Cardiogenic shock (CS) remains a major cause of in-hospital mortality in the setting of acute myocardial infarction. CS begins as a hemodynamic problem with impaired cardiac output leading to reduced systemic perfusion, increased residual volume within the left and right ventricles, and increased cardiac filling pressures. A critical step towards the development of future algorithms is a clear understanding of the treatment objectives for CS. In this review, we introduce the “door to support” time as an emerging target of therapy to improve outcomes associated with CS, define four key treatment objectives in the management of CS, discuss the importance of early hemodynamic assessment and appropriate selection of acute mechanical circulatory support (AMCS) devices for CS, and introduce a classification scheme that identifies subtypes of CS based on cardiac filling pressures. Despite early revascularization, an estimated one in three patients will die during their hospitalization for AMI-CS and one in five patients will die within the first year after discharge for AMI4. More sobering is the fact that over 30% of AMI-CS survivors develop recurrent heart failure (HF) within the first year after discharge5. The natural history of HF is a progressive decline in ventricular function as compensatory remodeling ultimately fails and patients present with recurrent episodes of acutely decompensated HF and ultimately CS owing to advanced HF (CS-HF). A recent analysis of the Interagency for Mechanical Circulatory Support (INTERMACS) registry identified that 52.5% of patients with advanced HF referred for surgical left ventricular (LV) assist device (LVAD) placement present with CS-HF defined as INTERMACS levels 1 or 2 HF6. By 2030, 8 million people in the United States alone will be diagnosed with HF7. Collectively, these data identify CS as a persistent clinical problem and further suggest that the distribution of CS patients may be shifting from CS-AMI to CS-HF over the next decade.Cardiogenic shock (CS) remains a major cause of in-hospital mortality in the setting of acute myocardial infarction (AMI). Several recent reports identified an increase in the prevalence of CS among patients with AMI from 6–7% to 10–12%8. At this stage, CS has transitioned from a potentially reversible hemodynamic problem to a more complex “hemo-metabolic” problem that may not respond to treatment of the underlying cause or hemodynamic support alone  circulatory support, 2) ventricular unloading, 3) myocardial perfusion, and 4) decongestion . AdequatPharmacologic approaches fail to solve the hemodynamic support equation. Often drug therapy will solve one part of the equation but at the cost of another. For example, early use of vasopressors such as norepinephrine in CS may increase mean arterial pressure but not microvascular organ perfusion. Furthermore, increased mean arterial pressure will increase LV afterload, thereby increasing myocardial work and wall stress, which promotes myocardial ischemia, impairs cardiac function, and increases cardiac filling pressures. Similarly, inotropic therapy in CS may increase mean arterial pressure but directly increases myocardial work, thereby potentially worsening myocardial ischemia. For these reasons, CS refractory to one or more vasopressors or inotropes is associated with increased in-hospital mortality.In the contemporary era, the hemodynamic support equation can be readily addressed with early and appropriate use of AMCS devices, which can be broadly categorized by their mechanism of action as pulsatile or rotary flow pumps .13. The magnitude of hemodynamic support generated by an IABP is directly related to LV cardiac output. Recent studies confirm that the more dysfunctional the LV, the less effective an IABP becomes16. In 2012, the IABP-SHOCK II study reported no benefit with IABP therapy in patients with AMI-CS. No large, randomized studies have evaluated the utility of IABP therapy in HF-CS17.The intra-aortic balloon counter-pulsation pump (IABP) is a catheter-mounted balloon that augments pulsatile blood flow by inflating during diastole, thereby increasing diastolic pressure in the aortic root and enhancing coronary blood flow, while also displacing blood volume in the descending aorta. During systole, rapid deflation of the intra-aortic balloon generates a pressure sink, which reduces LV afterload and increases LV cardiac output18. Axial-flow AMCS pumps are placed across the aortic valve and displace blood from the LV into the ascending aorta. The net result of these trans-valvular axial pumps is a reduction in LV pressure and volume with a concomitant increase in mean aortic root pressure. As a result, systemic perfusion is increased, LV wall stress is reduced, and the trans-myocardial perfusion gradient (aortic diastolic pressure – LV diastolic pressure) is increased. Furthermore, several prior studies have shown that under ischemic conditions, coronary blood flow is increased after activation of a trans-valvular axial-flow pump20. Trans-valvular axial-flow pumps directly solve three of the four major objectives in the hemodynamic support equation by increasing mean arterial pressure, reducing LV pressure and volume, and increasing coronary blood flow. Contemporary trans-valvular axial-flow pumps include the Impella  or the HeartMate percutaneous heart pump (PHP) 22. The PHP device is currently under investigation in the United States as part of the SHIELD II trial. The Impella devices are the only AMCS pumps approved by the US Food and Drug Administration for use in CS.In contrast to counter-pulsation balloons, rotary-flow pumps generate rotational kinetic energy, which increases blood flow. Rotary flow pumps can be further categorized based on the type of motor as axial-flow or centrifugal-flow systems22. The TandemHeart and VA-ECMO systems draw blood from the left or right atrium, respectively, into an extracorporeal pump that displaces the blood into the femoral artery, thereby pressurizing the arterial tree and increasing mean arterial pressure. Since VA-ECMO displaces venous blood into the arterial system, an oxygenator is placed in the circuit prior to the return of blood to the femoral artery. The distinct location of the inflow cannula has a profound impact on the hemodynamic effects of these two systems23. Since VA-ECMO drains blood from a large venous reservoir, at typical flow rates of 4 to 6 liters/minute, VA-ECMO does not significantly reduce LV volume. As a result, VA-ECMO increases LV pressure, wall stress, and myocardial work and fails to solve the hemodynamic support equation. In contrast to VA-ECMO, by displacing blood from the left atrium, the TandemHeart device effectively reduces LV preload, thereby reducing LV volume, wall stress, and workload, while increasing systemic mean arterial pressure and myocardial perfusion24. The TandemHeart system is able to solve the same three objectives of the hemodynamic support equation as do trans-valvular axial-flow pumps; however, a major technical limitation of the TandemHeart device is the need for a puncture across the interatrial septum to deliver the 21 French cannula that drains the left atrium.Centrifugal-flow pumps include the TandemHeart device  and veno-arterial extracorporeal membrane oxygenation (VA-ECMO)In summary, the trans-valvular axial-flow pumps and the TandemHeart left atrial-to-femoral artery centrifugal-flow pump successfully achieve three of the four major objectives of the hemodynamic support equation: circulatory support, ventricular unloading, and enhanced coronary perfusion.27, no guidelines regarding their use have been developed to date.Over the past 5 years, the introduction of right ventricular (RV) non-surgical AMCS devices has advanced our ability to support patients with CS and either isolated RV failure or biventricular (BiV) failure. Options for RV-AMCS include the Impella RP, the TandemHeart RVAD, and VA-ECMO . The Imp29. In CS, adequate circulating volume is necessary to maintain cardiac output; however, excess circulating volume may be detrimental to multi-organ function. As described above, AMCS devices can effectively address parts of the hemodynamic support equation. However, in isolation, AMCS devices alone cannot address the fourth objective, namely, decongestion. Decongestive approaches such as concomitant diuretic therapy or renal replacement therapy should be considered early in CS for patients with elevated BiV filling pressures refractory to diuretics and AMCS device support.A critical barrier to successful clinical outcomes in advanced HF and CS is persistent systemic volume overload or congestion. Recent studies have identified that elevated right heart filling pressures are directly related to worsening renal function and further that elevated BiV filling pressures are associated with increased short-term mortality30. At this stage, CS is becoming irreversible. Emerging evidence supports the use of pulmonary artery catheters (PACs) to identify CS before metabolic failure ensues and to define the hemodynamic condition of patients in advanced HF and CS31. PAC guidance must be strongly considered in patients with suspected CS to confirm the presence of CS (low cardiac output), define the congestive profile in CS (cardiac filing pressures), and to evaluate the patient’s response to therapeutic interventions.The contemporary definition of CS must evolve beyond metrics associated with the early stages of hemo-metabolic shock such as hypotension and evidence of low perfusion, including cold and clammy extremities and end-organ dysfunction34. The relationship between RA and pulmonary capillary wedge pressure (RA:PCWP ratio) has been used to identify RV failure in AMI and is associated with prognosis in advanced HF. Analogous to the 2×2 evaluation of patients with advanced HF as being “warm or cold and dry or wet”35, the RA:PCWP ratio allows us to classify CS based on congestive state into four hemodynamic profiles: hypovolemic, LV-, RV-, or BiV-dominant congestion36. For patients with CS failing to improve despite the initiation of one vasopressor or inotrope, each of these four categories may require a different therapeutic approach  early hemodynamic assessment of CS, 2) early use of AMCS devices for refractory CS, 3) identification of the optimal DTS time, 4) appropriate AMCS device selection based on the clinical scenario, and 5) early use of decongestive therapies to reduce the propensity for worsening metabolic failure despite adequate circulatory support.


