The aetiology and clinical significance of troponin release following endurance exercise is unclear but may be due to transient myocardial inflammation. Cardiovascular magnetic resonance (CMR) affords us the opportunity to evaluate the presence of myocardial inflammation and focal fibrosis and is the ideal imaging modality to study this hypothesis. We sought to correlate the relationship between acute bouts of ultra endurance exercise leading to cardiac biomarkers elevation and the presence of myocardial inflammation and fibrosis using CMR.17 recreation athletes (33.5 +/- 6.5 years) were studied before and after a marathon run with troponin, NTproBNP, and CMR. Specific imaging parameters to look for inflammation included T2 weighted images, and T1 weighted spin-echo images before and after an intravenous gadolinium-DTPA to detect myocardial hyperemia secondary to inflammation. Late gadolinium imaging was performed (LGE) to detect any focal regions of replacement fibrosis.Eleven of the 17 participant had elevations of TnI above levels of cut off for myocardial infarction 6 hrs after the marathon . Left ventricular volumes were reduced post marathon and a small increase in ejection fraction was noted . Right ventricular volumes, stroke volume, and ejection fraction were unchanged post marathon. No athlete fulfilled criteria for myocardial inflammation based on current criteria. No regions of focal fibrosis were seen in any of the participants.Exercise induced cardiac biomarker release is not associated with any functional changes by CMR or any detectable myocardial inflammation or fibrosis. Acute bouts of ultra-endurance exercise may depress global left ventricular (LV) diastolic and systolic function and in the majority of cases this is associated with elevations in circulating serum markers of cardiac damage, including troponin T and I, myoglobin, creatine kinase (CK), CK-MB, and brain natriuretic peptide (BNP) -5. DebatCardiovascular magnetic resonance (CMR) is the reference standard imaging modality for the assessment of ventricular volumes, function, and mass. Measurements are accurate with no geometrical assumptions about the ventricle and very reproducible ,11. UsinWe sought to assess the potential relationship between acute bouts of ultra endurance exercise leading to troponin release and the presence of myocardial inflammation and fibrosis using CMR.We studied 17 recreational athletes before and after a marathon run (26.2 miles). Exclusion criteria included the presence of pre-existing cardiovascular or pulmonary diseases, hypertension, diabetes, and peripheral vascular diseases. No participant had taken part in any significant endurance event in the preceding 12 weeks. Cardiac biomarkers  were collected at an initial assessment 24 hrs prior to, immediately after completion of the marathon, and again 6 hours later. Post marathon CMR was performed 6 hours after marathon completion. This time point was chosen based on an assumption that 6 hours would allow a sufficient amount of time for inflammation to develop and be detectable, corresponding with the time when TnI is typically detectable in ischaemic models representing the liberation of these proteins and enzymes from damaged myocytes . Each paAnalysis of cTnI was determined using the TnI-Ultra assay for the ADVIA Centaur . The detection limit of the instrument was 0.006 μg/L, upper limit of 50 μg/L. The claimed 10% CV was 0.03 μg/L with a 99th centile of 0.04 μg/L. The total assay imprecision was 2.7 to 5.3% in the range 0.8 to 27.2 μg/L. NTproBNP was analysed using the Elecsys 2010 system . The assay is an electrochemiluminescent sandwich immunoassay that uses two polyclonal antibodies directed at residues 1-21 and 39-50 of the NTproBNP molecule. The %CV of the assay is 3.2-2.4% from 20.7-585.5 pmol/L (175-4962 ng/L) with an analytical range of 0.6-4138.6 pmol/L .CMR data was collected 24 hrs pre- and 6 hrs post-marathon. A standard volumes and LGE sequence was performed on a dedicated scanner , with full myocardial coverage using an 8-channel phased array coil . VentricTwo CMR validated methods to image myocardial inflammation were performed.Focal regions of myocardial oedema/inflammation typically appear bright on T2-weighted imaging. Imaging was performed using a breath hold, black blood, T2 weighted triple inversion recovery TSE sequence (STIR)  in identical SA slices from base to apex. Typical slice thickness was 8 mm, 2 mm gap, and the FOV was adapted per patient. Regional oedema was identified visually. Global oedema is not recognisable to the naked eye, and quantitative analysis was performed by normalising the signal intensity of the myocardium to that of skeletal muscle . Endocardial and epicardial contours were manually drawn and a region within a skeletal muscle was defined in the same slice. The T2 ratio is calculated as follows:A value of > 1.9 was considered diagnostic of global myocardial oedema/inflammation .Regional vasodilatation occurs in areas of tissue inflammation and the increased blood volumes in these areas leads to an increased uptake of gadolinium contrast agents during the early vascular phase. To assess this, we performed T1 weighted spin-echo images before and after an intravenous gadolinium-DTPA infusion   in a single mid ventricular short axis slice with a wide field of view to include a substantial portion of skeletal muscle . Imaging was performed within 1 minute of injection and repeated every 30 seconds for 3 minutes. We measured the SI of the myocardium before and after contrast and also SI of neighbouring skeletal muscle. The Early Enhancement or relative gadolinium enhancement (rGE) ratio is calculated by the following formula:This was deemed to be positive if the ratio was > 4.0The enhancement of myocardium and skeletal muscle regions of interest being used for the formula above are calculated by:The ratio of SI increase before and after contrast for myocardium was deemed to be positive for hyperaemia if % SI myocardial increase was > 45% between pre and post contrast images using commercially available software  .2 was defined within the normal, remote myocardium in an area with uniform myocardial suppression free of artefacts. A multi-pass region-growing algorithm was used to identify the fibrotic boundaries based on the "full width half maximum" technique and myocardial LGE was expressed as present/absent , as gram mass, and a percentage of total LV mass [Imaging for late gadolinium enhancement (LGE) to identify fibrosis was performed 5-10 min after contrast injection in identical short-axis planes to cine images using a breath hold inversion-recovery (FLASH) gradient echo sequence . Inversi LV mass -26.All data values were presented as mean ± SD. Changes from pre-marathon to post-marathon were analysed using paired t-tests. Relationships between data indices CMR measures of systolic function against serum biomarkers of cardiac damage were examined via Pearson's product-moment correlation analysis. The critical α level was set at 0.05 and all analyses were carried out on SPSS 16.0 software.The participants included 17 men . The mean number of hours trained per week was 7 hours. All 17 runners completed the study protocol , Table No participant had elevations of TnI or NTproBNP at baseline. Eight participants were found to have cTnI elevations immediately post-marathon above the cut off level for acute myocardial infarction  and a corresponding small increase in LV EF 6 hrs post-marathon reached significance , Table No significant correlations between biomarkers of cardiac damage (cTnI and NTproBNP) at any of the time points and measures of CMR systolic function, inflammation, hyperemia, or myocardial fibrosis were found.This study demonstrates that exercise induced cardiac biomarker release is not associated with changes in biventricular systolic function or indeed any detectable myocardial damage  using current gold standard imaging modalities. The release of cardiac troponins (cTnT and cTnI) following prolonged exercise has been extensively documented and the high prevalence of cTnI and NTproBNP release following endurance exercise in this cohort is consistent with previous endurance studies -5. The rThe aetiology and clinical significance of post-exercise troponin release is yet to be elucidated. Shave et al. suggested that post-exercise release of troponin may represent either necrosis of cardiac myocytes leading to irreversible damage, or may be a transient and reversible change in membrane permeability of the myocyte . The mecA significant elevation in CMR EF was observed 6 hrs post-marathon, with no change in SV. This data contrasts with recent data that demonstrates persistent RV dysfunction post endurance exercise but is in agreement with the work of others -32. In oLike many studies of this type, the numbers our cohort studied are small and the findings may not necessarily be applicable to larger populations. The spatial resolution of the CMR technique may also be insufficient to image small focal areas of myocardial inflammation or scarring caused by subclinical myocyte damage. We chose a 6 hour time point to perform the post marathon CMR and this may have influenced our findings. It is possible that changes in inflammation may not be detectable until after 6 hours but it was reassuring that 4 participants that returned within 4 days for a repeat CMR were not found to have any demonstrable structural or functional changes. The ratio used to evaluate myocardial oedema and hyperaemia was similar to that used in the Lake Louise criteria although we acknowledge that there were some differences in the protocol used with regard to the slice thickness. Work from our group suggests that this does not significantly alter the interpretation.This study showed that cardiac biomarkers suggestive of myocyte damage are elevated after a marathon, but these elevations are not associated with any detectable myocardial damage or acute changes in left or right ventricular function. Biomarkers of myocardial cell damage following an acute bout of prolonged exercise are not associated with functional changes using CMR and do not seem to be associated with any detectable myocardial inflammation, oedema, or scarring. This investigation provides further evidence for the careful consideration in assessing and treating symptomatic athletes following arduous exercise in the presence of elevated cardiac troponins and ECG anomalies.CMR: Cardiovascular magnetic resonance; LV: left ventricle; BNP: Brain natriuretic peptide; CK: creatine kinase; CK-MB: creatine kinase-MB subunit; cTnI: cardiac troponin I; NT-proBNP: N-terminal brain natriuretic peptide; TSE: turbo spin secho; TR: repetition time; TE: echo time; RR: r-r interval; TI: inversion time; SA: short axis; FOV: field of view; LGE: late gadolinium enhancement; FLASH: fast low angle shot; ROI: region of interest; EF: ejection fraction; RV: right ventricle; STIR: short-tau inversion recovery; rGE: relative gadolinium enhancementDr Pennell is a consultant to, and receives research support from Siemens. DR Pennell is a director of Cardiovascular Imaging Solutions. All other authors declared that they have no competing interests.GW, SKP and RO'H conceived the study, MW, GW, RO'H and SKP helped plan and design the study, MW, GW, RO'H, DJP, SP, DO, DG and RG collected the data, ROH, MW, GW, FA, and JW analysed the data, ROH and MW wrote the preliminary draft of the manuscript and all authors supplied comments and corrections, ROH and SKP are the guarantors. All authors read and approved the final manuscript.


