Although it is important to analyze the hemodynamic factors related to the right ventricle (RV) after left ventricular assist device (LVAD) implantation, previous studies have focused only on the alteration of the ventricular shape and lack quantitative analysis of the various hemodynamic parameters. Therefore, we quantitatively analyzed various hemodynamic parameters related to the RV under normal, heart failure (HF), and HF incorporated with continuous flow LVAD therapy by using a computational model.In this study, we combined a three-dimensional finite element electromechanical model of ventricles, which is based on human ventricular morphology captured by magnetic resonance imaging (MRI) with a lumped model of the circulatory system and continuous flow LVAD function in order to construct an integrated model of an LVAD implanted-cardiovascular system. To induce systolic dysfunction, the magnitude of the calcium transient function under HF condition was reduced to 70% of the normal value, and the time constant was reduced by 30% of the normal value.Under the HF condition, the left ventricular end systolic pressure decreased, the left ventricular end diastolic pressure increased, and the pressure in the right atrium (RA), RV, and pulmonary artery (PA) increased compared with the normal condition. The LVAD therapy decreased the end-systolic pressure of the LV by 41%, RA by 29%, RV by 53%, and PA by 71%, but increased the right ventricular ejection fraction by 52% and cardiac output by 40%, while the stroke work was reduced by 67% compared with the HF condition without LVAD. The end-systolic ventricular tension and strain decreased with the LVAD treatment.LVAD enhances CO and mechanical unloading of the LV as well as those of the RV and prevents pulmonary hypertension which can be induced by HF. In left heart failure (LHF), pulmonary arterial hypertension is likely to occur and result in right ventricular hypertrophy, which alter the contractility of the right ventricle (RV). In addition, as the cardiac output (CO) decreases, other complications are likely to occur, including tricuspid regurgitation, hypertension in the hepatic venous causing hepatic dysfunction, and coronary ischemia due to the abnormal circulation in the coronary system .In LHF, left ventricular assist device (LVAD) implantation reduces left ventricular workload and increases CO. The increased CO reduces right ventricular workload and pulmonary blood pressure. However, alteration of ventricular septal position owing to LVAD implantation is likely to impair the contractility of the RV and cause tricuspid regurgitation –3.There are several studies on risk scores for stratification associated with right ventricular dysfunction after LVAD implantation. Grant et al.  examinedAlthough the quantitative analysis of the hemodynamic factors related to the RV after LVAD implantation is critical, previous studies have focused on the alteration of the ventricular shape and lack quantitative analysis of the various hemodynamic parameters. Furthermore, experimental studies consumed more time and have less cost-efficient. There are also various limitations of experimental study as it is likely to invasively harm an actual human heart. Simulation studies, on the other hand, can overcome those limitations and provide data on a variety of hemodynamic parameters in a noninvasive manner.In this study, various hemodynamic parameters related to the RV were quantitatively analyzed under normal, heart failure (HF), and HF incorporated with continuous flow LVAD conditions by using a computational model –10. The The mathematical model used to carry out this study consists largely of four components. First is an electrical conduction model of ventricular tissue. Second is electrical conduction model of Purkinje fiber, which is a pathway to transmit electrical signal to ventricular tissue. Third is a mechanical contraction model of ventricles. Fourth is a lumped parameter model of atrial function and vascular system, which constitute a whole cardiovascular system model with a ventricular mechanical model. Figure We used a previously reconstructed human ventricular model based on publicly available MR imaging with both fiber orientation information and cardiac tissue inhomogeneity information , 15. Theβ is the surface-to-volume ratio of cardiac cells, Itrans is the current density of the transmembrane stimulus, Cm is the membrane capacitance per unit area, Vm is the membrane potential, and Iion is the current density of the ionic current, which depends on the transmembrane potential and other state variables represented by υ. Iion is the sum of all transmembrane ionic currents given by the following equation [The mathematical description of electrical conduction is governed by the monodomain representation of cardiac tissue. A membrane kinetics model represented the electrical activity at the cellular level. We used the membrane dynamic model of ten Tusscher as it was originally formulated . The govequation  3\documeFor the electrophysiological simulation of the ventricles, finite tetrahedral linear elements were generated using HyperMesh software . An electrical impulse is generated at the AV node at the top of the Purkinje network and conduction occurs along the Purkinje network. Conduction through the Purkinje fibers maintained a clinical conduction speed of 200 cm/s. When the impulse reaches the 145 Purkinje terminal nodes at approximately the same time, it excites the ventricular tissue at the Purkinje terminal node, resulting in electrical conduction throughout the ventricles.To solve the governing equations, we used a forward Euler method with a time step of 0.01 ms for temporal discretization, and the Galerkin approach of the finite element method for spatial discretization. Solving the governing equations in this way will reveal all of the dependent variables included in the governing equations. The intracellular calcium concentration transients calculated at all of the discretized nodes are used as input to the cardiac mechanical contraction model.f = 8, bt = 2, and bfs = 4. The laminar sheet and fiber orientation information determined the orthotropic electrical conductivity and passive mechanical properties of the myocardium. A finite element mesh consisting of 462 nodes and 230 Hermite elements was used. A cross-bridge dynamics model [The mathematical description of the mechanical contraction of cardiac tissue is based on continuum mechanics , 21, witTo simulate hemodynamic responses, which are the interactions between the blood and ventricles, the finite element electromechanical model of the human ventricle was coupled with a circulatory model using the coupling method of Gurev et al. , 25. A sPhysiologically, depolarization of each myocyte occurs by electrical wave propagation of the heart. Depolarization of the myocyte activates the calcium channel to release calcium from the sarcoplasmic reticulum into the cytosol; this causes the calcium to bind to the troponin C followed by cross-bridge contraction cycle due to sliding of the myofilaments. The cross-bridge contraction cycling forms the basis for contractile protein movement and development of active tension in the myocyte, resulting in deformation of the ventricles. The process by which the calcium acts as the actuator to convert electrical activation into mechanical phenomenon was implemented by inputting the intracellular calcium concentration obtained from the electrophysiological model from each myocardial cell into the contractile myofilament dynamics model see Fig. .The finite element electromechanical model of the human ventricle was combined with a lumped model of the circulatory system, cardiovascular system, and continuous flow LVAD model Fig. . The conSingle cell simulation: The basic cycle length (BCL) was set as 800 ms, and the calcium transient scaling factor of HF was set as 0.7. In this study, 10 cycles were simulated under each of isometric and isotonic conditions, and the data was gained from last one cycle to observe changes on steady state Fig. .Fig. 2ReThree dimensional electromechanical simulation: A total of 25 cycles were simulated to attain a steady state (BCL = 800 ms). After electrical simulation, the EAT data as well as the calcium concentration data of normal and HF myocardial cells , aorta, right atrium (RA), right ventricle (RV), and pulmonary artery (PA); biventricular pressure–volume diagram; quantitative hemodynamic responses provided in Table Figure Figure Figure When the LVAD is applied under HF, the LVESV and LVEDV decreased from 85 to 69 mL and from 117 to 89 mL, respectively, and no isovolumetric contraction and relaxation were observed. In addition, the LVSV decreased from 32 to 20 mL, and the pressure also decreased in a manner to that of the results in Fig. Figure In HF with LVAD, the isovolumetric alterations were more or less eliminated. The RVESV and RVEDV decreased from 124 to 98 mL and from 157 to 144 mL, respectively. In addition, the right ventricular stroke volume (RVSV), which is the difference between the RVESV and RVEDV, increased from 33 to 46 mL, and the right ventricular stroke work (RVSW) decreased from 411 to 137 mmHg mL.Figure Figure Figure Under HF condition, the LVESP decreased and the LVEDP increased and the pressure in the RA, RV and PA also increased compared to the normal condition. When the continuous LVAD was applied, pressure in the LV, RA, RV and PA decreased Figs. , Table 1The biventricular PV loops in HF condition were shifted to the right side compared to the normal condition. When the LVAD was applied, the biventricular PV loops were shifted to the left side and the LVSV decreased but RVSV increased Fig. , Table 1Under HF condition, the fluxes (flow rates) through the MV, TV, and PV were lower and the duration of opening valve shorter compared to normal condition. But LVAD treatment increased the fluxes through the MV, TV and PV and the duration of opening valve Fig. .In case of HF, the end systolic ventricular contraction force and strain decreased from that in normal condition. When the LVAD was applied, the contraction force and strain also further decreased Fig. .In this study, we quantitatively analyzed various hemodynamic parameters related to the RV under the ideal case that represents no morphological influence to the geometric structure of ventricles despite of LVAD implantation through computational simulation. The main findings of this study were the following:In the case of HF, the contractile force is weaker Fig. a, b thanOwing to the lower ventricular contractility under HF, the intraventricular residual blood volumes were higher; therefore, both the ventricular PV loops were shifted to the right side in HF condition than in normal condition. The LVAD pumps the remnant blood continuously to the aorta such that no isovolumetric contraction and relaxation period was observed. Although the left ventricular CO (LVCO) and ejection fraction (LVEF) decreased from 2.4 to 1.5 L/min and from 27 to 22%, respectively, the practical CO, which is generated by natural LV and LVAD, increased, which resulted in increase of the right ventricular CO (RVCO) and EF (RVEF) from 2.5 to 3.5 L/min and from 21 to 32%, respectively. Furthermore, the fluxes (flow rates) through the MV, TV, and PV also increased Figs. .Under HF with LVAD implantation condition, the contraction force also decreased because the LVAD decreased the afterload of the ventricles by pumping a partial blood volume inside the ventricular cavity. Therefore, in case of HF, the contraction force decreased from that in normal condition; the negative strain also decreased because of decrease in volume by amount smaller than that in normal condition. Furthermore, in the case of LVAD application, the contraction force was lower than that under no LVAD condition; the negative strain also decreased Fig. .Previous studies on the effect of the LVAD on the RV had focused only on the right ventricular dysfunction due to the geometric structure of the ventricle associated with the alteration of the interventricular septum. There was a lack of studies to quantitatively analyze the various hemodynamic response associated with the RV, and clinical trials had several limitations. Therefore, this study quantitatively analyzed various hemodynamic responses related to the RV without alterations in ventricular septal position under normal, HF, and HF incorporated with continuous LVAD conditions through simulation using a three dimensional finite element electromechanical model of the human ventricles coupled with a lumped model of the circulatory system .As illustrated in Figs. There are several limitations of the present study. First, experimental or clinical data were not collected as part of this study. Instead, the validated cell model and methodologies from previous studies were applied. For example, the myofilament dynamics model from Rice et al.  was applThe continuous LVAD enhance CO and mechanical unloading of the LV as well as those of the RV and prevents pulmonary hypertension that can be induced by LHF. With enhanced LVAD technique and surgical skills, there would be no alteration in the position of the ventricular septum after LVAD implantation. Therefore, the effect of continuous LVAD on hemodynamic responses of the RV under ideal case could be predicted through this study.


