The heart carries out its pumping function by converting the chemical energy stored in fatty acids and glucose into the mechanical energy of actin-myosin interaction of myofibrils. Development of congestive heart failure is usually preceded by a period of compensated left ventricular hypertrophy (LVH) and alterations in myocardial bioenergetics have been considered to play an important role in this transition. Myocardial energetic state that is reflected by the ratio of Phosphocreatine to Adenosine Triphosphate (PCr/ATP) is significantly decreased in hearts with LVH. The severity of this abnormality is linearly related to the severity of cardiac hypertrophy as well as left ventricular (LV) dysfunction, and is independent of a persistent myocardial ischemia. The decrease in PCr/ATP is accompanied by a decrease in creatine kinase flux and alterations in substrate utilization in LVH hearts. Moreover, there is a profound heterogeneity in alterations in myocardial energy metabolism in hearts with post-infarction hypertrophy with the most severe abnormality present in the inner layers of the periscar border zone (BZ). This review will discuss various aspects of myocardial energetics in animal models of three different types of LVH  with a brief description of myocardial energetics in humans with LVH. The second component is oxidative phosphorylation which involves transfer of electrons from NADH to oxygen through the mitochondrial respiratory chain that creates a proton electrochemical gradient across the inner mitochondrial membrane subsequently driving the F1-F0 ATP synthase to produce Adenosine Triphosphate (ATP) by phosphorylating Adenine Diphosphate (ADP). The third component is ATP transfer and utilization that involves the creatine kinase shuttle. Cardiac energy metabolism has three components. The first is substrate utilization which involves the cellular uptake of substrates (mainly fatty acids and glucose) and their breakdown by beta-oxidation and glycolysis resulting in the formation of acetyl coenzyme A (CoA), which is fed into the Krebs cycle and produces Nicotinamide Adenine Dinucleotide (NADH) and carbon dioxide (CODerangements in cardiac energy metabolism occur with the development of left ventricular hypertrophy (LVH). LVH is a manifestation of cardiac remodeling and has been classified into pressure overload hypertrophy, volume overload hypertrophy and post-infarction hypertrophy. LVH is initially adaptive but ultimately leads to maladaptive hypertrophy and transition to congestive heart failure (CHF). The exact mechanisms underlying this transition from compensated LVH to CHF are likely multifactorial but alterations in myocardial bioenergetics have been considered to play an important role.in vivo is through Nuclear Magnetic Resonance (NMR) spectroscopy. Our laboratory has specialized in performing in vivo NMR spectroscopy in large animals to study abnormalities in high energy phosphate metabolism, oxidative phosphorylation, creatine kinase kinetics and flux and substrate utilization. In this review, we will focus on the myocardial energetics in different animal models of ventricular hypertrophy (summarized in Table 1).The principal method for studying myocardial energy metabolism Pressure overload hypertrophy leads to concentric hypertrophy due to an increase in wall thickness that can be seen clinically in patients with hypertension or aortic stenosis. Different animal models have been used to create pressure overload leading to concentric hypertrophy. The degree of ventricular hypertrophy varies in these models and thus the results of the studies vary slightly. The most commonly used method is placement of a constrictor band around the ascending aorta to cause an increase of left ventricular systolic pressure.  vs. 4.3±0.14 g/kg, p< 0.01) which represented a doubling of the relative LV mass in the banded dogs . FAO enzyme mRNA levels were coordinately downregulated (>70%) during both the LVH and HF stages in the SHHF rats compared with controls. In contrast, the activity and steady-state levels of medium-chain acyl-CoA dehydrogenase, which catalyzes a rate-limiting step in FAO, were not significantly reduced until the HF stage, indicating additional control at the translational or posttranslational levels in the hypertrophied but nonfailing ventricle [i), and fructose-2,6-bisphosphate , all activators of the rate-limiting enzyme phosphofructokinase (PFK), were increased (up to 10-fold) [2 and increased sarcolemma localization of glucose transporters, leading to coordinated increases in glucose transport and activation of PFK.Recent advances in molecular biology have enabled us to study the molecular mechanisms underlying the observed substrate switch in pressure overload hypertrophy. These studies have revealed the importance of peroxisome proliferator-activated receptor gamma co-activator (PGC-1α) and peroxisome proliferator-activated receptor (PPAR) in mitochondrial dysfunction. The expression of the PGC-1 gene, as well as nuclear respiratory factor 2 and mitochondrial transcription factor A, which act downstream from PGC-1 were shown to be downregulated in rats with pressure overload due to aortic banding . In a moentricle . In a ra10-fold) . This acVolume overload leads to eccentric hypertrophy as a result of increase in cardiomyocyte length. Left ventricular volume overload can be of two types: low-pressure or high pressure . Low preOur group has studied the myocardial energetics in a canine model of volume overload LV hypertrophy by tearing the chordae tendineae and causing severe mitral regurgitation (MR) . This re125I-iodophenyl 9-methylpentadecanoic acid was increased in the volume-loaded animals, suggestive of a greater fatty acid uptake and oxidation [Substrate metabolism has also been studied in volume overload LV hypertrophy. In a rabbit model of volume overload created by carotid-jugular shunt formation, eccentric hypertrophy developed as seen by an increase in LV end-diastolic dimension without an increase in anterior or posterior wall thickness . The myoxidation . In cont vs. 3.65±0.25 vs. 4.99±0.42). It caused a decrease in ejection fraction to about 35% and 27% in the LVR and LVR+CHF group respectively. LV end-systolic volume increased significantly in both groups of animals with remodeling and was significantly higher in LVR+CHF hearts than in LVR hearts. Both LV diastolic wall stresses and mean LV systolic wall stresses were significantly increased in hearts with LVR and were further increased in LVR+CHF hearts.Post-myocardial infarction hypertrophy is a complex phenomenon in which the stretched and dilated infarcted tissue increases left-ventricular volume with a combined volume and pressure load on non-infarcted areas . Our labThe bioenergetic abnormalities in our post-infarction LV hypertrophy model were characterized by a lower ATP, CP, creatine and PCr/ATP ratio in the LVR hearts and the LVR+CHF hearts had an even lower PCr/ATP ratio. The myocardial calculated free ADP levels were significantly increased only in CHF hearts. The increase in myocardial free ADP is associated with reductions in mitochondrial F0F1-ATPase protein expression . These HIt is known that the decrease of PCr/ATP in LVR animal during dobutamine infusion is not the result of insufficient myocardial oxygen availability . FurtherIt has been shown that the CK-MM and CK-mitochondrial protein levels are decreased in animals with pos-infarction hypertrophy while the CK-MB levels are increased . HoweverSubstrate utilization in post-infarction LV hypertrophy also exhibits shifts in fatty acid and glucose metabolism. In a post-infarction rat model, glucose oxidation was increased by 84% while there was no change in palmitate oxidation 8 weeks after MI . The patPost-infarction hypertrophy differs significantly from other forms of hypertrophy because of the presence of a discrete scar region. The alterations in myocardial HEP and mtATPase have been shown to be substantially more severe in the peri-infarct region than in the remote zone of hearts with compensated postinfarction LV remodeling . These a2) have shown similar results to previously obtained from animal studies. Clinical studies of cardiac energy metabolism (summarized in Table 2) than healthy control subjects . LV filling was impaired in patients, reflected by a decreased peak rate of wall thinning (PRWThn), E/A ratio, early peak filling rate, and early deceleration peak , whereas systolic function was still normal. The myocardial PCr/ATP ratio determined in patients at rest (1.20±0.18) and during stress (0.95±0.25) was lower than corresponding values obtained from healthy control subjects at rest  and during stress . The PCr/ATP ratio correlated significantly with PRWThn , early deceleration peak , and with the rate-pressure product . Creatine kinase kinetics is also affected in patients with pressure induced LVH. In hypertrophic human hearts in the absence of CHF, ATP flux through CK is reduced by 30% in LVH patients, and this reduction can be accounted for by a proportionate loss of substrate (PCr) [The PCr/ATP ratio is decreased in patients with pressure induced LVH , 37. In te (PCr) . Patientte (PCr) . These dPCr/ATP is also lower in humans with volume overload hypertrophy such as chronic MR and the severity of abnormal myocardial energetics is linked to disease severity as measured by dimensional indexes of left ventricular dilatation and hypertrophy . In pati201Tl scintigraphy, but ATP content was decreased significantly only in subjects with fixed thallium defects [There have been some myocardial energetic studies in ischemic heart disease patients. In patients with ischemic cardiomyopathy, PCr/ATP ratio was significantly lower as compared to controls . Cardiac defects . The data on substrate metabolism in patients with LV hypertrophy is scant, while in patients with congestive heart failure it is conflicting. In a study of NYHA class II and III patients, fatty acid uptake was increased while glucose uptake was decreased . This waLeft ventricular hypertrophy is characterized by derangements in cardiac energy metabolism including lower PCr/ATP, abnormal creatine kinase kinetics and deranged substrate utilization. The PCr/ATP is significantly decreased in hearts with LVH and the severity of this abnormality is proportional to the degree of cardiac hypertrophy and accompanying LV dysfunction. These myocardial energetic abnormalities are also not due to a persistent myocardial ischemic state. There is a profound heterogeneity in the myocardial energy metabolism in hearts with postinfarction LV remodeling with the most severe abnormality occurring in the inner layers of the periscar border zone (BZ). Increased wall stress and overstretching of myocytes could contribute to the observed decrease in energetic efficiency in the BZ. CHF probably develops as this energetically inefficient BZ expands over time and eventually involves the entire heart. Preserving myocardial energetic efficiency through metabolic therapies is a promising therapy for heart failure in the future. To achieve this goal, further molecular studies are required to understand the mechanisms underlying the myocardial energetic abnormalities. Furthermore, development of effective and time feasible methods of non-invasive NMR spectroscopy along with magnetic resonance imaging (MRI) will allow us to study temporal changes in myocardial energetics in patients with LVH and CHF and correlate these with structural changes in the hearts. Finally, new drugs need to be developed and tested that target energy metabolism pathways with the ultimate goal of improving survival in patient with LVH and CHF.