Background. This study sought to identify the pattern of electrocardiographic changes in steady state adult sickle cell anaemia. Methods. A case-control, cross-sectional study was conducted amongst sickle cell patients attending the sickle cell clinic of Lagos State University Teaching Hospital, Ikeja, and HbAA controls. All consenting participants had haemoglobin electrophoresis done and were subjected to electrocardiography (ECG). The descriptive data were given as means ± standard deviation (SD). The differences were considered to be statistically significant when the p value obtained was <0.05. Results. A total of ninety-three sickle cell anaemia (SCA) patients and ninety haemoglobin AA (controls) were enrolled. There was no significant difference in the age of the participants with SCA and that of the controls but the body mass index was significantly higher in controls (p = 0.0001). Overall, 73.1% (68 of 93) had abnormal ECG while only 2 of 90 (2.2%) of controls had abnormal ECG. The common abnormalities observed were left ventricular hypertrophy, biventricular hypertrophy, and right ventricular hypertrophy. Conclusion. Patients with SCA in steady state tend to have normal heart rate but about 50% of them would have had ECG changes before the age of 20 years. ECG being a noninvasive test may be used to identify patients at risk for early intervention. Sickle cell anaemia is a genetic abnormality involving the haemoglobin. Patients present with a wide spectrum of disorders because of a single-point mutation in which thymine substitutes for adenine, thereby encoding valine instead of glutamine in the sixth position of the beta-chain.The repeated sickling and unsickling damage the red cell membrane leading to irreversibly sickled red cell even when the oxygen pressure is increased. This causes reduced red cell life span as a result of membrane damage. Haemolysis consequent on the damaged red cell membrane could be intravascular or extravascular causing chronic anaemia.Chronic anaemia is largely responsible for cardiac manifestations of sickle cell disease . Sickle Electrocardiographic evidences of cardiomegaly and biventricular hypertrophy are common findings in sickle cell disease patients . These aSkin fat and thin chest wall in addition to normal racial variation in black population may contribute to high voltages recorded in black sickle cell population , 13. HenElectrocardiographic change is common in sickle cell anaemia and it is associated with chronic anaemia. It is a noninvasive procedure; it is affordable in low-income countries where patients pay for every investigation and does not require extensive training. Presently, there is paucity of validated means to assess adult at risk of organ failure in steady state so that early intervention can be commenced as in the use of transcranial carotid artery Doppler scan in children. The prognostic value of electrocardiography is yet to be determined. This study therefore sought to determine pattern of electrocardiographic changes in adult patients in steady state attending the outpatient clinic.A case-control, cross-sectional study was conducted amongst sickle cell patients attending the adult sickle cell clinic of Lagos State University Teaching Hospital, Ikeja, and HbAA controls between September and December 2014. Ethical approval was obtained from the institution's Ethics and Research Committee. Written and verbal consents were obtained from each participant. Participants were asked to fill structured questionnaires including demographic information, previous history of crises, date of last crisis, and cigarettes and alcohol intake. Inclusion criteria were patients with haemoglobin phenotype SS in steady state, no history of crises in the past 3 months established by a careful history, and complete physical examination. Exclusion criteria were haemoglobin phenotype SC patients, hypertensive patients, and HIV infected patients. Consenting participants consisting of medical students, nurses, administrative members of staff, and medical doctors with haemoglobin phenotype AA were also enrolled as controls. All consenting participants had haemoglobin phenotype confirmed, subjected to electrocardiography (ECG), and the females were nonpregnant.Age, weight, height, BMI, sex, and medications of all patients were recorded. Ten leads were placed at precise anatomical locations to obtain quality data. The four limb lead electrodes were applied to the extremities starting with the right leg and then the left leg, right arm, and left arm. All the chest leads were also applied at the precordial electrode locations (V1–V6). ECG was recorded after the connection of the limb and chest leads. ECG tracings were read and interpreted by a cardiologist. Randomly selected ECG tracing readings were double checked by an independent cardiologist. Measurements of heart rates, QTc, and PR intervals were done in the standard fashion . ECG ref p value obtained was <0.05.The descriptive data was given as means ± standard deviation (SD). The Pearson correlation was used for the analytical assessment. To assess association between two discrete parameters the Fisher Exact Test was used to determine the odds ratio. The differences were considered to be statistically significant when the2 with a median of 18.9 kg/m2 while the mean BMI in controls was 22.5 ± 3.1 kg/m2 and the median was 21.2 kg/m2. The difference was highly significant (p = 0.0001). Spearman correlation analysis of age and BMI showed positive correlation (r = 0.23 and p = 0.03).A total of ninety-three sickle cell anaemia (SCA) patients and ninety haemoglobin AA (controls) were enrolled. The proportion of females was 54% amongst SCA patients and 50% amongst controls . The meaThe following electrocardiographic abnormalities were observed in SCD participants: left ventricular hypertrophy (43%), biventricular hypertrophy plus right ventricular hypertrophy (28%), right atrial dilatation (1.16), premature ventricular complex (0.01%), 1st-degree atrioventricular block (0.06%), and myocardial strain (0.01%) . Left veOverall, 73.1% (68 of 93) had abnormal ECG while only 2 of 90 (2.2%) of controls had abnormal ECG. The percentage of SCA males with abnormal ECG was 88% while 60% of females had abnormal ECG. A total of 11 of 42 (26.1%) males with SCA had left ventricular hypertrophy and 7 of 42 (16.6%) males with SCA had biventricular hypertrophy and right ventricular hypertrophy. A total of 9 of 51 (17.6%) females with SCA had left ventricular hypertrophy while 7 of 51 (13.7%) had biventricular hypertrophy and only 2 of 51 (3.9%) had right ventricular hypertrophy.p = 0.847). The mean QTc interval of SCA patients was 0.38 ± 0.035 seconds and controls 0.37 ± 0.02 seconds (p = 0.123). The mean PR interval of SCA was 0.186 ± 0.06 seconds and controls 0.169 ± 0.036 seconds (p = 0.369). The mean QRS duration of SCA was 0.07 ± 0.09 and controls 0.043 ± 0.14 seconds (p = 0.055).Despite the similarity in mean heart rate of SCA patients and controls, 77.28 ± 14.61 and 77.19 ± 15.30 seconds, respectively, this was not statistically significant , Correlation analysis of changes in age and BMI with ECG intervals showed significant correlation only between age and the PR interval (p = 0.79), p = 0.43).There was no significant association between the presence of LVH and frequency of bone pain crisis using Fisher's Exact Test  despite similarity in values. Chronic anaemia associated with sickle cell anaemia minimally increases heart rate despite a marked increase in cardiac output [The mean heart rate of SCA was significantly different from that of controls (c output . This rep = 0.055). This is at variance with findings by others, where ECG intervals in SCA were significantly higher than in controls. This may be due to the exclusion criteria that excluded the patients that had crisis within 3 months of study. Patients that were doing well must have been selected. This suggests that even amongst SCA patients with low frequency of crisis there are ECG abnormalities. The presence of left ventricular hypertrophy may therefore be used to identify patients at risk for early intervention.The QTc and PR intervals were not significantly different in SCA and controls. However, the QRS duration was somewhat significantly higher in SCA than in controls in this study (In conclusion, cardiac abnormalities particularly pulmonary hypertension and diastolic left ventricular dysfunction have been known to be risk factors of syncope and sudden death in SCA . ECG bei


A common clinical scenario in electrophysiology practice involves patients with arrhythmia and left ventricular (LV) dysfunction. The concept that atrial fibrillation (AF) or other arrhythmias can induce cardiomyopathy in the absence of organic heart disease has been known since the 1950s.Journal of the American Heart Association, Addison et al present valuable results to aid patient selection for AF ablation in the setting of LV dysfunction.In this issue of the r=0.95; P<0.001). A small possibility for differential bias has not been excluded. Echocardiography or CMR measurements may be biased upward or downward depending upon the rhythm and/or the presence of LV dysfunction at the time of measurement. Such a differential bias would be missed in an analysis that compared the 2 modalities in a subcohort with persistent LV dysfunction and recurrent AF. Optimal medical therapy was used in the majority of patients, but the duration of optimal CHF therapy and rate control before ablation is unknown. Therefore, part of the LV function recovery may be attributable to rate and CHF control therapy before ablation. Also, the direction of association between ablation and recovery of LV function in the absence of LGE is unknown. Improved hemodynamics and LVEF with medical therapy in the absence of LGE may have increased the likelihood of rhythm control following AF ablation. On the other hand, the absence of LGE may have led to improved rhythm control attributed to AF ablation and led to subsequent improvement in hemodynamics and LVEF.The researchers have discussed limitations, including possible underestimation of AF recurrence attributed to the retrospective design as well as the lack of comparison to randomized controls treated with medical therapy. Baseline measurements were performed by CMR; however, LV function following ablation was measured by echocardiography in 77% of patients. This is mitigated by the fact that in the 20% of patients with both echocardiography and CMR follow‐up, the measurement bias was minimal , with an excellent overall correlation . The views expressed in this document reflect the opinions of the author and do not necessarily represent the official views of the National Institutes of Health or the National Heart, Lung and Blood Institute.


