To explore the role of contrast-enhanced magnetic resonance angiography (CE-MRA) in clinical routine for evaluating neonates with pulmonary atresia (PA) and to describe their pulmonary artery morphology and blood supply.CE-MRA studies of 15 neonates with PA  were retrospectively evaluated by two radiologists in consensus. Each study was judged to be either diagnostic or non-diagnostic depending on the potential to evaluate pulmonary artery morphology and pulmonary blood supply. In those cases where surgery or conventional angiocardiography was performed results were compared.CE-MRA was considered diagnostic in 87%. Pulmonary artery morphology was classified as "confluent with (n = 1) and without (n = 1) main pulmonary artery", "non-confluent" (n = 6) or "absent" (n = 7). Source of pulmonary blood supply was "a persistent arterial duct" (n = 12), "a direct" (n = 22) or "indirect (n = 9) aortopulmonary collateral artery (APCA)" or "an APCA from the ascending aorta" (n = 2). In no patient were there any additional findings at surgery or conventional angiocardiography which would have changed the therapeutic or surgical approach.CE-MRA is a useful diagnostic tool for the preoperative evaluation of the morphology of pulmonary arteries and blood supply in neonates with PA. In most cases diagnostic cardiac catheterization can be avoided. Pulmonary atresia (PA) is classified into pulmonary atresia with ventricular septal defect (PA-VSD) and PA with intact ventricular septum (PA-IVS). PA-VSD may occur with any form of congenital heart disease (CHD) like tetralogy of Fallot (TOF), double outlet right ventricle, double outlet left ventricle and transposition of great arteries  while PAThe site of atresia varies and any part of the right ventricular outflow tract - the infundibulum, the pulmonary valve and the main pulmonary artery - may be atretic. The main pulmonary artery may be completely absent while the right and left pulmonary arteries may be hypoplastic, either confluent or non-confluent, or absent . KnowledCardiovascular magnetic resonance (CMR) is regarded as a useful tool for diagnosis and preoperative evaluation of CHD as it is less invasive than conventional angiocardiography and does not involve ionizing radiation -9. ContrOur aim was to explore the role of CE-MRA in clinical routine for evaluating neonates with pulmonary atresia and to describe their pulmonary artery morphology and blood supply.This retrospective study was conducted at a cardiology centre of a tertiary paediatric hospital and was approved by the institutional research ethics board. Children with PA who underwent CE-MRA during the neonatal period for initial workup were identified, and their clinical charts and imaging studies were reviewed.Search of the electronic databases of the departments of cardiology and radiology, including the period from January 2002 to October 2008, revealed 40 neonates with PA  referred to the hospital during the first 28 days of life. Of the 26 patients with PA-VSD, 14 had CE-MRA during the neonatal period, whereas 2 underwent CE-MRA after the neonatal period. 10 of the 26 neonates with PA-VSD did not undergo CE-MRA preoperatively: one patient died during the first days of life, 2 underwent conventional angiocardiography at cardiac catheterization for interventional purposes, while during the introduction phase (2002-2004) of CE-MRA at our institution 7 patients had cardiac catheterization exclusively for diagnostic purposes. Of 14 patients with PA-IVS, only 1 had a preoperative CE-MRA, while 3 died within the first days of life without any angiography, 8 had diagnostic conventional angiography at catheterization for interventional purposes, and 2 had diagnostic catheterization solely to evaluate communications between the right ventricle and the coronary arteries.Thus, the study population included 15 patients  with PA  who underwent CE-MRA for initial diagnosis at a median age of 3 days (range: 1-27 days) with a median weight of 2900 g (range: 1500-3900 g). The main cardiac anomalies are listed in table 14 patients underwent surgery and/or a catheter guided intervention between 3 and 324 days (median: 28 days) following the initial CMR study, while 1 patient died prior to an intervention. In 3 patients total repair with a single stage unifocalization and reconstruction of the right ventricular outflow tract was performed. 8 patients received a modified Blalock-Taussig or central aortopulmonary shunt with concomitant reconstruction of the pulmonary arteries and unifocalization of APCAs in 6 cases. Unsuccessful stenting of bilateral PDAs in one patient and of a stenotic APCA in another patient was followed by surgery with placement of a modified Blalock-Taussig shunt and reanastomosis of the APCA to the aorta. The patient with PA-IVS underwent a Rashkind atrioseptostomy but died before surgery. Total anomalous pulmonary venous connections were repaired at the initial surgery in 2 of 3 patients.3 voxel size on average. A double dose (0.2 mmol/kg body weight) of gadolinium-based contrast material  was injected manually through a peripheral intravenous line over approximately 5 seconds, followed by an equivalent volume of saline solution. For optimal timing an automated bolus detection method  was used in 7 patients, while in 8 patients the scan was started manually after a delay of 4 to 6 seconds. All studies were performed under general anaesthesia with intubation allowing three sequential data acquisitions during a single breath hold of 45 - 60 seconds.The CMR studies were performed on a 1.5-T scanner  using a quadrature head coil. Coronal, axial and sagittal nongated steady-state free precession (SSFP) images covering the entire chest served as localizers. For CE-MRA, three-dimensional fast spoiled gradient echo (3D FSPGR) data sets were acquired with coronal partitions and following technical parameters: flip angle 30°; mean echo time 1.17 ms (range: 1.00-1.43 ms), mean repetition time 3.42 ms (range: 3.31-3.68 ms), mean section thickness 1.9 mm (range: 1.6-2.8 mm), mean field of view 216 mm (range: 200-290 mm), matrix 256 × 160. With zero fill interpolation in all three dimensions  the spatial resolution was reconstructed to 0.48 × 0.42 × 0.42 mmDepending on the underlying congenital heart disease or the associated cardiac anomalies in some cases CMR also included cine imaging with electrocardiographically gated fast gradient-echo sequences and velocity-encoded phase-contrast cine sequences.The CE-MRA was evaluated retrospectively by two radiologists in consensus, who were blinded to the results of other imaging studies and findings at surgery. The original image data were viewed on a workstation  using multi-planar reconstruction (MPR), maximum-intensity-projection (MIP) and volume rendering (VR) techniques. Each CMR study was judged to be either diagnostic or non-diagnostic depending on the potential to definitively affirm or negate the presence of native pulmonary arteries and to describe and classify pulmonary artery morphology and the source of pulmonary blood supply according to the classification mentioned below. If pulmonary arteries or pulmonary blood supply could not be completely evaluated and additional cardiac catheterization had to be recommended, the study was judged non-diagnostic. Findings of the consensus reading were compared to those of the initial CMR report, conventional angiocardiography report and cine documentation (n = 5), and to the description of the anatomy in the surgical report (n = 13). Comparison to angiocardiographic or surgical findings was available in all but one patient.A pulmonary artery was defined as a vessel entering the lung at the hilum with a typical branching accompanying the bronchial tree. According to Tchervenkov et al.  PA was dFor each vessel origin, destination and diameter were documented as well as the presence and localisation of a stenosis of more than 50% of the luminal diameter.All 15 neonates with PA underwent CMR without complication. The pulmonary vasculature was best delineated on the first acquisition of the CE-MRA in 87%, whereas the second set of images showed the pulmonary arterial anatomy more clearly in 2 cases . In all cases the pulmonary artery morphology table , APCAs wIn none of the 9 patients who underwent surgery only with CE-MRA were there any additional intraoperative findings that would have changed the therapeutic strategy or surgical approach. Nonetheless, there were discrepant findings between CE-MRA, surgery and conventional angiocardiography in 3 cases. In the first patient, an APCA arising from the left coronary artery was misinterpreted as a hypoplastic native pulmonary artery in the initial CMR report and the consensus reading. In knowledge of the surgical report, this vessel could be identified on CE-MRA as indirect APCA arising from the left coronary artery and supplying the right lower lobe. In the second patient, a direct APCA from the descending aorta branching into the right lower lobe was not described at surgery performed 8 weeks after the CMR study but was confirmed by angiocardiography 10 weeks later. In the third patient, an APCA arising from the left subclavian artery supplying the left upper lobe with a diameter of less than 1 mm was diagnosed only at cardiac catheterization for a Rashkind balloon atrial septostomy, although it could be identified retrospectively on CE-MRA.In 2 cases CE-MRA was judged as non-diagnostic because direct APCAs from the descending aorta could only be suspected but not clearly identified due to intensely enhancing surrounding atelectatic lung in one case and a vessel diameter of less than 1 mm in the other case. Catheter angiocardiography demonstrated the direct APCAs and confirmed the remainder of the pulmonary artery morphology in the first case, while in the second case the planned catheterization was not performed because the patient died of a gastrointestinal infection. Overall, 5 of the 15 patients underwent additional catheterization following CE-MRA, 2 for diagnostic and 3 for interventional purposes.The anatomy and morphology of the pulmonary circulation determines treatment planning and surgical approach in patients with PA . TraditiOur study demonstrates that CE-MRA is very well suited to depict small pulmonary vessels when the spatial resolution is optimized. We were able to correctly describe the presence and morphology or absence of native pulmonary arteries in 93% (14/15 patients) of the investigated neonates. Non-confluent pulmonary arteries were supplied by bilateral PDAs in all cases, which has been considered a rare condition by some  but alsoThe main limitation of this study is the lack of direct comparison between CE-MRA and conventional angiography in all cases. In our institution, since its introduction, CE-MRA has gradually replaced cardiac catheterization for the initial evaluation of the pulmonary vasculature in neonates and today it is the primary modality for evaluating patients with PA as long as no immediate intervention is required. Thus performing an invasive procedure such as additional cardiac catheterization for study purposes would have been unethical. The impact of changing the diagnostic algorithm, from cardiac catheterization to CMR, on the outcome of neonates with PA still needs to be demonstrated. Survival and quality of life of these children is primarily determined by the native anatomical conditions of the disease and by the ability of the surgeon in reconstructing a viable pulmonary arterial tree ,21. NeveBesides depiction of the pulmonary arterial anatomy, CMR may also provide haemodynamic information by obtaining additional velocity-encoded phase-contrast cine sequences. In patients with PA, flow volume measurements in the ascending aorta and in each pulmonary vein can be used to estimate the pulmonary-to-systemic blood flow ratio (QP/QS = QPV/(QAO-QPV)) and the amount of blood flow to each lung. The contribution of a PDA or large APCA to the pulmonary blood supply may be assessed, but investigation of all APCAs would be tedious and imprecise if they are small. With optimisation of current CMR techniques for imaging neonates, it should be possible to measure flow volumes with sufficient accuracy in vessels larger than 2 mm diameter ,23.In conclusion, CE-MRA is a useful diagnostic tool in clinical routine for the preoperative evaluation of the morphology of pulmonary arteries and pulmonary circulation in neonates with PA. In most cases additional diagnostic cardiac catheterization can be avoided.The authors declare that they have no competing interests.NK, RH, EV and CK were involved in the study concept and design and performed data acquisition. NK and CK were involved in data analysis/interpretation. NK, EV and CK were involved in either manuscript preparation or editing. All authors read and approved the final manuscript.


