Echocardiography is the most valuable tool for assessing cardiac abnormalities of chronic kidney disease (CKD) patients even though it has its limitations, including high equipment cost and the need for specialized personnel. Assessment of volume status is important not only for volume management, but also for prevention of cardiovascular disease of the CKD patients. Recently, bioimpedance is gaining acceptance as a way to quantitatively assess patient hydration status at bedside.127 patients who were admitted for planning their first dialysis treatment were enrolled. The echocardiography and bioimpedance spectroscopy (BIS) were performed. The association between echocardiographic data and clinical values such as NT-proBNP and OH/ECW was examined.OH/ECW, which indicates relative fluid overload, was positively associated with LA dimension , LAVI , and E/e´ ratio . While OH/ECW was not significantly associated with echocardiographic values such as LVEDD, LVEDV, LVMI, and LVEF, NT-proBNP were significantly associated with all echocardiographic parameters. Multivariate logistic regression analysis showed E/e´ ratio , 1.01 to 1.29]; P = 0.031), NT-proBNP , and albumin  were significantly associated with OH/ECW.Since OH/ECW measured by BIS is associated with echocardiographic parameters related to diastolic dysfunction, preliminary screening through laboratory findings, including serum albumin in conjunction with OH/ECW and NT-proBNP, may find patient with risk of diastolic dysfunction. Our study suggests that a timely detection of fluid overload in patients with CKD as well as their proper treatment may help reduce diastolic dysfunction. Further research may be needed to validate the consistency of this association across other stages of CKD. Early detection of cardiac abnormalities in patient with chronic kidney diseases (CKD) can prompt early intervention and may result in improvements in cardiac prognosis. There are various tools for detecting cardiovascular disease, from simple blood pressure or arterial stiffness measurement to more advanced screening via computed tomography, magnetic resonance imaging, and echocardiography. NT-proBNP, which has been used as a biomarker for heart failure in the general population, was found to be elevated in CKD patients due to decreased renal excretion . The useAssessment of volume status in patients with renal insufficiency, including those undergoing dialysis, is important not only for short-term volume management but also for long-term prevention of cardiovascular disease. However, the traditional methods have several limitations for detecting the degree and severity of overhydration . BioimpeHerein, we investigated the relationship between the echocardiography and the parameters of BIS in dialysis naive CKD5 patients.This is a retrospective cohort analysis where BIS, echocardiography, and serum measurement of NT-proBNP were performed on the patient who were admitted for planning their dialysis treatment. All tests were performed at the same time before the first dialysis, either hemodialysis or peritoneal dialysis. Between October 2014 to April 2017, 141 consecutive patients were included in the current study. Patients with malignancy (n = 5), infection (n = 2), liver cirrhosis (n = 1), atrial fibrillation (n = 1), valvular heart disease (n = 1), abnormal left ventricular (LV) segmental wall motion (n = 2) or acute kidney injury (n = 2) were excluded from analysis. Among 127 patients who were finally enrolled, three patients whose LV ejection fraction (LVEF) was less than 45% were included. The study was approved by the Institutional Review Board of Yonsei University Wonju Severance Christian Hospital based on the Helsinki declaration. All participants completed the consent form.Echocardiography was performed in harmonic imaging mode using a 3-MHz transducer and commercial ultrasound system .LV internal dimensions, LV wall thickness, LV fractional shortening (LVFS) and LVEF were measured according to the recommendations of the American Society of Echocardiography . LV massace area . Body suThe left atrial (LA) dimension was measured using 2D-guided M-mode echocardiography via the parasternal short-axis view at the base of the heart. Three LA dimensions were used to calculate the LA volume as an ellipse using the following formula:ectively . The LA Transmitral inflow velocities were measured using pulsed-wave Doppler in the apical four-chamber view with the sample volume placed at the mitral valve leaflet tips. Transmitral early diastolic (E wave) velocities were measured. Tissue Doppler imaging (TDI) in the apical four-chamber view was used to measure LV myocardial velocities, with the sample volume placed at the septal mitral annulus. We measured the peak early (e´) diastolic mitral annular velocity and calculated E/e´ ratio , 11.Echocardiography was performed by trained specialists who were completely blinded to patient information.™  was performed. BCM™ utilizes alternating electric currents across 50 different frequencies from 5 to 1000 kHz for the measurement of fluid status. ECW, ICW and total body water (TBW) were automatically calculated. The OH can also be calculated from the difference between the normal expected ECW and actually measured ECW. Whereas BIS can measure OH, bioimpedance analysis (BIA) using a single or several (5 to 10) electric current frequencies cannot be used to calculate OH. The validity of BIS in a study of healthy populations and dialysis patients has already been demonstrated in comparison to standard measurement methods [The BIS using the Body Composition Monitor methods . OH/ECW  methods , 14.The laboratory study was performed before the first dialysis application. NT-proBNP was measured using electrochemiluminescence immunoassay (ECLIA) on Modular Analytics E170 .t-test for continuous variables. The nominal variables  were compared using Chi-square test or Fisher’s exact test. Pearson’s correlation analysis was used to examine correlations between volume markers  and echocardiographic variables. We also examined the associations of LAVI, E/e´ ratio, NT-proBNP, and albumin with OH/ECW using multivariate logistic regression models. Statistical analyses were performed after dichotomizing the patients according to the median NT-proBNP value. We tested the predictive accuracy of a logistic regression model using the c-statistic . Goodness of fit for model was assessed using the Hosmer-Lemeshow test, whereby we considered a value of P < 0.05 to indicate that the model had a poor fit. In this analysis, we adjusted for age and sex (model 1) and for diuretics use and estimated glomerular filtration rate (eGFR) (model 2). Statistical significance was defined as P < 0.05.Statistical analysis was performed using SAS version 9.4 . Descriptive statistics were described as mean ± standard deviation for continuous variables. NT-proBNP was logarithmically transformed as it was not normally distributed. OH/ECW was categorized into two groups: OH/ECW <15%, and OH/ECW ≥15% (fluid overload). Differences in clinical variables between the two groups were tested with two-sample The characteristics of the study population are shown in Among the echocardiographic parameters, LAVI and E/e´ ratio were significantly greater in fluid overloaded group, while LA dimension, LVEDD, LVEDV, LVMI, and LVEF were not significant . Serum pNT-proBNP, which is known to reflect volume status and LV functional status, was positively correlated with OH and OH/ECW, while protein, albumin, calcium showed an inverse correlation .OH, which indicates absolute volume overload, was significantly correlated with LA dimension, LAVI, E/e´ ratio, and LVEDD while OH/ECW, which indicates relative fluid overload, was positively associated with LA dimension, LAVI, and E/e´ ratio. While OH/ECW was not significantly associated with echocardiographic values related to systolic function (LVEF), NT-proBNP was significantly associated with all echocardiographic parameters .Among the significantly different variables between the two OH/ECW groups, LAVI, E/e´ ratio, and NT-proBNP were positively associated with fluid overload, while the negative association was found for albumin in unadjusted model. The statistical analyses were performed after dichotomizing the patients according to the median NT-proBNP value of 4,003.5  pg/ml . E/e´ raAmong the data provided by BIS, OH (in liters), OH/ECW (in %), and ECW/TBW can be used for the assessment of volume status. An OH/ECW cutoff of 15% is correlated with an OH value of approximately 2.4 liters, which is generally accepted as the threshold for fluid overload, and in one study, it was suggested as a predictor of mortality in dialysis patients , 15. Altet al. reported NT-proBNP to be associated with volume overload, but not with cardiac dysfunction [Various studies of NT-proBNP were reported in the field of nephrology and the elevated NT-proBNP was associated with an increased incidence of heart failure . Booth efunction . Logaritfunction . Howeverfunction . Dialysifunction .Most prior studies on the association between volume status and echocardiography have included patients who are already undergoing dialysis and thus prone to constant change of hemodynamic and volume status due to pre-formed arteriovenous fistula, hemodialysis, or constant exchange of peritoneal dialysis fluid. In this study, we only included those who have not undergone dialysis , 23. In 2 for LAVI) even in CKD patients with OH/ECW less than 15%, implying that cardiac structural and functional abnormalities may manifest in the early stages of CKD regardless of the volume status.In this study, we found that NT-proBNP is associated with all echocardiographic parameters, while OH/ECW is associated only with LA dimension, LAVI, and E/e´ ratio. These three factors also differed between the two groups, but the variable reflecting systolic function (LVEF) did not show significant difference. Of note, mean LA dimension and mean LAVI were both greater than the reference values  and functional crises (such as heart failure) , 29. BioS1 Table(DOCX)Click here for additional data file.