Objectives. Normothermic hyperkalemic cardioplegia arrest (NHCA) may not effectively preserve hypertrophied myocardium during open-heart surgery. Normothermic normokalemic beating perfusion (NNBP), keeping hearts empty-beating, was utilized as an alternative to evaluate its cardioprotective role. Materials and Methods. Twelve hypertrophied pig hearts at 58.6 ± 7.2 days after ascending aorta banding underwent NNBP and NHCA, respectively. Near infrared myocardial perfusion imaging with indocyanine green (ICG) was conducted to assess myocardial perfusion. Left ventricular (LV) contractile function was assessed by cine MRI. TUNEL staining and western blotting for caspase-3 cleavage and cardiac troponin I (cTnI) degradation were conducted in LV tissue samples. Results. Ascending aortic diameter was reduced by 52.7% ± 0.4% at approximately fifty-eight days after banding. LV wall thickness was significantly higher in aorta banding than in sham operation. Myocardial blood flow reflected by maximum ICG absorbance value was markedly higher in NNBP than in NHCA. The amount of apoptotic cardiomyocyte was significantly lower in NNBP than in NHCA. NNBP alleviated caspase-3 cleavage and cTnI degradation associated with NHCA. NNBP displayed a substantially increased postoperative ejection fraction relative to NHCA. Conclusions. NNBP was better than NHCA in enhancing myocardial perfusion, inhibiting cardiomyocyte apoptosis, and preserving LV contractile function for hypertrophied hearts. Conventional cardioplegia confers sufficient myocardial protection for most patients with preserved ventricular function and leads to a complete postoperative recovery of cardiac function. In patients with compromised cardiac function, such as those with severe myocardial hypertrophy, conventional cardioplegia does not provide adequate myocardial preservation , 2. ThisMyocardial hypertrophy is associated with an increase in coronary vascular resistance and a significantly decreased capillary numerical and volume density , 4. CardRecently, beating heart valve surgery has emerged as an effective alternative method to prevent cardioplegia-associated detrimental effects. Preliminary clinical practice suggested that operative vision of beating heart valve surgery was equal to that of traditional valve surgery and technical accuracy was not compromised , 14. MorNormothermic normokalemic beating perfusion (NNBP), keeping the heart empty and beating, resembles close-normal physiological situation, avoids the utilization of high-potassium cardioplegia, and maintains the squeezing effect of heart contraction on vessels. Thus, we hypothesized that NNBP had the advantage over normothermic hyperkalemic cardioplegia arrest (NHCA) in improving myocardial tissue perfusion, depressing cardiomyocyte apoptosis and myocardial stunning, and preserving heart contractile function.This study was conducted under an approval by the Institutional Review Board and Animal Care Committee of National Research Council of Canada and Huazhong University of Science and Technology.Eighteen 6- to 8-week-old piglets were intubated and mechanically ventilated. A left thoracotomy was performed in the third intercostal space. A polyethylene band (5 mm in width) was tightened around ascending aorta with a peak systolic pressure gradient of 10 mmHg across the narrowing. Left ventricular (LV) hypertrophy occurred progressively as aortic constriction remained fixed with normal body growth. In six sham operated piglets, the band was pulled through ascending aorta; thus, no aorta narrowing developed after surgery. The chests were then closed, and the pigs were allowed to recover for 58.6 ± 7.2 days.Immediately, 28.6 ± 2.4 and 58.6 ± 7.2 days after aortic banding, all pigs underwent cine MRI to monitor the magnitude of LV hypertrophy. At 58.6 ± 7.2 days after banding, median sternotomy was accomplished under general anesthesia, and then pigs were transferred to MR region next to surgical room. Cine MRI was performed to assess heart function before cardiopulmonary bypass (CPB).n = 6 per group). Pigs in group I underwent the NNBP, and hearts were maintained at a empty and beating condition during a 60-minute preservation period. Pigs in group II received the NHCA, and hearts were kept in a quiescent and arrested situation at a similar period of time. Thereafter, CPB with standard cannulations was initiated during NNBP or NHCA. Krebs-Henseleit (K-H) solution was mixed with the pig blood in 1 : 1 ratio. The mixture was used to perfuse isolated hearts. Krebs-Henseleit solution is widely accepted as a physiologic perfusion medium and has been used for many years for heart perfusion. The K-H solution contained 118 mmol/L NaCl, 1.2 mmol/L MgSO4, 0.5 mmol/L ethylenediaminetetraacetic acid, 11 mmol/L glucose, 25 mmol/L NaHCO3, 1.75 mmol/L CaCl2, and 0.625% bovine serum albumin. The potassium concentration of the mixture was 3.4 and 16 mmol/L for NNBP and NHCA, respectively. Near infrared spectroscopic imaging was performed with the bolus administration of indocyanine green (ICG) to assess myocardial perfusion. After 60-minute CPB, the pigs were weaned off CPB and were transferred to neighboring MR area. Cine MRI was likewise performed to evaluate post-CPB myocardial function.The pigs with severe LV hypertrophy were divided into two groups  with a flow rate at 50 mL/kg/min. Pigs were placed on total CPB by snaring the vena cava. After stabilization, the ascending aorta was cross-clamped. A double-lumen aortic root cannula was inserted for antegrade delivery of perfusate and simultaneous measurement of infusion pressure. All infusions of myocardium were administered at the pressure of 40 to 50 mm Hg. The ascending aorta was cross-clamped for 60 minutes.The cryopreserved tissue sections were fixed in 4% paraformaldehyde. Then, tissue sections were stained by TUNEL with In Situ Cell Death Detection Kit  according to the manufacturer's instructions. After TUNEL, the sections were mounted with Prolong Gold antifade reagent with DAPI . Ten photographs  of each tissue section were taken under a fluorescence microscope and analyzed by two independent researchers. The number of apoptotic myocytes was expressed as the number of TUNEL-positive cells per 1000 total nuclei. Normal myocardium from sham operated pigs was used as negative control. Positive control was obtained from normal myocardial tissue kept at room temperature for one hour.Protein samples from the experimental animal myocardial tissues were fractionated on 12.5% SDS-PAGE and transferred to polyvinylidene (PVD) membrane  and then blocked for one hour at room temperature with 5% nonfat dry milk in PBS containing 0.1% Tween-20 (PBST). The membranes were incubated with a polyclonal anti- troponin I antibodies  and anti-caspase-3  at room temperature for two hours. The membranes were washed with PBST and then incubated with secondary antibodies either a rabbit anti-mouse or mouse anti-goat IgG conjugated to horseradish peroxidase. Immune complexes were visualized with the enhanced chemiluminescence detection system . Relative quantification of immunoreactive bands was performed by Quantity One imaging software . Each modified product was quantified as a percentage of the total amount of protein.An infrared-sensitive CCD-array camera was positioned overtop the chest cavity, so that the heart filled the field of view. Consecutive images were acquired at a single wavelength of 800 nm and total acquisition time for 120 sequential images was approximately 2 minutes. An ICG bolus (16 mg/10 mL) was injected through cardiac perfusate line after aorta cross clamp. The bolus administration was performed in the third images after onset of acquisition, allowing the achievement of at least three pre-ICG heart images. Three minutes after injection of ICG bolus, blood samples were taken and plasma was analyzed for ICG content spectrophotometrically at 800 nm. Following each trial, a uniform reflectance standard  was placed overtop the heart and a reference image sequence was acquired.2, flip angle: 30 to 40°, echo time: 3.5 ms, repetition time: 9.2 ms, matrix: 256 × 256, and temporal resolution: 50 ms. For quantitative determination of morphology and function, 12–14 contiguous ventricular short-axis slices of 6 mm thickness were acquired from apex to base to cover the entire LV.Cine MRI was performed on a 3-Tesla MR scanner . A phased array four-element body surface coil was utilized for signal reception. MR sequences were electrocardiography-triggered, breath hold, and acquired in oblique short-axis view. Cine images were acquired with a fast gradient echo sequence in oblique short-axis plane. The following parameters were used: field of view: 8 × 8 cmhttp://segment.heiberg.se). The epicardial and endocardial borders of the myocardium were manually traced on end-diastolic and end-systolic images at each anatomic level encompassing the entire LV. End-diastolic and end-systolic wall thickness were measured in six segments including the anteroseptal anterior, anterior-lateral, anterolateral, interior, and anteroseptal wall of LV in three contiguous midventricular slices. LV slice volumes were determined from end-diastolic and end-systolic images by multiplication of compartment area and slice thickness. Total LV volumes were calculated as the sum of all slices volumes. Stoke volume was calculated using the following equation: end-diastolic volume-end-systolic volume. Ejection fraction was determined as followed: end-diastolic volume-end-systolic volume/end-diastolic volume (%).Cine images data were analyzed by using freely available software . The resulting spectroscopic imaging was a two-dimensional (256 pixels × 256 pixels) image of absorbance at an ICG specific wavelength (800 nm). Each image was rationed to the reference image at 800 nm to provide absorbance data. Extraction of the absorbance values for a single pixel through the 120 images yielded the time course of relative ICG kinetics in specific region of hearts. Two regions of interest (ROIs) were located at the left anterior descending artery (LAD) region and myocardial tissue area, respectively. The comprehensive time courses of ICG absorbance were obtained at the two specific ROIs. Maximal absorbance was calculated from ICG time courses to evaluate myocardial blood flow. t-tests. The percentage of TUNEL-positive myocytes, the percentage of cleaved caspase-3 or degraded cTnI, LV end-diastolic volume, LV end-systolic volume, ejection fraction, and stroke