Electrical fusion between left ventricular pacing and spontaneous right ventricular activation is considered the key to resynchronisation in sinus rhythm patients treated with single-site left ventricular pacing.Use of QRS morphology to optimize device programming in patients with heart failure (HF), sinus rhythm (SR), left bundle branch block (LBBB), treated with single-site left ventricular pacing.We defined the "fusion band" (FB) as the range of AV intervals within which surface ECG showed an intermediate morphology between the native LBBB and the fully paced right bundle branch block patterns.Twenty-four patients were enrolled. Echo-derived parameters were collected in the FB and compared with the basal LBBB condition. Velocity time integral and ejection time did not improve significantly. Diastolic filling time, ejection fraction and myocardial performance index showed a statistically significant improvement in the FB. Interventricular delay and mitral regurgitation progressively and significantly decreased as AV delay shortened in the FB. The tissue Doppler asynchrony index (Ts-SD-12-ejection) showed a non significant decreasing trend in the FB. The indications provided by the tested parameters were mostly concordant in that part of the FB corresponding to the shortest AV intervals.Using ECG criteria based on the FB may constitute an attractive option for a safe, simple and rapid optimization of resynchronization therapy in patients with HF, SR and LBBB. Patients with heart failure (HF), low ejection fraction (EF) and left bundle branch block (LBBB) can be treated with cardiac resynchronization therapy (CRT). CRT is an adjunctive treatment currently indicated for patients remaining symptomatic in NYHA class III or IV despite optimal medical therapy -3.Many observational studies, as well as a series of randomized, controlled trials have demonstrated the safety, efficacy and long-term beneficial effects of CRT. These studies have shown statistically significant improvements in quality of life, NYHA functional class ranking, exercise tolerance -8 and leMost of the available clinical data have been derived from studies involving permanent biventricular pacing (BIVP). Single-site left ventricular pacing (LVP) confers similar improvements in clinical parameters to BIVP -13, evenIn patients with left ventricular conduction delay and sinus rhythm, LVP alone significantly increases LV systolic function. Although indications for LVP must still be clear defined, there is growing evidence suggesting that applying LVP is comparable with the BIVP mode in selected HF patients presenting LBBB. Two multi-centre randomized trials ,19 have Electrical fusion between LVP and spontaneous right ventricular activation is considered the key to resynchronisation in sinus rhythm patients treated with single-site LVP -26. DepeElectrical fusion can easily be detected through surface ECG: a simple morphological analysis may advise how to programme the device. The aim of this pilot study was to evaluate the use of the QRS morphology of fusion beats to optimise programming in CRT patients with sinus rhythm, LBBB and single-site LVP.Consecutive patients underwent CRT device implantation in accordance with current guidelines. During post-implantation (>1 month) echocardiographic evaluation, the device was tracked by spontaneous atrial activity thanks to a preserved sinus node function. Ventricular pacing was enabled only in the left ventricle.On shortening the programmable AV interval by 10 ms steps, we obtained a series of 12-lead ECG showing progressive transition in morphology from LBBB to a completely left preexcited right bundle branch block (RBBB), passing through intermediate QRS of "fusion". The transition was most easily detected in lead V1.We defined the "fusion band" as the range of AV intervals at which surface ECG showed an intermediate morphology between the native LBBB pattern and the fully paced RBBB pattern.We chose to set the upper limit of the band at an AV interval 40 ms shorter than the intrinsic conduction time , a choice that gives LBBB morphology but with a slight variation from that of the native QRS; the lower limit was set at the AV interval that produced an RBBB-like morphology, but not complete RBBB. The time between the limits was divided into three intervals, thus identifying two intermediate AV intervals fig .s of all 12 LV segments [Patients underwent a conventional echocardiographic examination including M-mode, two-dimensional and Doppler analysis to determine LVEF by means of the biplane Simpson's equation . Images were obtained during stable haemodynamic conditions by using a 3.5-MHz transducer in standard left parasternal and apical views. The following variables were calculated at each of the patient-specific predefined AV intervals, as mentioned above: LV diastolic filling time (DFT) was measured on the pulsed-wave Doppler of mitral inflow as the time interval from the onset of the E wave to the end of the A wave; mitral regurgitation (MR) was visualized by colour Doppler flow imaging in the 4-chamber apical view and its degree expressed as the percentage of the regurgitant jet area relative to the left atrial size ; acute csegments . All echThe study had the approval of the Ethics Committee of the Azienda Unità Sanitaria Locale di Ferrara, Via Cassoli 30, 44100 Ferrara , and informed consent to participate in the investigation was obtained from each patient before enrolment.All data are expressed as mean ± SD. An intra-patient analysis was performed and the data were compared by means of paired, 2-tailed Student's t-Test. A P value <0.05 was regarded as significant.We enrolled 24 consecutive patients with HF, sinus rhythm and LBBB, in whom a CRT device had been implanted. Table The fusion band, as assessed through surface ECG analysis, ranged from 95 ± 31 to 189 ± 45 ms. Mean basal QRS width of the patients was 166 ± 17 ms.LVEF had a slight but significant increase in the fusion band compared to LBBB fig .In comparison with the pattern observed during LBBB, VTI fig  and ET  did not To the best of our knowledge this pilot study is the first study to utilize the well-known electrical concept of fusion to guide the optimization of CRT in patients treated with single-site LVP. On the surface electrocardiogram, electrical fusion generates variation in the QRS complex morphology. In our study, we programmed AV intervals in such a way as to modulate the degree of fusion between spontaneous septum/right-ventricular activation and artificial left ventricular stimulation, while keeping the patient's spontaneous atrioventricular conduction unaltered. Optimization of the AV interval, as intended in patients with complete AV block, was not the aim of our study.CRT is an electrical approach that uses pacing and electrophysiologic principles to improve mechanical performance. When only the LV is stimulated, the interventricular conduction time from left to right allows normal conduction to occur over the right bundle at the longest AV intervals. This results in the fusion of LV pacing and intrinsic conduction, thereby producing biventricular activation by means of single-site pacing.Initially, the role of intrinsic conduction through the right bundle branch on the haemodynamic effect of left ventricular stimulation was studied in an animal model . The finSubsequently, the relationship between fusion and mechanical efficiency was acutely evaluated in CHF patients by measuring dP/dt . In thatWhile QRS duration is used as a criterion for patient selection, QRS narrowing in response to CRT has proved to be a disappointing index of haemodynamic improvement.As fusion induces mechanical resynchronization, QRS morphology, rather than duration, may be utilized to identify the desired re-homogenisation.Recently van Gelder  proposedIn patients with single-site LVP, ECG morphology depends on fusion of only two propagation waves due to LVP and intrinsic right bundle conduction. In this setting QRS morphology may provide a simple guide to the proper programming of the device, as progression in the degrees of fusion appears on the surface ECG as variation in the QRS complex .As it is still unclear which is the most reliable and reproducible echo parameter for evaluating CRT patients, we chose a set of parameters that quantify different aspects of cardiac function in order to explore the different levels of dyssynchrony that may be present in failing hearts. Similarly, it is still unclear whether the optimal haemodynamic effect of CRT coincides with maximal reduction in interventricular or intraventricular asynchrony ,26,33,34In the real world, programming devices usually means choosing the "best" value of one or more parameters, which are analyzed acutely, basically at rest, as we did in this pilot study. On the basis of our observations, it seems reasonable to programme single-site LV pacing at the AV intervals within the predefined band, mainly within the shorter half of the band, as is clearly shown in fig In the shortest part of the band, we observed the largest overlapping among the parameters. Moreover, setting an AV value inside the fusion band may guarantee the persistence of fusion, and thus of the haemodynamic benefits, even during the continuous variation of spontaneous atrioventricular conduction, and even during physical exercise.Naturally, the approach based on the ECG detection of the fusion band can be adopted only in sinus rhythm patients, as they provide a reliable trigger, in terms of atrial activity, for LV pacing. When possible, the use of single-site LV pacing enables the life of the implanted device to be significantly prolonged.This approach does not obviate the need for the RV lead, as only patients with LBBB and stable sinus rhythm can benefit from fusion with spontaneous RV activation, and therefore do without RV pacing. Data from the literature show that during atrial fibrillation (AF), provided that LV pacing is not inhibited by high rates, BIV pacing seems superior to single-site LV pacing ,36. As pMoreover, patients in whom an implantable defibrillator is indicated need an RV lead for appropriate sensing and defibrillation of the arrhythmia in any case.Finally, we did not compare LVP with BIVP because this was not the aim of this pilot study. Our objective was to find out an ECG based method to optimize LVP. It seems reasonable that a similar method may be applied even to optimize BIVP, as fusion band may be identified also with this pacing mode.As patients were evaluated at rest, the study yielded no data regarding the dynamic behaviour of the fusion band during exercise stress testing.We compared the parameters recorded in the fusion band with native LBBB, but we did not evaluate the extreme condition of complete RBBB corresponding to very early depolarization of the left ventricle. In practice, this evaluation is feasible only in patients with a relatively long PR interval, in whom the programmable AV intervals could be short enough to obtain full capture of the entire myocardium through left pacing, thereby anticipating the spontaneous right bundle branch conduction.Finally, we did not compare subgroups of patients with ischemic and non-ischemic cardiopathy, owing to the relatively low number of patients in these subgroups.Using ECG criteria based on the "fusion band" method to optimise single-site LV stimulation seems feasible and reliable. It may constitute an attractive option for the safe, simple and rapid management of devices implanted in patients with heart failure, sinus rhythm and left bundle branch block. Large-scale and long-term studies are needed to validate this method from a clinical point of view.The author(s) declare that they have no competing interests.LG conceived the study, participated in its design and drafted the manuscript. KB performed the analysis and interpretation of the data and reviewed the manuscript. BS and RV performed the analysis and interpretation of the data, reviewed the manuscript and participated in the design of the study. GC and PA conceived the study and reviewed the manuscript. All authors read and approved the final manuscript.


