ 3T) and Flip angle 20° (15° @ 3T). Images were analyzed and apical rotations were computed using Extrema Temporal Chaining (ETC) (3).The left ventricular apical systolic rotation measured by CMR tagging was increased and delayed in obese patients while the diastolic apical untwisting was prolonged, when compared to control subjects Fig..Our preliminary results confirm the presence of an abnormal pattern of left ventricular rotation in obese individuals that can be identified with CMR tagging. This abnormal pattern may reflect the remodeling secondary to increased hemodynamic requirements (volume-overload and sympathetic system activation) in obese subjects, while the delayed diastolic untwisting may precede a diastolic dysfunction. These preliminary data confirm that CMR with myocardial tagging may allow identifying early abnormalities of left ventricular function in obese individuals with normal left ventricular ejection fraction.


Myocardial T2* measurement is a valuable tool for non-invasive assessment of iron overload, and is clinically employed for planning and monitoring iron-chelating treatments for transfused thalassemia major patients . PresentAn ECG-triggered 2D multi-echo GRE sequence was implemented on a 1.5T MR scanner  with support for dark-blood preparation. To generate an inline T2*-map, an integrated image reconstruction performs pixel-wise T2* estimation using a robust fit, in which the signal at each TE is iteratively weighted to reflect its fidelity to monoexponential decay curve. Points farther from the ideal relaxation curve are weighted lower, reducing their influence on the fit.In five healthy volunteers, the method was used to acquire short axis images of the heart, accompanied by inline T2*-map computation. Additionally, to compare the accuracy of the robust-fit with a validated method, T2*-maps were retrospectively computed using multi-echo images of 32 patients. In all cases, a septal region-of-interest was manually drawn to obtain an average T2* value.Fig. The proposed technique computes pixel-wise T2* estimate which differs from region-based T2* assessment within CMRTools; however, the average T2* values within septum are highly correlated (R2=0.996) with the region-based estimates obtained using CMRTools. This is an encouraging result given that T2*-map is generated on the scanner without any need for user intervention to eliminate outliers, and that assessment of myocardial T2* is possible immediately following data acquisition. Prospective clinical studies are warranted to thoroughly validate this proposed method.