Aris Lacis

Follow‐up of the patients after stem cell transplantation for pediatric dilated cardiomyopathy

Dilated cardiomyopathy is a serious problem in pediatric cardiology. Despite the relatively low incidence, the mortality is high. The conservative therapy does not improve the prognosis, and possibilities of heart transplantation are limited. There are multiple trials of use of stem cells for ischemic heart disease in the adult population. This allows us to believe that the method has perspectives in pediatric cardiology. We performed the cell therapy for seven patients, six of them had complete one yr follow‐up after procedure. Five to 30 milliliters of bone marrow was aspirated from the iliac crest and 17 to 122 million BMCs were isolated. The average basal EF was 33.5%. We observed increasing of EF up to 54% (=9.54, p=0.00154) in a 6‐month period and up to 54.5% (=10.82, p= 0.00315) after one yr. The changes of LVEDV also were observed. The LVEDV decreased in average per 13.05%. There were no observed side effects or heart rhythm disorders. Intramyocardial administration of bone marrow‐derived progenitor cells proved to be a technically feasible and safe method. Up until now, the results obtained have been promising and we suppose that bone marrow‐derived progenitor cell intramyocardial transplantation can be used.

Intramyocardial administration of autologous bone marrow mononuclear cells in a critically ill child with dilated cardiomyopathy.

Almost half of the children with symptomatic dilated cardiomyopathy receive a transplant or die within 2 years; however, cardiac stem cell transplantation has become a promising therapeutic option. The present case demonstrates for the first time, to our knowledge, the intramyocardial administration of autologous bone marrow mononuclear cells in a critically ill 4-month-old child with severe dilated cardiomyopathy. Left ventricular ejection fraction increased from 20% before stem cell transplantation to 41% at 4 months of follow-up.

Giant fibroma of the right ventricle

Cardiac fibromas are rare benign tumours of connective tissue that occur most frequently in children within the left ventricle. Spontaneous regression has not been observed, and surgical intervention is usually required. We have successfully treated a 1-year old girl with a giant fibroma of the right ventricle using the principles of the Batista procedure. The diagnosis was primarily made using transthoracic echocardiography.

The Metabolic Changes in Fresh Versus Old Stored Blood Used in Priming of Extracorporeal Circuit in Cardiopulmonary Bypass for Pediatric Patients - First Results

The Metabolic Changes in Fresh Versus Old Stored Blood Used in Priming of Extracorporeal Circuit in Cardiopulmonary Bypass for Pediatric Patients - First Results Introduction. One of the main goal in modern pediatric bypass equipment is to reduce the size of the extracorporeal circuit in order to minimize the prime volume. High priming volume can produce a low hematocrit on CPB in small infants, which results in electrolyte imbalance and decreased tissue oxygenation, therefore the donor blood should be used in the prime. The use of donor blood itself has several disadvantages, including complement activation, induction of a transfusion reaction, infusion of lactate, glucose and potassium, therefore this should be avoided as much as possible. When blood is stored, many alterations occur in its constinuents, in particular an increase in potassium and lactate levels, and decrease in pH, which have been associated with severe complications. Aim of the study. To evaluate the effect of length of storage of packed red blood cells (PRBC) on the concentration of potassium, sodium, lactate, glucose and pH in PRBC used in pediatric cardiac surgery. Materials and methods. From October, 2006 until June, 2009 blood samples were drawn from 78 PRBC used in cardiopulmonary bypass before they were added to the priming solution. All PRBC were splited in two groups depending on the age of blood: 5 days ≥ (Group 1), n=44 and 5 days< (Group 2), n=34. Blood samples were analyzed by GEM PREMIER 3000. Results. Seventy eight PRBC used in pediatric cardiac surgery were included in the study. In 44 blood samples the age of PRBC was under 5 days (Group 1) and in 34 blood samples the age of PRBC was over 5 days (Group 2). The mean storage time of PRBC in Group 1 was 4 +/- 1 days and in Group 2 - 8 +/- 3. The pH value in Group 1 was higher than in Group 2 (6.7 +/- 0.1 vs 6.5 +/- 0.2, P=0.000859). There was a significant difference between both groups in terms of potassium level (6.1 +/- 1.8 vs 9.4 +/- 2.6, P <0.0001) and lactate level (7.2 +/- 1.4 vs 10.1 +/- 1.7, P <0.0001), but no significant difference in terms of sodium level (138.3 +/- 3.9 vs 135.6 +/- 4.7, P=0.056688) and glucose level (346.5 +/- 36.1 vs 336.3 +/- 50.7, P=0.509321). There was an intermediate correlation in both groups in terms of storage time and level of potassium, storage time and level of lactate, pH and level of potassium, pH and level of lactate, and the levels of potassium and lactate. There was a linear increase in the levels of potassium and lactate depending on the storage age of PRBC. Conclusions. It is absolutely crucial to use as fresh packed red blood cells as possible in pediatric cardiac surgery to avoid such unexpected complications as transfusion-induced cardiac arrest due to hyperkalaemia. There are also other metabolic changes such as hyperlactemia and low pH, should be avoided, when performing pediatric cardiopulmonary bypass. The research is going to be continued, possibly starting to evaluate the levels of potassium and acid-base balance, when circulating the priming solution for some time before the initiation of cardiopulmonary bypass.

