- 3D Bioprinted Functional and Contractile Cardiac Tissue Constructs. [Journal Article]
- ABActa Biomater 2018 Feb 13
- Bioengineering of a functional cardiac tissue composed of primary cardiomyocytes has great potential for myocardial regeneration and in vitro tissue modeling. However, its applications remain limited...
Bioengineering of a functional cardiac tissue composed of primary cardiomyocytes has great potential for myocardial regeneration and in vitro tissue modeling. However, its applications remain limited because the cardiac tissue is a highly organized structure with unique physiologic, biomechanical, and electrical properties. In this study, we undertook a proof-of-concept study to develop a contractile cardiac tissue with cellular organization, uniformity, and scalability by using three-dimensional (3D) bioprinting strategy. Primary cardiomyocytes were isolated from infant rat hearts and suspended in a fibrin-based bioink to determine the priting capability for cardiac tissue engineering. This cell-laden hydrogel was sequentially printed with a sacrificial hydrogel and a supporting polymeric frame through a 300-µm nozzle by pressured air. Bioprinted cardiac tissue constructs had a spontaneous synchronous contraction in culture, implying in vitro cardiac tissue development and maturation. Progressive cardiac tissue development was confirmed by immunostaining for α-actinin and connexin 43, indicating that cardiac tissues were formed with uniformly aligned, dense, and electromechanically coupled cardiac cells. These constructs exhibited physiologic responses to known cardiac drugs regarding beating frequency and contraction forces. In addition, Notch signaling blockade significantly accelerated development and maturation of bioprinted cardiac tissues. Our results demonstrated the feasibility of bioprinting functional cardiac tissues that could be used for tissue engineering applications and pharmaceutical purposes. Statement of Significance Cardiovascular disease remains a leading cause of death in the United States and a major health-care burden. Myocardial infarction (MI) is a main cause of death in cardiovascular diseases. MI occurs as a consequence of sudden blocking of blood vessels supplying the heart. When occlusions in the coronary arteries occur, an immediate decrease in nutrient and oxygen supply to the cardiac muscle, resulting in permanent cardiac cell death. Eventually, scar tissue formed in the damaged cardiac muscle that cannot conduct electrical or mechanical stimuli thus leading to a reduction in the pumping efficiency of the heart. The therapeutic options available for end-stage heart failure is to undergo heart transplantation or the use of mechanical ventricular assist devices (VADs). However, many patients die while being on a waiting list, due to the organ shortage and limitation of VADs, such as surgical complications, infection, thrombogenesis, and failure of the electrical motor and hemolysis. Ultimately, 3D bioprinting strategy aims to create clinically applicable tissue constructs that can be immediately implanted in the body. To date, the focus on replicating complex and heterogeneous tissue constructs continues to increase as 3D bioprinting technologies advance. In this study, we demonstrated the feasibility of 3D bioprinting strategy to bioengineer the functional cardiac tissue that possesses a highly organized structure with unique physiological and biomechanical properties similar to native cardiac tissue. This bioprinting strategy has great potential to precisely generate functional cardiac tissues for use in pharmaceutical and regenerative medicine applications.
- Carotid atherosclerosis and the association between nocturnal blood pressure dipping and cardiovascular events. [Journal Article]
- JCJ Clin Hypertens (Greenwich) 2018 Feb 16
- The impact of a nondipping blood pressure (BP) pattern, defined as (awake systolic BP - sleep systolic BP)/awake systolic BP < 0.1, on cardiovascular events in populations with different degrees of c...
The impact of a nondipping blood pressure (BP) pattern, defined as (awake systolic BP - sleep systolic BP)/awake systolic BP < 0.1, on cardiovascular events in populations with different degrees of carotid atherosclerosis is uncertain. The authors hypothesized that a nondipping BP pattern would show differential predictive power for cardiovascular events, including total cardiovascular death, sudden death, nonfatal cardiovascular events, and nonfatal stroke, between populations with and without carotid atherosclerosis. To test this hypothesis, the authors analyzed 493 patients (mean age 67.9 years, 47.5% men) from the J-HOP (Japan Morning Surge-Home Blood Pressure) study for whom ambulatory BP monitoring and carotid intima-media thickness data were available. Twenty-nine cardiovascular events occurred during follow-up (1867 person-years). A nondipping BP pattern was independently associated with cardiovascular events in the population without carotid atherosclerosis, defined as carotid intima-media thickness < 1.1 mm after adjustment for other cardiovascular risk factors including age, sex, diabetes mellitus, chronic kidney disease, and 24-hour systolic BP (hazard ratio, 8.15; 95% confidence interval, 1.76-37.78 [P < .01]). This association was not found in the population with carotid intima-media thickness ≥ 1.1 mm. Therefore, in the hypertensive population without carotid atherosclerosis, physicians should consider ambulatory BP monitoring to determine the nocturnal BP pattern as an alternative approach to assessing cardiovascular events.
