To review the pathogenesis of pulmonary vascular complications of liver disease, we discuss their clinical implications, and therapeutic considerations, with emphasis on potential reversibility of the hepatopulmonary syndrome after liver transplantation. In this review, we also discuss the role of imaging in pulmonary vascular complications associated with liver disease. Our objective was to review current knowledge and advances made in understanding pulmonary vascular complications of liver disease between 2000 and 2010. The MEDLINE data base was explored through PubMed, and bibliographies of 229 papers were reviewed. The selected papers included case studies and series reporting results from patients with the vascular complication of chronic liver disease (CLD). We added our own radiological and clinical experience during this period. As the success of liver transplantation (OLT) is the only available definitive treatment for CLD and its success is dependent on the presence or absence of pulmonary vascular complications associated with CLD; our primary search only included studies emphasizing these findings. Of importance are the hepatopulmonary syndrome (HPS) and portopulmonary hypertension (PPH). HPS is defined as a triad of liver disease, increased alveolar-arterial gradient at breathing room air, and evidence of intrapulmonary vascular dilatations. Quantifin = 8–15 mm) in HPS.[The HPS is characterized by a defect in arterial oxygenation induced by pulmonary vascular dilatation and pulmonary AV shunting in the setting of liver disease. HPS can affect all ages and occasionally occur in noncirrhotic patients with PoH and may also been reported with in mild liver disease. The exac) in HPS.2 and O2 content of blood leaving the lungs. Air trapping and poor ventilation in dependent parts of the lungs may present clinically as closing volume exceeding functional residual capacity. Decreased ventilation from air trapping leads to further V/Q mismatched in the dependent parts of the lungs. Lowered V/Q ratio results in elevated Δ (A-a) O2 correctable only by 100% oxygen inhalation. However hypoxemia caused by larger AV shunts does not respond to inhalation of 100% oxygen. A significant proportion of patients with HPS and advanced liver disease show diffusion impairment associated with decreased DLCO without concomitant increase of Δ (A-a) O2. This phenomenon explains the higher sensitivity of DLCO over Δ (A-a) O2 in the detection of pulmonary vasodilatation.[HPS has three major components, i.e. liver disease, IVPD, and a defect in oxygenation. Increased alveolar-arterial gradient occurs in HPS while breathing room air. The majo7latation.–13Due to pulmonary capillaries dilatation oxygen encounters difficulty in diffusing into the centre of the larger capillaries. Increased cardiac output and the associated reduced transition time of blood through the pulmonary vascular bed also impair diffusion, leading to a diffusion–perfusion defect or alveolar capillary oxygen disequilibrium.Early investigators attributed IVPD in HPS to inadequate synthesis or metabolism of pulmonary vasoactive substances by a failing liver.7 HoweverGram-negative intestinal endotoxemia in PoH associated with increased nitric oxide release and tumor necrosis factor have been proposed as a cause of excessive pulmonary vasodilatation. ImprovemA recent study has thrown doubt on vasodilatation being the sole cause of the pathophysiology underlying HPS. It has been shown that administration of inhaled l-NAME in HPS patients did not improve V/Q mismatch and arterial hypoxemia. This stuTypically HPS presents with dyspnea of insidious onset, platypnea and orthodeoxia. Physical192 but not Type 2 HPS.[Two types HPS have been described: Type I lesions are associated with vascular dilatations at the precapillary level close to the normal gas exchange units of the lung and Type II with focal larger dilatations amounting to AVS distant from the gas exchange units. Supplementary oxygen improves Type I HPS PaOpe 2 HPS.2(≤50 mmHg).[HPS is associated with an increase risk of death, worse functional status, and quality of life in patients evaluated for OLT. The medi50 mmHg).2or hypoxemia in suspected HPS. There is controversy in the use of cut-off values of PaO2.[2 <70 mmHg or below the age-related threshold predicted the presence of HPS with high probability in the absence of intrinsic cardiopulmonary diseases.[2 levels are abnormal a chest radiograph (CXR) and pulmonary function tests are used to help exclude other cardiopulmonary abnormalities. However, the demonstration of AV shunting despite the presence of other cardiopulmonary abnormalities by radiological means can achieve the diagnosis of HPS. In a cirrhotic patient suspected of HPS, it is important that other cardiopulmonary causes of hypoxia be excluded such as pulmonary atelectasis, ascites, chronic obstructive pulmonary disease, and hepatic hydrothorax.Diagnosis is usually based on imaging and arterial gas analysis. Arterial gases are analysed initially to identify elevated alveolar-arterial differences in O of PaO2. A varietdiseases. If PaO2 2 or hypoxemia.A definitive diagnosis of HPS can be made by demonstration of pulmonary vasodilatation associated with functional arteriovenous shunting. Imaging studies that can identify such shunts include contrast echocardiography and perfusion scintigraphy with 99mTc, which are usually carried out following analysis of arterial gases to identify elevated alveolar-arterial differences in O2 levels rise to ≥600 mmHg, the presence of AVS is unlikely, but if levels fail to exceed 500 mmHg, the presence of a shunt cannot be ruled out. If PO2 levels fail to rise to above 150–200 μmHg, shunt is most probably the main mechanism of hypoxemia.[In the setting of HPS administration of 100% oxygen can be used as a noninvasive test to quantify pulmonary AVS. This is an important parameter to measure as demonstration of AVS suggests that the hypoxemia may not resolve following OLT. In response to breathing 100% oxygen if the PO99Technetium macroaggregated albumin (99mTc-MMA) perfusion imaging or contrast echocardiography (CEE).[The presence of a ventilation–perfusion mismatch can be achieved by several means. The two methods available are hy (CEE). 99mTc-MMhy (CEE). In patiehy (CEE).–4. As toCEE is usually performed using intravenous microbubbles. These microbubbles are trapped in the pulmonary vasculature and absorbed. However in the presence of intracardiac right to left shunt, the microbubbles are seen in the left heart within the first three cardiac cycles. In HPS, 2 to less than 300 mmHg. However, presently PA is rarely performed in the diagnosis of HPS but has a role when CTA suggests an AVM when PA may be used when the AVM appears amenable to embolization. PA is also able to differentiate between Type I and II HPS.[Pulmonary angiography (PA) is an invasive procedure, which uses iodinated contrast media and is usually reserved in patients with an increase in the PaOd II HPS. Type I HMost patients being cared for in hospital setting would have undergone a conventional CXR, which is not only useful in the diagnosis of HPS but is also crucial for excluding other causes of hypoxemia. A CXR in HPS shows bibasilar nodular or reticulonodular opacities in 5–13.8% of patients with CLD and 46–100% of patients with HPS. These opTo summarise: the diagnostic flow chart of HPS generally starts with (1) arterial blood gas analysis performed in the supine position, (2) a CXR follows to rule out causes of hypoxemia other than HPS, (3) pulmonary function tests to include spirometry and DLCO. Spirometry is generally normal but may show a mild restrictive pattern due to pleural effusion or ascites. DLCO depicts decreased diffusion ability of lungs due to intrapulmonary vasodilatation, (4) 99mTNo effective medical treatment is available, but better knowledge of the pathophysiology should improve this situation in the future. Medical management, transjugular intrahepatic portosystemic shunts (TIPS), and pulmonary arterial coil embolization have been described as temporizing measures until OLT is performed.Allium sativum) powder capsules daily for a minimum of 6 months resulted in a modest improvement in arterial oxygenation in 6 out of 15 patients with HPS.[Several therapeutic trials in HPS have shown poor results such as somatostatin analogues, cyclooxygenase inhibitors, and immunosuppressive agents such as corticosteroids and cyclophosphamide. Almitrinwith HPS. PoH appewith HPS. Some repwith HPS. Another with HPS. Suprahepwith HPS.OLT provides the only definitive treatment of HPS. Over 85% of patients with HPS undergoing OLT show complete reversal of HPS or experience a significant improvement in hypoxemia. This reversal may take up to year. However, patients with HPS undergoing OLT have a significant mortality of 71% at 1 year.et al. It is presently considered a worthwhile therapeutic approach because of encouraging rate of response or stabilization. Initial work up includes assessment of the degree of AV shunt[Hepatic radioembolization with Yttrium-90 glass microspheres for treatment of inoperable primary liver cancer was first reported by Cao  AV shunt [Figures AV shunt–4, 8. It AV shunt.5; and normal pulmonary artery occlusion pressure (<15 mmHg) or an elevated transpulmonary gradient.[PPH is defined by criteria obtained by right heart catheterization in patients with PoH and include: Elevated mean pulmonary artery pressure ; increased pulmonary vascular resistance ; other symptoms, such as syncope, chest pain, and fatigue, are seen in a third of the patients. Auscultation may reveal an accentuated pulmonary component of the second heart sound and a systolic murmur. Hemodynamic findings included severe pulmonary hypertension with normal pulmonary capillary wedge pressure and cardiac output.Patients with PPH carry high perioperative mortality and have a mean survival of 15 months. As PPH iLung function tests in PPH are not generally helpful although diffusing capacity may be reduced. B-type natriuretic peptide testing is helpful in monitoring the severity of disease and the efficacy of treatment in PH; but its role in PPH has not been defined. EKG findings in PPH include right atrial or ventricular enlargement and a right bundle branch pattern. A CXR may show prominent pulmonary arteries and cardiomegaly in advance PH. Standard echocardiography is an excellent tool to detect signs of PH. FindingsRight heart catheterization (RHC) is regarded as a definitive test for confirmation of PPH, which allows accurate measurement of pulmonary artery pressures, pulmonary artery occlusion pressure, cardiac output, and pulmonary vascular resistance. RHC has the advantage of excluding other treatable causes of PH.A CXR may be normal in the early stages. As the disease advances the central pulmonary arteries become prominent with a right ventricular enlargement and tapering of the peripheral vessels. At CT, PH can be diagnosed when the diameter of the main pulmonary artery is greater than or equal to 29 mm accompanied by a segmental artery-to-bronchus ratio greater than 1:1 in three of four pulmonary lobes or/and the ratio of the main pulmonary artery diameter to the aortic diameter is greater than 1, particularly in patients less than 50 years of age53 Figu–13. HRCTOptimal treatment for PPH remains elusive. Mild PPH with pulmonary artery pressure <35 mmHg is generally not treated. Moderate-to-severe PPH attempts are made to improve symptoms and lower pulmonary artery pressures and pulmonary vascular resistance. Anticoagulant therapy in PPH is generally not considered because of gastroesophageal varices and coagulation abnormalities related to liver disease, but anticoagulation should be considered in the absence of contraindications. Diuretics provide standard therapy in patients with PH and PPH, for the underlying liver disease, especially if ascites or peripheral edema is present. Oxygen therapy is used to treat hypoxemia. β-Blockers are used in some patients as prophylaxis of variceal bleeding. However, the use of β-Blockers in PPH is controversial as a significant worsening of exercise capacity has been reported after its use.A variety of vasodilators have been used in PPH. However, most of the studies of the use of vasodilator drugs have been used in PH from other causes. Prostanoids have been used successfully to lower pulmonary pressures in PPH. Epoprostenol has short half-life, a complicated delivery regime and is associated with several complications but has been shown to improve exercise capacity in PPH, although a survival advantage has not been documented to date. IloprostOLT is not the treatment of choice for PPH, but after optimal hemodynamic and clinical improvement with medical therapy, OLT can be considered an option in selected patients. PPH incrPPH is an uncommon complication of ESLD in children. Epoprostenol can bridge PPH patients to OLT. OLT leads to rapid resolution of HPS and PPH and currently represents the only successful treatment for these children. Most sucThe major pulmonary vascular complications of CLD include HPS and PPH. The pathogenesis, imaging, treatment, and prognostic implications of these complications are discussed. In the context of ongoing uncertainty about causation and treatment of the HPS, future studies must focus on better understanding the pathogenesis of the HPS, predicting reversibility after OLT, and identifying other treatment options It is emphasized that appropriate knowledge of the pathogenesis of vascular complications and imaging of CLD would assist the clinician in initiating the appropriate treatment at the most appropriate time.