Which type of stem cells and what method for implantation should be preferred in pediatric cardiology (6 years of experience)

R heart disease occurring at a young age including juvenile mitral stenosis results in morbidity as well as mortality in adolescents and young adults, and also becomes one of the major cause of loss of the most productive years of life in developing countries like India. Rarely rheumatic MS may occur in < 5 years age, wherein rapid hemodynamic progression and cardiac morbidity and mortality occur. Our patient was 4 years old child with severe mitral stenosis (documented since 2 year 6 months of age) presenting with repeated pulmonary edema and the typical echocardiographic findings strongly indicated a rheumatic origin of this condition. Considering the fulminating nature of disease, patient was planned for early intervention and was taken for balloon mitral valvotomy with 20 mm Tyshak balloon. Percutaneous transmitralcommisurotomy (PTMC) may therefore become the only lifesaving intervention in these cases unless contraindicated, although the procedure entails considerable technical issues in this age group like sizing of peripheral venous sheath, choice of balloon, estimation of optimum balloon size by the height criteria. A few case series of balloon mitral valvotomy in patients aged 7 to 12 years have also been reported, and the procedure has been safe and effective even in this young population. To the best of our knowledge,our patient was the youngest documented case of established rheumatic heart disease and also one of the youngest PTMC procedure performed.C confers a poor prognosis. Early recognition and intervention is key to improve outcome. Classic methods of assessment of LV systolic dysfunction such Left Ventricular Ejection Fraction (LVEF) suffer from wide variance that limits their utility in detection of minor changes in systolic function on serial testing. In addition, the changes in LVEF appear late after significant myocardial damage has occured. This has been shown to affect prognosis of patients. Strain has been shown to be an accurate sensitive marker of LV function with leass varaiance than traditional methods of LV systolic function. It has been shown to drop early in the natural history of many systemic diease that affect the heart such as diabetic cardiomyopathy. Strain shows great promise in management of cardiomyopathies because its efficacy in early detection and potentially effects of treatment.Introduction: The lumenless, 4.1F diameter M3830 steroid pacing lead (Medtronic, Inc.) is a coaxial, solid core, non-styletdelivered design. Approved for use in 2005, the very long term performance is largely unknown, especially among congenital heart disease (CHD) pts and with implant at alternate (non appendage/apex) pacing sites (AP). This study presents 10 year post implant evaluation of this lead among CHD pts.P hypercholesterolemia is well known to be a major risk factor for the development of cardiovascular disease. Our studies focus on the impact of cholesterol on two types of inwardly-rectifying K+ channels expressed in cardiomyocytes: classical inward rectifiers Kir channels (Kir2) that play a major role in maintaining cardiac membrane potential and G-protein gated Kir (GIRK or Kir3) channels that play an important role in the regulation of atrial action potential. Paradoxically, our studies show that elevation of membrane cholesterol in vitro and in vivo has opposite effects on Kir2 and Kir3 channels in the same cells. Specifically, enriching cardiomyocytes with cholesterol in vitro suppresses the activity of Kir2 channels but enhances the activity of Kir3 channels. Furthermore, plasma dyslipidemia in vivo also have opposite effects on these channels in freshly-isolated cardiomyocytes. Both effects are mediated by a decrease or increase in the open probability of Kir2 and Kir3 respectively. Even more surprising, even though cholesterol has opposite effects on the function of Kir2 and Kir3, both effects are abrogated by a specific mutation indicating that they share some structural determinants. These studies are discussed in terms of the structural-mechanistic insights into cholesterol regulation of Kir channels and in terms of the physiological/ pathological impact of