- Position paper for the organization of ECMO programs for cardiac failure in adults. [Journal Article]
- ICIntensive Care Med 2018 Feb 15
- Extracorporeal membrane oxygenation (ECMO) has been used increasingly for both respiratory and cardiac failure in adult patients. Indications for ECMO use in cardiac failure include severe refractory...
Extracorporeal membrane oxygenation (ECMO) has been used increasingly for both respiratory and cardiac failure in adult patients. Indications for ECMO use in cardiac failure include severe refractory cardiogenic shock, refractory ventricular arrhythmia, active cardiopulmonary resuscitation for cardiac arrest, and acute or decompensated right heart failure. Evidence is emerging to guide the use of this therapy for some of these indications, but there remains a need for additional evidence to guide best practices. As a result, the use of ECMO may vary widely across centers. The purpose of this document is to highlight key aspects of care delivery, with the goal of codifying the current use of this rapidly growing technology. A major challenge in this field is the need to emergently deploy ECMO for cardiac failure, often with limited time to assess the appropriateness of patients for the intervention. For this reason, we advocate for a multidisciplinary team of experts to guide institutional use of this therapy and the care of patients receiving it. Rigorous patient selection and careful attention to potential complications are key factors in optimizing patient outcomes. Seamless patient transport and clearly defined pathways for transition of care to centers capable of providing heart replacement therapies (e.g., durable ventricular assist device or heart transplantation) are essential to providing the highest level of care for those patients stabilized by ECMO but unable to be weaned from the device. Ultimately, concentration of the most complex care at high-volume centers with advanced cardiac capabilities may be a way to significantly improve the care of this patient population.
- Understanding Spreading Depression from Headache to Sudden Unexpected Death. [Review]
- FNFront Neurol 2018; 9:19
- Spreading depression (SD) is a neurophysiological phenomenon characterized by abrupt changes in intracellular ion gradients and sustained depolarization of neurons. It leads to loss of electrical act...
Spreading depression (SD) is a neurophysiological phenomenon characterized by abrupt changes in intracellular ion gradients and sustained depolarization of neurons. It leads to loss of electrical activity, changes in the synaptic architecture, and an altered vascular response. Although SD is often described as a unique phenomenon with homogeneous characteristics, it may be strongly affected by the particular triggering event and by genetic background. Furthermore, SD may contribute differently to the pathogenesis of widely heterogeneous clinical conditions. Indeed, clinical disorders related to SD vary in their presentation and severity, ranging from benign headache conditions (migraine syndromes) to severely disabling events, such as cerebral ischemia, or even death in people with epilepsy. Although the characteristics and mechanisms of SD have been dissected using a variety of approaches, ranging from cells to human models, this phenomenon remains only partially understood because of its complexity and the difficulty of obtaining direct experimental data. Currently, clinical monitoring of SD is limited to patients who require neurosurgical interventions and the placement of subdural electrode strips. Significantly, SD events recorded in humans display electrophysiological features that are essentially the same as those observed in animal models. Further research using existing and new experimental models of SD may allow a better understanding of its core mechanisms, and of their differences in different clinical conditions, fostering opportunities to identify and develop targeted therapies for SD-related disorders and their worst consequences.
- Genetics, Clinical Features, and Long-Term Outcome of Noncompaction Cardiomyopathy. [Journal Article]
- JACCJ Am Coll Cardiol 2018 Feb 20; 71(7):711-722
- CONCLUSIONS: NCCM is a heterogeneous condition, and genetic stratification has a role in clinical care. Distinguishing genetic from nongenetic NCCM complements prediction of outcome and may lead to management and follow-up tailored to genetic status.
- Classification methods to detect sleep apnea in adults based on respiratory and oximetry signals: a systematic review. [Journal Article]
- PMPhysiol Meas 2018 Feb 15
- Sleep apnea (SA), a common sleep disorder, can significantly decrease the quality of life, and is closely associated with major health risk such as cardiovascular disease, sudden death, depression, a...