The Fontan circulation results from routing of the systemic venous blood to the pulmonary circulation without a hydraulic source of a ventricle. Although a hypertrophied right atrium was thought to be essential for this circulation, the current form of the operation has neither the right atrium nor any valves in the venous circulation that is connected to the pulmonary arteries directly. Modifications in the operative model was one of the early steps in improving outcome. Use of fenestration, staging of Fontan completion and better perioperative management have led to a significant drop in mortality rates in the current era. Despite this, there is late attrition of patients with complications such as arrhythmias, ventricular dysfunction, and unusual clinical syndromes of protein-losing enteropathy (PLE) and plastic bronchitis. Management of failing Fontan includes a detailed hemodynamic and imaging assessment to treat any correctable lesions such as obstruction within the Fontan circuit, early control of arrhythmia and maintenance of sinus rhythm, symptomatic treatment for PLE and plastic bronchitis, manipulation of systemic and pulmonary vascular resistance, and Fontan conversion of less favorable atriopulmonary connection to extra-cardiac total cavopulmonary connection with arrythmia surgery. Cardiac transplantation remains the only successful definitive palliation in the failing Fontan patients. We have entered the fourth decade after the first clinical report by Fontan and Baudet, of an operation for ‘surgical repair of tricuspid atresia’.Although the title implied a definitive and corrective operation, the basic principles of right heart bypass were expanded from the early reports in animal experiments by Rodbard and Wagner, and by Many people have quoted and referenced the original report by Fontan and Baudet, but few may realize some of the concepts tried by the pioneers of the Fontan circulation.All patients in the first series had tricuspid atresia, as they believed that ‘ventricularization’ of a hypertrophied right atrium in this morphological substrate would be adequate to support the pulmonary circulation. The atrium in the atriopulmonary connection was, in fact, thought to be a worthy substitute for a dimunitive right ventricle. In the first report, of the tThere are a few other pearls of wisdom from the pioneering report. The need for ‘large fluid infusions’ and to ‘maintain tachycardia’ for ‘correct hemodynamic balance’ was recognized in the early postoperative period. Detrimental effect of positive-pressure ventilation on the venous return was also indentified and early extubation recommended. The unpredictable hemodynamics resulting from atrial arrhthymias such as flutter or fibrillation was also recognized.In one sentence, the authors encompass the criteria for suitability thus, “patients were anatomically and haemodynamically privileged; they had pulmonary arteries of normal size and low pressure”.The basic principles of right heart bypass opened up a novel option for patients with a single dominant ventricle, be it left or right, and for patients with intracardiac mixing where septation of the atria or ventricles could not be achieved.The Fontan circulation, rather than the ‘Fontan operation’, thus, became the final step in surgical treatment of single dominant ventricle circulation.Early evolution of the Fontan operation involved modifications in achieving the cavopulmonary connection. The premise that a pulsatile chamber, namely the right atrium, is essential to propel blood into the pulmonary circulation was questioned. In a series of elegant experiments, de Leval and colleagues elucidated the detrimental effects of a pulsatile valveless right atrium in the cavopulmonary circuit. Instead of providing power, it contributed to turbulence, energy loss, and increased resistance to net forward flow. They proposed a hydrodynamically more efficient total cavopulmonary connection that proThe use of extracardiac conduits of biological or prosthetic tubes was the next step to exclude the right atrium from the venous rerouting. The total cavopulmonary connection is generally achieved with a low mortality in most centers. As the long-term complications of atriopulmonary connection were obvious during the late 1980s and early 1990s, the total cavopulmonary connection by various techniques was generally accepted as the final design of the Fontan circulation.The introduction of fenestration of the Fontan circuit–16 creatThe staging of cavopulmonary connection with introduction of an intermediary step of a hemi-Fontan or the bidirectional Glenn operation (superior cavopulmonary anastomosis) with its advantage of early volume reduction, further improved results and expanded the case selection to include some of the high-risk patients, by the then conventional indications.–24Although first described for tricuspid atresia, the Fontan circulation has been applied to a wide spectrum of complex congenital heart disease with a dominant single ventricle. Improvement in surgical techniques, improved understanding of perioperative physiology, and better selection and modification of the high-risk factors led to better results. In the early era of Fontan operation, mortality in large reported series was between 17–31%, compared26During this period of change, apart from the operative techniques and perioperative management, the timing of intervention and emphasis on Fontan ‘preparation’ have contributed significantly to this improvement in outcome. In an interesting single institutional analysis, there was no difference in the risk factors and patient characteristics between a higher and lower mortality-risk era, indicating that differing interventions and changing treatment algorithms along with some other factors such as use of modified ultrafiltration after bypass and the use of extracardiac conduits contributed to the improvement.More recently, the National Heart Lung and Blood Institute funded Pediatric Heart Network designed a cross-sectional study of children aged 6–18 years, from seven pediatric clinical centers, who had undergone a Fontan procedure as treatment for congenital heart disease. The aim It should not have been a surprise when Fontan and colleagues warned of late attrition after what was deemed to be a ‘perfect’ Fontan circulation. The esseVarious attempts have been made to delay the onset of failing Fontan circulation based on the pathophysiology of clinical syndromes that manifest in its failure.The superior and inferior caval veins are exposed to a higher pressure that generates the energy for pulmonary perfusion in absence of a hydraulic force, namely, the right ventricle. The Fontan circulation introduces a paradox of systemic venous hypertension (mean pressure > 10 mm Hg) and pulmonary arterial hypotension (mean pressure < 15 mm Hg), a step-down in the pressure as opposed to the normal step-up introduced by interposition of right ventricle, in a normal biventricular circulation.Systemic venous hypertension has detrimental effects on the infradiaphragmatic venous circulation, and more importantly the splanchnic circulation, due to the additional negative effect of gravity. There is loss of the hepatic venous pressure gradient due to passive distension and ‘open tube’ phenomenon, and the pressure is transmitted to the portal venous system leading to portal venous hypertension.34The splanchnic venous hypertension contributes to protein-losing enteropathy (PLE), albeit, not being its sole cause. Altered flow in the gut vasculature, low cardiac output state, persistent hypoxia, and inflammation are the other contributors.The dominant systemic ventricle may be of right ventricular or indeterminate morphology with unfavorable fiber arrangement that is mechanically inefficient to sustain systemic cardiac output. On this morphological substrate, additional loading insults before establishment of Fontan circulation predispose the systemic ventricle to fail. Volume overload related to systemic to pulmonary artery shunt or pulmonary artery band that is obligatory after early palliation, valvular regurgitation from the systemic atrioventricular or semi-lunar valves, or pressure overload related to suboptimal systemic outflow tract hemodynamics  all act as early determinants of the failing ventricle.From a volume overloaded, dilated, and hypertrophied ventricle, the superior cavopulmonary connection and finally the Fontan completion expose the systemic ventricle to volume unloading at suboptimal preloads. Following total right heart bypass, the preload of the systemic ventricle is reduced to 25–70% with respect to the ventricular size. This leads to systolic and diastolic dysfunction and myocardial dys-synchrony. Chronic Pulmonary vascular resistance (PVR) becomes an important determinant of cardiac output in the Fontan circulation where the systemic circulation is in series with the pulmonary circulation without an intervening hydraulic source of energy (viz. right ventricle).The pulmonary arteries may be morphologically abnormal, small, discontinuous, stenosed, or have abnormal arborization. The branch pulmonary arteries may be distorted during restriction of blood flow  or augmentation of flow . Ductal tissue could lead to coarctation of the branch pulmonary artery.The pulmonary venous drainage, if anomalous, particularly with isomerism, has a higher potential of being obstructive leading to altered pulmonary arteriolar growth and potentially elevated pulmonary arteriolar resistance.Even with morphologically ‘normal’ pulmonary arteries, a dominant single ventricle circulation exposes the pulmonary vasculature to different periods of too much or too little flow. The absence of pulsatile flow and a low pulmonary artery mean pressure underfills the pulmonary vascular bed and effectively increases PVR. Pulsatile flow is important for shear-stress-mediated release of endothelium-derived nitric oxide (NO) and for recruitment of pulmonary capillaries and to maintain their patency. The systolic pressure rise not only recruits the capillary bed and lengthens the capillaries but also keeps them open during diastole. After total cavopulmonary connection, there is loss of pulsatility in the pulmonary arterioles and capillaries with less recruitment of the pulmonary vascular bed. A chroniStasis, polycythemia due to chronic cyanosis, and abnormal coagulation profile in patients with Fontan circulation predispose them to increased incidence of pulmonary thromboembolism. Silent thromboembolic episodes have been documented in adults with Fontan circulation during late follow-up. However, there is no clear evidence that anticoagulation prevents thromboembolism in failing Fontan, or that in a hemodynamically stable circulation, routine anticoagulation is necessary to prevent morbidity and mortality.Collateral circulation through bronchial and other vessels remains a hidden unaccounted source of pulmonary blood flow that is difficult to quantify. AlthoughHistorically, chronic passive congestion in the systemic venous circuit, such as in chronic heart failure or constrictive