Sudden cardiac death (SCD) is the leading cause of death in maintenancehemodialysis (HD) patients, but there is little information about underlyingrisk factors.Evaluate the association between clinical and echocardiographic variableswith SCD on HD patients.Retrospective nested case-control study on chronic HD patients who wereprospectively followed. The primary endpoint was SCD. Variables werecompared by Student t test, Mann-Whitney or Chi-Square, and independentpredictors of SCD were evidenced by multivariate logistic regression.2.7  showedindependent association with SCD events.We followed 153 patients  for 23 ± 14months and observed 35 deaths, 17 of which were SCD events. When compared tothe control group  there wereno differences regarding time on dialysis, traditional biochemicalparameters, blood pressure, smoking, use of cardiovascular protective drugs,ejection fraction, left ventricular dimensions, and diastolic functionindices. On the other hand, in the SCD group, we found a higher prevalenceof previous heart failure, acute myocardial infarction and diabetes, greaterleft ventricular mass index, greater left atrial size and lower globalmyocardial performance. After multivariate logistic regression analysis,diabetes  and left ventricular mass index≥ 101 g/mHD patients with diabetes mellitus and left ventricular hypertrophy appear tohave the highest risk of SCD. Preventive and therapeutic strategies shouldbe encouraged in addressing these risk factors to minimize the occurrence ofSCD in HD patients. Although several variables have been linked to the occurrence of SCD interminal stages of CKD,6 there is alack of studies that simultaneously approach clinical and cardiacmorphophysiological aspects. It is known that the discovery of Dopplerechocardiographic alterations in the left ventricle (LV), such as hypertrophy,dilatation, systolic dysfunction and diastolic dysfunction, is an important step tocharacterize individuals with higher risk.7 It is believed that cardiac structural abnormalities, addedto the regular stress of traditional HD sessions (electrolyte and blood volumechanges), may trigger fatal cardiac arrhythmias.8 The objective ofthis study is to evaluate the association between clinical and Dopplerechocardiographic parameters and SCD occurrence in stable patients undergoingHD.Cardiovascular diseases are the main cause of morbidity and mortality in patientswith chronic kidney disease (CKD) in its more advanced stages, especially inpatients undergoing dialysis.9 Body surface was calculated according to Dubois &DuBois equation (0.20247 x weight0.425 x height0.725).Body mass index (BMI) was calculated through the division of weight (kg) by thesquare of the height (m). Blood pressure, heart rate, weight, and height weremeasured at the time of the exam. The ethics committee for research of theinstitution approved the study protocol in accordance to resolution 196/96 ofthe National Health Council, and informed consent was obtained from allpatients.Retrospective case-control nested study on a cohort of HD patients, withparameters prospectively collected in two renal replacement therapy centers.Inclusion criteria were as follows: age ≥ 18 years; maintenance HDtherapy ; and signed consent form. Exclusion criteria were:recent hospital admission (< 30 days); malignancies; active infection; nonsinus rhythm; significant valvular heart disease ; and pericardial effusion. All patients underwent HDwith standard dialysate , through equipment with polysulfone dialyzers regulated withminimal blood flow of 350 ml/minute and dialysate flow of 500 ml/minute. Theestimate of dry weight (volume to be removed by ultrafiltration in each HDsession) was done by clinical criteria of hydration, blood pressure behaviorduring the session, and electrical bioimpedance (when applicable), as determinedby the assisting doctor in the HD room.10 use of cardiovascularmedication and lab findings were obtained through record analyses. Cause ofdeath was obtained through the analysis of death certificates as well asinterviews with the responsible assisting physician when necessary. The outcomeof the study was SCD, defined as unexpected death, less than 1 hour afterappearance of symptoms. Other events, such as non-sudden cardiovascular deathand non-cardiovascular death, were excluded from the analysis.Demographics, traditional cardiovascular risk factors , previous cardiovascular diseases, intradialytic hypotension (2 or more episodes of symptomatichypotension requiring HD interruption for ≤ 6 months),7 All patients were examined with HDechocardiograph 7XE  equipped with 2.5MHz transducer, for the complete M-mode, bidimensional and Doppler  studies. The following parameters were obtainedby the M-mode: anteroposterior diameter of the left atrium; diastolicinterventricular septum thickness; diastolic thickness of the lower lateralwall; end-diastolic and end systolic LV diameter. Left ventricular mass wasestimated by the Devereux formula and indexed in two ways: by body surface insquare meters and by the height to the power of 2.7.11 Left ventricular hypertrophy was defined bythe presence of mass/height2.7 ≥ 45 g/m2.7 forwomen, and ≥ 49 g/m2.7 for men.11 Systolic function was assessed by calculatingthe ejection fraction through Simpson's method. Mitral transvalvular flow wasrecorded at apical 4-chamber view with a sample of the pulsatile Dopplerspositioned between the extremities of the cusps of the mitral valve, measuringthe velocities of early rapid filling (E wave), atrial contraction (A wave), E/Aratio, and deceleration time of the E wave (DT). Myocardial performance index, representing the global myocardial performance, wascalculated by the equation a-b/b, where a = intermitral interval ; and b = aortic flowejection time, obtained from LV outflow.12 Myocardial tissue Doppler velocities were recorded atapical 4-chamber view with a sample consecutively positioned in the junction ofthe lateral and septal walls of the LV and the mitral annulus. Early diastolicvelocity (e'), diastolic velocity of atrial or late contraction (a'), systolicvelocity (s') of the annulus were measured, and the ratios e'/a' and E/e' were calculated.13 Left atrium volume wasdetermined by the bidimensional through biplanar Simpson's and indexed in twoways: by body surface in square meters, and by the height to the power of2.7.14The exams were performed on an interdialytic day, between 12 and 6 pm, except forMondays, with the objective of minimizing the influence of afterload influenceon the various Doppler echocardiographic indices.The group that suffered SCD was retrospectively identified within the studypopulation and matched for gender, age and BMI in the proportion: 1 case: 2controls. The results were expressed as means and standard deviation (forcontinuous variables with parametric distribution), median (for continuousvariables with non-parametric distributions) and percentage . The groups were compared by unpaired Student's t test, Mann-Whitneyor chi-squared test. Independent association between the various studiedparameters and the occurrence of the outcome was tested by the multivariateconditional logistic analysis to derive odds ratios with 95% confidenceinterval. The significant univariate predictors were added to the multivariatemodel . Forthe definition of the partition value, we used a receiver-operator curveanalysis (ROC). The level of statistical significance was defined as p <0.05. The statistical program "SPSS 13.0 for Windows"  was used for all analyses.Basic demographic, clinical, biochemical and Doppler echocardiographcharacteristics of the individuals forming the study's general population aredepicted in There were 35 deaths during the 23 ± 14 month period of the study. Amongthe events, there were 8 deaths of non-cardiovascular etiology, 10 non-suddencardiovascular deaths, and 17 sudden cardiac deaths in the general studypopulation. This group of 17 patients, characterized as "cases", was matched bygender, age, and BMI, with 34 controls who were alive when their respective"case" died.2.7  showed higher risk of the outcome.Significant variables in the univariate analysis were included in themultivariate logistic regression model, corrected by gender, age, and BMI. Toavoid statistical collinearity and diminish the influence of weight/volume, wedecided to include the indexed left ventricular mass divided by the height tothe power of 2.7, instead of the indexed mass divided by body surface. There wasno independent association between the occurrence of SCD and history of heartfailure or myocardial infarction, left atrium size and global myocardialperformance by MPI . On the2 Recentestimates show that approximately 25% of deaths in patients on dialysis is due toSCD, especially after severe arrhythmias and/or unexpected heart arrest.2 Despite the high incidence of thephenomenon, understanding of risk factors and underlying pathophysiologicalmechanisms remains limited, which restricts the outlining of preventive therapeuticstrategies. It is noteworthy that the incidence of SCD is similar in prospectivestudies with populations of patients on HD15 or peritoneal dialysis.16 Pathophysiology of SCD is complex and uncertain, but it isbelieved that there needs to be an interaction between a transitory event  and a pathologicalsubstrate (such as "uremic cardiomyopathy"). The combination of these alterationswould be responsible for triggering complex arrhythmias and hemodynamic instability,followed by circulatory collapse.8The main finding of this study was to point out the independent association betweenthe presence of diabetes mellitus and left ventricular hypertrophy with higher riskof SCD in patients on HD. SCD is the main cause of death in patients under chronicdialytic treatment.7 The pathophysiology of LV hypertrophy in CKD ismultifactor and depends on the interaction of numerous factors, such as preloadincrease ,afterload increase , and otherparticular consequences of uremia .25Among clinical parameters, only diabetes mellitus was independently associated to theSCD phenomenon, after correction by gender, age, and BMI. Diabetes mellitus is, inmedical literature, a known independent risk factor for SCD. Severalpathophysiological mechanisms for the genesis of SCD in diabetic patients have beensuggested, such as long QT interval secondary to nocturnal hypoglycemia(proarrhythmic environment),21Accordingly, a study investigating the cause of SCD through autopsies in patientswho were on HD found acute myocardial infarction in only 5.7% of cases.26 In the present study, we did notexclude the presence of obstructive coronary artery disease through functional oranatomic tests; however, history of myocardial infarction did not have