3D bioprinting for enhanced vascularization, and gene editing to provide a more favorable immunological response are just some of the potential uses of carbon materials

2021 ◽  
Author(s):  
Moataz Dowaidar
Keyword(s):  
Large Scale ◽  
Gene Editing ◽  
Cardiac Development ◽  
Immunological Response ◽  
Extended Period ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
3D Bioprinting ◽  
Ventricular Ejection Fraction ◽  
Cardiac Tissues

While there are still a number of difficulties to overcome when it comes to practical use of large-scale tissue-engineered cardiac structures, there are some intriguing avenues to examine. Carbon is being employed in a number of fields to help solve various aspects of biological integration, biochemical and mechanical signals in cardiac development, 3D bioprinting for enhanced vascularization, and gene editing to provide a more favorable immunological response, to name a few. Clinical trials are particularly crucial when tissue-engineered cardiac tissues are utilized more broadly, since the design and execution of clinical studies will influence the findings in other research. To assess the most appropriate study endpoints, methods such as cardiac MRI with a high degree of reproducibility to measure surrogate markers of left ventricular ejection fraction and myocardial remodeling, as well as inclusion of multiple end points including biomarkers and quality of life metrics, should be evaluated. Furthermore, in order to determine a specific endpoint for morbidity and mortality, studies must include follow-up over an extended period of time.

Cardiomyopathy induced by cardiac Gs alpha overexpression

1997 ◽  
Vol 272 (1) ◽  
pp. H585-H589 ◽  
Author(s):  
M. Iwase ◽  
M. Uechi ◽  
D. E. Vatner ◽  
K. Asai ◽  
R. P. Shannon ◽  
...  
Keyword(s):  
Extended Period ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Sympathetic Stimulation ◽  
Ventricular Ejection Fraction ◽  
Heart Rates ◽  
Electrocardiographic Monitoring ◽  
Stimulatory G Protein ◽  
G Protein Alpha Subunit ◽  
Gs Alpha

The goal of this study was to determine whether chronic endogenous sympathetic stimulation resulting from the overexpression of cardiac stimulatory G protein alpha subunit (Gs alpha) in transgenic mice (15.3 +/- 0.1 mo old) resulted in a clinical picture of cardiomyopathy. The left ventricular ejection fraction, measured by echocardiography, was reduced in older mice with Gs alpha overexpression (50.4 +/- 5.4%) compared with age-matched control mice (70.9 +/- 1.6%; P < 0.05). When ejection fractions were compared at similar heart rates, the Gs alpha mice exhibited a greater left ventricular end-diastolic dimension than control mice (4.3 +/- 0.2 vs. 3.7 +/- 0.1 mm; P < 0.05). Baseline heart rates were elevated in conscious Gs alpha mice (722 +/- 27 beats/min; n = 5) compared with control mice (656 +/- 28 beats/min; n = 5). Moreover, electrocardiographic monitoring demonstrated a high incidence of arrhythmias. Increased mortality compared with control mice (31.6 vs. 3.0%; P< 0.01) was also observed. Thus older mice with Gs alpha overexpression exhibit many of the features of dilated cardiomyopathy. This study supports the concept that chronic sympathetic stimulation over an extended period of time, i.e., over the life of an animal, is deleterious and actually may result in cardiomyopathy.

scholarly journals Drastic Cardiac Reverse Remodeling Following Catheter Ablation in Patients with Atrial Fibrillation and Heart Failure

Medicina ◽  
2021 ◽  
Vol 57 (5) ◽  
pp. 511
Author(s):  
Takahisa Koi ◽  
Naoya Kataoka ◽  
Teruhiko Imamura ◽  
Koichiro Kinugawa
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Catheter Ablation ◽  
Large Scale ◽  
Hypertensive Heart Disease ◽  
Left Ventricular ◽  
Rhythm Control ◽  
Left Ventricular Ejection ◽  
Reverse Remodeling ◽  
Ventricular Ejection Fraction