Extracorporeal life support (ECLS) is a life-saving procedure used in the treatment of severe cardiogenic shock. Within this retrospective single centre study, we examined our experience in this critically ill patient cohort to assess outcomes and clinical parameters by comparison of ECLS with or without selective left ventricular decompression.n = 20, 41.7%) or ECLS without  integrated left ventricular vent in our retrospective single centre trial.Between 2004 and 2014 we evaluated 48 adult patients with INTERMACS level 1 heart failure (age 49.7 ± 19.5 years), who received either central ECLS with (n = 14), bridge to transplant in 10.4% (n = 5) and bridge to recovery in 8.3% (n = 4). Overall 30-day survival was 37.5%, 6-month survival 27.1% and 1-year survival 25.0%. ECLS support with left ventricular decompression showed favourable 30-day survival compared to ECLS without left ventricular decompression (p = 0.034). Thirty-day as well as long-term survival did not differ between the subgroups . Multivariate logistic regression adjusted for age and gender revealed ECLS without vent as independent factor influencing 30-day survival.Follow up was 100% with a mean of 0.83 ± 1.85 years. Bridge to ventricular assist device was feasible in 29.2% (ECLS is an established therapy for patients in severe cardiogenic shock. Independent of the ECLS approach, 30-day mortality is still high but with superior 30-day survival for patients with ECLS and left ventricular venting. Moreover, by unloading the ventricle, left ventricular decompression may provide an important time window for recovery or further treatment, such as bridge to bridge or bridge to transplant. Cardiogenic shock following acute or chronic heart failure is still associated with poor overall survival . For criPatients with severe cardiogenic shock often present with both left and right heart failure. Low-output LV failure causes concomitant insufficient organ perfusion, while inadequate decompression of the failing left ventricle (LV) causes a backlog of blood into the lung with subsequent pulmonary congestion and a failure of the right ventricle . Especiain situ, that ECLS itself can cause distension of the left ventricle, increasing preload and reducing subendothelial perfusion impairing myocardial ischemia  with ECLS ischemia . These pischemia . It has ischemia .Several case reports and small case series have described the potential for LV decompression to improve outcome of patients in cardiogenic shock . Kotani ECLS can be implanted either peripherally, usually by cannulation of the femoral, subclavian or axillary vessels, or centrally in combination with sternotomy. While peripheral ECLS (pECLS) by transcutaneously introducing venous and arterial cannulas into the target vessels is a simple and very fast technique, vessel injury, major bleeding and limb ischemia are common complications . Today bThe aim of this single centre study was to analyse the outcome of patients receiving peripheral and central ECLS and to evaluate whether decompression of the failing left ventricle by vent implantation has a positive influence on outcomes, with the view to optimize the therapeutic strategy in this complex patient cohort.n = 10, 22.8%), followed by acute myocarditis  and acute myocardial infarction  whereas only 20.8% (n = 10) obtained pECLS. All pECLSs were implanted by cardiologists on the Cardiology Intensive Care unit (CCU) and none of the pECLS patients received a LV vent catheter. If patients were not in clinical stable conditions and therefore ground transportation not reasonable (departments are located in separate buildings without immediate connection) patients received pECLS on CCU. All patients treated at the Department of Cardiac Surgery received a cECLS. In addition, it became standard practice to add in left ventricular decompression in recent years. However, at the beginning of our study period individual surgeon preference determined whether a left ventricular decompression was applied or not. In our cohort, all LV vent catheters were implanted at time of initiation of ECLS.Single-centre retrospective data was analysed of all patients with INTERMACS level 1 (cardiogenic shock with or without respiratory failure) who underwent ECLS implantation in our department between April 2004 and February 2014. The study design was approved by our institutional review board . Collectively, 48 adult patients with complete records could be identified (mean age 49.7  ± 19.5 years). Most common aetiology of cardiogenic shock was dilated cardiomyopathy : low cardiac index (CI) (<2.2 litres/min/m2), low systolic pressure (<90 mmHg for longer than 30 min) and specific clinical indications of central and peripheral hypoperfusion , which are refractory to fluid substitution and intravenous inotropic support. We defined respiratory failure as acute hypoxemia, which is refractory to protective pulmonary ventilation .® CentriMag blood pump  in combination with a D902 ECMO oxygenator . A detailed schematic illustration and postoperative picture of our cECLS setup is shown in Implantation of cECLS was performed as previously described . Central2 body surface area. During the implantation procedure, transesophageal echocardiography (TEE) was performed routinely to obtain a correct position of all cannulas. Postoperatively, echocardiography was re-performed daily during intensive care unit (ICU) stay to ensure sufficient decompression of the left ventricle and to evaluate the ability of weaning. The LV decompression was always applied at the time of ECLS initiation.We targeted an ECLS flow of 2.6 L/min/m®; Medtronic, Meerbusch, Germany). Continuous monitoring of ECLS flow was secured by using ultrasonic probes (Transonics Inc.). Ideal oxygenation and decarboxylation was measured in short intervals using point-of-care blood gas measurement. In addition, continuous brain oximetry  was monitored on ICU. By using the three-way-tap in the proximal venous line and the LV-decompression line, selective blood gas analyses from the left heart can detect left ventricular and pulmonary recovery. Increased blood flow of the left ventricular cannula with greater oxygen saturation enabled additional documentation of lung recovery.In case of peripheral cannulation, cannulas were inserted transcutaneousely into the femoral artery  and femoral vein  using the Seldinger technique. The position of the venous cannula (multi-drain cannula) was controlled by transesophageal echocardiography. Support was given by a portable centrifugal pump heart-lung support  no signs of right ventricular failure  (iv) pulsatile systolic arterial blood pressure of >90 mm Hg under only low dosage of inotropic support for at least twelve hours (v) serum lactate levels <3 mmol/l and (vi) central venous oxygen saturation >65%. If LV vent was implanted, left atrial blood flow and gas analysis were evaluated.Feasibility of weaning from ECLS was determined by evaluating the following: (i) possibility of intermittent reduction of the ECLS blood flow to a minimum of 1/3 individual cardiac output (ii) preserved lung function (Horovitz Index > 200 mm Hg) with inspiration pressure at ventilator <30 cm Ht test and chi-square test. Survival function was calculated by use of Kaplan–Meier estimator and differences in survival were determined using log rank test. Multivariate logistic regression model (stepwise and backward likelihood ratio selection) was performed to determine the influence of vent support on 30-day survival. To adjust the estimated benefit by venting we selected a priori the covariates age and gender. Two-tailed probability values less than 0.05 were considered as significant and values less than 0.01 as highly significant. Statistical analysis was performed using common statistic software .The study cohort was divided into two study groups: patients who underwent ECLS with LV venting and ECLS without LV venting. Furthermore, cECLS patient were divided into 2 subgroups, cECLS with and cECLS without LV venting for sub-analysis. Continuous variables are presented as mean ± standard deviation or as median combined with range. Categorical data are shown as percentage. Differences in preoperative, operative and postoperative data were elaborated by Student’s p = 0.001 and 23.1 vs. 27.2 respectively, p = 0.055), ventilation time (p = 0.091) and duration of in-hospital stay (p = 0.089) did not differ significantly between the study groups (ECLS with vent vs. ECLS without vent). Patients of the non-venting group more often had intra-aortic balloon pump support before ECLS was implemented .Follow up was completed successfully in 100%, with a mean follow up of 269 days . We distinguished between vent vs. no vent group as well as between pECLS and cECLS with and without vent . We saw a homogeneous distribution of sex between the study groups. Patients with ECLS and LV-vent were significantly younger and had lower body mass index than patients without LV-vent .Central ECLS plus LV vent was in use for significantly longer than cECLS without LV venting , whereas 6 (12.5%) patients underwent heart transplantation over the course of time . Sub-analysis revealed, that patients with cECLS and additional vent implantation were more frequently bridged to a VAD system than patients with cECLS without venting .Four patients (8.3%) were successfully bridged to recovery by cECLS (one with vent and 3 without vent). The majority of survivors were bridged to VAD Systems  in the overall study population. Patients with LV decompression by venting had a superior short-term survival after 30-days  but no favourable survival after 6 and 12 months  did not survive 30 days after ECLS implantation. Patients suffering from cardiogenic shock are by definition critically unwell and haemodynamically decompensated, with subsequently lung and end-organ dysfunction leading to fatal multi-organ failure.In general, ECLS therapy without LV decompression is mainly limited by lung failure (pulmonary oedema with impaired oxygenation) and unrecognized left ventricular distension resulting in ventricular pressure overload, restricted coronary blood flow and insufficient cardiac recovery. The importance of left side decompression in ECLS has been described before. However, these publications report the use of balloons, blades or stentings to achieve an interatrial left to right side shunt . AiyagarEnd-organ dysfunction is the result of three obvious risk factors. The first is hypoxemia, itself a result of lung failure due to an impediment of the failing LV (or isolated/combined right heart failure), causing destruction and apoptosis of parenchymal cells. Secondly ischemia, due to reduced organ perfusion and finally congestion due to increased venous backflow.Clinical parameters such as renal and liver function as well as parameters describing the lung function all failed to explain the beneficial outcome.An important advantage of ECLS is the ability to instantly and continuously measure the blood flow crossing the lungs by Doppler-ultrasound measurement and pO2 of the LV decompressing cannula is of vital importance in terms of evaluation and timing of a potential weaning from ECLS or bridging to a further long-term support . These sophisticated options for heart and lung function evaluation allowed a more accurate timing to wean and are an important key to keep ECLS support duration as short as possible, but as long as required.The optimal approach for utilizing ECLS remains debatable. The central approach via sternotomy allows a fast and excellent access to both right and left atrium as well as the ascending aorta. However, the surgical trauma is immense and early postoperative mobilization is limited. By comparison, peripheral support is of growing interest, due to a simple approach and a pervasively available technique in intensive care units without the need of immediate surgical support . At presOur analysis demonstrated that ECLS without venting has a significantly inferior outcome after 30 days compared to ECLS with venting. Furthermore, mortality rate was significantly lower in patients with LV venting during ECLS support and non-ventilatory support was determined as strong independent risk factor for 30-day mortality. Even though our sub-analysis of patients with cECLS did not reveal a definite survival benefit for LV venting, we propose a combination of cECLS approach with LV decompression to justify the increase of invasiveness compared to the simpler pECLS approach. Moreover, a de-novo sternotomy may be avoided by using alternative approaches. These techniques have been described before by Within our department, the vast majority of central ECLS procedures were performed using a LV vent within recent years, as a consequence of our growing experience with ECLS. Furthermore, the favourable results of LV-venting may be biased or confounded by generally improved perioperative management. This includes the continuous and systematic development of surgical strategies as well as the more sophisticated management on intensive care unit prior and post ECLS implantation.® system. A randomized multi-center study is required to address these essential major questions on this topic: (i) Is a routine peripheral support a non-inferior option to maintain ECLS compared to the central approach? (ii) Which technique (and/or device application) of LV decompression is best in pECLS, in a scenario where the central approach is not favoured or applicable?As presented in our data cECLS alone did not lead to improved outcomes compared to pECLS. In our opinion, LV-venting must be performed to justify the much more invasive cECLS procedure. However, at time of writing there are no large studies available presenting pECLS with LV decompression and comparing different strategies. If a pECLS is implemented, LV-decompression could also be achieved by draining left atrial volume via a trans-septal cannula by a transaortic ImpellaECLS is a powerful and oftentimes end-stage tool to overcome life threatening cardiogenic shock, regardless of the underlying disease. We were able to demonstrate the benefit of LV venting in terms of 30-day survival, the most critical time frame in the state of refractory cardiogenic shock, independently of underlying cause. If ECLS is implemented, we strongly recommend this be done alongside decompression of the left ventricle. The technique of a separate LV-decompression in cECLS allows sophisticated options to follow both, cardiac and pulmonary recovery. Cardiogenic shock remains a highly challenging condition to manage and morbidity and mortality outcomes remain poor. To improve survival and to allow for further treatment options, using all available resources including therapy-enhancing techniques like LV-decompression are a vital next step that require further data to support and qualify their use and optimisation.Our study demonstrates a relatively high number of ECLS patients with a specific LV decompression technique and a complete follow up. However, this study is limited by the fact that we performed a retrospective single-center analysis containing patients with a large variability of underlying diseases causing cardiogenic shock. Furthermore, all pECLS were implanted by Cardiologist on the Cardiology Care Unit and no LV venting was applied in pECLS patients, which leads to a certain bias.10.7717/peerj.3813/supp-1Supplemental Information 1Click here for additional data file.10.7717/peerj.3813/supp-2Supplemental Information 2Click here for additional data file.