these coupled effects on cardiac function.T echocardiography has a wide use in perioperative period. Heart chambers, valves, vessels, fluid management are all in view of TEE. But, limitations are appearing with experience progressing. A novel limitation is invisibility of the aortic arch. Undiagnosed atherosclerosis originating from ascending aorta is a major problem causing neurologic complications during cardiac surgery. Visualizing thoracic aorta is also important for transaortic heart valve implantation. TEEs lacking sensitivity for atherosclerosis in distal aortic arch is corrected with a view TEE. This technic is based on overcoming the air in trachea. Usage of A view TEE before sternotomy gives an advantage against epiaortic ultrasound. TEE allows continious monitoring and does not interfere with surgical site. This allows a complete visualization of distal aortic arch, thoracic aorta and origins of the cerebral arteries. Epiaortic ultrasound has the advantage of a high frequency probe on it for further analyzing the atherom plaque. Isala safety check and Katz classification helped for perioperative management, and mortality has reduced significantly. Preoxygenation and experience are important because of the time limitation. This procedure will help surgical team to review treatment plan. Adjustments of cannulation, distal arch cannulation, and intermittent ventricular fibrillating method and off pump surgery are the changes according to visualization. Further experience with a view TEE will help more for neurologic outcome in near future.S cardiac magnetic resonance imaging (CMR) has been shown to have excellent diagnostic accuracy for detection of significant coronary artery disease (CAD). CMR provides valuable clinical data on the evaluation of structural, functional and valvular heart disease. As a result, stress CMR is increasingly being used to assess chest pain in patients with known or suspected CAD. CMR potentials derive from its high-spatial resolution, image contrast, lack of ionizing radiation and excellent depiction of wall motion. An essential characteristic of stress modalities is the negative prognostic value. The detection of myocardial ischemia with stress CMR is typically based on first-pass perfusion imaging, to search for inducible perfusion defects, or on wall motion abnormality imaging. An important goal of any stress modality is to identify those patients with low cardiac event rate. We reviewed 300 patients with suspected or known CAD, who undergone adenosine stress-CMR. End-points, during a long-term follow-up (5.5 years) were all causes of mortality and major adverse cardiac events. An excellent outcome for adverse cardiac events was found. The power of CMR relies also on the evaluation of viability with late gadolinium enhancement (LGE) methods. The LGE differentiate viable myocardium from scar on the basis of differences in cell membrane integrity for acute myocardial infarction. In chronic infarction, the scarred tissue enhances much more than normal myocardium due to increases in extracellular volume. Beyond infarct size or infarct detection, LGE is a strong predictor of mortality and adverse cardiac events. CMR can also image microvascular obstruction and intracardiac thrombus. CMR can determine infarct size, area at risk and thus estimate myocardial salvage after acute myocardial infarction.A syndrome is an autosomal dominant disorder, also known as arteriohepatic dysplasia Alagille-Watson syndrome, or syndromic bile duct paucity. The syndrome expressivity is highly variable but when fully expressed patients have cardiac malformations, skeletal and ophthalmological abnormalities in conjunction with cholestasis and bile duct paucity. It has been identified that the multisystem involvement is due to defects in the Notch signaling pathway, with the main mutation identified in JAG1. Despite relative good prognosis, mortality by the age of 20 years reaches 70%. The major contributor to the previous is the complex congenital heart disease in addition to the hepatic pathology in these patients. This emphasizes the need for early and appropriate treatment in this population. This review examines the evidence surrounding the management of this syndrome, primarily from a cardiovascular perspective.