Non-ischemic dilated cardiomyopathy (DCM) is a relatively common cause of left ventricular dysfunction. Microscopic scar may be a cause of regional and global left ventricular dysfunction in DCM patients. The aim of this study was to evaluate changes in regional myocardial structure, function, and dyssynchrony using a novel non-invasive MR imaging protocol.Eleven patients with suspected non-ischemic cardiomyopathy underwent cardiac MRI (CMR) on a 1.5T magnet . In addition to the conventional CMR viability protocol, patients underwent both tissue phase mapping (TPM) and T1 mapping with a modified look-locker inversion recovery (MOLLI) technique pre and between 10 and 25 minutes post 0.2 mmol/kg adminstration of an extracellular gadolinium agent. These sequences were performed through the left ventricle in the short axis orientation at basal, mid-chamber, and apical levels. The hematocrit was collected within 48 hours of the CMR to calculate segmental ECV values as described by Kellman, et al., as a marker of microscopic fibrosis. TPM analysis was used to determine the degree of segmental wall motion abnormality. Radial, longitudinal and absolute velocities were measured from the TPM images. Short axis slices were analysed on a segmental basis using the AHA 16 segment model. Segments were classified into four ECV subgroups as detailed in Figure Longitudinal and absolute peak systolic and diastolic velocities were reduced in segments with increased fibrosis Figure . These tOur preliminary findings suggest a myocardial structure-function relationship linking myocardial fibrosis with altered myocardial function at a segmental level. Recruitment is ongoing to validate our results in a larger patient cohort.Kellman et al.: J Cardiovasc MR 2012, 14:63,64Not funded.


Feasibility of noninvasive monitoring of cardiac function after surgically induced ischemic cardiomyopathy with tissue Doppler and non-Doppler 2D strain echocardiography in rats.The optimal method for quantitative assessment of global and regional ventricular function in rats with chronic heart failure for research purposes remains unclear.20 rats underwent suture ligation of the left anterior descending coronary artery via a left thoracotomy to induce ischemic cardiomyopathy. Echocardiographic examination with estimation of left ventricular wall thickness, diameters, fractional shortening, ejection fraction, wall velocities as well as radial strain were performed before and 4 weeks after surgery.Mean LVEF decreased from 70 ± 6% to 40 ± 8% (p < 0.0001) one month after the operation. LVEDD increased from 7 ± 1 mm to 9 ± 1 mm (p < 0.0001), systolic anterior velocity decreased from 0.79 ± 0.25 cm/s to 0.18 ± 0.19 cm/s (p < 0.0001). Radial 2D strain was significantly reduced after myocardial infarction of the septal , anteroseptal , anterior , lateral  as well as posterior myocardial segments . Inferior segments  did not change at all.It is feasible to assess dimensions, global function, and regional contractility with echocardiography in rats suffering from chronic heart failure after myocardial infarction. Particularly regional function can be exactly evaluated if tissue Doppler and 2D strain is used. Echocardiography is a well established diagnostic tool for safe and accurate assessment of cardiac function in clinical practice. Spatial resolution of latest ultrasound imaging systems approach that of magnetic resonance imaging and echocardiographic temporal resolution is better than MRI. Furthermore, new features of echocardiography namely tissue Doppler and 2D strain better detect particularly regional myocardial dysfunctions. Therefore, there is increasing interest to use echocardiography according to current standards with its newer methods also in research dealing with laboratory animals Figure . HoweverA prospective, blinded animal study with paired samples was conducted in accordance with guidelines for the care and use of laboratory animals at our institutions and with approval by the local animal protection commission.20 Lewis rats with a mean body weight of 346.6 g  were obtained from a single breeding colony . Animals had free access to standard laboratory food and water ad libidum. Twelve hours of light per day were provided. All rats underwent surgical ligation of the LAD to produce myocardial infarction. They were anesthesized with xylazine (3.7 mg/kg i.p.) and ketamine (66.5 mg/kg i.p). After endotracheal intubation and ventilation a left lateral thorakotomy was performed. The pericardium was opened and the left coronary artery was proximally suture ligated using 8-0 Prolene. Myocardial ischemia could always be visualized as well as akinesia. The chest was closed and air aspirated. All rats resumed spontaneous breathing after mechanical ventilation was finished. There were no operative deaths.Echocardiographic studies were performed before and 4 weeks after myocardial infarction using a VIVID 7 dimension system . Images were obtained using a 10S transducer (5.5-12.0 MHz) with high temporal and spatial resolution. Rats underwent the same intraperitoneal anesthesia as for the infarct surgery which was maintained throughout the echocardiographic examination. The transducer was placed directly on the shaved chest wall. A complete 2-dimensional, M-mode (according to standards of the American Society of Echocardiography), color and tissue Doppler echocardiogram was performed. Color Doppler myocardial velocity data were acquired at a frame rate of 205-230 frames/s, a sector angle of 30 degrees and an adjusted image depth of approximately 15 mm using a zoomed image window. The tissue Doppler sample volumes were tracked manually throughout the cardiac cycle, in order to measure mid-myocardial signals.Data of 3 consecutive heart cycles were recorded digitally and analysed. Radial 2D strain was calculated from the parasternal short axis view. Strain profiles were analysed on the septal, anteroseptal, anterior, lateral, inferior and posterior myocardial segments. Peak systolic strain values were measured in each of 3 heart cycles. Systolic 2D strain measurements are based on real-time tracking of natural acoustic marker during two consecutive frames by 2-dimensional strain software  as previously described [® 5 . Values are expressed as mean ± standard deviation (SD) unless indicated otherwise. Paired samples of metric data were compared by t-test or Wilcoxon-test depending on the presence of Gaussian distribution. The level of significance was α = 0.05.Statistical analysis was done using PrismEchocardiographic measurements were possible in all rats before and after surgery. All animals survived and we did not encounter any hemodynamic or respiratory instability during sedation and examination.The echocardiographic measurements before as well as one month after LAD ligation are summarized in Table Majority of the echocardiographic mean values showed a significant change after myocardial infarction. Most of all there was a highly significant (p < 0.0001) decrease of LVEF Figure , systoliMurine experimental myocardial infarction models are of great value to study new heart failure therapy strategies like recently the concept of cell transplantation. They are easy to perform and cost effective. However, exact monitoring of cardiac function has always been challenging due to the small size of the hearts. Invasive techniques like manometry using microcatheters had been applied but are associated with a relevant morbidity and mortality. Furthermore, they allow mainly single evaluation but serial follow ups are needed.Transthoracic echocardiography which is a well established diagnostic tool in clinical practice was applied one decade ago to evaluate morphology as well as global ventricular function in rats despite resolution problems . Left ve1 we used it successfully especially to monitor regional functional changes after permanent LAD occlusion in rats. To our knowledge this is the first study demonstrating the feasibility of 2D strain echocardiography in rats for noninvasive quantification of regional ventricular function in a chronic ischemic rat model. Radial 2D strain was chosen because a good short axis view was always easy to find. Moreover it seems to be better validated than longitudinal or circumferential 2D strains. As the heart rate in rats is as high as 300/min, the frame rate had to be set between 180 and 230 for tissue Doppler measurements and between 60 and 80 for non-Doppler 2D strain, in order to obtain optimal temporal and spatial resolution.Based on our earlier published experience of monitoring cardiac function using Tissue Doppler and non-Doppler 2D strain echocardiography of non-operated rat heartsApparently, LAD-ligation led to a profound decrease of regional contractility not only of the anterior, anteroseptal and septal segments. Even adjacent regions like lateral and posterior segments were affected. This can be explained by the different coronary artery pattern of the rat compared to humans. In the rat the LAD is predominant and there is no true circumflex artery . TherefoA parallel group of sham operated rats could have been used to assess the existence and relevance of confounding effects not related to LAD ligation such as anesthesia.In conclusion, transthoracic echocardiography using tissue Doppler and 2D strain in rats with chronic ischemic heart failure is not only feasible. In fact it is a new powerful method for the evaluation and quantification of particularly regional cardiac function after permanent coronary occlusion in the rat. It should be used routinely and become a standard research tool for this model.The authors declare that they have no competing interests.SH, FK, GB and WK have designed and coordinated the study. SH and FK have equally contributed to this study and written the manuscript. SH and GH have performed the surgery and the statistical analysis. FK and ACB have performed echocardiographic measurements. All authors have read and approved the final manuscript.