Drosophila melanogaster, to understand the fundamental mechanics of the beating heart. We applied a live imaging technique to the beating embryonic heart combined with analytical imaging tools to study the dynamic mechanics of the pumping. Furthermore, we have identified one mutant line that exhibits aberrant pumping mechanics. The Drosophila embryonic heart consists of only 104 cardiac cells forming a simple straight tube that can be easily accessed for real-time imaging. Therefore, combined with the wealth of available genetic tools, the embryonic Drosophila heart may serve as a powerful model system for studies of human heart diseases, such as arrhythmia and congenital heart diseases. We, furthermore, believe our mechanistic data provides important information that is useful for our further understanding of the design of biological structure and function and for engineering the pumps for medical uses.The heart is a vital organ that provides essential circulation throughout the body. Malfunction of cardiac pumping, thus, leads to serious and most of the times, to fatal diseases. Mechanics of cardiac pumping is a complex process, and many experimental and theoretical approaches have been undertaken to understand this process. We have taken advantage of the simplicity of the embryonic heart of an invertebrate,  The heart is the center of the circulatory system, which is one of the vital organs for survival of organisms. Extensive experimental and theoretical approaches have been undertaken to understand the mechanics of human heart function One such model organism is zebrafish, which is one of the most popular model organisms for understanding the genetic and molecular basis of developmental and physiological processes. Zebrafish is a vertebrate and its heart consists of two chambers, ventricle and atrium Drosophila is one of the most popular invertebrate model organisms that have been used for centuries. The heart of Drosophila is a simple straight tube consisting of two rows of cardiac cells forming a linear tubular structure Drosophila heart have uncovered evolutionarily conserved molecular pathways that specify the identity of cardiac cells Drosophila heart Drosophila heart also provided some important insights into the molecular mechanisms underlying the cardiac functions Although zebrafish heart provides a useful model system to study the mechanics of the most primitive chambered heart, it may be as well useful to study the mechanics of cardiac pumping of the heart of even simpler structure. Drosophila heart. It is presumed that the major function of the Drosophila heart is to pump and distribute hemolymph throughout the body. It has been proposed that a valve structure that separates the aorta from the heart proper opens and closes, in coordination with openings/closings of ostia, to control unidirectional flow of hemolymph through the dorsal vessel In contrast to the existence of such extensive knowledge on the molecular and genetic controls of cardiac formation and function, almost nothing is known about the pumping mechanics of the Drosophila embryonic heart and analytical tools to gain insight into the mechanics of the beating Drosophila heart. In this report, we demonstrate several features of pumping mechanics of the beating embryonic heart of Drosophila. Our studies have also revealed a pumping mechanics of a simple tubular heart of invertebrate that surprisingly mimics an aspect of the beating human heart. Further, towards our understanding of the molecular basis of this pumping mechanics, we have also identified a genetic mutation that leads to an aberrant pumping mechanics.Although such description of pumping mechanics intuitively makes sense, the precise mechanical description of such pumping function is missing in the published literature. Therefore, we used a combination of live imaging of the beating Drosophila heart in live, we used a transgenic Drosophila line, Toll-nGFP, where GFP is expressed in the nucleus of all individual cardiac cells To study the dynamics of the pumping mechanics of The intermittent but rhythmic beating of the heart was observed by stage 17 during embryogenesis. The heart proper, a wider posterior portion of dorsal vessel, is ∼55 µm in length with ∼20 µm in diameter . As the The live imaging of the embryonic heart clearly shows rhythmic contraction of the cardiac cells in the systolic phase with a time period of ∼150 ms , and theAn experiment using another GFP line, DMef2::Gal4;Twist::Gal4;UAS::actinGFP, was carried out to further study the dynamics of the behavior of the ostia cells during the pumping . Movie SDrosophila heart, we tracked the movement of each cardiac cell using a particle tracking program . The expansion of the bulb is followed by the opening of the ostia valves, Cv2. This obvious reversed sequence of the opening/closing of valves and squeezing motion of the Vegfc2195 heart also remains in larval stage , the diffusion should be sufficient for the body fluid to be distributed. Also, this small size allows for the sufficient oxygenation of the whole embryo without any active transport systems. In larval and later stages, the extensive network of tracheal system suffices the uniform distribution of oxygen Drosophila allows the distribution of hemolymph throughout the body Drosophila embryonic heart is required for the morphogenesis of the developing heart. The third possibility is that the pumping in the embryonic stage allows for the fine-tuning in preparation for the synchronized mechanics of the beating heart in later stages.Another question is the role of pumping in Drosophila, how the sequential opening/closing of the valves related to the putative flow mechanics? It has been suggested that the ostia cells (Cv2) form channels for body fluid (hemolymph) to enter into the heart proper If, in fact, the hemolymph is flowing through the embryonic heart of Drosophila as a model system is the power of genetics that is available in this organism. Therefore, we have begun to isolate genetic mutations that affect the mechanics of the cardiac pumping. In this study, we show that the heart of one VEGFR mutant allele, c2195Vegf, exhibits reverse-sequence of the pumping mechanics , Mark Krasnow (Stanford University) and Mary Baylies (Sloan Kettering Research Institute), respectively. UAS-actinGFP line was obtained from Bloomington Drosophila Stock Center.Toll-GFP, VegfrEmbryos and larvae were harvested by manually removing the chorion membrane, and they were placed on 35 mm glass bottom culture dish (MatTek Corporation) for imaging. A thin layer of high vacuum grease (Dow Corning) was applied on the surface of glass bottom by a painting brush prior to placing embryos and larvae in order to minimize their movement during the imaging. Once they are placed with their dorsal side down on the culture dish, they were covered by halocarbon oil . The embryos and larvae were imaged by LSM LIVE (Carl Zeiss) in a temperature controlled stage set at 25°C throughout the imaging period. Typically, 5–10 embryos/larvae were placed on a single glass bottom dish for imaging. In each imaging experiment, the images of time series from several embryos and larvae were collected from the single culture dish simultaneously by using the Multi-Time mode system (Carl Zeiss) to minimize any variability from one experiment to another. The comparisons were made from embryos in the same culture dish that were imaged in a single experiment. The pin-hole size was set at 55 µm which allowed us to collect the entire depth of images of beating hearts in live action without collecting z-section series. In all experiments, 5–10 embryos were analyzed and they produced the consistently reproducible cardiac functions.http://biofluidics.mae.cornell.edu). Briefly, the positions of the cardiac cells are determined using the locations of the local light intensity maxima. The cross sectional area of the heart at a specific location along the heart tube is evaluated using the distance Positions of the cardiac cells are determined using an in house particle tracking software package  was calculated as described in the (0.43 MB TIF)Click here for additional data file.Movie S1Drosophila embryo (Toll-nGFP). Time between two consecutive images is 25 ms and the movie is played in real time. The images are enhanced and colored coded. The red and blue correspond to high and low light intensity respectively. The white circles indicate the locations of the tracked cells.A 5.00 sec. long movie of the beating heart of a normal transgenic (20.33 MB AVI)Click here for additional data file.Movie S2Drosophila embryo highlighting the opening and closing of the ostia valves (see locations of 6 white arrows) and the aortic valve Cv1. The movie is 8.25 s long, and the time between the consecutive images is 33 ms.A movie of normal beating heart of an DMef2::Gal4;Twist::Gal4;UAS::actinGFP (15.61 MB AVI)Click here for additional data file.Movie S3c2195Vegf (embryonic heart). The movie is 6.4 s long and the time between the two consecutive images is 25 ms.A movie of the heart of a VEGFR mutant allele, (15.95 MB AVI)Click here for additional data file.Movie S4c2195Vegf . The movie is 7.8 s long, and the time between the two consecutive images is 25 ms.A movie of the heart of a VEGFR mutant allele, (21.95 MB AVI)Click here for additional data file.