Bone marrow derived progenitor stem cell transplantation as a temporary measure before heart or lung transplantation in children

I the last decade, procedures in the Cardiac Catheterization lab become more complex, take longer time, and involve higher sick patients. That led to many changes in strategy, and move from the Operating Room to the Cathlab. This originated new challenges to attending physicians and Anesthesiologists particularly. More and more they are managing a large range of children of different ages, different cardiac anomalies (some very complex), requiring an intervention in the cathlab instead or as a supplement to the surgery. No need to say that the Cathlab is a remote location, creating a hostile and unfamiliar environment, that makes the management of these patients more challenging. Therefore, many of these procedures require General Anesthesia instead of Sedation. The Anesthesiology Department must be active in developing protocols and management guidelines. The aims of this lecture will be to: • Describe the different indications for cardiac interventional procedures • Discuss the choice of the anesthesia technique (General Anesthesia versus Sedation) • Explain the notion of sedation and its complications • Decide the level of expertise of the physicians in charge of these cases • Consider safety as an important concern in this special setupI the past, we have focused on heart failure with a reduced ejection fraction (HFrEF). Recently, we have begun to focus on heart failure with a preserved ejection fraction (HFpEF), in which patients suffer from a diastolic dysfunction with a normal or near normal cardiac contraction. Patients with HFrEF typically have hypertension, diabetes, and various cardiomyopathies. They have a stiff ventricle that is non-compliant compared with patients with HFrEF. Diastolic dysfunction or diastolic heart failure is commonly observed in pediatric patients with hypertrophic or restrictive cardiomyopathy, primary hypertension and diabetes. We have generated a transgenic mouse line modeling human restrictive cardiomyopathy (RCM). Using this animal model, we have demonstrated that myofibril hypersensitivity to calcium is a key that causes impaired relaxation, i.e. diastolic dysfunction in mice with RCM. Using a genetic way or desensitizing chemical molecules to reduce the myofibril hypersensitivity can correct the diastolic dysfunction and rescue the RCM mice. Calcium desensitization provides us with a promising option in the treatment of diastolic dysfunction and diastolic heart failure.S analysis shows that around 1% of children are born with congenital heart diseases that count for about 10% of all congenital anomalies. While as many as 70% have asymptomatic extra sounds which are sometimes confused with pathological heart sounds during auscultation. It is sometimes vital that the conditions of these children be screened as early as possible and before 12 years of age. Studies show that the screening errors (positive or negative), are still substantial in primary health care centers, a large number of pediatric referrals for cardiac evaluation have normal hearts. Based on our unique and internationally patented processing method on murmur characterization, the Arash-Band method and its derivatives, an original digital phonocardiograph is developed. The new digital phonocardiograph has been tested on more than 1000 cases. The device has proven to have a >90% sensitivity, specificity and efficiency with correct diagnosis in children with heart diseases and 100% diagnostic accuracy with normal hearts with or without innocent murmurs The development of the new digital cardiograph also required automated end-pointing and segmentation of children s heart sounds. For that purpose, we developed a novel method by paying special attention to physiological effects of respiration on pediatric heart sounds and using neural network classifiers. The new digital cardiograph exhibits superior performance than a pediatric cardiologist who relies on conventional or computer-assisted auscultation and drastically reduces unnecessary use of echocardiography. The new digital cardiograph is a children lives saver in developing countries and also it opens a new era for children heart states verification through telemedicine.A we know that heart failure is a complex pathology that maybe seen in children with congenital heart disease include development of cardiomyopathies due to myocarditis. In general, this severe clinical condition is associated with a high rate of morbidity and mortality and places a significant burden on families. Current medical and/or surgical treatment modalities are taken largely from the management of heart failure in adults, though clear survival benefit of these medications are lacking. There is no adequate published data on the overall prevalence or incidence of heart failure in children. However, the success of mechanical circulatory support in management of heart failure has raised the prospect of a previously unavailable treatment modality. Heart transplant remains the gold standard treatment, but the number of patients requiring this treatment far outweighs the donor availability. It is therefore not surprising to see the popularity of various circulatory support modalities, with devices ranging from veno-arterial extra-corporeal membrane oxygenation (ECMO) to ventricular assist deviceswhichhave different properties such as pulsatile or continuous flow management. Indication, timing and the choice of the type of mechanical support are critical in order to avoid lethal complications. In many patients we can see that hemorrhage due to continous anticoagulation requrement, thrombo-embolism and infections. In pediatric patients with heart failure, mechanical supporting system is used rarely for bridge to transplantation in many of centers. Active research is currently underway to develop newer and more durable devices that will assist the pediatric population across all age groups. Excellent results are currently achieved for most children who requiring surgery. There is an ongoing investigation to improve outcomes in high-risk populations, such as small infants and those with complex congenital heart disease.Additionally, there is an active investigation and interest in expansion of VADs beyond the predominant utilization as a bridge to a heart transplant into ventricular recovery, device explant without a heart transplantation (bridge to recovery), and placement of devices without the expectation of destination therapy. Survival four years after hospital admission has been reported as only 70%. In the United States, it is currently estimated that greater than five million adults have heart failure with projections reaching greater than eight million by 2030.The mortality at five-years after the diagnosis of heart failure remains at approximately 50%. The authors concluded that the costs of heart failure estimates in the United States will be

Intrapulmonary Administration of Autologous Bone Marrow Derived Mononuclear Cells in Congenital Heart Disease Complicated by Pulmonary Arterial Hypertension: A Case Report