Isolated ventricular noncompaction is an extremely rare cardiomyopathy, not fully clarified.It is characterized by persistent embryonic myocardium morphology without associated cardiac abnormalities.Since first description in 1984, few clinical studies were done. Data in the literature are lacking and most reports consist on a few case studies.Doppler ecocardiogram is considered the reference method for diagnosis.Diagnosis remains difficult since there are similarities with other cardiac defects, clinical manifestations are non-specific and echocardiographic criteria are not universally accepted.As a consequence diagnosis may be easily missed.Moreover, clinical and echocardiographic features were just recently clarified.Treatment is directed towards important clinical manifestations .We present a clinical case of severe cardio-respiratory failure in previously healthy and asymptomatic young male, which was the initial presentation of an isolated ventricular noncompaction.A brief review of available literature is done concerning to this case study. Isolated ventricular noncompaction (IVNC) is a rare cardiomyopathy, until now, not fully clarified. It is thought to result from an arrest of the compaction of loose myocardial meshwork during foetal development. It is generally associated with other congenital abnormalities such as obstruction of ventricular outflow tracts.IVNC is characterized by persistent embryonic myocardium morphology in the absence of other cardiac abnormalities.Engberding first described it in 1984 referring to a 33-year old woman with persistent "sinusoids" in the left ventricle as an isolated abnormality [Thirty-two years old, black male, born in Angola, mason and smoker. He was previously healthy, referring no prior cardiac or pulmonary complaints. He had a two-month history of asthenia, anorexia and mild to moderate progressive dyspnoea with a decreased exercise tolerance. About 72 hours before his admission to the hospital, he started with fever, cough, mucopurulent sputum, severe shortness of breath and total exercise intolerance.On admission to the Emergency Ward he was on acute pulmonary oedema with respiratory failure and acidosis. Chest x-ray demonstrated increased heart-thorax index and heterogeneous diffuse infiltrate sparing the upper lobes and bases. Figure He was referred to Intensive Care Unit (ICU) where he was intubated and submitted to mechanical ventilation. He was prescribed with antibiotics and diuretics.A former bedside echocardiogram was performed, six hours after admission, with the patient under ventilator support, showing mild mitral valve regurgitation. No additional abnormalities were found and left ventricle function was normal.The B-type natriuretic peptide (BNP) levels were 2152 pg/mL .Microbiological and immunological studies were negative.th day of mechanical ventilation he was extubated.Patient presented an adequate clinical response and on 5Two more episodes of acute pulmonary oedema occurred which were reverted by medical therapy and non-invasive ventilation.He started on angiotensin-converting enzyme (ACE) inhibitors therapy.Chest axial tomography Figure  showed cA new echocardiogram Figure  demonstrAfter nine days on the ICU, patient was clinically stabilized and was referred to a Cardiology ward. BNP although far beyond normal levels, had decreased to 1244 pg/ml.A cardiac Magnetic Resonance Imaging (MRI) Figure  was perfth day after admission and referred to a Cardiology clinic.A β-blocker was added to the treatment already prescribed and patient was discharged on the 15IVNC is considered a rare disease, although its exact prevalence of is unknown. According to one of the largest series published, its prevalence was 0,014% in a group of patients referred to an echocardiography laboratory for abnormal findings or congestive heart failure . Men appThe initial series published were related to paediatric population, but more recently there have been some cases described in adults -4.th and the 8th week of intrauterine development, when coronary circulation develops, ventricular myocardium becomes gradually compacted and those recesses turn into capillaries [IVNC is considered a congenital cardiomyopathy caused by intrauterine arrest of myocardial development. During early embryonic development, in the first months of intrauterine life the myocardium consists of a meshwork of loosely interwoven muscle fibres. In this spongy conformation, trabeculae alternate with recesses that communicate with the ventricular cavity to provide blood supply to the myocardium. Between the 5illaries ,5.Left ventricle is uniformly affected, while right ventricle involvement is referred in less than one-half of the patients .Familial recurrence has been associated to genetic linkage, related to a mutation in G 4.5 gene of Xq28 chromosome region and to a cardiac specific CSX gene [Clinical manifestations of IVNC are non-specific, heterogeneous and patients may be either asymptomatic or suffer from severe cardiac dysfunction. Although it is a congenital disease, the onset of symptoms is quite variable and may even occur at an advanced age. One of the most common manifestations of IVNC is a progressive left ventricular dysfunction, which may cause heart failure.Structural myocardial changes, consequent microvascular dysfunction and subendocardial perfusion defects, even in the absence of coronary disease, may contribute either to ventricular dysfunction or arrhythmias ,3,5,6. AEmbolic events resulting either from atrial fibrillation or from formation of thrombi in the ventricular trabeculae may occur quite frequently. Cerebrovascular accidents, transient ischemic attacks and mesenteric infarction related to IVNC have been described in the literature ,3,5.IVNC is generally detected by means of bidimensional echocardiography with Doppler, which is considered the reference method for the diagnosis ,7,8. EchCardiac MRI has good correlation with echocardiogram, being useful in patients with bad echocardiographic window and to clarify doubtful echocardiographic abnormalities ,8.Diagnosis of IVNC remains sometimes difficult and even controversial. IVNC often presents overlapping findings to other heart muscle diseases like dilated cardiomyopathy (DCM) and hipertrophic cardiomyopathy (HCM) . It's noThis clinical case refers to a previously healthy black male presenting an acute severe cardio-respiratory failure requiring ICU admition. Both echocardiogram and cardiac RMI were suggestive of IVNC. No other structural abnormalities or cause for acute heart failure were detected.Jenni and colleagues [Several diagnostic criteria have been proposed in the literature -9,12,13.lleagues . Accordilleagues . This allleagues .This clinical case also meets the Chin diagnostic criteria which are based in the ratio between distance from the epicardial surface to the trough of the trabecular recess/distance from the epicardial surface to peak of trabeculation ≤ 0,5 .Both images obtained by echocardiogram and cardiac RMI were suggestive of IVNC.Kohli and colleagues have proposed that diagnostic criteria of IVNC may be too sensitive for black individuals [Meanwhile recently ividuals . They reividuals . In factividuals .Extensive non compacted myocardial layer can be just a variant of normal maturation of the ventricular wall. The most important is to determine when its presence becomes clinically relevant rather than an incidental finding. In fact to decide the clinical significance of these findings in an asymptomatic individual with no additional findings may be a huge dilemma.Treatment of IVNC is not specific and is directed toward its three most important clinical implications: heart failure, cardiac arrhythmias and embolic events.Appropriate treatment for heart failure is essential and is similar to that of other causes which include diuretics, β-blockers and ACE inhibitors ,5,8. If Sports competition and exhausting activities are forbidden and pregnancy should be avoided . Due to New York Heart Association (NYHA), persistent ventricular tachycardia, atrial fibrillation and branch block are bad prognosis criteria [Prognosis is widely variable. Some patients remain asymptomatic throughout their lives, while others show a rapid deterioration of the cardiac function, causing early death ,7. In facriteria ,5,9. TheAs previously referred diagnosis and orientation of IVNC patients with relevant clinical presentation is usually difficult and complex.However not easier is the approach of asymptomatic individuals in which a routine echocardiogram reveals extensive hypertrabeculation or even suggests IVNC. These problems may surely increase as cardiac image techniques will continue to improve and until more accurate criteria become available.There is much work to be done in order to clarify this entity with such a heterogeneous spectrum. Additional studies are needed to determine the frontier between upper limits of normal trabecular patterns that may occur in asymptomatic individuals and clinically relevant IVNC.Isolated ventricular noncompaction is a rare and recently described congenital cardiomyopathy. Its impact on morbidity and mortality is gaining importance as it is recognized with increasing frequency. An early, reliable diagnosis is crucial and echocardiography represents a prominent role.Treatment is directed towards its most important clinical implications, which include heart failure, arrhythmias and systemic embolic events. Heart transplantation is the only definitive treatment.Our purpose with this case report was to point out attention to this entity as an important and often misdiagnosed cause of cardio-respiratory failure.IVNC: Isolated ventricular noncompaction; ICU: Intensive Care Unit; BNP: B-type natriuretic peptide; DCM: Dilated cardiomyopathy; HCM: Hipertrophic cardiomyopathyWritten informed consent was obtained from the patient for publication of this case report and accompanying images.A copy of the written consent is available for review by the Editor-in-Chief of this journal.The authors declare that they have no competing interests.JB, FM, JV, JM, PA, GB were staff from the ICU. All of them analyzed and interpreted the patient data regarding to the clinical presentation, complementary exams. They were responsible for the orientation of this clinical case in the ICU. They were major contributors in writing and reviewing the manuscript. LS performed the cardiological examination. He was responsible for cardiological orientation after discharge from ICU. All authors read and approved the final manuscript.