pericarditis has manifested in lymphatic dysfunction with pleural or peritoneal leaks or leak from the gastrointestinal system.High systemic venous pressure is the essence of the Fontan paradox where a higher than normal systemic venous pressure is necessary to maintain pulmonary blood flow. In failing Fontan, this systemic venous hypertension is transmitted to the venous and the lymphatic circulation. The true impact on the lymphatic system has not been fully understood due to the difficulties in imaging lymphatics.PLE is an unusual manifestation of failing Fontan circulation with an unknown etiology. Its true prevalence may never be known as the protein loss from gastrointestinal tract probably starts at subclinical levels well before hypoalbuminemia and fluid accumulation manifests overtly. Elevated systemic venous pressure may increase the risk; however, is by no means the only cause of PLE. Hence, i44147Abnormal flow distribution imposed by the low cardiac output state may cause impaired mesenteric flow contributing to development of PLE. Along wi55Low flow in chronic congestive heart failure is known to activate the cascade of inflammatory mediators includinPlastic bronchitis is an even rarer complication of Fontan failure. It manifests with chronic respiratory symptoms such as persistent cough, wheezing, and expectoration of bronchial casts. Although no clear etiological factors have been identified, elevated systemic venous pressure and elevated PVR are associated findings. Lymphatic dysfunction is also suspected, akin to that in PLE. The reason why some patients manifest with plastic bronchitis and others with PLE is not clearly understood. However, patients with Fontan circulation exposed to high altitude have been described to manifest both of these unusual symptom complexes.61The elevated systemic venous pressure has an important effect on the subdiaphragmatic venous hemodynamics that includes the splanchnic and the hepatoportal venous system. Chronic Biochemical liver dysfunction is common during late follow-up of Fontan patients, with elevation of transaminases, coagulation abnormalities, and elevation of bilirubin.–66 More The detrimental effects of gravity and abnormal respiratory function in patients with diaphragm paralysis may accelerate negative effects on the liver.Hemodynamic decompensation due to loss of sinus rhythm was identified by Fontan in his first report of three cases. Subsequently, the atriopulmonary connection was recognized as the basis of atrial re-entry and atrial flutter as a consequence of dilatation, hypertension, and atrial scarring.The early enthusiasm in the hydrodynamic benefit with lateral tunnel Fontan was tempered by lack of improvement in the early or late onset arrhythmias. The extr71Thus, control of arrhythmia is important to maintain good hemodynamics, prevent thromboembolism, and ventricular dysfunction.The earliest sign of failing Fontan circulation is a progressive deterioration in the absence of a clear precipitating cause, such as stenosis in the Fontan circuit. Every patient with suspected failure should have a detailed hemodynamic assessment of the Fontan circulation including meticulous imaging. Any correctable causes should be promptly treated, such as – stenting of branch pulmonary arteries, occlusion of systemic to pulmonary artery collaterals and occlusion of venous collaterals. Maintenance of sinus rhythm is paramount.Assessment of systolic and diastolic function of single ventricle is difficult and treatment modalities are usually extrapolated albeit wrongly from heart failure in biventricular circulation. Betablocet al, in postoperative period after Fontan operation.[et al, in a cohort of Fontan patients during late follow-up.[The impact of vasodilators on early pulmonary vascular dysfunction was clearly demonstrated by Goldman peration. Effect oollow-up. With theollow-up.78 Sildenollow-up. Despite ollow-up.The advances in treatment of heart failure have been applied to the failing single ventricle circulation. Initial 82The evolution of Fontan operation has made the atriopulmonary Fontan connection obsolete as a procedure, however, the late survivors of this operation have provided a better understanding of complications. Progressive dilatation of the right atrium, atrial arrhythmia, thromboembolism, and exercise intolerance are the late consequences that lead to evaluation of these patients for reinterventions. Removal of the dilated atrium from the Fontan circuit with arrhythmia surgery and repair of any residual or recurrent lesions are now undertaken by some groups.86The most common indication is refractory atrial arrhythmia with or without hemodynamic abnormalities.88 The prDespite increasing experience with Fontan conversion, Mavroudis and colleagues found that 5.4% of their 111 patients required cardiac transplantation. Hence, cWhen Fontan failure sets in, there is an inexorable hemodynamic and functional decline in the patients leading to death or cardiac transplantation. The early experience with transplantation in patients with Fontan circulation was of high operative mortality and morbidity.91 The asThe considerations for cardiac transplantation are quite different in patients with failing Fontan circulation. AnatomicChronic cyanosis leads to polycythemia and coagulation abnormalities which are further complicated by hepatic dysfunction. Presence of PLE adds a metabolic and immunologic burden on an already decompensated circulation. Risk of bleeding during and after surgery is compounded by the presence of multiple acquired systemic to pulmonary arterial and systemic venous collateral vessels. The presence of panel reactive antibodies due to the use of allograft material also interfere with optimal immunosuppression.The substrate for pulmonary vascular dysfunction starts well before the Fontan circulation is established due to either abnormal pulmonary arteries, increased pulmonary blood flow for varying duration, pulmonary venous or left atrial obstruction, or chronic pulmonary thromboembolism.Measurement of PVR in Fontan circulation is fraught with difficulties due to inability in accounting for collateral circulation, possibility of pulmonary arteriovenous malformation, low cardiac output state, presence of systemic venous obstruction, unequal distribution of flow to lungs, and possibility of pulmonary venous obstruction. All these factors multiply the error in accurate assessment of PVR.Pulmonary vascular disease was demonstrated in 10 patients who received a transplant late after a failing Fontan circulation (failure >1 year after Fontan completion), however, four patients who received a transplant within one year of their Fontan failure did not have pulmonary vascular disease. Apart frCardiac transplantation is a definitive palliation in the Fontan journey. Despite the difficulties related to pretransplant assessment in failing Fontan circulation, the medium term outcome is reasonably good.In a multi-institutional study in the United States, between 1993 and 2001, 70 patients had cardiac transplant for failing Fontan with a 5-year survival of 68%. Although the survival rates in postFontan patients as compared to other congenital heart disease were not significantly different, it remains slightly worse than patients with no congenital heart disease.96 The loThe Fontan circulation offers the only definitive surgical palliation for patients with a wide variety of complex congenital heart diseases with a single dominant ventricle. It, however, sets a stage for hemodynamic and electrophysiological sequence of events that manifest when the circulation starts to fail. Improved understanding of patient selection, patient preparation, and surgical techniques has allowed us to reach a steady state in the early outcomes after achieving the Fontan circulation. The two new problems facing this group of patients are likely to be related to the late attrition of survivors and the growing population of high risk and borderline patients undergoing single ventricle palliation creating a heretofore unknown cohort that will challenge cardiologists, electrophysiologists, and surgeons, not to mention, the patients and their carers. Advances in management of heart failure have improved the late outcome Fontan circulation to a certain extent. Implantable ventricular assist devices may probably change the course of this circulation; however, until then this imperfect circulation would still be the only surgical option for this difficult patient population.


Although cardiovascular magnetic resonance (CMR) is frequently performed to measure accurate LV volumes and ejection fractions, LV volume-time curves (VTC) derived ejection and filling rates are not routinely calculated due to lack of robust LV segmentation techniques. VTC derived peak filling rates can be used to accurately assess LV diastolic function, an important clinical parameter. We developed a novel geometry-independent dual-contour propagation technique, making use of LV endocardial contours manually drawn at end systole and end diastole, to compute VTC and measured LV ejection and filling rates in hypertensive patients and normal volunteers.39 normal volunteers and 49 hypertensive patients underwent CMR. LV contours were manually drawn on all time frames in 18 normal volunteers. The dual-contour propagation algorithm was used to propagate contours throughout the cardiac cycle. The results were compared to those obtained with single-contour propagation (using either end-diastolic or end-systolic contours) and commercially available software. We then used the dual-contour propagation technique to measure peak ejection rate (PER) and peak early diastolic and late diastolic filling rates (ePFR and aPFR) in all normal volunteers and hypertensive patients.Compared to single-contour propagation methods and the commercial method, VTC by dual-contour propagation showed significantly better agreement with manually-derived VTC. Ejection and filling rates by dual-contour propagation agreed with manual . However, the time for the manual method was ~4 hours per study versus ~7 minutes for dual-contour propagation. LV systolic function measured by LVEF and PER did not differ between normal volunteers and hypertensive patients. However, ePFR was lower in hypertensive patients vs. normal volunteers, while aPFR was higher, indicative of altered diastolic filling rates in hypertensive patients.Dual-propagated contours can accurately measure both systolic and diastolic volumetric indices that can be applied in a routine clinical CMR environment. With dual-contour propagation, the user interaction that is routinely performed to measure LVEF is leveraged to obtain additional clinically relevant parameters. Temporal changes in left ventricular (LV) volume over the cardiac cycle provides fundamental information regarding systolic and diastolic function of the heart but is difficult to measure by standard clinical techniques. Cine cardiovascular magnetic resonance (CMR) using serial short axis slices is well accepted as a gold standard for measuring geometry-independent ventricular volumes ,2. MeasuFully automated contouring techniques have been a research topic for many years -15, and,Consequently, we propose a semi-automated method which leverages the user interaction in drawing ED and ES contours by automatically propagating them to all other time frames in a typical cardiac scan. This dual-contour propagation technique has the potential to more accurately exclude papillary muscles from the LV wall than single-contour propagation techniques or fully automated techniques. The proposed dual-contour propagation technique will not require additional work by the user, because at most institutions contours are already routinely drawn at ED and ES to compute standard volumes, myocardial mass, and ejection fraction. The purpose of this study was to develop a novel semi-automated technique using dual-contour propagation to measure ventricular volumes throughout the cardiac cycle, and compare this method to manual and single-contour techniques in normal volunteers and hypertensive patients.The study was approved by the appropriate institutional review boards and informed consent was obtained from all the participants. 