Brugada syndrome (BrS) is characterised by the triad of coved ST elevation, lethal ventricular arrhythmia in an apparently structurally normal heart. The precise mechanisms responsible for the coved ST elevation and ventricular arrhythmias in this disease have been debated since its initial description in 1992. Indeed the recent recognition of early repolarisation J wave disorders linked to primary VF broadens the mechanistic importance of BrS in sudden cardiac death. It may lie on a spectrum of early repolarisation pathology which is becoming increasingly recognised as a marker of premature cardiovascular death. Mechanistically, abnormalities of both depolarisation and repolarisation in the right ventricular outflow tract, and heterogeneities of conduction between the endocardium and epicardium have been implicated in the electrographic manifestations of BrS and arrhythmogenesis.The initial belief of BrS as a single autosomal dominant ion channel disorder has been challenged. It has become apparent that sodium channel mutations only account for a maximum of 30% of cases and structural myocardial abnormalities have now been described in what was previously thought to be a purely functional condition. It is highly probable that BrS is an umbrella diagnosis for a number of conduction and repolarisation abnormalities which manifest as this syndrome and the coved ST elevation represents the final common pathway of both ion channel and structural derangements. This review will discuss the issues surrounding the mechanisms of lethal arrhythmia in BrS and summarise both basic science and clinical research findings. The Brugada syndrome (BrS) was formally characterised as a distinct clinical entity in 1992 . It has Abnormalities of repolarisation or depolarisation and heterogeneities in conduction both within the epicardium and between the epicardium and endocardium have been proposed to account for the electrocardiographic abnormalities and ventricular arrhythmia. There is increasing evidence that each of these mechanisms may play a role. BrS as a purely functional ion channel disorder is also being questioned by contradictory evidence gathered from cardiac biopsies, autopsy specimens and new high resolution imaging modalities.A re-entrant mechanism perpetuates ventricular tachycardia in BS, and requires an initiating mechanism or 'trigger' and a substrate capable of maintaining it. Since the right ventricular outflow tract is the main patho-physiological arena in this disease, its structure and embryological orgins will be reviewed before discussing the main hypotheses of arrhythmogenesis in BrS.In Brugada syndrome, the classic ECG findings are present in the right praecordial leads and ventricular arhythmias are more readily induced from the right ventricle -8. MoreoThe right and left ventricles and RVOT are formed along the craniocaudal axis of the heart along which signalling and other critical regulatory processes are polarised. This is suggested to account for anatomical differences and electrophysiological heterogeneity in the adult .A level of electrophysiological heterogeneity in the heart is vital for optimal cardiac function, facilitating co-ordinated contraction and relaxation. This heterogeneity is rooted in embryological development and modulated gene expression resulting in regional differences in tissue structure and ion channel distribution. Structural and electrophysiological heterogeneities exist on multiple levels: (i) between apex and base, (ii) left and right ventricles, (iii) RVOT and right ventriclular (RV) body, and (iv) between epicardium and endocardium . CriticaThe adult RVOT itself develops from the embryological outflow tract, which is formed at a later stage from the rest of the heart, and arises from the second heart field, an origin distinct from the ventricles (formed from the first heart field), with added influence from migratory cardiac neural crest cells. These developmental differences may account for the RVOT being critical in BrS pathogenesis. The program regulating cardiac neural crest development and formation is controlled by multiple distinct signals that originate in the pharyngeal endoderm and local mesoderm and the neural crest cell death program also plays an active role in stimulating outflow tract myocardialization -15. LikeTO), largely responsible for the rapid downstroke of phase 1. If there is a reduction in the amplitude of phase 0, this will result in a lower voltage level at which phase 1 begins. This affects the activation/inactivation kinetics of both ITO and the availability of the L-type calcium channel involved in phase 2, resulting in a loss of the AP dome and shortening of the epicardial AP duration (APD). The less pronounced phase 1 downstroke of endocardium due to lower ITO expression allows for conservation of the AP pattern, even with some reduction in phase 0 amplitude  has a prominent phase 1 resulting in a spike and dome morphology  Figure . This ismplitude . The traThe loss of the epicardial AP dome in some areas and retention in others results in the 'trigger' mechanism: a closely coupled extrasystole generated by phase 2 re-entry . The incAlthough this heterogeneity in AP duration could account for the corresponding ST changes inBrugada syndrome, it does not explain the T wave inversion that accompanies type 1  and sometimes type 2  electrocardiograms. It has been proposed that both an exaggeration of the notch and a prolongation of the epicardial AP beyond the endocardial action potential would be necessary to observe the raised J point, ST elevation and inverted T wave ,19 Figu.Although most of the data supportive of the repolarisation hypothesis has been derived from pharmacological manipulation of the canine wedge preparation, interesting observations have been made in man. Nagase et al reported a patient in whom they had inserted an epicardial electrode in the great cardiac vein a small distance from an endocardial catheter . During TO being a key channel involved in the Brugada ECG pattern, the right ventricle has a higher density of this channel compared with the left ventricle and it is suggested that the thinner endocardium of the right ventricle relative to its epicardium results in a more marked spike and dome pattern in this region , and fibrofatty replacement of cardiac myocytes has been reported in patients diagnosed with BrS ,52. It iA significant proportion of Brugada patients develop ventricular arrhythmias in the resting state or asleep, during which parasympathetic tone predominates. The typical ECG signs are unmasked or exacerbated by vagal stimulation, anti-adrenergic and parasympathomimetic drugs, and attenuated by exercise and isoproterenol infusion ,54-57. IIn a study by Babaee Bigi et al, 13 out of 28 patients with a type 1 Brugada ECG pattern were considered to have cardiac autonomic neuropathy, based on 2 non-invasive tests of sympathetic and parasympathetic function . 11 out Although autonomic dysfunction is not a prerequisite of BrS, it appears to be an important modulating factor in baseline ECG and arrhythmia occurrence. Why this is the case has not been elucidated but effects on the activity of ITO and the L-type calcium channel predominant during phase 2 of the action potential have been suggested ,61. EffePyrexia has also been seen to unmask the characteristic ECG pattern and there are case reports of fever induced polymoprphic VT in Brugada patients -65 and oBoth repolarisation and depolarisation abnormalities probably contribute to arrhythmogenesis in the Brugada syndrome. Early repolarisation could cause phase 2 re-entry resulting in closely coupled extrasystoles initiating VT/VF. Conduction delay due to abnormal ion channel kinetics and subtle structural derangements could contribute to this dispersion of repolarisation and provide the substrate for the maintenance of ventricular arrhythmia. These elements may be present to a variable extent in each individual patient, modulated by factors such as vagal tone and pyrexia, and account for both the different degrees of J point elevation on surface ECG. The embryological development of the RVOT and structural changes with age may also lead to intercellular uncoupling allowing repolarisation and depolarisation abnormalities to surface and contribute to individual variation in disease expression.These issues are also important in the newer J wave disorders responsible for primary VF which are the pathological extension of a normal electrocardiographic variant. Their aetiology probably mirrors that of BrS arising from abnormal ion channel behaviour during phase 0 and phase 1 of the action potential as well as potential dissociation between epi and endocardial repolarisation creating transmural voltage gradients. Indeed BrS may simply reflect a localised RV variant of an extreme form of J point elevation in a spectrum of early repolarisation disorders. These conditions provide an important clinically relevant experimental paradigm which could open the door to new approaches in the treatment and prevention of lethal ventricular arrhythmias.