We used T2-STIR (Short Tau Inversion Recovery) cardiovascular magnetic resonance to demonstrate carcinoid tumor metastases to the heart and liver in a 64-year-old woman with a biopsy-proven ileal carcinoid tumor who was referred because of an abnormal echocardiogram. A 64-year-old Middle-Eastern woman was referred to our center for cardiovascular magnetic resonance (CMR) for further evaluation of basal inferior left ventricular (LV) wall thickening that was detected by transthoracic echocardiography done in her home country. The echocardiogram was done to search for cardiac valvular manifestations of a biopsy-proven ileal carcinoid tumor. Multiple CMR imaging sequences were obtained which demonstrated that the basal inferior LV wall thickening was composed of an intramyocardial mass. In addition, there was another smaller (9 mm diameter) intramyocardial mass in the free wall of the right ventricle (RV) and there were multiple masses in the liver. All of these cardiac and hepatic masses had the same magnetic resonance imaging characteristics. Neither the RV mass nor the hepatic masses were reported to be detected by echocardiography. The CMR sequence which best distinguished the metastatic carcinoid cardiac and hepatic tumors from surrounding normal tissue in this case was T2-weighted Short Tau Inversion Recovery (T2-STIR). In addition, CMR demonstrated the absence of carcinoid valvular thickening. In this case, information learned from CMR, guided cardiac surgical and oncologic consultants' clinical decisions.Half-Fourier Acquisition Single-shot Turbo spin Echo (HASTE) showed multiple hepatic metastases up to 65 mm × 60 mm in size, and a large intramyocardial mass (43 mm × 35 mm × 32 mm) in the basal inferior wall of the LV. Cine balanced Steady State Free Precession images demonstrated that the intramyocardial mass had fused with the posterior leaflet of the mitral valve, restricting its motion and causing moderate mitral regurgitation. A small amount of pericardial effusion surrounding the mass was noted, but there was no evidence of extension of the mass into the pericardial space.Scans were carried out using a Siemens Sonata 1.5 Tesla scanner. Initial localizer images using electrocardiographically-gated A T2-weighted Short Tau Inversion Recovery (T2-STIR) sequence revealed the LV intramyocardial mass to have a high signal intensity which indicates a high water content that could be caused by active inflammation and/or edema. The same high signal intensity signal was noted in the hepatic masses. A small spherical intramyocardial mass (9 mm in diameter) with the same high signal intensity was identified in the free wall of the right ventricle (RV), which had not been detected by echocardiography nor identified as distinctly by other CMR sequences Fig. . Tissue No evidence of carcinoid valvular thickening was found on either side of the heart. The right ventricle and right atrium were normal in size and function. The left atrium was dilated secondary to mitral regurgitation that was attributed to the fixed posterior mitral valve leaflet. The anterior leaflet was normal in its motion and thickness.Carcinoid tumors are neuroendocrine tumors with an estimated annual incidence of 2 per 100,000 in the general population. [In a study of 74 patients with carcinoid heart disease  all had As a consequence of improvements in the treatment and the prognosis for patients with a carcinoid tumor, the incidence of carcinoid heart disease and cardiac metastases has also increased . Among pMetastatic tumors to the heart are 20–40 times more frequent than primary tumors of the heart . IntracaIndium-111-labeled somatostatin receptor imaging has been used to localize carcinoid tumors  and to vThe identification and localization of carcinoid myocardial metastases and the presence or absence of carcinoid valvular disease and its severity is pivotal for planning therapy. While some myocardial metastases are located in regions that are amenable to excision , others, like the large basal inferior LV mass attached to the posterior leaflet of the mitral valve, are more technically challenging for the surgeon, may be too large to remove and repair, and carry a greater surgical mortality.The relatively new T2-STIR technique, used to detect the presence and extent of myocardial edema in patients with a recent myocardial infarction, can be applied to estimate the water content of a cardiac mass . The higSurgical and oncologic consultants conferred after reviewing the case and the data provided by the CMR imaging. Considering the absence of cardiac symptoms, the presence of multiple cardiac lesions, the size of the basal inferior LV mass, its involvement of the posterior mitral valve leaflet, and the multiple large hepatic masses, a surgical cure was not attainable and the surgical risk was high, without immediate clinical gain. A decision was made to manage the patient without surgery. She left London for medical treatment at home.In this case, echocardiography done to determine the source of a systolic murmur did not find carcinoid valvular disease, but rather a curious basal inferior LV thickening. CMR, and especially the bright signal from the carcinoid myocardial metastases using the T2-STIR sequence, identified the large LV mass and a smaller RV mass that was not detected by echocardiography, in the absence of a pericardial effusion. In addition, the identification of hepatic metastases, the tissue characterization of the tumor masses by LGE, and the assessment of myocardial and valvular function made CMR the single best test for assessing the cardiac and hepatic sequellae of metastatic carcinoid tumor.The author(s) declare that they have no competing interests.WS supervised the CMR image acquisition, researched the subject and drafted the manuscript. SP interpreted the CMR, chose the sequences to highlight the pathology and offered ideas for the manuscript. CB provided the patient and used CMR results for patient management. All authors read and approved the manuscript.


The purpose of this study was to determine the ability of Blood Oxygen Level Dependent (BOLD) cardiovascular magnetic resonance (CMR) to detect stress-inducible myocardial ischemic reactions in the presence of angiographically significant coronary artery disease (CAD).Forty-six patients  with suspected or known coronary artery disease underwent CMR at 3Tesla prior to clinically indicated invasive coronary angiography. BOLD CMR was performed in 3 short axis slices of the heart at rest and during adenosine stress (140 μg/kg/min) followed by late gadolinium enhancement (LGE) imaging. In all 16 standard myocardial segments, T2* values were derived at rest and under adenosine stress. Quantitative coronary angiography served as the standard of reference and defined normal myocardial segments , ischemic segments  and non-ischemic segments (i.e. supplied by a non-significantly stenosed coronary artery in patients with significant CAD).Coronary angiography demonstrated significant CAD in 23 patients. BOLD CMR at rest revealed significantly lower T2* values for ischemic segments (26.7 ± 11.6 ms) compared to normal  and non-ischemic segments . Under adenosine stress T2* values increased significantly in normal segments only .Rest and stress BOLD CMR at 3Tesla proved feasible and differentiated between ischemic, non-ischemic, and normal myocardial segments in a clinical patient population. BOLD CMR during vasodilator stress identified patients with significant CAD. Cardiovascular magnetic resonance (CMR) is increasingly applied in clinical routine to determine myocardial perfusion -4 using Blood Oxygen Level Dependent (BOLD) CMR is based on the paramagnetic properties of deoxyhemoglobin as an endogenous contrast agent with increased deoxyhemoglobin content leading to signal reduction on T2*- or T2-weighted images. Thus, BOLD CMR directly reflects myocardial oxygenation status ,10. CoroHowever, data on myocardial BOLD CMR during vasodilator stress in patients with coronary artery disease (CAD) is limited to experimental studies -15 and sForty-six consecutive patients  referred for clinically indicated invasive coronary x-ray angiography due to chest pain syndromes were prospectively enrolled. Patients were eligible if they had suspected or known CAD . Patients with prior coronary surgery or typical contraindications for CMR  and administration of adenosine  were not considered.All study participants were instructed to refrain from ß-blockers, antianginal medication, cigarettes, tea and coffee for at least 24 hours prior to CMR. Written informed consent was obtained from all subjects, and the Charité Institutional Review Board approved the study.CMR was performed with the patient in the supine position using a 3T whole-body imager  equipped with a Quasar Dual gradient system . A six element cardiac synergy coil was used for signal reception and cardiac synchronization was done with the use of a Vector-ECG. All acquisitions were performed during short end-expiratory breath-holds. After acquisition of cine standard cardiac geometries for the assessment of left ventricular function a fast-gradient-echo multi-echo sequence for BOLD CMR (3-slices of short axis geometry) was performed. Then, adenosine infusion  was started and the identical BOLD CMR sequence was repeated after at least 3 minutes of adenosine infusion. After termination of adenosine infusion, a bolus of 0.2 mmol/kg of gadolinium-DTPA was administered followed by late gadolinium enhancement (LGE) imaging 10 minutes later in identical short axis geometry with full left ventricular coverage.Three short axis  and three long axis geometries  were acquired using an electrocardiogram-triggered balanced turbo field echo sequence  during repetitive end-expiratory breath-holding.BOLD CMR imaging was carried out in the identical three short axis geometries of the left ventricle using an electrocardiogram-triggered, spoiled segmented gradient-echo sequence with six echo times . Image data acquisition was restricted to end-diastole in order to minimize cardiac motion related artefacts. A black blood dual inversion prepulse was used to nullify signal from flowing blood in the left ventricular cavity. Figure Late gadolinium enhancement imaging was carried out in short axis orientation with full left ventricular coverage using a three-dimensional inversion prepared spoiled gradient echo sequence . The prepulse delay was determined from an inversion prepared cine scan (Look-Locker) and individually adjusted to optimally suppress signal from normal myocardium.All patients underwent invasive coronary angiography in standard Judkins technique within 48 hours after CMR. The procedure was done according to angiographic guidelines using a simultaneous biplane, multidirectional and isocentric x-ray system. At least two orthogonal views of every major coronary vessel and its side branches were acquired. Quantitative coronary angiography  was performed off-line by an independent observer being unaware of the results of CMR. The severity of coronary stenosis was derived from one single view showing the maximal reduction in absolute luminal diameter and a significant coronary stenosis was defined as ≥50% luminal diameter reduction in vessels with ≥2 mm diameter; significant left main stenosis was considered double-vessel disease. In addition, myocardial segments were assigned to the supplying coronary artery based on a consensus read of the interventionalist and the CMR imager taking the respective coronary dominance type into account.The BOLD CMR data sets were evaluated on a per segment basis according to the standardized 16-segment model [LGE images were analyzed visually on a per segment basis regarding the presence of myocardial scar ≥25% transmurality with each myocardial segment being classified as normal or scarred.