volume were compared with a paired t-test. Values of P < 0.05 were deemed significant.All data are presented as the mean ± standard deviation. Repeated measures analysis of variance was used to compare the ICG absorbance values varied with the passage of ICG. Differences among different regions at specific time points were isolated by BonferroniThe representative end-systolic aorta MR images immediately, average 28 and 58 days after ascending aortic banding, are illustrated in Ascending aortic diameter at the banding site remained unchanged. They were 9.7 ± 0.8, 9.7 ± 0.7, and 9.8 ± 0.6 mm immediately, average 28 and 58 days after aortic banding, respectively . AscendiLV end-diastolic and end-systolic short-axis images immediately, average 28 and 58 days after ascending aortic banding, are illustrated in Figures LV end-diastolic wall thickness was significantly greater in aorta banding than in sham operation  . LikewisA bolus injection of ICG was associated with a quick appearance of red color, initially in the epicardial coronary arteries and then in myocardial tissue. Representative myocardial ICG perfusion images are illustrated in Representative time courses for ICG passage through hearts are shown in Figures TUNEL-positive nuclei (red) were more frequent in NHCA when compared with those in NNBP . PercentThe cleavage of caspase-3 was consistently detected in pigs undergoing NNBP and NHCA. However, caspase-3 cleavage was more obvious in NHCA than in NNBP . The perIntact and degraded cTnI were present in pigs undergoing NNBP or NHCA . The speRepresentative short-axis MR cine images from end-diastole to end-systole during the whole cardiac cycle in pre-CPB, NHCA, and NNBP post-CPB are illustrated in LV end-diastolic volume was significantly lower in NNBP post-CPB (122.5 ± 2.9) than in NHCA post-CPB (130.6 ± 4.1 mL) . MoreoveThe recent study was undertaken to examine the cardioprotective effect of NNBP on myocardial tissue perfusion, cardiac myocyte apoptosis, myocardial stunning, and heart contractile function in hypertrophied hearts. The major findings of this study are as follows: (1) the approximately eight-week aortic banding was an effective technique to induce pressure-overloaded myocardial hypertrophy; (2) NNBP enhanced myocardial tissue-level blood perfusion, inhibited cardiac myocyte apoptosis, decreased myocardial stunning, and improved LV contractile function in comparison with traditional NHCA.Myocardial hypertrophy is associated with decreased capillary density, increased coronary arterial resistance, and comprised coronary vasodilator reserve , 4. AbnoSeveral myocardial stresses during cardioplegic cardiac arrest, including ischemia-reperfusion injury, coronary endothelium dysfunction, neutrophil-mediated pathologic events, and oxygen-derived free radicals, have been reported to trigger cardiomyocyte apoptosis , 21, 22.Cardiomyocyte apoptosis may be involved in irreversible myocardial tissue damage and persistent ventricular dysfunction after cardioplegia surgery. Myocardial stunning is characterized by reversible contractile dysfunction despite restoration of blood flow without myocyte necrosis. cTnI plays a crucial role in the calcium-dependent muscle contraction. The specific and selective proteolysis of cTnI has been proposed to be the key mechanism for myocardial stunning as a result of activation of calcium-dependent proteases during cardioplegia arrest . MyocardThe occurrence of cardiomyocyte apoptosis increases with exposure to prolonged ischemia during cardioplegic arrest , 23. CarThere are several limitations to our study. We did not perform the histological examination of myocardial hypertrophy to clarify the intracellular collagen deposition and the hypertrophied cardiomyocytes. However, MRI data have indicated the significantly increased wall thickness. Long-term supracoronary banding of the ascending aorta was utilized to create myocardial hypertrophy. Pathological changes of hypertrophied pigs might be somewhat different from these of the patient hearts. Therefore, the recent findings could not be directly extrapolated into the clinical scenario. Another limitation of the study was that the study did not investigate the beneficial effect of empty-beating on the morphological integrity of coronary endothelium, the apoptosis occurring in endothelial cells, and the patency of microvasculature. Further studies are required to prove whether empty-beating technique prevents coronary endothelial dysfunction following cardioplegic arrest.NNBP was superior to NHCA in enhancing myocardial tissue perfusion, inhibiting myocardial cTnI degradation, and alleviating cardiac myocyte apoptosis and preserving heart contractile function in hypertrophied hearts for valve surgery.


Macrophages play a central role in the cellular inflammatory response to myocardial infarction (MI) and predict subsequent clinical outcomes. We aimed to assess temporal changes in cellular inflammation and tissue oedema in patients with acute MI using ultrasmallsuperparamagnetic particles of iron oxide (USPIO)-enhanced MRI.Thirty-one patients were recruited following acute MI and followed up for 3 months with repeated T2 and USPIO-enhanced T2*-mapping MRI. Regions of interest were categorised into infarct, peri-infarct and remote myocardial zones, and compared with control tissues.Following a single dose, USPIO enhancement was detected in the myocardium until 24 hours (p<0.0001). Histology confirmed colocalisation of iron and macrophages within the infarcted, but not the non-infarcted, myocardium. Following repeated doses, USPIO uptake in the infarct zone peaked at days 2–3, and greater USPIO uptake was detected in the infarct zone compared with remote myocardium until days 10–16 (p<0.05). In contrast, T2-defined myocardial oedema peaked at days 3–9 and remained increased in the infarct zone throughout the 3-month follow-up period (p<0.01).Myocardial macrophage activity can be detected using USPIO-enhanced MRI in the first 2 weeks following acute MI. This observed pattern of cellular inflammation is distinct, and provides complementary information to the more prolonged myocardial oedema detectable using T2 mapping. This imaging technique holds promise as a non-invasive method of assessing and monitoring myocardial cellular inflammation with potential application to diagnosis, risk stratification and assessment of novel anti-inflammatory therapeutic interventions.http://public.ukcrn.org.uk) and also ClinicalTrials.gov .Trial registration number: 14663. Registered on UK Clinical Research Network ( More than one person every minute suffers a myocardial infarction (MI) in the USA.After early neutrophil infiltration, monocyte-derived macrophages dominate the cellular infiltrate in the first 2 weeks following MI and sequentially coordinate digestion of damaged tissue and promotion of infarct healing.Ultrasmall superparamagnetic particles of iron oxide (USPIO) consist of an iron oxide core surrounded by a carbohydrate or polymer coating and are small enough to extravasate through diseased microvessels, where they are engulfed and concentrated by tissue-resident macrophages.In current practice, T2-weighted MRI is used to evaluate myocardial oedema after MI.In a recent proof-of-principle pilot study,This was an open-label observational cohort study. Patients were recruited within 7 days of acute MI. The study was performed in accordance with the Declaration of Helsinki, the approval of the local research ethics committee and the written informed consent of all participants.2) and contraindication to MRI or ferumoxytol infusion.Participants were aged 18–80 years and had sustained a recent MI according to the third universal definition of MI,Intravenous infusion of USPIO  was performed immediately following the baseline magnetic resonance scan over at least 15 min using a concentration of 2–8 mg/mL, diluted in 0.9% saline or 5% dextrose. Haemodynamic monitoring was conducted throughout.MRI and tissue histology were performed as described in the online supplementary material. A variable study protocol was used that was purposely designed for imaging at different time points after acute MI. Over a 3-month period following MI, patients received up to seven MRI scans and up to three infusions of USPIO. Two principal analyses were performed using data from the same participants.First, to assess the duration of a single dose of USPIO, R2* values of only the participants who first received USPIO within 7 days of MI (21/30) were included in this analysis. They were followed on all subsequent MRI scans prior to receiving any further doses of USPIO . On receSecond, to assess the duration of myocardial macrophage activity, USPIO uptake was compared using repeated USPIO infusions over the 3-month follow-up period. All patients were included in this analysis. USPIO uptake was calculated by subtracting the baseline R2* value from values obtained at 24 hours following USPIO infusion . This alFollowing clinical guidance for the administration of ferumoxytol, participants were allowed a maximum of two doses of USPIO in a 1-month period, and a total of three over the 3-month follow-up period to prevent iatrogenic iron overload. Therefore, USPIO-enhanced data were collected up to three times for each patient, and it was not possible to perform repeated USPIO-enhanced imaging at every time point in the same patient.Finally, to assess myocardial oedema, T2 values were compared on unenhanced scans (prior to and at least 7 days following USPIO administration). All patients were included in this analysis.2>0.85) was used to exclude data that did not have an acceptable exponential decay when signal intensity was plotted against echo time. The relaxation rate, R2*, is the inverse of the mean T2*, and was calculated to assess the uptake of USPIO for each region of interest (ROI), where the higher the value, the greater the USPIO accumulation.All T2*-weighted multigradient-echo images for each patient were analysed using Circle CVI software . An experimentally determined threshold used in previous workLate gadolinium enhancement (LGE), ventricular volume and functional analyses were determined manually using QMass software .LGE images at the 3-month time point were used to determine the distribution and anatomy of the myocardial infarct, and served as reference images to which each series of T2 and T2* scans at each separate visit could be visually coaligned. This allowed myocardial ROIs to be selected on