Counter-pulsation control (CPC) by ventricular assist devices (VADs) is believed to reduce cardiac load and increase coronary perfusion. However, patients with VADs have a higher risk of arrhythmia, which may cause the CPC to fail. Consequently, CPC has not been applied by VADs in clinical practice. The phase-locked loop (PLL) algorithm for CPC is readily implemented in VADs; however, it requires a normal, consistent heartbeat for adequate performance. When an arrhythmia occurs, the algorithm maintains a constant pumping rate despite the unstable heartbeat. Therefore, to apply the PLL algorithm to CPC, the hemodynamic effects of abnormal heartbeats must be analyzed.This study sought to predict the hemodynamic effects in patients undergoing CPC using VADs, based on electrocardiogram (ECG) data, including a wide range of heart rate (HR) changes caused by premature ventricular contraction (PVC) or other reasons.A four-element Windkessel hemodynamic model was used to reproduce the patient’s aortic blood pressure in this study. ECG data from 15 patients with severe congestive heart failure were used to assess the effect of the CPC on the patients’ hemodynamic state. The input and output flow characteristics of the pulsatile VAD  were measured using an ultrasound blood flow meter , with the aortic pressure maintained at 80–120 mmHg. All other patient conditions were also reproduced.In patients with PVCs or normal heartbeats, CPC controlled by a VAD reduced the cardiac load by 20 and 40%, respectively. When the HR was greater for other reasons, such as sinus tachycardia, simultaneous ejection from the heart and VAD was observed; however, the cardiac load was not increased by rapid cardiac contractions resulting from decreased left ventricle volume. These data suggest that the PLL algorithm reduces the cardiac load and maintains consistent hemodynamic changes. Use of a ventricular assist device (VAD) is the most effective way to improve the survival rates of patients with end-stage heart failure –5. HowevMultiple studies of CPC using VADs have assumed normal HRs without considering the possible occurrence of arrhythmias. Lim et al. reported that CPC increased coronary perfusion and decreased cardiac load . KoshimoThe LibraHeart I  is a pulsatile VAD that analyzes prior heart beats and initiates its next pulse flow to keep the time interval between the pulses of the patient’s heart and the VAD constant according to the phase locked loop (PLL) algorithm . The PLLThe hemodynamic model was based on the four-element Windkessel model, which reproduces patient blood pressure and blood flow data , 23. BecThe purpose of this study was to predict the effects of a VAD in CPC mode on the cardiac and hemodynamic states using a four-element Windkessel model that includes the data for a VAD and arrhythmias that induced CPC failure.The conventional method of determining when to initiate VADs following heartbeat detection misses the appropriate counter-pulsation point. If the delay from the time of heart rate (HR) detection to actuator operation is not reduced to within 0.1 s , a normap) and calculating the beating period (TR-R). The heartbeat time (Tp) is determined from ECG data using the Tompkins method ., 26.6, 2s method . The HR R-R changed temporarily from 30 to 170%, which caused temporary CPC failure. In most cases, however, the VAD slowly adjusted its PR to the average HR according to the PLL algorithm, and it seemed to maintain a constant PR as opposed to changing the PR of the IABP for each heartbeat.When an arrhythmia occurred, TThe hemodynamic changes were investigated using the four-element Windkessel model. The conventional Windkessel model shows the relationship of diastolic and systolic blood pressure and blood flow . HoweverTo compare the characteristics of the cardiac load in the four-element Windkessel model and to analyze the effect of the VAD, the compliance of the LV, the resistance of the mitral and aortic valves, and the LA pressure were determined, as shown in Table LV is the ratio of volume to pressure in the LV when the internal pressure changes from 5 to 120 mmHg and the blood volume changes from 65 to 120 cc  with severe congestive heart failure (NYHA class 3–4) at a sampling rate of 250 per second. The data included 1260 heart beats and 28 arrhythmias . Nine paThe inflow and outflow data for the VAD  were measured using an ultrasonic blood flow meter  using a mock circulation system that reproduces the patient’s hemodynamic conditions . As showPVCs stopped the blood flow from the left atrium to the LV and reduced the maximum volume within the ventricle during a heartbeat, as shown in Fig. p-d/TR-R deviated significantly from the target value (45%), the cardiac output and the output of the VAD did not occur simultaneously, because the blood flow output period of the VAD was too short, so the VAD output finished before the start of the following PVC. As shown in Fig. The volume of the ventricle was reduced by the inflow to the VAD Fig. e. When Pt value 4%, the cat value 4%, the caWhen ST occurred, successive rapid heartbeats induced co-pulsation, as shown in Fig. p-d to TR-R also changed from 20 to 60% due to unknown HR changes and tachycardia (> 100 bpm). When the ratio of Tp-d to TR-R was within 20–60%, the cardiac load was expected to decrease by 20–40% (Fig. As shown in Fig. 40% Fig. a.Fig. 7aAlthough PVCs are not dangerous arrhythmias, their frequency affects the occurrence of dangerous arrhythmias such as ventricular fibrillation , 29. PVCThe results of this study were obtained from simulations; however, the input and output blood flow data of the VAD were measured under the same conditions based on patients and in vitro . The ECGThe model used in this study predicted the effects of the VAD on events that were difficult to reproduce in clinical or animal experiments. However, a limitation of this study is that predictions using other input conditions require a substantial volume of data to be collected beforehand. Because the cardiovascular characteristics of patients vary due to multiple factors, including the influence of sympathetic and parasympathetic nervous systems and the patient’s movement and posture, predictions must encompass a wide range of conditions. As the technologies for acquiring data become more encompassing, the limitations of numerical simulation will be minimized , 32.Previous studies of CPC were designed to detect heart rhythms and to maintain the VAD at constant intervals , 12. HowIn this study, the PLL algorithm showed a 97.3% success rate at CPC when tachycardia and arrhythmias appeared in patients and it could reduce the heart load. It predicted that CPC and temporary CPC failure would not induce an increased cardiac load, even when co-pulsation occurred.


