Dilatation Of Heart Chambers Research Articles

Apohemoglobin-Haptoglobin Complex Improves Cardiac and Pulmonary Function in Homozygous Townes (HbSS Townes) Mice

The constant ischemia-reperfusion injury and the release of hemoglobin and heme in patients with sickle cell disease (SCD) can affect the heart, lungs, and vasculature. While treatments have improved survival, cardiovascular complications are becoming more prevalent, including pulmonary hypertension and left ventricular diastolic dysfunction. Pulmonary hypertension is associated with increased mortality risk and linked to intravascular hemolysis, leg ulcers, renal insufficiency, iron overload, and liver dysfunction. Chronic anemia leads to heart chamber dilation and left ventricular mass increase, often accompanied by left ventricular diastolic dysfunction, both impacting exercise capacity. Additionally, it can cause Acute Chest Syndrome (ACS), which is characterized by inflammation and blockage of small blood vessels in the lungs. In some cases, the heart may enlarge (cardiomegaly) due to the increased workload it faces in pumping blood through narrowed or obstructed blood vessels. Sudden death is also emerging as a concern, necessitating further cardiac investigations and risk assessment for effective management. These issues are speculated to result from the high amount of hemoglobin and heme released into circulation. In this study, a synthetic protein scavenger for heme and Hb, the apohemoglobin (apoHb) was stabilized with haptoglobin (Hp) to create the apoHb-Hp complex, was used to study the cardiac and pulmonary changes in SCD mice resulting from heme and Hb. Homozygous Townes (HbSS Townes) mice (B6; 129-Hbatm1(HBA)Tow Hbbtm2(HBG1,HBB)Tow/Hbbtm3(HBG1,HBB)Tow/J) were used as the murine model of SCD, and HbAA Townes mice (homozygous for Hbatm1(HBA)Tow and Hbbtm3(HBG1,HBB)Tow) were used as the phenotypically controls. The results conclusively illustrate the benefits of using apohb-Hb, as it improves cardiac output, decreases pulmonary hypertension, and alleviates the immune response that is expected. In conclusion, our study provides strong evidence supporting the significant cardiovascular implication of heme and hemoglobin. We have demonstrated that apoHb-Hp complex effectively neutralizes these harmful activities, rendering these heme and free Hb nonreactive, leading to a marked reduction in hemolysis induced endothelial activation. These findings have important implications, suggesting that apoHb-Hp complex plays a protective role for cardiac and pulmonary cells exposed to elevated levels of heme and free Hb, a condition commonly seen in SCD. Furthermore, our study's consistency with prior research reinforces the role of apoHb-Hp complex in preventing P-selectin expression. Our SCD mouse model experiments reveal that apoHb-Hp complex effectively ameliorates vaso-occlusion, regardless of whether the vaso-occlusion was triggered by Hb or heme-independent factors like hypoxia-reoxygenation. Notably, the apoHb-Hp complex also demonstrated some efficacy, indicating that the protective effect extends beyond simple heme clearance and TLR4 signaling inhibition. While our results are promising, further experiments are required to gain a deeper understanding of the apoHb-Hp complex activity in both clearance-dependent and independent mechanisms of resolving vaso-occlusion. Overall, our research highlights the potential therapeutic value of the apoHb-Hp complex in combating the detrimental effects of Hb and heme, and offers valuable insights into its protective role in managing vaso-occlusive events associated with conditions like SCD.

Thyroid gland and heart: a cardiologist’s view on an endocrinological pathology. Review