the reference short-axis LGE images and manually applied to T2* images corresponding to (1) infarct zone (defined by the short axis slice showing greatest LGE volume), (2) peri-infarct zone , and (3) remote myocardium . Other selected regions included (4) liver, (5) spleen, (6) bone marrow, (7) kidney, (8) blood pool, (9) aortic wall (inside arch) and (10) skeletal muscle.T2 values were measured immediately prior to USPIO administration. USPIO-enhanced data were collected 24 hours following USPIO administration.All statistical analyses were performed with GraphPad Prism, V.6 . To assess the duration of USPIO enhancement in tissues following single administration in the first week after MI, R2* values on subsequent MRI scans (prior to any further USPIO dosing) were compared using one-way analysis of variance (ANOVA) with Tukey’s post hoc test for multiple comparisons.To assess variation and duration of myocardial inflammation, USPIO uptake (R2* increase from pre to 24 hours following USPIO) was compared using one-way ANOVA with Tukey’s post hoc test for multiple comparisons (repeated measures where appropriate). As a further method to assess USPIO accumulation within the heart, post-USPIO R2* 24 hours after administration (without baseline R2* subtraction) was compared in the same way.Finally, to assess variation and duration of myocardial oedema, T2 values for infarct, peri-infarct and remote myocardium were compared again using one-way ANOVA with Tukey’s post hoc test for multiple comparisons (repeated measures where appropriate). Statistical significance was defined as two sided, p<0.05.Thirty-one patients were recruited although 1 patient was excluded due to claustrophobia. A total of 147 MRI scans and 54 infusions of ferumoxytol were completed during the course of the study. Administration of ferumoxytol was well tolerated with no adverse reactions reported during or immediately after administration.Participants were predominantly middle-aged men with current or previously diagnosed hypercholesterolaemia or smoking habit . Around Twenty-one of the 30 participants received USPIO in the first week after MI and were included in this analysis.USPIO was detected by an increase in R2* in all myocardial regions, blood pool, kidney and aortic wall until 24 hours, being cleared by 4–9 days . USPIO w10.1136/heartjnl-2016-311018.supp1Supplementary dataMyocardial biopsies were taken from three of four patients undergoing CABG and revealed an abundance of inflammatory cells and early granulation tissue in keeping with a region of healing myocardium from around the infarct zone. Histological staining revealed colocalisation of the presence of iron (Prussian blue) and macrophages (CD68). No staining for iron or macrophages was seen within the adjacent regions of healthy myocardium .There were no differences in baseline (pre-USPIO) R2* value between infarct and remote myocardium at all time points. Time course variation in USPIO uptake was seen in the infarct zone over the 3-month period, peaking at days 2 and 3 . There w−1; 95% CI 33 to 79; p<0.001, +47 s−1; 95% CI 31 to 62; p<0.0001, and +33 s−1; 95% CI 4 to 61; p<0.05 at 2–3 days, 4–7 days and 10–16 days, respectively) but not thereafter  are ingested by tissue macrophages that can be visualised using MRI to highlight areas of inflammation after myocardial infarction (MI).The pattern of cellular inflammation after MI is distinct to tissue oedema. Myocardial macrophage activity is evident for 2 weeks after MI compared with the more prolonged period of myocardial oedema.USPIO-enhanced MRI may be of value in diagnosing active MI and ultimately may provide an additional diagnostic tool or provide risk stratification and serial imaging in assessing inflammatory processes affecting the heart.


However, LPoC and RPoC did not reduce the final infarct size , left ventricular volume , the incidence of microvascular obstruction  or the extent of microvascular obstruction . This meta-analysis shows that LPoC and/or RPoC improves myocardial salvage and decreases myocardial edema in STEMI patients without affecting final infarct size, left ventricular volume or microvascular obstruction.In this meta-analysis, we assessed cardiac magnetic resonance imaging data to determine the effects of local and remote ischemic postconditioning  on structural pathology in ST-segmentel elevation acute myocardial infarction (STEMI). We searched the Pubmed, Embase and Cochrane Library databases up to May 2017 and included 12 randomized controlled trials (10 LPoC and 2 RPoC)containing 1069 study subjects with thrombolysis in myocardial infarction flow grade 0~1. Weighed mean difference (WMD), standardized mean difference (SMD), and odds ratio (OR) were used for the pooled analysis. Random-effect model was used for the potential clinical inconsistency. LPoC and RPoC increased the myocardial salvage index ( Timely restoration of coronary perfusion is the most effective strategy to limit infarction size (IS) and improve clinical outcomesin patients with ST-segment elevation acute myocardial infarction (STEMI) . HoweverIschemic postconditioning (PoC) by brief, repetitive cycles of ischemia and reperfusion in the heart  , 6 or liCardiac magnetic resonance imaging (cMRI) has emerged as the most accurate and reliable tool for the evaluation of cardiac structure. Moreover, contrast-enhanced cMRI has been widely used to measure the infarct size with high spatial resolution –19. In an = 10), non-English reports (n = 3), had same trial numbers (n = 5), were non-RCT (n = 2), and endothelial trials (n = 8), studied STEMI patients with Thrombolysis in myocardial infarction (TIMI) flow grade ≥ 2 (n = 3), and non-STEMI patients (n = 20) and for not reporting the primary endpoints of interest (n = 28). Finally, we included 12 trials [n = 920; RPoC, (n = 149)undergoing cMRI assessment after percutaneous coronary intervention (PCI)  and demonstrated heterogeneity (I2 = 68.0%). Both LPoC and RPoC increased the potential of MSI(%), or RPoC  showed decreased percent myocardial edema  and showed significant heterogeneity . We observed that both LPoC and/or RPoC reduced the extent of MSI and myocardial edema, thereby offering cardioprotection. However, LPoC and RPoC did not affect final IS, LV volume, and the incidence or the extent of MVO. This meta-analysis is the first comprehensive analysis to evaluate structural effects of ischemic postconditioning in STEMI patients using cMRI.The protective potential of ischemic postconditioning (PoC) for STEMI patients has been confirmed in clinical trials by assessing cardiac enzyme levels and left ventricular function , 12 and ex vivo assessment of water content showed that LPoC reduced myocardial edema [in vivo myocardial edema by non-invasive T2-weighted imaging [et al. showed reduction in the extent of myocardial edema by LPoC in STEMI [During ischemia/reperfusion (I/R), the hydrostatic pressure within interstitial space increases and results in myocardial edema. This contributes to capillary compression and aggravates the extent of cell damage, which is characteristic of severe I/R injury. Since myocardial edema is central to I/R injury, it is critical to analyze the positive effects of ischemic postconditioning. In a dog model, al edema . Improve imaging , 33 has  imaging , 34. Thuin STEMI . Howeverin STEMI , 27, 30 in STEMI  have beein STEMI , 26 and in STEMI , 27, 30 in vivo without using radiation or contrast agents and accurately represents the size of area at risk [To address the effect of cardioprotective interventions on ischemia injury and myocardial edema, we selected T2 weighted cMRI, which is a water-sensitive technique that measures myocardial edema  at risk . Our ana at risk . Moreove at risk , 38. How at risk , 39. The2 ≥ 50% and assumed normalized distribution [The main strength of our meta-analysis was that we assessed multiple structural parameterssuch as final IS, MSI, left ventricular volume, MVO, and myocardial edema in two settings of ischemic postconditioning namely, LPoC and RPoC using cMRIin STEMI patients. On the other hand, there were several limitations in our study. First, we included veryfew trials and studies and were unable to access individual patient data. Therefore,we may have underestimated the potential influence of comorbid conditions such as diabetes, dyslipidaemia, multi-vessel disease, and LAD as well as effects of cardiovascular medications such as β-blockers , glycoprribution . But, weIn conclusion, our meta-analysis of cMRI data showed that both LPoC and/or RPoC reduced the extent of MSI and myocardial edema in STEMI patients. However, there were no improvements in final IS, LV volume, and the incidence or the extent of MVO.We performed this meta-analysis in accordance with PRISMA  . We searTwo investigators, Yadong Cui and Haiyang Gao, independently reviewed all abstracts and the full text according to the described search strategy and criteria. In case of disagreements, consensus was achieved by discussion. Quality assessment was performed according to the Jadad scoring system: randomization; blinding; withdrawals and dropouts. Each study obtained a score between 0 and 5 based on withdrawals and dropouts and those with a score ≥ 3 were considered high-quality .Data extraction included trial design parameters such asyear, country,protocol algorithm, conditioning delay, symptom-to-balloon time, and follow up, and demographic data of patients such as age, gender, and presence or absence of diabetes mellitus, hypertension, smoking, dyslipidemia, stenting technique, multi-vessel, left anterior descending artery disease(LAD), and treatment with glycoprotein IIb/IIIa inhibitor, β-blockers, and statins.We extracted endpoints assessed by structural cMRI imaging after PCI, which included primary endpoints such as final IS, MSI, and myocardial edema as well as additional endpoints such as LV volume and MVO. The final IS was assessed by late gadolinium enhancement of the cMRI images and expressed as percentage of LV mass . The MSI2 ≥ 50.0% as significant heterogeneity and used random-effects model for analyzing such parameters [P < 0.05 (2-sided) was considered statistically significant. All statistical analysis was performed by Stata version 9.0 and RevManversion 5.0 softwares.Data was expressed as mean ± standard deviation or median ± interquartile range for continuous variables. We calculated WMD or SMD for LVR to obtain the pooled estimates with 95% confidence intervals (CIs). For dichotomous ones (reported with incidence), we calculated odds ratio (OR) with 95% CIs. We set Irameters . P < 0.0