Danon disease is a rare X-linked dominant lysosomal glycogen storage disease that can lead to severe ventricular hypertrophy and heart failure. We report a case of Danon disease with cardiac involvement evaluated with cardiovascular magnetic resonance, including late gadolinium enhancement and perfusion studies. A 19 year old male with no previous history of heart disease was admitted with rest dyspnoea, found to be due to acute heart failure. He had felt fatigued with progressive limitation of exercise tolerance over the preceding 3 months. Symptoms were exacerbated by an upper respiratory tract infection one month before hospitalization. The patient was treated with antibiotics without noticeable improvement. The patient's mother had died suddenly at the age of 44 with a dilated cardiomyopathy of unknown cause for which she had had a pacemaker implanted.On admission, the patient was cachectic with a body mass index of 17 and in poor general condition, with rest dyspnoea, tachypnoea of 30/minute and tachycardia of 130/minute. His liver was enlarged, there was evidence of pulmonary oedema and a systolic murmur, maximal at the apex.Blood analysis showed elevated liver enzymes  and mildly elevated Troponin I and C-reactive protein levels. Chest X-ray confirmed pulmonary oedema and showed an enlarged heart shadow. Sinus tachycardia and left bundle branch block with QRS duration >200 ms were present on electrocardiogram.Echocardiography on admission revealed significantly enlarged left ventricle and both atria, severe hypertrophy of both ventricles muscle without left ventricular outflow tract (LVOT) obstruction. Moderate tricuspid and severe mitral valve insufficiency, decreased left ventricular (LV) ejection fraction to 30% with global hypokinesis were observed.The patient was referred for cardiovascular magnetic resonance (CMR), which was performed on a 1.5 T system with 4 element torso coil. Oxygen was supplied by mask throughout the study at a flow rate of 3 l/min. Function was assessed with steady state free precession (SSFP) sequence in short axis slices covering the ventricles and in 4-chamber, 2-chamber and LVOT orientations. Perfusion was assessed at rest only in 8 short axis slices using a gradient echo sequence with inversion recovery during and after intravenous administration of Gadopentate dimeglumine . Late gadolinium enhancement (LGE) images were obtained after 10–20 min in short axis and 4 chamber orientations. Inversion time was adjusted to null the signal from normal LV myocardium.The CMR study showed significantly reduced global function with left ventricular EF of 14%.  and the septum were taken. Electron microscopic analysis showed accumulation of autophagic vacuoles in affected cardiomyocytes. They were located within intrafibrillar spaces as well as in the perinuclear region Figure . Many ofDanon disease is a rare X – linked dominant, lysosomal glycogen storage disease that can lead to severe cardiac hypertrophy and heart failure especially in affected males. It was described first in 1981 in two boys by Moris J. Danon . The X-lWe present case of Danon disease confirmed by biopsy. As far as we know, this is the second description of CMR rest perfusion deficits and LGE in hypertrophic cardiomyopathy due to Danon disease ). In theWritten informed consent was obtained from the deceased patient's next of the kin (sister) for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.The authors declare that they have no competing interests.DPK and LKo contributed equally to this paper and should be considered joint first authors. They drafted the manuscript, performed CMR and interpreted CMR images. MK was patients cardiologists and wrote the clinical part of the manuscript. AK performed and interpreted ECHO. EW performed biopsy and established final diagnosis of Danon disease. EW and AF interpreted biopsy results. LKr helped write and rewrote the manuscript.Function. SSFP cine images – short axis slices covering the whole ventricleClick here for fileRest perfusion. "First pass" rest perfusion in 8 SA slices. Subendocardial and partly transmural perfusion deficits visible clearly within anterior and later walls and RV inferior junction point.Click here for file


Tricuspid Annular Plane Systolic Excursion (TAPSE) has independent prognostic value in heart failure patients but may be influenced by left ventricular (LV) ejection fraction. The present study assessed the association of TAPSE and clinical factors, global and regional LV function in 634 patients admitted for symptomatic heart failure.TAPSE were correlated with global and regional measures of longitudinal LV function, segmental wall motion scores and measures of diastolic LV function as measured from transthoracic echocardiography.2 = 0.28, p < 0.0001. The prognostic importance of TAPSE was not dependent of heart failure etiology or any of the other clinical factors analyzed, pinteraction = NS.LV ejection fraction, wall motion index scores, atrio-ventricular annular plane systolic excursion of the mitral annulus were significantly related to TAPSE. Septal and posterior mitral annular plane systolic excursion  and non-ischemic etiology of heart failure  were independent predictors of TAPSE, RTAPSE is reduced with left ventricular dysfunction in heart failure patients, in particular with reduced septal longitudinal motion. TAPSE is decreased in patients with heart failure of ischemic etiology. However, the absolute reduction in TAPSE is small and seems to be of minor importance in the clinical utilization of TAPSE whether applied as a measure of right ventricular systolic function or as a prognostic factor. Right ventricular (RV) dysfunction is an important entity in heart failure as patients with reduced RV ejection fraction have poorer exercise tolerance and prognosis than patients with preserved RV function regardless of left ventricular (LV) function and degree of pulmonary hypertension . TricuspMore recent validation studies have confirmed the relation between RV ejection fraction and TAPSE in various heart failure populations, although the association is modest in patients with preserved RV function -8. In adThe present study investigated the relation of TAPSE and other echocardiographic and clinical parameters, with emphasis on measures of regional LV function and clinical characteristics of heart failure patients.2 and α2 receptors. The trial was based on a screening population defined as consecutive patients, ≥ 18 years of age, admitted for symptomatic heart failure corresponding to New York Heart Association (NYHA) class III-IV within the last month, requirering treatment with diuretics. Patients were not eligible for screening if an acute myocardial infarction was diagnosed. Screening for the ECHOS trial included a transthoracic echocardiography (TTE) performed at rest in the left lateral position according to a predefined protocol ensuring standardized echocardiographic imaging for the assessment of LV ejection fraction by wall motion index (WMI) scoring. In addition to the echocardiographic imaging, demographic and clinical data were collected. All patients screened for participation in the trial was included in the present analysis since no effect on the primary end-point  in the randomized study was observed [The present study is a sub-study based on the population of Danish patients, consecutively screened for participation in the EchoCardiography and Heart Outcome Study (ECHOS). The ECHOS trial was a prospective, double-blind randomized, placebo-controlled multi-centre trial of a selective agonist of the pre-synaptic DAobserved . The ECHAll centers were encouraged to record additional predefined echocardiographic views and standardized training of physicians from the participating centers was performed prior to initiation of screening. Imaging were stored on videotapes and digitized at a core laboratory . All measurements were performed using electronic calipers on custom-made software following on-screen calibration, and were reported as the average of five measurements performed by two experienced readers, D.A. and J.K. The echocardiographic imaging included three apical views for assessment of LV function by WMI  in a 16 segment model , which aBaseline data recorded at screening included known cardiovascular risk factors associated with HF: demographic data, current tobacco use, diabetes, paroxysmal atrial fibrillation, and co-existing cardiovascular disease including arterial hypertension, ischemic heart disease. The local investigator also recorded the presence of Chronic Obstructive Pulmonary Disease (COPD) and chronic reduced renal function. Presumed heart failure etiology was reported by the local investigator as ischemic or non-ischemic .We have previously shown that TAPSE is an independent predictor of all-cause mortality in the present population . We sougt-test for categorical variables. Normal distribution of the continuous values was assessed by the Kolmogorov-Smirnov test. Multivariate linear regression models including all significant clinical and echocardiographic parameters from the univariate analysis were constructed to assess independent predictors of TAPSE. Survival analysis for the assessment of impact of differences in the etiology of heart failure on TAPSE was performed by proportional hazard regression analysis as previously described testing for the interaction of TAPSE and co-variates [Data was presented as mean ± standard deviation (SD) or number (%). The relations of parameters to TAPSE were tested by linear regression analysis for continuous variables and by variates . SAS sofKolmogorov-Smirnov = 0.08 and pKolmogorov-Smirnov>0.15, respectively.None of the demographic and anthropomorphic parameters available were related to values of TAPSE, whereas several of the clinical parameters were significantly related to TAPSE, Table Echocardiographic predictors of TAPSE were global LVEF, deceleration time of the early mitral inflow (E), the late mitral inflow (A) and E/A in univariate analysis, see Table interaction = not significant (NS).Multivariable analysis showed that septal and posterior longitudinal motion and HF etiology were independently related to TAPSE, see Table interaction = NS.While the independent prognostic value of TAPSE in the present population has previously been shown , the facTAPSE is a widely recognized, clinically useful and feasible marker of right ventricular dysfunction, and has been proven to be a valuable prognostic marker in various cardiac diseases, including heart failure. The present study adds that TAPSE may be influenced by left ventricular septal longitudinal motion in patients with symptomatic heart failure patients and that TAPSE is affected by the etiology of heart failure. None of identified factors however, induces significant limitation in the every day use of TAPSE as a prognostic marker in the assessment of heart failure patients.Reduced LVEF seem to have an impact on TAPSE, even in the setting of preserved right ventricular ejection fraction ,15. The Pulmonary disease and heart failure share a number of risk factors and as a result, co-existing pulmonary disease in heart failure patients is reported in about 25% of patients . In addiSeveral clinical factors were found to be related to decreased TAPSE although the reduction on average was in the order of 1 mm, and thus likely to be of limited clinical importance. These factors included a history of ischemic heart disease, previously diagnosed heart failure and paroxysmal atrial fibrillation and presumed ischemic origin of heart failure, of which only the latter was found to be an independent predictor of TAPSE when adjustments for echocardiographic parameters were made. TAPSE is known to be reduced in patients with atrial fibrillation and to normalize after conversion to sinus rhythm , and theTAPSE has previously been found to be independent of age and gender in healthy individuals ,28, and Heart failure etiology and presence of co-morbidity was reported by the local investigator, and although pre-specified definitions for these factors were provided, the accuracy of these data may be less than perfect. However, we find it unlikely that this would induce significant bias in the present analysis.Imaging for the centralized echocardiographic analysis was performed at the local centers. To limit variation, physicians from all centers received training in the acquisition of all pre-specified views included the optional imaging of the measures reported in the presents study. Differences between patients in whom imaging for analysis of TAPSE was not available and the present cohort have been previously described , and we TAPSE is reduced with left ventricular dysfunction in heart failure patients, in particular with reduced septal longitudinal motion. TAPSE is decreased in patients with heart failure of ischemic etiology. However, the absolute reduction in TAPSE is small and seems to be of minor importance in the clinical utilization of TAPSE whether applied as a measure of right ventricular systolic function or as a prognostic factor.The authors declare that they have no competing interests.JK and DA performed the analysis of the echocardiographic material. JK drafted the manuscript and performed initial statistical computations. KKI, JEM, LVK, CTP and CH had contributions to the statistical analysis and presentation of data. All authors read and approved the final manuscript.