® release 9.2.1.0.  was used. The areas under the curves were compared using the method of DeLong et al.[Statistical analysis was performed by using the SPSS software package release 17 . The paired Student's t test or Wilcoxon test and independent-samples t test or Mann-Whitney test were used to test for differences within and between groups. All tests were two-tailed. The Kolmogorov-Smirnov test was used to test for normality. A P value of less than 0.05 was considered significant. For ROC analysis and the comparison of the area under the curve MedcalcA total of 46 consecutive patients were enrolled in this study. In 4 patients, CMR scans could not be completed: 2 patients were claustrophobic, and 2 did not tolerate adenosine. Hence, 42 91%) of 46 patients of this study cohort successfully completed the CMR examination and were included in the final analysis.Patient characteristics and hemodynamic data are summarized in table % of 46 pOn BOLD CMR at rest, 15 patients showed excellent (35.7%), 21 patients good (50.0%), five patients moderate (11.9%) and one patient poor image quality (2.4%); under adenosine stress image quality was excellent in 11 patients , good in 21 patients (50.0%), moderate in eight patients (19.0%) and poor in two patients (4.8%). The mean visual score of BOLD CMR was 3.2 ± 0.8 at rest and 3.0 ± 0.8 under adenosine stress (p = 0.005). Though all studies were of sufficient quality for analysis, segments demonstrating poor image quality were excluded from analysis . The overall artifact score was significantly higher under adenosine stress than at rest  compared to normal segments  and non-ischemic segments . During adenosine stress T2* values demonstrated a significant increase in normal segments only . On the contrary, T2* values of non-ischemic  and ischemic segments  did not significantly differ for the comparison of stress versus rest. When comparing stress T2* values of normal versus non-ischemic and ischemic segments significant differences were found . Corresponding error bar charts are given in figure The global T2* value of patients without significant CAD was 32.2 ± 3.5 ms at rest and 37.4 ± 6.3 ms under stress (p = 0.0003). In patients with significant CAD the global T2* value was 30.3 ± 5.3 at rest and 30.7 ± 5.8 under stress (p = 0.78). Imaging examples are provided in figure The area under the curve (AUC) of the ROC analysis Figure  for the In the present study, BOLD CMR at 3T was shown to be feasible at 3T resulting in an overall good image quality at rest and during vasodilator stress. BOLD CMR at rest and under stress conditions distinguished between normal, ischemic and non-ischemic myocardial segments. In addition, adenosine stress BOLD CMR gave a good diagnostic performance with regard to the detection of angiographically defined coronary stenosis.The non-invasive detection of ischemic myocardium is one of the major strengths of CMR. BOLD imaging represents a promising alternative to first-pass CMR perfusion techniques, which rely on the application of exogenous contrast agents. BOLD imaging allows to directly assess the myocardial oxygenation status taking advantage of the paramagnetic properties of intravascular deoxyhemoglobin . During In the present study, ischemic myocardial segments showed significantly reduced T2* values under resting conditions, while during adenosine stress T2* values increased in normal myocardial segments only. Our findings were consistent with previous reports by Wacker et al. and Niemi et al. ,18, but Interestingly, in the present study non-ischemic myocardial segments did not show a significant increase of T2* values during stress. These findings may be explained by microvascular disease , which iThe T2* CMR values at rest in patients without CAD were within the range of previously published data by Story et al.   and O'ReImportantly, the current study population consisted of consecutive patients with a high proportion of known CAD and prior myocardial infarctions but such patients were usually not considered in previous studies ,12,21. HRest and stress BOLD CMR at 3T proved feasible and may be used to differentiate between ischemic, non-ischemic, and normal myocardial segments in a clinical patient population. BOLD CMR during vasodilator stress identified patients with significant CAD.RM: study design, data acquisition, image analysis, statistical analysis, manuscript drafting. IP: study design, image analysis, statistical analysis, manuscript drafting. BS: study design, literature research, manuscript drafting. EF: study design, manuscript drafting. RG: data acquisition, literature research. CJ: study design, statistical analysis, manuscript drafting, guarantator of integrity of entire study. All authors have made revisions to the manuscript and have read and approved the final version.Bernhard Schnackenburg is an employee of Philips Medical Systems, Hamburg, Germany.CMR: Cardiovascular magnetic resonance; CAD: Coronary artery disease; LGE: Late gadolinium enhancement; SNR: Signal-to-noise ratio; QCA: Quantitative coronary angiography; ROC: Receiver under the operator curve; BMI: Body mass index; PCI: Percutaneous coronary intervention.


During septic shock, resistance to the haemodynamic effects of catecholamine vasopressors and inotropes is a well-recognised marker of mortality risk. However, the specific cardiovascular or metabolic response elements that are most closely associated with outcome have not been well defined. The objective of this study was to assess cardiovascular and metabolic responses to dobutamine as correlates of outcome in patients with severe sepsis or septic shock.A prospective, non-randomised, non-blinded interventional study of graded dobutamine challenge  in adult patients who had undergone pulmonary artery catheterisation within 48 hours of onset of severe sepsis or septic shock (8 survivors/15 non-survivors) was performed. Radionuclide cineangiography during graded infusion was used to determine biventricular ejection fractions at each increment of dobutamine.2 were concordant with survival or death in 21 of 23 cases. Multivariate profile construction showed stroke volume index as the dominant discriminating variable for survival with the systolic blood pressure/left ventricular end-systolic volume index ratio alone among all other variables significantly improving the model.In univariate analysis, a variety of cardiovascular or haemodynamic and oxygen transport or metabolic variables (at the point of maximum cardiac index response for a given subject) were associated with survival including: increased stroke volume index (p = 0.0003); right ventricular end-diastolic volume index (p = 0.0047); left ventricular stroke work index (p = 0.0054); oxygen delivery index (p = 0.0084); cardiac index (p = 0.0093); systolic blood pressure/left ventricular end-systolic volume index ratio (p = 0.0188); left ventricular ejection fraction (p = 0.0160); venous oxygen content (p = 0.0208); mixed venous oxygen saturation (p = 0.0234); pulse pressure (p = 0.0403); decreased pulmonary artery diastolic pressure (p = 0.0133); systemic vascular resistance index (p = 0.0154); extraction ratio (p = 0.0160); and pulmonary vascular resistance index (p = 0.0390). Increases of stroke volume index of greater than or less than 8.5 mL/mSurvivors maintain cardiac responsiveness to catecholamine stimulation during septic shock. Survival from severe sepsis or septic shock is associated with increased cardiac performance and contractility indices during dobutamine infusion. Further studies are required to determine whether these parameters are predictive of outcome in a larger severe sepsis/septic shock population. One of the major areas of investigation has been the cardiovascular correlates of outcome. Early clinical studies, prior to the widespread adoption of the balloon-tipped pulmonary artery flotation catheter with thermodilution capability in the 1980s, tended to suggest that fatal sepsis and septic shock were characterised by a low cardiac output (CO) and high systemic vascular resistance (SVR) ,3. Sever2I) -7. Studi2I) . Evidenc2I) ,12.Bedside experience and several clinical studies suggest that blunted cardiovascular responsiveness to catecholamine support is also a marker of high risk of death in sepsis and septic shock . HoweverThis study received Institutional Review Board approval. Informed consent was obtained from all subjects or appropriate representatives prior to enrolment.Adult (more than 18 years of age) Intensive Care Unit patients were recruited into this prospective, non-randomised, open interventional study. In order to be eligible, patients were required to have developed severe sepsis or septic shock within the preceding 48 hours and to have both a pulmonary artery catheter and arterial pressure catheter in place . Study eligibility was further contingent on confirmation of correct placement of the pulmonary artery catheter based on appropriate pressure traces on insertion and position on chest radiography.2 <32 mm Hg and white blood cell count >12,000 cells/mm3, <4,000 cells/mm3 or >10 per cent immature (band) forms; and evidence of at least one organ failure.The presence of severe sepsis was defined by 1991 SCCM/ACCP Consensus Statement on Sepsis Definitions . These cSeptic shock was defined by the presence of post-fluid resuscitation hypotension  necessitating vasopressor support.Patients with known ischemic cardiac disease and mixed shock states with clinically significant primary cardiogenic, haemorrhagic or pulmonary embolic elements were excluded.99 cineangiography as described below. In addition, simultaneous arterial and mixed venous blood samples  were obtained for analysis of the serum pH, partial pressure of oxygen (pO2), partial pressure of carbon dioxide (pCO2), and oxygen saturation .After consent was obtained, each patient underwent graded dobutamine challenge as follows: If required, subjects initially received saline infusion to a pulmonary artery wedge pressure (PWP) of 15 mmHg as required because pilot studies had shown the potential for significant hypotension with dobutamine absent adequate intravascular volume as evidenced by PWP of 15 or higher. After documentation of a PWP of 15 mmHg or higher, baseline haemodynamic and vital parameters  were obtained. These included heart rate (HR), systemic arterial pressures, central venous pressure (CVP), pulmonary artery pressure (PAP), pulmonary wedge pressure (PWP) and CO. Thermodilution cardiac outputs were measured by the averaging of three of four successive