The review of the literature considered the mechanism of action and the role of thyroid hormones (TH) on cardiovascular hemodynamics and, subsequently, on changes in the myocardial structure. A brief description of the genomic and non‑genomic mechanisms of thyroid hormones is provided. The mechanisms of thyroid hormones’ effects on the development of arterial and pulmonary hypertension, atrial fibrillation are highlighted. Attention is focused on the fact that congestive heart failure of the dilatation type develops against the background of hyperthyroidism. A possible connection between thyroid hyperfunction and Takotsubo stress‑induced cardiomyopathy was investigated. The impact of subclinical hyperthyroidism on the development and progression of cardiac pathology is illustrated. The mechanism of influence of hypothyroidism on the parameters of the lipid spectrum, acute phase proteins, insulin sensitivity, but not only the contractile function of the myocardium was considered. Changes in the electrical activity of the heart and its structural and functional changes were determined. Attention is focused on the importance of achieving euthyroidism in both hyperthyroidism and hypothyroidism. Stress‑induced Takotsubo cardiomyopathy is closely related to the hyperthyroid state and is often accompanied by the development of cardiogenic shock. Hyperthyroidism is associated with an increased risk of permanent atrial fibrillation and hypercoagulability. The achievement of euthyroid state can result in the reversal of left ventricular hypertrophy and decrease in the heart chamber dilatation. Even subclinical hyperthyroidism increases the risks of overall mortality and cardiovascular events, especially in the elderly persons. Patients with hypothyroidism are characterized by the development of anemia, dyslipidemia, decreased sensitivity to insulin, which is associated with endothelial dysfunction. In hypothyroidism, in contrast to hyperthyroidism, the risk of atrial fibrillation development is lower due to an increase in the arrhythmogenic threshold, but more typical disorders include sinus bradycardia, atrioventricular blocks of various degrees and prolongation of the QT interval, which are associated with the early development of impaired myocardial relaxation. For patients with thyroid pathology, the achievement of euthyroidism is mandatory to ensure cardio‑ and vasoprotection.

Analysis of genetic mutation in dilated cardiomyopathy

BackgroundCardiomyopathies (CM) are heterogeneous group of genetic disorders, specifically damage the heart muscles that leads to the progression of many clinical symptoms such as congestive heart failure (CHF). Dilated Cardiomyopathy (DCM) is the most common cause of heart failure. This study focuses on genetic variations in DCM, which is chronic, generally nonreversible heart muscles disease characterized by heart chamber dilation mostly left ventricle and decreased systolic efficiency. MethodologyThis study includes two parts, First we identified 100 genes associated with DCM using deep literature survey. Genetic variants were extracted from 1000 Genome Project (1000 GP), ExAC and Simon Genome Diversity project, for the identification of deleterious variants using in silico prediction tools followed by population genetic differentiation. In Second part, we examined 21,469 patients related to cardiac diseases. Of these, 100 DCM patients were recruited for the identification of rare pathogenic variants rs143187236 in MYOM3 and an INDEL rs36212066 in MYBPC3 using ARMS-PCR and validation through Sanger sequencing. ResultsWe identified 1658, 15,058 and 461 deleterious variants in 1000 GP, ExAC and Simon Genomes project respectively predicted by both SIFT and PolyPhen2 prediction tools. Clinvar database revealed 10, 69 and one pathogenic and likely pathogenic variants associated with DCM in 1000 GP, ExAC and Simon genome. Population genetic differentiation analysis revealed South Asian populations are closely related to European and American while highly differentiated to East Asian and African populations. ARMS-PCR and Sanger sequencing data of enlisted DCM patients showed that rs143187236 in MYOM3 was found in heterozygous state in three patients while rs36212066 in MYBPC3 was not detected in studied patients. ConclusionBased on bioinformatics analysis and investigation of deleterious variants through Sanger sequencing, it is deduced that large sample size is necessary for further detection of variants that will aid in the early diagnosis of DCM.

Abernethy malformation: A case report

Congenital portosystemic shunts are rare congenital vascular malformations characterized by a partial or complete portal blood diversion into the systemic circulation. Congenital extrahepatic portosystemic shunts, known as Abernethy malformations, pose a diagnostic challenge due to their low incidence and clinical presentations.
 A 15-year-old male with a history of chronic epigastric pain and nausea, high arterial blood pressure, recurrent nose bleeds, chest pain, dizziness, dyspnea, low exercise tolerance, hematochezia, and itching was diagnosed with Abernethy malformation type Ib. Imaging studies revealed a dilated portal vein conduit flowing into the inferior vena cava, bypassing the porta hepatis. Multiple liver nodules, heart chamber dilatation, myocardial hypertrophy, and pulmonary hypertension were also discovered. Following multidisciplinary panel meetings, liver transplantation was advised due to the severity of the patients symptoms and shunt anatomy.
 Furthermore, diagnostic algorithms and other treatment options are discussed.

