Heart transplantation is an accepted therapeutic modality for end-stage congenital heart disease for both biventricular and univentricular anomalies. Many transplant centers have pushed the limits of transplantation to include patients with high pulmonary vascular resistance, high panel reactive antibodies, positive cross-matches, and ABO-incompatibility. Excellent results have been possible, particularly with the development of improved diagnostic and therapeutic algorithms to prevent and treat rejection, infection, and post-transplant lymphoproliferative disease. Late graft failure and chronic rejection remain vexing problems. The vast majority of patients with biventricular congenital heart disease have undergone prior cardiac surgical procedures. Indications for transplantation in this subgroup are primarily progressive refractory heart failure following prior cardiac surgical reconstructive procedures. Contraindications to transplantation mimic those for other forms of end-stage heart disease. A determination of pulmonary vascular resistance is important in listing patients with biventricular congenital heart disease for heart transplantation. Modifications in the implant technique are necessary and vary depending on underlying recipient anatomy. Risk factors for perioperative outcomes in patients with biventricular congenital heart disease include the need for reoperation, the degree of anatomic reconstruction necessary during the implant procedure, and the degree of antibody sensitization, in addition to a number of other recipient and donor factors. Postoperative outcomes and survival are very good but remain inferior to those with cardiomyopathy in most series. In conclusion, patients with end-stage biventricular congenital heart disease represent a complex group of patients for heart transplantation, and require careful evaluation and management to ensure optimal outcomes. The first pediatric heart transplant was performed in 1967 for an eighteen day old patient with congenital heart disease (CHD) consisting of Ebstein’s anomaly [There is an increasing body of literature concerning heart transplantation for CHD, both in pediatric and adult recipients. Since the majority of CHD lesions can be repaired or palliated, primary heart transplantation has a very limited role in the management of these patients. This is in contradistinction to the 1980’s, when a number of centers, including ours, performed primary heart transplantation for hypoplastic left heart syndrome (HLHS). Improved outcomes following staged palliation for single-ventricle lesions, including HLHS, as well as inevitable waiting list mortality, have swung the pendulum towards palliation or repair of CHD rather than primary transplantation. As a result, in the last two decades, the majority of CHD patients undergoing heart transplantation have failed prior cardiac surgical procedures. There is little data regarding heart transplantation for CHD patients with only biventricular physiology. Published studies have grouped all patients with CHD into one entity, and compared the outcomes of CHD patients to other patient populations, most notably cardiomyopathy. The largest single subset of patients with CHD who undergo heart transplantation have failed surgical palliation for single-ventricle lesions. End-stage CHD of the biventricular form is a heterogeneous group of patients, almost all of whom have undergone prior surgical repair. This monograph will highlight the indications, contraindications, recipient anatomic considerations, donor evaluation, surgical techniques, survival, and long-term outcomes following heart transplantation for biventricular CHD, both in adult and pediatric recipients. Since there are no randomized clinical trials, the recommendations are based on single-center or registry reviews as well as expert clinical opinion. Further, since results for patients with biventricular versus univentricular CHD have not been routinely compared in most studies, overall conclusions about survival and outcomes for patients with only biventricular CHD are difficult to determine, particularly considering the wide heterogeneity in recipient diagnoses, prior operations, age, and clinical status.The indications for heart transplantation are covered elsewhere in this issue. There are three broad subsets of patients: those with CHD, those with cardiomyopathy, and those undergoing retransplantation. Since 1990, the percentage of patients with CHD has been decreasing while the percentage of patients in the other two categories has been increasing. This is primarily due to the avoidance of heart transplantation as primary therapy for patients with HLHS. In the current era, CHD is present in two thirds of pediatric recipients, compared to 80% in earlier eras when transplantation was used as primary therapy for HLHS . Data frIn biventricular CHD, there are three main indications for heart transplantation:Refractory heart failure: this represents the most common indication for heart transplantation. While the long-term results of surgical repair for CHD are quite good, survival is inferior to that of the general population. A number of patients will have poor systemic ventricular function, often late following palliation or correction of CHD. This may be due to myocardial injury sustained during repair, poor myocardial preservation during surgery, or idiopathic progressive ventricular dysfunction, all of which are amenable to heart transplantation. While any patient with CHD can experience heart failure, the more common diagnoses are listed below:                        Transposition of the great arteries (TGA): Patients with D-TGA who underwent the Mustard or Senning atrial switch procedures in the 1970’s and 1980’s can experience progressive heart failure since the systemic ventricle is a right ventricle. This can result in progressive ventricular dysfunction, resulting in severe systemic atrioventricular valve insufficiency. Survival is inferior to age-matched controls [                        controls . AnotherTetralogy of Fallot: Patients entering the third decade of life following repair of tetralogy of Fallot have decreased survival compared to age-matched controls [                        controls . In someUnreconstructable CHD: with advancements in cardiac surgical techniques, this entity has become increasingly rare. With the plateau of pediatric heart donors in the United States at 360 annually, there is significant waiting list mortality, particularly for the youngest patients. As a result, every attempt is made to repair or palliate CHD, in order to prolong the use of the native heart as long as possible. A number of rare lesions not amenable to surgical intervention are listed below, most of which fall in the category of univentricular CHD:                        Coronary circulation anomalies: Patients with pulmonary atresia with intact ventricular septum (PAIVS) along with right-ventricle dependent coronary circulation are at high risk for sudden death due to tenuous coronary perfusion [                        erfusion . This isNeonatal Ebstein’s anomaly: Patients with severe neonatal Ebstein’s anomaly have marked cardiomegaly from severe tricuspid insufficiency, significant right atrial dilation, poor right ventricular function, and functional pulmonary atresia, with poor antegrade flow into the pulmonary arteries. Surgical repair carries high risk in symptomatic neonates with severe Ebstein’s anomaly [                         anomaly . PrimarySevere multi-valve disease: Most atrioventricular or semilunar valve insufficiency or stenosis can be addressed surgically without transplantation. In a subset of patients, the risks of valve repair or replacement are high, especially if multiple valves are involved, usually in the setting of single-ventricle physiology. Rarely, this may occur in patients with biventricular CHD. Primary heart transplantation should be considered on an individualized basis.                        Complex heterotaxy syndromes: The vast majority of heterotaxy patients undergo surgical intervention: most undergo staged palliation to achieve a single-ventricle circulation, while a minority undergo biventricular repair. A small subset of patients with heterotaxy syndromes with severe atrioventricular or semilunar valvar abnormalities along with associated total anomalous pulmonary venous return, may be considered for primary heart transplantation in select circumstances [                        mstances . Refractory life-threatening arrhythmias: this is seen in a minority of patients, most of whom have structurally normal hearts without CHD. These ventricular arrhythmias can not be controlled by automatic implantable cardioverter defibrillator devices, medications, or ablation techniques. Transplantation may be offered as an option of last resort.                        A recent analysis of 307 pediatric heart transplant patients from our institution transplanted over a 24 year period  revealedThe largest cohort of patients with biventricular CHD undergoing heart transplantation comes from Lamour and coworkers  who mergThe group at Columbia University analyzed 106 patients with complex congenital heart disease, both univentricular and biventricular, who underwent heart transplantation . Unlike As a result of the above studies, patients with biventricular CHD undergoing heart transplantation belong to the following three patient substrates:Progressive systemic right ventricular failure: This occurs in the setting of unrepaired or physiologically-repaired congenitally-corrected TGA or following atrial switch procedures for D-TGA [                        or D-TGA . It repror D-TGA .Progressive systemic left ventricular failure: A number of these patients may have septal defects . Patients with coronary complications following the arterial switch procedure for D-TGA also fall in this category.                         Progressive right ventricular failure: This occurs primarily in patients with tetralogy of Fallot or double outlet right ventricle following surgical repair, where the systemic ventricle is a left ventricle. Severe Ebstein’s anomaly also falls into this category.                        There are a number of contraindications to heart transplantation, which are covered elsewhere in this issue. The following list represents contraindications to transplantation, which applies to patients with biventricular CHD as well as any other patients undergoing consideration for heart transplantation:Multiorgan dysfunction or failure: severe hepatic or renal dysfunction is a relative contraindication since low cardiac output may be the reason behind the liver or kidney disease. Patients with either liver or kidney disease are at increased risk for early mortality following heart transplantation [                        antation . Often, Elevated irreversible pulmonary vascular resistance (PVR): A determination of PVR is essential for listing for heart transplantation, and is especially applicable to patients with biventricular CHD. In the past, a PVR > 4 Wood units*m2 without response to pulmonary vasodilators was considered a contraindication for heart transplantation [2 and a transpulmonary gradient below 15 mm Hg [2 may still be considered for transplantation albeit at increased risk. Other centers have used a cutoff of 5 Wood units*m2 and a transpulmonary gradient below 12 mm Hg [2, then physiologic testing with pulmonary vasodilators, such as inhaled nitric oxide, 100% oxygen, prostaglandins, or adenosine, should be performed. If the PVR drops below 7 Wood units*m2, then transplantation may be offered, although the perioperative mortality and morbidity will be increased due to pulmonary hypertension. Careful donor selection is important to achieve an acceptable outcome in these high-risk patients. Some have advocated the use of oversized male donors in order to improve perioperative outcomes. Pulmonary vasodilators, including inhaled nitric oxide and milrinone, should be used liberally in the postoperative period. If the PVR does not fall with physiologic testing during the pre-transplant evaluation, then patients should be placed on chronic pulmonary vasodilators such as intravenous prostacyclin, oral sildenafil or bosentan, in combination with inotropic support in order to decrease the left ventricular end diastolic pressure. Repeat determination of the PVR should be performed every 3-6 months. In some patients, pulmonary vascular remodeling may render them candidates for heart transplantation. In others, implantation of a ventricular assist device can result in a decrease in the PVR, thought to be due to unloading of the left ventricle, resulting in a decrease in the left atrial pressure [                        antation . With ad15 mm Hg . Patientpressure -18. AnotIncurable malignancy: Active malignancy in the recipient is a contraindication for heart transplantation. The dilemma arises when there has been remission for a period of time. Listing for heart transplantation in this setting should be individualized, taking into account the expected cancer-free survival of the patient.                        Uncontrolled infection: Heart transplantation should be deferred until the infection has been controlled. An exception is driveline infections in the setting of ventricular assist devices, which can be controlled but not eliminated. Heart transplantation will treat the underlying cardiac dysfunction as well as the infection by removal of the offending hardware.                        