This review discusses the management of ventricular septal defects (VSDs) and atrioventricular septal defects (AVSDs). There are several types of VSDs: perimembranous, supracristal, atrioventricular septal, and muscular. The indications for closure are moderate to large VSDs with enlarged left atrium and left ventricle or elevated pulmonary artery pressure (or both) and a pulmonary-to-systemic flow ratio greater than 2:1. Surgical closure is recommended for large perimembranous VSDs, supracristal VSDs, and VSDs with aortic valve prolapse. Large muscular VSDs may be closed by percutaneous techniques. A large number of devices have been used in the past for VSD occlusion, but currently Amplatzer Muscular VSD Occluder is the only device approved by the US Food and Drug Administration for clinical use. A hybrid approach may be used for large muscular VSDs in small babies. Timely intervention to prevent pulmonary vascular obstructive disease (PVOD) is germane in the management of these babies. There are several types of AVSDs: partial, transitional, intermediate, and complete. Complete AVSDs are also classified as balanced and unbalanced. All intermediate and complete balanced AVSDs require surgical correction, and early repair is needed to prevent the onset of PVOD. Surgical correction with closure of atrial septal defect and VSD, along with repair and reconstruction of atrioventricular valves, is recommended. Palliative pulmonary artery banding may be considered in babies weighing less than 5 kg and those with significant co-morbidities. The management of unbalanced AVSDs is more complex, and staged single-ventricle palliation is the common management strategy. However, recent data suggest that achieving two-ventricle repair may be a better option in patients with suitable anatomy, particularly in patients in whom outcomes of single-ventricle palliation are less than optimal. The majority of treatment modes in the management of VSDs and AVSDs are safe and effective and prevent the development of PVOD and cardiac dysfunction. In the current article, ventricular septal defects (VSDs) and atrioventricular septal defects (AVSDs) will be discussed. Whereas transcatheter (percutaneous) approaches are the mainstay in the management of secundum ASDs, the VSDs and AVSDs are at present managed largely by surgical methodology since a limited number of lesions are amenable for transcatheter and hybrid approaches. In this review, we will present a classification of the VSDs and AVSDs, indications for repair, and a discussion of surgical, transcatheter, and hybrid methodologies with a particular focus on advances in the management of these defects.Septal defects are the most common types of congenital heart defects (CHDs) with the exception of bicuspid aortic valve. Advances in the management of atrial septal defects (ASDs) have been addressed in an earlier review5. The membranous defects are most common among the VSDs , and supracristal (5 to 7%), AV septal (8%), and muscular (5 to 20%) defects are much less common. These defects may be large, medium, or small in size. Most of the defects are single; however, multiple defects may be present in the muscular septum, described as the “Swiss cheese” type of VSDs.Isolated VSDs are the most common CHDs  and constitute 20 to 25% of all CHDs. They are most commonly classified on the basis of their location in the ventricular septum and are divided into perimembranous (situated in the membranous ventricular septum in the subaortic region), supracristal , atrioventricular (AV) septal (defect located in the posterior septum), and muscular Left-to-right shunt across the VSD produces dilatation of the left atrium and left ventricle (LV). Owing to high pulmonary vascular resistance (PVR), this shunt may not manifest in the neonate and during the first weeks of life. As the pulmonary arterioles involute, PVR falls with resultant increase in left-to-right shunt. The right ventricle (RV) and main and branch pulmonary arteries may also be dilated in moderate to large defects. Whereas pulmonary vascular obstructive disease (PVOD) does not manifest until adulthood in patients with ASD, patients with VSD are likely to develop PVOD as early as 18 months to 2 years of age if a large VSD is left unrepaired.Discussion of VSDs seen in association with tetralogy of Fallot, pulmonary atresia/stenosis, transposition of the great arteries, tricuspid and mitral atresia, and double-outlet RV and heterotaxy (asplenia and polysplenia) syndromes will not be included in this article. Similarly, post-traumatic and post-myocardial infarction VSDs will not be addressed in this review.6. Closure of the VSD is not necessary in patients with a small VSD. Assurance of the parents and perhaps subacute bacterial endocarditis prophylaxis and occasional clinical follow-up are suggested. However, if the VSD has become smaller because of its closure by prolapsed aortic valve cusp into the defect with resultant aortic insufficiency, surgical closure of the defect with resuspension of the aortic valve leaflets is recommended. The development of aortic insufficiency is seen in both membranous and supracristal VSDs.The indications for intervention depend, to a large degree, on the size and type of the VSDIn moderate-sized VSDs, congestive heart failure (CHF), if present, should be treated. In the presence of failure to thrive, markedly enlarged left atrium and LV or elevated pulmonary artery pressures (or both), closure of the defect is generally recommended. An additional criterion is a pulmonary-to-systemic flow ratio (Qp:Qs) greater than 2:1.In large VSDs with systolic pressures in the RV and pulmonary artery close to left ventricular and aortic systolic pressures, closure should be undertaken. This should be done prior to 6 to 12 months of age (certainly no later than 18 months of age) irrespective of control of heart failure and adequacy of weight gain. The reason for this recommendation is to prevent irreversible PVOD. In babies with Down syndrome, such closure should be undertaken prior to six months of age since these patients tend to develop PVOD sooner than non-Down babies. In present-day practice, primary surgical correction is preferred in contradistinction to initial pulmonary artery banding followed by surgical closure of the VSD, a common practice in an earlier era. However, such a staged approach may be considered for the Swiss-cheese variety of muscular VSDs. Some clinicians may also use pulmonary artery banding in low-weight infants who may have an increased risk of heart block with repair, although the current trend is toward early complete repair.8. In patients with higher PVR values, pulmonary vascular reactivity testing with oxygen and nitric oxide (NO) should be performed9. If the PVR index drops below 6 to 8 units with oxygen or NO, then these patients become candidates for VSD closure.In cases with elevated PVR, most authorities would suggest intervention if the calculated PVR index is less than 6 Wood units or the pulmonary-to-systemic vascular resistance ratio (Rp:Rs) is less than 0.35 (or both) with a Qp:Qs greater than 1.5Patients with large VSD and severely elevated PVR  are not suitable for VSD closure. These patients eventually may become candidates for lung transplantation.The treatment of the VSD, as mentioned above, is largely dependent on its size and the clinical status of the patient. Several methods of available treatment options will be reviewed.Medical management. Infants with moderate to large VSDs with signs of CHF should receive aggressive treatment with anti-congestive measures to include digoxin, diuretics , and afterload reducing agents . Although the above order of drug administration has been used for a long time, recent doubts about the usefulness of digoxin have changed the order of administration to diuretics, afterload reducing agents, and digoxin (in that order). We continue to believe that digoxin is useful in the management of CHF in infants and children. When chronic administration of furosemide is required, aldactone may be added for its potassium-sparing effect. Optimization of nutrition, maintenance of adequate hemoglobin level, and appropriately addressing the associated respiratory symptoms should be a part of overall management of these babies.Clinical improvement may occur with adequate medical therapy; such improvement may be related to spontaneous closure or diminution in the size of the VSD, development of right ventricular outflow tract obstruction (Gasul’s transformation), or increased PVR. Careful clinical and echocardiographic follow-up evaluation and, when necessary, cardiac catheterization should be undertaken to ensure that the improvement is not secondary to elevation of PVR. As mentioned in the preceding section, VSD closure should be undertaken prior to 18 months of age to prevent the development of irreversible PVOD.As also mentioned in the previous section, large VSDs with severe increase of PVR (irreversible PVOD) should not have their VSDs closed. Recently described pulmonary vasodilators , which may improve symptoms, may be used. If severe polycythemia is present, erythropheresis to treat symptoms of polycythemia should be performed. Transcatheter creation of atrial communication may relieve symptoms of PVOD. Discussion of the pulmonary vasodilators and management of PVOD is beyond the scope of this article. Ultimately, patients with PVOD may need lung transplantation.Although it is extremely important that every effort be made to prevent PVOD, it should be recognized that 40% of the VSDs close spontaneously and an additional 25 to 30% of defects become small enough not to require intervention. Defects in the muscular septum tend to close more often than the defects in the perimembranous region. Small defects are likely to close more often than large VSDs (60% versus 20%). It is well documented that even large defects producing CHF or requiring pulmonary artery banding during infancy close spontaneously. Whereas most of the defects close by two years of age, the process of spontaneous closure continues through childhood, adolescence, and adulthood. These considerations should be kept in mind when decisions to recommend surgical or transcatheter closure of VSDs are being made.Surgical repair. Following the description of cardiopulmonary bypass techniques by Gibbon, Lillehei, and Kirklin in the 1950s to successfully close ASDs1, surgical techniques for repair of other CHDs, including VSDs, were soon developed. Median sternotomy incision is performed under general anesthesia and the aorta and vena cavae are cannulated to institute cardiopulmonary bypass. The majority of perimembranous VSDs are closed with a Dacron patch via right atriatomy with or without detachment of the tricuspid valve leaflets. Supracristal defects are addressed via the pulmonary valve. VSDs with associated aortic insufficiency, though small, should be closed to prevent progression of aortic insufficiency10. Moderate to severe aortic valve prolapse may require re-suspension of the aortic valve or other valvuloplasty techniques or both12.14. At that time, the pulmonary artery band is removed and the pulmonary artery is repaired, if necessary, to ensure that there is no residual stenosis at the prior band site. The senior author (PSR) observed several patients in whom the muscular VSD closed spontaneously following pulmonary artery band placement, and repeat thoracotomy to remove the pulmonary band was required. Absorbable pulmonary artery band may be a good option in such situations. The polydioxanone band (absorbable) reduces pulmonary blood flow and pressure initially and helps decrease symptoms of CHF. When the VSD closes spontaneously, the pulmonary artery band is also resorbed and will not require additional surgery to remove it. The principles are similar to those advocated for patients with tricuspid atresia with a large VSD16. Unfortunately, however, most surgeons are reluctant to use an absorbable pulmonary artery band in this situation.Small muscular VSDs are likely to close spontaneously and do not require surgery. In infants, large muscular VSDs, particularly of the “Swiss cheese” variety, are difficult to close from the right ventricular side. Pulmonary artery banding initially to control CHF and reduce the pulmonary artery pressures is performed in young (up to three months of age) babies. Closure of the VSD via an apical left ventriculotomy may be performed later during childhoodResults17 and more recent times18 is generally good with rare residual shunts, frequent right bundle branch block, occasional pulmonary hypertension, infrequent heart block or sinus node dysfunction, and modest progression of aortic insufficiency. Following VSD closure, the left ventricular volume and mass return to normal with preservation of normal left ventricular function19.Surgical closure of VSDs is safe; the mortality rate is less than 3%. The long-term outlook following surgery in both the early eraPercutaneous closure. Percutaneous closure of VSDs in animal models was first reported by Rashkind in the early 1970s20. He used hooked, single-disc, and