39 normal human volunteers (NLs) and 49 hypertensive (HTN) patients consecutively enrolled in a study of resistant hypertension (defined as requiring 3 or more anti-hypertensive medications to achieve blood pressure < 140/90 mmHg) participated in this study. All patients were in sinus rhythm at the time of CMR.CMR was performed on a 1.5-T scanner  optimized for cardiac application. ECG-gated, breath-hold steady state free precision technique was used to obtain standard  views using the following parameters – slice thickness 8 mm with no gap between short-axis slices, field-of-view 44 × 44 cm, scan matrix 256 × 128, flip angle 45°, typical TR/TE = 3.8/1.6 ms; typical acquired temporal resolution approximately 40 ms); data reconstructed to 20 cardiac phases.In all scans, LVED and LVES endocardial contours were manually drawn on all short axis slices between the mitral annulus and apex  with excNon-rigid registration (NRR)  was usedThe dual-contour propagation scheme shown in Figure The LV volume at each time frame was computed by summing the volumes defined by the contours in each slice. The contour propagation procedure, however, propagated contours in all slices that were contoured at ED, and, near the base, the LV margin may have moved through the image plane in systole. To address this problem, the NRR algorithm was used in a long-axis slice to track a user-selected point near the mitral annulus through the image sequence. The displacement of this point was used to determine how much each short-axis slice should be included in the volume computation ,25. For Once the volumes were computed in each time frame, a VTC curve was constructed and differentiated with respect to time. End-diastole was defined as the maximum-volume time frame, and end-systole was defined as the minimum-volume time frame. Early diastole and late diastole were defined as the first and second halves respectively of the diastolic interval. The peak ejection rate (PER) was defined as the maximum negative time derivative during the systolic interval. The early diastolic and late diastolic peak filling rates (ePFR and aPFR) were defined as the maximum derivative during the early and late diastole.Most existing contour propagation techniques propagate contours from either ED or ES time frames ,20-22,26To assess inter-user variability in volumes computed from propagated contours, nine normal studies (NV10-NV18) were randomly selected. For each study, two sets of contours were manually drawn at ED and ES by different users. Each user was a Level 3 trained CMR specialist or equivalent. Each set of ED and ES contours was propagated using the dual contour technique, and VTCs and ejection/filling rates were computed.To evaluate stability of dual-propagated contours throughout the cardiac cycle, LV mass measurements were computed in each time frame for studies NV10-NV18 from dual-propagated contours and compared to that from one set of manually-drawn contours.The dual-contour propagation algorithm was used to propagate contours to all time frames and compute VTCs and ejection/filling rates in all 39 normals and 49 hypertensives.Comparisons of LV volumes computed from different propagation schemes and comparisons of LV masses computed from dual-propagated and manual contours were performed using mixed modeling via PROC MIXED (SAS version 9.1). To account for the repeated measures within a subject, a compound symmetry correlation structure was assumed. In the LV volume study, confidence intervals on the differences based on the fitted mixed model were constructed each at 99% level to achieve a joint confidence level of at least 95% for this set of confidence intervals using Bonferroni adjustment .Comparisons of PER and PFR values computed from dual-propagated and manually-drawn contours and comparisons of contours propagated by two different users were performed using two-tailed paired t-tests, correlation analysis, and Bland-Altman analysis. PER and PFR values derived from dual-propagated contours in hypertensive patients were compared to normals using unpaired t-tests. In all these statistical tests, a P-value less than 5% was considered statistically significant.Differences between propagated contours and manual contours resulted in differences in VTCs. Figure Table The average computation time for dual-contour propagation  was 7.3 minutes for a single study on a 2.6 GHz dual-core personal computer with 4 GB of RAM. Automated contour propagation using CAAS MRV required less than 1 minute per study. Manual contouring of all slices and phases  required approximately 4 hours per study.Figure No statistically-significant differences were found between PER, ePFR and aPFR rates computed from manually-drawn contours and dual-propagated contours Table . The corNo significant difference was found between PER, ePFR and aPFR values computed from contours propagated with ED and ES contours drawn by two different users (User1 and User2). The differences (User2-User1) between PER, ePFR and aPFR values were 0.07 ± 0.16 EDV/s (P = 0.24), -0.03 ± 0.05 EDV/s (P = 0.11) and -0.01 ± 0.05 EDV/s (P = 0.50) respectively. The correlation coefficients for the PER, ePFR and aPFR values were 0.95 (P < 0.0001), 0.99 (P < 0.0001) and 0.99 (P < 0.0001) respectively. Figure No significant difference was found between normalized LV masses (LV mass/ED LV mass) computed from dual-propagated contours and manual contours. The normalized LV mass difference  was -0.015 ± 0.0077 (P = 0.08). Figure Figure Figure In this paper, we described a novel dual-contour propagation technique for measuring volume-time curves (VTCs), validated it against manually drawn contours, and demonstrated its utility in a clinically-relevant patient population. This method requires nothing more than standard short-axis and long-axis CMR acquisitions and routinely drawn ED and ES contours. We show that the dual-propagated contours can be used to accurately measure peak ejection and filling rates compared to the reference standard of manually-drawn contours. The dual-contour propagation technique provides a fast, practical means of measuring volume-based indices of systolic and diastolic ventricular function from routine clinical CMR.Several techniques have been proposed for propagating contours in CMR -22 and ovan Guens, et al.  proposedInvestigators have previously described use of volume time indices for measuring systolic and diastolic function ,35. CMR The inter-user and intra-user variability in the propagated contours depend on the inter-user and intra-user variability of the semi-automatically-drawn contours at ED and ES. This variability has been studied in ,36,37. IA limitation of contour propagation algorithms in general is that any errors in the seed contours get propagated to all other time frames. Consequently, it is especially important to ensure accurate seed contours before propagation. Also in this paper, papillary muscle volume was considered part of the LV blood volume. Since the papillary muscle volume is relatively constant throughout the cardiac cycle, subtracting the papillary muscle volume would reduce the blood volume by the same amount in all phases and would not significantly affect filling or ejection rates, which are the key parameters determined in this work. Although not evaluated in the present study, we believe that another potential advantage of the dual-contour propagation approach is that defining contours at two time points provides increased robustness to imaging artifacts.In conclusion, the dual-contour propagation technique provides a fast, accurate and practical means of measuring volume-based indices of systolic and diastolic ventricular function from routine clinical CMR.The authors declare that they have no competing interests.WF developed the dual-contour propagation algorithm, drew one set of contours for the inter-user variability study, and drafted the manuscript. HN performed manual contouring of normal datasets including one set of contours for the inter-user variability analysis. HG participated in the study design and helped draft the manuscript. SGL participated in the study design and helped draft the manuscript. IA participated in the study design and performed the statistical analysis. GJP helped draft the manuscript. DAC participated in study coordination. LJD participated in study coordination and helped draft the manuscript. TSD conceived of the study, participated in study design and coordination and helped draft the manuscript. All authors read and approved the final manuscript.First, a square region of interest (ROI) was defined that enclosed epicardial contours in the template image. Since the NRR was applied sequentially starting from either ED or ES, an epicardial contour  was always available in the template image.Next, a two-dimensional displacement field was defined on the template ROI. The deformation field was parameterized by a tensor product of quadratic, uniformly-spaced B-splines:pis a point in the template ROI, β(p) is a B-spline basis function, μi is a control point, C is the number of control points and vi is the knot location associated with the i-th control point. Eight control points were used in each dimension. The B-spline order and number of control points were determined empirically.where μ, were computed to minimize the sum of squared differences between the pixel intensities in the template image, It, and the source image, Is:The B-spline control points, where Ω is the set of pixels in the template ROI.The cost function in Eq. (1) was optimized using a multi-resolution strategy to speed up computation and avoid local minima in the cost function. First, the template ROI was resampled from 64 × 64 to 16 × 16 pixels and the number of control points was reduced to four in each dimension. The reduced resolution control points were then computed using Levenberg optimization algorithm with an analytical gradient and Hessian. This process was then repeated using template ROI resampled from 64 × 64 to 32 × 32 pixels. The number of control points was kept at four in each dimension, and the result of the coarser resolution optimization was used as the starting point for the optimization. Next, the displacement field was interpolated to eight control points in each dimension, and Eq. (1) was optimized on the full-resolution 64 × 64 template ROI. The source image was resampled accordingly in each multi-resolution layer to match the resolution of the template ROI. The result was a spatially continuous mapping of points from the template ROI to the source image. Finally, each contour point in the template ROI was mapped to the source image using the final displacement field.As described above, the NRR was used to propagate contours from both ED and ES to all other time frames in a sequence. These propagations resulted in two contours for each time frame (except at ED and ES). The two contours were combined into a single B-spline contour using a weighted-least-squares fit. The ED-propagated contour weight for a given time was computed using cubic-spline interpolation from the empirically-determined control points in Table