Heterogeneity in B-type natriuretic peptide (BNP) levels, especially among individuals with acute heart failure with normal left ventricular ejection fraction (HFNEF), can cause confusion in interpreting results. We investigated the characteristics of cases of acute HFNEF with only modestly elevated BNP.One hundred forty-two patients with acute or acute exacerbation of chronic HFNEF were divided into two groups by BNP level: BNP < 100 pg/ml  and BNP ≥ 100 pg/ml . We compared clinical findings, echocardiography results, and neurohormonal factors between these two groups.In the NB group, a history of open-heart surgery (OHS) was more frequent  and hypertension was less frequent (p = 0.0005). Left atrial diameter (LAd) was higher (p = 0.0026), while interventricular septal thickness, posterior wall thickness, relative wall thickness, left ventricular mass index were lower  in the NB group. In patients with HFNEF, a history of OHS remained an independent predictor of BNP level (< 100 pg/ml) after adjustment for hypertension, age, LAd, and interventricular septal thickness .We found associations between acute HFNEF with less elevated BNP and a history of OHS. In a patient suspected of HFNEF, a history of OHS is considered diagnostic evidence of presence of diastolic heart failure when plasma levels of BNP are less elevated. Heart failure with normal left ventricular ejection fraction (HFNEF), also called heart failure with normal systolic function or diastolic heart failure, accounts for 40–50% of cases of heart failure. This condition is commonly observed in elderly women, particularly those with a history of hypertension, left ventricular hypertrophy, or diabetes mellitus. Congestive symptoms, although generally milder, do not differ from those in systolic heart failure (SHF), in which ejection fraction is reduced. Although HFNEF is generally associated with a more favorable prognosis than SHF, the mortality rate for HFNEF and SHF are nearly equivalent in the elderly. Diagnosis of HFNEF must be made quickly to enable appropriate treatment, but this is often difficult, particularly in elderly patients who have comorbidities such as chronic lung or heart disease. B-type natriuretic peptide (BNP) level is a useful marker not only in the diagnosis and determination of the severity of heart failure, but also in the assessment of treatment effects -4. HowevOne hundred and forty-two cases of acute or acute exacerbation of chronic HFNEF seen in our department between 2003 and 2006 were studied. The present study was a cross-sectional observational study in which the diagnosis of heart failure was based on the Framingham Criteria . In all The determination of HFNEF was made from symptoms, signs, chest x-ray results, and ultrasonic echocardiography (UCG) criteria  within 24 hr of congestive heart failure event. Patients were divided into two groups with respect to BNP levels: BNP < 100 pg/ml  and BNP ≥ 100 pg/ml . Patients with acute or severe mitral or aortic valvular dysfunction, myocardial infarction and obvious pulmonary disease were excluded. Cardiac abnormalities in this study included the following conditions: hypertension, diabetes mellitus, atrial fibrillation (AF), hypertrophic cardiomyopathy, and mild to moderate valvular disease. We compared clinical findings, history of open-heart surgery (OHS), hypertension, diabetes mellitus, and dyslipidemia, chest radiograph and ECG findings, parameters from echocardiography, frequency of atrial fibrillation (AF) and moderate or severe tricuspid valve regurgitation (TR), neurohormonal factors and other prognostic factors such as serum creatinine, hemoglobin and serum sodium between the two groups.In some cases, maximal thickness of the pericardium was assessed by computed tomography . Measurement were performed without zooming the pictures, using an electronic caliper that was placed where the pericardium was clearly visible and with lesser variations in thickness, namely on the anterior surface of the heart in front of the right and left ventricles.Venous blood samples were obtained after 30 min of supine rest on admission for radioimmunoassay measurement of B-type natriuretic peptide (BNP), A-type natriuretic peptide (ANP), plasma norepinephrine, and plasma aldosterone concentration (PAC) levels. BNP level was measured by standard radioimmunoassay  within 24 hours. Values of BNP < 43 pg/ml were considered normal.All subjects underwent standard two-dimensional echocardiography with a commercially available system  using a multi-frequency MHz transducer. Cardiac function was evaluated by M-mode echocardiography guided by two-dimensional imaging; left atrial diameters (LAd), interventricular septal thickness (IVST), posterior wall thickness (PWT), left ventricular end-diastolic diameters (LVDd), end-systolic diameters (LVDs), and ejection fraction (EF) were measured. The ratio of peak early diastolic flow velocity to peak late atrial diastolic flow velocity (E/A), deceleration time of peak early filling velocity (Dct), and right ventricular systolic pressure (RVSP) were measured by Doppler imaging. Left ventricular mass index (LVMI) was measured using the method of Simone et al. , while rIn addition, as a sub-analysis, patients with a history of OHS were subdivided into B and NB group for comparison of UCG parameters, BNP levels, frequency of AF and TR and history of hypertension.Continuous variables are expressed as mean ± SD and median value. For the relationship between UCG parameters, neurohormone levels, blood pressure, heart rate, age, and other prognostic factors, Mann-Whitney's U test was performed. Differences between groups described by categorical variables were analyzed by the chi-square test for independence or Fisher's exact probability.The independent diagnostic value of HFNEF without elevated BNP was assessed in multivariate logistic regression model for all variables that proved to be significant by univariate analysis in patients with elevated BNP and those with less elevated BNP. The following dichotomous or continuous variables were evaluated in the multivariate model: medical history of OHS and hypertension, LAd, IVST, age, and PAC. All p values less than 0.05 are regarded as having statistical significance.Table The rate of exertional breathlessness was high and extrasounds were low in both groups, with no significant differences. However, the NB group had higher rates of general malaise (p = 0.0018) and hepatomegaly (p = 0.0244). The NB group also had a higher rate of history of OHS , with a mean postoperative period of 21.1 years. The B group had a mean postoperative period of 19.7 years, demonstrating no significant differences from the NB group. In the NB group (n = 31), surgery involved mitral valve replacement , mitral valve plasty (n = 1), double valve replacement (DVR) [mitral valve replacement + aortic valve replacement (MVR+AVR)] (n = 9), open mitral commissurotomy (OMC) (n = 6), and coronary artery bypass graft . In the B group (n = 21), surgery involved MVR (n = 8), AVR (n = 3), DVR , OMC (n = 1), atrial septal defect , and CABG (n = 4). Especially, the NB group also had a higher rate of mitral prosthesis ,No differences were observed for frequencies of high voltage, ST segment abnormality, intraventricular conduction delay, and AF on electrocardiography. Although cardiothoracic ratio on chest radiograph was greater in the NB group, no differences were observed for the frequencies of pulmonary congestion and pleural effusion. No intergroup differences were observed for mean heart rate and systolic and diastolic blood pressures on admission. The pericardial thickness in NB group tended to be thicker than that in NB group . No clear calcified lesions were observed on computed tomography in patients with HFNEF with less elevated BNP. The NB group had a significantly lower ANP level (p < 0.0001) and a significantly higher PAC level (p < 0.0001). The B group with a history of OHS had a significantly lower BNP level than that without a history of OHS (p = 0.0019) Figure . No signRegarding logistic regression analysis, history of OHS, hypertension, IVST, LAd, age, and PAC were shown to be significant in univariate analysis, while only a history of OHS was shown to be significant in multivariate analysis Table . The modThe present findings suggest a relationship between HFNEF with less elevated BNP and history of OHS. Furthermore, in the B group, patients who had a history of OHS had a significantly lower BNP level. HFNEF with less elevated BNP was associated with a lower rate of history of hypertension as well as low values for left ventricular hypertrophy parameters. Patients in the NB group who had a history of OHS had marked left atrial enlargement, which may indicate permanent atrial fibrillation and pericardial constriction. Pericardial involvement may be responsible for HFNEF with less elevated BNP.Brain natriuretic peptide is secreted from the ventricles in response to increased ventricular wall stress in addition to myocardial stretch. Because a clear correlation is generally observed between left ventricular end-diastolic pressure (LVEDP) and BNP levels, BNP is used in the differential diagnosis of heart failure . MeriselHowever, in constrictive pericarditis, BNP does not increase despite increases in LVEDP . TherefoIn developed countries, the most frequent causes of constrictive pericarditis are prior cardiac surgery, idiopathic pericarditis, and irradiation therapy . PericarB-type natriuretic peptide is also expressed and secreted in atrial tissue, and is stored in atrial granules along with ANP ,26. BNP In the present study, evidence for pericardial lesions was based only on history of OHS and tendency toward pericardial thickening. Although radiographic determination of pericardium thickness is often taken into account during the assessment of constrictive pericarditis, increased pericardial thickness dose not necessarily imply constriction. Conversely, constrictive pericarditis can occur in patients with normal pericardium thickness . It shouHemodynamic assessment using right heart catheterization was performed for only two patients. However, non-compliant patterns, which are regarded as characteristic findings in constrictive pericarditis, were also observed in restrictive cardiomyopathies such as right ventricular infarction and amyloidosis, and were thus not a definitive finding. Furthermore, no characteristic waveforms are thought to be associated with mild constrictive pericarditis and effusive pericarditis. For the definitive diagnosis of constrictive pericarditis, it is essential to clarify the presence of intracardiac and intrathoracic dissociation and the presence of ventricular discordance. Therefore, constrictive pericarditis is often difficult to diagnose requiring careful attention to detail during measurement of hemodynamics. Eventually, the diagnosis of constrictive pericarditis is often confirmed at surgery. Thus, a simple measurement of BNP may be useful for differentiating constriction from restriction in HFNEF. Further study is required to determine the involvement of pericardial lesions in HFNEF with less elevated BNP.Acute heart failure with less elevated BNP is associated with a history of open-heart surgery and marked atrial enlargement. No association is observed between the level of BNP and left ventricular function. Atrial degeneration and an extramyocardial factor, particularly pericardium, need to be taken into account in the interpretation of the pathophysiology of heart failure with less elevated BNP. In a patient suspected of HFNEF, a history of open-heart surgery  is considered diagnostic evidence of presence of diastolic heart failure when plasma levels of BNP are less elevated.The authors declare that they have no competing interests.KS conceived and designed this study, carried out the data analysis and statistical analysis and drafted the manuscript. NK, KM, MH, YK, AS, and EF performed the collection and analysis of data. MK helped to draft the manuscript and added important intellectual content.All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:


A 42 year old woman was admitted to our hospital for investigation of eosinophilia. There were no findings from the physical examination of the lungs and heart. The echocardiography showed a segmental hypokinesia of the interventricular septum and the apex causing left ventricular dysfunction with an ejection fraction 45% and mild pericardial effusion. Cardiac magnetic resonance was performed, for detection of lesions associated with the underline disease, using electrocardiogram-triggered T2-weighted and T1-weighted multislice spin-echo images (before and after an intravenous bolus of gadolinium).The analysis of T2-weighted images revealed increased signal on the mid part of interventricular septum, suggesting myocardial oedema. In the delayed-enhanced images, areas of late phase gadolinium enhancement (indicative of fibrosis) were identified in the mid part of interventricular septum. Methylprednisolone therapy was started. The patient had follow-up echocardiographic examination every month and on sixth month improvement of left ventricular dysfunction was shown with an ejection fraction 55%.In conclusion our case is a typical Churg Strauss Syndrome with characteristic myocardial involvement which improved after corticosteroid treatment. The cardiac magnetic resonance has significant role for early and accurate detection and differentiation of myocardial damage even in preserved cardiac wall motion and cavity size. Churg Strauss syndrome (CSS) is a rare necrotizing systemic vasculitis . In the A 42 year old Greek woman was admitted to our hospital for investigation of eosinophilia. On admission, the white blood cells were 24, 2 K/μl with 62.8% the eosinophils. She had suffered from bronchial asthma and recurrent sinusitis for the last 4 and 6 years respectively. There were no findings from the physical examination of the lungs and heart. The blood pressure was 110/70 mm/Hg whereas the electrocardiogram and chest x-ray were normal. The echocardiography showed a segmental hypokinesia of the interventricular septum and the apex causing left ventricular dysfunction with an ejection fraction (EF) 45% and mild pericardial effusion. Valvular disease or thrombus formations were excluded. Cardiac enzymes as serum creatine kinase-MB and troponin T were in normal levels. Cardiac magnetic resonance (CMR) was performed, for detection of lesions associated with the underline disease, using electrocardiogram-triggered T2-weighted and T1-weighted multislice spin-echo images (before and after an intravenous bolus of 0.1 mmol/kg gadolinium). The analysis of T2-weighted images revealed increased signal on the mid part of interventricular septum, suggesting myocardial oedema. In the delayed-enhanced images, areas of late phase gadolinium enhancement (indicative of fibrosis) were identified in the mid part of interventricular septum. The EF of the left ventricle (LV) was 50% whereas a mild pericardial effusion was also noted . Other cCSS is a rare necrotizing vasculitis of small blood vessels (arteries and veins), with eosinophilic infiltration of them . An estiCardiac involvement is common in CSS and it has important prognostic role. It occurs in 40-47% of the cases . More ofCorticosteroids are the first line therapy of CSS causing remission and survival improvement. Prednisone 1mg/kg day is the recommended dose for 1 month with gradual taper up to 1 year ,9. When In conclusion our case is a typical CSS syndrome with characteristic myocardial involvement which improved after corticosteroid treatment. Since cardiac involvement is a leading cause of mortality it is crucial to detect cardiac involvement as early as possible . The CMR


Congenital left ventricular diverticulum is a rare cardiac malformation characterized by a localized outpouching from the cardiac chamber. The patient is usually asymptomatic. However, complications like embolism, infective endocarditis, arrhythmia and, rarely, rupture can be the initial presentation. Diagnosis can be established by USG, echocardiography, CT angiography, and MRI. We report here two neonates with congenital left ventricular apical diverticulum associated with epigastric hernia. Congenital left ventricular diverticulum is a rare cardiac abnormality consisting of a localized outpouching from the free wall of the cardiac chamber. Commonly, this is from the left ventricular apex; however, non-apical diverticula also occur.Case 1A 1-day-old newborn baby presented with epigastric pulsation and umbilical hernia and underwent routine postnatal investigation.thmonth of intrauterine life showed normal atrioventricular concordance and normal relation of the great vessels with the ventricular chambers. A large subaortic VSD, a patent foramen ovale, and a large ductus arteriosus were also noted. Ventricular function was normal.Antenatally, the 21-year-old mother, a known case of epilepsy on regular treatment, was diagnosed to have a baby with a ventricular septal defect (VSD). Fetal echo at the 7A chest radiograph at birth showed peripheral pruning of pulmonary vascular markings and a dextrorotated heart .USG of the abdomen showed a thick-walled vascular channel arising from the left ventricular apex; it was seen extending up to the umbilicus, which showed arterial pulsations in concordance with ventricular contractility . CommuniUnder mild sedation, a non-gated CT angiogram was performed using a 64-channel, multidetector CT scanner. The parameters used were as follows: 120 kV, 100 mA, scan delay of 2 seconds and total scan duration of 3 minutes; an automated bolus-tracking technique was used. To minimize radiation to the newborn, only a contrast angiogram study was done.The angiogram showed a large tubular contrast-filled channel arising from the left ventricular apex , narrowiCase 2A 15-day-old girl was referred for investigation of an umbilical swelling and epigastric pulsations that had been present since birth.The baby was the first child of normal parents and there was no significant antenatal history. Examination showed a well-looking infant with epigastric pulsations.USG showed a thick tubular channel with pulsatile flow in the anterior abdominal wall, posterior to the abdominal musculature; the channel extended in the midline from the left ventricle apex in the xiphisternal region up to the umbilicus.A contrast-enhanced CT scan of the thorax and upper abdomen showed an elongated, tubular, thick-walled structure extending from the left ventricle downward and medially across the diaphragm up to the umbilicus, where it ended blindly . A midliThe child died in the hospital due to bilateral bronchopneumonia that was unresponsive to antibiotics and oxygen therapy.Congenital left ventricular diverticulum starts in the 4th embryonic week. Possible etiologies are intrinsic abnormalities of embryogenesis or in utero acquired malformations .The first description of a cardiac diverticulum was by Klein in 1953.There have been reports of cardiac diverticulum with pericardial effusion being detected in the second trimester.–5 Intrau4The diverticulum may be apical (70%) or non-aSyndromic association was well described by Cantrell et al. in 1958.12 Congen11Abnormal communication of a diverticulum with the portal system through the obliterated umbilical vein can be associated with complex cardiac abnormalities, especially in trisomy 13, 18, and 21.  Congenit1819Differentiating a ventricular aneurysm from a diverticulum is of importance in adult patients. A narrow mouth and synchronous contractility characterize a diverticulum. On the other hand, aneurysms show akinesia or paradoxic contractility of the outpouching, which is asynchronous with the rest of heart.A diagnosis can be confidently made with USG and echocardiography. CT angiography, MRI, and invasive ventriculography give a clearer picture of the problem. Functional hemodynamic evaluation can be done and any associated intracardiac complex abnormalities can be detected with echocardiography.Management of the diverticulum depends on the clinical situation and associated abnormalities. Most asymptomatic diverticula can be managed with a conservative approach. Treatment options for high-risk cases include surgery, anticoagulants, and management of arrhythmias in symptomatic patients.Click here to view as Video 1Click here to view as Video 2


Longitudinal wall motion of the right ventricle (RV), generally quantified as tricuspid annular systolic excursion (TAPSE), has been well studied in pulmonary hypertension (PH). In contrast, transverse wall motion has been examined less. Therefore, the aim of this study was to evaluate regional RV transverse wall motion in PH, and its relation to global RV pump function, quantified as RV ejection fraction (RVEF).fractional-SFD) were computed and related to RVEF. Longitudinal measures, including TAPSE and fractional tricuspid-annulus-apex distance change  were evaluated for comparison.In 101 PH patients and 29 control subjects cardiovascular magnetic resonance was performed. From four-chamber cine imaging, RV transverse motion was quantified as the change of the septum-free-wall (SF) distance between end-diastole and end-systole at seven levels along an apex-to-base axis. For each level, regional absolute and fractional transverse distance change . For TAPSE and fractional-TAAD, weaker relations with RVEF were found .Transverse wall motion was significantly reduced at all levels compared to control subjects (p < 0.001). For all levels, Regional transverse wall movements provide important information of RV function in PH. Compared to longitudinal motion, transverse motion at mid RV reveals a significantly stronger relationship with RVEF and thereby might be a better predictor for RV function. Pulmonary hypertension (PH) is characterized by increased pulmonary pressure, leading to right ventricular (RV) overload. The course of the illness varies from patient to patient, with the worst prognosis seen in patients with the greatest degree of RV dysfunction ,2. This In general, RV ejection fraction (RVEF) is assumed to be a major determinant of systolic RV function, and has been shown to be of prognostic value in PH ,4. HowevLess attention has been paid to RV transverse wall motion in the literature -14, despTherefore, the aim of the present study was to measure RV transverse motion in PH and to assess its relationship with RVEF employing CMR. Longitudinal RV motion measurements were included for comparison purposes. Results in PH patients were compared to control subjects.The local Ethics Committee of the VU University Medical Center approved the study protocol and all participants gave written informed consent. Between September 2004 and September 2008, 658 patients were referred to our hospital for evaluation of PH. PH was diagnosed according to a standard protocol , includi2,peak) was considered to express the patient's exercise capacity, which was measured using a metabolic cart . To ensure accuracy, the measurements were time-averaged over a minimum of 20 seconds. The equipment was calibrated according the manufacturer's specifications.In a subset of patients (n = 66), cardiopulmonary exercise testing was performed on an electromagnetically braked cycle ergometer . A progressive increase in pedaling workload (5-20 W/min) was applied until maximum tolerance was reached. Peak oxygen consumption , equipped with a 6-element phased-array coil. ECG-gated cine imaging was performed using a balanced steady-state free precession pulse sequence, during repeated breath-holds. Long-axis slices were acquired in the four, three and two-chamber views.The four-chamber image plane was localized by the following steps: a basal short-axis image at end-diastole was used as the first localizer. Orthogonal to this short-axis image, the four-chamber view was obtained by rotating the planning line to such an orientation that it passes through the middle of the mitral and tricuspid valvular rings. The LV vertical long-axis view was used as the second localizer, to assure that the planned four-chamber cine passes through the most apical point of the LV cavity.3, flip angle 60°, receiver bandwidth 930 Hz/pixel, TR/TE 3.2/1.6 ms, matrix 256 × 156.Additionally, short-axis slices were obtained with a typical slice thickness of 5 mm and an interslice gap of 5 mm, fully covering both ventricles from base to apex. The MR parameters used were: temporal resolution between 35 to 45 ms, voxel size 1.5 × 1.8 × 5.0 mmAn apical four-chamber view was used to analyze longitudinal and transverse movements of the RV myocardium Figure . The sofTransverse RV movements were analyzed using a method that quantifies regional changes from septum to free-wall (SF) between end-diastole and end-systole. First, lines were drawn between the right-lateral point of the tricuspid annulus and the apex, and between the left-lateral point of the mitral annulus and the apex. Then, the line intersecting the centers of the left and right lateral annulus-apex lines was drawn Figure , both infractional-SFD) was then computed as SFD divided by the SF dimension at end-diastole.Subsequently, SF dimensions were computed at seven different levels covering the whole RV cavity, indicated as apex-1 through base-7, with level mid-4 exactly halfway through the RV. For each level, the absolute SF distance change (SFD) was determined, and the fractional SF distance change  was calculated as TAPSE divided by the tricuspid annulus-apex dimension at end-diastole.Longitudinal RV movements were quantified as modified TAPSE, adapted from echocardiography . CMR TAPRV area