Human immunodeficiency virus: Most centers still consider this an absolute contraindication for heart transplantation, although advances in retroviral therapy have led some to offer heart transplantation in this setting [                         setting . Significant psychosocial problems: The success of organ transplantation depends on the presence of a supportive family to keep regular follow-up appointments and to comply with various treatment protocols. Medication non-compliance is a significant problem especially in the teenage transplant recipient who is doing well. This represents a leading cause of late graft failure. Developmental delay is commonly seen in patients with CHD considered for heart transplantation [                        antation ; this alIt should be emphasized that there are very few recipient anatomic factors that contraindicate heart transplantation. Significant recipient pulmonary artery hypoplasia or pulmonary vein stenosis result in increased perioperative mortality and morbidity; transplantation in those settings should be individualized. Various recipient anatomic considerations are discussed separately below. Our donor evaluation and harvesting technique has been standardized, and is described in detail elsewhere . We avoiIt is important to obtain as much donor tissue as is feasible, in order to aid in the surgical reconstruction at the time of implantation. Using recipient anatomy as a guide, this advance planning simplifies the implant procedure. We prefer to harvest the entire length of the superior vena cava, the left innominate vein, and the entire aortic arch including the proximal portion of the descending thoracic aorta. If the lungs are not harvested, then we prefer to harvest the branch pulmonary arteries from hilum to hilum. In addition, donor pericardium should be harvested, as it can serve as additional tissue for reconstruction. We do not trim the donor organ until the time of implantation.The technical challenges in performing the cardiac transplant procedure have been overcome, even for the most anomalous recipient anatomic lesions. In the setting of experienced surgical transplant centers, outcomes of heart transplantation for CHD approach but remain inferior to those for cardiomyopathy, due to recipient factors and the increased complexity of the surgical implant procedure.Care should be taken during redo sternotomy to avoid catastrophic mediastinal hemorrhage. It is important to carefully plan for the operation, including review of prior operative reports and imaging studies. We routinely obtain preoperative chest CT scans with intravenous contrast in order to identify retrosternal structures and locations of major vessels. The groin vessels often need to be exposed. Following recipient cardiectomy, it is important to achieve surgical hemostasis prior to allograft implantation.Residual recipient anatomic lesions that are not addressed by recipient cardiectomy should be addressed and repaired. Failure to address residual lesions is one reason for the higher mortality seen in earlier eras for patients transplanted for CHD . In mostMost cyanotic CHD patients who have undergone prior surgery will have aortopulmonary collaterals, which can result in a large amount of pulmonary venous return entering the left atrium. In addition to obscuring the surgical field, this increased return also rewarms the allograft during implantation. This can be addressed by using a left ventricular vent, decreasing the flow rate on cardiopulmonary bypass (CPB), and cooling to a lower temperature. There are three options for implantation of the allograft in the recipient: Bicaval technique: This is the most common method used for implantation, as studies have shown a lower associated risk of tricuspid insufficiency, improved right atrial transport function and less atrial arrhythmias. Some patients may develop stenosis at the superior vena cava (SVC) anastomosis, which is amenable to balloon dilation and stent implantation. This technique also allows for greater flexibility in anatomic reconstruction of the underlying CHD anomaly.                        Biatrial technique: In recipients smaller than 1 year of age, the SVC may be small and fragile, and the risk of a postoperative anastomotic stricture may be high. In that setting, a biatrial technique is advocated, whereby the donor right atrium is anastomosed to the recipient right atrium, instead of performing individual caval anastomoses.                         Individual pulmonary vein technique: There is little data to support performing isolated right and left pulmonary venous anastomoses, although this has been advocated by some in adult heart transplantation, in order to decrease the incidence of left atrial thrombus formation and resultant thromboembolism [                        embolism . In the Various anatomic subtypes of biventricular CHD require variations in the implant technique. These are discussed below.en bloc, which is sutured to the donor inferior vena cava . Alternatively, the left SVC may be anastomosed to the donor innominate vein, although this can result in stenosis or bleeding due to the fragile nature of the innominate vein, especially in smaller patients . A left SVC, when present, most commonly drains into the right atrium through a dilated coronary sinus. We prefer to alter the recipient cardiectomy so as to keep the coronary sinus and inferior vena cava together 1B) or by construction of an intraatrial baffle from the roof of the left atrium to the right atrium . The latter technique increases CPB time and myocardial ischemia time, and may negatively impact early perioperative outcomes.In rare instances, a left SVC may drain directly into the roof of the left atrium, known as a Raghib association. In this situation, the left SVC is repaired either by an anastomosis to the left innominate vein .During implantation, the pulmonary artery anastomosis is done before the aortic anastomosis, in order to allow a clear and unobstructed view of the surgical field. The donor ascending aorta is kept long and anastomosed to the distal as pect of the recipient ascending aorta. This moves the position of the ascending aorta rightward, corresponding to the leftward move in the main pulmonary artery anastomosis done earlier .Situs inversus occurs at a rate of 2/10,000 population. Patients may have severe CHD associated with single ventricle physiology, or may have isolated cardiomyopathy as in biventricular CHD. In situs inversus, the right atrium is left-sided, along with the SVC and inferior vena cava. The left atrium and pulmonary veins are right-sided. Dextrocardia is often present, with the cardiac apex pointing to the right. The aorta is to the left of the main pulmonary artery .The main surgical challenge lies in routing of the systemic venous return in the transplanted heart. During cardiectomy, the atrial septum should not be resected, as it will be used to reroute pulmonary venous drainage. The aorta and main pulmonary artery are transected distally. The recipient atrial septum is mobilized by dividing it superiorly and inferiorly for extra mobility. This is then anastomosed to the left atrial free wall, anterior to the right pulmonary veins. A separate atriotomy is made anterior to the left pulmonary veins, which will serve as the recipient neo-left atrium, which is now left-sided, corresponding to the donor heart. The leftward aspect of the right atrial cuff is closed, which moves the right atrial cuff rightward. The right atrial anastomosis is performed after the left atrial anastomosis. The pulmonary artery anastomosis is performed next, using a similar technique as described above for CCTGA, whereby an incision is made in the left pulmonary artery, which moves the pulmonary artery anastomosis leftward  often accompany situs inversus lesions. There are abnormalities of systemic and pulmonary venous return. The majority of heterotaxy patients fall in the univentricular CHD category. The recipient operation combines elements of CCTGA and situs inversus. Our technique has been presented elsewhere , and is Often, dextrocardia is associated with situs inversus, which was addressed previously. If dextrocardia is present with a normal situs solitus, then heart transplantation is challenging, as this may lead to a rightward rotation of the cardiac apex, which may distort the tricuspid valve and the interventricular septum. If the pericardial space is dilated, this is not a major concern. If the pericardial space is not enlarged, then the left pericardium should be excised in order to allow the cardiac allograft to be positioned normally in the left chest.Overall survival following heart transplantation for all types of CHD (univentricular and biventricular) is lower compared to patients with cardiomyopathy, based on large registry studies. This is true for both pediatric and adult heart transplant recipients, and is primarily related to increased perioperative mortality. After excluding the perioperative period, survival for patients with CHD is similar to other diagnoses .Based on the most recent analysis of the International Society for Heart and Lung Transplantation Registry, CHD is a risk factor for one-year survival . The higDecreased survival for patients with CHD undergoing heart transplantation is likely due to several reasons:Reoperation: most cardiomyopathy patients have not had previous surgery, while most CHD patients have had prior surgical procedures. This increases the risk of bleeding and the technical complexity of the operation. Of the 488 patients with univentricular and biventricular CHD patients older than six months of age that were analyzed by Lamour and coworkers, 93% had undergone previous cardiac surgical procedures [                        ocedures . It is dReconstruction: most patients with CHD will need to undergo reconstruction of the pulmonary arteries or aorta, or need reconstructive procedures on their systemic or pulmonary venous drainage pathways. This is especially true for heterotaxy or situs inversus patients, some of whom may have biventricular CHD, although most will have single-ventricle anatomy. As a result, the reconstructive procedures that need to be performed along with the heart transplant procedure add to the technical complexity of the procedure, prolong cardiopulmonary bypass time, and increase short-term morbidity and mortality.                        Antibody sensitization: Previous surgical procedures with exposure to blood products, along with prior use of homograft tissue, increase the amount of preformed antibodies measured by the panel reactive antibody (PRA) test. A PRA > 10% typically limits the donor pool to the local transplant region, increasing waiting list mortality. Alternatively, patients may be transplanted across a positive cross-match, which often increases post-transplant mortality and morbidity due to increased episodes of rejection  and the need for augmented immunosuppression.                        Elevated pulmonary vascular resistance: Some CHD patients have an elevated PVR, which often requires prolonged postoperative sedation and neuromuscular blockade. This increased postoperative pulmonary vascular lability contributes to worse perioperative outcomes.                        Other factors contributing to operative mortality in patients with CHD include the clinical status of the recipient at the time of transplantation, the mismatch between donor and recipient sizes, the presence of aortopulmonary collateral vessels, the degree of pulmonary and systemic venous return anomalies, and the malalignment of the great vessels in patients with CHD , 27.Graft failure is the most common cause of early mortality following heart transplantation, especially in neonates. Supportive strategies include maximal medical management, especially aimed at treating right ventricular dysfunction, including nitric oxide and prostacyclin, neuromuscular blockade, and ventilation with 100% FiO2. Mechanical circulatory support, if needed, is extracorporeal membrane oxygenation (ECMO) in neonates and young infants. Older children may benefit from temporary centrifugal circuits such as the CentriMag ventricular assist device.The course of mechanical circulatory support is usually one week or less, in order to allow improvement and recovery of cardiac allograft function. A number of risk factors associated with early phase mortality and constant phase mortality have been identified in CHD patients with biventricular and univentricular lesions . Those aIn a study from Columbia University on heart transplantation for complex congenital heart disease, there was a trend for various anatomic subgroups to have different odds ratio for overall mortality, although this was not statistically significant due to small sample sizes and variable periods of follow-up . Patient4. This result, however, may be due to the small sample size, as this has not been reproduced in most studies.A recent analysis by the Great Ormond Street Hospital for Children of 73 patients with CHD treated since 1988 revealed similar survival for patients with univentricular and biventricular CHD anomalies . One-yeaA number of post-transplant complications have been recognized following heart transplantation, applicable to all recipient subgroups. These have been extensively reviewed elsewhere , and areThe need for redo sternotomy in the setting of palliated or repaired biventricular CHD increases the incidence of postoperative bleeding. Since aprotinin is no longer available, other antifibrinolytic agents such as tranexamic acid or epsilon aminocaproic acid have been used, although their efficacy has not been demonstrated. Although neonates and young infants have higher perioperative mortality, they experience lesser rates of acute rejection and often can be managed with decreased levels of immunosuppression. This is due to a naïve and immature immune system, which also allows for ABO-incompatible heart transplantation. Patients with biventricular CHD often have elevated panel reactive antibodies, which increase the incidence of acute cellular rejection and antibody-mediated rejection. This is thought to be a major factor influencing the lower survival following heart transplantation in this group compared to patients with cardiomyopathy.This complication occurs in 5-10% of patients postoperatively. Specific studies in patients with biventricular CHD have not been performed.When compared to cardiomyopathy, CHD increases the incidence of CAV within five years following heart transplantation, with a relative risk of 1.36 based on the most recent ISHLT Registry analysis, p=0.08 [Patients with biventricular CHD represent a heterogeneous group of patients with varied anatomic substrates, prior surgeries, age, and clinical status. With increasing experience, results for heart transplantation in this subgroup continue to improve, although are still inferior to transplantation for cardiomyopathy. It is hoped that further refinements in patient selection, techniques, and postoperative management will result in continued improvements in outcomes of heart transplantation for patients with biventricular congenital heart disease.