Echocardiographic ratio of peak tricuspid regurgitant velocity to the right ventricular outflow tract time-velocity integral (TRV/TVI rvot) was presented as a reliable non-invasive method of estimating pulmonary vascular resistance (PVR). Studies using this technique in patients with moderate to high PVR are scarce. Left ventricular outflow tract time-velocity integral (TVI lvot) can be easier to measure than TVI rvot, especially in patients with severe pulmonary hypertension (PH) with significant anatomical modifications of the right structures.We wanted to determine whether the TRV/TVI rvot and TRV/TVI lvot ratios would form a reliable non-invasive tool to estimate PVR in a cohort of patients with moderate to severe pulmonary vascular disease.Doppler echocardiographic examination and right heart catheterisation were performed in 37 patients. Invasive PVR was compared with TRV/TVI rvot and TRV/TVI lvot ratios using regression analysis. Two equations were modelled and the results compared with invasive measurements using the Bland-Altman analysis. Using receiver-operating characteristics curve analysis, a cut-off value for the two ratios was generated.Correlation coefficients between invasive PVR and TRV/TVI rvot then TRV/TVI lvot were respectively 0.76 and 0.74. Two new equations were found but the Bland-Altman analysis showed wide standard deviations (respectively 3.8 and 3.9 Wood units). A TRV/TVI rvot then TRV/TVI lvot ratio cut-off value of 0.14 had a sensitivity of 93% and a specificity of 57% for the first and a sensitivity of 87% and a specificity of 57% for the second to determine PVR > 2 Wood units.Echocardiography is useful for the screening of patients with pulmonary hypertension and PVR > 2 WU. It remains disappointing for accurate assessment of high PVR. TVI lvot may be an alternative to TVI rvot for patients for whom accurate TVI rvot measurement is not possible. Assessment of pulmonary vascular resistance (PVR) is crucial in the diagnosis and management of cardio pulmonary diseases such as pulmonary arterial hypertension (PH). Invasive measurement of PVR by right heart catheterisation remains the gold standard method ,2. EchocWe aimed to determine whether the TRV/TVI rvot ratio would form a reliable non-invasive tool to estimate PVR in a cohort of patients with moderate to severe pulmonary vascular disease and whether TRV/TVI lvot ratio could be an alternative.Patients monitored in our Pulmonary Hypertension centre were prospectively recruited. All patients underwent right-heart catheterisation within 24 hours (mean time: 6 hours) of the time of their echocardiography. Exclusion criteria included tricuspid regurgitation grade > 2, intra-cardiac shunt, aortic stenosis or aortic insufficiency grade > 2 to avoid modifying the TVI rvot or TVI lvot measurement. All subjects gave their written informed consent for the participation to the study.Patients underwent standard right heart catheterisation using a Swan-Ganz catheter with jugular or femoral venous access. The following pressure measurements were obtained: right atrial pressure (RAP), right ventricular pressure (RVP), pulmonary artery systolic pressure (PASP), pulmonary artery diastolic pressure (PADP), mean pulmonary artery pressure (MPAP) and right pulmonary capillary wedge pressure (PCWP). Cardiac output (Qp) was determined by thermodilution (mean of three consecutive measurements without variation > 10%). The PVR was calculated using the formula: PVR = (MPAP - PCWP)/Qp.®) equipped with an S3 transducer, before catheterisation. The TVI rvot (cm) was obtained by placing a pulsed wave Doppler sample volume just within the pulmonary valve from the parasternal short axis view. TRV (m/s) was obtained using continuous wave Doppler from apical 4-chamber, parasternal and subcostal views and the highest peak value was retained. TVI lvot was obtained from the apical 5-chamber view by placing a pulsed wave Doppler sample volume in the left ventricular outflow tract just below the aortic valve. TVI rvot and TVI lvot were measured 3 times and averaged. Left ventricular ejection fraction (LVEF) was assessed from an apical 4-chamber view using the monoplane modified Simpson's rule. All measurements were made off-line. The sonographer was blinded to the results of cardiac catheterization. Contrast echocardiography  was not used.Echocardiographic assessment was performed using a Sonos 5500 ultrasound system . Linear regression analysis was realized between invasive cardiac output and TVI rvot then TVI lvot, and between invasive PASP and TRV, leading to Pearson's correlation coefficient. 40% of the Doppler images were re-evaluated to quantify the intra- and inter-observer reliability by calculating the intraclass correlation coefficient.Overall, 37 consecutive patients  , diagnosed with pulmonary hypertension were enrolled in this prospective cohort between June 2005 and December 2007. Mean PVR was 4.8 ± 3 Wood units with preserved LVEF (mean LVEF: 66 ± 6%) and cardiac output. Invasive haemodynamic data are shown in Table Linear regression analysis between invasive PVR and TRV/TVI rvot demonstrated good correlation for all patients . Similarly, good correlation was found between invasive PVR and TRV/TVI lvot  for all patients . Correlation between invasive cardiac output and TVI rvot or TVI lvot was poor (respectively R = 0.37 and R = 0.44).The intraclass coefficient correlation for the intra- and inter-observer reliabilities were 0.99 for both.We found that TRV/TVI rvot and TRV/TVI lvot determined by transthoracic echocardiography were significantly correlated with invasive PVR in a cohort of patients with moderate and high PVR. However, the agreement between PVR determined by echocardiography and invasive PVR was poor.et al. used this method to demonstrate that there was no linear or logarithmic relationship between TRV/TVI rvot and PVR in patients with PVR > 8 Wood units [et al. were able to report good agreement between invasive PVR and PVR evaluated by echocardiography in a cohort of patients less severe than ours with a mean PVR of 2 Wood units [Echocardiography plays a key role in the diagnosis, prognosis and follow-up of patients with PH. PASP measurement should ideally be completed by a PVR estimation . First pod units . Only Abod units . The throd units -5,7-9. COur results did not demonstrate any advantage derived by the use of both TVI rvot and TVI lvot. We estimate the best practical approach remains the use of TVI rvot in first intention as TRV/TVI rvot has more physiological basis than TRV/TVI lvot. Correct alignment of the ultrasound beam is a vital factor to ensure adequate determination of TVI rvot. Sometimes anatomical variations of the right-heart structures may make difficult accurate measurements of the TVI rvot in patients with PH, with a risk to introduce significant errors in right ventricular stroke volume estimation. Using TVI lvot to estimate right ventricular stroke volume may give more acurate estimation and may be an alternative, provided that no significant cardiac shunt or aortic valvulopathy are present.While TRV in echocardiography and invasive PASP had a good correlation, correlation between invasive cardiac output and Doppler measurement  remained weak. Limits of our equations seems to be the assimilation of TVI to the cardiac output and not localization of its measurement. Contrary to a recent work which considered heart rate to estimate non invasively PVR , we did Right heart catheterisation is indicated in all patients with suspected PH to confirm the diagnosis, assess the severity and test the vasoreactivity of the pulmonary circulation  but screEchocardiography and right heart catheterization were not performed simultaneously in this study. We tried to minimize this potential source of error by performing the echocardiography before the invasive measurements under comparable loading conditions. Measurements of cardiac output using thermodilution may be problematic due to tricuspid regurgitation.We are aware of a quite significant fraction of patient with severe pulmonary hypertension were excluded of our study because of tricuspid regurgitation grade > 2. As severe tricuspid regurgitation is a well known pitfall of thermodilution cardiac output measurement, we prefered exclude these patients in order to obtain the most reliable invasive cardiac output.While TRV/TVI rvot and TRV/TVI lvot determined by transthoracic echocardiography significantly correlates with invasive PVR, accurate measurement of PVR by echocardiography remains disappointing, especially in case of a high level of PH. However, echocardiography can identify patients with PVR greater than 2 Wood units with high sensitivity and remains a clinically useful tool when screening patients with PH and high PVR.COPD: Chronic obstructive pulmonary disease; LVEF: Left ventricular ejection fraction; MPAP: Mean pulmonary artery pressure; PH: Pulmonary arterial hypertension; PADP: Pulmonary artery diastolic pressure; PASP: Pulmonary artery systolic pressure; PCWP: Pulmonary capillary wedge pressure; PVR: Pulmonary vascular resistance; Qp: Cardiac output; RAP: Right atrial pressure; TRV: Peak tricuspid regurgitant velocity; TVI lvot: Left ventricular outflow tract time-velocity integral; TVI rvot: Right ventricular outflow tract time-velocity integral; WU: Wood unitThe authors declare that they have no competing interest.VR participated in the echocardiographic measurements and drafted the manuscript. FL participated in the echocardiographic measurements and corrected the manuscript. AP and SG participated in the echocardiographic measurements. RS and TL carried out the right heart catheterisations. EB, PM and GG participated in the design and the coordination of the study. ES conceived the study, performed the statistical analysis and participated in its design and coordination. All authors have read and approved the final manuscript.