independentprognostic significance for an outcome of SCD, as observed in a previousreport.21Obstructive coronary artery disease, although frequently observed in patients withadvanced CKD, does not seem to have a clear association with the occurrence of SCDin patients on HD. A prospective study evaluating risk factors for SCD in an HDcohort did not point to coronary artery disease as a variable that was significantlyassociated to the outcome.21 One of thelimitations of our study, during the research observation period, is that it was notpossible to retrieve potassium serum levels from all patients. However, the group ofpatients received dialysis treatment with potassium concentration in the dialysateof 2.0 meq/L, which offers greater protection against serum variations when comparedto potassium concentrations in the dialysate of under 2.0 meq/L.27 Finally, bone and mineralmetabolism disorders, often observed in HD patients,28 may be related to the phenomenon of SCD. It hasbeen shown that patients with hyperphosphatemia on HD seem to be more atcardiovascular risk and risk of SCD than patients with normal parathormone andphosphorus levels.29 However, inour analysis, calcium and phosphorus levels were similar among those who sufferedSCD and those in the control group. Our study has, besides the aforementioned, otherlimitations: retrospective design, relative low number of events , rigour of exclusion criteria, and the absence of the dosageof serum biomarkers (such as proBNP and troponin).It is known that hyperkalemia may determine a higher risk of ventricular arrhythmias,and a pre-dialysis potassium serum level > 6.0 meq/L is associated to a higherrisk of SCD.We concluded that, in clinically stable patients, the occurrence of SCD, duringregular maintenance HD treatment, was independently associated to the history ofdiabetes mellitus and to the left ventricular mass. Preventive and therapeuticstrategies must be encouraged in the approach of these risk factors to decrease theoccurrence of SCD. It will be necessary to have new, more comprehensive, and moreprospective studies, capable of corroborating our findings, showing other variablesthat are potentially related to SCD in CKD environment and investigating theadoption of interventions that minimize the risk of the event in this group ofindividuals.


Cardiac resynchronisation therapy has been shown to be an effective treatment to improve functional status and prolong survival of patients in advanced chronic heart failure. This study assessed the surgical outcomes of left anterior mini-thoracotomy for the implantation of left ventricular epicardial pacing leads in cardiac resynchronisation therapy.Our study consisted of 30 consecutive patients who underwent cardiac resynchronisation therapy with a left thoracotomy between November 2010 and April 2012 in our clinic. Postoperative follow up included the assessment of New York Heart Association (NYHA) functional class, electrocardiography and echocardiography.There were 22 male and eight female patients with a mean age of 68 ± 5.04 years. All patients were in NYHA class III or IV. Pre-procedure mean left ventricular ejection fraction was 28.1 ± 4.5% and post-procedural ejection fraction improved to 31.7 ± 5.1%. The pre-operative QRS duration changed from 171.7 ± 10.8 to 156.2 ± 4.4 ms after the operation. Also there was a significant reduction in left ventricular end-diastolic dimension from 6.98 ± 0.8 to 6.72 ± 0.8 mm (p < 0 .05), but no change in left ventricular end-systolic dimension and severity of mitral regurgitation. All patients had successful surgical left ventricular lead placement. There was no procedure-related mortality. The mean follow-up time was 40.4 months.Surgical epicardial left ventricular lead placement procedure is a safe and effective technique in patients with a failed percutaneous attempt. Cardiac resynchronisation therapy (CRT) improves the symptoms of congestive heart failure (CHF), increases exercise tolerance and decreases rates of hospital readmission. Furthermore, CRT improves ejection fraction and survival rate.While this approach is least invasive, it can be challenging due to restriction of the coronary sinus anatomy, epicardial scar, and unintended stimulation of the left phrenic nerve.The ethics committee of Istanbul Bilim University approved this study, which consisted of 30 consecutive patients who underwent surgical placement between November 2010 and April 2012 of a left ventricular (LV) lead with a left thoracotomy after failure of the percutaneous attempt. This study included patients with New York Heart Association (NYHA) functional class III or IV heart failure, ischaemic (25%) or non-ischaemic cardiomyopathy (75%) with a left ventricular ejection fraction (LVEF) ≤ 35% and QRS duration > 120 ms.Pre- and postoperative follow up involved assessment of NYHA functional class, electrocardiography (ECG), determination of QRS duration, and echocardiographic data. LVEF, left ventricular end-diastolic dimension (LVEDD) and severity of mitral regurgitation (MR) data were collected to analyse the effect of CRT via epicardial LV lead placement on reverse ventricular remodelling. The procedures followed were in accordance with institutional guidelines.A mini-thoracotomy was performed under deep sedation with no need for selective intubation. The patients were placed in a 45° rotation to the right side. A 3- to 4-cm long left minithoracotomy was performed through the fourth intercostal space between the anterior and mid-axillary line. The pericardium was opened longitudinally anterior to the phrenic nerve and suspended with traction sutures to better expose the lateral wall. Epicardial leads were implanted posterior to an obtuse marginal branch, avoiding areas of scarred myocardium.Once a site with satisfactory pacing threshold was identified , the lead was sewn with 5/0 polypropylene sutures. The connector of the lead was tunnelled submuscularly to the device pocket and the pacemaker. Patients were generally extubated in the operating room and observed in the cardiac surgery recovery unit.SPSS 21.0 software  was used for the statistics. For data processing, besides descriptive statistical methods such as frequency, percentage, mean values and standard deviation, the Kolmogorov–Smirnov test was used to evaluate the data distribution. For comparison of the parameters in specific groups, the Wilcoxon Z-test and kappa analysis were used. Survival analysis was obtained with the Kaplan–Meier method. The results were evaluated for significance (p < 0 .05).Between November 2010 and April 2012, 30 patients  with a mean age of 68 ± 5.04 years underwent epicardial LV lead placement following a failed attempt at percutaneous CRT. All patients were in NYHA functional class III or IV. Pre-procedure mean LVEF was 28.1 ± 4.5% and ejection fraction improved to 31.7 ± 5.1% post procedure .The pre-surgery QRS duration reduced from 171.7 ± 10.8 to 156.2 ± 4.4 ms post surgery . In addiPatients spent an average of 1.3 ± 0.4 days in the intensive care unit post operation. Mean length of hospital stay was 4.9 ± 2.2 days. Mean duration (skin-to-skin) of procedure was 52.6 ± 12.5 minutes for left ventricular lead implantation through the mini-thoracotomy.All patients had successful surgical LV lead placement. There was no procedure-related mortality. Intravenous therapy was commonly administered, with diuretics used in 92% of patients and inotropes in 10% of patients.In total, one patient underwent heart transplantation within five months of surgical lead placement. Ten patients (30%) died during the observation period. The mean follow-up time was 40.4 months .CRT has been well-documented to improve left ventricular ejection fraction, heart failure symptoms and survival.The advantage of surgical epicardial LV lead positioning is that direct visualisation helps to select the most suitable surface and avoid epicardial fat or fibrosed areas, which can cause changes in pacing thresholds. Mair et al.In terms of lead function, the pacing threshold in our patients was lower or comparable to that of CS leads.Transvenous insertion of LV leads is currently the route of choice for CRT. Unfortunately, its success rate is about 75 to 93%, as it is totally dependent on the inconsistent coronary venous anatomy.6In the original reports of CRT, epicardial LV leads were placed surgically via a left thoracotomy. These procedures were associated with high apparent success rates.8Puglisi et al.Similarly, we had no surgical complications. In our study we observed that 10 patients in NYHA functional class IV died at the time of percutaneous implantation.Mair et al.12Putnik et al.2In our study, a greater percentage of patients referred for epicardial LV lead placement after a failed coronary sinus approach had non-ischaemic heart failure, which suggests that heart failure aetiology may be predictive of failure of transvenous CRT. It is possible that a greater degree of cardiac chamber and/ or coronary sinus enlargement in patients with non-ischaemic cardiomyopathy may limit access to appropriate pacing sites via the coronary sinus, although this remains to be proven. By contrast, the presence of scarred myocardium may be more likely to lead to unacceptable pacing and sensing thresholds in patients with ischaemic cardiomyopathy.Our results of epicardial LV lead placement demonstrate a clear advantage of avoiding lead-related complications and the necessity of re-operations. Surgical LV lead placement offers the advantage of direct access to the lateral left ventricular wall. Direct visualisation provides an almost unrestricted opportunity to implant the leads at the optimal target site, so that the pre-determined lead position was achieved in all patients.Our analysis is limited by small sample size, lack of data regarding ventricular capture post implantation and the retrospective design.The mini-thoracotomy approach for left ventricular lead implantation is feasible and may avoid some of the limiting factors of transvenous procedures. Furthermore, our observed early functional and haemodynamic improvements show a similarity with that in the literature. This method allows optimal lead implantation under direct vision and therefore reduces the incidence of non-responders, resulting from sub-optimal lead placement. We believe that with improvement in epicardial leads, it may even have potential benefits as primary intervention in a specific subset of patients. With further development of minimally invasive surgical techniques and refinement in choice of pacing leads and lead positions, epicardial left ventricular lead placement may become a reasonable alternative for select patients with heart failure.