Isolated Dilation of Right Heart Chambers in Fetal Echocardiography: Correlation with Postnatal Findings in a Quarterly Hospital

Background: Despite technological advances in fetal echocardiography, the assessment of the aortic arch is challenging due to the particularities of fetal anatomy and physiology. Both isolated dilatation of right heart chambers, direct visualization and measurements of the aortic arch are related to left obstructive heart disease, such as Coarctation of the Aorta (CoAo). So far, there is still no consensus in the published literature about which echocardiographic finding is of greater value for prenatal diagnosis of these changes. Objectives: To determine possible correlation between right cardiac chambers dilatation and direct aortic arch measurements with the presence of postnatal CoAo. Methods: A retrospective study of fetal and postnatal echocardiograms was carried out at Hospital Israelita Albert Einstein (HIAE) between 2011 and 2017. Morphological and functional parameters of the fetal circulation and the transitional circulation period in the newborn were analyzed. Fetal echocardiogram findings were compared with postnatal echocardiograms (presence or absence of congenital heart disease). Results: Of 2,869 exams performed, 22 fetuses with right chamber dilatation were born at our institution; 20 (90%) had postnatal echocardiogram with normal findings, and only 2 newborns (10%) presented aortic arch obstruction, 1 newborn had critical obstruction and required neonatal intervention. Among all fetal echocardiographic parameters evaluated, only the direct measurement of the aortic isthmus showed correlation with postnatal changes. Conclusion: In our series, isolated dilation of right heart chambers on fetal echocardiography was not associated with CoAo, but the association of right heart chamber dilatation with aortic arch diameter reduction was, however, more studies with larger numbers of patients are still needed.

Myocarditis: diagnosis and treatment in a period of pandemic

The novel coronavirus infection pandemic, officially declared in early 2020 and has been continuing till now, led to a significant increase in the rate of myocarditis, drew the attention of multi-discipline specialist to this problem and set new accents in it. In the acute phase of COVID-19, the rate of myocarditis in the most severe (dead) patients is estimated to be 7.2%, however, its real prevalence in different course of the disease is unknown; life-time diagnostics is complicated by the difficulties of transporting patients to expert centers for cardiac magnetic resonance imaging and endomyocardial biopsy. A troponin test is not sufficiently specific; chest pain, arrhythmias, and pericardial effusion are most common findings indicating heart damage (up to 20%). Cardiovascular signs and symptoms generally correlate with D-dimer levels and prognosis. In the acute phase of the disease, elevated anticardiac antibody titers are detected in almost 3/4 of patients, that reflect the systemic immune response and is one of the important mechanisms of heart damage. SARS-CoV-2 RNA is revealed in the myocardium both during COVID-19 and up to 68 months after it, that is accompanied by the morphological and clinical signs of subacute/chronic post-COVID myocarditis. Its main manifestations are arrhythmias and heart chamber dilation with impaired contractility. COVID-19 can lead to a significant worsening of symptoms of pre-existing myocarditis if there is no basic therapy, but in patients taking immunosuppressive therapy, its course is relatively favorable and usually does not lead to an exacerbation of myocarditis. A novel coronavirus (SARS-CoV-2) is an etiological factor not only for acute myocarditis in the initial (infectious) phase of the disease, but also for subacute (within 1 to 3 months) and chronic post-COVID myocarditis, which are due to not only the virus persistence in the myocardium, but, mainly, due to autoimmune reactions, which requires the determination of indications for immunosuppressive therapy, its volume and duration.

CMR assessment of right ventricular remodeling after transcatheter therapy for severe tricuspid regurgitation