We report a case of a 69-year-old male with non-ischemic cardiomyopathy, having drug- and antitachycardia pacing-refractory ventricular tachycardia resulted in multiple ICD shocks. The sustained and intractable ventricular arrhythmia was mapped and ablated with the aid of the three-dimensional electroanatomic mapping system, initially performed but unsuccessful from the endocardial site then performed successfully from the epicardial site via the coronary sinus. In some instances, catheter ablation from the epicardial aspect of the ventricles is needed although the majority of ventricular tachycardia (VT) is located and ablated in the right or left ventricular endocardium . EpicardA 69-year-old male patient with NICM was referred to our department for multiple antiarrhythmic drug- and antitachycardia pacing-refractory ventricular tachycardia (VT) episodes resulted in electrical storm and depletion of the battery of his VVI-ICD. No secondary abnormalities causing the tachycardia were detected. Surface electrocardiogram during VT revealed a possible focus of the basal posterolateral wall of the left ventricle . VoltageAlthough automaticity and triggered activity may responsible from the electrophysiological mechanisms of VT in NICM, the proven histopathological relation between cardiomyopathic changes including myocyte hypertrophy and fibrosis and, the inducibility of VT with extrastimuli may also suggest the susceptibility to reentrant arrhythmias. Most of the cases with VT can be successfully mapped and ablated from the endocardial site. When this is not possible, however, invasive percutaneous epicardial route may be required to map and ablate VT. Previously published several recent reports have demonstrated that the venous system of the heart seems to be alternative route for mapping and ablation of VTs originating from an epicardial region -6. Li et


To assess the utility of cardiovascular magnetic resonance (CMR) in acute cardiac rejection using T2 mapping.Cardiac transplantation is the treatment for some patients with end-stage heart failure. After transplantation asymptomatic acute allograft rejection is a major factor impacting survival in the first 12 months. Current transplant monitoring requires frequent right heart catheterizations, endomyocardial biopsies (EMB), and echocardiography. CMR imaging, comparatively less invasive, has been studied previously in the transplanted heart and prolonged T2 relaxation has shown correlation to transplant edema and rejection [Patients were recruited from the transplant clinic for CMR within the first year of transplantation or if admitted to hospital for rejection. All MRI scans were performed within 24 hours of EMB. Biopsies were graded according to the International Society for Heart Lung Transplant grading system for cellular rejection with or without immunohistochemistry (IF) marking humoral rejection.We used a non-contrast multiplanar single-shot and cine TrueFISP imaging sequence. Each patient also underwent a novel four-chamber and three short axis quantitative T2 mapping sequence using a single-shot T2-prepared SSFP acquisition with three T2-prep echo times: 0, 24, and 55 msec. T2 maps were analyzed using the AHA 17 segment model independently by two reviewers (AU and MW) blinded to outcomes for inter-rater and intra-rater reliability.A control cohort of 20 cases demonstrated a normal T2 average of 51.2 ± 2.7 ms. A total of 25 transplant scans were performed with average age 55.8 ± 13.8. All patients were on immunosuppressant regimen of prednisone, tacrolimus, with or without mycophenolate mofetil. There were two cellular and one humoral rejections. The average T2 relaxation time in patients with 0R/1R and negative IF was 52.1 ± 2.4 ms versus 61.6 ± 3.1 ms in rejections (p<0.05). The average ejection fraction for the rejection versus non-rejection cases was not significantly different, 58.7 ± 12.7% versus 53.1 ± 2.2% (p>0.05). All rejection cases were rescanned and demonstrated T2 value resolution with treatment. Figure 1Preliminary results demonstrate that T2 mapping offers a novel non-invasive tool for transplant monitoring for both cellular and humoral rejection. A larger multi-institution study will help elucidate the sensitivity and specificity of T2 mapping and the possibility of becoming an adjunctive tool in routine transplant monitoring.


Cardiovascular morbidity is a well known late complication of chemotherapy, for example for treatment of testicular cancer. In addition, development of a combination of overweight, hypertension and abnormal lipid profiles has been observed in these patients suggesting increased risk of developing the metabolic syndrome and diabetes. The early effects of chemotherapy on myocardial function and metabolic profile are largely unknown. Therefore, the purpose of this study was to assess short-term effects of chemotherapy in testicular cancer on myocardial function in relationship with alterations in metabolic profile.Fourteen patients with testicular cancer were treated with bleomycin, etoposide and cisplatin.Before and after chemotherapy, magnetic resonance imaging techniques were used to assess cardiac systolic and diastolic function, and abdominal fat volume (summation of 3 slices at the level of the L5 vertebra). In addition, hepatic and myocardial triglyceride content were assessed using MR spectroscopy. Blood samples were taken at both occasions to obtain plasma lipid profile and to estimate insulin sensitivity.After chemotherapy, an unfavorable shift in metabolic profile was observed: Visceral abdominal fat volume was increased significantly (from186 ± 125 ml to 227 ± 162 ml. P< 0.05) without significant changes in BMI. Hepatic triglyceride content increased, although non-significant (from 3.23 ± 2.72 % to 4.65 ± 4.85% P> 0.05). In addition proxy-measures of insulin sensitivity (Quicki) decreased from 0.39 ± 0.05 to 0.36 ± 0.05 P < 0.05 and serum LDL-cholesterol increased significantly after chemotherapy treatment from 3.12 ± 1.15 mmol/l to 3.74 ± 1.41 mmol/l.These metabolic derangements were paralleled by subclinical changes in myocardial function. Diastolic function, as assessed as the E/A ratio, decreased (from 1.87 ± 0.43 to ± 1.64 ± 0.45 P< 0.05.) Furthermore, left ventricular end-diastolic volume was decreased (from192 ± 27 ml. to 175 ± 26 ml. P< 0.05), indicating disturbed ventricular relaxation. Myocardial systolic function and myocardial triglyceride content were unaltered.Chemotherapy for testicular cancer induces unfavorable metabolic changes, which are paralleled by impairment in diastolic heart function.None.