E/e′, systolic pulmonary artery pressure, severity of mitral regurgitation, left ventricular global longitudinal strain, NYHA functional classification, radiologic score, and NT-proBNP. However, there was no significant correlation between ULC score and left ventricular ejection fraction, left ventricle diameter, left ventricular volume, or left atrial volume. A multivariate analysis identified the E/e′, systolic pulmonary artery pressure, and radiologic score as the only independent variables associated with ULC score increase. The simplified 7-zone ULC score is a rapid and noninvasive method to assess lung congestion. Diastolic rather than systolic performance may be the most important determinant of the degree of lung congestion in patients with heart failure.Ultrasound lung comets (ULCs) are a nonionizing bedside approach to assess extravascular lung water. We evaluated a protocol for grading ULC score to estimate pulmonary congestion in heart failure patients and investigated clinical and echocardiographic correlates of the ULC score. Ninety-three patients with congestive heart failure, admitted to the emergency department, underwent pulmonary ultrasound and echocardiography. A ULC score was obtained by summing the ULC scores of 7 zones of anterolateral chest scans. The results of ULC score were compared with echocardiographic results, the New York Heart Association (NYHA) functional classification, radiologic score, and N-terminal pro-b-type natriuretic peptide (NT-proBNP). Positive linear correlations were found between the 7-zone ULC score and the following: In patients with congestive heart failure or intravascular volume overload, redistribution of fluids within the lungs leads to pulmonary edema. Excessive extravascular lung water (EVLW) accumulates in the interstitial and alveolar spaces, due to elevated left ventricular (LV) filling pressures . The mosLung ultrasound is a noninvasive and nonionizing imaging technique that has been previously proposed as a bedside tool for evaluating pulmonary congestion in patients with heart failure . LichtenEchocardiography is a noninvasive tool which provides a good understanding of the functional and hemodynamic information in heart failure patients. The ability to evaluate ULCs on lung ultrasound may provide further insight into the clinical and pathophysiological involvement of the lungs. The present study assessed the performance of a simplified ULC scoring system for evaluating pulmonary congestion and investigated clinical and echocardiographic correlates of the ULC score.This was a prospective study. The Ethics Committee of Beijing Chaoyang Hospital approved the protocol, and all patients provided informed consent.During a 6-month period, from August 2015 to January 2016, we studied patients with congestive heart failure who satisfied the modified Framingham criteria  and werePatients with the following were excluded: age < 18 years, atrial fibrillation, mitral stenosis, and pulmonary disease. A diagnosis of pulmonary disease was based mainly on clinical symptoms, chest radiograph, and blood tests. Also excluded were patients with an abnormal pleural line observed by linear probe because B-lines can arise due to interstitial lung disease  or pneumCardiac and lung echographic examinations were performed before intravenous diuretic therapy. All patients were analyzed in the supine, near-to-supine, or lateral position. An experienced operator (HL) with 8 years of echographic examination experience and 2 years of lung ultrasound experience performed the examinations, using Philips CX50  with S5-1 phased-array probe (1–5 MHz) and L12-3 linear probe (3–12 MHz).Before the echographic examinations, a bedside anteroposterior chest X-ray was performed with the patient in the supine position. Scoring of pulmonary congestion was determined through a previously validated radiologic score incorporating assessment of variables  14]. Th. Th14]. E) and late (A) diastolic flow and the ratio of E to A (E/A) were measured from the apical 4-chamber view. A 1.5 mm sample volume was placed at the septal and lateral corner of the mitral annulus. An analysis was also performed for early (e′) and late diastolic velocity, and the average E/e′ ratio was calculated. The severity of mitral regurgitation was assessed semiquantitatively  by color flow Doppler [All patients underwent transthoracic echocardiography examination at bedside. In accordance with the recommendations of the American Society of Echocardiography, the LV end-diastolic and end-systolic diameters  were measured from the M-mode trace, obtained via a parasternal long-axis view. Left ventricular end-diastolic and end-systolic volumes (LVEDV and LVESV), ejection fraction (LVEF), and left atrial volume were obtained from 2-chamber and 4-chamber views using the biplane Simpson's method and indexed to body surface area. The peak Doppler velocities of early . We initially adopted an 8-zone protocol, but inclusion of the anterior lower area on the left side was subsequently removed, because most of the study population had an enlarged heart which intervened with the area. Therefore, the 7-zone protocol was adopted.The elementary findings that were evaluated were the ULCs , defined as hyperechogenic, vertical comet tail artifacts with a narrow base, spreading from the pleural line to the further border of the screen .According to the increasing order of severity of interstitial or alveoli involvement, images were classified as zero, septal syndrome, interstitial-alveolar syndrome, or white lung  Figure . Zero waThe stored images of each patient were scored one month after the baseline assessment, by the same investigator (HL) who performed the corresponding transthoracic ultrasonography examination. Interobserver reliability was assessed by another observer (WZ) by dynamic clips in a set of 20 cases. Each investigator was blinded to the previous results.We also scanned the pleural line with a high-resolution linear probe, to exclude pneumogenic ULCs  and GraphPad 5.0.Standard descriptive results are expressed as mean and standard deviation, and categorical data are expressed as percentage. Correlations between variables were assessed by Spearman's 2-tailed method. Independent correlates of ULC score were identified by multiple linear regression analyses after logarithmic transformation of NT-proBNP. The coefficient of differences among 3 groups was compared using one-way analysis of variance. To assess intraobserver and interobserver reliability, the ULC scores were calculated by a weighted kappa statistic. The diagnostic utility of transthoracic echocardiography in detecting moderate or severe pulmonary congestion symptoms was determined using receiver-operating characteristic (ROC) curves. The best threshold was obtained by selecting the point on the ROC curve that maximized both sensitivity and specificity. Comparisons of the values of two groups were performed using the independent-samples Student's During the study period, 93 heart failure patients with dyspnea were enrolled .Assessments of ULCs were performed in all patients (feasibility = 100%). Bilateral diffuse B-lines were identified in all patients by lung ultrasound . The durThe kappa values for the intra- and interobserver reliabilities of the simplified ULC score assessment were 0.92 and 0.90, respectively.r = 0.60; P < 0.0001), NT-proBNP values , and NYHA functional class .Significant linear correlations were found between the simplified ULC score and radiologic score , SPAP . The correlation between simplified ULC score and GLS was also significant , but rather weak. No significant correlation was found between ULC score and any of the following parameters: LVEF, end-diastolic or end-systolic diameter, volume, or volume index. There was also no significant correlation between ULC score and left atrial volume, left atrial volume index, or TAPSE.There was a significant correlation between the simplified ULC score and each of the following: average E/e′ was significantly reduced, SPAP was increased, and LV GLS was mildly reduced, but LVEF was normal. E/e′ , SPAP , and the radiologic score .The multivariate analysis showed that the only variables independently associated with ULC score weren = 28, 30%), 25–39% , or <25% . Among these groups, the ULC scores were statistically similar (P > 0.5). However, the ULC scores of the 3 grades of diastolic dysfunction  were significantly different , and the sensitivity and specificity was 78.6% and 76.9%, respectively. Compared with patients with ULC < 8, those with ULC ≥ 8 were older, with higher E/e′, SPAP, radiologic score, NT-proBNP, LV diastolic function, and NYHA functional class and more severe mitral regurgitation . The argitation . E/e′ according to the ROC curve was 18.4  and SPAP, and evaluate LV filling pressure . Existinpatients . These dHowever, unlike the above studies, we found that the LVEF was somewhat less informative for predicting the degree of lung congestion. The discrepancy in results could be due to different study populations. Ours was limited exclusively to a cohort of identified left heart failure patients with pulmonary congestion. In some contexts, it has been shown that the signs and symptoms of congestive heart failure correlate poorly with LVEF , 33. GanAn enlarged left heart is suggestive of chronically elevated LV filling pressure. A normal left heart volume is often noted in patients with acute increase in LV filling pressures or in the earliest stage of diastolic dysfunction. However, our study population included patients with a history of chronic heart failure; and this may be the reason for the inconsistency between left heart volume and pulmonary congestion degree.In the present study, we offer a simplified ULC scoring method to estimate the degree of congestion that considered only 7 thoracic zones. This tool is less refined than counting all the B-lines in 28 sectors but provides easy-to-acquire data in an emergency setting, and it is much easier to differentiate 4 types of ULC patterns than it is to count B-lines.The study may be considered limited by the lack of patients with atrial fibrillation and mitral stenosis. A goodly proportion of patients with heart failure experience these conditions, especially those with preserved LVEF . On the Our conclusions are based only on imaging evaluations and echocardiographic indices. While B-lines are thought to reflect EVLW, there is no reference standard available to verify the EVLW volume and left atrial pressure (LAP) by invasive catheter.This novel simplified ULC scoring method is a rapid, noninvasive, and reliable tool to assess pulmonary congestion in patients with heart failure. Diastolic rather than systolic performance may be the most important determinant of the degree of lung congestion in these patients.