Abstract Funding Acknowledgements Type of funding sources: Private hospital(s). Main funding source(s): Helios Clinical Research Institute Background/Introduction Patients with severe tricuspid regurgitation (TR) are characterized from severe dilatation and negative remodeling of the right heart chambers causing functional right ventricular (RV) failure and increased mortality and morbidity. The transcatheter tricuspid edge-to-edge repair (TTVR) is a new treatment option associated with symptom improvement and reduced hospitalization. The cardiac magnetic resonance imaging (CMRI) remains the gold standard for evaluating the right ventricular morphology and function and could be a useful in assessing the RV reverse remodeling after TTVR. The Tricuspid Regurgitation REgistry (TRuE) is an ongoing national prospective register of patients with severe TR that aims to identify morphofunctional parameters of the right heart chambers related to improve outcomes after TTVR. Purpose The present is a subanalysis of patients with serial CMRI examinations recruited in the ongoing prospective TRuE registry. Methods After excluding patients with intracardiac RV leads, seven patients (age 70 ±12 years) with completed thirty-day follow up were included in the present analysis. Retrospective gated steady state free precession cine images were acquired in the long and short-axis views covering the entirety of both ventricles. Aortic and pulmonary flow data were acquired with a flow-sensitive gradient echo sequence. Assessment of left ventricular (LV) and RV volumes was performed manually in the short-axis cine images (Circle Cardiovascular Imaging, Calgary, Alberta, Canada). The TR fraction was calculated as: ({total RV stroke volume (SV) – total pulmonary forward flow}/total RVSV) × 100. All volumes and flow measurements were indexed for body surface area and expressed in ml/m2. The ratio between the diameter of pulmonary artery (PA) and ascending aorta (AA) was used as indirect measurement of pulmonary arterial hypertension (PAH). CMRI parameters assessing TR quantification, RV morphology and function were analyzed at baseline and follow-up with Fisher´s test or paired t-test. Results At thirty days there was a significant reduction of the TR fraction (45% to 20%, p < 0.001), RV dilatation (RV-end diastolic volume (EDV): 106 ± 12ml/m2 to 86 ± 9.4ml/m2, p = 0.002, RV- end sistolic volume (ESV):55 ± 6.5 to 43 ± 6.6ml, p = 0.003) and improvement of function (RVEF: 47 ± 3.6 to 53 ± 2.4 %, p = 0.006). On the left heart side, there was an improvement of LV filling, with increased LVEDV and LVESV and of the LVSV (36 ± 5.3 to 41 ± 3.7ml/m2, p = 0.040), causing an improvement of the cardiac index (2.2 ± 0.9 l/min/m2 to 2.9 ± 0.7 l/min/m2; p = 0.019. Furthermore, the PA/AA ratio improved significantly (0.91 ± 0.15 to 0.81 ± 0.14, p = 0.006). Conclusion TTVR is associated with positive reverse remodeling of the RV with reduction of dilatation, PAH and function improvement.

The Effects of Ethanol on the Heart: Alcoholic Cardiomyopathy.

Alcoholic-dilated Cardiomyopathy (ACM) is the most prevalent form of ethanol-induced heart damage. Ethanol induces ACM in a dose-dependent manner, independently of nutrition, vitamin, or electrolyte disturbances. It has synergistic effects with other heart risk factors. ACM produces a progressive reduction in myocardial contractility and heart chamber dilatation, leading to heart failure episodes and arrhythmias. Pathologically, ethanol induces myocytolysis, apoptosis, and necrosis of myocytes, with repair mechanisms causing hypertrophy and interstitial fibrosis. Myocyte ethanol targets include changes in membrane composition, receptors, ion channels, intracellular [Ca2+] transients, and structural proteins, and disrupt sarcomere contractility. Cardiac remodeling tries to compensate for this damage, establishing a balance between aggression and defense mechanisms. The final process of ACM is the result of dosage and individual predisposition. The ACM prognosis depends on the degree of persistent ethanol intake. Abstinence is the preferred goal, although controlled drinking may still improve cardiac function. New strategies are addressed to decrease myocyte hypertrophy and interstitial fibrosis and try to improve myocyte regeneration, minimizing ethanol-related cardiac damage. Growth factors and cardiomyokines are relevant molecules that may modify this process. Cardiac transplantation is the final measure in end-stage ACM but is limited to those subjects able to achieve abstinence.

P1490 Congenital right coronary artery fistula into right atrium diagnosed with help of multimodality imaging

Abstract Introduction Coronary artery fistula (CAF) is an anomaly in which abnormal connections are present between the coronary artery and the cardiac chambers or a major vessel. It is an uncommon anomaly with an estimated incidence of 1 in 50,000 live births and usually occurs in isolation. We report a case of CAF into right atrium in a patient who admitted to our outpatient department with dyspnea and fatique. With help of transthoracic echocardiography (TTE), transesophageal echocardiography (TOE) and cardiac computerized tomography (CCT) we put the definite diagnosis and decided to close this fistula percutaneously with a PDA occluder. Case A 43-year- old male admitted to our outpatient department with complaints of exertional dyspnea and fatique for 5 years. His physical examination revealed a holosystolic murmur on the aortic valve area. His TTE showed enlarged right heart chambers with a high pulmonary artery systolic pressure (50 mmHg) and a suspicious flow from the aortic root into right atrium. Qp/Qs was 2.1. TOE depicted a shunt between aorta and right atrium as well, we couldn’t truly demonstrate the connection though . In order to define the defect precisely, we performed a cardiac CT. Cardiac CT clearly showed a markedly dilated and mildly tortuous and calcified fistula arising from the osteal part of right coronary artery draining into right atrium. Right coronary artery was thin and there was no stenosis. Cardiac CT helped us to exclude coronary arter disease as well. As it was suitable to close percutaneously, we decided to close it with a PDA occluder. Conclusion CAF is a rare, generally congenital anomaly and may cause right heart chamber dilatation and pulmonary hypertension if the diagnosis is missed. It is important to support and clarify the underlying pathology with help of other cardiovascular imaging modalities like cardiac CT and cardiac magnetic resonance imaging (CMR), if TTE and TOE cannot demonstrate us the exact pathology.In our case our choice of extra method was cardiac CT, as we wanted to exclude accompanying coronary artery disease at the same time. In today’s era, the use of multimodality imaging is increasing with a tremendous rate and it helps clinical cardiologists, cardiovascular imaging specialists and interventional cardiologists all. Abstract P1490 Figure. 2D,3D TOE and CCT images of CAF