If inhibitor, acts primarily on the sinoatrial node and is used to reduce the heart rate with minimal effect on myocardial contractility, blood pressure, and intracardiac conduction. Heart rate reduction is an important aspect of care in patients with chronic stable angina and heart failure. Many patients with coronary artery disease have coexisting asthma or chronic obstructive airway disease, and most of them are unable to tolerate beta blockers. Ivabradine may thus be a useful medicine in therapeutic heart rate management especially in patients who are intolerant of beta-blockers.Ivabradine, an  If inhibitor ivabradine trial  showed that a heart rate greater than 70 beats per minute (bpm) is associated with increased cardiovascular death [A higher heart rate is associated with an increase in cardiovascular mortality both in general population and in patients with established cardiovascular disease –4. Previar death .  Lower heart rate reduces myocardial oxygen consumption and increases oxygen supply to heart via prolongation of diastole . This pr Persistent elevated heart rate is also commonly seen in patients with congestive heart failure (CHF). Studies in the past using drugs either increasing or reducing heart rate showed survival benefit when treatment group had lower average heart rate than placebo. By contrast, survival was poorer when average heart rate of the treated cohort had increased compared with placebo . If inhibitors that blocks the If current in sinoatrial node may have a role in therapeutic heart rate management and angina control [If inhibitor will be reviewed in this article.In addition to existing beta-blockers and non-dihydropyridine calcium channel inhibitors,  control . This co control . The conIf current, first described by Brown et al. in 1979, is activated in phase 4 of action potential in the sinoatrial node by accelerating diastolic depolarisation [+/K+ current during diastole, that is, phase 4 action potential [I for current, f for funny) [Ik, IcaL, IcaT. Ik is activated by preceding action potential and results in outward movement of potassium through the slow delayed rectifier potassium channels. The two inward calcium currents are IcaL (L type/long-lasting Ca channel) and IcaT (T type/transient Ca channel). The action potential reaches its threshold (approx. −40 mv) by If current which in turn controls the successive action potential and heart rate  . Three oIf current. There are four isoforms of HCN channels that is, HCN1–HCN4 which can be found in heart, brain and retina. The main isoform found in the heart is HCN4 and it is highly expressed in sinoatrial node [If current might be involved in the pathological role of congestive heart failure and ventricular hypertrophy, therefore, it is attractive to search for potential pharmacological inhibitors which could result in heart rate reduction with minimal side effects.The hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels are responsible for ial node . HCN4 chIf inhibition in the past; the first of which is Alinidine, a clonidine derivative, that was soon abandoned due to its relative inotropic action [Few agents were developed for c action . Later, c action , 21. If current inhibitor, was first described by Thollon et al. more than a decade ago [ Ivabradine, a unique specific cade ago . It exhicade ago . At the cade ago , 25.Common side effects from Ivabradine resulting in withdrawal of treatment are; visual symptoms such as blurred vision, phosphenes and visual disturbance. Clinical trials suggest dose-dependent reversible visual side effects are relatively small in treatment dose up to 10 mg twice daily , 26, 27. In the BEAUTIFUL trial, symptomatic bradycardia was the most common adverse effect leading to discontinuation of treatment, however, 87% of enrolled patients were receiving beta-blockers at the same time .  Since ivabradine targets sino-atrial node for heart rate control, its use was discouraged in the presence of atrial fibrillation, persistent pacemaker rhythms and second/third degree atrio-ventricular block , 22, 26.P = .001), myocardial infarction or unstable angina , and coronary revascularisation . These findings suggest a heart rate of 70 or greater in the presence of coronary artery disease and moderate systolic failure is associated with increased cardiovascular death, hospital admission for heart failure or myocardial infarction and coronary revascularisation. The study also implies that a heart rate of 75 or less could be target for therapeutic heart rate management in this group of patients who have higher baseline heart rate. The international BEAUTIFUL trial is, to date, the largest randomized, double-blinded, placebo-controlled trial of ivabradine , 23. Pat The efficacy of ivabradine as monotherapy in angina control was tested in a randomized double-blinded trial by Borer et al.  360 patiP = .04) at the dose of 10 mg twice daily. Resting and exercise heart rate in ivabradine groups are significantly lower than placebo (P < .05). In addition, the dose-dependent response was observed. The frequency of angina attacks and use of short-acting nitrates were also decreased in patients into the open-label extension (P = .001). During the randomized withdrawal, the frequency of angina increased in placebo group but remained unchanged in ivabradine group.  Of the 360 eligible patients, 103 were excluded due to protocol violation and the majority of them had negative exercise tests at the time of randomization. In the remaining 257 patients, the time to horizontal ST segment depression of ≥1 mm, onset of angina and limiting angina is longer in all ivabradine dose groups compared with the placebo, reaching a statistical significance  INITIATE study involved 939 patients with stable angina randomized into ivabradine 5 mg bid for 4 weeks followed by either 7.5 or 10 mg bid for 12 weeks or atenolol 50 mg od for 4 weeks then 100 mg od for 12 weeks . All patn = 400), ivabradine 10 mg bid (n = 391) and amlodipine 10 mg od (n = 404). Patients underwent bicycle exercise tolerance tests at randomisation and every month for three months. The exercise tolerance, time to limiting angina, time to angina onset and time to 1 mm ST segment depression were consistently increased in all groups without significant difference. Of interest, heart rates at rest and exercise were significantly lower in ivabradine groups compared with amlodipine.  The Antianginal property of ivabradine was also compared with amlodipine  in a 3 months double-blind trial . 1195 pa Combination of ivabradine and dihydropyridine calcium channel blockers was noted to be safe and well tolerated in another trial which allowed concomitant medications including long-acting nitrates or dihydropyridine calcium channel blockers . The resIf inhibitor, ivabradine, provides an alternative way of heart rate reduction in addition to beta-blockers and calcium channel blockers. This could become particularly useful in patients who are intolerant of beta-blockers, for example, in the presence of asthma or severe chronic obstructive airway disease. At the treatment dose, it reduces heart rate to a similar extent as atenolol and can be used together with beta-blockers. Ivabradine is well tolerated in all the clinical trials with minimal side effects. The most common adverse effect is reversible visual symptoms. However, the absence of sinus rhythm is currently the contraindication of its use. Available knowledge to date indicates that heart rate over 70 bpm in patients with coronary artery disease and systolic heart failure of ejection fraction of less than 40% is associated with adverse cardiac events. Currently, the optimum therapeutic heart rate in these groups of patients remains uncertain. The selective If inhibitor is likely to become another useful group of medicine in cardiovascular disease management in the near future. Further research is required to evaluate the mortality benefit of ivabradine in patients with known coronary artery disease and systolic heart failure who are unable to take beta-blockers. Clinical data suggests that ivabradine can be used as an antianginal medication as monotherapy or in combination with beta-blockers or calcium channel blockers. Its Antianginal effects are comparable to atenolol and amlodipine in clinical trials. Selective


External electrical cardioversion was first performed in the 1950s. Urgent or elective cardioversions have specific advantages, such as termination of atrial and ventricular tachycardia and recovery of sinus rhythm. Electrical cardioversion is life-saving when applied in urgent circumstances. The succcess rate is increased by accurate tachycardia diagnosis, careful patient selection, adequate electrode (paddles) application, determination of the optimal energy and anesthesia levels, prevention of embolic events and arrythmia recurrence and airway conservation while minimizing possible complications. Potential complications include ventricular fibrillation due to general anesthesia or lack of synchronization between the direct current (DC) shock and the QRS complex, thromboembolus due to insufficient anticoagulant therapy, non-sustained VT, atrial arrhythmia, heart block, bradycardia, transient left bundle branch block, myocardial necrosis, myocardial dysfunction, transient hypotension, pulmonary edema and skin burn. Electrical cardioversion performed in patients with a pacemaker or an incompatible cardioverter defibrillator may lead to dysfunction, namely acute or chronic changes in the pacing or sensitivity threshold. Although this procedure appears fairly simple, serious consequences might occur if inappropriately performed. External electrical cardioversion (EEC) was first performed in the 1950s.The current external electrical cardioversion technique relies on the application of a selected amount of energy, which is generally between 50-360 J, via two electrodes (paddles). The mechanism of defibrillation is not known exactly. Zipes et al have suggested that failure to maintain the reentrant tachycardia by the remaining myocardial tissue after depolarization of a critical mass is the main factor in the mechanism of electrical defibrillation.A lower limit of vulnerability also exists for the ventricular myocardium. This is the minimum voltage required by an electrical stimulus to induce fibrillation during the vulnerable period. It was also observed that the strengths of these shocks at “the upper limit of vulnerability” were approximately equivalent to the shocks at defibrillation threshold. The upper limit of vulnerability hypothesis for defibrillation states that to defibrillate, a shock not only must halt the activation fronts of fibrillation, but it also must not reinitiate fibrillation by the same mechanism that a shock of the same strength during the vulnerable period of sinus or paced rhythm initiates fibrillation.5Currently, electrical cardioversion is mostly performed to convert AF and atrial flutter into sinus rhythm. AF, encountered in intensive care units after cardiac surgery, is not suitable for electrical cardioversion since it is paroxysmal. In the treatment of recurrent AF attacks, prevention of trigger mechanisms, application of specific antiarrhythmic therapies and improvement of electrolyte imbalance and hypoxia avert inappropriate cardioversion applications by blocking such episodes. AF treatment, on the other hand, includes anticoagulant therapy to minimize the risk of embolus and stroke during elective cardioversion. If AF persists for longer than 48 hours, anticoagulant therapy for 3 weeks is recommended with the international normalized ratio (INR) maintained >2.0. In case atrial activity is not achieved, therapy should be extended for 4 weeks, even after restoring sinus rhythm by electrical effective cardioversion.Emergency electrical cardioversion is performed in unstable ventricular tachycardia that causes hemodynamic deterioration. If a patient with ventricular tachycardia is hemodynamically stable, sinus rhythm should be achieved by intravenous antiarrhythmics. Anticoagulation therapy is usually not necessary for cardioversion of ventricular tachycardia. Emergency electrical cardioversion is performed in unstable ventricular tachycardia that causes hemodynamic deterioration. The aim of ventricular tachycardia treatment is the prompt termination of this impairment. Electrical cardioversion should be the next step in case of unsuccessful antiarrhythmic treatment and vagotonic manoeuvres such as carotid sinus massage for sustained supraventricular tachycardia. The success rate with cardioversion of ventricular tachycardia is generally around 95%.8Electrical shock treatment is ineffective in the termination of automaticity related tachycardies. Multifocal atrial tachycardias of this kind are generally confused with AF, which may lead to the inappropriate application of direct current (DC) shocks. Since electrical cardioversion may cause resistant VF in patients with digitalis toxicity, it is contraindicated in the presence of this condition.8Energy is a combination of voltage and current. The overall success of the electrical cardioversion is related to the size of electrodes (paddles), application site, transthoracic impedance, and the applied current. For a given amount of energy, the amount of current reaching the myocardium depends in part on the electrical impedance between the two defibrillator