Background: Coronary artery calcification (CAC) is common in patients with chronic kidney disease on hemodialysis (CKD-5D) and is an important predictor of mortality. However, cardiac functional links between CAC and mortality have not been well established. This study tested the hypothesis that CAC increases mortality by adversely affecting cardiac function. Methods: Patients were recruited from 37 regional dialysis centers. 2-D and Doppler echocardiographic analyses were performed, and CAC was measured using 64-slice computed tomography. Relationships between CAC and echocardiographic measures of left ventricular (LV) function were analyzed. Survival was assessed with median follow-up of 37 months. Results: There were 157 patients: 59% male, 46% Caucasian, 48% diabetic. Median age was 55 years, and median duration of CKD-5D was 45 months. Agatston CAC scores > 100 were found in 69% of patients, with 51% having a score > 400. CAC was associated with measures of LV systolic and diastolic function ), peak LV systolic velocity , and estimate of LV filling pressure . Multivariate regression confirmed these relationships after adjustment for age, gender, LV ejection fraction, and coronary artery disease. Valvular calcification varied linearly with CAC (p < 0.05). Both LV diastolic and systolic functional measures were significant predictors of mortality, the strongest of which was LV diastolic dysfunction. Conclusions: These findings show a link between CAC, cardiac function, and mortality in CKD-5D. LV diastolic function (E:E’), peak LV systolic velocity, and GLS are independent predictors of mortality. Valvular calcification may be an important marker of CAC in CKD-5D. These effects on cardiac function likely explain the high mortality with CKD-5D and describe a potentially-valuable role for echocardiography in the routine management of these patients.  CKD-5D is characterized by a high coronary artery calcification (CAC) burden that is strongly associated with adverse global cardiac function. Additionally, cardiac valvular calcification detected by echocardiography is common in CKD-5D and is linked to both CAC severity and abnormal LV function. Abnormal cardiac function manifested from CKD-5D adversely impacts survivability. Therefore, these findings support the recommendation that a comprehensive echocardiographic evaluation be part of the cardiovascular risk stratification in CKD-5D patients. Patients with chronic kidney disease (CKD) are at increased risk of developing cardiovascular (CV) disease and have a higher mortality attributed to cardiac causes compared to patients without CKD , 2, 3. BWe hypothesize that CAC impacts mortality in this patient population by adversely affecting global cardiac function. To this end, our objectives for this retrospective study are 1) to define the spectrum of cardiac structural and functional changes occurring in patients with CKD-5D and 2) to determine how strongly CAC is associated with the structural and functional cardiac manifestations in CKD-5D patients. Patients with CKD-5D were recruited from 37 dialysis centers across the state of Kentucky to participate in a large prospective cohort study evaluating the relationship between CAC and mineral bone disorder. Inclusion criteria were: age 18 years or older; chronic maintenance dialysis of at least 3 months duration; and calcidiol levels within normal range. Exclusion criteria included pregnancy; systemic illnesses or organ diseases (except diabetes mellitus); clinical conditions that may limit study participation ; chronic alcoholism and/or drug addiction; participation in a study of an investigational drug during the past 90 days; on active transplant list; treatment within the last 6 months with drugs that may affect bone metabolism . Out of this population, a parallel sub-study was designed as a prospective cohort followed to investigate the link between CAC and structural and functional changes within the heart. Over a 2-year period from 2012 to 2014, a total of 157 patients consented and were enrolled in this sub-study. Patients were required to undergo both echocardiography and noncontrast computed tomography (CT) scanning to evaluate cardiac morphology and function as well as CAC, respectively. The investigators adhered to the Declaration of Helsinki in the conduct of the study and registered the IRB-approved study with ClinicalTrials.gov (#NCT00859612). Blood samples were obtained from all participants, and the following traditional and nontraditional bone markers were measured: plasma intact parathyroid hormone (PTH), bone-specific alkaline phosphatase (BSAP), tartrate-resistant acid phosphatase-5b (TRAP-5b), sclerostin, Dickkopf-1 (DKK-1), and fibroblast growth factor-23 (FGF-23). Serum calcium and phosphorus levels were also measured. Methods employed to measure levels of these markers are as described previously . 2 with a density of ≥ 130 HU and quantified by the Agatston scoring method [3. A square root of the volume transformation was performed to facilitate data interpretation (CAC SRVT (square root volume transformed)) [CAC Agatston scores were obtained by noncontrast multiple-slice computed tomography using a SOMATOM 64 × 0.6 collimation scanner for all scans . Images were acquired from the carina to the left ventricular (LV) apex. Scan parameters additionally included ECG gating, 120 kVp, 80 mAs/rotation, 0.33 s gantry rotation time, and 3 mm slice thickness. Images were analyzed on a 3D workstation using calcium-scoring software . Calcifications were identified as a plaque of ≥ 1 mmg method . Additioformed)) . IntraobEchocardiograms were performed by an experienced sonographer using a Phillips IE-33 ultrasonography machine , with the patient breathing quietly in the left decubitus position. Resting blood pressure, heart rate, and morphometric measurements were obtained at the time of echocardiographic examination. Echocardiographic measurements were performed from standard American Society of Echocardiography (ASE) views, including the parasternal long axis and short axis, apical 4-chamber, apical 2-chamber, and sub-costal views. Two-dimensional images, flow and tissue Doppler images, and M-mode were analyzed. Tissue Doppler imaging was accomplished using a 2 mm-length sampling volume with the transducer positioned at the mitral annulus in both the lateral and septal positions from the apical 4-chamber view and anterior and inferior positions from the apical 2-chamber view. All reported cardiac morphological and functional measurements were obtained based on current ASE guidelines . Cardiac valvular calcification was defined as the presence of bright echogenic areas of at least 1 mm in length in the affected valve involving one or more leaflets of the mitral or aortic valves, mitral or aortic annulus, or the papillary muscles or chordal structures. The severity of calcification was graded on a semi-quantitative scale of 0 – 3, where 0 represents the absence of calcification, 1 represents mild calcification, 2 represents moderate calcification, and 3 represents severe calcification. Severity was judged by the number of leaflets involved (≤ 1 vs. > 1), the number of valves involved (≤ 1 vs. > 1), and the extent of involvement  . LV systolic function was determined by estimation of LV ejection fraction (LVEF) using the modified Simpson’s biplane method as detailed in the ASE guidelines . In addiLV diastolic function was assessed using mitral valve inflow Doppler as well as tissue Doppler imaging. The ratio of early passive LV diastolic filling (E) to late LV diastolic filling (A) was determined for initial classification of diastolic grade. The average of the septal and lateral mitral annular velocities from tissue Doppler imaging was used to determine the velocity of diastolic LV excursion corresponding to early LV diastolic filling (E’). This allowed for a calculation of the ratio of E:E’, which correlates with LV filling pressure. 2-tests, as appropriate. Due to the number of comparisons made, the significance threshold was set at p < 0.01. Statistical calculations were performed using SPSS™ software  version 22. Association between variables was calculated using Spearman’s Rho nonparametric test for correlation. Group comparisons of continuous variables were performed with nonparametric Mann-Whitney U or Kruskal-Wallis tests as appropriate. Dichotomous variables were compared using Fisher’s exact or χ2). A total of 157 CKD-5D patients were enrolled, for whom demographic and clinical information is shown in A total of 51% of patients had CAC scores greater than 400, 18% had CAC scores between 100 and 400, and 31% had CAC scores < 100, including 17% who had a CAC score equal to 0 . Male suAmong the structural parameters assessed using echocardiography, only cardiac valvular calcification was found to be strongly correlated with CAC by univariate analysis  . ValvulaLVEF and peak LV systolic velocity were largely preserved in this cohort, however, within the range of peak LV systolic velocity values, they varied inversely with both CAC  and cardiac valvular calcification score  by univariate analysis  Table 4Table 4. Approximately half of the study subjects were found to have abnormal values for global longitudinal strain (GLS). Similar to the findings for LV systolic velocity, GLS correlated with CAC . As with LV systolic velocity, no relationship was found between GLS and age, race, or duration of CKD-5D. Notably, LV systolic velocity and GLS were more