Left ventricular (LV) hypertrophy is common among patients on hemodialysis. While a relationship between blood pressure (BP) and LV hypertrophy has been established, it is unclear which BP measurement method is the strongest correlate of LV hypertrophy. We sought to determine agreement between various blood pressure measurement methods, as well as identify which method was the strongest correlate of LV hypertrophy among patients on hemodialysis.This was a post-hoc analysis of data from a randomized controlled trial. We evaluated the agreement between seven BP measurement methods: standardized measurement at baseline; single pre- and post-dialysis, as well as mean intra-dialytic measurement at baseline; and cumulative pre-, intra- and post-dialysis readings (an average of 12 monthly readings based on a single day per month). Agreement was assessed using Lin's concordance correlation coefficient (CCC) and the Bland Altman method. Association between BP measurement method and LV hypertrophy on baseline cardiac MRI was determined using receiver operating characteristic curves and area under the curve (AUC).Agreement between BP measurement methods in the 39 patients on hemodialysis varied considerably, from a CCC of 0.35 to 0.94, with overlapping 95% confidence intervals. Pre-dialysis measurements were the weakest predictors of LV hypertrophy while standardized, post- and inter-dialytic measurements had similar and strong (AUC 0.79 to 0.80) predictive power for LV hypertrophy.A single standardized BP has strong predictive power for LV hypertrophy and performs just as well as more resource intensive cumulative measurements, whereas pre-dialysis blood pressure measurements have the weakest predictive power for LV hypertrophy. Current guidelines, which recommend using pre-dialysis measurements, should be revisited to confirm these results. Hypertension is common among patients on hemodialysis (HD) and is associated with an increased risk of coronary artery disease, congestive heart failure, cerebrovascular complications, mortality and left-ventricular (LV) hypertrophy-3. CardiAlthough the most accurate BP measurement technique among patients on HD is unknown, it has been demonstrated that casual dialysis-unit BP measurements differ considerably when compared to ambulatory and standardized BP measurements-14, and By using more sensitive measures of LV mass, and more frequent measurements of BP, we sought to determine the agreement between various BP measurement methods, at different times  among patients on HD. We also sought to determine the association between BP measurement methods and LV hypertrophy. Further, we hypothesized that BP values obtained by a standardized BP protocol  would be more closely associated with LV hypertrophy than BP values obtained by other techniques.This study involves a post-hoc analysis of data collected within a previously reported randomized controlled trial, where details of the subjects and protocol are previously described. SubjectEligible subjects were 18 years of age or older, receiving in-center, self-care or home hemodialysis three times a week. The study protocol was approved by the University of Calgary bioethics committee.Standardized BP measurements were obtained at baseline by a physician using a mercury sphygmomanometer in accordance with the Canadian Hypertension Education Programs protocol for blood pressure measurement. Three sA single pre- and post dialysis BP measurement was taken by a dialysis unit nurse with patients in a sitting position, within 30 minutes prior to and following the dialysis session using either the automated GAMBRO Phoenix or manually using a mercury sphygmometer on the non-fistula arm. Intra-dialytic BPs were recorded every 15-30 minutes during dialysis. The average value of all of the BP measures taken during a single dialysis session, which ranged from 2 to 11 readings per dialysis session (median 7), was used to determine the intra-dialysis BP.Monthly pre-, intra- and post-dialysis BP measurements were retrospectively collected from hemodialysis records for a single hemodialysis session each month during the 12 month period prior to the cMR examination. These casual BP measurements were obtained by dialysis staff or by the patient .® or Sonata®; Siemens Medical Solutions, Erlangen, Germany) with 8-channel cardiac coils. Standard, breath-held, retrospectively electrocardiogram-gated gradient-echo sequences  in contiguous short-axis views  were applied. The evaluation of the cMR images was performed in a professional core lab  by readers blinded to BP measurement data. Papillary muscles were included in the LV myocardial mass calculation. The formula by DuBois and DuBois[2 >83 for males and LV mass/m2 >67 for females[cMR was performed on 1.5-T MRI systems  as these have been linked to alterations in LV structure. Serum cSubject characteristics are presented as mean ± standard deviation (SD) or median and inter-quartile range (IQR) for continuous variables as appropriate, and number (percent) for categorical data. All BP measurements are reported as mean ± SD. Agreement between BP measurement methods was assessed using two statistical methods. Lin's,23 concoMultivariate linear regression analyses, with LV mass corrected for body surface area as the dependent variable and BP parameters as independent variables, were used to determine the potential confounding effects of hemoglobin, calcium-phosphate product, PTH, age and dialysis vintage. Receiver operated characteristic (ROC) curves, and area under the curve (AUC) statistics, with their respective 95% CI, were generated to compare the test performances of various BP methods in detecting the presence of LV hypertrophy. Only the results for systolic blood pressure (SBP) are shown as the results of the diastolic blood pressure analysis did not appreciably change the outcomes of this study. All analyses were performed using Stata 9.2 .A total of 39 patients were included in the study. The mean age of study subjects was 54 years and two-thirds were male Table . The majThe agreement levels for the different methods for SBP measurements are shown in Table Although not statistically significant, standardized, post- and intra-dialysis measurements (baseline and cumulative) had moderate to high agreement (CCCs 0.67 to 0.94), while the comparison of each method with baseline pre-dialysis BPs showed lower levels of agreement (CCCs 0.35 to 0.62).Correlations between BP measurement methods and LV mass are shown in Table ROC curves for the SBP measurements and LV hypertrophy are shown in Figure In this study we investigated the agreement between standardized and casual  BP measurement methods, and their association with left ventricular mass in hemodialysis patients. Current guidelines ,26 recomIntra- or post- dialysis BP measurements collected over several months may provide a more accurate assessment of BP in a stable, chronic HD patient rather than a single pre-dialysis measurement. However, this is resource intensive and often impractical in the clinical setting. Furthermore, in spite of extremely high agreement (CCC of 0.94), cumulative intra- and post-dialysis BP measurements were not the strongest predictors of LV hypertrophy, which is the more clinically significant outcome. BP values obtained by the standardized BP measurement protocol were closely associated with LV mass, but no more so than a single intra-dialysis or single post-dialysis measurement, all three of which had similar and strong predictive power for determining LV hypertrophy.While the relationship between BP and mortality in ESRD patients is not clear,27,28, iTwo previous studies of BP as a predictor of LV geometry both found pre-dialysis BP's to be strong determinants of LV hypertrophy,16. ThesBP management in HD patients is partly dependent on the ability of physicians to accurately assess BP levels, which remains a challenge. In the absence of a universally accepted method for BP assessment among patients on hemodialysis, we selected standardized BP as the gold standard for the purpose of this study, as it was based on a protocol established and endorsed by national hypertension guidelines. PreviouOur results should be interpreted in the context of the study limitations. Firstly, our sample size was small, including 39 patients. Despite the small sample size, our use of cMR enabled us to use a more accurate measure of LV mass; thus our point estimates are more precise than those of previous studies. SecondlIn summary, we found that a single standardized BP measurement has strong predictive power for LV hypertrophy, but is not significantly better than casual post- and intra-dialysis BP measurements taken at a single point in time or over several months. For ease of practice, a single standardized measurement performs just as well as the more resource intensive cumulative measurements. Given the poor agreement with other methods, and relatively poor predictive power of a single pre-dialysis measurement in predicting LV hypertrophy, the results of this study also suggest that the current practice guidelines, which advocate the use of pre-dialysis measurements for chronic hemodialysis patients, warrants further study. This study does not however provide strong evidence to disregard current guidelines.HD: hemodialysis; LV: left ventricular; ESRD: end stage renal disease; BP: blood pressure; cMR: cardiac MRI; PTH: parathyroid hormone; SD: standard deviation; IQR: inter-quartile range; CCC: concordance correlation coefficient; ROC: receiver operated characteristic; AUC: area under the curve; CI: confidence intervals; SBP: systolic blood pressure; ACE: angiotensin converting enzymeThe authors declare that they have no competing interests.BRH, MT, SWK, BJM, and BFC made substantial contributions to conception, design and acquisition of data and funds. JP, BRH, JZ, BJM and BFC made substantial contributions to conception and design. All authors made substantial contributions to interpretation of the data, all authors were involved in revising the manuscript for important intellectual content, and all authors have read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2369/11/13/prepub


A 24-year-old patient was admitted for dyspnoea and syncope. He had a previous history of complete atrio-ventricular septal defect and trisomy 21. At the age of 6 months, in 1984, cardiac catheterization revealed a quasi-systemic pulmonary arterial hypertension with a bidirectional shunt corresponding to an Eisenmenger syndrome. Corrective cardiac surgery was not performed at this time because surgical risk was considered too high. Until the age of 20 years old, he showed few symptoms while under medical treatment. But since 2006, his functional status became worse with an increased dyspnoea, syncopes, and severe cyanosis. In these conditions, haemodynamic parameters have been re-evaluated in 2006 and 2008.They highlighted a late and progressive development of a valvular and infundibular pulmonary stenosis leading to a normalisation of pulmonary arterial pressures. At the age of 24 , the patient underwent corrective cardiac surgery which was successful. Late development of both infundibular and valvular pulmonary stenosis have not been described before in non operated congenital ventricular septal defects, but development of one or the other abnormality would be found in 8% of patients. The physiopathological mechanism of this obstruction is unclear. Nevertheless, in unoperated congenital cardiac shunt lesions, reversibility of severe pulmonary arterial hypertension should be reconidered and re-assessed during follow up. A 24 year-old-man, was admitted to hospital for repeated syncopes and increased dyspnea. He was treated for a severe pulmonary arterial hypertension (PAH), secondary to atrio-ventricular septal defects (AVSD) associated with trisomy 21. Indeed, the first cardiac catheterization was performed in 1984 at the age of 6 months, at Robert Debré Hospital, and confirmed the "Eisenmenger syndrome" associated with a large posterior and complete atrio-ventricular septal defect, with grade 1 mitral regurgitation. Right-to-left shunt was moderate and the left-to-right still predominant. Left ventricular systolic pressure was 85 mmHg and pulmonary artery (PA) systolic pressure almost systemic at 75 mmHg with pulmonary to systemic vascular resistance ratio of 0,3, and pulmonary-systemic outflow ratio of 2,7. The right ventricular (RV) systolic pressure was 85 mmHg so catheterization showed at this time a non significant RV-PA outflow gradient of 10 mmHg. Right heart was very dilated and non hypertrophic. At physical examination, the young boy had a good psychomotor and weight development, no cyanosis and no sign of cardiac failure under digitalo-diuretic treatment. Pulmonary resistance was considered in the borderline operable range values but spontaneous prognosis was estimated equal to post-operative prognosis so corrective surgery was not proposed.Treatment digitalo-diuretic was stopped in 1987. Few cardio-respiratory complications occurred during his childhood, and cyanosis was moderate with a good exertion capacity until 2004.By then, his functional status started becoming worse with progressive increased dyspnea, pulmonary infections, cyanosis due to a severe chronic hypoxemia and secondary erythrocytosis.Taken in charge at Grenoble Hospital in 2006, oxygen saturation was 80%, NYHA functional class II-III, without any sign of cardiac failure. The 6 minutes walking test was 180 m. Echocardiography found a persistant complete atrio-ventricular defect of 2 cm with moderate mitral regurgitation, but revealed a non dilated hypertrophic RV . Pulmonary valvar was strongly calcified and narrow. Outflow tract was muscular and thick. The surgeon closed the atrial and ventricular parts of the ASVD, replaced the pulmonary valve with a biological prothesis, and reconstructed 6 cm of pulmonary infundibulum. Patient needed a pacing implantation because of a paroxystic atrio-ventricular bloc in the post-operative period. He is today asymptomatic. Post-operative echocardiography found a RV-PA residual outflow gradient of 12 mmHg, a mean PA pressure of 26 mmHg and no residual shunting.AVSD account for approximately 3% of all congenital heart diseases, frequently associated with other malformations such as in trisomy 21 [The natural history of large AVSD is the evolution to the "Eisenmenger syndrome", which refers to the development of bidirectional or predominant right-to-left shunt accompanied by oxygen-unresponsive hypoxemia due to a severe PAH . SurgerySome cases of "masked" infundibular pulmonary obstruction in young patients have been previously reported in ventricular septal defect with severe pulmonary hypertension by J Vogel and S Blount in 1965 . CatheteMost centers tend to rely on catheterization-based calculations of pulmonary blood flow resistance and pulmonary pressure to assess PAH reversibility and likelihood of surgical success, with a better surgical outcome if pulmonary vascular resistance is below 15 Woods units and pulmonary-systemic resistance ratio below 2/3. This attitude remains the consensus of opinion based on surgical experience rather than rigorously tested standards.PAH: pulmonary arterial hypertension; PA: pulmonary artery; RV: right ventricular; AVSD: atrio-ventricular septal defects; PS: pulmonary stenosis.Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.The authors declare that they have no competing interests.EB wrote the manuscript. HB performed the two last cardiac catheterizations. GN performed the surgery. GV and SM supervised manuscript redaction.All the authors read and approved the final manuscript.