paddles. The distance between electrodes, electrode-skin interface and pressure , previous shocks (reduced impedance), time span between shocks (3-minute wait may cause resistance reduction), and physical characteristics  decrease the rate of success.Defibrillator paddles can be used in different configurations, which affect the success rate of defibrillation. According to the International Liaison Committee on Resuscitation (ILCOR) guidelines, the sternal paddle should be placed ‘just to the right of the upper sternal border below the clavicle and the apical paddle to the left of the nipple with the centre of the electrode in the midaxillary line.Thoracic impedance is another important factor in treatment by electrical cardioversion. The paddle area is the main determinant of transthoracic impedance. Current is inversely related to impedance. The optimal paddle size varies between 8 cm to 12 cm. Air between the chest wall and the paddles prevents the effective conduction of the shock wave by increasing transthoracic impedance. Any conductive material between paddles, such as gel or similar materials, increases conductance and decreases transthoracic impedance between the chest wall and the metal electrodes. Either special adhesive pads or special gels are used for this purpose. Contact between paddle area and chest wall must be provided. Gel between paddles should not touch in order to prevent current disorientation.16In pediatric patients ≤10 kg, pediatric paddles should be used for electrical cardioversion, with an applied pressure of 2.9 kgf. If the child is >10 kg, adult-type paddles should be used, with an applied pressure of 5.1 kgf.18In a pilot study, Sutton et al demonstrated that atropine administration increased the success rate of direct current cardioversion for atrial fibrillation.23Patients may feel pain even at low energy levels (1 J). Electrical cardioversion with high levels of energy should never be performed in conscious patients, since it may cause lifelong emotional disorders and psychological trauma.26Transthoracic monophasic defibrillators have been employed for the management of ventricular arrhythmias. European Resuscitation Council guidelines recommend a 200 J, 360 J sequence with subsequent shocks at 360 J if the arrhythmia is uncorrected.28An initial energy level for AF of 100-200J is recommended. The success rate of electrical cardioversion is approximately 50%. In a recent study, an initial energy level of 360 J was suggested for persistent AF lasting more than 48 hours.34The risks and benefits of recurrent electrical shock therapy must be taken into account. Unnecessary recurrent DC shock treatment should be avoided. The upper shock limit applied by several defibrillators currently used is 360 J, and the waveform is monophasic. As technology progresses, biphasic shock waves are employed. ICDs are the best example of such application. The transvenous activity, the accessible implantation, and the smaller dimensions have contributed to the wide therapeutic adoption of ICD devices. Lown mentioned that higher energy levels were required to terminate AF in congestive heart failure. Restoration of cardiac compensation and achievement of a dry weight before cardioversion increased the success rate. In cases of polycytemia, it may be difficult or impossible to revert until adequate phlebotomy lowers the hematocrit to less than 50. Patients with severe mitral valve disease having giant scarred atria who have had valve repair or replacement are recalcitrant to cardioversion and do not persist in sinus rhythm.In new devices, the electrodes are placed within the right atrium and the left pulmonary artery for internal cardioversion. Superior homogeneous electrical dispersion and cardioversion effectiveness have been reported with such electrode placement.Complications are minimal. Potential complications include VF due to general anesthesia or lack of synchronization between the DC shock and the QRS complex, thromboembolus due to insufficient anticoagulant therapy, non-sustained VT, atrial arrhythmia, heart block, bradycardia, transient left bundle branch block, myocardial necrosis, myocardial dysfunction, transient hypotension, pulmonary edema and skin burn. Pain at the application site is associated with the number of applications.Atrial and ventricular tachycardias are frequent in patients being treated at intensive care units due to the presence of multiple triggers. Hypoxia, endogenous or exogenous catecholamines, congestive heart failure, fever and pulmonary embolus are particular causes of tachycardia. Patients unable to receive the drugs orally or with poor absorption are more prone to side effects, such as hypotension, which may especially occur with intravenous drugs like amiodarone. Rapid and through-out examination prior to the electrical cardioversion is important. Improvement of trigger and underlying etiologic factors enhances the success rate of cardioversion.Internal cardiac cardioversion is safe and effective in patients with resistant AF.35Some investigators have reported that electrical cardioversion is safe during pregnancy.4042Electrical cardioversion performed in patients with a pacemaker or ICD may lead to dysfunction, namely acute or chronic changes in the pacing or sensitivity threshold.Cardioversion/defibrillation equipment is of the utmost importance to clinicians. Electrical cardioversion is a life-saving when applied in emergency circumstances. In elective cardioversion, accurate tachycardia diagnosis, careful patient selection, adequate electrode (paddles) application, determination of the optimal energy and anesthesia levels, prevention of embolic events and arrythmia recurrence, and airway conservation increase the success rate while minimizing possible complications. Although this procedure appears fairly simple, serious consequences might occur if inappropriately performed.


Both insulin and thiazolidinediones (TZDs) are effective in the treatment of hyperglycaemia and amelioration of insulin resistance in type 2 diabetes but have side effects including weight gain and fluid retention. The use of TZDs has been further hampered by the risk of adverse cardiovascular events including heart failure. The present study evaluated the effect of pioglitazone or insulin glargine on cardiac function and size as well as on surrogate markers of fluid retention such as weight, haemoglobin and natriuretic peptides.Thirty patients with inadequate glycaemic control on metformin and sulfonylurea were randomised to receive add-on therapy with insulin glargine or pioglitazone for 26 weeks. Echocardiographic data and blood samples were collected from the two groups before the start of the treatment and after 26 weeks. Left ventricular end-diastolic and left atrial end-systolic volumes were quantified, weight measured and blood samples analyzed.After 26 weeks of treatment, the changes in HbA1c, weight and haemoglobin were similar between the two groups. HDL increased significantly in the pioglitazone group. While there was an increase in natriuretic peptides in the pioglitazone group , the difference between the treatment groups was not significant. Left ventricular end-diastolic volume increased by 11% and left atrial end-systolic volume by 17% in the pioglitazone group . There was a borderline significant increase in ejection fraction in the pioglitazone group.This randomised pilot-study showed that six-month treatment with pioglitazone induced significant increases in natriuretic peptides and alterations of cardiac size. These changes were not observed with insulin glargine, which also is known to induce fluid retention. Larger randomised trials are warranted to confirm these findings. The hyperglycaemia in type 2 diabetes (T2D) is associated with enhanced risks of micro- and macrovascular complications. The continuous deterioration of metabolic control is considered independent of mode of therapy and ascribed to deterioration of both insulin secretion and action. Consequently, there is no widely agreed consensus on how to intensify therapy in patients who fail on initial treatment with metformin and/or a sulfonylurea, especially whether to add a third oral agent, e.g., thiazolidinedione (TZD) or insulin. Both treatment alternatives are considered to result in weight gain and fluid retention. While insulin therapy requires injections and can be associated with hypoglycaemia, TZD therapy is associated with increased risk of heart failure. In a recent meta/teleo-analysis Singh et al. concluded that heart failure might occur at both high and low doses, usually weeks to months after initiating TZDs and in patients without a history of heart failure . There aThirty patients with T2D and inadequate glycaemic control were included in a 26-week randomised open-label trial. Inadequate glycaemic control was defined as treatment with metformin and sulfonylurea/meglitinide in doses > 50% of maximum recommended doses and HbA1c > 6.2% measured with Mono-S method . Patients with known heart failure or clinical signs of heart failure (New York Heart Association class II–IV) were excluded. Also excluded from the study were patients with significant valvular dysfunction , reduced ejection fraction EF (< 50%) or inappropriate acoustic window. Patients who met the criteria for the study were randomly assigned to receive add-on therapy with insulin glargine or pioglitazone for 26 weeks. Insulin was up-titrated to achieve fasting plasma glucose < 6 mmol/l. Pioglitazone was increased to 45 mg/day after 16 weeks if HbA1c > 6.2%. Weight and height were measured, and BMI was calculated at inclusion and after 26 weeks of treatment. Blood samples were collected for measurement of haemoglobin, liver enzymes, plasma lipids, and natriuretic peptides (BNP and NT-proBNP). Blood samples were drawn after an overnight fast, and after at least 10 minutes rest in the supine position.3-LVDD3 +0.6 [Standard transthoracic echocardiography examinations were performed with Sonos 5500  at baseline and after 26 weeks of treatment. A single observer blinded to all clinical data performed the echocardiography measurements, which were performed twice with the mean value used in all analysis. From 2-D echocardiography, left ventricular end-diastolic diameter (LVDD), posterior wall thickness (POST) and interventricularseptum thickness (IVS) were measured and left ventricular mass (LVM) was calculated from the formula LVM = 0.8 × 1.04 × (LVDD+IVS+POST)Plasma glucose was measured with a HemoCue glucose analyser . HbA1c was analyzed using the Variant II chromatographic method from Bio-Rad (ref. 4–5.3%) measured by Swedish Mono-S (high performance ion-exchange liquid chromatography). BNP was measured with an immunoassay system from Beckman  with a CV of 3.5% and NT-proBNP using an immunometric method  with a CV of 4.4%.Data are presented as means ± SD where appropriate. Non-parametric tests were used to test differences in changes of measured variables within and between treatment groups. A two-side significance level of < 0.05 was considered statistically significant. Statistical analyses were carried out using SPSS version 15 and Microsoft office Excel 2003.All 30 patients completed the study. There were no significant differences in patients' anthropometrical characteristics at baseline or at the end of the study Table . After 2Baseline BNP and NT-proBNP correlated with change during intervention in all subjects . There was a doubling of BNP and NT-proBNP concentrations in the pioglitazone group  and no change in the glargine group . The difference between the treatment groups, however, was not significant. The increase in BNP and NT-proBNP correlated inversely with the changes in haemoglobin  in the whole group. The inverse correlation between increase in NT-proBNP and the change in haemoglobin was even greater in the group treated with pioglitazone  while there was no correlation in the group treated with insulin glargine . The NT-proBNP values at baseline correlated strongly with changes from baseline during treatment with pioglitazone . None of the subjects developed clinical heart failure. There were no significant differences in baseline echocardiography measurements between the groups, whereas significant increase in LVD vol and LA vol could be observed after six-month treatment with pioglitazone. There were no differences in change of LVM or EF between the two groups. Table Although one patient in the pioglitazone group developed a significant mitral regurgitation during treatment, the condition was reversible, shown by the results of an echocardiography examination six months after discontinuation of pioglitazone medication .Both pioglitazone and insulin glargine added to treatment with metformin and sulfonylurea/meglitinide in patients with T2D was well tolerated and improved glycaemic control. In both groups a similar weight gain was observed. In addition, pioglitazone therapy led to alterations in cardiac volumes. The pioglitazone therapy resulted in a significant increase in LVD vol and LA vol, as measured by echocardiography as well as increase in levels of BNP and NT-proBNP. However, the difference in changes of natriuretic peptides between groups was not significant, probably due to the small sample size and the high intra-individual variation. Pioglitazone also increased HDL cholesterol in keeping with previous studies. To our knowledge, this