Electrograms were acquired from 10 LV and 10 RV endocardial sites in 15 patients with normal ventricles. APD and APD adaptation were measured during an increase in heart rate. Analysis of in vivo electrograms revealed longer APD in LV than RV , and slower APD adaptation in LV than RV . Following rate acceleration, LV/RV APD dispersion experienced an increase of up to 91% in 12 patients, showing a strong correlation (r2 = 0.90) with both initial dispersion and LV/RV difference in slow adaptation. Pro-arrhythmic implications of measured LV/RV functional differences were studied using in silico simulations. Results show that LV/RV APD and APD adaptation heterogeneities promote unidirectional block following rate acceleration, albeit being insufficient for establishment of reentry in normal hearts. However, in the presence of an ischemic region at the LV/RV junction, LV/RV heterogeneity in APD and APD rate adaptation promotes reentrant activity and its degeneration into fibrillatory activity. Our results suggest that LV/RV heterogeneities in APD adaptation cause a transient increase in APD dispersion in the human ventricles following rate acceleration, which promotes unidirectional block and wave-break at the LV/RV junction, and may potentiate the arrhythmogenic substrate, particularly in patients with ischemic heart disease.Left-to-right ventricular (LV/RV) differences in repolarization have been implicated in lethal arrhythmias in animal models. Our goal is to quantify LV/RV differences in action potential duration (APD) and APD rate adaptation and their contribution to arrhythmogenic substrates in the  We hypothesized that the human ventricles exhibit LV/RV heterogeneity in both APD and APD rate adaptation, which result in increased interventricular heterogeneity in APD shortly after heart rate acceleration. In our study, LV/RV differences in APD and APD rate adaptation were quantified from in vivo electrograms obtained at 10 LV and 10 RV endocardial locations of 15 patients using two decapolar catheters. Ethical limitations prevent the in vivo investigation of the pro-arrhythmic consequences of these LV/RV heterogeneities in the patients. We therefore conducted a simulation study to extend the implications of our in vivo findings. A human ventricular tissue model was constructed based on the in vivo recordings. Simulations were conducted using different stimulation protocols to systematically investigate the contribution of LV/RV heterogeneity in APD and APD rate adaptation to the pro-arrhythmic substrate following rate changes. Based on the higher incidence of in-hospital complications and post-discharge mortality in patients with ischemic regions near the LV/RV junction The goal of our study is to quantify LV/RV heterogeneities in APD and APD rate adaptation in the human ventricles using Fifteen patients  to a faster cycle length (CL) of median 500 ms see , in agreAPDs were quantified as the activation-recovery intervals from each unipolar electrogram using the Wyatt method of analysis , which hf) and slow (τs) phases of APD adaptation for each electrogram by fitting each curve to a double exponential decay  was quantified for each patient as the difference between the longest and shortest APD in each ventricle at each time point (LV-RV), following the approach of Ramanathan et al.LV-RV was then quantified at each time point as the difference between these average APD adaptation curves.Intraventricular APD dispersion in LV and RV  specifically calculated for human ventricular tissue In all tissue simulations an isotropic monodomain model was used to simulate propagation of electrical excitation, with a diffusion coefficient  model in agreement with our u is rescaled to physiological range by means of the mapping m = 92u−83V (mV), with initial conditions given by u = 0, v = 1, w = 1, s = 0, c = 1, and ∞ = 1.w The slow phase of APD adaptation is independently regulated by model parameter τs  is −83 mV, AP amplitude 130.7 mV, and maximum upstroke velocity 234.3 V/s, all in agreement with previously published physiological data enerated . CompariThe simulation software was written in Fortran. The human AP model was integrated using a second-order Euler method in time, with constant time step of 0.025 ms, and a Fourier spectral method in space, allowing a space discretization of 0.03 cm due to the high-order convergence of these methods in vivo electrograms revealed significant LV/RV differences in steady-state APD and slow APD adaptation dynamics , whereas no statistical LV/RV differences were found for the time constant of the fast phase of APD adaptation . As shown in s = 47.0±14.3 and 35.6±6.5 s, respectively). The range of τs is also wider in LV than in RV, with τs = 26.9–85.2 in LV and τs = 25.8–44.0 s in RV. No significant correlations were observed between steady-state APD values and estimated time constants of adaptation (data not shown).The analysis of the LV-RV) experienced an increase of up to 91%  of their initial value in 12 patients, following the pattern illustrated in LV-RV following rate acceleration. The percent of ΔAPDLV-RV increase over their initial value is shown for all patients in in vivo data showed a strong correlation (r2 = 0.90) of maximum ΔAPDLV-RV with both initial ΔAPDLV-RV and the LV/RV difference in slow adaptation time constant.Following rate acceleration, LV/RV differences in APD  to fast pacing (CL = 400 ms) and either suddenly (solid lines) or linearly over a period of 60 s (dashed lines), the latter replicating rate changes occurring gradually. ΔAPDLV-RV at normal and fast pacing in all scenarios was in range with the one reported in our in vivo electrograms, and also in agreement with the average ΔAPDLV–RV of 32 ms reported at normal heart rate by Ramanathan et alA simulation study was conducted to further investigate the implications of LV/RV heterogeneity in APD and APD adaptation shown in the LV-RV during the fast phase of APD adaptation, followed by a transient increase in ΔAPDLV-RV before a gradual decrease towards the final ΔAPDLV-RV value. For human tissue exhibiting moderate interventricular APD dispersion at normal heart rate (ΔAPDLV-RV = 22 ms), and slow APD adaptation time constants of τs = 30 and 50 s in RV and LV .In all the considered scenarios, sudden rate acceleration results in a sudden decrease in ΔAPDV and LV , maximum = 32 ms  results LV-RV following rate acceleration increases the likelihood of unidirectional block and reentry in human ventricular tissue. An ectopic stimulus was applied near the LV/RV border at the time of maximum ΔAPDLV-RV, and subsequent dynamics were investigated. As shown in LV-RV generated by moderate LV/RV heterogeneity in the slow phase of APD adaptation is not able to produce conduction block following the ectopic excitation (t = 20). The ectopic wavefront propagates as an almost circular pattern with its curvature only affected in a small region of the LV (t = 30 to 60).Simulations were conducted to test the hypothesis that a transient increase in ΔAPDt = 20, asterisk), setting the stage for initiation of reentry (t = 30). However, the two wave fronts eventually merge, producing an excitation pattern similar to the one displayed in LV-RV at normal heart rate as considered in scenario C (data not shown). Therefore, our results suggest that heterogeneous APD adaptation dynamics between LV and RV, as reported in the in vivo electrograms, favor unidirectional block of propagation. However, additional conditions are required for the establishment of reentrant circuits. Our simulation results are therefore consistent with the lack of ventricular arrhythmias in the patients considered in this study, even considering larger LV/RV differences in rate adaptation than the ones reported experimentally , and the ectopic stimulus circumvents the injured region with a normal excitation pattern (t = 60 to 160). However, as shown in t = 20), with the establishment of a reentrant circuit facilitated by the scar region (t = 60). Importantly, this irregular excitation pattern self-perpetuates in the tissue, eventually finding new areas of conduction block (t = 110), and ultimately producing wave-break and fibrillatory-like activity (t = 220).Given the high incidence of arrhythmic events in the presence of ischemic regions at the LV/RV junction An appropriate timing of the extra stimulus depending on ectopic location was required in our computer simulations in order to yield establishment of reentry. This is in line with previous studies highlighting the existence of a vulnerable window for reentry following ectopic stimulation Our results therefore show that LV/RV heterogeneity in rate adaptation facilitates unidirectional block and initiation of reentry at the interventricular junction. Previous studies have suggested a possible role of the slow phase of APD adaptation in the transition from ventricular tachycardia to ventricular fibrillation, by modulating wave-break In the clinical scenario, reentrant arrhythmias are generally considered to be multifactorial in origin, whereby a number of factors combine to generate an appropriate trigger and substrate at a given moment. In order to achieve as complete a mechanistic picture as possible, it is important to identify all the potential individual components.in vivo from humans with normal ventricles, exhibit significant LV/RV heterogeneity in APD and APD rate adaptation dynamics. In most patients, LV/RV APD heterogeneity transiently increases following rate acceleration due to LV/RV heterogeneity in rate adaptation. Computer simulations further demonstrate the importance of LV/RV heterogeneity in APD rate adaptation in increasing ventricular dispersion of repolarization following changes in rate and facilitating unidirectional block at the LV/RV junction. In structurally-normal ventricles, the transient increase in LV/RV APD heterogeneity following rate acceleration is insufficient for the establishment of a reentrant circuit. However, in the presence of an ischemic region at the LV/RV junction, LV/RV heterogeneity in APD and APD rate adaptation promotes initiation and establishment of reentrant circuits and their degeneration into fibrillatory activity, due to unidirectional block at the LV/RV junction.Electrophysiological recordings from multiple LV and RV endocardial sites, acquired in vivo study reports longer APDs in LV than in RV in the human ventricles , due to a higher likelihood of conduction block, reentry and wave-break which could degenerate to ventricular fibrillation. Our combined in vivo and in silico study provides new insights that offer a mechanistic explanation of the increased risk of cardiac arrhythmias and sudden cardiac death in patients exhibiting protracted QT adaptation, emphasizing the importance of this biomarker in arrhythmic risk stratification.We report for the first time Figure S1Unipolar electrocardiogram (UEG) postprocessing flowchart.(TIF)Click here for additional data file.Figure S2The slow phase of APD adaptation does not facilitate reentrant wave-break. A: Sustained wave-break when reentry is initiated in a steep APD restitution region, with homogeneous slow time constant of APD adaptation (τs = 50 s). B: Stable reentry pattern after reentry initiation in a flatter APD restitution region, with linear apico-basal gradient in the slow time constant of APD adaptation (τs = 20–80 s). Times indicated since initiation of reentry (ms); colorbar denotes transmembrane potential (mV).(TIF)Click here for additional data file.Table S1Calibration of the methodology for estimation of slow time constants of APD adaptation.Top: Parameter sets used to generate the synthetic APD series. Bottom: Estimated slow time constants of APD adaptation (mean±SD) for different noise instantiations (n = 100). Compare results with the last row of the top part of the table.(DOC)Click here for additional data file.Text S1Expanded methods and results.(DOC)Click here for additional data file.