change in 4-chamber view was quantified from the endocardial contours at end-diastole and end-systole. Fractional area change (FAC) was calculated as the absolute area change divided by the end-diastolic area.Endocardial surfaces were carefully manually traced from the stack of short-axis cine images, using Mass Analysis software  to obtain RV end-diastolic and end-systolic volumes. Trabeculae and papillary muscles were excluded from these measurements. The RV end-systolic image was identified by selecting the smallest ventricular surface. Based on these volumes, RVEF and stroke volume were calculated.fractional-SFD) and RVEF, and between the longitudinal measures  and RVEF. In the regression analysis only patients were included in order to avoid regression bias by the control group.Normal distribution of the data was verified using a normal probability plot and log transformed if necessary. All data are presented as mean ± SD, unless stated otherwise. A p-value < 0.05 was considered statistically significant. Data between controls and patients were compared using the 2-tailed Students t-test for unpaired data or using one-way ANOVA when more than two groups were tested. The Fisher exact test was used for categorical data. Linear regression was performed to test the relationships between the transverse measures (SFD and Receiver operating characteristic (ROC) analysis was used to test sensitivity and specificity of all measures to detect a RVEF less than the median RVEF value in patients. To correct for multiple testing, the threshold for significance was adjusted using Bonferroni correction for families of tests with 0.05 divided by the amount of tests giving the adjusted threshold for significance.Intra-observer and inter-observer variability of the endocardial wall measurements were assessed using the analysis of agreement method described by Bland and Altman . To thisAll statistical analyses were performed with SPSS Statistics 15.0 .There was no difference between the 101 PH patients and 29 control subjects with respect to age  and gender . Table Baseline CMR measurements of PH patients and control subjects are presented in Table Figure fractional-SFD, evaluated for seven levels ranging from apex to base, and fractional-TAAD in patients and controls. In PH patients, virtually no regional variation in fractional-SFD was found. In contrast, control subjects showed the highest fractional-SFD at the apical segment, and the lowest at the basal segment. At all levels, there were significant differences in transverse movements between patients and control subjects  compared to the longitudinal dimension (TAA).Figure ts Table . From TaNo significant differences were found in longitudinal and transverse motion between the patients from WHO group 1 and 4 (data not shown).Fractional-SFD was correlated positively with RVEF at each level of the RV free wall . Weaker relationships were found for SFD, fractional-TAAD and TAPSE . Compared to fractional-SFD, there were statistically significant differences among the areas under the curves for SFD (p = 0.005), fractional-TAAD (p = 0.003) and TAPSE (p < 0.001) after Bonferroni correction.Figure 2,peak and VO2,peak-predicted  in comparison with fractional-SFD and fractional-TAAD. A significant difference was found for fractional-SFD (p = 0.002) but not for fractional-TAAD.In a subset of patients (n = 66) exercise capacity was measured using VOed Table . Figure Figure We have evaluated regional transverse motion of the RV myocardium, defined as movements of the RV free-wall to the septum, in a group of PH patients and control subjects. The most important finding of this study was that RVEF was more closely related to fractional transverse movements than to longitudinal movements. The former might consequently be used as an alternative measure of RV pump function. In addition, we observed that fractional transverse movements in control subjects were largest near the apex, but smaller near the base of the heart, while PH patients showed consistently smaller movements and little regional variation.fractional-SFD and RVEF was found for all levels, with the strongest relation at mid RV level . The relationship between TAPSE and RVEF, however, was much lower . Although this value corresponds to what was found by Kjaergaard et al. [2 = 0.23), other studies have reported higher correlations (R2 > 0.38) [A significant relationship between d et al.  (R2 = 0. > 0.38) ,11. Thisfractional-SFD appears clinical useful. A cutoff value of 17.7% was used to differentiate between patients with a low (< 35%) or preserved (>35%) RVEF , which had a significantly higher discriminatory power compared to SFD, fractional-TAAD or TAPSE , it is an easy and accurate way to assess RV function with CMR. The clinical value of the transverse measures would be even stronger if these could be measured using echocardiography. This should be investigated in future research.RV function is the primary determinant of prognosis in PH. Therefore, clinicians need simple and reproducible tests to assess RV function in order to improve their management of PH. In general, RVEF is assumed to be a major determinant of systolic RV function. However, its determination is time consuming and is limited by large inter and intra-observer variability. TAPSE has been shown to correlate with RVEF and has been considered a simple method for semi-quantitative assessment of RV function. In this study we have showed that Some limitations of the current study should be noted. Firstly, geometry and heavily trabeculated myocardium of the RV make it sensitive to errors in the determination of endocardial definition. Secondly, four-chamber views were acquired with equal geometric orientation at end-diastole and end-systole, without accounting for through plane motion. It is unknown whether RV torsion may affect the end-systolic dimension. A previous study reported regional differences in rotation in the systemic RV. However, when values were averaged over different segments, this resulted in almost absent rotation at the basal and the apical level with no absolute global ventricular torsion .fractional-SFD at mid level is as feasible and reliable to measure as TAPSE, it might be a better predictor of RV function in PH. Further studies are needed to evaluate the usefulness in clinical practice.In PH, transverse myocardial motion is significantly declined. Moreover, measures of transverse movement at mid RV reveal a significant relationship with RVEF, which is much stronger than for measures of longitudinal movement. Since CMR: Cardiovascular magnetic resonance; LV: left ventricle; PH: pulmonary hypertension; RV: right ventricle; RVEF: right ventricle ejection fraction; SF: septum-free wall dimension; TAA: tricuspid annulus-apex dimension; SFD: septum to free wall distance change; TAAD: tricuspid annulus to apex distance change; TAPSE: tricuspid annular systolic excursion.The authors declare that they have no competing interests.TK: study design, manuscript preparation and revision, writing the Matlab software, data collection, analysis and interpretation. GJM: study design, data collection and interpretation. MV: data collection, analysis and interpretation, manuscript revision. JTM: data collection, manuscript revision. AVN and NW: study design, data interpretation, manuscript revision. All authors read and approved the final manuscript.


Myocardial infarction remains as a major cause of mortality worldwide and a high rate of survivors develop heart failure as a sequel, resulting in a high morbidity and elevated expenditures for health system resources. We have designed a multicenter trial to test for the efficacy of autologous bone marrow (ABM) mononuclear cell (MC) transplantation in this subgroup of patients. The main hypothesis to be tested is that treated patients will have a significantly higher ejection fraction (EF) improvement after 6 months than controls.6 MC suspended in saline with 5% autologous serum in the culprit vessel, while the latter will receive placebo .A sample of 300 patients admitted with ST elevation acute myocardial infarction (STEMI) and left ventricle (LV) systolic dysfunction, and submitted to successful mechanical or chemical recanalization of the infarct-related coronary artery will be selected for inclusion and randomized to either treated or control group in a double blind manner. The former group will receive 100 × 10Many phase I/II clinical trials using cell therapy for STEMI have been reported, demonstrating that cell transplantation is safe and may lead to better preserved LV function. Patients with high risk to develop systolic dysfunction have the potential to benefit more. Larger randomized, double blind and controlled trials to test for the efficacy of cell therapies in patients with high risk for developing heart failure are required.This trial is registered at the NIH registry under the number NCT00350766. Acute myocardial infarction (AMI) is a major cause of mortality worldwide. Many survivors of AMI develop heart failure, associated with a high morbidity that worsens their quality of life and generates elevated expenditures for health system resources..Heart Failure (HF), which has ischemic cardiomyopathy as its most frequent cause, is an epidemic disease of this century. It affects from 2 to 4 million people in the United States (US), and 15 million people around the world..Different medical therapies are efficient for patients who develop systolic dysfunction after AMI, as ACE inhibitors and beta blockers, which aim to improve the infarct repairing response. Recently, cell therapy has appeared as a new perspective. Growing evidence suggests benefits of cell therapies in repair or regeneration the myocardium, and several types of cells have been used. However, cellular and molecular mechanisms responsible for the ventricular function improvements, which have been reported in most of the studies, are still poorly understood. Among other questions, the best pathway to introduce stem cells into the heart has been investigated for the treatment of ischemic cardiomyopathy.To our knowledge, five other clinical trials of autologous bone marrow (ABM) mononuclear cell (MC) transplantation through intracoronary injection after AMI were published, with more than 300 patients tested and followed for at least 1 year. -10 ImporEven though these are still preliminary data, the results have led us to investigate cell therapy as an alternative treatment of ischemic cardiomyopathy following acute myocardial infarction.The main hypothesis of this trial is that patients submitted to autologous bone marrow stem cell transplantation will present, on average, at least 5% higher EF in comparison with the placebo group after 6 months follow up.This research protocol integrates the Multicenter Randomized Trial of Cell Therapy in Cardiopathies (MiHeart Study) which has been already published. MiHeart Multicenter, double blind, randomized and placebo controlled trial.Three hundred patients with ST elevation AMI (STEMI) submitted to successful mechanical (TIMI flow grade 3) or chemical recanalization of the culprit coronary artery up to 24 hours after symptoms onset, and presenting EF ≤ 50% will be selected for inclusion.Patients will be eligible if presenting all the following characteristics:  STEMI;  age betwPatients will be excluded if presenting any of the following: obstruction >50% on Left Main Coronary Artery or multivessel coronary disease, indicating the need for CABG ; coronary anatomy presenting no need for angioplasty with stent implant; final diastolic pressure of left ventricle (LV) higher than 30 mm Hg during initial ventriculography; cardiac arrest or Killip IV at admission with the need of ventilatory support; cardiogenic shock persisting up to the third day after symptoms onset; mechanical complications of AMI; significant valve disease; chronic use of immunosuppressant agents; >2,0 mg/dl creatinine or previous dialysis treatment; sepsis; sustained ventricular tachycardia after 48 hours post-AMI; illicit drugs abuse or alcohol abuse (based on DSM IV); myocarditis; active liver disease; severe COPD (Chronic Obstrutive Pulmonary Disease); hematological disease, neoplasm, bone disease or haemostatic disturbances; inflammatory disease or chronicle infectious disease; presence of definitive implantation of a cardiac pacemaker or cardiac defibrillator or any co-morbidity, with survival impact in 2 years.Patients will be included only after signing Informed Consent form, written in accessible language and with information about all relevant aspects regarding the research protocol.A computer-random number generator will perform randomization procedure in the day of injection as previously published in Trials. Briefly,th and 7th day after myocardial reperfusion therapy under local anesthesia and sedation at an intensive care unit or surgical center. The aspiration procedure will be done by using a 1.8 mm Jamshidi needle.About 100 ml of bone marrow aspirate will be harvested from iliac crest between the 5® (Amersham Biosciences) and manipulated under aseptic conditions. 