Increased muscle mass index of the left ventricle (LVMi) is an independent predictor for the development of symptoms in patients with asymptomatic aortic stenosis (AS). While the onset of clinical symptoms and left ventricular systolic dysfunction determines a poor prognosis, the standard echocardiographic evaluation of LV dysfunction, only based on measurements of the LV ejection fraction (EF), may be insufficient for an early assessment of imminent heart failure. Contrary, 2-dimensional speckle tracking (2DS) seems to be superior in detecting subtle changes in myocardial function. The aim of the study was to assess these LV function deteriorations with global longitudinal strain (GLS) analysis and the relations to LVMi in patients with AS and normal EF.50 patients with moderate to severe AS and 31 controls were enrolled. All patients underwent echocardiography, including 2DS imaging. LVMi measures were performed with magnetic resonance imaging in 38 patients with AS and indexed for body surface area.The total group of patients with AST showed a GLS of -15,2 ± 3,6% while the control group reached -19,5 ± 2,7% . By splitting the group with AS in normal, moderate and severe increased LVMi, the GLS was -17,0 ± 2,6%, -13,2 ± 3,8% and -12,4 ± 2,9%, respectively , where LVMi and GLS showed a significant correlation .In conclusion, increased LVMi is reflected in abnormalities of GLS and the proportion of GLS impairment depends on the extent of LV hypertrophy. Therefore, simultaneous measurement of LVMi and GLS might be useful to identify patients at high risk for transition into heart failure who would benefit from aortic valve replacement irrespectively of LV EF. The therapeutic management of patients with aortic stenosis (AS) depends on the severity of the stenosis and the presence of symptoms or the presence of left ventricular (LV) dysfunction, since the onset of symptoms and LV dysfunction determines a poor prognosis ,2. PartiThe pathophysiological starting point in the development of subclinical LV dysfunction in AS is still a matter of debate. LV hypertrophy is a very common finding in AS and can result in early impairment in the LV performance. In order to compensate the elevated wall stress, the LV wall thickness increases, maintaining normal ejection fraction (EF) . As therIn the present study, we hypothesized that an increased LVMi in subjects with moderate to severe AS is reflected in abnormalities in GLS and that the proportion in GLS impairment depends on the extent of LV hypertrophy. In addition, we investigated whether GLS is sensitive enough to detect early recovery of global myocardial function after AVR.This study was planned for patients with moderate to severe AS who underwent conventional and 2 D speckle tracking echocardiography as part of clinical trial protocol. A total of 50 patients were enrolled. The study protocol was approved by the local ethics committee. Magnetic resonance imaging (MRI) was performed to assess LVMi and LV function. Exclusion criteria were concomitant mitral valve disease, severe low gradient AS, EF < 35%, hypertrophic obstructive cardiomyopathy, uncontrolled hypertension, severe ventricular arrhythmias, and general exclusion criteria for MRI.2/m2 with a Pmean ≥ 40 mmHg.Standard and tissue Doppler echocardiography were done with a commercially available system . LV EF was calculated by the biplane Simpson's method. Left ventricular mass index was obtained by normalizing LVMi to body surface area according . DopplerDeformation analysis of the datasets was performed off-line using EchoPac PC8.0 . For this purpose, recordings of 3 consecutive 2 D images were used to analyze regional deformation on grey-scale images recorded from the parasternal LV short-axis (at the level of papillary muscles and LV apex) and apical four-, two- and three chamber views, respectively. The cardiac cycle with the best image quality and without any artefacts was selected for reporting results. Strain and strain rate analysis was performed as described previously . In brieA 1.5-Tesla Achieva MRI scanner  equipped with a 5-element cardiac synergy coil was used. Cine-Images were acquired in breath hold SSFP sequences . Images were evaluated with the cmr42 research edition toolkit  combining long and short axis views. The program calculated end- and endsystolic volumes, as well as stroke volume, ejection fraction and finally LVMi. Subjects were subsequently subdivided into three groups according the LVMi : group 1All analyses were performed using SPSS statistical software . The data is presented as mean ± SD unless otherwise specified. An p < 0.05 was set considered statistically significant. Comparison of the 2 groups of subjects for various parameters was performed by 1-way analysis of variance (ANOVA). Pearson's linear correlation coefficients were calculated for pairs of continuous variables. We first analyzed associations without any adjustments and then with adjustments for potential confounders by multiple linear regression for continuous and logistic regression for categorical variables.50 patients with moderate to severe aortic stenosis and 31 controls without valvular heart disease and with normal EF were included. In 12 subjects with AS, either MRI or 2DS measurements was not performed because of bad image quality, low frame rate or claustrophobia. Therefore, both MRI measurements of LVMi and echocardiographic determination of GLS were done in 38 subjects. The baseline demographics and clinical characteristics are highlighted in table Echocardiographic and MRI measurement results are summarized in Table AVA, Pmean or EF did not differ between groups 1-3, respectively. In a multiple linear regression analysis including age, gender, hypertension, CAD, EF, history of myocardial infarction or history of coronary bypass surgery, AVAindex and Pmean, only LVMi remain a significant predictor variable for GLS impairment . Left ventricular EF (determined with MRI) and GLS  or LVMi  were not correlated.The average peak radial systolic strain values (PRS) obtained from the parasternal short axis view at the level of the LV apex were tended to be higher in subjects with mildly increased LVMi compared to normal LVMi or moderately to severe increased LVMi .A follow up visit at 3 month was done in 15 subjects. The average GLS values improved from -15,2 ± 3,6 to -17,6 ± 3,2%. All patients irrespectively of LVMi shows an augmentation of GLS , EF or the severity of AS. In particular, in this study population, patients with more advantaged stages of LV hypertrophy had the lowest average GLS, demonstrating that this type of hypertrophy is characterized by low myocardial function. Secondly, impaired myocardial function can be detected by global myocardial longitudinal function assessment but not by LV EF measurements. Finally, GLS improved after AVR three month after surgery.From the pathophysiological point of view, these observations are consistent with the concept that pressure overload results in extensive LV remodeling leading to hypertrophy, keeping wall stress normal. Since wall stress is a key determinant of ejection performance, its normalization is important in maintaining a normal EF. Because the EF is based solely on endocardial radial motion, the EF tends to increase relating to the extent of LV hypertrophy in early stages. In our study, radial strain, as a measurement of radial contraction , was preFurthermore, it was shown that patients with LV hypertrophy have an increased incidence of cardiac events, including fatal ones . DespiteNevertheless, until now, the relation of GLS impairment to the extent of LV hypertrophy has not yet been clearly established. Echocardiographic imaging is the most widely available clinical tool to detect LV hypertrophy, as determined by the calculated LVMi. A major limitation of previous studies investigating the association between LVMi and GLS is the fact that the reproducibility of LVMi measurement by echocardiographic techniques is still controversial and prone to imaging artefacts. Therefore, MRI is a more precise and reliable method to quantify the mass of the left ventricle . MRI is Previous studies demonstrated that longitudinal strain measurement is superior to other indices of LV systolic function to predict symptoms, exercise tolerance and outcomes in AS patients ,21. ConsAdditionally our study showed that GLS improved an average by - 2,5% 3 month after AVR, which previous studies confirmed as well ,24. AfteIn summary, our results demonstrate that the association between average GLS and LVMi is independent of age, CAD, severity of AS and LV EF. Because of the relationship between LV hypertrophy and subtle LV dysfunction, our findings may help to explain why concentric LV hypertrophy has been associated with higher in-hospital mortality after aortic valve replacement . This isThere are several limitations to our study. First, MRI determination of LVMi was not done in controls and either GLS or MRI was not possible in 12 subjects with AS. Nevertheless, the control group only serves to provide a basis for the measurements of GLS values in subjects without AS and comparable age and co-morbidities like CAD or hypertension. Furthermore, the study population was heterogeneous including subjects with or without concomitant coronary artery disease (CAD). However, CAD is a very frequent associated co-morbidity in AS and therefore our study population is reflecting clinical daily routine. Additionally, to date only 15 patients have been followed up, and LVMi was only measured with echocardiography at follow up visit. However, even statistically arguable, the overage improvement of GLS is consistent with reported literature and shows the appropriateness of 2DS analysis in the detection of subtle improvements early after AVR. Lastly, antihypertensive treatment was not standardized and left to the decision of the general practitioners managing the individual patients. Thus, impact of antihypertensive treatment on deformation parameters could not be assessed in the study.Our findings provide new insights into the mechanical adaptation of the LV to chronic afterload elevation and its response to unloading. In patients with AS, increased LVMi is associated with a progressive reduction in GLS assessed by 2DS. The degree of hypertrophy parallels the severity of overload, and GLS improves after AVR. However, left ventricular hypertrophy does not necessarily imply myocardial dysfunction. Therefore, assessment of GLS can identify subtle contractile dysfunction triggered by increased LV mass and might be useful to identify patients at high risk who would benefit from AVR. The prognostic implications of our findings remain to be assessed in future longitudinal studies.The authors declare that they have no competing interests.WD conceived of the study, participated in the study and drafted the manuscript and performed statistical analysis. WN participated in the study and drafted the manuscript and performed statistical analysis. JS performed MRI analysis. FK helped to draft the manuscript. TS participated in the study design of the study and performed statistical analysis. MC-B participated in echocardiographic studies. HB performed MRI analysis. TK participated in echocardiographic studies and helped to draft the manuscript. ML participated in the study design and coordination and helped to draft the manuscript. RF participated in echocardiographic studies and participated in the study design.All authors have read and approved the final manuscript.