double-disc Rashkind devices. Afterwards, other cardiologists followed his lead and used Rashkind’s double-disc patent ductus arteriosus (PDA) umbrella, Rashkind’s ASD double-umbrella, and clamshell devices for transcatheter occlusion of VSDs26. Subsequently, other devices were used to percutaneously occlude the VSDs: buttoned device 28, CardioSEAL and STARFlex devices 29, Nit-Occlud device 33, Amplatzer Muscular VSD Occluder device 39, detachable steel coils 40, Gianturco coils (Cook)41, flipper, 0.052ʺ Gianturco, or 0.035ʺ platinum coils (Cook)42, wireless devices such as detachable balloon and transcatheter patch 43, Amplatzer Duct Occluder 44, Shanghai symmetrical perimembranous VSD occluder 45, Amplatzer Duct Occluder II 56, Cera devices 57, and perhaps other devices (not known to the authors).58 so that the aortic end of the left ventricular disc is made to be shorter (0.5 mm) while the other end is designed to be longer (5.5 mm). The lower pole of the left ventricular disc was impregnated with a platinum marker in order to aid appropriate device positioning during deployment of the device. This redesigned device, now called Amplatzer Membranous VSD Occluder , was used in patients with small- to medium-sized VSDs68, including in US Food and Drug Administration (FDA)-approved US clinical trials67. The results were generally considered acceptable. In addition to the usual complications seen with complex procedures, complete heart block76 was detected both immediately after and during follow-up after implantation of Amplatzer Membranous VSD occluders, raising concerns78 regarding the advisability of using this device.The majority of the above mentioned (with exception of coils and Amplatzer Duct Occluder) are double-disc devices and require septal rims to hold the device in place. Therefore, they can be used only in occluding muscular VSDs and perimembranous defects with a good-sized aortic rim. Owing to lack of aortic rim and proximity of the aortic valve to the defect, it may not be feasible to close the more common perimembranous VSDs. In an attempt to address this challenge, the device was redesigned78. This is likely to be the mechanism for reported development of heart block76 and conduction abnormalities72. The described incidence of complete heart block varied between 1 and 22% and many of them required pacemaker therapy76. This is in contradistinction to 1% incidence of heart block following surgical closure79. Therefore, it is difficult to justify the use of membranous VSD Occluder to transcatheter-occlude the VSDs. It has been suggested that the device be redesigned to make its edges supple or soft such that less or no pressure is exerted on the conduction system78. However, to the best of authors’ knowledge, no such modifications seem to have been undertaken by the device manufacturer.The connecting waist of most double-disc devices is located within the VSD, is small, and is not likely to stretch the defect. The mechanism of defect closure is by stop-flow by the discs on both sides of the VSD. However, the Amplatzer Membranous VSD Occluder indeed “stents” the defect and, with time, stretches the defect since the device size is generally larger than the size of the VSD. Since the conduction system is situated along the rims of the VSD, the device possibly exerts pressure on the conduction system42, Nit-Occlud device75, Amplatzer Duct Occluder44, and Amplatzer Duct Occluder II56 are also being used on an off-label basis. Discussion of devices used on an off-label basis will not be included in this review; the interested reader may review the respective publications75.Most of the devices described above had experimental device closures in animal models. Clinical trials in human subjects followed with local institutional review board, CR Mark (in Europe), or FDA (in the USA) approval. Feasibility, safety, and effectiveness of occluding the VSDs have been shown for the majority of the devices. However, at this time, only the Amplatzer Muscular VSD Occluder has received approval for clinical use by the FDA. Although CardioSEAL Septal Occlusion System with QwikLoad and the STARFlex Septal Occlusion System have received FDA approval in the past, they are not widely used at present. Free and detachable Gianturco coilsAmplatzer muscular ventricular septal defect occluder.Description of the deviceThe device is constructed with 0.004ʺ to 0.005ʺ Nitinol (nickel–titanium compound) wire with shape memory and consists of two equal-sized discs connected with a 7-mm-long waist. The discs on either side of the waist are 4 mm longer than the waist. Dacron polyester patches are sewn into both discs. The device size is determined by the diameter of the connecting waist. Available device sizes are 4 to 18 mm. The device is easily retrieved and redeployed.Method of implantation80. Administration of heparin , antibiotics  and anti-platelet therapy (aspirin or clopidogrel or both), in accordance with institutional protocol for intracardiac device implantations, is undertaken.Following recording of the usual hemodynamic data, a biplane left ventricular cine-angiogram is performed in a sitting-up  and lateral views to define the size and location of the VSD. Balloon sizing of the VSD, performed at the beginning, is no longer routinely performed; instead, transesophageal echocardiographic (TEE) and angiographic diameters are used to measure the VSD size. Additional angiography in other views is obtained if the required data on the VSD size and location could not be clearly defined. Initially, a right coronary artery, multipurpose, or balloon wedge catheter is advanced from the LV into the RV via the VSD with the aid of a soft-tipped guide wire, and an exchange-length guide wire  is passed and its tip is positioned either in the superior vena cava or in the pulmonary artery. The tip of the wire is snared from the femoral venous route and the wire exteriorized, establishing an arterio-venous guide-wire loop. Now, the selected delivery sheath is advanced from the femoral vein and positioned into the left ventricular apical region and the guide wire and catheters are removed. A right internal jugular venous approach may be required in some cases, especially when kinking of the sheath introduced via the femoral vein occurs. Alternatively, the device may be delivered from the arterial route. A pigtail catheter is placed retrogradely into the LV. An Amplatzer Muscular VSD Occluder that is 1 to 2 mm larger than the diameter of the VSD is selected for deployment. The device is screwed onto a delivery wire and loaded into the delivery sheath while taking precautions to eliminate air bubbles in the system. The device is advanced within the delivery sheath, and the left ventricular disc is delivered into the LV under fluoroscopic and TEE guidance. After making sure that the device does not impinge on the mitral valve apparatus, the left ventricular disc is pulled back against the ventricular septum under fluoroscopic and TEE guidance. If necessary, left ventricular angiography is performed to verify the position of the device. The waist of the device is delivered into the defect. Then the right ventricular disc is deployed on the right side of the ventricular septum by slow withdrawal of the sheath, again while monitoring by fluoroscopy and TEE. Left ventricular angiography and TEE are repeated to ensure good position of the device which is still connected to the delivery wire. At this point, the device is still retrievable back into the delivery sheath and redeployed as seen fit. Once the device position is satisfactory, the device is disconnected from the delivery wire. A final left ventricular angiogram and TEE are performed prior to removal of the catheters and sheaths. If additional muscular VSDs are present, they may also be occluded by placement of additional Amplatzer Muscular VSD Occluders as previously described elsewhereResults83. Most reports involving single-institution studies stated that some degree of contrast foaming through the device was seen immediately after device deployment with almost complete resolution of shunt by the next day. However, the multi-institutional US Registry study80 reports a complete closure rate of 47% at 24 hours after the procedure, which increased to 70% at 6 months and 92% at 12 months after the procedure. Reported complications include transient complete left bundle branch block; transient junctional rhythm; complete heart block, both transient and permanent (the latter requiring pacemaker implantation); tamponade resulting in death; cardiac perforation; device embolization (some retrieved by transcatheter methodology and others by surgery), device malposition requiring surgical removal; severe hemolysis ; and death84; however, these complications are rare. Follow-up results were reported in a few studies but with no additional complications.Immediate results of implantation of Amplatzer Muscular VSD Occluders in 1 to 119 patients have been reportedHybrid (perventricular) device delivery. Because of inherent limitations of both surgical and percutaneous device closure of muscular VSDs in small infants, a hybrid approach, also called “perventricular closure”, was introduced86. The initial descriptions included six infants85 and seven mini pigs86. Feasibility of this approach was demonstrated in both young infants and animal models without cardiopulmonary bypass86. A number of other investigators101 subsequently adopted this technique.The procedureUnder general anesthesia, a median sternotomy or a subxiphoid incision is made and the right ventricular free wall is needle-punctured via a purse-string suture. The soft end of a guide wire is introduced across the VSD into the LV under TEE guidance. The needle is removed and an appropriate-size delivery sheath with a dilator is advanced over the guide wire into the LV and the dilator and guide wire are withdrawn, leaving the tip of the sheath in the LV. An appropriate-size device (1 to 2 mm larger than the TEE diameter of the VSD) is advanced through the sheath. Once the device reaches the tip of the sheath, the sheath is retracted to extrude the left ventricular disc in the mid LV. Then the entire system is slowly withdrawn so that the LV disc is apposed to the interventricular septum. Further slow retraction of the sheath is undertaken, delivering the device waist within the defect and the right ventricular disc on the right side of the ventricular septum—all while the procedure is being monitored by TEE and while the heart is beating. Once the position of the device is satisfactory as evaluated by TEE, the delivery wire is disconnected and the sheath is removed while the purse-string suture is tightened. A final TEE is performed to ensure appropriate position of the device and to detect any additional VSDs.Results101. The number of subjects included was anywhere between 6 and 408 patients. Successful device implantation is reported from 82 to 100% of patients. In most studies, unsuccessful implantations were converted to conventional open-heart surgical repair, irrespective of the reason for failure. Residual shunts were not significant. Complications were few and the occasional pericardial effusion occurred.Immediate results of hybrid procedures to close perimembranosus and muscular VSDs have been reported90. The devices used were similar to Amplatzer VSD devices but manufactured in China by the Shanghai Alloy Material Corporation; 213 (54.2%) were symmetric devices and 180 (45.8%) were asymmetric devices. Follow-up from three months to two years after the procedure exhibited no residual shunts, stable device position, and no increase in aortic insufficiency.In one large study involving 408 patients with perimembranous VSDs with a mean age of 3.1 years (± 1.7 years), an age range of 5 months to 15 years, and a weight range of 4.5 to 26 kg, successful closure was accomplished in 393 patients (96.3%)91. In the remaining patients, the device was removed because of arrhythmia, malposition, or additional defects. At a mean follow-up of 1.4 years, only one patient had more than trivial shunt. No other complications occurred.In a multicenter retrospective study from Europe, investigators reported closure of muscular VSDs in 21 patients; the device was successfully implanted in 89% of patientsSince the perimembranous VSD closure with devices is likely to result in heart block as described in the “Percutaneous closure” section, we do not advocate their closure by a hybrid procedure. Detailed review of these hybrid procedure reports reveals that many patients had small VSDs (<5 mm) or aneurysmal formation of membranous ventricular septum, a natural attempt for spontaneous closure, and the authors of this article question the advisability of closure of such VSDs.This hybrid technique is especially helpful in small babies with large muscular VSDs in whom there is a higher prevalence of adverse events for percutaneous device closure when compared with older children.There are a limited number of studies comparing one method of VSD closure with the other.Percutaneous versus surgical closure. In one study, the results of