Intramyocardialhemorrhage (IMH) reflects severe reperfusion injury in acute myocardial infarction. Non-invasive detection of IMH by cardiovascular magnetic resonance (CMR) may serve as a surrogate marker to evaluate the effect of preventive measures to reduce reperfusion injury and hence provide additional prognostic information. We sought to investigate whether IMH could be detected by CMR exploiting the T1 shortening effect of methemoglobin in an experimental model of acute myocardial infarction. The results were compared to T2-weighthed short tau inversion recovery (T2-STIR), and T2*-weighted(T2*W) sequences.IMH was induced in ten 40 kg pigs by 50-min balloon occlusion of the mid LAD followed by reperfusion. Between 4–9 days (average 4.8) post-injury, the left ventricular myocardium was assessed by T1-weigthed Inversion Recovery(T1W-IR), T2-STIR, and T2*Wsequences. All CMR images were matched to histopathology and compared with the area of IMH. The difference between the size of the IMH area detected on T1W-IR images and pathology was −1.6 ± 11.3% , for the T2*W images the difference was −0.1 ± 18.3% , and for T2-STIR the difference was 8.0 ± 15.5% . By T1W IR the diagnostic sensitivity of IMH was 90% and specificity 70%, for T2*W imaging the sensitivity was 70% and specificity 50%, and for T2-STIR sensitivity for imaging IMH was 50% and specificity 60%.T1-weigthednon-contrast enhanced CMR detects IMH with high sensitivity and specificity and may become a diagnostic tool for detection of IMH in patients with myocardial infarction. A marked decline in mortality from acute myocardial infarction (AMI)has been achieved over the last decade. Primary percutaneous coronary intervention and thrombolysis has contributed to the improved prognosis by reducing the amount of myocardial necrosis because blood flow to the jeopardized myocardium is rapidly restored ,2. HowevCardiovascular magnetic resonance (CMR) provides a comprehensive evaluation of myocardial function and morphology in patients with AMI including myocardial viability, perfusion, infarct size, microvascular obstruction (MVO), and edema -11. PrevTen female Danish Land Race pigs weighing 40 kg were used for the experiments. All the pigs were treated in accordance with the Danish law on animal experiments.The pigs were pre-sedated with an intramuscular injection of stressnill (1 ml/kg), and midazolam (1 ml/kg). After induction of anesthesia with intravenous propofol (5 mg/kg) and endotracheal intubation, anesthesia was maintained with isoflurane (2.5%) in oxygen and continuous rate infusion of fentanyl (3 mg/kg/hr). The pigs were mechanically ventilated with a tidal volume of 450 ml (respiratory rate 12/min).The right common femoral artery was exposed by a surgical cut down, and a 8 F introducer sheath was inserted into the artery followed by a bolus injection of heparin (100 IU/kg) administrated through the sheath. Coronary occlusion was induced by placing a 2.5 mm over-the-wire angioplasty balloon in the LAD distal to second diagonal branch artery and inflating it to 5 atm. The LAD was occluded for 50 minutes, shown to be sufficient for creating IMH in a previous pilot study. Subsequently the balloon was deflated and removed. An angiogram was performed after balloon inflation and deflation to confirm coronary occlusion and coronary reperfusion, respectively. To prevent ventricular fibrillation, 150 mg of amiodarone was administered through the sheath prior to the induction of myocardial infarction. If ventricular fibrillation was encountered, non-synchronized direct current defibrillation (200 J) was performed. With ultrasound gel applied, the paddles were pressed against the anterior chest wall above the sternum on the right side and below the sternum on the left side.All pigs underwent CMR between three and nine days  after the ischemia-reperfusion injury, using the same sedation and respiratory protocol as described above. The anesthetic regimen yielded a low cardiac frequency of around 40 beats/min. CMR was performed on a 1.5 T MR system  using a five-element cardiac synergy coil. All pigs were imaged in the supine position. After a survey scan to localize the heart and diaphragm, a multi-heart phase steady-state free precession (BTFE) cine scan (repetition time (TR) 2.6 ms; echo time (TE) 1.3 ms; flip angle 60°; 50 heart phases) was obtained in the cardiac short-axis, vertical and horizontal long axis. In the cardiac short-axis, the LV was completely encompassed by contiguous 8 mm slices. To accomplish optimal delineation of left ventricular (LV) myocardium, 10–12 short-axis images was acquired encompassing the entire left ventricle using balanced steady state free precession (SSFP) scans with the following parameters: Echo time (TE) = 1.3 ms; repetition time (TR) = 2.6 ms; number of averages (NSA) = 1; slice thickness (ST) = 8 mm; in-plane image resolution = 2 x 2 mm.T1W IR (GRE), T2-STIR (SE), and T2*W (GRE) imaging was obtained in the same short-axis slices. All three sequences were navigator-gated, free-breathing and cardiac-triggered. The specific imaging parameters for each sequence are summarized in Table Following this, gadolinium enhanced first-pass myocardial perfusion and late gadolinium enhancement (LGE) was performed for the purpose of identifying areas of MVO. An intravenous bolus dose of 0.2 mmol/kg Gd-DTPA  was administered manually. First-pass perfusion imaging was performed using a fast gradient echo sequence with the following parameters: Repetition time (TR) 2.3 ms, echo time (TE) 1.3 ms, flip angle 18°, spatial resolution (2.8) mm x (x3.0) mm x 10 mm, field of view (FOV) range 360 mm, 3 slices acquired in the left ventricular (LV) short-axis using a 10 mm inters lice gap.Fifteen minutes after gadolinium injection, a 'Look Locker' sequence was performed to obtain the most appropriate TI to null the signal intensity of normal myocardium. The TI was in the range of 300-350 ms. Subsequently, LGE was acquired using a 3D phase sensitive inversion recovery-prepared T1-weighted gradient echo sequence with the following parameters: TR 4.9 ms, TE 1.9 ms, flip angle 15°, spatial resolution 1.35 mm x1.35 mm x10 mm, FOV 350 mm, 8 slices was acquired in the left ventricular (LV) short-axis and no inters lice gap.After completion of CMR imaging, the pig was kept under anesthesia and transported directly to the operating room. A midline sternotomy was performed, and a snare was placed around the LAD distal to the second diagonal branch, at the same level as the previously performed balloon occlusion. The heart was perfusion stained by an injection of 25 ml 10% Evans blue dye into the left atrial appendage to delineate the area of risk (AAR). Subsequently, the animal was euthanized and the heart was excised. The heart was then cut into 5–7 consecutive 8 mm-thick slices in short-axis planes in concordance with the previously recorded CMR images. Each slice was photographed with a digital camera  for the purpose of registering IMH within the AAR.The CMR images were analyzed by two observers using the research software Segment . First, Contrast to noise ratio (CNR) was calculated for T1W IR, T2-STIR, and T2*W images from the signal to noise ratios (SNR) of IMH and healthy myocardium:CMR mapping was performed on the short-axis images using the MOLLI sequence . T2 valuTwo examiners blinded to the pathology data visually inspected the CMR images and scored them as being either positive or negative for IMH. On T1W IR images, IMH was defined as an area with hyper intense signal intensity, on T2*W images IMH was defined as a hypo intense area that was clearly distinguishable from the surrounding myocardium, and on T2-STIR images it was defined as a hypo intense area in the core of a hyper intense area .One observer (SAT) reviewed all the digital photos of the freshly cut myocardial slices. Based on the presence or absence of a distinct red blood-stained area in the left ventricular myocardium, each segment was being categorized as being either positive or negative for IMH. The IMH size was manually measured using the Adobe Photoshop software . The IMH size in each short-axis slice was expressed as a percentage of the myocardial surface area (IMH area/myocardium area x 100%).The short-axis CMR images of the myocardium were matched with the corresponding photos of the histopathology by using the distance from the apex and gross morphological features such as the overall size and shape of the myocardium.The CMR findings of each of the T1W IR, T2-STIR and T2*W images were compared to the pathological findings and the sensitivity and specificity to IMH was determined for each sequence. Finally, the area of hyper intense signal intensity on the T1W IR and the hypo intense signal intensity on T2-STIR and T2*W images were compared to the IMH area detected by the pathology.Bland-Altman analysis was used to compare agreement between the CMR methods and pathology . The undTen pigs were subjected to the experimental protocol; two of the pigs died while awaiting CMR investigations leaving eight pigs for further investigation. All CMR examinations and pathological procedures were successfully performed.95 [14% to 23%] of the LV. The two pigs that did not show IMH on pathology were excluded from the Bland-Altman analysis since this statistical analysis aimed to evaluate the agreement for quantification of the area of IMH. The IMH sensitivity and specificity for the quantitative analysis of T1W IR, T2*W, and T2-STIR images are summarized in Table The pathology showed that all the pigs had suffered myocardial infarction and IMH was observed in six of the eight pigs with an average area of 19% CI5 14% to 3% of the95 [36% to 51%]. The first pass perfusion scan and LGE showed that MVO was present in all of the eight pigs with IMH. All pigs showed LGE enhancement with an average area of 32% CI95 [26% to 39%].Cine images demonstrated impaired regional left ventricular contractility in all pigs corresponding to the LAD infarction with an average ejection fraction of 43% CI95 [16% to 25%] of the LV (Movie 1) whereas hyper intense signal intensity was not present in any of the IMH negative pigs. The mean difference between the area of IMH detected by pathology comparedwith T1W IR images was: -1.6%, (limits of agreement were −24% to 21%)    and all IMH negative pigs (n = 2) Figure  with an 95 8% to 3% of the95 = [0.82 to 0.99]) for T2*-weighted images it was 0.91  and for T2-STIR-weighted images it was 0.90 . By visual inspection, rating each image slice as positive or negative for IMH, no disagreement was present between the two observers.The interobserver agreement for the assessment of IMH on cross sectional T1-weighted CMR images was, 0.95  was superior to T2-STIR and T2*W imaging .The CNR of T1W  than in the remote