In adults, low ejection fraction (<30–35%), global peak systolic strain <-7.6%, increased EDV, ESV, LBBB, diastolic dysfunction, and left ventricle dyssynchrony were the main independent risk factors for major cardiac events and need for CRT or transplantation . Our conclusions were that in children and adults, DCM is a diverse disorder with outcomes that depend largely on cause, age, heart failure status at presentation, and echocardiographic parameters of the heart . This study will present new findings in the diagnostic area.Dilated cardiomyopathy (DCM) is the most common form of cardiomyopathy and cause of cardiac transplantation in children and young adults; mortality is high among this patient population. However, mortality, clinical course, and illustrative echocardiographic data of DCM in children and adults are not well established. Our objective was to provide a research article of detailed descriptions of the incidence, causes, outcomes, related risk factors, and new echocardiographic criteria of risk of death from DCM. Our results showed that independent risk factors at DCM diagnosis for subsequent death or transplantation in children cohorts were older age, congestive heart failure, lower left ventricular ejection fraction (EF ≤ 25%), low global strain, significant mitral valve incompetence, pulmonary hypertension, diastolic dysfunction, right ventricular involvement, and cause of DCM (


In the current era, cardiovascular disease is the leading cause of death in patients with Duchenne muscular dystrophy (DMD). Pathological studies demonstrate myocardial fibrosis that begins in the subepicardium of the left ventricular free wall. Late gadolinium enhancement (LGE) images demonstrate a similar pattern of extracellular matrix (ECM) expansion. However, based on a baseline pro-inflammatory state and reports of possible myocarditis in DMD subjects, it is unclear whether this LGE represents edema or fibrosis. Our objective was to use extracellular volume (ECV) and T2 mapping to better characterize LGE in boys with DMD.21 DMD subjects and 11 healthy male controls were prospectively enrolled. Subjects underwent cardiac MRI including standard functional analysis and LGE as well as T1 and T2 mapping in the short axis at the level of the papillary muscles. Pre and post-contrast T1 maps and a hematocrit were used to calculate ECV maps. Manual contours were traced on ECV and T2 maps to determine global and segmental values. Focal regions of interest (ROI) in areas of significant LGE were traced on ECV maps. Values were compared between DMD and controls using a Wilcoxon rank-sum test.DMD subjects were younger than controls  and had a similar LVEF . 4 DMD subjects had LVEF < 55% and 12 had positive LGE. Global ECV was significantly elevated and global T2 was decreased in all DMD subjects compared with controls . Normal cut-offs of 0.27 and 50.5 ms were derived for ECV and T2, both of which represent 2 standard deviations above the mean of control subjects. One DMD subject had global T2 greater than 50.5 ms Figure . AnalysiIn this cohort, two DMD subjects had subjectively elevated T2 suggestive of focal inflammation or edema. The majority of DMD subjects had normal or decreased T2 and increased ECV in segments with LGE, suggesting that fibrosis is the primary etiology of ECM expansion.


Conventional 2 dimensional (2D) cine MRI of myocardial motion is limited in its ability to describe the complex 3 dimensional (3D) motion of the heart due to sparse coverage and inconsistent breath-holding. So far, clinical feasibility of 3D cine imaging has been limited due to the long acquisition times and requirements for acceleration techniques that are not routinely available.We demonstrate the use navigator-gated 3D cine acquisition that can be performed with routine acceleration techniques within the time constraints of clinical MRI scans.We compared the accuracy, reproducibility and image quality of 3D steady-state-free-precession (SSFP) cine imaging of the heart with conventional 2D SSFP cine imaging for the assessment of cardiac volumes, global and regional myocardial function.10 female subjects from the Twins UK cohort with no overt cardiac disease were prospectively recruited for a CMR study. Both conventional 2D short axis and 3D whole heart SSFP cine images were acquired in all ten cases. Patients with atrial fibrillation, valvular disease, regional wall motion abnormalities or areas of myocardial enhancement were excluded from the analysis. 3D scan parameters: FOV 320-400 mm; Acquired in-plane resolution 2 × 2 mm. Slice thickness 2 mm; b-FFE; parallel imaging acceleration 2; half-Fourier-factor 0.6; TR 3.7 / TE 1.87; flip angle 60; cardiac phases 25; scan duration 3 to 3.3 min, acquired in 10-12 breath-holds with navigator tracking. Volumetric and deformation analyses were done using semi-automatic contouring techniques with manual correction (Circle Cardiovascular Imaging v5.1.0).Right (RV) and left (LV) ventricular volumes, global and regional strain and the LV systolic dyssynchrony index (LV-SDI) were compared for the two acquisitions. Intraclass correlation (ICC), Blant-Altman, inter- and intra-observer variability were analysed.r=.96, p<.01; LV-ESV -.58 ± 4.7 ml, r = .88 p < .01; LV-SV 3.1 ± 6.8 ml, r=.84 p = .01; RV-EDV 3.3 ± 7.9 ml, r = .92 p < .01; RV-ESV 0.8 ± 4.0 ml r = .89 p < .01; RV-SV -0.7 ± 4.2 ml, r = .96 p < .01), global circumferential strain (r=.85 p < .01) and global radial strain (r = .90 p < .01). The LV systolic dyssynchrony index is lower in the 3D acquisition when compared to the 2D SSFP images. Overall mean inter- and intra-observer correlation show better correlation for 3D than for 2D acquisition . Image quality was no different between sequences .3D SSFP cine images showed good agreement with conventional 2D SSFP cine imaging for cardiac volumes (LV-EDV 2.3 ± 4.7 ml, Routine 3D SSFP cine imaging is feasible within clinical time constraints and without a loss of image quality or loss of agreement in absolute functional parameters compared to 2D measurements. More detailed coverage results in improved inter-observer agreement and reduced LV-SDI. The navigator-correction for the 3D approach also removed inaccuracies from slice mis-registration due to inconsistent breath-holding.


Indexed left atrial volume (LAVi) is a robust predictor of adverse cardiovascular events. A minority of patients with moderate-to-severe left ventricular (LV) systolic dysfunction maintain normal LAVi. We followed clinical and echocardiographic parameters for at least 6 months to understand how this population is different from patients with similar systolic dysfunction and dilated left atria. n=817) and “severely dilated” (n=1094) LA size and LV ejection fraction (EF) ≤ 35% on echocardiogram reports from 2009 to 2015. We analyzed 115 subjects for LAVi, biplane EF, and diastolic parameters over 2 echocardiograms at least 6 months apart. Younger age, white race, being on an angiotensin-converting enzyme inhibitor, smaller end-diastolic LV volume (LVEDV), and longer deceleration time (DT) were associated with having a normal LAVi. The receiver-operating characteristic curve has an area under the curve of 0.95 (p < 0.0001) for this model. An increase in LVESVi and early mitral flow velocity and a decrease in DT explain 32% of the variance seen in LAVi increase over time.  We searched our electronic medical records for “normal” ( In patients with moderate-to-severely reduced EF, younger age, being on heart failure therapies, and better diastolic dysfunction were independently associated with a normal LAVi. Improvement in systolic and diastolic performances was associated with decreasing LAVi with 6-month to 1-year follow-up. Indexed left atrial volume by body surface area (LAVi) is a robust predictor of advanced cardiovascular diseases, including atrial fibrillation, heart failure, stroke, and mortality –4. In thWe searched our electronic medical records using a natural language search tool PennSeek for “normal” and “severely dilated” LA size and “severely depressed ejection fraction” or “EF ≤ 35%”  on the echocardiogram (TTE) reports from 2009 to 2015. From this list, we excluded subjects on mechanical circulatory support, with heart transplant, greater than mild valvular heart disease, congenital heart disease, and atrial fibrillation. Only subjects with at least 2 TTEs 6 months apart with adequate images for assessment were included. Subgroup analysis was performed on a select group with at least 1 year between the baseline and follow-up TTE. We then performed biplane LVEF on these TTEs and excluded those with LVEF > 40% on the baseline TTE . Baselin2, mild and moderate: 35–48 ml/m2, and severe: >48 ml/m2) [We measured LAVi by the biplane area-length method using apical 2- and 4-chamber views and indexed by body surface area . Volume 8 ml/m2) . Measuret-test. Categorical variables were expressed as count and frequency and were compared using a chi-squared test. The significance was considered at the 2-sided alpha level of 0.05.The baseline characteristics of the study population were summarized by normal LAVi versus dilated LAVi groups as defined above. Continuous variables were expressed as mean ± standard deviation and compared using a 2-group p value of forward selection and backward selection both equal to 0.2. For the multivariate stepwise selection process, the significant level is usually larger than the traditional level of significance. As discussed by Bendel and Afifi [To explore the factors that may affect subjects being in the normal or dilated LAVi groups, a multivariate logistic regression was conducted using a stepwise variable selection approach with nd Afifi  and Micknd Afifi , more trp value of forward selection and backward selection both equal to 0.2 for the 6-month follow-up cohort and 0.05 for the 1-year follow-up subgroup. The dependent variable for this multivariate general linear model was the LAVi change between the two assessments, and the independent variables included age, race, baseline LVEDVi and LVESVi, creatinine, ACE-I use, nitrate use, LVEF, early and late mitral inflow velocities and their ratio, deceleration time, septal, mitral, and average mitral annular velocities, the ratio of the mitral inflow velocity to the average mitral annular velocity, and the changes in these variables between the two assessments. The final