is the first study in patients with T2D demonstrating differences in the effect of insulin vs. a TZD on cardiac function. The findings should, however, be viewed with caution due to the modest sample size.BNP and NT-proBNP are peptide hormones released from the cardiac ventricles in response to myocyte stretch, and have generated attention in recent years as potential diagnostic and prognostic markers for cardiac disease. Natriuretic peptides have been shown to correlate with cardiac dysfunction, and NT-proBNP has been shown to be independent risk marker for cardiovascular disease in patients with diabetes ,5. For eThere were no significant differences for echocardiography measurements at baseline between the two groups, whereas significant increase in LVD vol and LA vol could be observed after 26-weeks treatment with pioglitazone. These changes were of moderate magnitude as LVD vol increased by 11% and LA vol by 17% in the pioglitazone group. There where no significant differences in EF at baseline and only a borderline significant increase in the pioglitazone group after 26-weeks treatment. There are, to our knowledge, no previous randomised studies that have evaluated the effect of pioglitazone versus insulin glargine on cardiac function and size in patients with T2D. St John Sutton et al. evaluated the effect of rosiglitazone versus glyburide in 203 patients with T2D . MoreoveOne patient in the pioglitazone group developed a significant mitral regurgitation during the treatment, but this was proved to be a reversible condition. An echocardiography examination six months after discontinuation of the pioglitazone medication showed regression of the mitral regurgitation . This fiIn the last few years, two TZDs have been available on the market, namely pioglitazone and rosiglitazone. Recent meta-analyses point to differences in the effect of these two drugs on cardiovascular outcomes. There is evidence that the increased risk of developing congestive heart failure is greater with rosiglitazone . The incEchocardiography is considered "gold standard" method, in daily clinical practice, for evaluating cardiac function. While an echocardiography examination is broadly available and relatively inexpensive in the western World (150–250 Euros per examination in Sweden), the screening costs for larger groups of patients would be substantial. There is, therefore, a need for less expensive screening-tests. Taking our results into consideration, one could suggest that an initial assessment of a natriuretic peptide could be used for identifying individuals at risk of responding negatively to pioglitazone treatment. Serial monitoring of these peptides along with the clinical registration of weight and haemoglobin values during treatment could also be helpful to identify those few individuals, who should undergo an echocardiography evaluation and subsequently reduce the rate of unwanted side-effects.When choosing pioglitazone as an add-on treatment in patients with insufficiently controlled T2D, an increase in LVD vol by 11% and LA vol by 17% could be observed. This was parallel with an increase in natriuretic peptids. These changes in cardiac volume and natriuretic peptid-levels were not observed with insulin glargine. Larger randomised trials are warranted to confirm these findings. There is a need for tools to help clinicians to identify subsets of patients for whom this kind of therapy is likely to have particularly favourable/unfavourable effect, using readily identifiable clinical and laboratory factors. Knowledge is increasing in this field and hopefully the results will enable clinicians to select the proper therapy for individual patients in the future.T2D: Type 2 diabetes; TZD: thiazolidinedione; BNP: brain natriuretic peptide; NT-proBNP: N-terminal pro brain natriuretic peptide; LVDD: left ventricular end-diastolic diameter; POST: posterior wall thickness; IVS: intraventricularseptum thickness; LVM: left ventricular mass; LVD vol: left ventricular end-diastolic volume; LVS vol: left ventricular end-systolic volume; LA vol: left atrial end-systolic volume; and EF: ejection fraction.Mozhgan Dorkhan has signed a speaker contract with Eli Lilly and received a scholarship from Sanofi-Aventis. Magnus Dencker has no conflict of interest to declare. Martin Stagmo has received speaker's fees from Sanofi-Aventis and through his spouse owns shares and stock options in NovoNordisk A/S.All authors participated in the design of the study. MDo and MDe wrote the manuscript. All authors edited and approved the final version of the manuscript.


The method used to delineate the boundary of the right ventricle (RV), relative to the trabeculations and papillary muscles in cardiovascular magnetic resonance (CMR) ventricular volume analysis, may matter more when these structures are hypertrophied than in individuals with normal cardiovascular anatomy. This study aimed to compare two methods of cavity delineation in patients with systemic RV.Twenty-nine patients (mean age 34.7 ± 12.4 years) with a systemic RV  and 17 with atrially switched (TGA) underwent CMR. We compared measurements of systemic RV volumes and function using two analysis protocols. The RV trabeculations and papillary muscles were either included in the calculated blood volume, the boundary drawn immediately within the apparently compacted myocardial layer, or they were manually outlined and excluded. RV stroke volume (SV) calculated using each method was compared with corresponding left ventricular (LV) SV. Additionally, we compared the differences in analysis time, and in intra- and inter-observer variability between the two methods. Paired samples t-test was used to test for differences in volumes, function and analysis time between the two methods. Differences in intra- and inter-observer reproducibility were tested using an extension of the Bland-Altman method.The inclusion of trabeculations and papillary muscles in the ventricular volume resulted in higher values for systemic RV end diastolic volume  and for end systolic volume . Values for ejection fraction were significantly lower  if structures were included. LV SV did not differ significantly from RV SV for both analysis methods (p = NS). Including structures resulted in shorter analysis time (p < 0.001), and showed better inter-observer reproducibility for ejection fraction (p < 0.01).The choice of method for systemic RV cavity delineation significantly affected volume measurements, given the CMR acquisition and analysis systems used. We recommend delineation outside the trabeculations for routine clinical measurements of systemic RV volumes as this approach took less time and gave more reproducible measurements. The number of adult patients with a congenital heart defect is steadily increasing with the constant improvement of cardiac surgery. A substantial portion of these patients has a morphologic right ventricle (RV) supporting the systemic circulation  or a complete transposition of the great arteries (TGA) after an atrial switch operation). Medium term survival in patients with a systemic RV is relatively good. However, long-term outcome is unknown, and morbidity is worrisome, with RV dysfunction, tricuspid valve regurgitation, and arrhythmias being the main constituents. -4Assessment of ventricular function is of particular importance, as European guidelines consider it an important part of preoperative assessment, (peri-operative) management and follow-up of patients with any congenital heart defect.  MoreoverFor the assessment of subpulmonary and systemic RV volumes and function Cardiovascular Magnetic Resonance (CMR) is considered the gold standard. -15 In inTo our knowledge, no study has ever addressed the issue of CMR analysis methods in this patient group. Aim of the present study was to evaluate the impact of trabeculations and papillary muscles on systemic RV measurements, by comparing a CMR analysis method in which trabeculations and papillary muscles were included in the RV volume to an analysis method in which these structures were excluded from RV volume figure . AdditioA total of 29 adult patients  with a systemic RV underwent CMR for the evaluation of RV volumes and function. Twelve patients had a ccTGA, 17 patients an atrially switched TGA. The Institutional Review Boards of all three participating tertiary referral centers approved the study protocol. Written informed consent was obtained from all patients prior to participation in the study.Image acquisition was performed by CMR, using a 1,5 Tesla scanner , using standardly available sequences to assess ventricular volumes. After visualizing the long and short axes of the heart, a multi-phase steady-state free precession sequence (SSFP) with retrospective electrocardiographic triggering was applied to visualize two-chamber, three-chamber and four-chamber views. Guided by these views, a multislice and multiphase SSFP sequence was applied perpendicular to the ventricular septum, encompassing the total heart. These sequences were individually adjusted to acquire short axis slices with optimal spatial and temporal resolution. Typical parameters were: flip angle: 50–70 degrees; repetition time: 3–4 msec; echo time: 1–2 msec; temporal resolution: 40 msec, 1–2 × 1–2 mm/pixel in-plane spatial resolution, 8 mm slice thickness, and 1 mm interslice gap. This resulted in 9 to 15 slices to cover the whole heart. CMR images were acquired during repeated end-expiratory breath holds.For CMR image analysis two independent observers  used MASS Analytical Software System . Cine loops were used to choose end diastole (ED) and end systole (ES). ED was defined as the phase with the largest RV (and left ventricular (LV)) area and ES as the phase with the smallest RV (and LV) area. The slices at the base of the heart were considered to be in the ventricle if the blood was at least half surrounded by ventricular myocardium. Cine loop movies in phase and slice were used in case the distinction between the ventricles, atria and great vessels was unclear. Moreover, four-chamber views in phase with the short axis views were available. Tracing was performed manually on each ED and ES short-axis view.The sums of the traced contours in ED en ES were used to calculate ED volume (EDV) and ES volume (ESV) using a disc summation technique. EDV and ESV were used to calculate Stroke Volume (SV) and Ejection Fraction (EF). SV was defined as EDV - ESV, and EF as [(EDV - ESV)/EDV] × 100%.Method A: Contour tracing was first performed including the papillary muscles and trabeculations in the ventricular cavity, by tracing immediately within the apparently compact layer of the myocardium. A continuous movie display of the slice being evaluated was used to enhance differentiation between trabeculations, papillary muscles and the ventricular free wall. Although the exclusion of complex RV trabeculations and papillary muscles is relatively easy in ED, optimal differentiation is especially important in the ES phases as trabeculations and papillary muscles compress and fold during systole making the end-systolc border of trabeculations and blood volume less distinct. This method resulted in smooth contours  for Windows was used. P values < 0.05 were considered statistically significant. The shift between the two tracing methods was compared with the two-tailed paired  Altman.  Agreement test of the logged squared differences was performed thereafter.