100 × 106 cells will be resuspended in 10 ml saline solution with 5% autologous serum and filtered through 100 μm nylon mesh to remove cell aggregates for injection. A fraction of the cell suspension will be used for cell counting and viability testing with trypan blue exclusion. Cell viability must be above 90% to be injected. Post-hoc characterization of leukocyte differentiation markers by flow cytometry , reinforcing the blind application, for injection.In order to guarantee the quality of the material, imunophenotyping and clonogenic capacity analysis will be all done at a Core Lab as detailed in the appendix [see Additional file Exceeding material and cells collected from patients in the placebo group will be stored, duly frozen, until the end of the trial.Bone marrow collected from patients included in control group will be used for phenotyping and cell analysis, which will be correlated with patients' clinical evolution.Cell delivery is predicted to be performed about 6 hours after bone marrow cell harvesting. Arterial accesses will be performed using femoral or radial approach. All patients will receive 10,000 IU of heparin IV after sheet insertion. When non-infarct related vessel intervention is planned, it will be performed before cell transfer. Electrocardiography, pulse oximetry, and vitalsigns will be monitored throughout the procedure, as well as symptoms.A 6-F guiding catheter will be placed at the ostium of the infarct-related coronary artery. After positioning the catheter inside the coronary ostium, a dosage of isossorbide mononitrate will be administered . Then, a coronary will be performed in a calibrated system in order to visualize the coronary blood flow before injection. At least one projection for evaluating "TIMI frame count" will be performed with a 30 frame/sec filming, attempting to visualize the distal coronary bed.® Over-The-Wire balloon, Boston Scientific, Natick, MA, USA) will be positioned inside the previously implanted stent in the culprit vessel to transiently interrupt anterograde blood flow during infusions through a stop-flow technique. The use of the over-the-wire balloon with over 0.5 mm of the reference lumen diameter in a low pressure (< 4ATM) is recommended. The ideal balloon extent is 9 mm, limited to the edge of the previously implanted stent.After TIMI 3 flow scrutiny, an over-the-wire (OTW) balloon catheter , patients will be submitted to another clinical evaluation, including an EKG, an echocardiogram and laboratory tests, from which results will be used as baseline data for the research protocol, before injection procedure. A new CK-MB mass and troponin dosage will be performed in the morning preceding the injection procedure and timely in the 24 hours following the injection.The baseline cardiac magnetic resonance imaging (MRI) will be performed between day 6 and 9 after the AMI-related coronary artery recanalization. This exam may be performed either in the hospital or at a reference hospital. All imaging exams will be evaluated off line by the core lab specified in the appendix [see Addition file Hospital discharge is predicted 24 hours after cell transplantation unless otherwise indicated, making a total length of stay of approximately 7 days. Patients will be provided with clopidogrel, aspirin and pravastatin during the entire study and treated at the discretion of the attending physician.Patients will be followed for 1 year after the procedure according to the chronogram of the study shown in table Cardiac MRI will be done by the local centers with commercially available software, electrocardiographic triggering, and cardiac-phased array coil. LV function will be assessed by the use of steady-state free-precession gradient-echo sequence (SSFP). Eight to twelve short axis slices will be acquired during a 10–15 seconds breath-holding allowing for coverage of the entire LV. Additionally, 3 long-axis views will also be acquired: 2-chamber and 4-chamber views and left ventricle out flow tract. Regional LV function will be assessed by measuring systolic wall thickening in the infarct region, the adjacent border zone and remote myocardium and semi-quantitatively assessed, using a 17-segment model.Transmural extent of late hyper-enhancement within each segment will be graded according to the following classification: 0–25%, 26–50%, 51–75%, and more than 75% hyper-enhancement. Segmental functional recovery is defined as an increase from hypokinetic to normokinetic, from akinetic to hypokinetic or normokinetic, or from dyskinetic to akinetic, hypokinetic, or normokinetic. Infarct size will be measured by planimetry.Microvascular obstruction will be defined on late enhanced images taken early (within 2–5 min) after injection of 0.20 mmol/kg of gadopentetate dimeglumine (Gd-DTPA), in the LV short and long axis at the same locations used for cine-MRI–as a dark, subendocardial zone within the infarct area.For assessment of global and regional LV function and calculation of LV mass, endocardial and epicardial borders will be traced in end-diastolic and end-systolic short-axis slices. LV end-diastolic and end-systolic volumes (LVEDV and LVESV) will be calculated and indexed to body-surface area. All MRI studies will be independently analyzed on an off-line workstation, core laboratory as defined in the appendix [see Additional file Sample size calculation was performed according to the following assumptions:▪ Based on Pró-Cardíaco Hospital and InCor's coronary care databank, after selecting AMI patients Killip I; II or III, we have concluded that the left ventricle EF presented a Gaussian distribution with an average of 37.35% and standard deviation of 7.9%).▪ An expert panel has evaluated that an improvement of +5% (relative gain of +15.9%) on the EF would represent a significant clinical improvement for the patient.Considering as clinically beneficial a 5% increase in EF% with a standard deviation of 5%, 143 patients per arm are needed to detect a significant difference between groups with 95% confidence and 80% power. Considering a 5% loss during follow up, we estimated 150 patients per arm.The primary endpoint of this trial is the global left ventricular EF change from baseline to 6 month follow-up.The following secondary endpoints will be evaluated for up to 1 year of follow up: major cardiovascular events ; reintervention of the AMI-related artery and of non-related arteries; by MRI regional wall motion, wall thickening, and volume of late contrast enhancement; quality of life assessment using the Short-Form 36, Minnesota Living with Heart Failure and Seattle Angina questionnaires; cost-effectiveness and cost-utility evaluation of ABMMC implant versus conventional treatment.All outcomes will be analyzed by intention to treat.Primary outcome will be analyzed by comparing EF, measured by MRI, between groups, using student t test or Mann-Whitney according to the sample distribution. Two evaluations are programmed:1. Interim analysis, which will use data related to patients 1 to 150;2. Final analysis, which will use data related to all 300 patients.Secondary outcomes will only be evaluated after the main final analyses. Mortality and functional class improvement will be analyzed by non-corrected chi-square test. Continuous variables with normal distribution will be analyzed by t student test and ANOVA for repeated measures. Continuous variables with asymmetric distribution and quality of life scores will be analyzed by Mann-Whitney test and ANOVA for repeated measures.The frequency of serious adverse events (which brings eminent risk of death or permanent disability) will be analyzed by chi-square or Fisher's test.The trial can be interrupted after interim analysis; using the O'Brien and Fleming rule for two sequential tests and the 5%, in which the null hypothesis is rejected if:• p ≤ 0,0050 in the first analysis;• p ≤ 0.04806 in the final analysis.The MiHeart trial is supervised by an executive committee and coordinated by a study coordination committee. Members of both committees are listed in the appendix [see Additional file The names of all participating centers and their representatives are provided in the appendix [see Additional file Stem cell therapy still remains as a promising modality to occupy a real gap of conventional AMI therapy, especially when this acute event is followed by LV remodeling and chronic heart failure. There is increasing evidence that stem cells contribute to the regeneration of cardiac tissue as a natural healing process following STEMI, thus opening new possibilities for the treatment of this condition.The safety of ABMMC intracoronary transplantation after AMI has been shown previously and although data supporting the improvement of ventricular function are conflictant, -17 the pAs demonstrated in the REPAIR AMI trial,  patientsNevertheless, the current evidence is insufficient to prove that BM cell therapy after an acute MI can provide additional beneficial effects on LV function beyond those achieved by early reperfusion therapy.Therefore, we have designed a randomized large placebo-controlled trial, to inject ABMMC using the intracoronary route in patients with left ventricular dysfunction following AMI who were successfully treated with either chemical or mechanical reperfusion. The purpose of this study is to test for additional benefits of stem-cell therapy in this scenario where patients have ventricular dysfunction due to irreversible myocardial damage. If this assumption proves to be correct stem cell therapy will be a valid strategy for treating this obscure and harmful condition, reducing morbidity, mortality, heart transplantation indication, costs of the treatment and improving life quality.The authors declare that they have no competing interests.HD is the PI of this study and AC is the study coordinator. All authors contributed to the development of the protocol and were involved in the writing of the manuscript.Appendix. The data provided describes all committees involved in the coordination of this study, as well as core lab and collaborating centers members.Click here for file


To assess regional systolic function and global contractile function in patients with WPW Syndrome.pRS) or range (difference between maximum and minimum peak RS i.e. RangepRS). Spectral Doppler (continuous wave) measurements were acquired through the left ventricular outflow tract to determine Pre Ejection Period (PEP), Left Ventricular Ejection Time (LVET) and measures of left ventricular systolic performance.Eleven cases with manifest Wolff-Parkinson-White (WPW) syndrome in sinus rhythm were compared to 11 age matched controls. 2D strain analysis was performed and peak segmental radial strain (pRS) values obtained from basal ventricular parasternal short-axis images (70 ± 5 frames/sec) using a dedicated software package. Heterogeneity of radial strain pattern in six circumferential basal left ventricular segments was measured in terms of standard deviations of peak RS  and corrected PEP  were significantly longer in WPW patients compared to controls. The PEP/LVET ratio was also significantly greater in WPW cohort  suggesting global systolic dysfunction.LV segmental radial strain was profoundly heterogeneous in WPW cases in contrast to fairly homogenous strain pattern in normal subjects. Wide SDPatients with manifest preexcitation (predominantly those with right-sided pathways) have regional and global contractile dysfunction resulting from aberrant impulse propagation inherent to the preexcited state. Abnormal electrical activation of the accessory pathway results in characteristic electrocardiographic abnormalities and clinical symptoms manifesting as WPW syndrome .  Data oTraditionally, regional left ventricular function has been evaluated using visual wall-motion analysis as well as by other quantitative methods such as integrated backscatter, automatic border detection and tissue Doppler imaging (TDI) -9. HowevIt has recently become evident that chronic right ventricular apical  pacing induced dyssynchrony leads to  deleterious effects on left ventricular systolic function  ,13.  AccTo the best of our knowledge, no data on the prevalence of left ventricular dysfunction in patients with accessory pathway conduction exists in the literature. We sought to characterize regional left ventricular function in patients with manifest WPW syndrome by examining radial myocardial strain patterns. We also attempted to investigate the presence of global dysfunction using systolic time intervals.The study included 11 cases with manifest pre-excitation on surface ECG and an equal number of age-matched controls .  