results were presented as variables selected into the final model, along with the variance of each of these variables explained in LAVi variance seen in this patient population. Both of the above analyses were done in the original cohort as well as a subgroup with at least 1 year between the baseline and follow-up TTE. Statistical analyses were performed using STATA 13.0  and SAS 9.4 .To better understand the impact factors for LAVi changes, we applied a multivariate general linear model using the same stepwise variable selection technique, with n=26), persistently dilated (n=48), or change  in LAVi. In the 115 patients included for analysis, the mean age was 58.4 ± 14.2 years and 32% were female. Demographic and baseline characteristics of persistently normal and persistently dilated subjects are summarized in We found 816 patients in the normal LAVi group and 1094 in the dilated LAVi group. The majority of patients met at least one exclusion criterion ; thus, wp < 0.01), body mass index , N-terminal pro-brain natriuretic peptide , creatinine , and LVEF , white race , being on ACE-I therapy , decreased LVEDVi , and longer deceleration time . The model predicted an area under the curve of 0.95, p < 0.0001 , white race , being on ACE-I therapy , and higher E-to-A ratio . The model predicted an area under the curve of 0.94, p < 0.0001 , there were many patients who experienced a significant increase or decrease in LAVi over the 2 time points. Using a multivariate model with stepwise variable selection, we found that changes in LVESVi , early mitral inflow velocity , and deceleration time  between time points 2 and 1 were each significantly associated with change in LAVi  and LVESVi  were associated with a change in LAVi (total variance accounted for was 24%; Subgroup analysis and the multivariate model with stepwise variable selection on patients with one year between the initial and follow-up TTE similarly showed that changes in early mitral inflow velocity (0.16 ± 0.04, We examined a group of patients with reduced LVEF and normal LA size for clinical factors and echocardiographic parameters which distinguished them from their counterparts with severely dilated LA. Baseline factors including younger age, white race, being on ACE-I therapy, decreased LVEDVi, higher early-to-late mitral inflow velocity, and longer deceleration time were independently associated with having a normal LAVi. Longitudinally, an increase in LVESVi and early mitral inflow velocity as well as a decrease in deceleration time was associated with an increase in LAVi.In this study, we found younger age to be an independent predictor of normal LA size in the setting of reduced LVEF. A number of studies have similarly demonstrated that LAVi increases with increasing age , 13–16. In our study, patients with normal LA size were more likely to be white compared to other nonwhite races. There is little known about the relationship between the race and LA size. The Cardiovascular Health Study examined LAVi as a predictor of prevalent and incident heart failure and found that control subjects free of cardiovascular disease were less likely to be black and a higher percentage of black patients with prevalent heart failure had systolic heart failure compared to diastolic heart failure . In a reThe relationship of the LA size and diastolic function has been extensively studied in patients with normal LVEF , 22–24. In the present study, smaller LVEDVi correlated with having a normal LAVi, consistent with our physiological understanding of pressure volume loops. Zile et al. studied patients with clinical heart failure with a normal LVEF and plotted pressure volume loops that showed that, in patients with a normal LVEF, a small increase in LVEDVi results in an exponential increase in LV end-diastolic pressure, indicating low compliance. These patients are said to have diastolic dysfunction arising from a stiff ventricle . PatientOur study is limited by the small sample size and the retrospective nature of the study. The small sample size of the normal LAVi group in the setting of LV systolic dysfunction might be inherent in the patient population that we were attempting to study. Additionally, we used echocardiographic parameters to estimate diastolic function due to limited availability of cardiac catheterization data, and isovolumetric relaxation time was not included in the parameters for assessment of diastolic function.In a carefully assessed group of patients with moderate-to-severely reduced LVEF, younger age, white race, being on ACE-I therapy, smaller LVEDVi, and longer deceleration time were associated with maintaining a normal LAVi over a period of at least 6 months. Over a longer period of a year, in addition to the clinical parameters, better systolic performance as indicated by smaller LVESVi and better diastolic performance were associated with decreased LAVi.


Several studies have reported the accuracy and reproducibility of HeartModel for automated determination of three-dimensional echocardiography (3DE)-derived left heart volumes and left ventricular (LV) ejection fraction (LVEF) in adult patients. However, it remains unclear whether this automated adaptive analytics algorithm, derived from a ‘training’ population, can encompass adequate echo images in Chinese adolescents.The aim of our study was to explore the accuracy of HeartModel in adolescents compared with expert manual three-dimensional (3D) echocardiography.Fifty-three Chinese adolescent subjects with or without heart disease underwent 3D echocardiographic imaging with an EPIQ system (Philips). 3D cardiac volumes and LVEF obtained with the automated HeartModel program were compared with manual 3D echocardiographic measurements by an experienced echocardiographer.r = 0.875–0.965, all P < 0.001). Automated LV and left atrial (LA) volumes were slightly overestimated when compared to expert manual measurements, while LVEF showed no significant differences from the manual method. Importantly, the intra- and inter-observer variability of automated 3D echocardiographic model was relatively low (<1%), surpassing the manual approach (3.5–17.4%), yet requiring significantly less analyzing time .There was strong correlation between HeartModel and expert manual 3DE measurements (Simultaneous quantification of left heart volumes and LVEF with the automated HeartModel program is rapid, accurate and reproducible in Chinese adolescent cohort. Therefore, it has a potential to bring 3D echocardiographic assessment of left heart chamber volumes and function into busy pediatric practice. Precise and fast as well as reproducible measurements of left atrial (LA) and left ventricular (LV) volumes and systolic function are the most common and important tasks of transthoracic echocardiography (TTE), which is clinical relevant in the diagnosis, prognosis and risk stratification of various congenital and acquired heart diseases in the young. Conventional M-mode and two-dimensional echocardiography 2DE) are the most ubiquitous and non-invasive tools for chamber quantification and cardiac function, the aforementioned methods however are limited by geometric assumption, image foreshortening and inter/intra-observer variability, and thus compromise the accuracy and reproducibility in clinical decision making and research investigations , 2, 3. RDE are thConsequently, with evolvement in Anatomical Intelligence Ultrasound (AIUS), a novel automated 3DE software (HeartModel) emerged and offers an option of simultaneous quantification of LA and LV volumes and LVEF within seconds avoiding any human interaction. HeartModel is reliable to measure LA and LV volumes in adults (age >35 years), which has been validated with cardiac magnetic resonance (CMR) , 14, 15.Thus, the aim of this study was to explore the accuracy and reproducibility of the HeartModel program for automated measurement of LA, LV volumes and LVEF from 3DE datasets in the adolescents, using expert manual 3DE as reference.This study was a part of a community-based follow-up study for persistent masked hypertension in Hong Kong pediatric population in 2015/2016. The inclusion criteria were adolescents with persistent masked hypertension who had been initially screened from the Hong Kong community in 2011/2012 according to the local ambulatory blood pressure reference . The comComprehensive transthoracic with standard 3D echocardiography was performed using an EPIQ ultrasound system with X5-1 matrix array transducer . For 3DE section, imaging settings were optimized for endocardial visualization before each acquisition. A novel single-beat acquisition mode (HM ACQ key on EPIQ 7C) was utilized to obtain one-beat full-volume 3DE datasets. Special care was taken to include the entire LA and LV cavity within the pyramidal 3D volume. At least three dynamic pyramidal datasets were acquired and stored for each individual, and the best single-beat 3DE full-volume dataset was selected for offline analysis. All 3D images were respectively analyzed offline with both manual  and prototype-automated software packages  by an experienced reader to calculate LV/LA volumes and LVEF.Using an adaptive analytics algorithm, the HeartModel program automatically determines global cardiac shape orientation and detects LA and LV endocardial surfaces from a 3DE database, containing approximately 1000 3D-TTE datasets of varying image quality in patients with a wide range of function and morphologies. The program matches relevant image features of the given LV volume to the database. This selected model is then locally adapted to the LV volume under study using a series of adaptations. LV end-diastolic volume (EDV) was selected using motion analysis near the peak of the electrocardiographic R-wave. LV end-systolic volume (ESV) was determined using motion analysis to identify the minimal volume , 14. TheManual 3D quantification of LV volumes and LVEF as well as LAV at LVES was performed offline on a QLAB workstation  by an experienced investigator blinded to the results of automated 3D model. Cardiac chamber quantification starts by aligning the extracted LV 4-chamber and orthogonal views to avoid foreshortening. Subsequently, the end-diastolic (largest LV volume) and end-systolic  frames are identified. On both ED and ES frames, 4 mitral annular and 1 apical points were then placed on the LV as landmarks in each of the views. LV endocardial contours were tracked in every slice semi-automatically frame by frame throughout the