70 billion in the near future.W (WPW) is a relatively common problem in the pediatric population occurring in 1 in 500-1000 children. WPW can present with supraventricular tachycardia, ventricular dysfunction due to pre-excitation or sudden death due to rapid conduction of atrial fibrillation through the accessory pathway. As patients may present with sudden death as their first symptom, evaluation of patients with WPW is indicated, even if they are asymptomatic. In 2012, Pediatric and Congenital electrophysiology Society (PACES) and the Heart Rhythm Society (HRS) in conjunction with the American College of Cardiology Foundation (ACCF), the American Heart Association (AHA), the American Academy of Pediatrics (AAP), and the Canadian Heart Rhythm Society (CHRS) created a consensus statement on the management of asymptomatic young patient with WPW which serves as a guideline for evaluation and management of these patients.C athletes are those who participate in an organized team or individual sports that require regular competition against others. Athletic activities substantially increase the sympathetic drive, resulting in surge in catecholamine level that increases blood pressure, heart rate, myocardial contractility and oxygen demand. This can cause myocardial ischemia and arrhythmia that may lead to sudden death in athletes with known and unrecognized heart conditions during athletic activities. There are many structural and acquired heart conditions that are not clinically manifested. Many physicians are involved in medical clearance of children for participations in school sports activities. Physicians have to recognize them to protect athletes from catastrophic events. In order to prevent sudden cardiac death, physicians should be aware of cardiac conditions that may cause problem. Also physicians should be familiar with general guidelines for evaluation of an athlete and clearance for participation in athletic activities. Guidelines vary in different parts of the world. In this presentation I will discuss guidelines for European, Italian and in USA outlined by American heart Association. In this presentation the causes of congenital and acquired heart conditions and arrhythmias that can cause sudden cardiac death will be discussed with authors experience and literature review.Methods & Results: We have investigated the role of succinate-GPR91 signaling in a Pulmonary Arterial Banding (PAB) model of RVH in SD rats due to pressure overload. We found that GPR91 was located in cardiomyocytes. In both sham and PAB rats, treated with succinate further aggravated RVH, up-regulated RVH genes and increased the p-Akt/t-Akt level in-vivo. In-vitro, succinate up-regulate the levels of the hyper trophic gene marker and also the p-Akt/tAkt levels in cardiomyocytes. All these effects were inhibited by an antagonist of PI3K, wortmannin, both in vivo and in vitro. Finally, we noted that the GPR91-PI3K/Akt axis was also up-regulated compared with that in human RVH.

The proper delivery pressure for cardioplegic solution in neonatal cardiac surgery – an investigation of biomechanical and structural properties of neonatal and adult coronary arteries

Pulmonary arterial hypertension (PAH) is a devastating, progressive disease with increasingly debilitating symptoms that leads to right heart failure and ultimately death if untreated.

Biomechanical Properties of the Aorta in Neonates and Infants

When cardioplegic solution is injected into coronary arteries with a pump in order to ensure myocardial protection, it is necessary to determine the correct delivery pressure to avoid damage of the heart. Biomechanical and structural properties of the neonatal coronary artery wall should be taken into account when determining the delivery pressure. We investigated twelve coronary artery specimens without cardiac pathology retrieved from autopsies of neonates 9.3 ± 9.7 days old and compared them to adult specimens with no detected atherosclerosis. There was a rapid increase in the strain until the inner pressure reached 80 – 100 mmHg, whilst the increase of stress in the wall of the neonatal coronary arteries was less rapid. When the pressure exceeded 100 mmHg, the increase in the strain slowed down, whilst the wall stress and modulus of elasticity began to increase rapidly. Morphologic examination of tensile properties revealed prominent affection of the vascular wall of the neonates, with accentuated redistribution (loosening) of medial myocytes and the adventitial vasa vasorum. Collectively, a raised inner pressure applied to cardioplegic solution injected into the coronary artery of a neonate may increase the risk of structural damage to the vascular wall.

Biomechanical Properties of Coronary Arteries Neonates: Preliminary Results

The study to examine biomechanical properties of the aorta in neonates and the biomechanical properties of infantile aorta in case of different anastomoses used for surgical correction of aortic coarctation was started to detect the influence of the surgical technique on the biomechanics of infantile aorta and, therefore, the possible further changes in hemodynamics and blood flow. We analyzed seven specimens of native aorta and three specimens with the anastomosis end-to-end. We observed a non-linear relationship between stress and strain in the neonatal and infantile aorta. The strain of the end-to-end anastomosis was much smaller than in the native aorta. The modulus of elasticity of the aortic wall increased with the increase of inner pressure. However in the case of anastomosis end-to-end the modulus was almost constant and was relevant to the modulus of elasticity of the aorta with the inner pressure 100–120 mmHg. The results show that the stiffness of the anastomosis did not change with the changes in inner pressure which might affect hemodynamics.