abnormal in study subjects with a history of CAD . Multivariate analysis demonstrated CAC SRVT to be an independent predictor of GLS after adjustment for age and gender . Further adjustment for known CAD resulted in CAC no longer being predictive of GLS , likely due to their strong correlation. Taken together, these results suggest a link between CAC severity and LV systolic dysfunction. In general, echocardiographic-derived measures of LV diastolic function indicate that more than 25% of this cohort have elevated LV filling pressure as defined by an E:E’ ratio ≥ 15. No relationship was found between age, race, gender, dialysis vintage, or history of CAD and E:E’. CAC and cardiac valvular calcification scores, however, demonstrate significant correlations by univariate analysis with estimates of LV filling pressure, a measure of LV diastolic function  . In addiWe found no association between CAC and sclerostin, DKK-1, FGF-23, PTH, BSAP, and TRAP-5B, nor between these markers and cardiac function or structure. Interestingly, serum levels of FGF-23 correlated positively with GLS  and negatively with LVEF . FGF23 remained an independent predictor of GLS  with adjustment for male gender, CAD, and dialysis vintage (n = 87). Multivariable analysis taking into account FGF-23 status did not alter the relationship between CAC SRVT and GLS or LV systolic velocity. No other biomarkers demonstrated associations with LV function. th year, the differences in survival narrowed to 74 vs. 79%, and the overall difference between the groups did not reach significance (Wilcoxon p = 0.067). Several echocardiography measures were independently predictive of survival, including advanced LV diastolic dysfunction associated with an elevated LV filling pressure (E:E’), peak LV systolic velocity, and GLS. LVEF did not impact survival in this population. There were 27 deaths recorded among our cohort over the course of this study, representing a 17% mortality rate. The median duration of follow-up was 37 months . The overall Kaplan-Meier survival curve is shown in E:E’ remained a strong predictor of mortality after adjusting for CAD, LVEF, age, and diabetes status (E:E’ Z-score hazard ratio (HR) of 1.8; 95% CI 1.2 – 2.6; p = 0.003; N = 142). Peak LV systolic velocity conferred a protective effect on mortality in this population b. After In this cross-sectional, prospective study of contemporary CKD-5D patients, several key findings are evident: 1) CKD-5D patients as a group are faced with a significant CAC burden, not simply in terms of prevalence but also in relation to CAC severity, such that 69% of patients had CAC scores above 100, which has been associated with high risk of cardiovascular events, and over half were at very high risk, with CAC scores above 400; 2) detection of CAC is often linked with evidence of adverse cardiac systolic and diastolic function; 3) cardiac valvular calcification detected by echocardiography is common in CKD-5D is also tied to adverse cardiac function and may serve as a marker of CAC; and 4) CAC and adverse cardiac function are strong predictors of mortality in CKD-5D. Our cohort consisted of patients with advanced kidney disease on hemodialysis who, not surprisingly, also had other identifiable CV risk factors. Interestingly, while 26% of these patients reported a history of CAD, 83% were found to have evidence of CAC, and more than half had a CAC score above 400, which has been associated with an elevated risk of future CV events including myocardial infarction and death. Furthermore, our results demonstrate a significant association between CAC burden and LV function. Specifically, both LV systolic and diastolic function are adversely affected by the presence of CAC. Despite the fact that patients in our cohort were mostly found to have preserved LV systolic function on the basis of LVEF assessment alone, more sensitive measures of LV systolic function, including tissue Doppler-derived peak LV systolic velocity and speckle-tracking-derived GLS, demonstrate worsening LV systolic function as a function of CAC severity. Multivariate analysis adjusted for age, diabetes, gender, and CAD showed CAC to be a significant predictor of LV peak systolic velocity. Similarly, multivariate analysis demonstrated a significant and independent association between CAC and GLS after adjustment for gender and age. This relationship between CAC and cardiac function is further strengthened by an association between CAC burden and echocardiographic-derived measures of LV diastolic dysfunction. In fact, CAC burden was a significant predictor of advanced LV diastolic dysfunction as measured by LV filling pressure estimates (E:E’) after adjustment for age, diabetes status, and CAD. Taken together, our findings show the development of subclinical LV systolic and diastolic dysfunction in CKD-5D patients and that this is tied to underlying CAC, thereby corroborating and extending previous reports linking loss of kidney function with CAC and abnormal cardiac function , 35, 36.In our cohort, the presence of advanced LV diastolic dysfunction (E:E’), low peak LV systolic velocity, or abnormal GLS was associated with worse survival. The strongest predictor of survival in our cohort was LV diastolic dysfunction. These factors remained significant predictors of survival even after adjustment for age, gender, CAD, and diabetes status. This is in contrast to a more recently-published study in patients with CKD-5 who were just starting hemodialysis . In thatValvular calcification is more common in patients with CKD compared to persons without CKD, and so it is not surprising that a large proportion of the participants in our study have valvular calcification , 39. ImpFinally, we assessed the association of echocardiographic parameters with serum levels of several bone markers known to be involved in the pathophysiology of chronic kidney disease – mineral and bone disorder (CKD-MBD). Among these, only FGF-23 was found to have a modest, but statistically – significant relationship with LV GLS after adjustment for age, gender, and CAD. The significance of this finding is not clear, although it is novel and potentially highlights the impact of the mineral bone disorder aspect of CKD on cardiac function. Other studies have shown a strong correlation between FGF-23 levels and left ventricular hypertrophy (LVH) in patients with CKD , 47, 48.Some limitations of our study should be noted. First, this is a cross-sectional cohort of patients with CKD-5D who were clinically stable. Therefore, our findings may not be applicable to hospitalized patients, patients with milder stages of CKD, or post-kidney-transplant patients with CKD. These findings, however, are derived from a population representative of CKD-5D patients in a real-world outpatient setting with a significant proportion of African American and diabetic participants. In this regard, we believe that these findings will have relevance across the general CKD-5D population. Second, considering that a large proportion of the study population had evidence of mitral annular calcification, our ability to adequately assess LV diastolic function is limited. However, when patients with moderate to severe mitral annular calcification were removed from the analysis, the relationship between CAC, cardiac valvular calcification, and LV diastolic function remained. Thirdly, we report on 157 study participants among whom there were 27 deaths.  Despite the low absolute number of deaths, we were able to show a significant difference in survival on the basis of CAC score at years 1 and 3, but not at year 4. Since these events are spread over the span of 4 years, the number of patients available for analysis becomes smaller over time and may impair our ability to detect a statistically meaningful difference between the groups with higher vs. lower CAC scores.  Additionally, these patients have numerous other comorbidities that undoubtedly influence their risk of mortality, thereby potentially diluting the effect of CAC on survivability over time. In conclusion, CKD-5D is characterized by a high CAC burden, which is tied to adverse diastolic and systolic cardiac function and mortality. The findings underscore the importance of CAC and its serious clinical relevance in this patient population. Cardiac valvular calcification detected by echocardiography is common in these patients and is independently linked to both CAC severity and abnormal LV function. Finally, the bone biomarker FGF-23 is associated with subclinical LV systolic dysfunction. These findings support the value of a comprehensive echocardiographic evaluation for cardiovascular risk stratification in CKD-5D patients. The authors have no conflicts of interest to disclose. Research reported in this publication was supported by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health under award number R01DK080770 and the Kentucky Nephrology Research Trust. The project was supported by the National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health, through Grant UL1TR000117. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. We would like to acknowledge the contribution of the University of Kentucky echocardiography staff and most notably Paul A. League who served as principal sonographer on this study. We also recognize the research coordinators Kimberly McLaughlin, PA-C, and Nedda Hughes, PA-C, who enrolled the patients, recorded all data, and guided patients through all study activities.