Sinus of Valsalva aneurysm dissecting the inter­ ventri­cular septum with rupture into the right ven­ tricle (RCD code: I 1B.O)

Sinus of Valsalva aneurysm (SVA) is a rare congenital heart disease. A possible complication of SVA is rupture into a heart chamber, causing volume overload, which could lead to heart failure and the requirement for surgical correction. Transthoracic echocardiography is a readily available diagnostic tool for assessment, while other methods of cardiac imaging (cardiac CT and MRI) confirm the diagnosis and are necessary for preoperative assessment of the pathology. We present a very rare case of right sinus of Valsalva aneurysm dissecting the interventricular septum which ruptured into the right ventricle, causing volume overload of the right heart chambers and progressive heart failure. The diagnosis was established by transthoracic echocardiography and confirmed by ECG‐gated CT. Successful surgical correction resulted in regression of dilatation and dysfunction of heart chambers and to functional recovery of the patient. JRCD 2019; 4 (3): 51-54.

P694 Late shunt closure: is it the only cause of pulmonary hypertension after surgical repair?

Abstract Introduction Atrial septal defects (ASD) may be a cause of pulmonary hypertension (PH) specially when they are only detected in adulthood. Sinus venosus type ASD are rare, with an estimated prevalence of 4-11%, and frequently they are associated with anomalous venous return of the right superior pulmonary vein (RSPV). Surgical closure is safe and effective, and it is associated with normal life expectancy when performed before age 25; the risk of PH is higher in untreated defects or late closure. Clinical case The authors present the case of a 74-years old female patient with previous diagnosis of a sinus venosus type ASD. Closure of the shunt and correction of venous return was performed when the patient was 36. Follow up in the following years was normal, and the patient was discharged from the congenital surgical center. The patient was referred to our PH unit due to symptomatic PH for etiological investigation (PSAP of 70 mmHg in transthoracic echocardiogram). After excluding PH related to left heart disease and lung disease, the most likely cause was pulmonary arterial hypertension due to late closure of left to right shunt, but complete investigation was performed. A transesophageal echocardiogram showed dilatation of right heart chambers and a communication of 36 mm at the high atrial septum between the RSPV and superior vena cava entrance with spontaneous left to right shunt. A severe dilation of coronary sinus (maximal dimension 33.4mm) suggestive of persistent left superior vena cava (PLSVC) was also found. A cardiac magnetic resonance was performed showing dilated right chambers, abnormal drainage of right superior pulmonary vein to right atrium, a dilated coronary sinus with a PLSVC and Qp/Qs 1.7. Right heart catheterization showed a mean pulmonary artery pressure of 25 mmHg with normal pulmonary vascular resistance (2.4 UWood) suggesting that the intracardiac shunt is the responsible for the PH with reversible pulmonary vascular disease. The patient was proposed to surgical repair. Conclusion The authors present a rare clinical case of an undiagnosed persisting sinus venous ASD after surgical repair. Failure of shunt closure led to the development of PH, emphasizing the need to maintain lifelong follow up of these patients in specialized centers. Abstract P694 Figure.

PH Grand Rounds: A Case of Pulmonary Hypertension Associated With High Cardiac Output State from Arteriovenous Fistula–Or Is It?

PH Grand Rounds: A Case of Pulmonary Hypertension Associated With High Cardiac Output State from Arteriovenous Fistula–Or Is It?