In the management of atrial fibrillation in patients with heart failure, rate control is recommended, whereas the implication of rhythm control remains controversial. We experienced a 65-year-old man who had compensated heart failure due to hypertensive heart disease and atrial fibrillation with well-controlled heart rate (<100 bpm). At three months following the catheter ablation procedure, the left ventricular ejection fraction improved from 40% up to 65%. The implication of rhythm control using catheter ablation in improving cardiac reverse remodeling should be validated in large-scale clinical studies.

scholarly journals Adipose-targeted overexpression of mitochondrial-targeted catalase does not improve cardio-metabolic parameters in mice with diet-induced obesity

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
A J Croft ◽  
C Kelly ◽  
D Chen ◽  
L Murtha ◽  
S Sugito ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Metabolic Dysfunction ◽  
Metabolic Complications ◽  
Ventricular Ejection Fraction ◽  
Cardiac Tissues ◽  
National Budget ◽  
Diet Induced Obesity ◽  
National Heart Foundation

Abstract Background Obesity is associated with significant cardio-metabolic complications. Adipokines, and cytokines released from adipose tissue (AT) stimulate excessive mitochondrial production of reactive oxygen species (ROS). ROS-mediated oxidative modifications is associated with development of insulin resistance and impaired cardiac function. We hypothesised that adipose-targeted overexpression of mitochondrial-targeted catalase (AT-mCAT) could lead to improvement in diet-induced cardio-metabolic dysfunction. Methods/Results mCAT (floxed) and AdipoQ-Cre mice were crossed to generate mice overexpressing catalase with a mitochondrial-targeting sequence predominantly in AT (AT-mCAT). Wild-type (WT) and AT-mCAT male mice were fed normal chow (NC) or high-fat/high-sucrose (HFHS) diet (36%fat/34%sucrose) for 4 months. At endpoint, echocardiography showed reduced cardiac output in all groups v WT NC (p&lt;0.05); reduced IVSd in AT-mCAT NC and HFHS groups v WT NC (p&lt;0.01); reduced left ventricular ejection fraction in AT-mCAT HFHS v WT NC (p&lt;0.05) and no differences in fractional shortening or E/A ratio between groups. Glucose tolerance tests (2g/kg) showed impairment in WT HFHS and AT-mCAT HFHS v WT NC (p&lt;0.01, p&lt;0.05 respectively). Triglyceride levels were increased in WT HFHS and AT-mCAT HFHS v WT NC (p&lt;0.05). Analysis of hypertrophic signalling in cardiac tissues by ELISA showed p-AKT/total Akt levels were decreased in AT-mCAT hearts regardless of diet (WT NC v AT-mCAT NC p&lt;0.01; WT HFHS v AT-mCAT HFHS p&lt;0.05). Conclusion Our results confirm previous findings that diet-induced obesity is a systemic condition. Targeting adipose tissue with mitochondrial catalase may not be adequate to prevent development of cardio-metabolic dysfunction. More systemic approaches may be required to combat obesity-induced cardio-metabolic impairment. FUNDunding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Heart Foundation of Australia

Abstract 542: Chronic Doxorubicin Cardiotoxicity Assessed in Engineered Cardiac Tissues Generated in Biowire™ II Platform

2020 ◽  
Vol 127 (Suppl_1) ◽  
Author(s):  
Roozbeh Aschar-sobbi ◽  
Julia E Napolitano ◽  
Danielle R Bogdanowicz ◽  
Michael P Graziano
Keyword(s):  
Action Potential ◽  
Action Potential Duration ◽  
Cardiac Fibroblasts ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Resting Membrane Potential ◽  
Ventricular Ejection Fraction ◽  
Cardiac Tissues