[Intra- and inter-observer reproducibility of the two analysis methods was determined from the mean value and the differences between the two measurements. The coefficient of variability was calculated as the standard deviation of the difference of the paired measurements divided by the mean of the average of the paired measurements, and expressed as a percentage. An extension of the Bland-Altman method was used to assess the statistical significance of differences in intra- and interobserver reproducibility between the two analysis methods. A log transformation of the squared differences between the two measurements was performed. If the squared difference was zero, we replaced the value by the next smallest value multiplied by 0.5. A two-tailed paired ereafter.Including trabeculations and papillary muscles in the systemic RV volume (Method A) resulted in significantly higher outcome measures for EDV with a mean difference of 28.7 ml , and for ESV with a mean difference of 31.0 ml , compared to when structures were excluded from the ventricular volume (Method B). This resulted in a significantly lower calculated systemic RV EF with a mean difference of 7.4% . No significant changes were found for SV and CO. Bland-Altman plots were used to visualize the systematic differences between Method A and B , neither when structures were excluded from the RV and LV volumes .Analysis time was significantly shorter when using Method A (20 ± 3 min) compared to Method B (26 ± 4 min); p < 0.001.Analysis Method A lead to a lower coefficient of variability for all outcome measures compared to Method B. This indicates superior intra- and inter-observer reproducibility when including trabeculations and papillary muscles in the ventricular volume compared to excluding these structures. Although these differences were not found to be statistically significant for the intra-observer measurements, we found statistically significant difference in the inter-observer reproducibility of systemic RV SV (p < 0.05) and EF (P < 0.01), favoring the inclusion of structures in the ventricular volume  has been studied previously, using similar analysis protocols as were used in our study.,17 In anAlthough the true values of systemic RV volumes and function remain unknown, and in spite of tricuspid valve regurgitation in some patients, we found no significant differences between the measured RV and LV SV by either method of analysis. However, delineation of the RV cavity boundary outside the trabeculations and papillary muscles had the advantages of shorter analysis time and better inter-observer reproducibility. We therefore recommend the use of this approach in routine CMR measurements of systemic RV volumes, at least when comparable systems for CMR acquisition and volume analysis are being used.The sample size of 29 patients in two distinct clinical categories is relatively small. The methods used were not suitable for determining which of the analysis approaches measured systemic RV volumes more accurately. Measurements of systemic RV mass were not attempted, and remain challenging given the relative amount of trabeculated RV myocardium. The slice thickness of 8 mm may not have been optimal for clear delineation of the trabeculations, making the definition of the boundaries between trabeculations and blood, and between trabeculations and apparently compact myocardium hard to define in some cases. Moreover, as myocardial boundaries were first defined at end diastole, detecting the corresponding boundary at end systole could be difficult, due to elimination of blood from the inter-trabecular spaces at end systole. The important issue of inter-study reproducibility was not addressed by this study. Between studies, volume measurements might be affected by variation in the relative positioning of the basal short axis slice, and by variables such as the shimming of the magnet and the reliability of ECG triggering.We found the method of systemic RV cavity delineation to affect the measurements of cavity volume, given the CMR acquisition and analysis systems used. We recommend cavity delineation inside the apparently compact myocardium of the RV but outside the trabeculations and papillary muscles for routine clinical measurements of systemic RV volumes as this approach took less time and gave more reproducible values.ccTGA: congenitally corrected transposition of the great arteries; CHD: congenital heart defect; CMR: cardiovascular magnetic resonance; CO: cardiac output; EDV: end diastolic volume; EF: ejection fraction; ESV: end systolic volume; LV: left ventricle; RV: right ventricle; SV: stroke volume; TGA: transposition of the great arteriesThe authors declare that they have no competing interests.MW designed the study format, carried out the literature search, the data collection, and analysis, the statistical analysis and the interpretation of data, carried out the manuscript writing, and gave final approval. FB designed the study format, carried out the literature search, the data collection, and analysis, the statistical analysis and the interpretation of data, carried out the manuscript writing, and gave final approval. MG substantially contributed to the conception and design of the study, performed data acquisition, critically revised the article, and gave final approval. BB substantially contributed to the conception and design of the study, the analysis of data, critically revised the article, and gave final approval. AD substantially contributed to the conception and design of the study, the analysis of data, critically revised the article, and gave final approval. WH substantially contributed to the conception and design of the study, the analysis of data, critically revised the article, and gave final approval. JT substantially contributed to the conception and design of the study, the statistical analysis of data, critically revised the article, and gave final approval. BM substantially contributed to the conception and design of the study, the analysis of data, the interpretation of data, critically revised the article, and gave final approval.Measurements of systemic right ventricular volumes and function by mean of CMR.Click here for fileIntra- and inter-observer reproducibility of measurements.Click here for file


Recent studies suggested that bone marrow (BM) cell implantation in patients with severe chronic coronary artery disease (CAD) resulted in modest improvement in symptoms and cardiac function. This study sought to investigate the functional changes that occur within the chronic human ischaemic myocardium after direct endomyocardial BM cells implantation by cardiovascular magnetic resonance (CMR).P = 0.04) and increase in global LVEF , the percentage of regional wall thickening  and MPR  over the target area at 6-months compared with baseline.We compared the interval changes of left ventricular ejection fraction (LVEF), myocardial perfusion reserve and the extent of myocardial scar by using late gadolinium enhancement CMR in 12 patients with severe CAD. CMR was performed at baseline and at 6 months after catheter-based direct endomyocardial autologous BM cell (n = 12) injection to viable ischaemic myocardium as guided by electromechanical mapping. In patients randomized to receive BM cell injection, there was significant decrease in percentage area of peri-infarct regions (-23.6%, Direct endomyocardial implantation of autologous BM cells significantly improved global LVEF, regional wall thickening and myocardial perfusion reserve, and reduced percentage area of peri-infarct regions in patients with severe CAD. Recent clinical studies -5 suggesAmong those 28 patients enrolled into a Phase I-II randomized PROTECT-CAD trial to evaluate the safety and feasibility of using a catheter-based intramyocardial autologous BM cells implantation , we perfIn brief, all patients enrolled into PROTECT-CAD trial were suffered from severe CAD with reversible perfusion defects detected by single-photon emission computed tomography and had no other option for conventional revascularization therapies. All patients gave informed consent, and the protocol was approved by the institutional review boards. The study population was randomized to receive direct intramyocardial injection of either BM cells (BM group) or autologous plasma (controls) into chronic ischemic myocardium as guided by electromechanical mapping in 2:1 ratio .7 cells per ml were prepared by Ficoll density gradient centrifugation of autologous BM cells harvested from the right iliac crest in each patient. The cell viability was >95% and intramyocardial injection was performed immediately after preparation (~3 hours after harvesting). All patients underwent non-fluoroscopic LV electromechanical mapping  to identify targeted ischaemic myocardium which was matched SPECT and CMR perfusion imaging [In this sub-study, all patients were randomized to the BM group. As reported previously ,15, monoCMR was performed at baseline and at 6 months after catheter-based direct endomyocardial autologous BM cell, and within one week after the single-photon emission computed tomography examination. All patients were examined in the supine position with a 1.5 T system , using a four-element phased-array cardiac coil. All images were obtained during repeated breath-holds. Cine images were performed in multiple parallel short-axis planes covering the entire LV using an ECG-gated segmented K space, steady state free precession pulse sequence as previously reported -16.An intravenous bolus of 0.05 mmol/kg gadolinium-DTPA  was administered at a rate of 5 ml/s by a power injector 4 minutes after continuous adenosine infusion at 140 mg/kg/min. All patients were under continuous blood pressure, pulse oximetry and electrocardiogram monitoring. First-pass perfusion imaging was performed simultaneously with contrast injection for the first 30 to 60 heart beats, using a saturation recovery interleaved fast gradient echo-echo planar pulse sequence at three short-axis left ventricular level  as previously reported . After aAccording to a previously described inversion recovery pulse sequence , LGE imaAll images were reviewed and analyzed off-line with specialized post-processing software  by two investigators (WSC and RYK). Analysis and interpretation of all imaging data were blinded to the clinical data and outcome. The LV volume measurement, calculation of ejection fraction and regional wall thickening were analyzed using the same technique which was reported in the previous study ,16. The All first-pass perfusion images were analyzed in short-axis planes according to the standardized myocardial segmentation and nomenclature for tomographic imaging of the heart , with eatotal) [core) and the peri-infarct mass (MDEperi-infarct) based on signal-intensity thresholds of 3 SDs and 2 to 3 SDs above the remote reference segment, respectively. Infarct size  was expressed as a percentage of LV mass. Furthermore, normalized MDEperi-infarct and MDEcore as percentages of the MDEtotal were calculated as previously described [The endocardial and epicardial contours on delayed enhancement images were traced manually Figure . By usintotal) ,22,23. Iescribed .Data are reported as means ± 1 standard derivation. Comparisons between paired variables were performed using Student's t test, with a significance level of P < 0.05. All statistical analyses were conducted with SPSS version 13.The baseline characteristics of the study population are shown in Table P = 0.02) and regional LV wall thickening over the targeted regions  at 6-month. However, there were no significant changes in the LV end diastolic volume  and LV mass  between 6-month and baseline.There was no significant difference in terms of the haemodynamic conditions of patients at 6 months compared with baseline. Compared with baseline, there were significant improvement in LV ejection fraction , suggestive of significant myocardial ischaemia at the targeted regions.Table P = 0.03). Nevertheless, there was no change in myocardial perfusion reserve at the non-targeted regions between 6-month and baseline .As shown in Figure total at 6-month  after BM cell injection. Nevertheless, there was a significant decrease in %MDEperi-infarct at 6-month as compared with baseline LGE was present in all patients, consistent with prior myocardial infarction. 75% patients had <50% transmural infarction while the remaining patients had 50-75% transmural infarction. Compared with baseline, there was an insignificant modest reduction in the %MDEThe results of this study demonstrate that direct intramyocardial implantation of BM cells was associated with increased myocardial perfusion reserve and regional LV wall thickening at the targeted ischemic regions. Furthermore, there was a reduction in the extent of ischemic peri-infarct area detected by CMR, without any significant decrease in the extent of core infarct area after BM cells injection. Taken together, these CMR findings suggest that BM cells implantation improve myocardial perfusion reserve and reduce ischaemic peri-infarct region in human ischemic myocardium, which subsequently contribute to an improvement in regional LV function.In this study, the mean myocardial perfusion reserve in the targeted ischaemic regions was significantly lower than the non-targeted regions, indicating that the targeted regions have more tissue ischaemia at baseline. The improvement in myocardial perfusion reserve was related to an increase in peak flow rather than a decrease in baseline flow, suggesting enhancement of stress induced myocardial blood flow after BM cell implantation. This postulation is further evidenced by the reduction in the extent of ischaemic myocardium at 6-month after BM cells implantation compared with baseline.Furthermore, the lack of significant reduction in core infarct area after BM cells implantation indicates the lack of significant myocardial regeneration over the scar area. These results are consistent with the findings in recent experimental studies which showed limited capability of BM cells to trans-differentiate into cardiomyocytes and continued to differentiate along the hematopoietic lineage after transplantation ,6,24. HoFirst, a small sample size of this study is a limitation as only patients with detailed CMR examination using the same protocol and machine were included in this analysis. Therefore, our results need to be confirmed by larger, prospective, randomized studies. Second, although the cutoff of remote +2 SD for the entire infarct has been validated in previous studies and currently being practicing in daily clinical application, future studies are still needed to validate the used a pre-specified, arbitrary signal intensity threshold (remote+ 3 SD) above the remote myocardium to delineate the core infarct on LGE. Final, whether the treatment effects of BM cells implantation noted after 6 months are sustained over time needs to be studied.In conclusion, our data from CMR provide insights into the potential functional effects of catheter-based direct intramyocardial delivery of BM cells in the chronic human ischemic myocardium.The authors declare that they have no competing interests.WSC and RYK were responsible for CMR study design, reading, data analysis and manuscript preparation. HFT, YLK and CPL were responsible study design, patients recruitment and procedure, and manuscript preparation.