percutaneous closure in 852 patients were compared with 1,326 patients who had conventional surgical repair102. Procedure success rates and prevalence of major complications were similar. However, the rates of minor complications (6.4% versus 0.6%) and requirement of blood transfusions (10.3% versus 0%) and duration of hospitalization (12.9 versus 3.2 days) were higher in the surgical than in the percutaneous group. The authors concluded that the percutaneous approach is an effective and reasonable alternative to surgery in the management of patients with VSD102.103. The patients in the percutaneous group were older than those in the surgical group (mean age of 12.2 versus 5.5 years), but the VSD sizes were similar. Procedural success rates, major complications such as need for reoperation, early deaths, and requirement for permanent pacemaker implantation were similar as were the residual shunts, significant aortic and tricuspid insufficiency, and advanced heart block at follow-up. The higher requirement for blood transfusion and longer duration of hospital stay were seen in the surgical group. The authors concluded that percutaneous intervention and surgical closure of perimembranous VSDs had similar procedural success rates and that percutaneous closure did not manifest higher rates of valvar insufficiency and heart block than surgical closure103.In another study, the results of percutaneous versus surgical closure of perimembranous VSDs were compared by examining the results of seven previously published articles; there were 1,312 percutaneous device implantations and 1,822 surgical closuresHybrid versus surgical closure. A comparison of 49 hybrid device closures with 41 surgical closures was made98. The ages were similar, but the VSDs were slightly larger (6.03 versus 5.03 mm) in the surgical group. Major complications, namely death, severe valvar insufficiency, significant residual shunts, and lethal arrhythmias, did not occur in either group. Complete closure rates immediately after procedure and at follow-up were similar for the two groups. The requirement for blood transfusion was higher and the length of the stay in intensive care unit was longer in the surgical than in the hybrid group. The authors conclude that hybrid VSD closure may be an alternative to surgical closure98.Comments on comparisons. Although the authors of the above studies have made considerable efforts to compare various groups, all studies appear to be retrospective and non-randomized and may not be as definitive as the authors would like us to believe. In addition, it should be observed that the above-mentioned comparative studies do not compare identical patient populations and there is a selection bias in the patients managed with device closure because only ideal candidates are managed with device closures, and more complex VSDs were referred for surgery. Additionally, they do not take into account that repair under cardiopulmonary bypass will entail a period of ventilation and intensive care stay.When one carefully examines the data of patients undergoing VSD closure, many VSDs are less than 5 mm in size and the Qp:Qs was less than 2:1. The availability of less invasive transcatheter approaches should not, in the authors’ opinion, relax the indications for closure and these indications should be the same as those used for standard surgical closure. In addition, the natural history studies indicate that spontaneous closure occurs in VSDs and such closures continue to occur during childhood, adolescence, and adulthood. The pediatricians and the general pediatric cardiologists should serve as gatekeepers to prevent intervention by pediatric cardiac surgeons and interventional pediatric cardiologists for “small” VSDs that do not strictly fit established criteria for closure, irrespective of the type of intervention, whether it is conventional surgical, percutaneous, or hybrid.Based on clinical experience for over 45 years in caring for patients with VSDs by the senior author (PSR) and an extensive review of the subject at the time of this writing, the following recommendations may be made. Open-heart surgical closure remains the main treatment option for large and non-restrictive perimembranous VSDs. Timely intervention to prevent PVOD is highly important and is in the purview of the pediatrician and pediatric cardiologist caring for the child. Percutaneous closure seems to be a valuable option for closure of large muscular VSDs. A hybrid procedure is a good option for large muscular VSDs in small infants. When that is not possible, particularly in babies with the Swiss-cheese type of VSDs, banding of the pulmonary artery as an initial palliative procedure with later closure of VSD is likely to be beneficial to these infants.What were formerly known as AV canals and endocardial cushion defects are now termed as atrioventricular septal defects (AVSDs). The characteristic features of this CHD include defects in atrial and ventricular septa along with deficiency in one or both AV valves. The AVSDs constitute 4 to 5% of all CHDs. The AVSD is the most common defect in babies with Down syndrome.104. The partial form usually had a large ASD in the anterior portion of the lower part of the atrial septum along with a cleft in the anterior leaflet of the mitral valve. A cleft in the septal leaflet of the tricuspid valve may also be present in some patients. In the transitional form, there is an additional small inlet VSD and the physiology is similar to that of the partial form. The management of the partial form, also called ostium primum ASD, and transitional form is similar and was discussed in our previous review1 and will not be repeated here. The complete form has one AV valve annulus, a large ostium primum ASD, and a contiguous large inlet VSD. The intermediate form is similar to the complete form with the exception that the single AV annulus is divided into two orifices by a tongue of tissue. The complete forms are further divided into Rastelli types A, B, and C on the basis of the characteristics of the anterior bridging leaflet105. Another classification based on relative ventricular sizes is balanced and unbalanced AVSDs; the unbalanced defects constitute 10 to 15% of all complete forms of AVSDs. The unbalanced forms may be LV-dominant  or RV-dominant ; the RV-dominant AVSDs are more common. The unbalanced AVSDs require different types of surgical approaches.The AVSDs are classified into partial, transitional, intermediate, and complete formsHemodynamic abnormalities in patients with AVSD are secondary to the left-to-right shunt across the ASD and VSD components and mitral valve insufficiency. As mentioned in the “Ventricular septal defects” section, the left-to-right shunt across the ASD and VSD may not manifest in the neonate and young infant and this is due to high PVR. As the pulmonary arterioles involute and PVR falls, left-to-right shunt occurs, resulting in dilatation of the left atrium and LV; this may take several weeks unless there is an anomalous and rapid fall in PVR. Because the ASD and VSD components are large, there is dilatation of the right atrium, RV, and main and branch pulmonary arteries. If there is moderate to severe mitral insufficiency, further dilatation of the left atrium and LV ensues. PVOD may develop as early as six months to one year of age in patients with complete AVSDs and even earlier in babies with Down syndrome.Discussion of AVSDs seen in association with tetralogy of Fallot, pulmonary atresia/stenosis, transposition of the great arteries, and double-outlet RV will not be included in this review.106 may be performed. At present, primary complete repair is performed at most institutions. Pulmonary artery banding may be considered for babies weighing less than 5 kg in whom the CHF could not be controlled and babies with other significant co-morbidities109.Most, if not all, complete and intermediate types of AVSD have large ASD and VSD components and therefore all patients with AVSD should have their defects repaired. Alternatively, pulmonary artery banding8 and pulmonary vascular reactivity testing9 are similar to those described in the “Ventricular septal defects” section and will not be repeated. Patients with AVSDs and severely elevated PVR  are not suitable for AVSD repair. These patients eventually may become candidates for lung transplantation.In patients with elevated PVR, the considerations for operabilityMedical and surgical treatment options for balanced and unbalanced AVSDs will be reviewed separately.Balanced atrioventricular septal defects (complete and intermediate).Medical managementNeonates with AVSDs with no signs of CHF do not need treatment in the newborn period; however, we usually begin treatment with infrequent doses of furosemide (once every other day) since a predictable decrease of PVR with time occurs with a resultant increase in pulmonary blood flow and development of CHF. In a few weeks, these infants will develop CHF; at that time, they should be managed with aggressive anticongestive treatment, as reviewed in the “Ventricular septal defects” section above, including optimization of nutrition, maintenance of adequate hemoglobin level, and appropriately addressing the associated respiratory symptoms.Similar to what was discussed in the preceding section on VSDs, patients with a severe increase of PVR (irreversible PVOD) should not have their AVSDs closed. The management of PVOD associated with AVSDs is the same as that discussed in the VSD section.Surgical management110. Pulmonary alveolar and capillary hypoplasia111 and chronic upper airway obstruction with resultant hypoventilation producing hypoxia and hypercarbia may be responsible in part for higher PVR112 and early PVOD in babies with Down syndrome.In order to prevent the development of irreversible PVOD, timely surgical repair, preferably prior to six months of age, should be performed. Although it is our general impression that babies with Down syndrome develop PVOD earlier than non-Down babies, histological studies do not seem to indicate any difference in pulmonary vascular changes between Down and non-Down childrenCorrective surgery. Surgical correction is performed after placing the patient on cardiopulmonary bypass and consists of patch closure of atrial and ventricular septal defects along with repair and reconstruction of AV valves. Closure of ASD and VSD components may be performed by using either a single-patch technique  or two-patch technique . In all instances, the common AV valve is separated into left and right components; the left AV valve cleft is completely or partially closed on the basis of subvalvar anatomy, and the right AV valve cleft may be closed as indicated. In some instances, the Australian repair  may be considered. A recent metal analysis comparing single-patch with two-patch technique demonstrated no significant difference between two groups with comparable outcomes113; however, the cardiopulmonary bypass and aortic cross-clamp times were shorter in the single-patch method of closure of the defect113. AV valves are repaired/reconstructed by using the techniques described by Carpentier114, Puga and McGoon115, or Chopraet al.116. Associated defects such as patent ductus arteriosus and left ventricular outflow tract obstruction  should be addressed at the same sitting. In the present day, TEE is performed to evaluate mitral and tricuspid valve function  and residual shunts prior to decannuation from cardiopulmonary bypass. Re-repair of mitral  valve is generally undertaken if the degree of insufficiency or stenosis is more than mild.Pulmonary artery banding. As mentioned above, banding of the pulmonary artery may be performed in babies weighing less than 5 kg in whom the CHF could not be controlled and when associated with significant co-morbidities. The banding should be tight enough to produce near normal pressures distal to the band, but care should be taken to avoid any deterioration in LV function based on intra-operative transesophageal echocardiogram. Corrective surgery along with the removal of the band may be performed a few months later when the infant improves clinically. However, the trend is for complete repair at most institutions.Surgical results125, which included 37 to 1,917 patients. The immediate mortality rates varied between 2 and 62%125. Some studies compared the results of the earlier era with those of the present time, these comparisons have consistently shown improvement of mortality rates in recent years. More recent studies demonstrated a substantial fall in mortality rates (down to 2 to 3%)125. Although there are differences in risk factors for surgical mortality from one study to the next, the most commonly found risk factors were preoperative severity of mitral regurgitation and New York Heart Association (NYHA) functional class. Other risk factors identified in some studies were very young age, small size of the babies, postoperative residual mitral valve regurgitation, ventricular hypoplasia , additional muscular VSDs, and double-orifice mitral valve.A large number of investigators reported results of surgical repair of AVSDs. We