None oAll accessory pathways were localized using the algorithm proposed by Milstein and colleagues  on a staContinuous wave Doppler measurements were acquired through the left ventricular outflow tract. PEP was defined as the time from the beginning of the QRS complex to the onset of ventricular ejection (opening click). LVET was measured from the onset of ventricular ejection (opening click) to the closure of the aortic valve (closure click) . CorrectAll patients and controls were in sinus rhythm and image acquisition was performed in the resting state in the left lateral position. Standard short axis views at the level of mitral valve were obtained from the left ventricle (LV) at a frame rate of 70 ± 5 frames/second during end-expiratory apnea and stored in cine-loop format for subsequent offline analysis . The endocardial border was then traced using the built-in software at end-systole by a 'point-and-click' approach with care taken to adjust tracking of all endocardial segments. Upon defining this endocardial circle, a larger concentric circle was automatically generated outlining the epicardium with a default width of 11 mm and perimeter adjusted manually as needed to track the myocardium. Strain tracings were then generated using a dedicated software package  from a  six segment  LV model . Radial strain values at peak systolic period  were obtained for each individual LV segments using online calipers .pRS): One standard deviation of six  pRS   in each case. Range of pRS (RangepRS): Arithmetic difference between maximum and minimum of six pRS values in each case.For descriptive purpose, following parameters were calculated: Global LV Peak radial strain = Arithmetic mean of pRS of six individual segments for each case as a surrogate marker of overall LV peak systolic radial strain. To measure heterogeneity, following dispersion indices were calculated ): Standard Deviation of pRS . Data are presented as mean ± SD unless stated otherwise. Non-parametric Wilcoxon's signed rank and the Mann-Whitney U test were used to compare the continuous variables in WPW patients and controls. All measurements were done by two independent observers with a minimal degree of variability. Intraclass correlation coefficients (ICC), commonly used as a measure of reliability, with a value of 1 representing a perfect correlation was used to quantify the intraexaminer and interexaminer variation. The ICC was calculated  from mean values according to Portney ,19.  TwoThe study cohort consisted of eleven cases  and age-matched eleven controls . Baseline characteristics of the study population and accessory pathway location are shown in pRS as well as RangepRS) were profoundly greater for WPW cases compared to healthy controls (p<0.001)  . This siAs shown in pRS and RangeSDpRS although the average global LV radial strain was similar to the healthy subjects (mean of pRS)}. Moreover, global systolic contractile function appeared to be depressed as well, as evident from systolic time interval analysis.Our findings suggest that patients with manifest WPW have evidence of regional contractile dysfunction. This is evidenced from a wide dispersion of pRS {higher SDEjection fraction (EF), the most frequently used index to assess global cardiac function is the LV stroke volume expressed as a percentage of the end-diastolic volume. This measure has gained popularity largely because it is widely available, easily obtainable and also because no other alternative optimal measures of myocardial contractility have emerged despite extensive investigation. Nevertheless, accurate EF calculation using the recommended Simpsons biplane method requires precise measurement of LV end-diastolic and end-systolic volumes in multiple views with special attention to avoid foreshortening of the LV cavity. Averaged values from both 4-chamber and 2-chamber views, preferably from 2 or 3 beats are recommended for more reliable estimation of ventricular volumes and EF. However, this technique is predicated on geometric assumptions  and although it is fairly accurate in ventricles with symmetric contractility, it is less reliable in ventricles with overt/subtle regional wall motion abnormalities or geometrically deformed ventricles such as ventricular aneurysms. This limitation of the Simpsons method to reflect regional asymmetry of LV function is the reason why EF was not selected as the preferred metric to assess global systolic function in the present study.Systolic and diastolic 'wall motion' abnormalities have been well described  in patients with WPW Syndrome -3,5,20. In our study, WPW cases exhibited a wide dispersion in pRS values of LV segments during systole suggesting markedly heterogenous strain pattern and contractility. It has to be emphasized that wall motion abnormalities are not necessarily always associated with altered contractility. Toyoda et al studied interventricular septal (IVS) contractile patterns in patients post coronary artery bypass surgery (CABG) and reported that peak tissue Doppler velocities in the IVS were attenuated . HoweverRadial strain data obtained in our patients extends the well-recognized observations of pre-excitation on wall motion and unequivocally demonstrates its detrimental effects on regional left ventricular function.The transmural arrangement of myocardial fibers is not uniform across the wall of the LV. Subendocardial and subepicardial muscle bundles are aligned longitudinally (long axis contraction), with a slight spiral arrangement, and midwall fibers are aligned circumferentially . Although the precise mechanism for abnormal contractile function in the pre-excited state remains speculative, we believe that accessory pathway conduction leads to ventricular depolarization via myocyte-myocyte conduction as opposed to the normal orderly propagation of the impulse via the His-Purkinje system. Depending on the degree of pre-excitation, ventricular insertion site of bypass tract and/or layer of muscle fibers/bundles being recruited, further heterogeneity of depolarization may ensue. As observed with dependent right ventricular apical pacing  it is plSystolic time intervals have been reported as reliable surrogate parameters of left ventricular systolic function. Electromechanical systole comprises the PEP and LVET. LVET is the effective contraction phase during electromechanical systole. Weissler and co-workers -18 have During the cardiac cycle, regional deformation of the myocardium occurs in three major directions: longitudinally, circumferentially and radially, all of which can be quantified using 2-dimensional strain techniques providing real-time automatic assessment of regional cardiac function. This technique analyzes myocardial motion objectively by tracking natural acoustic markers in grey scale ultrasonic images in two dimensions (speckle tracking) and is a validated Doppler-independent method of quantifying regional cardiac deformation ,11,27. TWe found the dispersion indices like standard deviation or range segmental radial strain to be superior estimate of heterogeneity of regional contractility compared to mean radial strain. Interestingly, we also observed hypercontractility in segments diametrically opposite to those with impaired radial strain probably accounting for the lack of difference in mean radial strain values and ejection fraction between groups.Abnormal motion does not always imply contractile dysfunction. With 2D strain imaging, an angle-independent quantification of regional cardiac deformation, relatively independent of wall motion is possible. Our data suggests that the preexcited state is associated with an impairment of regional and global left ventricular contractility. In some respects, the mechanism by which RV apical pacing or left  bundle branch block adversely influence LV contractility in the setting of congestive heart failure appear to be similar to those responsible for impaired contractility in the pre-excited state; both essentially mediated by  electromechanical delay. The extent, progression and reversibility of left ventricular dysfunction in the setting of  chronic  preexcitation  however, is unknown but  certainly merits further study.The number of patients enrolled was limited and they predominantly appeared to have right-sided pathways, even though we enrolled consecutive patients; whether or not patients with left sided pathways have disordered contractility is uncertain. The accuracy of pathway localization using the surface ECG has inherent drawbacks; clearly localization of pathways by electrophysiological studies would be desirable. Speckle Tracking Imaging is very image quality dependent and short axis images cannot eliminate longitudinal motion entirely. We found frame rates in the range of 65 Hz  to be most suitable for speckle-tracking analysis and the algorithm performed poorly with frame-rates of > 100 Hz.We used a modified method for systolic time interval assessment using Doppler-based data but had a control group for comparison; however, direct comparison of normative values with established techniques would have to be done with caution. Controversy exists regarding 'rate' correction for systolic time intervals; it is also not clear whether the prolonged PEP intervals ought to be corrected in the setting of LV conduction blocks. No specific recommendations relating to PEP adjustments in patients with pre-excitation could be found in the literature.Our observations indicate that patients with manifest WPW (predominantly right-sided pathways) have impairment of regional contractility as ascertained by radial strain dispersion parameters, resulting from the abnormal temporal sequence of activation in the pre-excited state.  Differences in surrogate measures of global contractility such as PEP/LVET seem to indicate global LV dysfunction in this cohort of patients. Our findings will need to be validated in a larger group of patients that includes left-sided pathways.


We discuss the case of a 63 years old female who required repeated intubation due to recurrent pulmonary edema. She was found to have hypertrophic cardiomyopathy with a gradient of 82 mmHg across the left ventricular outflow tract. Initially adequate rate control and treatment with negative inotropes did not help her condition. Finally a dual chamber pacemaker implantation and atrioventricular node modification lead to successful extubation. Hypertrophic cardiomyopathy has been reported as a cause of failure to wean from mechanical ventilator .We repor63-year-old Caucasian female, with past medical history of failure of transplanted kidney, persistent atrial fibrillation, hypertension and hypothyroidism was admitted to the intensive care unit with acute respiratory failure secondary to pulmonary edema. She was intubated and treated with intravenous diuretics. An echocardiogram revealed severe hypertrophic cardiomyopathy with a left ventricular outflow gradient of 82 mm Hg . She wenLung congestion and low cardiac output syndromes are commonly encountered in critically ill and mechanically ventilated patients. These disturbances may impede weaning from mechanical ventilator and require repeated intubations if left unaddressed. Proper management of congestive heart failure in mechanically ventilated patients has been associated with favorable outcomes, and by optimizing the treatment patients have successfully been weaned from mechanical ventilators. Hypertrophic Cardiomyopathy (HOCM) may be one of the conditions responsible for such a scenario and the routine treatment for systolic heart failure may be detrimental in such patients.Adamopoulos et al  reports In patients who are refractory to medical management permanent pacing in the form of dual chamber pacing (DDD) has been introduced as an alternative treatment modality. By altering the pattern of ventricular depolarization pacing may result in decreased left ventricular outflow tract gradient and improve functional status in such patients .The imprOur patient in addition to hypertrophic cardiomyopathy had atrial fibrillation which might have independently contributed to worsening of the outflow gradient. Inspite of good rate control during atrial fibrillation in addition to negative inotropic medication, patient continued to have repeated intubations. Although alcohol septal ablation is a recommended procedure in a selected group of patients, it was not contemplated in this patient who was critically sick. The long-term results of dual chamber pacing in hypertrophic cardiomyopathy are controversial ,4. ThereIn patients with difficult weaning and extubation from a mechanical ventilator due to congestive heart failure in an intensive care unit setting, an underlying cause including hypertrophic cardiomyopathy should be ruled out.