injections of 10 mL of cold (6 to 10°C) dextrose 5 per cent in water at end-expiration . Recorded values for PAP, PWP and right atrial pressure (RAP) were also obtained at end-expiration from graphic recordings. Right and left ventricular ejection fractions (EFs) were assessed through first-pass gated technetiumAfter baseline values were obtained, a graded dobutamine challenge was performed. Dobutamine infusion through the pulmonary artery catheter introducer port was initiated at 5 μg/kg/min. After 15 minutes, repeat non-invasive and invasive haemodynamic parameters were obtained over approximately five minutes. At this time, subjects also underwent repeat first pass radionuclide assessment of biventricular ejection fractions and arterial and mixed venous blood gas analysis. The dobutamine infusion rate was increased by 5 μg/kg/min at 20 minute intervals to a maximum of 15 μg/kg/min with the assessment process repeated during the final five minutes of each interval. During the infusion, fluid and additional vasopressor support (beyond baseline needs) to maintain a minimum PWP of 15 mmHg and a mean arterial pressure (MAP) of 65 mmHg was mandated; however, no subject required such support. During the period of the study environmental stimulation was minimised. All subjects were continuously monitored with continuous electrocardiographic (ECG) monitoring and pulse oximetry according to standard protocol in the intensive care unit. The protocol required discontinuation of dobutamine if any transient adverse effects were noted including significantly increased ventricular ectopy or decreased blood pressure. After study completion, dobutamine was tapered over 20 minutes and then discontinued. The patient's subsequent intensive care and hospital course were directed by normal clinical practice.99-DPTA. Tc99-DPTA was injected as a tight bolus into the central veins using the pulmonary artery catheter introducer. In this study, the baseline radionuclide tracer dose was 2 mCi with subsequent increments to 5, 12 and 25 mCi. The study was performed in a 30° right anterior oblique projection with a slant hole collimator fitted on to a small field gamma camera interfaced with a dedicated computer system . The data was acquired in frame mode with 440 frames, each of 60 milliseconds duration. The first transit cardiac data was reformatted into a multi-gated study using the subject's electrocardiogram recorded with the first pass data. This method provides independent cinematic display of the right as well as left ventricle. Ejection fractions (EFs) are calculated from the reformatted gated first pass studies using standard dual region of interest and background correction [Sequential measurement of biventricular ejection fraction was performed by repeat first-pass radionuclide cineangiography using technetiumrrection ,16.Stroke volume (SV) was derived by dividing thermodilution CO by the concomitant HR. End-diastolic volume (EDV) was obtained by dividing SV by EF and end-systolic volume (ESV) was calculated as EDV-SV. SVR was calculated as 79.9(MAP-RAP)/CO and pulmonary vascular resistance (PVR) as 79.9(mPAP-PWP)/CO where MAP = mean arterial pressure and mPAP = mean pulmonary artery pressure. Where appropriate, cardiovascular variables were indexed to body surface area.Haemodynamic and oxygen transport/consumption variables at the baseline and at each dobutamine infusion rate were pooled for all subjects to derive means and standard errors of the mean. The infusion rate at the point of maximum cardiac index (CI) during dobutamine administration was determined for each subject and the corresponding haemodynamic/clinical/oxygen metabolism values at that point were used for comparison to baseline (before dobutamine but after fluid resuscitation) values. Haemodynamic values at the point of maximum CI response were compared to pre-dobutamine infusion baseline values as correlates of survival to hospital discharge using two-tailed paired Student's t-test analysis. Fisher's Exact test was used for proportional analysis and independent-samples t-tests with Levene correction for unequal group variances was used for continuous measures Tables  and 2. STwenty-three subjects  were recruited for the study. Average (± standard error) age was 62.6 ± 4.0 years. Only eight of twenty-three (35 per cent) patients with severe sepsis survived to hospital discharge. Median and inter-quartile survival duration from the day of the study among non-survivors was six days and two to nine days respectively. No clinically significant adverse effects occurred during the course of the experimental dobutamine challenge. Similar proportions of subjects in each group failed to tolerate the highest planned infusion rate (15 μg/kg/min) of dobutamine (two of eight survivors and five of fourteen non-survivors). In all but one case (a non-survivor), the next highest dose (10 μg/kg/min) was tolerated.2/FiO2) ratio. The presence of renal and other individual organ failures was similar between the groups but the mean number of organ failures at the time of study entry was significantly higher in non-survivors. Similarly, the Simplified Acute Physiology Score II (SAPS II) at the time of the study were significantly higher in non-survivors; Acute Physiology and Chronic Health Evaluation II (APACHE II) scores were not. The most common underlying diagnoses in non-survivors were a post-operative state and malignancy. Among survivors, an absence of a major primary underlying disease condition was most common. Pneumonia was the most common underlying infection in both groups accounting for seven of fifteen and six of eight cases in non-survivors and survivors respectively.Subject characteristics of the entire group, survivors and non-survivors are shown in Table Mean difference tests for baseline and dobutamine-stimulated haemodynamic/oxygen transport variables in survivors and non-survivors are shown in Table 2), venous oxygen content (CvO2), oxygen delivery index (DO2I) and oxygen extraction ratio (OER); 3) peripheral resistance including diastolic pulmonary artery pressure (dPAP), systemic vascular resistance index (SVRI) and pulmonary vascular resistance index (PVRI); 4) left ventricular contractility including left ventricular ejection fraction (LVEF), peak systolic pressure/left ventricular end-systolic volume index ratio (sBP/LVESVI) and left ventricular stroke work index (LVSWI); and 5) right ventricular lusitropy including right ventricular end-diastolic volume (RVEDVI) and right ventricular end-diastolic volume:right atrial pressure ratio (RVEDVI/RAP).Survivors and non-survivors exhibited divergent responses to dobutamine in several different areas Table , 4a, 5a.2 increase in SVI could differentiate between survivors and non-survivors in 21 of 23 cases with just one subject mismatched in each group  were similarly associated with improved outcome. However, calculated oxygen consumption as reflected by VO2I was not. Several variables associated with vascular resistance were also found to be significantly associated with survival on univariate analysis including decreases in SVRI, PVRI and dPAP. Decreases in diastolic systemic arterial pressure did not reach significance in this regard.Other cardiac performance variables related to SVI also were associated with survival on univariate analysis including CI and pulse pressure (PP)Table . GreaterIn terms of the mechanics of cardiovascular performance, greater increases of left ventricular contractility indices were associated with survival in patients with septic shock Table . IndicesUsing multivariate forward entry discriminant analysis, several alternative models with similar predictive accuracy were identified depending on the significance level used to add and retain variables in each model. In each case, the SVI response was, by far, the most predictive variable. However, the most parsimonious discriminant model achieved maximal accuracy with the addition of sBP/LVESVI response as a 2nd factor in the model. Using this model, outcome in 22 of 23 cases could be appropriately categorised . sBP/LVESVI, a relatively load-independent index of left ventricular contractility [In our study, cardiovascular performance as indicated by SVI response was the dominant correlate to outcome with a single cut off value of 8.5 mL/min able to differentiate 21 of 23 outcomes. The predictive power of most other parameters appeared to be physiologically linked to this response and did not persist in multivariate analysis  may be critical to survival. This concept of preserved physiologic reserve as a marker of good prognosis in septic shock has previously been postulated by Hayes et al [et al [The fact that both cardiac performance and contractility increases in response to dobutamine stress are highly associated with outcome in septic shock is consistent with the possibility that the presence of es et al  and Rhodl [et al  albeit ipreload reserve used most commonly in reference to ischemic heart disease associated limitations in cardiac performance may also apply to septic shock [This study may also demonstrate that the concept of ic shock . Severalic shock ,34. No dSimilarly, our observations of an association of right ventricular dilatation Table  in respopreload reserve is a critical but late response during high degrees of cardiovascular stress. If that is the case, then a lack of ability to recruit ventricular volume at any point during cardiovascular stress may indicate that the subject is already operating at the maximum efficacy of the Frank-Starling response and has no additional cardiovascular reserve. In this formulation, patients with chronic systolic dysfunction would be more likely to be symptomatic, while patients with septic shock would be more likely to die if such reserve was limited. The nature of the limitation of cardiovascular reserve in conditions of high stress would be a combination of the baseline cardiovascular fitness and the degree of acute cardiovascular stress.One possibility to tie these observations together is that recruitment of The study demonstrates that cardiovascular hypo-responsiveness to catecholamine stimulation is strongly associated with mortality in severe sepsis and septic shock. Compared to baseline differences in heart rate, dobutamine stress-induced variations in stroke volume responses are much more closely related to outcome. Dobutamine-induced differences in contractility responses also appear to possess independent correlative power with respect to mortality. One physiological mechanism supporting increased cardiac output appears to involve ventricular dilatation in survivors suggesting an important role for "preload reserve" in optimal cardiovascular response to severe sepsis and septic shock. This response may be related to previous observations demonstrating that increased ventricular dilatation is characteristic of survival from septic shock.This study makes several novel observations. However there are significant limitations to the results. First, despite the fact that dobutamine-stress induced cardiovascular responses are highly associated with outcome, their utility for risk stratification as related to research or clinical