myocardium . Likewise, T2 values of IMH were shorter  than in the remote myocardium .The T1 values of areas containing IMH were shorter  by means of hyper intense signal intensity and normal myocardium with hypointense signal intensity. In contrast, the T2-STIR and T2*W techniques depict both IMH and normal myocardium by means of hypointense signal intensity. The T1-weighted technique may therefore provide superior image contrast and thereby allow for improved IMH identification.We found that in one of the pigs, IMH could not be detected onT2*W images and only weakly on T2-STIR images despite verification of severe IMH by pathology Figure . In thisOn the T2-STIR images, we observed the opposite situation: In two of the pigs, a hypo intense infarct core was detected in the myocardium, but IMH could not be detected in the corresponding pathology Figure . A hypo While the data were convincing in demonstrating the ability of T1W IR imaging for detection of IMH, the sample size was small. Larger studies would be useful to confirm our findings. Matching CMR images to pathology is a challenging task that involves some inaccuracy, even when matching is carefully performed. Since there was no disparity in slice thickness between histopathology slices and CMR images (both 8 mm), we believe that this inaccuracy was minimal. In the present study, the ability of T1W IR, T2-STIR, and T2*W techniques to detect IMH were assessed in the subacute phase after ischemia-reperfusion. The diagnostic performance of the different CMR techniques in the acute and chronic phase when the hemoglobin breakdown products is mainly based on the form of deoxyhemoglobin and hemosiderin, respectively, is likely to be different and needs further investigation.T1W IR CMR enabled detection of porcine IMH with a high sensitivity and specificity and has the potential to become a useful non-invasive diagnostic tool for assessment of IMH in patients with myocardial infarction.The authors declare that they have no competing interest.SFP formulated the study, carried out all the procedures related to the animal model, contributed to performing the CMR scans, contributed to the statistical analyses, obtained all illustrations, wrote the manuscript, and merged all feedback from the co-authors into the final manuscript. ST performed the analysis of the acquired CMR and histological data, contributed to the statistical analyses, the illustrations and drafting the manuscript and revised it critically for intellectual content. MPR contributed to the study design, drafting the manuscript, and revised it critically, for intellectual content. WP took part in formulating the study, revised the manuscript critically and contributed to important intellectual content of the manuscript. SR contributed to the CMR sequence setup, revised the manuscript critically and contributed to important intellectual content of the manuscript. HEB revised the manuscript critically and contributed to important intellectual content of the manuscript. ESSH revised the manuscript critically and contributed to important intellectual content of the manuscript. WYK contributed to the study design, the CMR sequence setup, drafting the manuscript and revised it critically for intellectual content. All authors have read and approved the final manuscript.


Left and right ventricular function was assessed with cardiac magnetic resonance imaging (MRI) and in-vivo myocardial calcium influx with manganese enhanced MRI. In the mdx mice at baseline there was reduced stroke volume, cardiac index, and end-diastolic volume with preserved left ventricular ejection fraction. These abnormalities were no longer evident after treatment with beta-blockers. Right ventricular ejection fraction was reduced and right ventricular end-systolic volume increased in the mdx mice. With metoprolol there was an increase in right ventricular end-diastolic and end-systolic volumes. Left and right ventricular function was normal in the Sgcd-/- mice. Metroprolol had no significant effects on left and right ventricular function in these mice, though heart/body weight ratios increased after treatment. In-vivo myocardial calcium influx with MEMRI was significantly elevated in both models, though metoprolol had no significant effects on either. In conclusion, metoprolol treatment at an early stage in the development of cardiomyopathy has deleterious effects on right ventricular function in mdx mice and in both models no effect on increased in-vivo calcium influx. This suggests that clinical trials need to carefully monitor not just left ventricular function but also right ventricular function and other aspects of myocardial metabolism.Beta-blockers are used to treat acquired heart failure in adults, though their role in early muscular dystrophy cardiomyopathy is unclear. We treated 2 different dystrophic mouse models which have an associated cardiomyopathy ( In Duchenne muscular dystrophy the absence of dystrophin causes subclinical or clinical dilated cardiomyopathy mdx mice, which lack the protein dystrophin as in Duchenne muscular dystrophy that there are benefits in terms of left ventricular pressure-volume derived data with early beta- blocker treatment, though detrimental effects in the delta sarcoglycan deficient mouse model  Beta-blockers are established treatments for acquired heart failure in-vivo calcium influx using 2 properties of the manganese ion 1 contrast agent with MRI. Thus, manganese influx results in a relative increase in contrast-enhancement on T1 weighted images.However, left ventricular pressure and volume measurements are not the only physiological measurements that can assess the effects of a systemic treatment. Right ventricular function is frequently abnormal in cardiomyopathy. Both left and right ventricular function can be assessed non-invasively with cardiac magnetic resonance imaging (MRI). Increased intracellular calcium is an important feature of muscular dystrophy cardiomyopathy and plays a central role in its pathophysiology in-vivo myocardial calcium influx.The purpose of this study was to treat 2 different mouse models of muscular dystrophy cardiomyopathy with beta-blockers at an early stage in the development of the cardiomyopathy to determine if there are beneficial effects on left and right ventricular function and to determine whether beta-blockers reduced mdx (n = 15) from Jackson laboratories , Sgcd-/- mice (n = 11) and C57 Bl10 mice (Jackson Laboratories) (n = 6) were treated with metoprolol and compared to age matched controls (mdx (n = 21), Sgcd-/- (n = 20), C57 Bl10 (n = 19)). Mice were housed under controlled temperature (17–28°C) and light conditions (12:12h light: dark cycle). Animals had free access to food and water. The investigations conformed with the Guide for the Care and Use of Laboratory Animals published by the US National Institutes of Health . All experiments were performed at the animal care facility of Newcastle University, UK. The work was approved by the Ethical Review Committee of Newcastle University.Male mdx mice at 16 weeks and at 8 weeks in the Sgcd-/- mice, timepoints which are early in the development of left ventricular dysfunction mdx mice at 24 weeks of age and 16 weeks in Sgcd-/- mice; ages at which cardiac function has previously been shown to be impaired in these mouse models mdx and Sgcd-/- mice.Metoprolol (2.5 mg/kg/day)  was administered orally via the drinking water, which was refreshed every 48 hours. From our previous studies http://segment.heiberg.se) to give LV and RV functional parameters. Segment automatically delineated the endocardial and pericardial borders at end systole and end diastole and manual adjustments were made if necessary. LV mass, RV and LV volumes, ejection fractions and cardiac output were calculated.Following induction of anaesthesia with 5% isofluorane in an anaesthetic chamber, mice were cannulated via the tail vein and laid prone on a cradle that allowed monitoring of body temperature, respiratory rate and heart rate heart rate . Mice were placed in the magnet and anaesthesia was maintained using 1–1.8% isofluorane via a nose cone. Their body temperature was maintained using a warm air blower. Images were acquired on a 7 Tesla horizontal bore Varian microimaging system equipped with a 12-cm microimaging gradient insert (maximum gradient 40 gauss/cm), . Mice were scanned in a 39 mm diameter quadrature birdcage volume coil . Following power calibration and global shimming a series of four pilot transverse images were acquired over the heart. Single slice coronal and sagittal images were then obtained in order to view the apex and mitral valve planes. These images were used to plan for the true short axis plane. To measure ventricular function, up to twelve contiguous short axis slices were acquired to cover the entire left and right ventricles using a spoiled gradient-echo cine sequence . Images were ECG triggered to the R wave with a cine delay of 15 ms and typically 30 phases were acquired distributed through the cardiac cycle. Images were zero-filled to a matrix size of 256×256. Scans were converted to matfiles using a matlab script  and analysed using the freely available analysis software Segment v1.8  were taken. Prior to manganese infusion four baseline images were acquired in order to average any variations due to changes in TR as a result of fluctuations in heart rate. Infusion was begun and images were taken at 2.5 mins, 5 mins and then at 5 minute intervals thereafter, for 30 minutes. A relative increase in T1 weighted contrast indicates increased manganese uptake. The time course stack of images were analysed in ImageJ (http://rsb.info.nih.gov/ij). An area of interest was drawn to fit inside the myocardium and average signal intensity was measured. If necessary, minor adjustments of this drawn region were made for subsequent images in the stack and the increase in myocardial contrast enhancement was expressed as a percentage increase from the average of the four baseline images (which showed little or no variation). MEMRI data is expressed as an enhancement ratio over baseline.Manganese chloride  was given by intravenous infusion through the tail vein canula at a flow-rate of 0.6 ml/hour. Flow time was adjusted according to weight to give a total dose of 190 nmol/g body weight . Single slice gradient echo short axis images at the level of the papillary muscles  with elevated heart to body weight ratios with and without metroprolol, and the Sgcd-/- mice had an increased heart to body weight ratio after metroprolol only  and left ventricular ejection fraction were not significantly different from controls  and steady state (10 – 25 minutes) stages following the start of the infusion  .There were no significant effects of beta-blocker treatment on the