To assess the relationship between improved regional and global myocardial function in patients with ischemic cardiomyopathy in response to β-blocker therapy or revascularization.Cardiovascular Magnetic Resonance (CMR) was performed in 32 patients with ischemic cardiomyopathy before and 8 ± 2 months after therapy. Patients were assigned clinically to β-blocker therapy (n = 20) or revascularization (n = 12). CMR at baseline was performed to assess regional and global LV function at rest and under low-dose dobutamine. Wall thickening was analyzed in dysfunctional, adjacent, and remote segments. Follow-up CMR included rest function evaluation.Augmentation of wall thickening during dobutamine at baseline was similar in dysfunctional, adjacent and remote segments in both patient groups. Therefore, baseline characteristics were similar for both patient groups. In both patient groups resting LV ejection fraction and end-systolic volume improved significantly (p < 0.05) at follow-up. Stepwise multivariate analysis revealed that improvement in global LV ejection fraction in the β-blocker treated patients was significantly related to improved function of remote myocardium (p < 0.05), whereas in the revascularized patients improved function in dysfunctional and adjacent segments was more pronounced (p < 0.05).In patients with chronic ischemic LV dysfunction, β-Blocker therapy or revascularization resulted in a similar improvement of global systolic LV function. However, after β-blocker therapy, improved global systolic function was mainly related to improved contraction of remote myocardium, whereas after revascularization the dysfunctional and adjacent regions contributed predominantly to the improved global systolic function. Recent estimations reveal that 4.9 million patients suffer from chronic heart failure in the United States, indicating the magnitude of this major health care problem . IschemiBeta-blocking agents have shown substantial benefit in patients with various degrees of heart failure -4. The mThe beneficial effect of revascularization of dysfunctional myocardium in patients with ischemic cardiomyopathy has traditionally been measured by its effect on improvement of resting regional and global LV function ,10. RevaCardiovascular magnetic resonance (CMR) is a validated and reliable method to assess global and regional myocardial function in normal and diseased hearts. Functional CMR is well suited to assess resting wall motion -17 as weWe sought to define the contribution of regional myocardial segments to the improvement of global systolic LV function in patients after medical therapy or revascularization. We hypothesized that a differential effect on regional myocardial segments occurs depending on the type of therapy. Systemic medical therapy is expected to have a more global effect on both ischemic, dysfunctional myocardial segments and on non-ischemic, remote myocardium, whereas revascularization will have a more local effect on the ischemic, dysfunctional myocardium depending on the territory of the revascularized vessels.Therefore, the purpose of the present study was to assess the relationship between improved regional and global myocardial function in patients with ischemic cardiomyopathy in response to β-blocker therapy or revascularization.Thirty-two patients with chronic ischemic cardiomyopathy and LV ejection fraction (EF) <40% on gated resting Tc-99m-SPECT, were included. All patients were in sinus rhythm. Patients with a recent infarction (<3 months), unstable angina, valvular disease pacemakers and/or intracranial clips were excluded.Patients were included consecutively. Patients that did not qualify for revascularization were assigned to the β-blocker therapy group. Patients did not qualify for revascularization because: 1. Patients had poor target vessels  2. Patients had prior existing co-morbidity ; 3. Patients refused to undergo revascularization. β-blocker therapy was started at an initial dose of 3.125 mg carvedilol twice daily. Subsequently, carvedilol was titrated at 1-week intervals as tolerated, up to target dose of 25 mg twice daily .β-Blocker treated patients were compared to patients who underwent revascularization. In the revascularization patients, coronary artery bypass surgery was performed in 75% and percutaneous coronary intervention in 25%. Each patient gave informed consent to the study protocol that was approved by the local ethics committee.Patients were studied by CMR before therapy and at 8 ± 2 months after therapy. At baseline, the CMR protocol consisted of a resting cine CMR, Late Gadolinium Enhancement (LGE) and low-dose dobutamine (10 μg/kg/min) cine CMR. Follow-up CMR included rest function evaluation only. The congestive heart failure classification by the New York Heart Association (NYHA) was determined at baseline and follow-up by the patient's cardiologist, who was blinded to the CMR data.2, matrix size 256 × 256, slice thickness 10.00 mm, flip angle 50°, time to echo 1.82 ms and time to repeat 3.65 ms. Temporal resolution was 25-39 ms, depending on heart rate. Geometry settings of rest cine CMR scans were stored and repeated for LGE and low-dose dobutamine stress CMR.A 1.5-Tesla Gyroscan ACS-NT CMR scanner  and a 5 elements cardiac synergy coil were used. Patients were studied in supine position. All images were acquired during breath-holds of approximately 15 seconds and were gated to the vector ECG; blood pressure was monitored continuously during the examination . The heart was imaged from apex to base with 10 to 12 imaging levels (dependent on heart size) in short-axis view using a steady-state free-precession sequence. Typical acquisition parameters were: field of view 400 × 400 mm2, matrix size 256 × 256, slice thickness 5.00 mm, slice gap - 5 mm, flip angle 15°, time to echo 1.36 ms and time to repeat 4.53 ms.LGE images were acquired approximately 15 minutes after bolus injection of gadopentate dimeglumine  with an inversion-recovery gradient echo sequence; inversion time was determined using real time planscan. Typical parameters were the following: field of view 400 × 400 mmFor evaluation of myocardial function under pharmacological stress, intravenous dobutamine infusion was started at a rate of 5 μg/kg/min and increased after 5 min to 10 μg/kg/min. Then, after 5 min (at steady state), low-dose dobutamine images were acquired in 2- and 4-chamber and short-axis views. The same parameters were applied as described for rest imaging.Data were analyzed on a remote workstation using MASS software . The endo- and epicardial borders of the end-diastolic and end-systolic frames were manually traced with exclusion of papillary muscles, trabeculae, and epicardial fat . LV end-The amount of infarcted tissue was determined by drawing  regions of interest around the scar tissue. In addition, the percentage of myocardium was calculated that was affected by infarction, relative to the total LV mass. LGE images were scored visually by two experienced observers  using a 17-segment model. Each segment was graded on a 5-point scale  with 0: absence of LGE, 1: LGE of 1-25% of LV wall thickness, 2: LGE extending to 26-50%, 3: LGE extending to 51-75%, and 4: LGE extending to 76-100% of the LV wall thickness .To determine regional wall motion at rest, cine CMR images were visually interpreted by two experienced observers  using a 17-segment model. Each segment was assigned a wall motion score using a 5-point scale with 0: normal wall motion, 1: mild hypokinesia, 2: severe hypokinesia, 3: akinesia, and 4: dyskinesia . In the Myocardial segments with a visual wall motion score at rest from 1 to 4 were considered as dysfunctional segments. The myocardial segments next to these dysfunctional segments in 3-dimensions, were considered as adjacent segments. The remaining myocardial segments were considered as remote tissue  paired data when appropriate. Stepwise multivariate analysis was performed to determine the relation between regional improvement in myocardial function and improvement in global LVEF at follow up. All tests were two-tailed and a P-value < 0.05 was considered statistically significant.The authors had full access to the data and take responsibility for its integrity. All authors have read and agree to the manuscript as written.Baseline characteristics are summarized in Table The response to low-dose dobutamine at baseline in the dysfunctional, adjacent, and remote myocardial segments is summarized in Figure Clinical assessment revealed that the NYHA classification changed from 2.3 ± 0.5 at baseline to 1.8 ± 0.6 at follow-up (P < 0.05) in the β-blocker treated patients, and from 2.2 ± 0.5 to 1.5 ± 0.5 in the revascularization patient group (P < 0.05). After β-blocker or revascularization therapy, LV end-diastolic volume did not change significantly in both patient groups while LV end-systolic volume and LVEF improved significantly in both the β-blocker and revascularization groups to the same extent  in wall thickening between the dysfunctional and remote segments Figure , top, thThe present study demonstrates the relation between regional and global myocardial function in patients with ischemic cardiomyopathy after β-blocker or revascularization therapy. Following β-blocker therapy, improved global systolic function is mainly related to improved contraction of remote myocardium, whereas after revascularization the dysfunctional and adjacent regions contributed most to the improvement in global systolic function.At baseline, NYHA classification was similar for β-blocker treated and revascularization patients. In addition, global systolic function, the % scar tissue or the number of segments with contractile reserve were similar in both patient groups at baseline. Furthermore, both patient groups showed the same response to low-dose dobutamine at baseline in the dysfunctional, adjacent, and remote myocardial segments. Accordingly, the clinically defined patient groups were comparable at baseline concerning myocardial function.Following β-blocker or revascularization therapy, LV systolic function improved significantly, and to a similar extent. Accordingly, the global functional response to therapy was comparable between both patient groups. This finding is consistent with results from previous studies ,12,24,25++-channel function in failing myocardium. Remote myocardium in the current study may be regarded as myocardium with relatively preserved myocyte function as compared to adjacent and dysfunctional regions.Stepwise multivariate analysis in β-blocker patients revealed that improvement in LVEF after therapy was mainly related to improvement in function of the remote myocardium. The present results concerning β-blocker therapy effect on remote tissue are in agreement with previous studies by Reiken et al. Both in a canine model  and in a++-channel function by administration of β-blockers, whereas the adjacent and dysfunctional tissue cannot. Furthermore, recent data demonstrated that the effect of β-blocker therapy could be predicted by the increase in LVEF during low-dose dobutamine infusion [However, in remote tissue, myocardial hypertrophy may develop when excessive pressure or volume overload is imposed to sustain the burden of a dysfunctional segment . The reminfusion . Since dinfusion .Stepwise multivariate analysis in revascularization patients revealed that improvement in LVEF was mainly related to improvement in function of the dysfunctional and adjacent myocardial segments. This observation is in agreement with data obtained in previous studies ,31. RecoThe number of patients was relatively small and therefore the observations need confirmation in larger cohorts. Myocardial tagging was not performed; this could have provided a more detailed strain assessment across the myocardial segments of interest.In patients with chronic ischemic LV dysfunction, β-Blocker therapy or revascularization resulted in a similar improvement of global systolic LV function. However, after β-blocker therapy, improved global systolic function was mainly related to improved contraction of remote myocardium, whereas after revascularization the dysfunctional and adjacent regions contributed predominantly to the improved global systolic function.The authors declare that they have no competing interests.TK wrote the manuscript, designed and carried out the study; JB, HL have been involved in writing the article and made substantial contributions to it's conception and design. SB participated in the design of the study and performed the statistical analysis; DP, EV, EvdW and JD have made substantial contributions to acquisition and interpretation of data; AdR conceived of the study, and participated in its design and coordination and helped to draft the manuscript. All authors read and approved the final manuscript.