prognostication remains unproven. A prospective study would be required to validate their utility for that purpose. Second, these data do not suggest that any of the variables associated with outcome drive these are responsible for these outcomes. It is much more likely that these associations are correlations without causality. For example, reduced stroke volume response to dobutamine likely indicates underlying severity of illness rather than being a direct contributor to risk of death. Finally, there may be significant unmeasured confounders for some of the documented responses. Higher mean intra-thoracic pressures due to more severe lung disease and greater ventilatory requirements could contribute to the smaller RVEDVI and RVEDVI/RAP responses to dobutamine. These patients could also be at higher risk of death. Unfortunately, mean airway pressures are not available for analysis.Although a variety of dobutamine-stimulated cardiovascular and ventricular responses are associated with outcome in sepsis and septic shock, SVI increases are most strongly correlated with survival. Since this stimulation test involves transient administration of dobutamine, this response is probably indicative of preservation of cardiac signalling mechanisms and of cardiovascular reserve in the septic patient. Notably, the predictive strength of these responses is substantially more powerful than that generated by initial HR, the only baseline haemodynamic index associated with outcome.Further research is required to better understand the mechanisms underlying differing cardiovascular responses during severe sepsis and septic shock both at baseline and under exogenous catecholamine stress.1) Survival from sepsis and septic shock is closely associated with dobutamine-stimulated increases in stroke volume.2) Survivors of sepsis and septic shock are characterised by preserved cardiovascular reserve including preload reserve.2 = inspired oxygen fraction; HR = heart rate; LVEDVI/PWP = left ventricular end-diastolic volume index: pulmonary wedge pressure ratio; LVEF = left ventricular ejection fraction; LVSWI = left ventricular stroke work index; MAP = mean arterial pressure; mPAP = mean pulmonary artery pressure; MVO2 = mixed venous oxygen saturation; OER = oxygen extraction ratio; PaO2 = arterial partial pressure of oxygen; PAP = pulmonary artery pressure; pCO2 = partial pressure of carbon dioxide; pO2 = partial pressure of oxygen; PP = pulse pressure; PWP = pulmonary wedge pressure; PVR = pulmonary vascular resistance; PVRI = pulmonary vascular resistance index; RAP = right arterial pressure; RVEDV = right ventricular end-diastolic volume; RVEDVI/RAP = right ventricular end-diastolic volume: right atrial pressure ratio; RVEF = right ventricular ejection fraction; RVSWI = right ventricular stroke work index; sBP/LVESVI = peak systolic pressure: left ventricular end-systolic volume index ratio; sPAP/RVESVI = peak systolic pulmonary artery pressure: SV = stroke volume; SVI = stroke volume index; SVR = systemic vascular resistance; SVRI = systemic vascular resistance index; VO2I = oxygen consumption index; right ventricular end-systolic volume index ratio.CI = cardiac index; CO = cardiac output; CvO2 = venous oxygen content; CVP = central venous pressure; DO2I = oxygen delivery index; dPAP = diastolic pulmonary artery pressure; ECG = electrocardiographic; EDV = end-diastolic volume; EF = ejection fraction; ESV = end systolic volume; FiOThe authors declare that they have no competing interests.Anand Kumar had overall responsibility for this study including study design, administration, and execution. He was also was primarily responsibility for data analysis and manuscript development. Elizabeth Schupp (study execution), Eugene Bunnell (study execution), Amjad Ali (nuclear ventriculography) and Barry Milcarek (statistics) assisted with specific aspects of the project. Joseph Parrillo was involved in study design and manuscript preparation.


Since its original description in 1994, alcohol septal ablation (ASA) has emerged as a minimally invasive modality for treatment of hypertrophic obstructive cardiomyopathy compared to surgical myomectomy. This catheter-based intervention relies on the injection of absolute alcohol into the septal perforator to induce a controlled infarction of the hypertrophied septum and consequently abolish the dynamic outflow obstruction. This gradient reduction has been correlated with a significant clinical improvement in the patient’s symptomatology and with left ventricular remodeling. The procedure has been refined throughout the years, especially with the introduction of myocardial contrast echocardiography for localization of the area at risk of infarction and the reduction in the amount of alcohol used. Major complications of ASA are uncommon in large referral centers but conduction system disturbances has been the most commonly reported complications of ASA with 10% of patients necessitating permanent pacemaker implantation for complete heart block. ASA has not been compared to the gold standard surgical myomectomy in a randomized prospective study. We review the clinical aspects of this procedure and provide some historical background. Hypertrophic cardiomyopathy (HCM) is a genetic cadiomyopathy inherited as an autosomal dominant trait and characterized by asymmetrical septal hypertrophy unexplained by any other cardiac disease. Microscopically, this disease process is notable for a distinct abnormal disorderly array of myofiber orientation. The disease has a wide spectrum of clinical presentation varying from totally asymptomatic individuals with normal life expectancy to severely symptomatic patients with increased mortality due to sudden death or congestive heart failure. The overall prognosis of HCM patients is favorable with an annual mortality of about 1% and adverse events are mostly related to sudden cardiac death, obstructive symtoms or progressive heart failure. Left ventricular outflow obstruction is present in 25-30% of patients with HCM and constitutes the pathophysiological basis for many aspects of the disease. It is also an important prognostic factor of the disease. In fact, it has been clearly shown that a gradient of 30 mmHg or more is associated with an increased risk of disease progression, congestive heart failure, stroke and death. While the treatment of obstructive HCM has largely relied on pharmacologic management of the disease with beta-blockers and calcium channel blockers, a small but important subgroup of patients are refractory to medical therapy. Surgical myectomy and percutaneous alcohol septal ablation have proven efficacy in the symptomatic management of this drug-refractory population. Alcohol septal ablation was developed as a less invasive approach to reduce left ventricular outflow obstruction by inducing a partially controlled infarct of the basal septum with resultant scar formation and left ventricular remodeling.et al., the mean NYHA class was 2.9 (±0.01), and only 51-53% percent were on beta-blocker or calcium channel blocker therapy  aet al. reported on a single center experience with ASA where 644 patients were followed for up to 10 years. In their report, they described a significant decrease in the incidence of complications correlating with decreasing alcohol dosage (from a mean of 2.9 ml to 0.8 ml). In fact, in-hospital mortality decreased from 1.8% to 0.6% and was mostly ascribed to non-cardiac causes of death [Early mortality occurring within the first 30 days after ASA has been reported to be 1.5% (0-5%) and results usually from hemodynamic collapse due to ventricular failure or tamponade, ventricular fibrillation or LAD dissection . Unfortuvs. 17%) [Since its introduction by Sigwart in 1994, ASA has been performed in thousands of patients with good short term results. Acute anatomical changes after ASA and myomectomy have been evaluated by cardiac MRI; ASA results in a larger area of tissue necrosis (16±7 grams compared to 6±4 grams) often involving a transmural infarct with varying location and depth at the junction of the anterior and inferior segments of the basal septum . Some pavs. 17%)  and an ivs. 17%) .Few reports compared the clinical outcomes of ASA to surgical myomectomy and no comparison of long term outcomes has been performed. In a recent meta-analysis of three retrospective studies including 171 patients -40, bothASA has developed as a safe and attractive modality to treat patients with HCM whose symptoms are refractory to optimal medical therapy with negative inotropic agents. The procedure has been refined over the past decade since its development with steadily improving outcomes and reduced complications especially PPM implantation. However, concerns over the higher risk of complete AV block and development of a potentially arrhythmogenic scar after ASA have been raised . The gol


Surgery for congenital heart disease has progressed by leaps and bounds in the last few decades, but the right ventricular outflow tract continues to pose a challenge to the congenital heart surgeon. A sizeable proportion of congenital heart defects have a component of right ventricular outflow tract abnormality. This may be in the form of a simple stenosis or a more complicated atresia, discordant ventriculo-arterial connection, absent pulmonary valve or rarely a common systemic and pulmonary outflow as in truncus arteriosus. Pulmonary stenosis (PS) is relatively easily treated by opening the stenosed pulmonary valve, resecting obstructive muscle and if necessary further enlarging the narrowed portion with a patch of autologous pericardium. Since a portion of the natural right ventricle (RV) to pulmonary artery (PA) connection is preserved, the outflow tract can be expected to enlarge in keeping with the growth of the patient and recurrent stenosis is rather uncommon.Absence of continuity between the RV and PA either because of atresia or a discordant arterial connection calls for a more complicated intervention. Valved conduits were first used by Ross and soonA wide range of conduits are currently in use - cryopreserved or fresh antibiotic sterilized aortic and pulmonary homografts, dacron tubes with porcine aortic valves, bovine pericardial tubes with porcine aortic valves, porcine aortic roots and more recently bovine internal jugular vein. Most non-homograft conduits are commercially available in most parts of the world in a wide range of sizes. Homografts are largely harvested and prepared by individual institutions in valve banks that are specially set-up for this purpose. Availability of homografts is dependant on the supply of cadaver hearts and is generally limited, in the smaller sizes. However, when available they are the preferred conduit of choice because of their superior handling characteristics and longevity. Commercially available conduits overcome the problem of availability but are generally prohibitively expensive, precluding their widespread use in countries with meager financial resources. Surgeons often resort to handmade conduits made in the operating room from autologous or bovine pericardium, dacron or polytetrafluoroethylene (PTFE).6 The seaGiven the problems with the use of conduits, it is not surprising that surgeons have constantly endeavored to evolve surgical techniques that would obviate their use. The common surgical principle in all these so called ‘non-conduit options’ is: 1) direct autologous tissue approximation of the opened out main PA or PA bifurcation to the superior margin of the right ventriculotomy, thus creating the posterior wall of the RV outflow, and 2) roofing this with a generous patch of autologous pericardium to create the anterior wall of the outflow. The assumption is that, as in correction of tetralogy of Fallot with a transannular outflow patch, there is a direct continuity of right ventricular muscle with native PA along, at least some part of the circumference of the reconstructed outflow and this would allow age-related growth. Additionally, some attempt is made at containing severe pulmonary regurgitation by incorporating a monocusp made of autologous pericardium, homograft cusp, bovine pericardium or PTFE membrane. However, unlike conduits the competence of the monocusp valve is dependant on the surgeon's skill.Conduitless repair is most easily performed in patients with ventricular septal defect (VSD) and short segment pulmonary atresia. Here the gap between the RV outflow and the PA is short, and approximation of the mobilized main pulmonary artery stump to the right ventriculotomy is relatively easily achieved without too much tension on the PAs. ApproximThe first of these types of repair for transposition with VSD and PS was described by Lecompte in 1982 and he named the operation ‘Reparation L'etage Ventriculaire’ or REV procedure in short.