The anthracycline doxorubicin is an effective anti-tumor agent widely used in both adults and children. One major adverse effect of doxorubicin therapy is dose-dependent cardiotoxicity, ranging from asymptomatic reduction in left ventricular ejection fraction to more serious, potentially fatal symptoms including arrythmias and congestive heart failure. The exact mechanism of doxorubicin-induced cardiotoxicity remains unknown. Recently, human induced pluripotent stem cells (hiPSC) have emerged as a potential tool to model cardiac toxicity, but their fetal-like phenotype raises concerns about the translatability of in vitro data to in vivo cardiotoxicity. To overcome this limitation, Biowire™ II platform was used to generate 3D engineered cardiac tissues (ECTs) from hiPSC-derived cardiomyocytes and human cardiac fibroblasts. Using long-term electrical stimulation, ECTs with a phenotype approaching that of adult human myocardium were obtained. The ECTs were then exposed to 1 μM doxorubicin for 8 days followed by 7 days of washout. Measurements of contractile force amplitude at 1 Hz stimulation showed a transient increase in force within 24 hours of doxorubicin exposure followed by decrease in force after 2 days. Intracellular recordings of action potential (AP) showed a decrease in maximum upstroke velocity (dV/dt), AP amplitude (APA), and resting membrane potential (RMP) after 8 days of doxorubicin treatment. In addition, action potential duration (APD) at 30% (APD30) repolarization was increased in doxorubicin-treated ECTs, whereas APD50 and APD90 were decreased. Following 7 days of washout, no difference in force or AP parameters was found between doxorubicin and vehicle-treated ECTs with the exception of APD50 and APD90 which remained abbreviated. A global untargeted analysis of the conditioned media from doxorubicin-treated ECTs identified 204 analytes and revealed an upregulation of redox homeostasis, differential fatty acid metabolism, altered glycolysis and TCA cycle metabolites, and decreased nucleoside metabolism compared to vehicle-treated ECTs. These results show that doxorubicin not only increases oxidative stress, but also irreversibly affects action potential duration which may predispose to cardiac arrhythmias.

scholarly journals Cardiac structural and functional findings in Persian cats with autosomal dominant polycystic kidney disease

2020 ◽  
Vol 50 (9) ◽  
Author(s):  
Juliana Mariotti Guerra ◽  
Arine Pellegrino ◽  
Alexandre Gonçalves Teixeira Daniel ◽  
Mariana Ferreira de Freitas ◽  
Natália Cavalca Cardoso ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Large Scale ◽  
Autosomal Dominant ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Polycystic Kidney ◽  
Ventricular Ejection Fraction ◽  
Cardiac Phenotype ◽  
Autosomal Dominant Polycystic Kidney

ABSTRACT: Autosomal dominant polycystic kidney disease (ADPKD) has been related to left ventricular structural and functional abnormalities in human patients. The present study aimed to evaluate the cardiac structural and functional findings in Persian cats with ADPKD. Client-owned ADPKD (n=12) and non-ADPKD (n=12) Persian cats were enrolled in this study. The animals underwent echo- and electrocardiographic (ECG) examinations, and non-invasive measurements of systolic blood pressure (SBP) were obtained. Both groups were similar regarding hematological and biochemical parameters, including white blood cell count and levels of blood urea nitrogen, creatinine, total protein and thyroxine. There were no differences related to ECG parameters between ADPKD and non-ADPKD cats. Left ventricular hypertrophy (LVH) was demonstrated in 6/12 (50%) normotensive ADPKD cats with preserved renal function. There were no differences between animal groups regarding the echocardiographic parameters, including left ventricular ejection fraction and shortening fraction; however, basal interventricular septal thickness at end-diastole near the left ventricular outflow tract and aortic artery flow velocity showed slightly elevated values in ADPKD-cats. Our study revealed that Persian cats with ADPKD do not reproduce the functional and structural cardiac phenotype reported in human patients; however, large-scale cohort studies are necessary to distinguish the possibilities of a true linkage between ventricular myocardial hypertrophy and ADPKD in this breed.

scholarly journals Expert Comment: Is Medication Titration in Heart Failure too Complex?

2017 ◽  
Vol 03 (01) ◽  
pp. 25 ◽  
Author(s):  
John J Atherton ◽  
Annabel Hickey ◽  
◽  
◽  
Keyword(s):  
Heart Failure ◽  
Large Scale ◽  
Beta Blockers ◽  
Point Of Care ◽  
Angiotensin Receptor Blockers ◽  
Angiotensin Converting Enzyme Inhibitors ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Converting Enzyme Inhibitors ◽  
Ventricular Ejection Fraction

Large-scale randomised controlled trials (RCTs) have demonstrated that angiotensin-converting enzyme inhibitors, angiotensin receptor blockers and beta-blockers decrease mortality and hospitalisation in patients with heart failure (HF) associated with a reduced left ventricular ejection fraction. This has led to high prescription rates; however, these drugs are generally prescribed at much lower doses than the doses achieved in the RCTs. A number of strategies have been evaluated to improve medication titration in HF, including forced medication up-titration protocols, point-of-care decision support and extended scope of clinical practice for nurses and pharmacists. Most successful strategies have been multifaceted and have adapted existing multidisciplinary models of care. Furthermore, given the central role of general practitioners in long-term monitoring and care coordination in HF patients, these strategies should engage with primary care to facilitate the transition between the acute and primary healthcare sectors.