Left ventricular diastolic dysfunction (DD) is defined as the inability of the ventricle to fill to a normal end-diastolic volume, both during exercise as well as at rest, while left atrial pressure does not exceed 12 mm Hg. We examined the concept of left ventricular diastolic dysfunction in a cardiac surgery setting.Literature review was carried out in order to identify the overall experience of an important and highly underestimated issue: the unexpected adverse outcome due to ventricular stiffness, following cardiac surgery.Although diverse group of patients for cardiac surgery could potentially affected from diastolic dysfunction, there are only few studies looking in to the impact of DD on the postoperative outcome; Trans-thoracic echo-cardiography (TTE) is the main stay for the diagnosis of DD. Intraoperative trans-oesophageal (TOE) adds to the management. Subgroups of DD can be defined with prognostic significance.DD with elevated left ventricular end-diastolic pressure can predispose to increased perioperative mortality and morbidity. Furthermore, DD is often associated with systolic dysfunction, left ventricular hypertrophy or indeed pulmonary hypertension. When the diagnosis of DD is made, peri-operative attention to this group of patients becomes mandatory. Left ventricular diastolic dysfunction (DD) is defined as the inability of the ventricle to fill to a normal end-diastolic volume, both during exercise as well as at rest, while left atrial pressure does not exceed 12 mm Hg . It has Pertinent medical literature in the English language was identified through a Medline computerized literature search and a manual search of selected articles using the key words "left ventricular diastolic dysfunction", "left ventricular diastolic impairment", "transmitral flow Doppler", "pulmonary venous flow patterns". The search terms were combined using the Boolean operator term "or" to find all abstracts pertaining to the chosen search terms. These individual terms were then combined using the Boolean operator term "and" to find articles that contained information of all search terms. The reference lists of articles found through these searches were also reviewed for relevant articles. Links provided on the web sites of published articles were searched for relevant articles.a) left atrial-left ventricular pressure gradient at the time of mitral valve opening, b) left atrial chamber compliance, c) left ventricular chamber compliance, d) grade of left ventricle relaxation, e) visco-elastic forces of the myocardial wall, f) pericardial restraint and finally g) left-right ventricular interaction. Left ventricular relaxation-similar to contraction- is an energy-dependent process, because it requires the re-uptake of calcium into the sarcoplasmic reticulum [DD is present when an elevated filling pressure is necessary to achieve normal ventricular filling. So, DD is related to abnormal left ventricular relaxation and filling during diastolic phase of cardiac cycle -24. Durieticulum . When paeticulum ,2,16. Fueticulum . Decreaseticulum . In conteticulum . In a sieticulum .Another aspect of DD is the relationship between systolic and diastolic left ventricular dysfunction ,29,30 InAssessment and diagnosis of DD can be performed with non-invasive  and invasive techniques . Typical findings of primary DD in chest radiograph include absence of cardiomegaly and presence of pulmonary congestion. Electrocardiogram/ECHO reveals the presence of excessive concentric hypertrophy in combination with normal ejection fraction . Measure1) Prolonged relaxation pattern: characterized by prolonged isovolumetric relaxation time and deceleration time, low E and high A wave velocities with an E/A wave ratio typically 1. It is related to the remodelling process including hypertrophy or scarring of an infarct zone leading to a non-uniform LV relaxation.2) Pseudonormal pattern: an intermediate stage between prolonged relaxation and restrictive filling as a consequence of disease progression. There is an association with atrial dilatation and prominent pulmonary venous wave reversal.3) Restrictive pattern: associated with shortened isovolumetric relaxation time, increased peak E wave velocity with very short deceleration time and small A wave, leading to an E/A wave ratio of 2. This pattern might be due to increasing LV volume and also to increased myocardial stiffness. DD is severe when the transmitral filling pattern E/A ratio is 2 and the deceleration time is 150 ms.For patients undergoing cardiac surgery, Doppler assessment of transmitral flow has been used to estimate postoperative left ventricular filling pressure, relaxation, and stiffness . The mosa) most variables measuring diastolic function depend on loading conditions, heart rate and age [b) no single individual measurement can fully characterize left ventricular diastolic dysfunction, and c) ECHO estimation may give different results whether it is performed with the patient awake and breathing spontaneously, or anesthetized and receiving positive pressure ventilation [Intraoperative diagnosis of diastolic dysfunction is difficult, ,42 becau and age -34,43, btilation . Diastoltilation ,34,39. Atilation , first dtilation ,39. It htilation ,45. Thertilation . Fluid rtilation . In tablFollowing coronary artery bypass grafting, DD is temporarily deteriorated  . This deAccording to a multivariate analysis by Bernard et al , left veThere are only few studies looking in to the impact of DD on the outcome following cardiac surgery. Without doubt DD with elevated left ventricular end-diastolic pressure can predispose to increased perioperative mortality and morbidity. Furthermore, DD is often associated with systolic dysfunction, left ventricular hypertrophy or indeed pulmonary hypertension. The mainstay of management of DD starts with the prompt recognition and diagnosis of this entity and relies on the aggressive management of the underlie aetiology of this insidious disease.The authors declare that they have no competing interests.All authors: 1. have made substantial contributions to conception and design, or acquisition of data, or analysis and interpretation of data; 2. have been involved in drafting the manuscript or revisiting it critically for important intellectual content; 3. have given final approval of the version to be published.


Although it has been considered a safe procedure, computed tomography scanning useshigh doses of radiation and can cause malfunctioning in those patients with ICD when the radiation is directly incident on the device. We present a case of ventricular oversensing during a thoracic computed tomography. A 65-year-old woman with a history of mixed connectivopathy (systemic scleroderma and lupus erythematosus) since 1984 and coronary artery disease with myocardial infarct since 1994 suffered a syncopal episode in March 2004.During the electrophysiological study, a syncopal monomorphic ventricular tachycardia with a 240 milliseconds cycle length was induced. Ejection fraction was 45%.R wave 20 mV, pacing impedance 614 Ohm and shocking impedance 48 Ohm, and right atrial pace/sense lead .On 12 March 2004 an ICD was implanted  with a right ventricular pace/sense and defibrillation lead ; values measured in at implant: capture threshold of 1.2 V at 0.5 milliseconds, measured Detection of VT was programmed at 180 beats/min, and VF at 220 beats/min. Ventricular sensitivity was programmed at 0.27 mV.In January 2008 the elective replacement indicator (ERI) was reached and the device was replaced with Vitality 2 EL-T167 (Boston Scientific), maintaining the same programming. No ventricular arrhythmia had been detected by the device.On 5 November 2008, as part of a study of pulmonary involvement by her rheumatic disorder, she underwent a high-resolution thoracic CT scan.This exam was conducted with a CT Volume Access Somaton . The study began at 19 : 25 and ended at 19 : 34; it yielded 36 images in 6 series together with the initial topogram . No compOn 26 November 2008 the patient underwent ICD followup. All measurements of the battery and the leads remained within normal ranges; however, measurement of the intrinsic amplitude of the ventricle was impossible because the patient was pacing dependent.The interrogation of the device-stored electrograms reveals an episode of nonsustained ventricular fibrillation which started capacitors charge that was diverted 3 seconds later .Analysis of the stored electrograms of the episode, which coincided with the time of the thoracic CT scan, reveals an oversensing in the right ventricular channel interpreted by the device as ventricular activity. The oversensing provokes the charge of the capacitors and at the same time causes significant pauses due to inhibition of ventricular pacing . The patDiaphragmatic or other usual causes of oversensing were excluded from the beginning by performing extreme breathing movements, left arm movements, and pocket manipulation in different patient positions.Stability and integrity of both leads was confirmed with several followups during 6 months.The causes of interference affecting electronic cardiac devices are numerous and of diverse origin , but untCT did not appear in lists of potential sources of electromagnetic interference . The firIn order to confirm these results a prospective study was set up to analyse 13 pacemakers and 8 defibrillators, manufactured by Medtronic, subjected to ionizing radiation using CT systems with the production of images in spiral and dynamic mode at different dosage levels . The devOversensing was detected in the majority of the units, with inhibition of up to 4 seconds in some devices. It is not specified whether episodes of oversensing occur in the defibrillators that cause a diagnosis of tachycardia and the activation of a therapy.A recent study  repeatedShort episodes of oversensing were observed on 3 pacemakers, but none of the ICDs appeared to be affected. In addition, there were two curious observations. The units affected were those of most recent manufacture, and the 3 pacemakers that were affected remained undamaged during the repetition of the test when protected by a thin layer of copper.Clinically implanted devices have shown the influence of CT on neurostimulators.Three patients showed unexpected electrical stimulation when the radiation was directly incident on the device .None of these reports show examples of electrograms with oversensing.In July 2008, the [US]FDA collected all this information and issued a preliminary notification [Both the FDA and ECRI Institute , 8 issueUse the lowest possible dose of radiation and during the shortest possible time.Programme the device to “Off” (ICD) or in safety mode (pacemakers).Have a pacemaker/defibrillator programmer, an external defibrillator and emergency medication available.After the examination, reprogramme the device to “On” or back to the initial programming. Check the full and correct functioning of the device.Due to the coincidence in time of both and the absence of other known interference causes, we can conclude that the oversensing is caused by the CT scan.This is the first case demonstrating that an ICD implanted in a human subject may be affected during a CT scan; oversensing may occur, causing pacing inhibition and starting a VF episode detection with charge of the capacitors of the high-voltage circuit.Although it has been considered a safe procedure, computed tomography scanning uses high doses of radiation and can cause malfunctioning in those patients with ICD when the radiation is directly incident on the device.Radiologists need to be aware of this possibility so that they may avoid this radiation as far as possible and will have to be prepared to treat those patients if complications arise.In addition, the patient should be examined by his/her doctor after the scan to check that the device has not been damaged.