[Although the REV procedure is a theoretically attractive procedure that obviates the use of a conduit it is not feasible in all patients with discordant ventriculo-arterial connection. Patients who have had prior systemic to pulmonary shunts tend to have fibrosis and thickening of the PAs that makes the Lecompte maneuver difficult or unsafe. In patients with a large ascending aorta as might be seen in transposition with pulmonary atresia, there can be excessive stretching of the PA bifurcation leading to outflow obstruction. In patients with a limited retrosternal space or in those with pectus excavatum, the anteriorly placed pericardial hood is at risk of compression.In 1984, Nikaidoh further extended this principle in his technique for non-conduit repair of transposition with VSD and PS. In his tEarly attempts at conduitless RV-PA connection were confined to conditions with decreased pulmonary blood flow, because it was feared that in patients with increased pulmonary blood flow, postoperative pulmonary incompetence in the face of pulmonary hypertension would not be well tolerated and lead to adverse outcomes. The first successful attempt at non-conduit repair for truncus arteriosus was reported by Reid in 1986. SubsequeAlthough conduit sparing procedures have now been in use for over two decades, long-term data in large groups of patients is lacking, unlike follow-up data for the Rastelli procedure.14 Meanin1516In truncus arteriosus, it appears that beyond the neonatal period non-conduit repairs seem to be associated with a greater early mortality, possibly20


Prolonged P wave duration and P wave dispersion (PWD) have been associated with an increased risk for atrial fibrillation (AF). Hyperthytodism is a frequent cause of atrial fibrillation (AF). Forty-two patients with newly diagnosed overt hyperthyroidism and 20 healthy people were enrolled in the study. Transthoracic echocardiography, 12 lead surface ECG and thyroid hormone levels were studied at the time of enrollment and after achievement of euthyroid state with propylthiouracil treatment.Maximum P wave duration (Pmax) , PWD , deceleration (DT)  and isovolumetric relaxation times (IVRT)  were significantly higher in hyperthyroid patients compared to control group. Pmax and PWD were significantly correlated with the presence of hyperthyroidism. Pmax  Pmin , PWD  and DT  were significantly decreased after achievement of euthyroid state in patients with hyperthyroidism. Diastolic dyfunction was seen in 5 patients at hyperthroid state but only in one patient at euthyroid state.Hyperthyroidism is associated with prolonged P wave duration and dispersion. Achievement of euthyroid state with propylthiouracil treatment results in shortening of P wave variables.  Diastolic function may have a partial effect for the increased Pmax and PWD. Shortening of Pmax and PWD may be a marker for the prevention of AF with the anti-thyroid treatment. Hyperthyroidism has profound effects on the heart, including increased heart rate, slightly enhanced systolic function, left ventricular (LV) hypertrophy, and diastolic dysfunction -9. AtriaP-wave duration and P-wave dispersion (PWD) are electrocardiographic (ECG) signs of prolongation of intraatrial and interatrial conduction time and inhomogeneous propagation of sinus impulses that are well known electrophysiological characteristics of the atrium prone to fibrillate -17.In the present study, we aimed to evaluate P wave variables and LV diastolic function in hyperthyroid patients and to search the effects of shortterm propyl thio uracil (PTU) treatment.Forty two consecutive hyperthyroid  patients followed at out patient clinic of the endocrinology and metabolism department of the hospital and 20 healthy euthyroid healthy voluntary people were evaluated with 12-lead ECG and transthoracic echocardiography. Patients with systemic hypertension, diabetes mellitus, history of structural or ischemic heart disease, chronic obstructive pulmonary disease or any associated systemic disease and patients using systemic drugs, like steroids, antiarrythmics or antipsychotics, were excluded. The study was approved by the Yuzuncu Yil University, Faculty  of Medicine Ethics Committee in accordance with the Declaration of Helsinki. All participants were informed about the study and their consents were obtained.In the patient group ECG and echocardiographic examinations were performed before treatment and after achievement  of euthyroid state with PTU treatment.The evaluation of thyroid morphology and function was performed by clinical examination, assessment of serum free thyroid hormone T3 and T4 (FT3 and FT4) and throid stimulating hormone (TSH) levels, and ultrasound examination of the thyroid gland. A total of 5 ml of venous blood samples were drawn and then centrifuged at 2000 rpm for 10 min in a refrigerated centrifuge to separate serum. Serum FT3, FT4, TSH, levels were measured using the commercial Immulite kits, which are solid-phase, two-site chemiluminescent immunumetric assay in Immulite autoanalyser . The normal reference intervals were 0.80 - 1.80 ng / dl, 1.8 - 4.2 pg/ ml and 0.40 - 4.0 mIU / ml for FT4, FT3 and TSH respectively.The echocardiographic examination was performed at rest, with the patient at left lateral decubitis position, using a commercially available echocardiographic device  with a 3 MHz transducer, by two experienced echocardiographers who were blinded to the clinical data. Using M-mode echocardiography, long-axis measurements were obtained at the level distal to the mitral valve leaflets according to current recommendations of the American Society of Echocardiography .  The puTissue Doppler imaging (TDI) was acquired to assess diastolic function. The pulsed wave spectral mode was used for TDI. Filters and baselines were corrected when the velocity ranged between -20 and 20 cm/s. From the apical 4-chamber view, a 5-mm sample volume was placed at the lateral corner of the mitral annulus.  Early (Em) and late (Am) diastolic velocities were obtained. All values were measured on three separate beats and then averaged for all parameters.Impaired left ventricular relaxation was defined as having an E/A ratio of <1 (< 0.5 for >50 years), DT > 200 msec and IVRT > 100 msec (>105 msec for >50 years), all together and/or E/Em ratio of >10 and Ea < 10 cm/sec in the presence of a preserved ejection fraction .Twelve-lead ECGs were obtained at rest, with 20 mm/mV amplitude and 50 mm/sec rate with standard lead positions. ECGs were manually measured by the use of a magnifying glass by two blinded cardiologists having no information about the patients. The beginning of the P wave was defined as the point where the initial deflection of the P wave crossed the isoelectric line, and the end of the P wave was defined as the point where the final deflection of the P wave crossed the isoelectric line. The difference between maximum and minimum P wave duration was defined as PWD .Intra-observer and inter-observer coefficients of variation for echocardiographic parameters and P wave variables were found to be less than 5% and nonsignificant.Data were presented as mean ± standard deviation (SD). Using an SPSS package 10.0  the changes of parameters after treatment were compared with paired t-tests. Differences in mean values between groups were assessed using the Student t test and with Mann-Whitney's U-test for variables without normal distribution. Pearson correlation analysis was used to assess the correlation between variables. A two-tailed p value < 0.05 was considered significant.Maximum P wave duration, PWD, DT and IVRT were significantly higher in hyperthyroid patients compared to control group . PWD wasEuthyroid state was achieved during a 2,5±0,8 months. Pmax, Pmin, PWD and DT were significantly decreased after achievement of euthyroid state in patients with hyperthyroidism . The sliIn this study we found that P maximum and PWD values were increased in hyperthyroidism and treatment with PTU results in improvement in Pmax, PWD and LV diastolic function parameters.The correlation between the presence of intraatrial conduction abnormalities and the induction of paroxysmal AF has been well documented  -20. P-waFrequency of AF is increased in hyperthyroidism . The carIncrease in Pmax and PWD values have been reported in hyperthyoidism . Direct Impaired left ventricular relaxation has been reported to effect PWD [31]. It has been reported that hyperthyrodism has profound effects on cardiac diastolic function that are at least in part reversible after restoration of euthyroidism ,32,35. ISmall number of study patients and short-term follow-up are the  major limitations. Another important limitation of our study is manual calculation of P-wave parameters using magnifying lens instead of computer-assisted P-wave calculations. We do not have automated measurement facilities for PWD. However, thermal, digital, and signal-averaging ECG systems have been used to evaluate PWD which was measured manually either on paper or on a high-resolution computer screen.  Although, several studies have demonstrated a low error of the measurement of P wave dispersion on paper printed ECGs ,7  otherHyperthyroidism is associated with prolonged P wave duration and dispersion. Achievement of euthyroid state with PTU treatment results in shortening of P wave variables. Diastolic function may have a partial effect for the increased Pmax and PWD.  However, there is need for larger prospective studies to elucidate the role of P wave disturbances in prediction and early treatment of AF in hyperthyroid patients.