P1029Catheter ablation outcome and heart failure hospitalization in atrial fibrillation patients: insights from the Kansai plus atrial fibrillation (KPAF) registry

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
N Tanaka ◽  
K Inoue ◽  
A Kobori ◽  
K Kaitani ◽  
T Morimoto ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Large Scale ◽  
Independent Predictor ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Heart Failure Hospitalization ◽  
Ventricular Ejection Fraction ◽  
Multicenter Observational Study ◽  
Af Recurrence

Abstract Background Heart failure (HF) is the leading cause of death in patients with atrial fibrillation (AF). Radiofrequency catheter ablation (RFCA) for AF is effective to maintain sinus rhythm. Purpose We sought to clarify whether AF ablation outcome influenced incidence of HF hospitalization after the procedures. Methods We conducted a large-scale, prospective, multicenter, observational study. A total of 5010 consecutive patients who underwent an initial RFCA for AF in 26 centers were enrolled (average age, 64±10 years; non-paroxysmal AF, 35.6%). The median follow-up duration was 2.9 years. Results The 3-year cumulative incidence of AF recurrence after a single procedure was 40.2%. The 3-year incidence of hospitalization for HF was observed in 92 patients (1.8%) and was significantly higher in patients with AF recurrence than those without it (3.3% vs 0.84%, log-rank p<0.001). After adjustment by advanced age,(≥65 years), reduced left ventricular ejection fraction (≤50%), low estimated glomerular filtration rate (≤60ml/min), and history of HF, all of which were statistically associated with a risk of HF hospitalization (p<0.1, respectively), AF recurrence after the index RFCA was an independent predictor of HF hospitalization (hazard ratio [HR]; 3.17, 95% confidence interval [CI]; 2.06–5.04, p<0.001).Even after multiple procedures (1425 re-ablation sessions in 1274 patients [25.4%]), AF recurrence after the last procedure was an independent predictor of HF hospitalization (HR; 2.83, 95% CI; 1.89–4.24, p<0.001). Conclusions Among AF patients receiving RFCA, those with AF recurrence were at greater risk of heart failure hospitalization than were patients without AF recurrence. These differences should be noted when treating AF patients in actual clinical practice. Acknowledgement/Funding This study was supported by the Research Institute for Production Development in Kyoto, Japan.

New insights of tricuspid regurgitation: a large-scale prospective cohort study

2020 ◽  
Author(s):  
José María Vieitez ◽  
Juan Manuel Monteagudo ◽  
Patricia Mahia ◽  
Leopoldo Perez ◽  
Teresa Lopez ◽  
...  
Keyword(s):  
Right Ventricle ◽  
Tricuspid Regurgitation ◽  
Large Scale ◽  
Heart Association ◽  
Percutaneous Treatment ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Surgical Risk ◽  
High Surgical Risk

Abstract Aims To evaluate the burden of tricuspid regurgitation (TR) in a large cohort, determine the right ventricle involvement of patients with TR and determine the characteristics of isolated TR. Methods and results Prospective study where consecutive patients undergoing an echocardiographic study in 10 centres were included. All studies with significant TR (at least moderate) were selected. We considered that patients with one of pulmonary systolic hypertension &gt;50 mmHg, left ventricular ejection fraction &lt;35%, New York Heart Association III–IV, or older than 85 years, had a high surgical risk. A total of 35 088 echocardiograms were performed. Significant TR was detected in 6% of studies. Moderate TR was found in 69.6%, severe in 25.5%, massive in 3.9%, and torrential in 1.0% of patients. Right ventricle was dilated in 81.7% of patients with massive/torrential TR, in 55.9% with severe TR, and in 29.3% with moderate TR (P &lt; 0.001). Primary TR was present in 7.4% of patients whereas secondary TR was present in 92.6%. Mitral or aortic valve disease was the most common aetiology (54.6%), following by isolated TR (16%). Up to 51.9% of patients with severe, massive, or torrential primary TR and 57% of patients with severe, massive, or torrential secondary TR had a high surgical risk. Conclusion Significant TR is a prevalent condition and a high proportion of these patients have an indication for valve intervention. More than a half of patients with severe, massive, or torrential TR had a high surgical risk. Massive/torrential TR may have implications regarding selection and monitoring patients for percutaneous treatment.