Estimating an individual's risk for ventricular tachyarrhythmia (VTA) and sudden cardiac death (SCD) and identifying patients at high risk who would benefit the most from an implantable device remain key challenges for the cardiac electrophysiologist. A sudden onset and broad spectrum of precipitating mechanisms and triggers are the hallmarks of these life-threatening events, making them particularly difficult to foresee. Additional challenges arise because of variations in anatomy and tissue composition when cardiac electrical activity is measured at the body surface, relatively far away from its electrical sources in the heart.2 The proarrhythmic effects of spatial repolarization heterogeneity can be amplified or diminished by the dynamic relationships between cardiac cycle length  and action potential duration (APD).3 The analysis of these relationships, referred to as electrical restitution, proved useful for understanding the mechanisms linking the dynamics of heart-rate dependent APD adaptation to arrhythmogenesis and for determining critical parameter regimes that can be proarrhythmic. In particular, the steepness of the restitution curve has been identified as one of the key factors precipitating T-wave alternans, a proarrhythmic form of repolarization instability.3 The analysis of theoretical properties and experimental relationships between APD restitution and arrhythmias has been the subject of intensive research in the past decade.4 Dynamically induced elevation of spatial repolarization heterogeneity has been shown to promote inducibility of ventricular fibrillation in experimental studies.3 Nevertheless, because of the complexity of restitution relationships in a real-life setting, with freely varying cycle lengths and other confounding factors, analysis of the APD restitution has not translated to the clinical practice of cardiac electrophysiology.Despite these formidable challenges, significant progress has been made in arrhythmia risk stratification. A large body of evidence collected from theoretical, experimental, and clinical studies has shown that spatial repolarization heterogeneity can precipitate regional conduction slowing and unidirectional block and can ultimately lead to the initiation of reentrant arrhythmias.Journal of the American Heart Association (JAHA), Nicolson et al5 present a pilot study of a single-valued composite index, referred to as the Regional Restitution Instability Index (R2I2), which incorporates both (1) an estimated spatial heterogeneity across the 12 surface ECG leads and (2) restitution-related characteristics of repolarization over a range of pacing-induced cardiac cycle lengths. The proposed lumped-parameter metric uses the location of the T wave's peak as a key fiducial point, and thus it is also influenced by the symmetry and waveform characteristics of the T wave, which can undergo changes in the presence of ischemia and repolarization heterogeneity.8In this issue of the peak – Tend interval, and the latter 2 indices had no statistically significant association with the occurrence of arrhythmias in this patient population.To test the accuracy of R2I2, the authors conducted a small but well-designed retrospective study that included 3 groups: (1) a Control group of 29 patients with supraventricular tachyarrhythmias, (2) a Primary Study group in which the method was refined, and (3) a Replication group in which the method was tested. The study showed that R2I2 identified the subjects who experienced VTA/SCD independently of the demographic and clinical factors included in the analysis. Moreover, using cardiac magnetic resonance imaging, the authors showed that R2I2 correlates with the extent of the peri-infarct zone. In contrast, there was no correlation between R2I2 and either QT dispersion or T5 show potential utility of R2I2 for predicting arrhythmic events and warrant further investigation in a larger patient population. In addition, this pilot study raises, as does virtually every novel approach, several nontrivial research questions that deserve discussion.The pilot results reported by Nicolson et al9 introduced it as a measure of activation-independent repolarization heterogeneity. Composite, spatio-temporal descriptors of T-wave morphology in the form of T-wave vector loop and its dispersion have proved useful for VTA/SCD risk stratification after myocardial infarction.10First, we note that R2I2 is a composite index that incorporates both spatial heterogeneity across the 12 leads and restitution-related temporal features. Combining such disparate spatial and temporal features in a single index can be useful for summarizing the most important properties of a complex, multicomponent process in a simple form. This approach is often applied in computational biology and biophysics, despite a tradeoff associated with the difficulties of post hoc analysis, to discern the effect of each participating factor included in a composite metric. In electrocardiography, combining depolarization and repolarization properties in a single index  also has been used for several decades, since Wilson et alpeak (the period from S2 QRS onset to the S2 Tpeak) and TpeakQ (period from Tpeak on the last beat of the drive train to the S2 QRS onset) intervals as a surrogate marker of restitution have practical benefits. In most cases, the location of the T wave's peak on the surface ECG is easier to determine than the end of the T wave, which gradually merges with the isoelectric line, often obscured by noise and baseline wander.11 Selecting the peak of the T wave as a key fiducial point and analyzing the relationship between the QT12 However, the 2-dimensional space of QTpeak and TpeakQ intervals represents a significant departure from the traditional restitution relationship, expressing adaptation of the cardiac APD to changes in the diastolic interval. Indeed, the QTpeak interval entails both depolarization and the early part of repolarization, whereas the TpeakQ interval includes late repolarization and the entire ventricular diastolic interval. Thus, the slope of the relationship between the 2 intervals, utilized in the R2I2 index, is equivalent to a ratio (R):In each individual body-surface ECG lead, the location of the T-wave peak represents a combination of local  gradients and global (apex–base) effects. These locations are clustered around the mean repolarization time, which can be accurately determined by using the time of the T-wave peak on the root-mean-square curve.DRI indicates depolarization interval; ERI, early repolarization interval; LRI, late repolarization interval; and VDI, ventricular diastolic interval. Given that the repolarization interval is usually longer than depolarization and that changes in depolarization time are usually smaller than those in repolarization time, the R ratio could be influenced significantly by changes in T-wave symmetry and waveform pattern. As mentioned earlier, changes in T-wave morphology have been linked to the risk of VTA/SCD in patients with ischemic cardiomyopathy and prior myocardial infarction.10 Further complicating this conundrum, an upsurge in depolarization heterogeneity reported shortly before VTA initiation in patients with heart failure may affect the R ratio as well.2 It remains to be seen how the R2I2 index is affected by depolarization and conduction aberrations and how those changes can be differentiated from enhanced repolarization heterogeneity.where 5 appropriately point out that there is room for improvement and refinement of the R2I2 approach. Perhaps most important for making this method practically useful is the replacement of cardiac pacing by noninvasive maneuvers that can modulate heart rate . Another area for potential improvement that warrants further investigation is the incorporation of experimentally established indices of mean activation and recovery times .12 Hypothetically, this could pave the way for measuring mean repolarization time and quantifying the differences between the global mean and local peaks of the T wave in individual leads. This approach also could provide a validated measure of the global activation-recovery interval.12 Another area for future research is the potential use of the width of the T wave, which correlates with both ventricular dispersion and ischemia.8Nicolson et al13 QT variability,14 T-wave alternans,15 and the width of the T wave, which can be modulated by ischemia.7 It would be particularly interesting to compare the performance of R2I2 with second central moments, which recently have been described as quantifiers of spatial heterogeneity of cardiac depolarization and repolarization in the surface ECG, and which could predict the occurrence of arrhythmic events.2In addition, it will be important to investigate (1) stability of the R2I2 index over time in the same individual; (2) the impact of β-blockers and other medications; (3) the importance of individual differences in heart rate; and (4) the impact of changes in T-wave morphology, particularly its biphasic and notched forms, on the R2I2 behavior. It is also important to examine the effect of anatomic differences in the orientation of the electrical vector of the heart and the associated interlead differences in depolarization and repolarization vectors on the performance of the R2I2 index. Further research also is needed to identify the relationship between R2I2 and other ECG markers of arrhythmia risk, including rhythm instabilities,5 also show that inclusion of restitution properties in composite risk assessment leads to a qualitative improvement in the predictive accuracy as compared with QT dispersion, which by itself has not proved to be a consistent measure of repolarization heterogeneity or its dispersion.12 One can hypothesize that the lumped-parameter approach could be further extended by incorporating a more complete set of nonredundant, proarrhythmic instabilities of rhythm, depolarization, and repolarization, as described above. Adaptive approaches that use an individual's own data as a reference for personalized calibration might also contribute to the improvement of lumped-parameter risk stratification.13To summarize, the novel R2I2 index shows promise in identifying patients who are at risk for VTA/SCD. The authors are to be commended for introducing this innovative approach and conducting a small but well-designed feasibility study that included an independent test group. If the pilot results are replicated in larger studies, this approach may find a place among clinical tools for arrhythmia risk stratification. The data presented by Nicolson et alFinding an optimal combination of nonredundant features within a simple metric to create an accurate, practically useful test for arrhythmia risk stratification remains an open challenge. Because of the complexity and broad spectrum of underlying mechanisms of arrhythmogenesis, the number of possible parameters and their combinations may become prohibitively large for manual analysis. This is a good place and a good time to start thinking about computational methods of combinatorial optimization, which could lead us to further improvements in arrhythmia risk stratification.