entire cardiac cycle. Unsatisfactory delineation of the endocardial border was manually edited, and the final LVEDV, LVESV and LVEF were then displayed. For the manual 3D measurement of LA volume, the long-axis of the LA was identified at LVES in the 4- and 2-chamber cut-planes, and the blood–tissue interface was traced semi-automatically to obtain maximum LAV. The time required to manual measurements of LVEDV, LVESV, LVEF and LAV at LVES from 3DE datasets was also recorded.To determine the reproducibility of 3D volumetric quantification by each imaging modality, HeartModel and manual 3DE analysis were repeated in a randomly selected group of 30 study subjects by another investigator (novice) as well as by the same primary reader (expert) at least 10 days later. Inter-observer and intra-observer variability were calculated as the mean percentage error, defined as the absolute difference of the corresponding pair of repeated measurements as a percentage of their mean in each patient and then averaged over the study group.In addition, test–retest reproducibility was assessed in 30 separate subjects. After obtaining the initial 3DE dataset, the sonographer stopped echo scanning for 5 min, and then repositioned the subject and the transducer to obtain a second dataset. LV/LA volumes and LVEF were measured in a fully automated manner as described here. During all repeated analyses, the investigators were blinded to the results of all previous measurements.s.d. and nominal variables as percentages. The agreement of HeartModel program with the expert manual 3DE reference values for LVEDV, LVESV, LVEF and LAV was evaluated using Bland–Altman analysis to assess the bias (mean difference) and the limits of agreement . To verify the significance of the biases, paired t-test with a two-tailed distribution was performed. The relationship between HeartModel and the manual measurements was evaluated using linear regression with Pearson correlation coefficients. The paired t-test was also used to compare chamber volumes and LVEF between the two analyzing programs. Two-tailed P values <0.05 were considered statistically significant.Statistical analysis was performed with the IBM SPSS Statistics, version 21 (IBM) software. Continuous variables are expressed as mean ± Patient characteristics are presented in r = 0.875–0.965, all P < 0.001) (P < 0.001) (P = 0.38)  , C and D< 0.001) . However = 0.38) . Mean di = 0.38) , G and HThe results of the reproducibility analysis were summarized in P = 0.14), 39 ± 11 mL vs 40 ± 11 mL (P = 0.20), 63 ± 5% vs 63 ± 5% (P = 0.66), and 38 ± 9 mL vs 38 ± 10 mL (P = 0.69). The corresponding Pearson r values were 0.97, 0.97, 0.92 and 0.95 , respectively. Bland–Altman analysis showed minimal bias between the two measurements with excellent agreement (Test–retest variability (2.5–5.9%) of the automated program by using a different dataset was higher than the inter-observer variability. The LVEDV, ESV, LVEF and LAV at LVES for the first and second measurements were as follows: 104 ± 22 mL vs 105 ± 22 mL , approximately a tenth of the time using manual method (P < 0.001).The average time needed for volumetric analysis was significantly shorter using HeartModel compared to manual 3DE method , high reproducibility and shorter analysis time in adult patient group , using endocardial contouring settings at 40% at end-diastole and 8% at end-systole set by our center. The automated LVEF measurement using HeartModel was accurate and similar to the expert manual measurements, whereas LV volume measurements using this automated program were slightly overestimated. Hence, we can infer that HeartModel represents an accurate and rapid method in pediatric clinic to quantify cardiac volumes and LVEF from 3DE datasets when endocardial boundary recognition is properly setting.To date, several recent publications indicated that HeartModel had strong correlations with the expert manual 3DE and CMR , Food and Health Bureau, Hong Kong SAR Government, Peoples’ Republic of China.


Patients were divided into two groups (HF and non-HF) based on left ventricular ejection fraction and plasma proBNP level. After CABG, 67% of patients developed HF. The mean distance 1 month after CABG in HF was 397 ± 85 m versus 420 ± 93 m in non-HF. PPARγ mRNA expression was similar in both HF and non-HF groups. 6MWT distance 1 month after CABG was inversely correlated with PPARγ level only in HF group. Higher PPARγ expression was related to smaller LVEF change between 1 month and 1 year , especially in patients with HF. Higher initial levels of IL-6 in HF patients were correlated with longer distance in 6MWT one month after surgery and lower PPARγ expression. PPARγ expression is not related to LVEF before CABG and higher PPARγ expression in the myocardium of patients who are developing HF following CABG may have some protecting effect.Activation of PPARs may be involved in the development of heart failure (HF). We evaluated the relationship between expression of PPAR Heart failure (HF) is characterized by reduced reserve of the cardiac output. Impaired functional capacity in patients with heart failure is common and results from inability to achieve sufficient oxygen and nutrients delivery and altered washout of metabolites from working muscles.α or IL-6, which is characteristic for chronic HF, may be responsible for altered muscular structure and function . Informed consent was obtained from all participants.p < 0.05 was considered statistically significant. Analysis was performed using Statistica 9.0PL.Data are presented as mean ± SD for quantitative variables or percent of study group for qualitative variables. Specific parameters of both groups (group with and without heart failure at baseline) and change in parameter values during follow-up were compared using chi square test and ANOVA with post hoc analysis. Correlations between variables were tested using Pearson's method. A value of p = 0.002) and 24 months after CABG it was significantly longer than in HF group . However the distance of 6MWT one month after CABG was inversely correlated with myocardial PPARγ level  only in patients developing HF during the follow-up and was not present in those without HF (γ gene in the myocardium was not correlated with left ventricular ejection fraction (LVEF) before or after CABG . The relation described was more pronounced in those patients, who developed HF during the follow-up  and was not significant in patients without HF (p < 0.0001 for the trend). Before CABG there was negative correlation between concentration of IL-6 in plasma and PPARγ expression . In patients who developed heart failure higher initial levels of IL-6 were correlated with longer distance in 6MWT one month after surgery .157 patients were qualified to the study. All patients did not have heart failure before CABG. After 1 month of CABG, 67% of patients developed heart failure. During 2-year follow-up the number of patients has been reduced in 1 year to 124 and in 2 years to 86 because of the loss of connection. In the HF group one patient died because of myocardial infarction in 1 year after CABG. The baseline characteristics of the study group were presented in the previous paper . One monthout HF . Althougter CABG , higher thout HF . The conThe six-minute walk test (6MWT) is a submaximal exercise test for evaluating physical functional capacity. Fiorina et al. suggest that 6MWT is feasible and well tolerated in adult and older patients shortly after uncomplicated cardiac surgery and provides reference values for distance walked after cardiac surgery . In our γ expression and cardiac function or exercise capacity after CABG is very scant. In addition existing experimental data present contrasting results about the influence of PPARγ on cardiac function. On one hand, overexpression of PPARγ in transgenic mice was reported to evoke accumulation of lipids and glycogen and distortion of mitochondrial architecture leading to dilated cardiomyopathy [γ with its agonist reduced lipotoxicity and improved cardiac function [γ in the myocardium of anthracycline-induced cardiomyopathy in rodents, and treatment with an angiotensin converting enzyme inhibitor restored normal level of PPARγ but was not sufficient to restore normal cardiac function [Literature describing potential links between myocardial PPARmyopathy . On the function . Expressfunction . Cerneckfunction .γ expression at the time of CABG and left ventricular size or ejection fraction at any time point. The level of PPARγ in the myocardium was not able to predict development of heart failure after CABG, as was shown in our previous work [γ level seems to preserve the systolic function of the left ventricle. On the other hand, also only in patients developing HF, PPARγ expression was inversely correlated with exercise capacity during the follow-up. It should be emphasized that left ventricular systolic function, if not significantly depressed, is not related to the exercise tolerance, but abnormalities of its diastolic function are independently associated with exercise capacity [γ in the myocardium at all. Possible protective effect of PPARγ on the cardiac function may be related to suppression of the excessive inflammatory process and inhibition of apoptosis [α, ET-1, and IL-6, plays a pathogenic role in heart failure [γ expression and IL-6 level only before CABG, when none of patients had features of heart failure. A subgroup of patients who developed HF and had higher initial levels of IL-6 had also better exercise capacity at one-month follow-up, which may reflect the protective role of IL-6 on skeletal muscle physiology, which is more important for skeletal muscle function and exercise capacity than weak PPARγ-related phenomena affecting cardiac muscle.Our data showed no clear relation between PPARous work . Howevercapacity . In our poptosis , 26. Per failure , 28. In  failure , 30 and  failure  that res failure . We founγ in myocardium of patients who developed HF after CABG were correlated with smaller attenuation of LVEF, reduced plasma level of IL-6, and worsening of exercise tolerance.Higher levels of PPARγ expression in the myocardium was not related to left ventricular systolic function before CABG. However higher levels of PPARγ gene transcript in the myocardium of patients who develop heart failure following CABG may have some protecting effect on cardiac contractility, which seem not to be directly related to exercise capacity.These results indicate that PPAR