C57 Bl10 mice on manganese influx. Manganese influx was increased in both , ANOVA)  a-d as pmdx mice without treatment there is ventricular hypertrophy, reduced left ventricular stroke volume with a small left ventricular cavity size, normal left ventricular ejection fraction but reduced right ventricular ejection fraction. Consistent with our previous invasive catheter based studies there are benefits of metroprolol on left ventricular function in the mdx mice, but here we also demonstrate deterioration in right ventricular function. The Sgcd-/- mice develop ventricular hypertrophy with metoprolol (compared to untreated C57 Bl10 mice), but have normal left and right ventricular function without treatment with no significant effects of treatment on left or right ventricular function relative to C57 Bl10 mice. Despite these heterogeneous patterns of ventricular function in the 2 models, both exhibit increased intracellular calcium influx that is unaffected by metoprolol. Thus, overall responses to metoprolol in both models are largely either absent or potentially detrimental.In two mouse models of muscular dystrophy cardiomyopathy treated with the beta-blocker metoprolol at an early stage in the development of the cardiomyopathy, we show that there are differences in left and right ventricular function and the responses to treatment. In the mdx mouse model, right ventricular dysfunction has also been shown to be an important early feature, and similarly to the clinical studies above, right ventricular dysfunction precedes left ventricular dysfunction mdx mice would suggest caution for early beta-blocker usage. One potential explanation linking the apparent improvement in left ventricular function and deterioration in right ventricular function is that the relatively low stroke volume from the left ventricle without treatment protects the abnormal and susceptible right ventricle from excessive volume overload. However, the beta-blockers restore stroke volume and cardiac output to wild type levels and this increased flow to the right side of the heart then causes greater dilatation of the right ventricle. This is a phenomenon that is well recognized when patients with biventricular dysfunction have left ventricular output restored with a left ventricular assist device that then aggravates right ventricular dysfunction In clinical heart failure, right ventricular dysfunction is an important predictor of outcomes mdx mouse), there are clearly differences between the 2 methods Sgcd-/- mice, though is unaffected in the current study relative to C57 Bl10 mice. There are several potential reasons for this. Firstly, a different anaesthetic regimen was previously used  as opposed to isoflurane in the current study, and it is known that different anaesthetic agents can have markedly different effects on cardiac function P/dtmax and min and pressure-volume calculations of left ventricular contractility. Finally, it is possible that the two methods have different sensitivities to detect subtle changes in ventricular volumes. There are potential discrepancies in the ex-vivo measurements of heart to body weight ratios and the MRI measurements of left ventricular mass. The heart to body weight ratio involves both right and left ventricles, and with the dilatation of the right ventricle in the mdx mouse this is a plausible reason why left ventricular mass is not increased, although heart to body weight ratio is. In the Sgcd-/- mice the heart to body weight ratio increases after metoprolol, and this may be reflected in the higher left ventricular volumes relative to untreated mdx mice after metoprolol treatment, and is consistent with our previous conductance catheter studies in these mice with metoprolol showing deterioration in systolic and diastolic function.Whereas our findings with respect to left ventricular function and beta-blockade in these models are similar to those that we have found with pressure volume loop based conductance catheter studies  reduces calcium influx, and so the exact relevance of this finding pending further studies is unclear.Increased calcium influx into the cardiac myocyte is an important phenomenon in muscular dystrophy cardiomyopathy leading to progression of left ventricular dysfunction. Recurrent membrane injury leads to an increased influx of calcium mdx mouse, and in both models has no effect on calcium influx. This suggests that clinical studies with beta-blockers and other heart failure medications should comprehensively evaluate not only left ventricular function but also right ventricular function and other aspect of myocardial metabolism.Treatment with the beta-blocker metoprolol at an early stage in the development of the cardiomyopathy leads to worsening right ventricular function in the


Intramyocardial hemorrhage commonly occurs in large reperfused myocardial infarctions. However, its long-term fate remains unexplored. We hypothesized that acute reperfusion intramyocardial hemorrhage leads to chronic iron deposition.Fifteen patients , who underwent successful angioplasty for first STEMI, were recruited following informed consent. Cardiovascular Magnetic Resonance (CMR) imaging (1.5T) was performed on day 3 and month 6 post-angioplasty. 2D T2* maps  and Late Gadolinium Enhancement (LGE) images of the entire left ventricle (LV) were acquired. Threshold-based image analysis was performed to identify remote, hemorrhagic (Hemo+) and non-hemorrhagic (Hemo-) myocardium.Fourteen canines, subjected to ischemia-reperfusion (I-R) injury (3 hours of LAD occlusion followed by reperfusion), underwent CMR (1.5T) on days 3 and 56 post-I-R injury. Three sham-operated animals (Shams) were also studied using CMR at similar time points. 2D T2* maps  and LGE images of the entire LV were acquired. Threshold-based image analysis was performed to identify remote, Hemo+ and Hemo- myocardium. Subsequently, animals were euthanized (day 56), hearts were excised and imaged ex-vivo. Sections of Hemo+, Hemo-, remote and Sham myocardium were isolated and histology was performed. The concentration of iron ([Fe]) within each type of tissue was measured using mass spectrometry.Six months post-angioplasty, mean T2* of the scar tissue in patients with Hemo+ infarctions  at both 3 days and 56 days post-I-R injury Figure . SimilarAcute reperfusion intramyocardial hemorrhage leads to regional chronic iron deposition within the infarct zones. T2* CMR can accurately characterize localized chronic iron deposition following reperfusion-induced myocardial hemorrhage. The clinical significance of this finding remains to be investigated.This work was supported in part by grants from American Heart Association (SDG 0735099N) and National Heart, Lung, And Blood Institute (HL091989).


Peripartum cardiomyopathy (PPCM) is a rare cardiac disorder characterized by the development of heart failure in the last month of pregnancy or up to 5 months postpartum in women without other identifiable causes of cardiac failure. The combination of left ventricular (LV) systolic dysfunction and hypercoaguability can cause thromboembolic complications including intra-cardiac thrombi.A 25-year-old Caucasian female with PPCM demonstrated multiple thrombi in the LV on transthoracic echocardiography. Following anticoagulation with parenteral heparin, a cardiac MRI four days later demonstrated near resolution of the thrombi.We review the presentation, diagnosis and management of LV thrombi in the clinical setting of PPCM. Peripartum cardiomyopathy (PPCM) is a rare cardiac disorder characterized by the development of heart failure in the last month of pregnancy or up to 5 months postpartum in women without other identifiable causes of cardiac failure. The combination of left ventricular (LV) systolic dysfunction and hypercoaguability can cause thromboembolic complications including intra-cardiac thrombi. Although there are two case reports of PPCM with rapid resolution of intracardiac thrombi diagnosed by transthoracic echocardiography (TTE) in the literature to date, our case illustrates the use of multimodality cardiac imaging including TTE and cardiac MRI (CMR) in this patient population. We review the presentation, diagnosis and management of LV thrombi in the clinical setting of PPCM.A 25-year-old G4, P4 Caucasian female presented with a history of worsening dyspnea, orthopnea and paroxysmal nocturnal dyspnea seven months post-partum. On physical examination, she was tachycardic with a heart rate of 110 bpm and a normal blood pressure of 110/70 mmHg. The heart sounds were within normal limits with decreased breath sounds bilaterally and lower limb edema. Initial blood work including the complete blood count, electrolytes, liver function tests and cardiac biomarkers were within normal limits. The electocardiogram demonstrated sinus tachycardia and the chest x-ray confirmed cardiomegaly with pulmonary venous congestion. Transthoracic echocardiography (TTE) demonstrated biventricular dilation, biatrial enlargement, global hypokinesis of the left ventricle (LV) with an ejection fraction less than 20%. There were multiple echodense masses within the LV, consistent with thrombi Figure . With a Peripartum cardiomyopathy (PPCM) is a disorder of unknown cause in which LV ventricular systolic dysfunction and symptoms of heart failure occur between the last month of pregnancy and the first 5 months postpartum. The incidence of PPCM varies from the infrequent one case per 4000 live births in the US to the more frequent one case per 1000 live births in South Africa or one case per 299 live births in Haiti[Women with PPCM are at high risk for thrombus formation and thromboembolism due to both the hypercoagulable state of pregnancy and stasis of blood due to severe LV systolic dysfunction. Although two-dimensional TTE is the most commonly used technique for the non-invasive identification and follow-up of LV thrombus, the recent introduction of contrast echo and cardiac MRI (CMR) may improve thrombus detection. In a recent study evaluating 361 patients, 2D TTE was compared to both TEE and CMR for the identification of LVT. Although TTE had a sensitivity and specificity of 23±12% and 96±4% for the diagnosis of LVT, CMR had a higher sensitivity and specificity of 88±9% and 99±2%, respectively[In women with PPCM, LV thrombus (LVT) is detected in up to 17% of patients, in whom the risk of systemic embolization is high. A revieThe use of multimodality cardiac imaging including TTE and CMR can provide complementary information for the management of LVT in the clinical setting of a PPCM.Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.The authors declare that they have no competing interests.WA, DJ, IK and AS contributed to the writing of the manuscript. All authors read and approved the final manuscript.