examined the results of some of these studies126 compared the outcomes and complications between Down and non-Down babies. There was no postoperative mortality in either group. Cardiac complications such as the prevalence of junctional ectopic tachycardia, the need for early reoperation, and the requirement for insertion of a permanent pacemaker for complete heart block were similar in the two groups. However, there was higher prevalence of non-cardiac complications such as pneumothorax, pleural effusions, and infections in infants with Down syndrome than in those without Down syndrome. However, these non-cardiac complications did not increase duration of stay in the pediatric intensive care unit. These data affirm our thinking that babies with Down syndrome should receive the same treatment as those without. In fact, non-Down babies tend to have more abnormal left AV valve morphology, and AVSD repair in children with Down syndrome is more straightforward than that in babies without Down syndrome. In the current era, surgery is the therapy of choice in all infants and ideally is performed between three and six months of age.There is some early concern regarding poor tolerance for surgery in the patients with Down syndrome. One relatively recent study123, and 85%, 82%, and 71% at 10, 20, and 30 years, respectively124. The estimated rates of freedom from late reoperation were 96% at 1 year, 89% at 5 years, and 89% at 15 years123. Reoperation may be required in 10 to 15% of patients; mitral valve regurgitation (7 to 10%) is the most common reason for late reoperation, followed by left ventricular outflow tract obstruction (3.5%). A small percentage of patients may require surgery for tricuspid regurgitation, mitral stenosis, or residual shunts. Risk factors for late reoperation were other cardiovascular anomalies, mitral valve dysplasia, and absence of mitral cleft closure during the initial surgery123.In studies in which long-term follow-up data were available, actuarial survival rates were reported be 91%, 91%, and 89% at 1, 5, and 15 years, respectivelyUnbalanced atrioventricular septal defects.Medical managementThe medical management at presentation is similar to that described for balanced AVSDs.Surgical managementSeveral surgical options are in use for treating unbalanced AVSDs and will be reviewed. Single-ventricle palliation (Fontan)131. Remarkable changes in the concepts and methods of surgery have occurred since the initial description of right ventricular bypass by a complex procedure by Fontan125 and a simpler atriopulmonary anastamosis by Kruetzer126. The descriptions of bidirectional Glenn134, total cavopulmonary connection135, extracardiac non-valved conduits137, staged procedures134, creation of fenestration140, and device closure of fenestration139 have resulted in the evolution of the procedure such that it is now a staged (three-stage) total cavopulmonary connection with an extracardiac conduit and fenestration with subsequent device closure of the fenestration131.The reparative techniques described above for balanced AVSDs cannot be used in unbalanced AVSDs because of hypoplasia of the RVs or LVs which after the repair may not be able to support the pulmonary or systemic circulations, respectively. Marginal-sized RVs may be addressed with a combination of biventricular repair and bidirectional Glenn procedure. By and large, these patients require a staged Fontan surgery similar to that described for tricuspid atresia and other single-ventricle (SV) lesions131, and the interested reader is referred to that article.Following control of CHF, as described above in the “Balanced atrioventricular septal defects” section, pulmonary artery banding is performed to limit the pulmonary blood flow, control CHF, and normalize the pulmonary artery pressures (stage I of Fontan). At about six months of age, a bidirectional Glenn procedure is performed (stage II of Fontan). Prior to the procedure, one must be assured of normal pulmonary artery pressures; if this cannot be done by echo-Doppler studies, cardiac catheterization may be required. In the presence of a persistent left superior vena cava, a bilateral, bidirectional Glenn procedure may be required, especially if the bridging left innominate vein is absent or small. If there is significant AV valve regurgitation or other hemodynamically significant abnormalities, they should be appropriately addressed at this stage. One year after the bidirectional Glenn (or between one and four years of age), the inferior vena caval flow is diverted into the pulmonary artery by either a lateral tunnel or an extracardiac non-valved conduit (stage IIIA); most surgeons seem to prefer extracardiac conduit with fenestration. Cardiac catheterization and selective cine-angiography are recommended  prior to stages II and III to ensure suitability for proceeding with the next stage of surgery. Six months to one year after stage IIIA, the fenestration is closed percutaneously with a device (stage IIIB). Detailed angiographic anatomy at each Fontan stage is demonstrated in a prior publicationResults of single-ventricle palliation (Fontan). The operative mortality in patients who had staged, cavopulmonary connection with fenestration appears to be between 4.5 and 7.5%141. On follow-up, actuarial survival rates were 93% at 5 years and 91% at 10 years142. In another study, the actuarial survival was 85% at 15 years143. The re-intervention  rate was 12.7%. It should be noted that the patients in these studies included all types of SV lesions, namely tricuspid atresia, double-inlet left (single) ventricle, hypoplastic left heart syndrome, mitral atresia with normal aortic root, unbalanced complete AVSDs, pulmonary atresia with intact ventricular septum with markedly hypoplastic RV, and any complex heart defect with one functioning ventricle. When one examines Fontan procedures in patients with unbalanced AVSDs, the mortality rates (17 to 31.7%) were higher145 and actuarial survival rates (66.5% at 5 years and 64.4% at 15 years) were lower146 and there were more surgical and catheter re-interventions (51.9%)145. Equally poor results with an overall long-term survival rate of 50% were observed in another study; these results were poorer than for a cohort with hypoplastic left heart syndrome patients operated during the same period146. It should be noted that complications, namely arrhythmias, Fontan pathway obstruction, cyanosis, paradoxical emboli, formation of thrombus, collateral vessels, and protein-losing enteropathy, may be seen on long-term follow-up, although most of these complication are less common with staged total cavo-pulmonary connection than with earlier versions of Fontan131.Two-ventricle repair151. In the staged procedure, the residual defects are repaired surgically after demonstration of growth of the hypoplastic ventricle.The AV valves are repaired to create nearly equal-sized AV valves along with complete (single stage) or partial (staged) closure of ASD and VSD components159.The criteria used to select a given patient to SV versus two-ventricle (TV) route are not clearly established. Several investigators examined this issue by evaluating potential echocardiographic LV volume after normalization of septal bowing, ventricular cavity ratio between the two ventricles (estimated as left ventricular length × width/right ventricular length × width), AV valve index , a different type of AV valve index , ventricular dimensions, LV end-diastolic volume index, RV/LV inflow angle in systole, left AV valve color diameter at smallest inflow, left AV valve color diameter at annulus, indexed ventricular septal defect , left ventricular inflow index , and other indices149, more than 0.65150, or more than 0.67152 for right dominant unbalanced AVSDs. Other suggestions for selecting TV repair are indexed potential LV volume of more than 15 mL/m2151, left ventricular inflow index greater than 0.5154, and indexed ventricular septal defect smaller than 0.2158. The last group of investigators158 also recommended that patients with indexed VSD values between 0.2 and 0.35 may be considered for TV repair on the basis of other factors. If the indexed VSD value is between 0.35 and 0.5, SV palliation may be required. Other investigators examined various echo-Doppler parameters and made a correlation between these parameters and survivals but did not include definitive cutoff points for TV repair. Another group of investigators used angiographic measures and suggested that patients with LV-to-RV long axis ratio of more than 0.65 on cine-angiograms may be suitable for TV repair150. Perhaps a combination of indexed VSD, AV valve index, and RV/LV inflow angle in systole may guide the selection of patients for TV repair160.At present, no clear-cut, uniform echocardiographic criteria are established for selecting a given unbalanced AVSD patient for TV repair. However, some investigators advocate TV repair if AV valve index  is more than 0.5Results of two-ventricle repair. There are limited data with regard to the results of TV repair. The mortality rates varied between 10.4 and 18%153, although it was a higher (40%) in an earlier series152. Long-term survival was good and ranged from 88 to 90%150. However, surgical (17.4 to 34%) or transcatheter (13.4%) re-interventions were frequently required150. But improvement of AV valve Z-scores (−2.8 to −7.4 versus −0.6 to −2.7 )147, ventricular dimension Z-scores (−1.0 to −7.5 versus −2.0 to +1.8)147, and LV end-diastolic volume Z-scores (from a median of −3.15 to +0.42)144 occurred at follow-up.Conversion from single-ventricle to two-ventricle repair159. Rehabilitation of the left heart is undertaken by promotion of flow through the LV by relief of inflow or outflow tract obstructions (or both) and resection of endocardial fibroelastosis (if present). Restriction of the atrial septum to promote flow through the LV is also undertaken. This group involves patients who initially had SV palliation but were later converted to TV circulation. This approach was precipitated by suboptimal long-term outcomes after SV palliationResults of conversion from single-ventricle to two-ventricle repair. The reported mortality following conversion to TV circulation is low (1 to 11%)161. Surgical (19%) and catheter (38%) re-interventions were required during follow-up161. Although the initial Z-scores of the LV prior to stage I SV palliation were not significantly different, the LV Z-scores increased significantly in the SV to TV group but decreased in the SV palliation group without conversion159. Another study from the same institution162 demonstrated improvement of left ventricular end-diastolic volume by echocardiography from 28.1 to 58.5 mL/m2 in a small group of the unbalanced AVSD group following SV-to-TV conversion162.145.A recent study examined mid-term outcomes of primary and staged biventricular repair and SV-to-TV conversion of unbalanced complete AVSDs and concluded that these methods result in low morbidity and mortality although re-interventions  in 52% of patients were requiredComparison of various methods of intervention for unbalanced atrioventricular septal defectset al. compared the outcomes of patient cohorts who had SV palliation, TV repair, and conversion from single-ventricle to two-ventricle (SV to TV)144. The TV repair and SV-to-TV groups were reasonably similar with regard to mortality and the need for heart transplantation but were lower than that seen with the SV palliation cohort during a mean follow-up of 35 months. Although the surgical re-interventions were similar in the three groups, catheter re-interventions were lower in the TV repair group than in the other two groups. They conclude that TV repair and SV-to-TV conversion may be accomplished with lower mortality and morbidity rates in children with unbalanced AVSDs, although the study was critiqued163 for allowing survivorship bias in favor of TV repair and SV-to-TV groups. Conversion from SV palliation and biventricular recruitment remains an important option for children with Down syndrome and heterotaxy syndrome for physiologic and anatomic reasons. Patients with Down syndrome tolerate SV physiology poorly164. Patients with heterotaxy syndrome have complex and abnormal AV valve anatomy and require complex and innovative repair techniques. They also tolerate AV valve regurgitation poorly when palliated via the SV pathway.NathanTreatment of CHF (if present) followed by surgical repair with closure of atrial and ventricular septal defects along with repair and reconstruction of AV valves is a standard approach in babies with balanced AVSDs. Pulmonary artery banding may be performed to palliate infants weighing less than 5 kg as well as those with significant co-morbidities. Timely intervention to prevent PVOD is exceedingly important. The management of unbalanced AVSDs is complex; staged SV palliation (Fontan) is performed at most institutions, but recent data seem to indicate that primary or staged TV repair or converting SV to TV repair may be better choices. The management of babies with Down syndrome should be similar to that used for non-Down infants.


