A-Kinase Anchoring Protein 2 Promotes Protection against Myocardial Infarction

Myocardial infarction (MI) is a leading cause of maladaptive cardiac remodeling and heart failure. In the damaged heart, loss of function is mainly due to cardiomyocyte death and remodeling of the cardiac tissue. The current study shows that A-kinase anchoring protein 2 (AKAP2) orchestrates cellular processes favoring cardioprotection in infarcted hearts. Induction of AKAP2 knockout (KO) in cardiomyocytes of adult mice increases infarct size and exacerbates cardiac dysfunction after MI, as visualized by increased left ventricular dilation and reduced fractional shortening and ejection fraction. In cardiomyocytes, AKAP2 forms a signaling complex with PKA and the steroid receptor co-activator 3 (Src3). Upon activation of cAMP signaling, the AKAP2/PKA/Src3 complex favors PKA-mediated phosphorylation and activation of estrogen receptor α (ERα). This results in the upregulation of ER-dependent genes involved in protection against apoptosis and angiogenesis, including Bcl2 and the vascular endothelial growth factor a (VEGFa). In line with these findings, cardiomyocyte-specific AKAP2 KO reduces Bcl2 and VEGFa expression, increases myocardial apoptosis and impairs the formation of new blood vessels in infarcted hearts. Collectively, our findings suggest that AKAP2 organizes a transcriptional complex that mediates pro-angiogenic and anti-apoptotic responses that protect infarcted hearts.

Longitudinal analysis of cardiac abnormalities in pediatric patients with sickle cell anemia and effect of hydroxyurea therapy

Cardiac abnormalities such as left ventricular hypertrophy, dilation and pulmonary hypertension in sickle cell anemia, have been previously described. Hydroxyurea, a disease modifying therapy for sickle cell anemia, has been used for several decades. Longitudinal assessment of echocardiographic abnormalities in children and young adults with sickle cell anemia on hydroxyurea therapy is lacking. In this retrospective study, we aim to determine the prevalence of echocardiographic abnormalities in children and young adults with sickle cell anemia and to examine the effects of hydroxyurea on reverse cardiac remodeling. We reviewed the records of patients with sickle cell anemia who underwent routine cardiac screening at Cohen Children's Medical Center between 2010 and 2017, followed by retrospective longitudinal analysis of echocardiograms performed on patients receiving treatment with hydroxyurea. Data on a total of 100 patients with sickle cell anemia were analyzed; 60 (60%) were on hydroxyurea. Twenty-five (41.6%) of the patients on hydroxyurea had been treated for less than 1 year; these patients had a significantly greater prevalence of left ventricular dilation compared to those who had been on treatment for more than 1 year. Serial echocardiograms were then analyzed on patients receiving hydroxyurea. Left ventricular dilation and hypertrophy improved significantly with hydroxyurea treatment. Additionally, the left ventricular volume and mass correlated negatively with duration of treatment with hydroxyurea. Our study provides evidence that prolonged hydroxyurea therapy may lead to reverse cardiac remodeling. Future studies should attempt to follow this patient cohort for a longer duration.

Characterization of Cardiac Diseases in Dogs Prevalent in Indian Conditions

Background: Cardiac diseases defined as structural, functional, mechanical and electrical abnormality of heart. Characterization of different cardiac diseases in dogs prevalent in North Indian conditions is least studied. Methods: Out of total 2582 registered dogs, 41 were suspected for cardiac diseases based on clinical signs. Further confirmation and characterization was done by electrocardiography, radiography, echocardiography and cardiac biomarkers. Statistical analysis was done through SPSS 23. Result: Present study inferred, Dilated cardiomyopathy (DCM) as the most prevalent cardiac affection. Left ventricular dilation, interventricular septum thinning, increased E point septal separation and left atrial enlargement were characteristic echocardiographic indices in DCM. Echocardiographic indices in hypertrophic cardiomyopathy were increased interventricular septum, left ventricular posterior wall and reduced left ventricular lumen. Labrador retriever found to be most predisposed breed for DCM while Rottweiler reported to be most affected with pericardial effusion. Cardiac Troponin-I (cTnI) was statistically (p less than 0.05) increased in all cardiac categories with cut off value above 92 ng/l indicating cardiac affection, while Lactate dehydrogenase serve as screening biochemical marker with significant increase in all the cardiac cases ranging from 291 IU/l to 586.4 IU/l.

Major clinical impact of patent foramen ovale after HeartMate3 implantation: periprocedural diagnosis and its pitfalls

We report a clinically significant right-to-left intracardiac shunt through a patent foramen ovale, diagnosed during investigations for hypoxemia and left ventricular dilation on the late postoperative period of a HeartMate3 implantation. We discuss diagnostic pitfalls and haemodynamic influences in this scenario, as well as the possibility of successful percutaneous treatment.