Emerging cardiovascular biomarkers, such as speckle tracking echocardiography (STE) and aortic pulse wave velocity (aPWV), have recently demonstrated the presence of subclinical left ventricular dysfunction and arterial stiffening in patients with chronic kidney disease (CKD) and no previous cardiovascular history. However, limited information exists on the prognostic impact of these biomarkers. We aimed to investigate whether STE and aPWV predict major adverse cardiac events (MACE) in this patient population. In this cohort study we prospectively analysed 106 CKD patients with no overt cardiovascular disease (CVD) and normal left ventricular ejection fraction. Cardiac deformation was measured using STE while aPWV was measured using arterial tonometry. The primary end-point was the composite of all-cause mortality, acute coronary syndrome, stable angina requiring revascularization (either using percutaneous coronary intervention or coronary artery bypass surgery), hospitalization for heart failure and stroke. Over a median follow up period of 49 months (interquartile range 11–63 months), 26 patients (24.5%) reached the primary endpoint. In a multivariable Cox hazards model, global longitudinal strain (GLS)  and aPWV  were significant, independent predictors of MACE. GLS and aPWV independently predict MACE in CKD patients with normal EF and no clinically overt CVD. Chronic kidney disease (CKD) patients are a group at significantly increased risk of cardiovascular (CV) events, as a result of prolonged exposure to an ever-growing array of traditional and non-traditional risk factors . Most riConventional echocardiographic measures of left ventricular (LV) geometry, structure and function are significant predictors of outcomes in the CKD population. Prevalence of LV hypertrophy (LVH) , 5, diasPrevious studies have also shown that aortic stiffness as measured by aortic pulse wave velocity (aPWV) predicts cardiovascular mortality in patients with CKD  and ESRFThe current study hypothesized that subclinical markers of myocardial (STE) and vascular (aPWV) disease can provide important prognostic value in predicting major adverse cardiac events (MACE) in CKD patients  with no overt CVD and normal LVEF by conventional echocardiography.A prospective, observational cohort study was conducted involving 121 consecutive patients, recruited from outpatient nephrology clinics at Hammersmith and Charing Cross Hospitals, Imperial College Healthcare NHS, London, UK. Written informed consent was obtained from all participants and the study was approved by the UK National Research Ethics Committee Service (REC 10/H0704/81). The study conforms to the principles outlined in the Declaration of Helsinki. Patients on haemodialysis, or those with clinical or echocardiographic evidence of LV systolic dysfunction (Simpson biplane LVEF < 55%), presence of regional wall motion abnormalities, significant valvular abnormalities (moderate or severe), presence of atrial fibrillation or flutter, known pulmonary hypertension, congenital heart disease, cardiomyopathy, pericardial disease, or inadequate echocardiographic acoustic windows were excluded from this study.All patients were asymptomatic from a cardiovascular point of view, and had normal systolic function, as assessed by conventional echocardiography. We carefully reviewed the clinical notes for all patients and any patient displaying evidence or signs of heart failure was excluded from the study.CKD etiology, cardiovascular risk factors, and detailed drug history were recorded. Bio-chemical results were obtained from the most recent renal clinic review, provided that there was no evidence of superimposed acute kidney injury during the time of blood sampling. The value of estimated glomerular filtration rate (eGFR) was calculated using the four-variable equation in the Modification of Diet in Renal Disease (MDRD) study .All participants were followed up for a median time of 49 months (interquartile range 11–63 months). The primary end-point was a composite of all-cause mortality, acute coronary syndrome, stable angina requiring revascularization [either using percutaneous coronary intervention (PCI) or coronary artery bypass surgery (CABG)], hospitalization for heart failure and stroke. Deaths were identified from the office of national statistics (ONS). All patients were followed up either in outpatient clinics or by telephone conversation.All echocardiographic parameters were obtained using the VIVD 7 echocardiographic machine . The images obtained were stored and subsequently analyzed offline in EchoPac version 12  by a single, accredited investigator blinded to all baseline data.LVEF was obtained using the modified Simpson’s rule . LV dimeCustomized software performed the speckle tracking analysis for VIVID 7 . Global longitudinal strain (GLS) Fig. On the same day, approximately 10 min after performing the echocardiogram, blood pressure was measured with the subjects still in a supine position. Pressure waveforms were recorded on the carotid and femoral arteries using applanation tonometry . Carotidt test and categorical variables using the Chi square or Fisher’s exact test as appropriate. Estimated primary outcome free survival in different groups was calculated using the Kaplan Meier method, and comparisons were made using the log-rank test. Multivariate Cox proportional hazards regression analysis was performed to identify independent predictors of the primary outcome. Two tailed p values of <0.05 were considered statistically significant.SPSS V22  was used for statistical analysis. Normality of the variables assessed was tested using the Kolmogorov–Smirnov test. Data are presented as mean ± SD. Continuous variables were compared using a Student’s Following the exclusion of patients with poor endocardial definition (9) and pre-existing structural heart disease (6) at baseline echocardiography, the final patient population included 106 patients.We previously demonstrated excellent intra and inter-observer agreement of STE and aPWV values between individuals .Median follow up was 49 months (interquartile range 11–63 months). Overall 26 patients (24.5%) reached the primary end point. During the follow up period, five deaths (4.7%) , four ST elevation MI (3.8%), two non-ST elevation MI (1.9%), three admissions for urgent PCI (2.8%), five admissions for an elective PCI (4.7%), three CABG revascularizations (2.8%), one unstable angina [leading to CABG revascularization (0.9%)], one admission for heart failure (0.9%) and two strokes (1.9%) occurred.The baseline clinical and imaging characteristics are shown in Table As shown in Table In a multivariable analysis Table , GLS , and aPWV with a cut-off value of 10.2 m/s (76.1% sensitivity and 69.6% specificity) had the best discriminatory power to predict the occurrence of the primary outcome (Table log rank = 0.001). Aortic PWV was a significant predictor in later CKD stages . Although we didn’t find any statistical significance from the speckle tracking parameters between the groups we saw a considerable trend toward significance with GLS  Table Cox univariate regression sub-analysis between CKD groups demonstrated that more advanced CKD stages 4 and 5) had more outcomes when compared with earlier stages CKD  to predict MACE. Another interesting finding of the current study is that, at baseline, patients that reached our composite primary endpoint (MACE) had significantly impaired GLS compared to patients who did not suffer MACE, even though LVEF was similar in both groups. This fact suggests that GLS may be able to detect CKD-related myocardial changes early in its course, as it primarily evaluates the function of subendocardial longitudinal fibres that are more sensitive to cardiac injury . In factNone of the remaining deformation parameters were significant predictors of CV events. Due to the derivation of strain, SR is inherently noisier than strain, and previous correlations between MRI tagging and STE were poorer for SR when compared with strain , which mLV rotational mechanics are altered with advancing age and various medical conditions such as MI, hypertension, diabetes mellitus and dilated cardiomyopathies –45, howeFrom the conventional echocardiographic parameters, only E/e′ (average) was a significant, independent predictor of MACE in our cohort. LV diastolic dysfunction, characterised by abnormalities of ventricular filling, including decreased diastolic distensibility and impaired relaxation, is a very common structural abnormality in patients with CKD . E/e′ halog rank = 0.019).Arterial remodelling is known to be present even in the early stages of CKD. Compared with normotensive and hypertensive controls, patients with CKD stages 2–5 had significantly larger internal carotid artery diameters but comparable intima-media thickness, resulting in significantly increased circumferential wall stress . When itlog rank = 0.001). Nevertheless, in CKD stages 4–5, we found that aPWV is the most robust parameter to predict MACE in our cohort, which is in line with previous research [We also aimed to perform a sub analysis to assess predictors of outcome in patients with early (stages 1–3) versus advanced  CKD. A few authors already established that cardiac and arterial changes start to develop early in the uremic milieu , 56. In research . In statThe current study presents a number of strengths. It includes a comprehensive assessment of subclinical myocardial and vascular parameters in an asymptomatic from the cardiovascular point of view CKD cohort with a long follow-up period (49 ± 9 months). However the results of this study may require careful interpretation due to some limitations. (1) Although STE measurements as strain or LV twist have been validated against sonomicrometry and CMR, vendor reproducibility , the neeIn CKD patients with no clinical or conventional echocardiographic evidence of significant CVD, GLS and aPWV independently predict the occurrence of MACE. If our findings are validated in larger prospective studies, GLS and aPWV may become a useful addition to the current risk stratification tools, aiming to prevent future cardiovascular events in this high-risk patient cohort.