Drug and Drug-Device Therapy in Heart Failure Patients in the Post-COMET and SCD-HeFT Era

2005 ◽  
Vol 10 (4_suppl) ◽  
pp. S45-S58 ◽  
Author(s):  
James A. Reiffel
Keyword(s):  
Heart Failure ◽  
Sudden Cardiac Death ◽  
Cardiac Death ◽  
Large Scale ◽  
Left Ventricular Systolic Dysfunction ◽  
Systolic Dysfunction ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Device Therapy ◽  
Ventricular Ejection Fraction

Reduced left ventricular ejection fraction and heart failure are the most important risk factors for sudden cardiac death. Recent trials have contributed to the knowledge base of critical therapies for the treatment of left ventricular systolic dysfunction and heart failure as it relates to arrhythmic and sudden cardiac death. Both pharmacologic and device therapies can reduce sudden cardiac death. The trials discussed in this paper have identified the pharmacologic and device interventions that are likely to improve the length and quality of life of the patient with left ventricular dysfunction and reduce the risk of sudden cardiac death. The mortality and anti-arrhythmic effects of angiotensin-converting enzyme inhibitors and β-blockers have been confirmed in large-scale controlled clinical heart failure trials. Recent trials have evaluated which agents are most effective and which patients will derive the most benefit from device therapy in terms of the reduction in the risk of sudden cardiac death and in the amelioration of heart failure. The recent data from the Carvedilol or Metoprolol European Trial (COMET) and the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) are discussed as the latest in the series of landmark studies that have shaped the current approaches to treating patients with heart failure and that have altered the heart failure treatment paradigm.

scholarly journals Differential Factors for Predicting Outcomes in Left Main versus Non-Left Main Coronary Bifurcation Stenting

2021 ◽  
Vol 10 (14) ◽  
pp. 3024
Author(s):  
Jung-Joon Cha ◽  
Soon Jun Hong ◽  
Hyung Joon Joo ◽  
Jae Hyoung Park ◽  
Cheol Woong Yu ◽  
...  
Keyword(s):  
Large Scale ◽  
Second Generation ◽  
Small Diameter ◽  
Target Lesion ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Left Main ◽  
Ventricular Ejection Fraction ◽  
Maximal Diameter ◽  
Main Vessel

Background: No large-scale study has compared the clinical and angiographic predictors of cardiovascular events in patients with left main bifurcation (LMB) and non-LMB stenting after second-generation DES implantation. Herein, we investigated differential clinical and angiographic factors for predicting outcomes in LMB versus non-LMB stenting. Methods: A total of 2648 patients with bifurcation lesions treated with second-generation DESs from the retrospective patient cohort were divided into an LMB group (n = 935) and a non-LMB group (n = 1713). The primary outcome was the 7-year incidence of target lesion failure (TLF), defined as the composite of cardiac death, myocardial infarction, and target lesion revascularization. Results: The incidence of TLF was 9.8%. Those in the LMB group were associated with a higher risk of TLF (14.2% versus 7.5%, p < 0.001) than those in the non-LMB group. Regarding the LMB group, independent predictors of TLF were chronic kidney disease (CKD), reduced left ventricular ejection fraction (LVEF), and two-stenting. Regarding the non-LMB group, CKD, reduced LVEF, old age, diabetes, and small diameter of the main vessel stent were independent predictors of TLF. Conclusions: The two-stent strategy could potentially increase TLF for the LMB lesions, and achieving the maximal diameter of the main vessel stent could result in better clinical outcomes for non-LMB lesions.

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