Post partum cardiomyopathy (PPCM) can occur between the last trimester of pregnancy or within 5 months post partum, in the absence of any history of heart disease. Although rare, it may become unresponsive to medical treatment and can in such cases, require mechanical support or even a heart transplant. Predicting its evolution is unfortunately not possible.Late gadolinium enhancement CMR (LGE) can identify myocardial fibrosis and has shown its prognostic significance in DCM. However, the role of LGE in PPCM as a predictor of outcome has not been reported.The purpose of this study was to assess whether LGE imaging provides prognostic information in the outcome in post partum cardiomyopathy.From 2003 to 2012, 36 women (mean age 34±10 years) diagnosed as PPCM underwent standard CMR with LGE following Gd-DTPA injection at the time of PPCM suspicion and after a mean follow-up period of 33 ±20 months for 21 of them (58%).At the time of diagnosis: All patients showed increased left ventricular (LV) volumes , 17 patients showing reduced LVEF (mean LVEF 47.8% ±14%) and 15 patients had additionally dilated RV . Only 7 patients displayed additionally reduced right ventricular (RV) function (mean RVEF 54.85±13.5%).CMR data analysis from all patients in Table Initial study showed mid wall LGE in 6 patients (30%) indicating myocardial fibrosis. Among them, one patient had a follow-up scan displaying persistence of myocardial enhancement but improvement in LV volumes and ejection fraction (EF). Four patients out of 6 had dilated LV with reduced LVEF; one showed increased volumes but normal EF and 1 had normal volumes with impaired EF. The RV appeared dilated with impaired EF in 3 patients at baseline (3/6 pts) without improvement on the follow up scan.All the remaining patients without LGE (30/36 pts) had initially a dilated LV,  with associated reduced LVEF in 13 pts. Among them, 3 had a complete normalization of their LV volumes and 4 patients had normal LVEF at follow up. RV volumes and RVEF did not change significantly at follow up in this subgroup.None of the patients showed active myocardial inflammation or oedema on STIR images.In our cohort, the presence or absence of myocardial late gadolinium enhancement was not predictive of LV functional recovery in PPCM suggesting that mechanisms other than myocardial fibrosis are involved in the genesis of ventricular dysfunction. None of our patients displayed myocardial edema. However, follow-up results are still awaited.None


Single ventricle heart defects affect 2 per 1000 live births in the US and are lethal if left untreated. The Fontan procedure used to treat these defects consists of a series of palliative surgeries to create the total cavopulmonary connection (TCPC) which bypasses the right heart. In the last stage, the inferior vena cava (IVC) is connected to the pulmonary arteries (PAs) using one of two main approaches: an extracardiac conduit (EC), where a synthetic graft is used as the conduit; and the lateral tunnel (LT), where the atrial wall is used along with a synthetic patch to create the pathway. The LT pathway is anticipated to grow in the long term because it is formed partially with native atrial tissue, as opposed to the EC that retains its original size ; however, growth of LT pathways has not been systematically quantified. The objective of this work is to quantify cavopulmonary pathway growth from serial MR images of LT patients.Cardiac magnetic resonance (CMR) steady-state free precession cine axial image stacks  were analyzed. The anatomy was reconstructed using state of the art techniques developed in our research group; the inferior cavopulmonary pathway was isolated by cutting above the inferior venous confluence and before the PAs (figure). A geometrical analysis to quantify growth was performed using the Vascular Modeling Toolkit (VMTK). Results were normalized to changes in body surface area (ΔBSA=0.43±0.14m2) in order to compare changes occurring in different patients over different time spans. The metrics were compared to an EC conduit (n=1) as a control.Imaging data from 6 patients with a completed TCPC were analyzed. The time interval between subsequent CMR scans was 4.71±1.79 years. For the LT conduits considerable changes were observed between scans in the diameter, cross sectional area and length , while small changes were observed in the EC (Table Serial CMR images were used to non-invasively compute the geometrical parameters in patients with LT, where changes were observed in the transverse and longitudinal direction. These results show the growth potential of the LT conduit in the long term, which will be important to consider when choosing the IVC connection type.National Heart, Lung, and Blood Institute Grants #HL67622 and #HL098252.


Left ventricular diastolic impairment and consequently elevated filling pressure may contribute to stasis leading to left atrial appendage thrombus (LAAT) in nonvalvular atrial fibrillation (AF). We investigated whether transthoracic echocardiographic parameters can predict LAAT independent of traditional clinical predictors.We conducted a retrospective cohort study of 297 consecutive nonvalvular AF patients who underwent transthoracic echocardiogram followed by a transesophageal echocardiogram within one year. Multivariate logistic regression analysis models were used to determine factors independently associated with LAAT.2 scores , higher E:e’ ratios , and lower mean e’ velocities . Both E:e’ and e’ velocity were associated with LAAT formation independent of the CHADS2 score, warfarin therapy, left ventricular ejection fraction (LVEF), and left atrial volume index (LAVI) . Similarly, diastolic function parameters were independently associated with spontaneous echo contrast.Nineteen subjects (6.4%) were demonstrated to have LAAT by transesophageal echocardiography. These patients had higher mean CHADSThe diastolic function indices E:e’ and e’ velocity are independently associated with LAAT in nonvalvular AF patients and may help identify patients at risk for LAAT. Nonvalvular atrial fibrillation (AF) is the most common sustained cardiac dysrhythmia and the most frequent cause of cardio-embolic stroke . It is wIt is physiologically plausible that impaired diastolic function and consequent elevation in the left ventricular filling pressure (LVFP) lead to left atrial stasis which results in LAAT formation and subsequent risk of systemic thromboembolism. Prior reports suggest that two-dimensional echocardiographic parameters such as left ventricular ejection fraction (LVEF), left atrial volume index (LAVI) and LVEF/LAVI are associated with LAAT in patients with AF ,8. In thA retrospective cohort study design was implemented. We queried the echocardiography laboratory database at Rush University Medical Center to identify all consecutive adult patients with nonvalvular AF who underwent a TEE to “rule-out” left atrial appendage thrombus between January 1, 2005 and December 31, 2009. Of those, we only included patients who had a previous transthoracic echocardiogram (TTE) within 1 year of the TEE. Patients with atrial flutter, without intervening episodes of atrial fibrillation, were not included. We excluded patients with valvular AF due to mitral stenosis and those with conditions known to alter E and e’ velocities; namely mitral regurgitation greater than 2+ in severity , post mitral valve surgical or percutaneous intervention, and post orthotopic heart transplantation status. Patients with isolated aortic valvular disease, aortic valve prostheses and right-sided valvular heart disease were not excluded , SEC and depressed left atrial appendage emptying velocity (<40 cm/sec) by pulsed-wave Doppler. LAAT was defined as a circumscribed and uniformly echodense intracavitary mass distinct from the underlying left atrial or left atrial appendage endocardium and the pectinate muscles, and present in more than one imaging plane . Left atAll TTEs were reviewed offline by a board-certified (NBE) echocardiographer who was blinded to TEE and clinical data (HG). The mitral inflow early-diastolic pulsed-wave Doppler velocity (E) and the lateral mitral annulus tissue Doppler early-diastolic velocity (e’) were measured (cm/sec) and the E:e’ ratio was calculated Figure . We did 2 score was calculated from the sum of risk predictors of CHF, hypertension, age ≥75, diabetes mellitus, stroke or transient ischemic attack (TIA); weighing each by “1” except for prior stroke/transient ischemic attack (TIA) which was weighed by “2” . The Spearman’s method was used to evaluate linear correlations.The two-tailed Student’s Multivariate logistic regression analysis models were used to determine clinical and echocardiographic predictors of outcome measures independent of known confounders. Risk was expressed as odd-ratios (OR) with 95% confidence intervals (CI). The Hosmer-Lemeshow test was used to test regression models’ goodness of fit.P value representing the likelihood of the null hypothesis (AUC = 0.5). A two-tailed P value ≤0.05 was considered statistically significant in all analyses. PASW-18 software  was used for all data analyses with the exception of the comparisons between ROC curves for which STATA-11  was used. The study was funded by an internal research grant and was approved by the Rush University Medical Center institutional review board.The receiver operating characteristic (ROC) methodology was used to analyze the discriminatory capacity of various predictors of LAAT. ROC analyses were expressed as curve plots with the associated area under the curve (AUC) with 95% CI and a 2 score, along with an increase in warfarin use , AF ablation in 99 (33.3%), implantation and testing of an implantable cardioverter-defibrillator in 45 (15.2%), and revision and testing of an implantable cardioverter-defibrillator in 22 (7.4%) subjects. The median interval between the TTE and TEE was 7.5 days (interquartile range 2–93 days). The mean INR within 30 days prior to the TEE for warfarin-treated patients was 1.7 ± 0.8. Nineteen subjects (6.4%) had a TEE proven LAAT. At the time of the TTE, 98 (33%) subjects were in sinus rhythm, 178 (60%) in AF or atrial flutter, and 21 (7%) in paced ventricular rhythm. Notably, patients with LAAT had a significantly higher mean CHADSP = 0.62], mean age , mean CHADS2 score , and gender distribution . Furthermore, they had a similar prevalence of CHF, age ≥75 years, diabetes, stroke/TIA history, and warfarin use .Compared to the 297 analyzed subjects, the 63 patients excluded for lacking a qualifying TTE had no significant differences in the prevalence of LAAT . Conversely, the e’ velocity was significantly lower among LAAT(+) subjects   and −0.32 (P < 0.001), respectively. Since only a minority of the patients (33%) were in sinus rhythm at the time of TTE, and thus had no A wave in the mitral inflow Doppler waveforms, it was not feasible to classify the patients based on their grade of diastolic dysfunction .The mean E:e’ among LAAT(+) patients was significantly higher than those who were LAAT(−) , while warfarin use had a borderline association with LAAT , e’ velocity was independently “protective” of LAAT after adjusting for other covariates . These models maintained a good model fit . Similar findings were noted with the CHA2DS2-VASc score.Additionally, E:e’ and e’ velocity were also associated with LAAT independent of the individual components of CHADSP = 0.33).We did not test E:e’ and e’ velocity in a single regression model due to inherent co-linearity between these parameters. However, we compared  the diagnostic performance of the predicted probabilities of LAAT derived from an E:e’ based regression model (Model-3) versus an e’ velocity based one (Model-5). This analysis demonstrated that the contribution of E:e’ and e’ velocity to the prediction of LAAT was comparable, as the AUC associated with models 3 and 5 were similar  vs. 9.6 (±3.4) cm/sec, P < 0.001]. In multivariate logistic regression analyses, E:e’ and e’ velocity were associated with SEC independent of LVEF, LAVI, CHADS2 score, and warfarin therapy (Table 2DS2-VASc for the CHADS2 score.One-hundred fourteen subjects (38%) had significant SEC by TEE, including all 19 subjects (100%) with LAAT Table . These p. 9.6 ±3. cm/sec, 2 score , as shown in Figure 2 score of zero was “protective” from LAAT.The receiver operator characteristics (ROC) curves demonstrated that the E:e’ and e’ velocity have good discriminatory capacity in predicting LAAT with respective areas under the curve (AUC) of 0.72 and 0.74, which trended to be larger than the 0.65 AUC associated with the CHADS2 (or CHA2DS2-VASc) score and warfarin use. Furthermore, diastolic function parameters seem to negate the predictive value of the CHADS2 or CHA2DS2-VASc score. If prospectively validated, these findings would indicate that echocardiographic diastolic function parameters may help physicians identify patients at very low risk of LAAT, given their excellent sensitivity. Previous reports have demonstrated that reduced LVEF is associated with LAAT [This retrospective cohort study of patients with nonvalvular AF demonstrates that the Doppler diastolic function parameters of E:e’ and e’ velocity are associated with LAAT formation and SEC independent of LVEF, LA volume, and other clinical predictors such as CHADSith LAAT ,19,20. Dith LAAT  we demonith LAAT . These fAfter the inception of this study Iwakura et al. reported that E:e’ is associated with LAAT independent of other echocardiographic parameters such as LVEF and LA dimensions . Our invA previous report has demonstrated that permanent AF is an independent predictor of LAAT,  a findinThis study showed an association between warfarin use and LAAT (Model-1). Clearly, this is not a cause and effect relationship, but rather it is the result of a clinical bias as physicians are likely to use warfarin in patients perceived to be at high risk for LAAT and stroke. This association dissipated once we introduced diastolic parameters, LVEF and LAVI into the regression model.The authors are cognizant of the small sample size and infrequent LAAT events, which impaired our ability to analyze many covariates within a single regression model. Thus, we meticulously chose the covariates to be analyzed in the logistic regression models and we applied rigorous examination of the goodness of fit of all these models. Nevertheless, it is plausible that some weakly associated parameters may have been missed. Furthermore, the secondary SEC endpoint analyses were consistent with the primary endpoint analyses; thus adding validity to the study conclusions. Moreover, we chose not to test E:e’ and e’ velocity within a single regression model, as the inherent co-linearity between these indices is likely to negate the effects of one another. However, we demonstrated that the predictive values of regression models containing E:e’ and e’ velocity (Models 3 and 5) are similar. Our data does not demonstrate significant superiority of either parameter.2) when e’ velocity (rather than E:e’) was included in Model-5 (Table LAVI was shown to be a strong independent predictor of LAAT in multiple reports; ,8 a find-5 Table . This se2 risk factors and systemic embolism [Predicting LAAT is certainly important in some clinical scenarios, such as prior to electrical cardioversion ,26. Sincembolism . We are embolism ,29 theseOur study has a few limitations. First, the retrospective design is an obvious limitation. Second, although the majority of the TTEs were performed within a few days prior to the TEE, some preceded the TEE by as long as 12 months. Thus, the loading conditions at the time of the TTE and TEE may be different for many subjects. However, analysis of the relatively “volume independent” e’ velocity yielded similar results to those observed with E:e’,  supportiOur investigation demonstrates that the diastolic function indices of E:e’ and e’ velocity are associated with LAAT in patients with nonvalvular AF, independent of clinical and echocardiographic covariates. These findings need to be externally validated, and could potentially be incorporated into a prediction rule that could be utilized clinically for risk stratification for LAAT in patients with nonvalvular AF.AF: Atrial fibrillation; AUC: Area under the curve; CHF: Congestive heart failure; CI: Confidence intervals; E: Mitral inflow early-diastolic flow velocity; e’: Mitral annulus early-diastolic tissue velocity; INR: International normalized ratio; LA: Left atrial; LAAT: Left atrial appendage thrombus; LAVI: Left atrial volume index; LV: Left ventricular; LVEF: Ventricular ejection fraction; LVFP: Left ventricular filling pressure; OR: Odd-ratio; ROC: Receiver operating characteristic; SD: Standard deviation; SEC: Spontaneous echo contrast; TEE: Transesophageal echocardiography; TTE: Transesophageal echocardiogram.The authors declare that they have no competing interests.RD, MD: Concept, design, statistical analysis, final manuscript approval. EG-S, MD: Echo image interpretation, manuscript drafting and editing. HG, MD: Echo image interpretation, design, manuscript drafting and editing. VN: data collection, cohort definition, data management, manuscript drafting and editing. AD, MD: data collection, data management, manuscript editing. MC, MD: data collection, data management, manuscript editing. NTN, MD: data collection, clinical adjudication. GJK, BS: data collection and management. RT, MD, MBA: critical review and editing. RK, MD, MSc: design, concept, critical review and editing. All authors read and approved the final manuscript.


T2-weighted magnetic resonance imaging (MRI) and the endocardial surface area (ESA) assessed by late gadolinium enhanced (LGE) have been introduced as relatively new methods for myocardium at risk assessment in ST-elevation myocardial infarction (STEMI).However, data on the utility and validation of these techniques are limited. Purpose was therefore to assess the area at risk (AAR) with these 2 MRI methods and to compare them to the validated angiographic APPROACH-score in a large consecutive patient cohort.One-hundred-ninety-seven patients undergoing primary percutaneous coronary intervention (PCI) in acute STEMI were included. AAR (assessed with T2-weighted edema imaging and the ESA method), infarct size and myocardial salvage were determined by MRI 2-4 days after primary PCI. Angiographic AAR scoring was performed by use of the APPROACH-score.The AAR assessed by T2-weighted imaging showed a good correlation with the angiographic AAR , whereas the ESA showed only a moderate correlation either to T2-weighted imaging  and the APPROACH-Score . Mean AAR by ESA (20.0±11.7%LV) was significantly smaller than AAR by T2-weighted imaging and APPROACH-Score (p<0.001 respectively) and showed a significant negative dependence on myocardial salvage index.Myocardium at risk and subsequently the salvaged AAR can be reliably assessed by T2-weighted edema imaging, whereas assessment of the AAR by ESA seems to be dependent on myocardial salvage and underestimates the AAR especially in patients with high myocardial salvage and aborted infarction. Thus, assessment of the AAR with the ESA method cannot be recommended.


We compared the performances of two different fat suppression T2-weighted fast spin echo sequences and demonstrated that T2-weighted CMR has high specificity but overall low sensitivity for detection of myocardial injury. More robust CMR techniques are needed for the detection of acute myocardial injury.Edema-sensitive T2-weighted cardiac magnetic resonance (CMR) based on fast spin-echo (FSE) imaging is a useful modality to detect acute myocardial injury. Conventional T2-weighted CMR uses three inversion-recovery (IR) pulses, the first two to null the blood signal, and the last one (STIR) to null fat signal, but suffers from reduced myocardial signal and signal dropout. We compared the performances of two different fat suppression T2-weighted FSE sequences: a) STIR (FSE-STIR) and b) spectral adiabatic inversion recovery fat suppression (FSE-SPAIR) for detection of myocardial injury in patients with cardiomyopathy.65 consecutive patients referred for CMR evaluation of myocardial structure and function underwent FSE-STIR and FSE-SPAIR in addition to cine and late gadolinium enhancement CMR as part of the routine clinical protocol. T2-weighted FSE images were independently evaluated by two readers, blinded to the clinical history and type of sequence, for image quality and artifacts , and presence of increased myocardial T2 signal suggestive of edema. Disagreements in interpretation of myocardial edema were resolved by consensus. In addition, presence of increased T2 signal suggestive of myocardial edema based on the clinical CMR interpretation, incorporating all CMR sequences available in the study, was also recorded for comparison. Troponin levels acquired during the time of the referral were recorded, and patients with recent (<30 days) troponin elevation greater than 2 times upper limit of normal were diagnosed with acute myocardial injury. The diagnostic performance of each T2-weighted FSE technique for detection of myocardial injury was evaluated.There were 22/65 patients (34%) with evidence of acute myocardial injury. Image quality and artifact scores were significantly better with the FSE-SPAIR technique compared to FSE-STIR . The sensitivity, specificity, positive predictive value and negative predictive value are as follows: 27%, 93%, 67%, 71% for FSE-SPAIR, 36%, 91%, 67%, 74% for FSE-STIR and 68%, 98%, 94%, 84% for clinical interpretations. There was a statistically significant difference in sensitivity between the clinical interpretation and each of the T2-weighted techniques, but not between the independent T2-weighted techniques.Isolated interpretation of T2-weighted CMR for myocardial edema demonstrates high specificity but overall low sensitivity for detection of myocardial injury. However, real world interpretation in combination with cine and late gadolinium enhancement techniques significantly improves overall sensitivity and diagnostic performance. Newer techniques, such as cardiac T2 mapping, may overcome limitations associated with conventional T2-weighted CMR.1K12HS019473-01 NIH/AHRQ/OEREP.


Late gadolinium enhancement (LGE) accurately detects myocardial fibrosis in hypertrophic cardiomyopathy (HCM), which has been recently shown to be an independent risk factor for cardiac events in this setting. Endoglin is an accessory protein for the TGF-β receptor, which stimulates myocardial fibrosis through modulating the response to Angiotensin II. We sought to explore the relationship between the myocardial fibrosis (tissue substrate) as identified by LGE and Endoglin (biomarker) in the setting of HCM.We studied 133 HCM patients  using a whole body 1.5 T CMR scanner (Philips Achieva) with 32 channel image aquisition. Vector-ECG gated short axis, two and four chamber cine slices with parallel image aquisition covering the entire left ventricle (LV) were acquired using a regular SSFP sequence. Matched LGE images were acquired after IV Gadolinium DTPA (0.2mmol/kg bodyweight) in all image planes. Two independent observers assessed LV volumes and myocardial mass that were acquired by manual drawing of endo- and epicardial borders. LGE was defined as signal intensity increase of >2SD of normal myocardium and after semi-automatic delineation on a commercially available workstation (Philips Viewforum) areas were quantified and expressed as percentage of the previously measured LV mass. Obstruction was determined using echocardiography gradient measurements at rest and under Valsalva.P<0.05 was considered statistically significant.79 patients (59%) exhibited intramural areas of LGE which averaged 7±12% of the LV mass. Patients with LGE had significantly higher levels of Endoglin compared with patients with no LGE lesions . There was a weak but almost significant correlation between percent of LGE and Endoglin . Endoglin levels however were not related to obstruction  and were not related to age, gender or LV mass.Our results provide preliminary evidence that Endoglin, a pro-fibrotic glycoprotein may be involved in the pathogenesis of late enhancement i.e. myocardial fibrosis in HCM. This molecular mechanism can have relevant clinical implications on the therapy of these patients since Endoglin expression  can be suppressed using Angiotensin inhibitors although further studies on the prognosis and risk stratification of this new bio-imaging parameter have to be conducted.None.