Interaction of Obesity and Hypertension on Cardiac Metabolic Remodeling and Survival Following Myocardial Infarction

Background Obesity and hypertension are risk factors for myocardial infarction (MI); however, their potential interactions on post‐MI outcomes are unclear. We examined interactions of obesity and hypertensionon post‐MI function, remodeling, metabolic changes, and recovery. Methods and Results Male and female C57BL/6J mice were provided standard chow or high‐fat/fructose diet for 8 weeks and then infused with angiotensin II for 2 weeks to induce hypertension. MI was then induced by surgical ligation of the left coronary artery for 7 days. Obesity alone did not cause cardiac injury or exacerbate hypertension‐induced cardiac dysfunction. After MI, however, obese‐normotensive mice had lower survival rates compared with chow‐fed mice (56% versus 89% males; 54% versus 75% females), which were further decreased by hypertension (29% males; and 35% females). Surviving obese‐normotensive males displayed less left ventricular dilation and pulmonary congestion compared with chow‐fed males after MI; hypertension reversed left ventricular dilation because of high‐fat/fructose diet and promoted significant pulmonary congestion compared with chow‐fed controls. Obese‐normotensive males displayed higher left ventricular α‐MHC (alpha‐myosin heavy chain) protein, phosphorylated Akt (protein kinase B) and AMPK (adenosine‐monophosphate activated kinase), PPAR‐γ (peroxisome proliferator activated receptor gamma), and plasma adiponectin levels after MI, indicating favorable contractile and metabolic changes. However, these favorable contractile and metabolic changes were attenuated by hypertension. Obese‐hypertensive males also had lower levels of collagen in the infarcted region, indicating decreased ability to promote an adaptive wound healing response to MI. Conclusions Obesity reduces post‐MI survival but is associated with improved post‐MI cardiac function and metabolism in surviving normotensive mice. When hypertension accompanies obesity, favorable metabolic pathways associated with obesity are attenuated and post‐MI cardiac function and remodeling are adversely impacted.

Diagnosis dan Tatalaksana Terkini Penyakit Jantung Hipertensi

Hypertensive heart disease is a response to a prolonged increase in blood pressure that causes various changes in the myocardial structure. This study was aimed to obtain the recent diagnosis and management of hypertensive heart disease. This was a literature review study using 4 databases, as follows: Pubmed, Clinical Key, Science Direct, and Google Scholar. The keywords used were Hypertensive Heart Disease diagnosis of Hypertensive heart disease OR Screening of hypertensive heart disease OR imaging of hypertensive heart disease AND therapy OR treatment OR management of hypertensive heart disease. The results showed that there were 10 literatures that fulfilled the criteria, consisting of 6 randomized controlled trials and 4 article reviews. Among patients with hypertensive heart disease, left ventricle hypertrophy, left ventricular dilation, and diastolic and systolic disfunction were the most commonly found in ECG, echocardiography, chest X-ray, and CMR. Therapy of hypertensive heart disease was according to ACC/AHA guidelines with non-pharmacological therapy by adopting the DASH diet and pharmacological therapy of choice was ACE-I or ARB. In conclusion, in hypertensive heart disease, the most common structural changes were left ventricle hypertrophy, left ventricular dilation, diastolic and systolic disfunction found in ECG, echocardiography, chest X-ray, and CMR. Therapy of hypertensive heart disease was according to ACC/AHA guidelines.Keywords: hypertensive heart disease Abstrak: Penyakit jantung hipertensi merupakan respon terhadap peningkatan tekanan darah berkepanjangan yang menyebabkan berbagai perubahan pada struktur miokard. Penelitian ini bertujuan untuk mendapatkan diagnosis dan tatalaksana terkini mengenai penyakit jantung hipertensi. Jenis penelitian ialah literature review menggunakan 4 database, yaitu Pubmed, Clinical Key, Science Direct, dan Google Scholar. Kata kunci yang digunakan ialah Hypertensive Heart Disease diagnosis of Hypertensive heart disease OR Screening of hypertensive heart disease OR imaging of hypertensive heart disease AND therapy OR treatment OR management of hypertensive heart disease. Hasil penelitian mendapatkan 10 literatur yang memenuhi kriteria penelitian, terdiri dari 6 randomized controlled trial dan 4 review article. Pada penyakit jantung hipertensi kelainan struktural yang sering ditemukan ialah hipertrofi ventrikel kiri (konsentrik maupun eksentrik), dilatasi ventrikel kiri, disfungsi diastolik dan sistolik, yang dapat dideteksi lewat pemeriksaan EKG, ekokardiografi, rontgen toraks, dan CMR. Terapi penyakit jantung hipertensi menurut pedoman ACC/AHA yakni nonfarmakologi seperti pola diet DASH dan terapi farmakologi pilihan yaitu ACE-I atau ARB. Simpulan penelitian ini ialah pada penyakit jantung hipertensi terdapat hipertrofi ventrikel kiri, dilatasi ventirkel kiri, disfungsi diastolik maupun sistolik, dideteksi menggunakan EKG, ekokardiografi, rontgen toraks dan CMR. Terapi penyakit jantung hipertensi sesuai dengan pedoman penatalaksanaan ACC/AHA.Kata kunci: penyakit jantung hipertensi

Genetic Determinant of Familial Dilated Cardiomyopathy and Genotype-Targeted Therapeutic Strategy

Dilated cardiomyopathy (DCM) is a myocardium disease characterized by left ventricular dilation and systolic dysfunction. Genetic susceptibility contributes significantly to the disease progression in familial DCM. Mutations in more than fifty different genes have been identified to cause DCM, accounting for up to 50% of familial DCM cases. Elucidation of genetic basis for the remaining familial DCM probands promises to substantially increase the efficiency of genetic testing for early disease diagnosis and intervention. Dissecting genetic pathways linked to DCM and related pathogenic mechanisms can provide valuable insights into the understanding of disease pathophysiology that can be leveraged for development of genotype-targeted therapeutic strategy. Here, we review genetic variants, with a focus on affected genes most commonly implicated in DCM, and highlight their underlying pathophysiological mechanisms of action. We discuss recent progress on gene-based therapeutic strategy which holds the opportunities to implement individualized medicine and ultimately to improve patient outcome in the future.