Strain, and particularly Longitudinal Peak Systolic Strain (LPSS), plays a role in investigating the segmental and overall contractility of the heart which is a particularly interesting feature in athletes in whom regular training determines several morphological and functional modifications in both the ventricles, that normally work at different loads. Speckle tracking techniques assess the LPSS of LV and RV from B-mode imaging in real time, with uniform accuracy in all segments, and can verify the possible dissimilar segmental contributions of the two chambers to overall myocardial contraction. The aim of the study is to quantify the LPSS in real time in both the ventricles in order to estimate any possible different deformation properties in them during a systolic period.32 subjects (20 athletes and 18 controls) were submitted to a standard echocardiographic examination at rest and after a Hand Grip (HG) stress. From a four-chamber-view image, the LPSS parameter was measured with Speckle Tracking analysis in the basal and medium-apical segments of the two ventricles, at rest and after HG.medium-apical -23.87 ± 4.94; basalfreewall -25.04 ± 4.12 at rest) and controls  than in the LV of both  With the HG test a significant enhancement of the LPSS(with P < .05) in the medium-apical segments of LV and RV was evident, but only in athletes; there was no modification of the standard echo-parameters in either group.In both athletes and controls, LPSS values were significantly higher in the RV of athletes (RV LPSS ST analysis is an easy method for investigating the contractility of the RV through deformation parameters, showing greater involvement of the RV than LV at rest. In athletes only, after isometric stress the two ventricles show particular myocardial deformation properties of the regions around the apex where the curvature of the wall is more marked. The clinical application of this new approach in athletes and normal subjects requires further investigation. Regular sporting activity induces several morphological and functional modifications in all the heart chambers  and bothNormally the RV is considered a low-charge and therefore "passive" chamber, and its function has usually been assessed in a bi-dimensional echo exam by measurement of Right Ventricle Area Change (RVAC). This parameter has been found to correlate best with MRI-derived Right Ventricle Ejection Fraction (RVEF) and to beAn innovative investigation of overall and segmental heart performance is now possible, using new parameters such as quantification of strain (S) on the walls -6. S is Of the deformation parameters currently used, Longitudinal Peak Systolic Strain (LPSS) is one of the most common and validated for determining global and segmental myocardial contractility in normal subjects and in athletes -11In athletes, the LPSS measurement has recently been proposed to complete the evaluation of LV myocardial function at rest and after a brief isometric stress ,11. On tThe aim of the present study is to quantify LPSS in the basal and medium- apical segments of the RV chamber in real time in a group of regularly-trained athletes, and to compare these values with the LV LPSS ones in order to verify any possible difference between them. For this reason, the ST method was preferred, since its angle independence can be applied to all segments of the two ventricles, including the regions with the greatest curvature like the wall segments near the apex. In order to highlight any possible dissimilar properties of the single segments in the deformation of the two ventricles analyzed, a brief isometric exercise, the Hand Grip (HG) test, was introduced into the study protocol.This study included 50 subjects: 32 competitive athletes aged 25 ± 8.1 years who regularly trained at high dynamic and low-moderate static component  three tiAll were submitted to a general check-up to exclude cardiovascular, metabolic or familiar diseases.The study protocol was divided into two phases: an echocardiographic examination at rest, and re-measurement of echo parameters at the peak of the HG test. The HG test consisted of an isometric stress test performed with a graduated handle dynamometer held in the dominant arm for three minutes The handle dynamometer (baseline hydraulic hand dynamometer No. 10533 USA) was regulated at 30% of the previously- established maximum effort. A short, acute effort such as HG was chosen in order to create a pressure load enhancement in both ventricle chambers and thus in the deformation of the myocardial wall. During both the rest and stress phases, a clip of an echo-image in the four-chamber view, including three beats, was captured for each subject in order to perform strain analysis.Systolic and Diastolic Blood Pressure  and heart rate (HR) were measured both at rest and at the end of the acute effort.All the echo-studies were performed with the subjects lying in a supine position. The images were acquired using the My Lab 30 echocardiograph equipped with a 2.5 MHz probe, and later processed with the X-Strain software for evaluating 2D strain. The traditional echo parameters, including Left Ventricle End Diastolic diameter (LVEDd), Left Ventricle End Systolic Diameter (LVESd), thickness of Inter Ventricular Septum (IVS) and Posterior Wall (PW), were obtained from a long-axis view and according to AHA guidelines . Ejectio. All theImages were acquired with the subjects at rest, lying in the lateral decubitus position with data acquisition at the expiration stage so as not to create "artefacts". The 2D images of four-chamber views were post-processed with X-Strain software to provide an angle-independent tool for the evaluation of velocities and strain. This software allows automatic evaluation of the dynamic properties of the endocardial border and of the sub-endocardial tissue from 2D B-mode echocardiographic clips . Strain Thanks to the angle-independence, the LPSS measurements were performed in basal and medium-apical segments of the RV free lateral wall and LV lateral wall of the images acquired at rest and after HG . Statistical and power analysis were performed using Statview and STATA (Stata – Corp 2003) software. The comparisons among athletes and controls at rest and at peak stress were performed with Student's two-tailed unpaired test, while the comparison between basal (resting) state and Hand Grip for each group was performed with Student's paired "t" test. We considered results significant at a value of p < 0.05. The inter-observer variability was calculated as the SD of differences in ST strain measurements by two independent observers for 6 randomly-selected echocardiographic examinations.athletes up to 63%, EF controls up to 64%). The RVAC showed a mild but non-significant decrease at the end of the HG test in both groups  and after HG  than in LV both at rest  and after HG .medium-apical from -18.14 ± 4.16 at rest to -24.07 ± 7.51; RV LPSS medium-apical from -23.87 ± 4.94 at rest to -26.63 ± 3.72 with HG; P < .05 for all) in the athlete group alone.  and controls  than in the LV of both groups . Despite the data are in agreement with the results previously found in healthy young normal subjects [Considering that heart contractility in the young athletes investigated matched that of the healthy sedentary controls subjects, the former seem to maintain a trend similar to the latter when they are in the same conditions. However in the RV of athletes, as in the LV, isometric stress produces a peculiar deformation involving the medium-apical segments, with higher negative values of LPSS, and in the presence of unchanged RVAC. The same behavior is not recognizable in controls.In addition, the non-significant modification of the PP values found in both groups after isometric stress confirm that RV strain performance in athletes does not directly depend on PP variation. Probably a particular morphology and function of the RV chamber of athletes as compared to normal subjects, despite the divergent pressure- work-load of the two ventricles, might be involved in the different level of their deformation properties. Thus the Speckle Tracking method can be helpful to distinguish the two different levels of contractility of both chambers in athletes vs normal subjects even if the evaluation of the intimate properties of the myocardial fibers is outside the scope of the present investigation. Nonetheless it is reasonable to suppose that several clinical applications will be found for this pioneering non- invasive approach in athletes. It may be possible to discover the early stages of dissimilar or deficient contractility in the presence of an asymptomatic myocardial or valve disease where an involvement of one of the two ventricles is more evident.The study includes a restricted number of subjects due to the need to have a homogeneous group. We must thus consider the importance of enrolling and evaluating larger numbers of controls and athletes who are matched for BSA and age. It is reasonable to think that this might be one of the reasons for some dissimilar strain values found in this study. Despite this limitation, the purpose to use real-time investigation of LV and RV myocardial strain could be acceptable if we consider the possibility of several other clinical implications of this approach in patients and athletes where the early stages of impairment of heart performance are not yet associated with evident symptoms .These results, in agreement with the previous data in literature ,9,10, leThe authors declare that they have no competing interests.The initial idea for the study was of LS. LS, GG designed the study, and LS, GG, GP, NM, ADL performed all the measurements and statistical analyses. LS wrote the manuscript and all the authors contributed to, read, and approved the final version.Image 1. Image 1: Image of "feature tracking" calculation of LPSS (using X-Srain) in left ventricle, including one systolic cycle at rest. All peak strain values are represented as negative. A different colour curve corresponds to the LPSS value of the single myocardial segment. For example in this section the purple curve corresponds to the strain value in the basal segment of LV lateral wall, while the white curve for example corresponds to the LPSS of the interventricular septum.Click here for fileImage 2. Image of "feature tracking" calculation of LPSS (using X-Strain) in right ventricle, including one systolic cycle at rest. All peak strain values are represented as negative. A different colour curve corresponds to the LS value of the single myocardial segment. The red curve represents the LPSS in the medium apical segments of the free wall of RV while the orange curve is an example of the application corresponding to the LPSS measurement in the interventricular septum. The same procedure can be applied during stress.Click here for fileClips 1. This clip shows the use of X-Strain software to obtain measurement of the LPSS in all the segments of the LV chamber during a systole.Click here for fileClip 2. This clip shows the use of X-Strain software to calculate the LPSS in all the segments of the RV during a systole.Click here for file