Cardiac involvement in systemic lupus erythematosus (SLE) is a common complication and is associated with a considerable morbidity and mortality in these patients. As affected individuals often present with subclinical or non-specific symptoms the betimes confirmation of cardiac manifestations is challenging. Cardiovascular magnetic resonance (CMR) with late gadolinium enhancement (LGE) is the current gold-standard for non-invasive tissue characterization as well as for the evaluation of systolic and diastolic function. In this study we assessed the cardiac morphology and function in SLE patients with low disease activity.We studied twenty-nine SLE patients  fulfilling the SLE diagnostic criteria of the American College of Rheumatology and compared them to thirty age-matched healthy volunteers. All patients were in a stable clinical condition and only patients with a low disease activity (SLEDAI Index < 5) were included. All of them received an individually optimized medication. CMR images were acquired on a 1.5 T whole-body MRI  using a 32-element cardiac phased-array coil. Short and long axis views were obtained applying a standard clinical steady-state free-precession sequence and LGE CMR imaging was performed  in 27 patients. Left and right ventricular  end-diastolic and end-systolic volumes , stroke volume (SV), ejection fraction (EF) as well as the mitral/tricuspid annular plane systolic excursion (M/TAPSE) and LV wall mass were measured.SLE patients and healthy controls had comparable demographic and clinical characteristics. SLE patients had significantly higher LV-EDV, LV-ESV and LV-EF. LV-SV and MAPSE did not differ significantly between patients and healthy controls. However SLE patients had significantly higher RV-EDV, RV-ESV, RV-SV, RV-EF and TAPSE values. LV mass showed no significant differences. Nineteen of twenty-seven assessed patients (70%) showed LGE CMR as a sign of myocardial involvement.Even in SLE patients with a low disease activity there is a high prevalence of myocardial and functional alterations. Especially the RV function is affected which could be due to early onset pulmonary manifestations of SLE. Regarding the high morbidity and mortality of cardiac complications in SLE patients, CMR may be an important non-invasive method for the early diagnosis of cardiopulmonary involvement.none


Hypertension results in structural and functional changes in the heart. Early detection of abnormalities of cardiac structure and function is important in the assessment and treatment of hypertensive subjects. The aim of this study was to evaluate the utility of the tissue Doppler echocardiographic technique in characterising diastolic and systolic functions in untreated native black African hypertensive subjects.Forty consecutive, newly diagnosed, untreated hypertensives with adequate conventional echocardiographic  and tissue Doppler echocardiographic images were recruited into the study. The control subjects were apparently normal individuals. Each arm of the study consisted of 21 male and 19 female subjects.p = 0.844) and gender distribution (M/F: 21/19 in both groups). Other baseline characteristics, except for blood pressure parameters, which were predictably higher in the hypertensive subjects, were comparable between the two groups. The hypertensive subjects had a lower systolic myocardial velocity (Sm) and early diastolic myocardial velocity (Em) in comparison with the controls . The late diastolic myocardial velocity (Am) was comparable in the two groups (p = 0.430).The two groups were comparable by age (48.6 ± 11.35 years in the hypertensives vs 48.1 ± 11.33 years in the controls; Tissue Doppler echocardiography demonstrates diastolic dysfunction relatively early in native African hypertensives and may be useful for detecting subtle deterioration in systolic function. Hypertension has worldwide prevalence5Tissue Doppler imaging is a newer echocardiographic imaging technique that is believed to be superior to the older conventional techniques in assessing abnormalities of cardiac function in many conditions affecting the heart. It has also been postulated that it may detect subtle abnormalities in cardiac function.The aim of this study was to assess the utility of the tissue Doppler imaging technique in evaluating left ventricular function in newly diagnosed, untreated native black African hypertensive subjects, among whom there is a paucity of data about the utility of tissue Doppler imaging techniques. Interestingly, this population has a relatively low prevalence of coronary artery disease; hence findings from subjects in this population are less likely to be influenced by sub-clinical coronary artery disease than in many other populations.7The study was carried out at the Cardiology Unit in the Department of Medicine of the University College Hospital, Ibadan, Nigeria. Subjects were 80 adult men and women, aged 18 years and older. There were two groups of subjects (matched for age and gender). The first group consisted of 40 consecutive subjects, newly diagnosed with hypertension, with adequate echocardiograms, who met the inclusion criteria. The second group consisted of 40 apparently normal controls.Hypertension was defined as blood pressure, measured according to standard guidelines, of 140/90 mmHg or higher on at least two occasions.Ethical approval was obtained from the institutional ethical review committee and informed consent was obtained from each patient.Echocardiography was carried out with an ALOKA SSD-1700 echo machine, which was equipped with 2.5–5.0 MHz linear array transducers.Two-dimensional guided M-mode echocardiography was performed on each subject in the left lateral decubitus position. All measurements were made according to the American Society of Echocardiography leading-edge-to-leading-edge convention.10et al. and the ejection fraction was calculated using the standard formula.Left ventricular (LV) volume was estimated using the formula of Teichholz LVIDd-LVIDsLVIDd ×100where LVIDd is the left ventricular internal diameter in diastole and LVIDs is the left ventricular internal diameter in systole.Left ventricular mass (LVM) was calculated using the Devereux-modified ASE cube formula:123 – (LVID)3 + 0.6LVM = 0.8 × (1.04 × (VSTd + PWTd + LVIDd)where VSTd is the ventricular septal thickness in diastole and PWTd is the posterior ventricular wall thickness in diastole.Relative wall thickness (RWT) was calculated as:13RWT= VSTd+PWTdLVIDd2.7 was used since this was the only criterion that demonstrated the optimal threshold value for left ventricular hypertrophy in blacks, irrespective of gender. A partition value of 0.45 was used for the RWT.15Four left ventricular geometric patterns were identified: normal geometry, when indexed left ventricular mass and relative wall thickness were normal; concentric remodelling, when indexed left ventricular mass was normal but relative wall thickness was increased; concentric hypertrophy, when both indexed left ventricular mass and relative wall thickness were increased; eccentric left ventricular hypertrophy, when indexed left ventricular mass was increased but with normal relative wall thickness.Doppler echocardiography: the mitral inflow velocities were measured from the apical four-chamber view. Measurements included the peak early mitral inflow velocity (E-wave), the peak atrial mitral inflow velocity (A-wave), the E/A ratio, and the deceleration time (DT) .Pulmonary venous flow was obtained using the right upper pulmonary vein in the apical four-chamber view. The measurements obtained were S-wave (systolic forward flow), D-wave (diastolic forward flow) and A-wave .16m), early diastolic myocardial velocity (Em), late diastolic myocardial velocities (Am), the duration of Sm and Em, Am with isovolumic relaxation time (IVRT), and isovolumic contraction time (IVCT).17Tissue Doppler: pulsed tissue Doppler imaging was performed in the apical four-chamber view. The filter setting was decreased to exclude high-frequency signals, and the gain minimised to allow for clear tissue signals with minimal background noise. The sample volume was positioned as parallel as possible with the lateral mitral annular motion. Variables of the tissue velocity evaluated were peak systolic myocardial velocity .Comparison of categorical variables between the groups was by chi-squared test, while continuous variables were compared with the student’s p < 0.0001), but comparable posterior wall thickness, left ventricular internal diameters, fractional shortening and ejection fraction. Except for atrial mitral inflow velocity (A velocity), which was higher in the hypertensives (p = 0.006), all other measured parameters of mitral inflow and pulmonary venous flow were comparable.Comparison of the M-mode and conventional Doppler measurements between the two groups Fifteen (37.5%) of the hypertensive subjects had normal LV geometry, 10 (25%) had concentric remodeling, 11 (27.5%) had concentric hypertrophy, and four (10%) eccentric hypertrophy. The corresponding values for the normal controls were 20 (50%), 14 (35%), 0 (0%) and six (15%), respectively. Hence, 37.5% of the hypertensives had left ventricular hypertrophy compared with 15% in the control group.m)  and early diastolic myocardial velocity (Em) , but a higher Am duration . The groups had comparable atrial myocardial velocity (Am). The E/Em ratio showed a trend towards a higher value in the hypertensive group. The presence of left ventricular hypertrophy did not result in E/Em that was significantly different from the ratio in subjects without hypertrophy .m) was inversely related to the diastolic and systolic blood pressures, the septal and posterior wall diameters in diastole, and the E/Em ratio, and directly related to Sm.The early diastolic myocardial velocity  in which the majority of the study population was untreated, the LV ejection fraction was higher in the black study group. This difference may be indicative of the fact that our study population may have been more heterogeneous with regard to the duration of hypertension, with the unifying factor being the absence of previous pharmacological interventions and the absence of symptoms of cardiac decompensation. It may, however, be reinforcing the speculation that findings in African-American populations or Africans in diasporas may not necessarily be applicable to native African populations.m) in the hypertensives is a pointer to abnormality of diastolic filling in the subjects with hypertension. Em is known to be the most striking tissue Doppler index of impaired relaxation. 31The probable heterogeneity of our study population is further emphasised by the significantly higher left ventricular mass and wall thickness in the hypertensive subjects compared with that of the control subjects. Lower peak early diastolic myocardial velocity  and left ventricular structure.