The first part of the article dealt with the basic science behind the evolution of ventricular restoration procedures and the rationale for the use of novel surgical techniques. The second part describes the preoperative workup of patients in advanced heart failure, the core information required to determine the surgical approach and the essential principles and techniques of ventricular restoration. It then examines the effects of ventricular restorative procedures on pump function and clinical outcomes, the results of the worldwide experience with ventricular restoration and concludes with more recent advances in this field. Cardiac magnetic resonance imaging (MRI) allows a complete evaluation of these quantities .The scar is the nidus for subsequent dilation of remote muscle and asynergy >35% of the ventricular perimeter by ventriculography generally causes LV dilatation. Contiguous asynergy > 25% is amenable to SVR. The region to be surgically excluded is evaluated for wall motion and thickening. Late contrast enhancement helps characterize both infarcted and remote muscle. The region of asynergy whether dyskinetic or akinetic lacks contractility. Viability of the asynergic region  predicts functional recovery with revascularization alone, while predominant non-viability (>50% enhancement) may preclude contractile recovery following revascularization alone. SVR excludes this nidus for dilation and reduces LV volume in such cases.Tagging labels a specific volume of tissue whose motion is tracked through the cardiac cycle. Local myocardial contractility can be determined by the distortion of the tagged element boundaries. This is useful when a region of viable, contractile myocardium is adjacent to and tethers a region of nonviable, noncontracting muscle, thereby making the nonviable region appear contractile. Tagging clarifies this issue, since a viable, contracting segment exhibits ‘squeezing’ deformation of tagged tissue, while a nonviable segment that is tethered shows a ‘stretching’ deformation.Remote muscle function provides the compensatory element for survival. Documentation of remote muscle contractility, or its viability if hypokinetic predicts functional recovery after SVR. The remote myocardium could be normal, infarcted, stunned or hibernating. Hibernating muscle (due to right or circumflex coronary stenoses), if inadequately revacularized, may lead to pump failure after SVR, if contractility is inadequate to support circulatory needs.Scarring of remote myocardium determines prognosis and is critical in patient selection. Remote muscle viability helps decide if revascularization of the circumflex or right coronaries is likely to be beneficial, as extensive scarring may preclude contractile recovery.Viability analysis by MRI includes assessment of regional function and morphology. Myocardium with diastolic wall thickness < 5.5 mm may be nonviable.2.The fundamental principle of SVR is to exclude dead muscle and revascularize damaged remote muscle. This restores contractile capacity of the dilated hibernated remote muscle, which compresses the intraventricular patch, thereby improving mechanical performance. Evidence of patch movement has been observed by echocardiography and colour kinetics. The patch acts as an active endocardium and no significant dysfunctional zone is evident. LAD grafting is important to revascularize the upper septum. RCA/LCX grafting is crucial to revascularize the remote muscle which provides postoperative pump function .3.The concept of SVR consists of complete revascularization to relieve ischemia, ventricular reconstruction to restore elliptical shape, reduction of volume and wall stress to improve hemodynamics and when necessary, endocardectomy and cryoablation for VT -5. MitraFollowing initiation of cardiopulmonary bypass and cardioplegic arrest, coronary revascularization and mitral repair are performed as necessary. With fibrotic, dyskinetic LVA, there is a clear transitional zone between dysfunctional tissue and viable contracting myocardium. Traditionally a linear repair technique has been used on thin-walled left ventricular aneurysms but this does not allow for septal exclusion. Lundblad  demonstrThe LV is opened through the infarcted, scarred area, which often collapses on cardiopulmonary bypass and venting. The ventriculotomy is extended parallel to the LAD. Clots are removed. A subtotal nonguided endocardectomy is performed on the septum and anterior wall if spontaneous or inducible VT exists. Linear cryo lesions are applied at the edge of the endocardial resection.Akinetic areas must be recognized. With post-MI revascularization, the classic myocardial scar that collapses on venting may not be evident. It is important to exclude the entire segment to delete the midmyocardial and endocardial scar.SVR can be performed on an arrested or beating heart. SVR on a beating heart has distinct advantages in thick walled akinetic ventricles where visual demarcation between scar and healthy muscle is not obvious.2 to optimize size and shape of the new ventricle. The mannequin is useful when the ventricle is not much dilated  or when the infarct is not clearly demarcated. Mannequins therefore prevent excessive reduction of ventricular volume, help position the new apex, create an elliptical shape and provide adequate volume reduction in huge ventricles where the scar is not readily apparent. Creation of a small LV results in a low cardiac output state, while a residual box like LV is characterized by diastolic dysfunction. Residual sphericity causes papillary muscle malalignment and MR.Menicanti  introducAn endoventricular circular suture (Fontan stitch) is placed at the transitional zone starting from the new apex, going medially toward the septum, superiorly toward the aortic valve, laterally toward the base of the papillary muscles and ending at the  level of the apical reference stitch. The Fontan stitch is tightened to approximate the ventricular wall to the balloon.A Dacron or pericardial patch is sewn to the ridge created by the purse-string suture. The ventriculotomy is then folded over the patch and closed. Patients are weaned from cardiopulmonary bypass with inotropes and/or an intraaortic balloon pump (IABP) as necessary.Retention of spherical shape may persist when patch placement is limited to the scar, since extensively stretched remote muscle stretch is retained. This results in a spherical LV, with a box like apex on post-operative angiograms. This is the pitfall of using the scar as the guide in grossly dilated ventricles.The SAVE or Pacopexy procedure  was init3A.et al. demonstrated that outcome is more strongly linked to the extent of asynergy than to the type of asynergy (akinetic vs dyskinetic)  is a hormone released from the ventricles in response to wall stress and ischemia. SVR induces a persistent reduction of NT-pro-BNP and BNP 6 months postoperatively and at late follow-up respectively. Increasing ejection fraction and decreasing LVESV correlated significantly with lower BNP and NT-pro-BNP levels 6 months after surgery . No sign7.The return of heart failure after the surgery is attributed to (1) recurrent MR, (2) continued LV remodelling; (3) too small a LV caused by excessive excision, (4) removal of the kinetic area while retaining poorly contractile and more fibrotic regions, (5) evolution of coronary artery disease or repeated ischemic episodes and (6) improper identification of the transition between scar and normal muscle in akinetic regions, leading to possible salvage of an excess of scarred ventricle.8.Maxey  and Ribe9.The STICH trial will address the management of patients with heart failure who have CAD amenable to revascularization. This is a prospective randomized study with 2800 patients from 100 centres. Patients with left ventricular dysfunction and coronary artery disease amenable to CABG will be randomized to combinations of three different treatment strategies: CABG, SVR, and intensive medical therapy (MED).The revascularization hypothesis states that coronary artery bypass grafting (CABG) with intensive medical therapy (MED) improves longterm survival compared to MED alone.The reconstruction hypothesis states that in patients with anterior LV dysfunction, surgical ventricular restoration (SVR) to a more normal LV size improves survival free of subsequent hospitalization for cardiac cause in comparison to CABG alone.When compared with MED alone, CABG is expected to confer a 20% reduction in mortality. These data are expected to solidify the role of bypass surgery in the treatment of ICMPY. Ventricular restoration is also expected to improve hospitalization-free survival by 20% when compared with CABG alone. This will also serve to dramatically improve outcomes in a patient population that has a 50% 3-year survival rate without SVR.2, the intervention decision relates to comparing the effects of either using medical treatment or adding CABG. When LVESVI > 60 ml/m2, the decision question relates to how SVR fits into the treatment scheme in 1200 patients.The STICH protocol uses LVESVI measurement to make decisions about placing patients into the 3 study groups. If LVESVI is less than 60 ml/m10.1. An analysis of the use and outcomes of SVR in a national sample in a real world application reveals that perioperative events are somewhat higher than prior selected series.Contemporary results following SVR and the risk factors for mortality are included in Table et al. [et al. showed excellent functional outcomes in such patients, with nearly ¾ of the patients improving from NYHA class III/IV to NYHA class I or II following surgery.The performance of SVR in patients after a recent MI or in an emergent setting is contrary to what was done in RESTORE group, where the surgery was performed an average of 4.4 years after an anterior infarct. However, Di Donato et al.  have demet al. . The pat11.The effects of shape restoration may be combined with cell implantation into remote muscle  to enhan