P<0.001 for bPEP and PEP; r  = 0.850, P<0.001 for bET and ET; r = 0.708, P<0.001 for bPEP/bET and PEP/ET). The disagreement between brachial and echocardiographic STIs  was 28.55 ms for bPEP and PEP, -4.15 ms for bET and ET and -0.11 for bPEP/bET and PEP/ET. The areas under the curve for bPEP/bET and PEP/ET in the prediction of LVEF <50% were 0.771 and 0.765, respectively. Brachial STIs were good alternatives to STIs obtained from echocardiography and also helpful in prediction of LVEF <50%. Brachial STIs automatically obtained from an ABI-form device may be helpful for evaluation of left ventricular systolic dysfunction.Systolic time interval (STI) is an established noninvasive technique for the assessment of cardiac function. Brachial STIs can be automatically determined by an ankle-brachial index (ABI)-form device. The aims of this study are to evaluate whether the STIs measured from ABI-form device can represent those measured from echocardiography and to compare the diagnostic values of brachial and echocardiographic STIs in the prediction of left ventricular ejection fraction (LVEF) <50%. A total of 849 patients were included in the study. Brachial pre-ejection period (bPEP) and brachial ejection time (bET) were measured using an ABI-form device and pre-ejection period (PEP) and ejection time (ET) were measured from echocardiography. Agreement was assessed by correlation coefficient and Bland-Altman plot. Brachial STIs had a significant correlation with echocardiographic STIs (r = 0.644,  Systolic time interval (STI) is an established noninvasive technique for the quantitative assessment of cardiac performance and remains valuable for clinical application A clinical device, ABI-form , has been developed to automatically and simultaneously measure blood pressures in both arms and ankles and records pulse waves of the brachial and posterior tibial arteries using an automated oscillometric method. Using this device, we can easily and automatically calculate the brachial pre-ejection period (bPEP) and brachial ejection time (bET) by analyzing the signals of electrocardiogram, phonocardiogram and brachial pressure volume waveform Study subjects were randomly included from a group of patients who arranged for echocardiographic examinations at Kaohsiung Municipal Hsiao-Kang Hospital from April 2010 to October 2011 because of suspicion of coronary artery disease, heart failure, hypertension, abnormal cardiac physical examination, and so on. Patients with significant aortic or mitral valve disease, atrial fibrillation or inadequate image visualization (n = 43) were excluded. We did not include all patients consecutively because bPEP and bET must be measured within 5 min after the completion of an echocardiographic examination. A total of 849 patients  were included.The study protocol was approved by the institutional review board of the Kaohsiung Medical University Hospital (KMUH-IRB-20120157). Informed consents have been obtained in written form from patients and all clinical investigation was conducted according to the principles expressed in the Declaration of Helsinki. The patients gave consent for the publication of the clinical details.3– LVIDd3] –13.6 g 2 in men and more than 95 g/m2 in women, with LVRWT more than 0.42; eccentric LVH was defined as LVMI more than 115 g/m2 in men and more than 95 g/m2 in women, with LVRWT less than 0.42. The left atrial volume was measured by the biplane area–length method The echocardiographic examination was performed by one experienced cardiologist with a VIVID 7 , with the participant respiring quietly in the left decubitus position. The cardiologist was blind to the other data. Two-dimensional and two-dimensionally guided M-mode images were recorded from the standardized views. The Doppler sample volume was placed at the tips of the mitral leaflets to obtain the left ventricular inflow waveforms from the apical 4-chamber view. All sample volumes were positioned with ultrasonic beam alignment to flow. Pulsed tissue Doppler imaging was obtained with the sample volume placed at the lateral corner of the mitral annulus from the apical 4-chamber view. The wall filter settings were adjusted to exclude high-frequency signals and the gain was minimized. The echocardiographic measurements included left ventricular internal diameter in diastole (LVIDd), left ventricular posterior wall thickness in diastole (LVPWTd), interventricular septal wall thickness in diastole (IVSTd), E-wave deceleration time, transmitral E wave velocity (E), transmitral A wave velocity and early diastolic mitral velocity (Ea). Left ventricular systolic function was assessed by LVEF. Left ventricular mass was calculated using Devereux-modified method, i.e. left ventricular mass = 1.04 × [(IVSTd+LVIDd+LVPWTd)2) was measured from the onset of the QRS complex on the electrocardiogram to the first high-frequency vibrations of the aortic component of the second heart sound on the phonocardiogram. The bPEP was also automatically calculated by subtracting the bET from the QS2 . Bland-Altman plots were used to assess the agreements between brachial and echocardiographic STIs. The regression of the average and the difference between brachial and echocardiographic STIs  was analyzed. Receiver operating characteristic (ROC) curve was constructed for the prediction of LVEF <50%. A difference was considered significant if the P value was less than 0.05.Statistical analysis was performed using SPSS 15.0 for windows . Data are expressed as percentages or mean ± standard deviation. The differences in items between brachial and echocardiographic STIs were checked by paired Student’s There were 849 patients included in this study. The clinical characteristics of these patients were listed in P<0.001), respectively and those of bET and ET were 286.0±33.3 and 290.2±34.6 ms (P<0.001), respectively. Besides, the values of bPEP/bET and PEP/ET were 0.36±0.09 and 0.26±0.08 (P<0.001), respectively. The measurement time of bPEP/bET derived from 20 consecutive patients, starting from placement to removal of cuffs and electrodes, was 4.74±0.35 minutes and the cost was around $17 for each person.The values of bPEP and PEP were 101.6±17.9 and 73.1±16.4 ms (P<0.001) (A), bET and ET  (B) and bPEP/bET and PEP/ET  (C). To assess the agreement between brachial and echocardiographic STIs, Bland-Altman plots are produced  and PEP, 1/ET and PEP/ET (B) in the prediction of LVEF <50% are shown in P = 0.029), bET , ET , bPEP/bET  and PEP/ET , but not achieving significance with PEP . Because heart rate, a history of coronary artery disease and left ventricular systolic function might influence the STIs, we also further performed subgroup analyses of patients divided by median of heart rate (68 beats/min), a history of coronary artery disease and LVEF (50%). In a univariate correlation analysis, heart rate had a significant correlation with bPEP  but there was no difference between ET determined by the two methods (P>0.9). In our study, the bPEP overestimates PEP  and the bET underestimates ET . In this study, PEP+ET was measured from the onset of the QRS complex on the electrocardiogram to the end of LVOT systolic flow. However, bPEP+bET was equal to QS2, the onset of the QRS complex on the electrocardiogram to the first high-frequency vibrations of the aortic component of the second heart sound on the phonocardiogram. Hence, the bPEP+bET should be very close to the time interval measured from the onset of the QRS complex on the electrocardiogram to the end of “aortic” systolic flow. Because the end of aortic systolic flow was preceded by the end of LVOT systolic flow, the bPEP+bET was inherently longer than the PEP+ET. Furthermore, the bET was slightly shorter than the ET, so the bPEP was certainly longer than the PEP in the present study. In addition, the ET was measured from the onset to the end of LVOT systolic flow, but the bET was measured from the foot to the dicrotic notch of the pulse volume waveform. The different measurement methods and sites might be the possible explanation for the small difference between bET and ET. Although brachial and echocardiographic STIs were not the same, when compared to their counterparts, these parameters were all helpful and comparable in the prediction of impaired left ventricular systolic function.Cybulski et al. In the physiologic range, the PEP is less influenced by heart rate than ET Paiva et al. There are several limitations to this study. The majority of our patients were treated chronically with antihypertensive medications. For ethical reasons, we did not withdraw these medications. Hence, we could not exclude the influence of antihypertensive agents on the present findings. Besides, because the measurements of bPEP, bET, PEP and ET during atrial fibrillation were difficult because of beat-to-beat variation, we excluded patients with atrial fibrillation. Hence, our results could not be applied in these patients.In conclusion, the present study demonstrated that brachial STIs were good alternatives to STIs obtained from echocardiography. Although brachial and echocardiographic STIs were not the same, brachial STIs for identifying left ventricular systolic dysfunction were as good as the echocardiographic STIs. Hence, brachial STIs automatically obtained from an ABI-form device may be helpful for identification of patients with left ventricular systolic dysfunction.


Atelectasis is a major cause of hypoxemia after coronary artery bypass grafting (CABG) and is commonly ascribed to general anesthesia, high inspiratory oxygen concentration and cardiopulmonary bypass (CPB). The objective of this study was to evaluate the role of heart-induced pulmonary compression after CABG with CPB.Seventeen patients without pre-operative cardiac failure who were scheduled for coronary artery bypass graft underwent pre- and postoperative thoracic computed tomography. The cardiac mass, the pressure exerted on the lungs by the right and left heart and the fraction of collapsed lower lobe segments below and outside of the heart limits were evaluated on a computed tomography section 1 cm above the diaphragmatic cupola.−2 versus 3.2±1.2 g.cm−2, p<0.05) and left heart . The proportion of collapsed lung segments beneath the heart markedly increased [from 6.7% to 32.9% on the right side (p<0.001) and from 6.2% to 29% on the left side (p<0.001)], whereas the proportion of collapsed lung segments outside of the heart limits slightly increased [from 0.7% to 10.8% on the right side (p<0.001) and from 1.5% to 12.6% on the left side (p<0.001)].In the postoperative period, cardiac mass increased by 32% , leading to an increase in the pressure that was exerted on the lungs by the right (2.2±0.6 g.cmThe pressure that is exerted by the heart on the lungs increased postoperatively and contributed to the collapse of subjacent pulmonary segments. Atelectasis is a highly prevalent pulmonary complication in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) and an important cause of postoperative hypoxemia. Little is known about the contribution of heart-induced pulmonary compression to the development and perpetuation of dependent pulmonary atelectasis following cardiac surgery with CPB. In the supine position, large segments of the lower lobes are located beneath the heart In patients undergoing coronary artery bypass, systemic inflammatory response, positive fluid balance and cardiac wall edema may contribute to an increase in the weight of the heart, thereby augmenting heart-induced pulmonary compression. The objective of this study was to evaluate the contribution of the cardiac mass to postoperative atelectasis in patients undergoing coronary artery bypass grafting (CABG) with CPB.This study was approved by an institutional ethics committee , and informed consent was obtained from all participants after the study protocol was fully explained. Twenty patients who were scheduled for surgical treatment of coronary artery disease were included in this prospective study. All patients had normal preoperative left ventricular function, characterized by ejection fractions greater than 50%, and were submitted to pre- and postoperative whole-lung CT scans. Exclusion criteria were as follows: chronic obstructive pulmonary disease, preoperative pulmonary congestion, the need for any form of positive pressure ventilator support in the first postoperative day, transfusion of more than 3 packed red cell units and perioperative hemodynamic instability requiring vasopressors.