Rituximab prevents and reverses cardiac remodeling by depressing B cell function in mice

B lymphocytes have been shown to contribute to autoimmune diseases via producing antibodies and proinflammatory cytokines. Depletion of B cells by blocking CD20 can inhibit these diseases. Here we examined whether an antibody against CD20, rituximab (RTX) (Rituxan@), used clinically in oncology could have similar anti-inflammatory effects in cardiac remodeling and heart failure (HF) in mice. Cardiac remodeling was established by pressure overload induced by transverse aortic constriction (TAC). Wild-type (WT) male C57BL/6 J mice were subjected to pressure overload by using transverse aortic constriction and then received RTX for 4 weeks. Administration of RTX markedly improves in vivo heart function, and suppressed heart chamber dilation, myocyte hypertrophy, fibrosis and oxidative stress in mice after TAC operation. RTX treatment also reversed established hypertrophic remodeling induced by TAC. Moreover, TAC-induced activation of multiple signaling pathways including calcineurin A, ERK1/2, STAT3, TGFβ/Smad2/3 and IKKα/β/NF-kB were remarkably attenuated in RTX-treated hearts compared with controls. These inhibitory effects of RTX were associated with inhibition of proinflammatory cytokine expression and Th2 cytokine-mediated IgG production from B cells. In conclusion, this study identifies that administration of RTX can inhibit pressure overload-induced cardiac remodeling and dysfunction in mice, and suggest that RTX may be a promising drug for treating hypertrophic disease.

Abstract 280: Cardiac Deletion of the Mitochondrial Pyruvate Carrier Results in Dilated Cardiomyopathy with Preservation of Fatty Acid Catabolism

Pyruvate is an important metabolic substrate for the heart that is formed in the cytosol by glycolysis or conversion of lactate, and then must be transported into the mitochondrial matrix for further metabolism. The mitochondrial pyruvate carrier (MPC) is composed of MPC1 and MPC2 proteins that are each required for complex stability and transport activity. Indeed, mice with cardiac-specific knockout of MPC2 (CS-MPC2-/- mice) exhibited concomitant MPC1 degradation and marked reduction in pyruvate-stimulated mitochondrial respiration. While cardiac function and heart size was normal in 6 week old CS-MPC2-/- mice, serial echocardiograms demonstrated drastic increases in heart size, chamber dilation, and loss of contractile function at 10 and 16 weeks of age. Gene markers of heart failure, hypoxia, and fibrosis were markedly increased in CS-MPC2-/- hearts. Mitochondria isolated from 16 week old failing CS-MPC2-/- hearts exhibited normal respiration on glutamate/malate, succinate, palmitoylcarnitine, and 3-hydroxybutyrate/malate, indicating preservation of mitochondrial energetics with anaplerotic malate, or substrates to produce acetyl-CoA independent of pyruvate. Expression of genes encoding fat and ketone oxidation enzymes was not down-regulated in failing CS-MPC2-/- hearts as is typically observed in heart failure, suggesting these hearts may rely on fat or ketone body oxidation for ATP production. However, targeted metabolomics of hearts from 6 week old CS-MPC2-/- chow-fed mice suggested TCA cycle dysfunction due to decreased acetyl-CoA levels that are insufficient to condense with oxaloacetate, causing an accumulation of oxaloacetate/aspartate, malate, and fumarate. To determine whether increasing the availability of usable substrates (fatty acids and ketones) would rescue the cardiac dysfunction, CS-MPC2-/- mice were fed a high fat, low carbohydrate (ketogenic) diet. Ketogenic diet strikingly decreased hypertrophy and improved functional parameters in 10 week old mice. In conclusion, loss of mitochondrial pyruvate utilization leads to altered cardiac substrate metabolism and inability to maintain TCA cycle flux, resulting in dilated cardiomyopathy that can be corrected by administration of a ketogenic diet.

Clinical benefits, echocardiographic and MRI assessment after pulmonary sequestration treatment