Speckle tracking echocardiography derived left ventricular systolic function was impaired in chronic alcoholic patients when compared with healthy controls.By using two-dimensional speckle tracking echocardiography, we aimed to investigate the structural and functional changes on myocardium in chronic asymptomatic alcoholics without any cardiovascular disease. Forty-one consecutive asymptomatic male alcoholics who were admitted to the outpatient alcoholism unit and 30 age matched healthy male volunteers selected as the control group were enrolled in the study. The study group were investigated by using standard two-dimensional echocardiography and speckle tracking echocardiography. The left ventricular (LV) global longitudinal strain and LV global circumferential strain were significantly lower in alcoholics when compared with control subjects. There was no difference in global radial strain between the two groups. To demonstrate the effect of total life time dose of ethanol (TLDE) on echocardiographic abnormalities, we assessed the correlation analysis. There was a nonsignificant weak correlation between global LV circumferential strain and TLDE ( Chronic excessive alcohol consumption is related with cardiomyopathy where alcoholic cardiomyopathy has been seen in about 10% of alcoholics and prevalence ranges from 23% to 40% [Transthoracic echocardiography can detect mild left ventricular hypertrophy, diastolic dysfunction, and left ventricular dilatation in asymptomatic alcoholics . AlthougOur study aims to analyze the structural and functional changes on myocardium using two-dimensional speckle tracking echocardiography in chronic asymptomatic alcoholics without any cardiovascular disease and any disease which could impair myocardial functions.Forty-one consecutive asymptomatic male alcoholics who were admitted to the outpatient alcoholism unit which is located in Mediterranean region of Turkey were enrolled in this study. Thirty age matched healthy male volunteers were selected as the control group. None of them had any history, signs, or symptoms of cardiovascular diseases.The exclusion criteria were a history of congenital heart disease, hypertension, diabetes mellitus, coronary artery disease, valvular heart disease, atrial fibrillation, and systemic and metabolic disease such as chronic liver disease or renal dysfunction. All the patients were questioned about the amount and duration of alcohol consumption.Total lifetime dose of ethanol (TLDE) was calculated by first multiplying the daily consumption of ethanol by the number of days of the periods of exposure to alcohol and then dividing the product by the body weight of the patient .Echocardiographic examinations including conventional, pulsed Doppler, tissue Doppler, and speckle tracking echocardiography were performed in 41 alcoholics and 30 age matched controls. Echocardiographic study was done by ultrasound machine GE-Vingmed vivid 7 system  and 3S-RS (3.5 mhz) probe.Speckle tracking echocardiography analysis was performed from apical and parasternal short axis views, respectively. Standard grayscale 2D images were obtained at a frame rate of 70–90 frames/s during three cardiac cycles and software package  was used for offline analysis. Endocardial border of the left ventricle was traced manually from the end systolic frame. The software automatically detected the epicardial border and created a region of interest which was adjusted manually to include the entire myocardial wall. Apical and short axis views of left ventricle were processed by software to select natural acoustic markers. Then these markers were tracked frame by frame during cardiac cycle to measure strain and strain rate of left ventricle at any point of the myocardium. To obtain optimal tracking, necessary corrections were done for the quality tracking verification and region of interest modification. All echocardiographic measurements were done according to the guidelines of American Society of Echocardiography.2) and body surface area  of all subjects were calculated. Venous blood count was obtained from all subjects on admission as a routine part of clinical examination. A detailed questionnaire was applied to evaluate the real dose of alcohol consumed and then confirmed by family members because of the known characteristics of alcoholics.After a complete physical examination, anthropometric measurements of height and weight were done and body mass index  or Fisher's exact test, as appropriate. Spearman's test was used for correlation analysis. A p value of less than 0.05 was regarded significant for all analyses. Analyses were performed with PASW 18  software and two-tailed p value less than 0.05 was considered statistically significant.Continuous and categorical variables were expressed as mean ± standard deviation (SD) and percentages, respectively. The Kolmogorov-Smirnov test was used to verify the normality of the distribution of continuous variables. Continuous variables were compared using one-way ANOVA test. Categorical variables were compared using chi-square test . There were no differences in LV mass index, EDD, ESD, E/A ratio, IVRT, and IVCT among two groups. Deceleration time was longer in alcoholics .Left ventricular ejection fraction did not show any difference between healthy subjects and the alcoholics. Compared to controls, alcoholic group had a significant difference in left atrium diameter .The LV global longitudinal strain and LV global circumferential strain were significantly lower in alcoholics when compared with control subjects. There was no difference in global radial strain between two groups. Strain measurements of two groups were given in Using two-dimensional speckle tracking echocardiography to evaluate alcoholic cardiac damage, inter- and intraobserver variability results showed a good reproducibility and small variability.In our study we demonstrated that left ventricular global longitudinal strain and left ventricular global circumferential strain were deteriorated in chronic alcoholic patients. It has been shown that global longitudinal strain is a quantitative index for global left ventricle function . Two-dimChronic alcoholic consumption causes several histological and cellular changes in the myocardium. These changes include myocyte death, intracellular dysfunction, deterioration of mitochondrial ultrastructure, and sarcoplasmic reticulum . Also itThe subclinical cardiac damage in chronic alcoholic patients was investigated in various studies using conventional and tissue Doppler echocardiography. Previous clinical studies evaluating the effect of chronic alcohol consumption on LV systolic and diastolic functions showed conflicting results. Impaired ejection fraction, preserved ejection fraction, and normal and impaired LV filling parameters were reported as a result in these studies –19.Although the natural course of chronic alcoholic cardiomyopathy could not be defined clearly, it has been shown that abstaining from alcohol is associated with improvement in ejection fraction , 21. As Two-dimensional speckle tracking echocardiography (STE) is a new noninvasive ultrasound imaging technique which allows measuring LV rotation, torsion, and strain as an evaluation of global and regional myocardial function. Speckle tracking echocardiography is angle independent and is less affected by artifacts, acoustic noise, and translational movements , 23. SpeIn our study all asymptomatic alcoholics had normal cardiac structure and ejection fraction, except that alcoholic patients had a significant difference in left atrial diameter. Similar to our study, Singh et al. demonstrated that modest levels of alcohol consumption were associated with significant left atrium enlargement . DiffereOur present study showed the limitations of conventional echocardiographic evaluation of early deterioration in cardiac systolic function and the value of speckle tracking echocardiography in subclinic alcoholic cardiomyopathy. The novel echocardiographic modalities would allow for demonstration of heavy alcohol consumption outcomes on systolic function.The gross limitation of our study was the small sample size. Only male subjects were included in our study; therefore the effects of chronic alcoholism on LV functions in women could not be evaluated. Since there are no clear data related to classification, we could not group patients according to amount and duration of alcohol consumption for subgroup analysis. Clinical follow-up was not planned so the effect of subclinical dysfunction on cardiovascular prognosis remains unclear. The importance of these subclinical findings should be determined with a well-designed prospective study including cardiovascular prognosis.Even with the abovementioned limitations we can conclude that speckle tracking echocardiography derived left ventricular systolic function is impaired in chronic alcoholic patients when compared with healthy controls.