−1; 2) respiratory rate to maintain PaCO2 values between 35 and 40 mmHg; 3) inspiratory time of 33% of the total respiratory cycle time; 4) inspired oxygen fraction of 0.6; and 5) positive end-expiratory pressure (PEEP) of 5 cmH2O.General anesthesia was induced with fentanyl, etomidate and atracurium and was maintained with isoflurane, fentanyl and pancuronium bromide. During the surgical procedure, patients were monitored with electrocardiography, capnography, pulse oximetry, esophageal temperature and an invasive arterial pressure line. After anesthesia induction, a fiberoptic thermodilution pulmonary artery catheter  was placed through the right internal jugular vein. Mechanical ventilator settings throughout the study were as follows: 1) tidal volume of 8 mL.kg−1 of heparin was administered intravenously. Aortic bi-caval CPB was performed using an extracorporeal circuit and a membrane oxygenator  that was primed with 1500 mL of lactated Ringer solution, mannitol 1 g.kg−1 and heparin 10,000 UI. Cardiac protection was achieved using hypokalemic, hypothermic blood cardioplegia solution. During CPB, mechanical ventilation was stopped. Coronary grafts were performed at the discretion of the surgeon. Vasoactive drugs were infused to facilitate CPB weaning according to the attending anesthesiologist’s decision. When mechanical ventilation was resumed at the end of CPB, a lung recruitment maneuver was performed using an airway pressure of 30 cmH2O, which was applied for 15 seconds. The aim was to fully re-expand the lungs that had collapsed following interruption of the mechanical ventilation and surgical manipulations.Before vascular cannulation, 400 U.kg−1 and maintain a PaO2>80 mm Hg at FiO2 0.4 and a spontaneous tidal volume >5 mL.kg−1. After extubation, oxygen was supplemented to the patients with a Venturi mask that delivered known oxygen concentrations. Postoperative pain was prevented by tramadol combined with morphine boluses whenever necessary. Non-invasive positive pressure ventilation was not used postoperatively. According to institutional standard care protocol, hemodynamic measurements, including analysis of the arterial and venous blood samples, were performed after intubation, after CPB, at ICU admission and 24 h after surgery. In addition, a baseline arterial blood sample was collected before anesthesia induction.In the intensive care unit (ICU), patients were allowed to wake up and were extubated as soon as they could spontaneously breathe with a respiratory rate <30.minDigital Imaging and Communications in Medicine (DICOM) images. Images were recorded in the hospital’s Picture Archiving and Communication System and were transferred to a personal computer for quantitative CT image analysis.On the day before surgery, a fast spiral thoracic CT scan  was obtained. Thoracic CT scanning was performed from the apex to the diaphragm, and the exposures were taken at 120 kV and 250 mAs. During image acquisition, the patients were asked to hold their breath at the end of a normal expiration for 15 to 20 seconds to acquire the volumetric CT images at functional residual capacity. To reach this specific respiratory condition, the patients were instructed about the respiratory hold maneuver and repeated it at least 10 times before thoracic CT scanning. During the entire procedure, electrocardiography, non-invasive arterial pressure and pulse oximetry were monitored using a Philips M3 transport monitor . A second CT was obtained in the same respiratory condition during the first postoperative day, approximately 24 h following admission in the ICU and extubation. All volumetric tomographic studies were reconstructed by the CT scan console as 10-mm-thick contiguous The sternovertebral distance, the maximal thoracic transverse distance and the left and right anteroposterior sagittal distances were measured using the caliper tool of a software program designed to analyze radiological DICOM images  in each individual 10-mm-thick CT section . Left an15,22 Briefly, after manually delineating the external boundaries of the left and right lung parenchyma using the Osiris software . All variables were tested for normal distribution using Kolmogorov-Smirnov, D’Agostino and Pearson omnibus normality and Shapiro-Wilk tests. Hemodynamic and metabolic measurements were examined over time using one-way analysis of variance for repeated measures. The overall cardiac mass, different pulmonary volumes and masses of the left and right lungs and the left and right lower lobe segments located beneath and outside of the heart protrusion limits were compared in the preoperative and postoperative CT images using a paired Student T test or the Wilcoxon matched-pairs signed-rank test when indicated. The cardiac and thoracic dimensions, the mass and the pressure exerted by the left and right cardiac protrusions on the subjacent pulmonary parenchyma were compared between pre- and postoperative moments using a two-way analysis of variance for repeated measures. Because the collapsed pulmonary parenchyma fraction was not normally distributed, the comparison between the lower lobe segments located beneath and outside of the heart protrusion limits during pre- and postoperative moments was performed using the Wilcoxon matched-pairs signed-rank test. The post-hoc analysis following the analysis of variances was performed using the Bonferroni method. The statistical analysis was performed using the SPSS 20 statistical package . All of the parametric data were expressed as means ± SD, unless otherwise specified. Boxplot whiskers were plotted according to the Tukey method. −1. min) was infused in 15 patients to facilitate CPB weaning and was stopped within 12 hours. In the first postoperative 24 hours, a mean volume of 1550±257 mL crystalloid solution was administered.From the 20 patients who were initially enrolled in the study, 3 were excluded due to the presence of respiratory motion artifacts on CT scans that rendered an accurate analysis impossible. Individual characteristics of the 17 patients who were enrolled in the study are presented in 2/FiO2 ratio that reached its nadir after CPB and returned to post-anesthesia conditions by the 24th postoperative hour, but it remained significantly lower than preoperative values  were measured on the CT section located 1 cm above the diaphragm . This de2 and 2.4±0.7 g.cm2, respectively). During the first postoperative day, the pressures that were exerted by the right and left cardiac protrusions on the lower lobes increased by 45% and 75%, respectively (p<0.05). The cardiac protrusion-induced pressure was significantly greater in the left than in the right side. As shown in As displayed in This study describes several original findings: (1) CABG with CPB induced a 5-fold increase in collapsed lung parenchyma, accounting for 38% and 42% of the preoperative masses of the right and left lungs, respectively; (2) concomitantly, gas volumes of the right and left lungs decreased by 32% and 28%, respectively, whereas tissue volumes increased by 47% and 59%; (3) following surgery, the masses of the right and left heart increased by 22% and 34%, respectively, significantly increasing the orthogonal pressure exerted on subjacent lower lobes; (4) the fractions of atelectasis increased by 22% in lung segments located beneath the right cardiac chambers and by 6% in lung segments outside of the right heart limits; (5) the fractions of atelectasis increased by 17% in lung segments located beneath the left ventricle and by 5% in lung segments outside of the left heart limits; and (6) postoperative changes in lung morphology were associated with a 27% decrease in arterial oxygenation.Immediate postoperative reduction of pulmonary aeration leading to hypoxemia is a highly prevalent pulmonary complication in patients undergoing CABG with CPB Most of the previous CT studies on pulmonary alterations after CABG focused on the amount of postoperative atelectasis, ignoring postoperative alterations affecting pulmonary structures and intrathoracic organs that are anatomically related to the lungs. Recently, we reported that pulmonary tissue mass significantly increased during the postoperative period due to the accumulation of lung water in the interstitial space. The excess of lung mass that is related to CPB-induced high-permeability interstitial lung edema If the excess lung tissue mass largely contributes to the vertical gradient of pulmonary aeration, it does not explain why the fraction of collapsed lung is greater in the lower lobe segments located beneath the heart than in the segments located outside of the cardiac limits. In fact, both areas are subjected to the same transpulmonary pressure and should be characterized by similar aeration. Physiologically, the pressure that is exerted by the heart on the lower lobes impacts regional aeration. Two main mechanisms may explain the increase in cardiac mass after CABG. First, per-operative fluid loading increases both the volumes of the cardiac chambers and the cardiac index during the postoperative period. During the study period, patients received 6686 mL to compensate for fluid restriction that resulted from preoperative fasting and priming of the CPB circuit. Second, CPB and myocyte ischemia, resulting from cardioplegic arrest, induce an inflammatory reaction that increases microvascular permeability, impair myocardial lymphatic function and produce lung and myocardial interstitial edema. Some factors may introduce bias and reduce the accuracy of the CT assessment of lung aeration, heart mass and cardiac dimensions. The moment of the respiratory cycle at which the patient holds their breath determines the amount of gas present within the lungs during CT section acquisition and may impact the assessment of lung aeration. To avoid respiratory motion artifacts and changes in lung aeration resulting from CT acquisition at different lung volumes, patients were preoperatively trained to hold their breath for 15 seconds after a normal expiration. However, 3 patients breathed during postoperative CT section acquisition, rendering the analysis of the lung aeration changes impossible. Reproducible conditions of CT acquisition between pre- and postoperative periods are indirectly confirmed by the unchanged antero-posterior, sagittal and transverse dimensions of the rib cage before and after surgery.Another source of error concerns the method that was used to calculate the pressure that is exerted by the heart on the lower lobes. Cardiac protrusion mass was divided by the subjacent linear surface that delimited the upper limit of the lung segments beneath the heart. This method of calculating cardiac superimposed pressure is rough and ignores non-orthogonal forces exerted by the heart on the pulmonary surface. The method also ignores the influence of the heart beats on lung compression. Cardiac dimensions and masses that are reported in this study were measured at different moments of the cardiac cycle and are representative of “mean” values across the cardiac cycle. As a consequence, the respiratory effects of cardiogenic oscillations and their impacts on lung aeration cannot be taken into account Lastly, the studied population comprised uncomplicated, spontaneously breathing patients who were free of ARDS or abdominal complications. It is highly likely that the presence of such complications would have amplified the loss of lung aeration resulting from cardiac compression, as previously demonstrated In conclusion, following CABG, the pressure that is exerted by the heart on subjacent lung segments increases and is an important cause of the regional loss of aeration in lower lobes. This finding explains why, despite the disappearance of several factors known to induce atelectasis during anesthesia and surgery, lung collapse and hypoxemia persist for several days during the postoperative period. Further studies are necessary to assess whether maintaining the patient in a strict, half-sitting position early during the postoperative period would improve postoperative lung aeration.


TMAD provides the possibility for the assessment of global systolic longitudinal function in patients with STEMI and correlates well with the extent of myocardial infarction, determined by LGE-CMR. TMAD is a novel, ultra-fast, sensitive and easily reproducible parameter and therefore a valuable predictor for the extent of myocardial infarction. Further prospective studies have to be conducted to test TMAD as a promising tool for clinical routine.In clinical routine, fast assessment of infarct size is crucial for accurate early risk assessment. Global left ventricular (LV) longitudinal strain is associated with infarct size and outcome. The measurement of global longitudinal function is often dependent on image quality, experience of the observer and it is time-consuming. We investigated global systolic LV longitudinal function with TMAD (tissue motion annular displacement), a novel method based on a 2-D strain tissue tracking algorithm, and compared it with contrast-enhanced magnetic resonance imaging (CMR). The aim of the study was to investigate whether TMAD is able to diagnose LV infarct size early after successful revascularization in patients with first acute ST-segment elevation myocardial infarction (STEMI).Twenty-one patients underwent CMR and trans-thoracic echocardiography 3 ± 1 day after successfully reperfused STEMI. On a whole-body 1.5T 32 channel MRI system (Philips Achieva), vector ECG-gated short axis, 2-3-4 chamber SSFP cine images as well as late gadolinium enhancement CMR (LGE-CMR) in similar planes were acquired using a standard inversion-recovery sequence. TMAD was measured by standard transthoracic echocardiography (GE vivid 7000). Serological markers for infarction  were measured from plasma samples.There was a high correlation for the percentage of LGE-CMR infarcted LV  as well as absolute LV infarct mass  with TMAD. TMAD also showed a significant correlation with serological markers . Time for analysis of TMAD was less than 15sec. The intra- and inter-observer variability for TMAD was very low (1.4 ± 1.1 % and 1.8 ± 1.3 %).TMAD provides the possibility for the assessment of global systolic longitudinal function in patients with STEMI and correlates well with the extent of myocardial infarction, determined by LGE-CMR. TMAD is a novel, ultra-fast, sensitive and easily reproducible parameter and therefore a valuable predictor for the extent of myocardial infarction. Further prospective studies have to be conducted to test TMAD as a promising tool for clinical routine.No funding.