BackgroundThis study aimed to explore systematically procedural results, clinical benefits with echocardiographic and chest-MRI assessment of pulmonary sequestration percutaneous treatment. Methods13 consecutive infants and children with diagnosis of isolated pulmonary sequestration (PS) had percutaneous closure of the aberrant artery supplying pulmonary sequestration between 2010 and 2015. By protocol, echocardiographic and chest-MRI assessment was performed before and respectively at 6–12months and 1year with the aim to study the effects of embolization on heart volume overload and regression of pulmonary sequestration. ResultsMedian age at diagnosis was 1year (95%CI 0–2.6); median age at treatment was 1.3years (95%CI1.01–2.85). In all pts the PS was confirmed by chest-MRI. Procedural success was 100%. After treatment, pts experiencing previously respiratory symptoms/infections remained asymptomatic at 2.9year follow-up. In pts with significant shunt due to PS, treatment resulted in amelioration in left or right cardiac chamber enlargement at 6 and 12month follow-up. At distance from PS closure (median 14months), chest-MRI confirmed the closure of the aberrant artery and PS regression in 12 patients. In one case, despite the acute procedural success and the supplying artery remained closed, MRI detected residual PS revascularization. ConclusionsPercutaneous PS closure in infants and children is safe and provide regression in respiratory symptoms and heart chamber dilatation if significant shunt is present. MRI is able to define aberrant artery course and PS parenchima, and might represent a valid instrument to study residual PS parenchima during growth.

Alcoholic Cardiomyopathy: Old and New Insights

Alcohol cardiomyopathy (ACM) is a chronic dilated heart disease with decreased left ventricular ejection fraction that may be detected in one-fourth of high-dose alcohol consumers. It causes progressive diastolic and systolic dysfunction, supra and ventricular arrhythmias leading to heart failure and increased mortality. The main etiological factor for ACM is ethanol consumption that affects the myocardium in a dose-dependent manner. The mechanisms of ACM are diverse, synchronic and synergistic. Alcohol alters the channel and receptor structure of the cell membrane, decreases intracellular calcium transients, increases oxidative and inflammatory damage, decreases structural protein synthesis and interferes with excitation-contraction coupling mechanisms. Subjects with excessive alcohol consumption may have a subclinical cardiomyopathy with atrial and LV diastolic dysfunction measured by echocardiography or cardiac MR. Subclinical LV dysfunction may progress and later appear clinical features of heart failure. Cardiac myocytes adapt to ethanol aggression by cell and nuclear hypertrophy and dilatation of heart chambers. Progressive myocyte structure disarray and apoptosis produce myocyte loss, hypertrophy of the remaining cells, subendocardial and interstitial fibrosis and low-degree myocyte regeneration. In addition, ethanol also interferes with cardiac repair and adaptation mechanisms. Thus, local cardiomyokines (FGF-21) and growth factors (myostatin, IGF-1, leptin) are modified by ethanol, limiting cardiac remodeling and myocyte regeneration, and leading to abnormal hypertrophy and eccentric ventricle dilatation. This imbalance between aggression and protection mechanisms induces progressive myocyte loss and heart dysfunction. Alcohol abstention is the main goal in ACM, although control drinking (<-60 g/day) may allow recovery of LV function. Monitoring of systemic mediated alcohol-damage, and correction of vitamin and ion deficiencies is needed. Heart failure in ACM should be treated similar to other dilated cardiomyopathies. Heart transplantation is limited to subjects without other organ damage who are able to abstain from alcohol. New preventive and therapeutic strategies are under development to decrease alcohol-mediated myocyte damage and increase heart protective and repair mechanisms.

Cardiomyopathy With Restrictive Physiology in Sickle Cell Disease

ObjectivesThe aim of this study was to identify a unifying cardiac pathophysiology that explains the cardiac pathological features in sickle cell disease (SCD). BackgroundCardiopulmonary complications, the leading cause of adult death in SCD, are associated with heart chamber dilation, diastolic dysfunction, elevated tricuspid regurgitant jet velocity (TRV), and pulmonary hypertension. However, no unifying cardiac pathophysiology has been identified to explain these findings. MethodsIn a 2-part study, we first examined patients with SCD who underwent screening echocardiography during steady state at our institution. We then conducted a meta-analysis of cardiac studies in SCD. ResultsIn the 134 patients with SCD studied (median age 11 years), significant enlargement of the left atrial volume was present (z-score 3.1, p = 0.002), shortening fraction was normal (37.6 ± 4.7%), and lateral and septal ratios of mitral velocity to early diastolic velocity of the mitral annulus (E/e′) were severely abnormal in 8% and 14% of patients, respectively, indicating impaired diastolic function. Both TRV and lateral E/e′ correlated with enlarged left atrial volume in SCD (p = 0.003 and p = 0.006, respectively). Meta-analysis of 68 studies confirmed significant left atrial diameter enlargement in patients with SCD compared with controls, evidence of diastolic dysfunction and enlarged left ventricular end-diastolic dimension with normal shortening fraction. The majority of patients with catheter-confirmed pulmonary hypertension had mild pulmonary venous hypertension consistent with restrictive cardiac physiology. ConclusionsPatients with SCD have a unique form of cardiomyopathy with restrictive physiology that is superimposed on hyperdynamic physiology and is characterized by diastolic dysfunction, left atrial dilation, and normal systolic function. This combination results in mild, secondary, pulmonary venous hypertension and elevated TRV. Sudden death is common in other forms of restrictive cardiomyopathy. Our finding of this unique restrictive cardiomyopathy may explain the increased mortality rates and sudden death seen in patients with SCD with mildly elevated TRV.