The RWT tended to be higher among athletes (p = 0.09) indicating LV concentric remodeling geometry. Soccer players had significantly larger RV size (p < 0.04) with similar function and mass. Also, the LA volume (p = 0.01), LA area (p = 0.03) and LA diameter (p = 0.009) were significantly greater in players than in controls. Cardiac adaptations in pre-adolescent soccer players are characterized by an increased LV mass without any changes in LV size and systolic function, which is typical of resistance training with tendency to concentric remodeling. This is accompanied by increase of LA and RV size. It should be taken into account during annual pre-participation evaluation.Physical training is associated with changes in cardiac morphology called the “athlete’s heart”, which has not been sufficiently studied in children. The aim of the study was to analyze cardiac adaptation to exercise in pre-adolescent soccer players. Thirty-six soccer players (mean age 10.1 ± 1.4 years) and 24 non-athlete male controls (10.4 ± 1.7 years) underwent cardiac magnetic resonance. Measurements of myocardial mass, end-diastolic and end-systolic volume, stroke volume and ejection fraction for left and right ventricle  were performed. Additionally, left and right atrial  areas and volumes were analysed. Relative wall thickness (RWT) was calculated to describe the pattern of cardiac remodeling. Interventricular wall thickness and LV mass were significantly higher in athletes, but remained within the reference (6.9 ± 0.8 vs. 6.2 ± 0.9 mm/√m According to the World Health Organization (WHO), physical activity in school-aged children provides fundamental health benefits, improves cardiorespiratory and muscular fitness and reduces cardiovascular risk in the future life . The WHOUnfortunately, almost all the studies have been carried only on adult and young adolescent players , 11. OnlSoccer is the most popular sport in Europe , which rThe aim of our study is to investigate the effects of prolonged soccer training on cardiac morphology and function in school-aged players using CMR.2) volunteered to take part in the study. All of the participants have been engaged in regular training (2 × 90 min per week with 60 min league matches on weekends) for at least 2 years during most months of the year (except July and August). CMR examinations took place during their competitive (active) season.Thirty-six male, Caucasian soccer players, age 8–12 years old  who volunteered for the study. They have practiced recreational sport during school classes and seasonally, but were not engaged in any formal physical training or organized physical activity. All the subjects were healthy and were not taking any medications that would affect cardiovascular fitness. BSA was calculated according to the Mosteller formula [The findings were compared with the 24 healthy male, Caucasian, age- and BSA-matched controls  including initial scout images, followed by cine steady-state free precession (SSFP) breathhold sequences in 2-, 3-, and 4-chamber views. The short axis was identified using the 2- and 4-chamber images and included the whole heart from ventricular apex up (including the atria). Imaging parameters were as follows: field of view 340 mm, matrix 208 x 256, repetition time approximately 39.24 ms, echo time 1.43 ms, flip angle 39 degrees, slice thickness 6 mm, gap 2 mm, in-plane image resolution 1.6 × 1.6, temporal resolution 25 phases per cardiac cycle. Quantitative measurements were preceded by venc-scout velocity range assessment in the aorta at the level of the sino-tubular junction .Images were analysed with the use of dedicated software. Initially, short axis SSFP cine images were previewed from the base to the apex in a cinematic mode, then endocardial and epicardial contours for end-diastole and end-systole of both ventricles were manually traced. Trabeculae and papillary muscles were considered as ventricle cavities. Delineated contours were used for the quantification of LV and RV end-diastolic and end-systolic volumes , stroke volumes , ejection fractions  and masses . Obtained values were internally validated against flow measurement in the ascending aorta. Then the parameters were indexed for BSA and presented as LVEDVI, LVESVI, LVSVI, LVMI, and RVEDVI, RVESVI, RVSVI, RVMI.The LV internal diameter (LVEDd), interventricular wall thickness (IVS) and LV posterior wall thicknesses (PWD) in end-diastole and aortic bulb (AB) diameter and ascending aorta (AA) diameter in end-systole were measured on the 3-chamber images and based on the above, the relative wall thickness (RWT) was calculated as , 19:\docIn measuring IVS, care was taken to exclude right ventricular septal bands. In measuring the PWD, care was taken to exclude posterior wall chordae. A RWT was considered to be abnormal if > 0.42 , 17.Subsequently, the volumes of the left and right atria  were also manually traced on end-systole and end-diastole to get the maximal and minimal volumes . Additionally the area of both atrias was measured on end-systole in 4-chamber view  and LA diameter was measured on end-systole in 3-chamber view (LAD). Area and volume measurements  were adjusted to BSA and linear measurements  to the square root of BSA and were presented as LAVol_max_I, LAVol_min_I, RAVol_max_I, RAVol_min_I and LA_area_I, RA_area_I and LADI.Furthermore, to simply assess RV volume and systolic function, two parameters were measured: (1) RV diameter in the 4-chamber view in end-diastole in the widest possible place below tricuspid annular ring and indexed as RVDI, and (2) tricuspid annular plane systolic excursion (TAPSE) towards the apex in the 4-chamber view, measured by marking position of RV free wall and tricuspid annulus junction point in end-diastole and in end-systole and measurement of the distance between the two positions. The following criteria served as reference ranges .All of the CMR measurements were assessed by a European Society of Cardiology certified Level 3 expert with 9 years of expertise in the field (Ł.A.M.) and by a second reader (M.B-F.) with over 1 year of expertise.χ2 test or the Fisher exact test, depending on the abundance of the individual subgroups. In order to assess differences between means and medians, the Student’s t test for independent variables or the Mann–Whitney test for independent variables was used, respectively. In order to assess the correlation between continuous variables, the r-Pearson or Spearman test were applied, respectively. Inter-observer and intra-observer variability for CMR measurements of LVMI, RVEDVI and LA volume was assessed respectively in ten and five randomly selected patients using the Bland–Altman repeatability analysis method and interclass correlation coefficient (ICC). Bias was expressed as an average ± 2 SD. All tests were bilateral and p < 0.05 was considered as statistically significant. MedCalc software version 10.0.2.0  was used for statistical analyses.Nominal variables were presented as absolute numbers and percentages, continuous variables in the form of means and standard deviations  or medians and interquartile range . Normality of distribution was assessed with means of the Kolmogorov–Smirnoff test. Comparison of percentage distribution of individual nominal variables between groups was made with the 3 with SD ± 3 cm3 for LA or RA volume) given two-tailed α = 0.05 and 1.75 allocation between groups.Sample size was determined with G*power . We estimated that a sample size of at least 31 individuals in the study group and 17 controls would have a power of 90% to detect an approximately 10% between-group difference . All soccer players had normal LV systolic function. There were no significant differences in LV size and LVEF between study and control group.p = 0.036 for RVEDVI and p = 0.037 for RVESVI).End-diastolic RV volume was increased in four soccer players (11.1%). All soccer players had normal RV systolic function. However, when compared to controls, the study group had significantly higher RV size (p = 0.0006) in players as compared to controls (57.1 ± 7.4 vs. 50.0 ± 7.1 g/m2). However all LVMI values in athletes were within the reference range (38–86 g/m2) according to normal values published by Kawel-Boehm et al. [p = 0.003 for IVS, p = 0.08 for PWD).LVMI in end-diastole was significantly increased  and in five of them (13.9%) exceeded 0.42, indicating LV concentric remodeling geometry . There were no significant differences in RVMI between both groups.In the study group there was no correlation between RWT and LVMI, in contrast to the control group where good correlation of these parameters was observed (p = 0.01), LA area (p = 0.03) and LADI measured in 3-chamber view (p = 0.009) were significantly higher in soccer players than in controls. There was also a tendency to higher RA minimal volume among athletes (p = 0.06).The values of minimal LA volume (There was a very good agreement for LVMI between two readers and for the repeated assessment of the same operator (Ł.A.M.). The Bland–Altman plots showed average difference in estimates of − 0.5 ± 2.8% for inter-observer variability and 0.0 ± 1.8% for intra-observer variability. ICC was 0.92 for inter-observer variability and 0.96 for intra-observer variability. Similar results were obtained for other analyzed parameters (RVEDVI and LA volume).Morphological cardiac changes in response to physical conditioning depend on the type, duration and intensity of training . In 1975This is the first study to examine cardiac effects of soccer on the pre-adolescent population using CMR. We showed that the LV wall thicknesses  were significantly increased in soccer players compared to controls with no changes in LV cavity size and function, which, in correlation with increased LVMI (by about 14%), suggest cardiac changes characteristic for resistance sports.p < 0.001), whereas there were no differences in absolute values of LV septal and posterior wall thicknesses and LVM [Our results are different from the findings of Zdravkovic et al. who used echocardiography to analyse 94 pre-adolescent male footballers (mean age 12.85 ± 0.84 years). The author showed significant increase of absolute LV dimensions  or concentric remodeling (RWT > 0.42) . In our Similar results were recently demonstrated by Finocchiaro et al., who used echocardiography to analyze athletes practicing approximately 40 sport disciplines subdivided into static, dynamic, or mixed (8% of them were soccer players classified as a dynamic type of sport). The study demonstrated that most athletes had normal LV geometry, although concentric remodeling or hypertrophy in male athletes engaged in dynamic sports was also observed (15% of subjects) .We should also note that the cardiac remodeling with predominant LVM increase may result from specificity of training in the pre-adolescent soccer players, which differs significantly from training plans in adults. It consists mainly of ball control exercises, jumps and run-ups with lots of repetitions and systematicity to improve motion automation with less attention to fitness training and long-distance running. A CMR study by Sharf et al. on adult soccer players showing remodeling typical for endurance and resistance training may support this hypothesis .Understanding RV adaptation to intense training has been, similar to the LV, previously documented in adult athletes –27, but We observed significant increase of RV size. Our findings are in line with the findings of D’Ascenzi et al.  but diffThe LA and RA have received even less attention that RV. Iskandar et al. in their meta-analysis have observed either LA diameter or LA volume increase in elite adult athletes . The larThere are several limitations of the present study. First of all, our study group size was relatively smaller in comparison to above quoted publications based on echocardiography , 12, 21.Secondly, there are limited normal values available for CMR variables in children, especially for measures of myocardial mass, and these cannot be readily extrapolated from adult data. We have based our study on the most commonly used ones .Finally, our study was based on a male Caucasian population. Previous research demonstrated that there are gender and race differences in cardiac remodeling in relation to exercise. Therefore, our results should not be extended to the general population.In summary, the present study is the first CMR study investigating the pattern of juvenile myocardial remodeling in school-aged male soccer players. Cardiac adaptations in that group are characterized by an increased LV wall thickness and mass without any changes in LV size and systolic function, which is typical for resistance training with tendency to concentric remodeling. This is accompanied by increase of LA and RV size, which completes the picture of a juvenile athlete’s heart. These findings should be taken into account during pre-participation evaluation to lower the risk of false positive findings, where physiological adaptation may be misinterpreted as a sign of the disease with all the consequences. Finally, it would be also interesting to see how these early changes transfer to later life and health benefits, which warrant further studies.