The relationship between Tei Index (TI) and left ventricular (LV) geometric patterns has not been previously well described. The present study therefore set out to describe the nature of this relationship if any, and to also assess whether a relationship exists between the geometric patterns and LV ejection fraction (LVEF) so as to establish a basis for comparison.The study was carried out in the echocardiography laboratory of Aminu Kano Teaching Hospital (AKTH) in Kano, North-Western Nigeria. The study was cross-sectional in design. Hypertensive subjects referred for echocardiography to AKTH were serially recruited from October 2008 to September 2009. TI was defined as the sum of isovolumic contraction and relaxation times divided by the ejection time, and values of LV TI < 0.40 were considered normal, while higher values were considered abnormal. Four patterns of LV geometry  were determined from the LV mass index and LV relative wall thickness as previously described. Binary logistic regression models and Pearson's Correlation (r) Coefficient were used to analyse the associations between TI or LVEF and a number of variables.A total of 142 subjects were recruited into the study. The prevalence of abnormal TI  in the total population was lower than that of reduced LV ejection fraction (< 50%)  (p = 0.335). There was no association between any LV geometric pattern and abnormal TI. However, there was significant relationship between the geometric patterns and low LVEF (< 50%); tested in a binary logistic regression model. HR was a significant predictor of TI with regression coefficient of -0.218, 95% confidence interval (CI) of -0.005 - < -0.001 and p-value of 0.011. Similarly, HR was the only variable that significantly predicted abnormal TI in a binary logistic regression model with an odds ratio of 1.058 , and also the only variable that correlated with TI significantly .This study has found that LV geometric patterns and LVEF were not associated with TI in hypertensives, but there was strong association between LV geometric patterns and LVEF. TI was found to be dependent on HR. Myocardial Performance Index or Tei Index (TI) was first described by Tei and Colleagues in 1995 as a "simple and reproducible Doppler index of combined systolic and diastolic myocardial performance in patients with primary myocardial systolic dysfunction" ,3. TI isThe study was carried out in the echocardiography laboratory of Aminu Kano Teaching Hospital (AKTH) in Kano, North-Western Nigeria.The Research Ethics Committee of the Hospital reviewed and approved the study protocol, which conformed to the ethical guidelines of the Declaration of Helsinki, on the principles for medical research involving human subjects . The stuAll the recruited subjects were hypertensive in sinus rhythm and on treatment, whether or not blood pressure (BP) was controlled. Subjects with other conditions that could cause LVH or myocardial diseases were excluded, such as ischemic heart disease (IHD), valvular heart disease and cor-pulmonale. IHD was excluded if all of the following were absent: history of angina or IHD, electrocardiographic changes suggestive of myocardial infarction, and regional wall motion abnormalities on echocardiography.Transthoracic echocardiography was performed by the author and Colleagues using Aloka Cardiac Ultrasound System (model SSD 4000 PHD), and the procedures were carried out according to standard guidelines . Left veIn adults, values of LV TI < 0.40 were considered normal, while higher values were considered abnormal, as they were found to correspond to worse pathological states, and to overall cardiac dysfunction .2 for all subjects [The four patterns of LV geometry were classified and defined as: normal geometry  and LVMI); concentric remodelling ; concentric LVH (increased LV RWT and LVMI); and eccentric LVH . RWT was calculated as: RWT = 2/LV end-diastolic dimension . Increassubjects .t-test, Fisher's exact and Chi square (χ2) tests were used for comparison between groups as appropriate. Binary logistic regression models, and Pearson's Correlation (r) Coefficient, were used to analyse the associations between TI or LVEF and a number of variables. A p-value < 0.05 was regarded as significant.Data were analysed with SPSS version 16.0. Means and standard deviations were computed and presented for quantitative variables. Student's A total of 142 subjects were recruited into the study, and the results presented in Tables The result also showed that there was no association between any LV geometric pattern and abnormal TI. There was also no relationship between LVH (eccentric LVH + concentric LVH) and abnormal TI . This result contrasts significantly with the relationship between the geometric patterns and reduced LVEF (< 50%); tested in a binary logistic regression model and shown in Table Subjects with normal and increased TI were on similar antihypertensive drugs, including angiotensin converting enzyme inhibitors, angiotensin II receptor blockers, beta-adrenoceptor blockers, calcium channel blockers and thiazide diuretics. The mean systolic BP for all patients was 155.22 ± 29.83 mmHg, while their mean diastolic BP was 94.74 ± 20.13 mmHg.This study has found that LV geometric patterns as defined by Ganau et al , LVH andWe also found that TI was dependent on HR, which does not agree with some earlier reports that suggested that TI is independent of HR . That TIA cross-sectional study carried out in Osogbo, south-western Nigeria, has just been published . The maiFrom the foregoing therefore, it could be said that there are conflicting reports on the relationship between TI and clinical and echocardiographic variables. To sort out these conflicts, large prospective studies are needed which should also assess the impact of TI on all-cause and cardiovascular mortality.Aside from the estimation of TI, tissue Doppler imaging has several other clinically-applicable roles. These include assessment of ventricular diastolic dysfunction even in the presence of atrial fibrillation, diagnosis of acute myocardial ischemia, ventricular long-axis systolic function, and more recently in assessing mechanical ventricular dyssynchrony -19.The limitations of the present study include those inherent to the TI, such as This study has found that LV geometric patterns, LVH and LVEF were not associated with TI in hypertensives, but there were strong relationships between all LV geometric patterns and LVEF. The lack or existence of a relationship between TI or LVEF respectively, and LV morphology, could possibly be related to whether or not they depend on LV dimensions in their determination. In addition, the study found that TI was dependent on HR, in agreement with some earlier reports. The results of the present study have further clarified the relationship between a measure of ventricular performance (TI) and LV geometric patterns, as well as their relationships with LVEF.The author declares that they have no competing interests.The author (KMK) conceived and carried out the study, analysed data, and wrote and approved the manuscript.


Despite inclusion in the diagnostic criteria for arrhythmogenic right ventricular cardiomyopathy, this study of 87 consecutive patients with isolated frequent LBBB-morphology PVCs and high PVC burden (mean 19%) demonstrated only a rare association with CMR diagnostic criteria for ARVC, no cases of ARVC diagnosis, no association of minor wall motion abnormalities (hypokinesis) with markers of ARVC, and no cardiac events in follow-up. Interestingly, however, RV dilation was very common and paralleled LV dilation.Frequent premature ventricular contractractions (PVCs) is typically a benign disorder, but has become a common indication for cardiac magnetic resonance imaging (CMR) due to inclusion in diagnostic criteria for arrhythmogenic right ventricular cardiomyopathy (ARVC). A recent study also suggested a worse prognosis in these patients associated with findings on CMR. The purpose of this study was to correlate CMR data with electrophysiology study (EP) findings and clinical outcomes in patients with frequent PVCs.We studied 87 consecutive patients referred for catheter ablation of isolated frequent left bundle branch block morphology PVCs. The 2010 ARVC Task Force criteria were used to define major and minor criteria for ARVC. The CMR exam included steady-state free precession imaging for wall motion and volume/function quantification and black blood imaging for fatty infiltration. Major RV wall motion abnormalities (WMA) were defined by akinesis, dyskinesis, or dyssynchrony, while minor wall motion abnormalities were defined by hypokinesis. The EP study included program stimulation for inducibility of VT and either activation or pace mapping for determination of PVC origin.2=0.69, see Figure). RV dysfunction was present in 34 (39%). During a median follow-up of 16  months, no syncope, VT, heart failure, or sudden death was documented.The mean PVC burden was 19 + 13%, and no patients had a history of syncope or family history of early sudden death. 15 patients met a minor (10) or major (5) Task Force criterion for ARVC by EKG. Major WMAs by CMR were present in 2 (2%) of patients, but only 1 of these had RV dilation and the PVCs in this case mapped to the left ventricle. No patients met full diagnostic criteria for ARVC. Hypokinetic segments were present in 7 patients, but did not correlate with EKG criteria for ARVC (p=0.41), NSVT on 24-hour EKG (p=0.51), RV dilation (p=0.43), RV fatty infiltration (p=1.0), inducibility of VT (p=1.0), or RV versus LV site of origin of the PVC (p=0.67). RV dilation was present in 74 (84%) patients, and correlated with LV dilation (RDespite frequent RV dilation that paralleled LV dilation, other CMR findings diagnostic of ARVC in patients with isolated LBBB-morphology PVCs are rare. Hypokinetic segments do not correlate with EKG criteria for ARVC, NSVT, RV dilation, fatty infiltration, inducible VT, or site of origin of the PVC. Frequent PVCs were associated with a benign clinical course, regardless of the presence of RV dilation or hypokinetic segments.None.