Features of cardiac hemodynamics at chronic heart failure with overweight and obesity depending on the functional state of the kidneys

Several researches had demonstrated connection between the kidney dysfunction and worse prognosis in patients with both acute and chronic heart failure (CHF). The aim of research was to study the special features of cardiac hemodynamics at CHF with overweight and obesity depending on functional state of kidneys.Methods. There were examined 347 patients with CHF 0f 1-111 functional class on the background of overweight and abdominal obesity of 1-111 degree and different functional state of kidneys. There was calculated the speed of glomerular filtration (on MDRD formula) and carried out Doppler echocardiography for all examined persons. There was used an unpaired Student t-criterion or Mann-Whitney U-criterion depending on the size of sample and distribution of indicators.Results. Concomitant kidney functional state disorder complicates the clinical course of CHF on the background of overweight and obesity. It is demonstrated as an increase of functional class of disease at moderate and heavy kidney dysfunction. It is based on an increase of the degree of dilatation of the left and right atrium, left ventricle (LV) and the more degree of myocardium hypertrophy. The more significant calcination of mitral and aortic valves, the growth of degree of mitral regurgitation takes place. Simultaneously with structural changes in heart there take place functional disorders namely the worsening of contractility of LV and spread of systolic and diastolic myocardium function of 1 type, development of kidney hypertension. The remodeling of myocardium in this category of patients is mainly presented as concentric hypertrophy although at progression of kidney dysfunction the tendency to gradual elevation of excentric hypertrophy of LV takes place.Conclusions: It was established that CHF on the background of overweight and obesity associated with kidney dysfunction is characterized with heavier clinical course, elder age and more representation of women, dilatation of heart chambers, progression of hypertrophy of LV, calcination of valves and complication of mitral regurgitation. There took place a decrease of contractility of LV and spread of systolic and diastolic function by the type of relaxation disorder, kidney hypertension was forming. Among the types of myocardium remodeling the most widespread is concentric hypertrophy of LV that tends to decrease in favor of ecxentric hypertrophy at intensification of kidney dysfunction

HDAC inhibition: A novel therapeutic target for attenuating myocardial ischemia and reperfusion injury by reversing cardiac remodeling

Myocardial reperfusion therapy is the most important therapeutic strategy for myocardial infarction (MI) by reversing myocardial ischemia and reducing the infarct size. However, the ischemia and reperfusion (I/R) injury may dramatically alleviate this therapeutic benefits [ [1] Takemura G. Nakagawa M. Kanamori H. Minatoguchi S. Fujiwara H. Benefits of reperfusion beyond infarct size limitation. Cardiovasc. Res. 2009; 83: 269-276 Crossref PubMed Scopus (43) Google Scholar ]. A series of preclinical studies support the point of view that myocardial I/R injury may involve in a complex pathophysiological process which can further induce cardiac remodeling [ [2] Sun Y. Myocardial repair/remodelling following infarction: roles of local factors. Cardiovasc. Res. 2009; 81: 482-490 Crossref PubMed Scopus (234) Google Scholar ]. Cardiac remodeling leads to progressive heart chamber dilation, ventricular wall thinning, and eventually heart failure [ [3] Murdoch C.E. Zhang M. Cave A.C. Shah A.M. NADPH oxidase-dependent redox signalling in cardiac hypertrophy, remodelling and failure. Cardiovasc. Res. 2006; 71: 208-215 Crossref PubMed Scopus (289) Google Scholar ]. Hence, reversing myocardial I/R injury-induced cardiac remodeling may become a novel therapeutic target.

AB0607 Heart Transplantation in 2 Patients with Systemic Sclerosis and Primary Cardiac Involvement

BackgroundThere is no specific treatment for primary cardiac involvement in systemic sclerosis (SSc). Even if heart transplantation is an option, only 1 case has been reported1.ObjectivesAnalyse data of patients with...