Sleep apnea (SA), a common sleep disorder, can significantly decrease the quality of life, and is closely associated with major health risk such as cardiovascular disease, sudden death, depression, and hypertension. Normal diagnostic process of SA using polysomnography (PSG) is costly and time consuming. In addition, the accuracy of different classification methods to detect SA varies with the use of different physiological signals. If an effective, reliable, and accurate classification method is developed, then the diagnosis of SA and their associated treatment will be time-efficient and economical. This study aims to systematically review the literature and present an overview on classification methods to detect SA using respiratory and oximetry signals and address the automated detection approach. Sixty-two included studies revealed the application of single and multiple signals (respiratory and oximetry) for the diagnosis of SA. Both airflow (AF) and oxygen saturation (SaO2) signals alone were effective in detecting SA in case of binary decision-making, whereas multiple signals were good for multi-class detection. In addition, some machine learning (ML) methods were superior to the other classification methods for SA detection using respiratory and oximetry signals. To deal with the respiratory and oximetry signals, a good choice of classification method as well as the consideration of associated factors would result in high accuracy in detection of SA. An accurate classification method should provide high detection rate with an automated (independent of human action) analysis of respiratory and oximetry signals. Future high-quality automated studies using large samples of data from multiple patient groups or record batches are recommended.
- ZBTB17 loss-of-function mutation contributes to familial dilated cardiomyopathy. [Journal Article]
- HVHeart Vessels 2018 Feb 14
- Dilated cardiomyopathy (DCM) is a common primary myocardial disease leading to congestive heart failure, arrhythmia and sudden cardiac death. Increasing studies demonstrate substantial genetic determ...
Dilated cardiomyopathy (DCM) is a common primary myocardial disease leading to congestive heart failure, arrhythmia and sudden cardiac death. Increasing studies demonstrate substantial genetic determinants for DCM. Nevertheless, DCM is of substantial genetic heterogeneity, and the genetic basis for DCM in most patients remains unclear. The present study was sought to investigate the association of a genetic variant in the ZBTB17 gene with DCM. A cohort of 158 unrelated patients with idiopathic DCM and a total of 230 unrelated, ethnically matched healthy individuals used as controls were recruited. The coding exons and splicing boundaries of ZBTB17 were sequenced in all study participants. The functional effect of the mutant ZBTB17 was characterized by a dual-luciferase reporter assay system. A novel heterozygous ZBTB17 mutation, p.E243X, was discovered in an index patient. Genetic scan of the mutation carrier's available relatives showed that the mutation was present in all affected family members but absent in unaffected family members. Analysis of the proband's pedigree revealed that the mutation co-segregated with DCM, which was transmitted in an autosomal dominant pattern with complete penetrance. The nonsense mutation was absent in the 460 control chromosomes. Functional assays demonstrated that the truncated ZBTB17 protein had no transcriptional activity as compared with its wild-type counterpart. This study firstly associates ZBTB17 loss-of-function mutation with enhanced susceptibility to DCM in humans, which provides novel insight into the molecular mechanism underpinning DCM, implying potential implications for genetic counseling and personalized management of DCM.
- Chronic intermittent hypoxia promotes myocardial ischemia-related ventricular arrhythmias and sudden cardiac death. [Journal Article]
- SRSci Rep 2018 Feb 14; 8(1):2997
- We investigated the effects of intermittent hypoxia (IH), such as that encountered in severe obstructive sleep apnea (OSA) patients, on the development and severity of myocardial ischemia-related ven...
We investigated the effects of intermittent hypoxia (IH), such as that encountered in severe obstructive sleep apnea (OSA) patients, on the development and severity of myocardial ischemia-related ventricular arrhythmias. Rats were exposed to 14 days of IH (30 s at 5%O2and 30 s at 21%O2, 8 h·day-1) or normoxia (N, similar air-air cycles) and submitted to a 30-min coronary ligature. Arterial blood pressure (BP) and ECG were recorded for power spectral analysis, ECG interval measurement and arrhythmia quantification. Left ventricular monophasic action potential duration (APD) and expression of L-type calcium (LTCC) and transient receptor potential (TRPC) channels were assessed in adjacent epicardial and endocardial sites. Chronic IH enhanced the incidence of ischemic arrhythmias, in particular ventricular fibrillation (66.7% vs. 33.3% in N rats, p < 0.05). IH also increased BP and plasma norepinephine levels along with increased low-frequency (LF), decreased high-frequency (HF) and increased LF/HF ratio of heart rate and BP variability. IH prolonged QTc and Tpeak-to-Tend intervals, increased the ventricular APD gradient and upregulated endocardial but not epicardial LTCC, TRPC1 and TRPC6 (p < 0.05). Chronic IH, is a major risk factor for sudden cardiac death upon myocardial ischemia through sympathoactivation and alterations in ventricular repolarization, transmural APD gradient and endocardial calcium channel expression.
- Clinical Usefulness of Wearable Cardioverter Defibrillator (WCD) and Current Understanding of Its Clinical Indication in Japan. [Journal Article]
- CJCirc J 2018 Feb 14
- Prevention of sudden cardiac death (SCD) has become an important issue in today's cardiovascular field, together with various developments in secondary prevention of basic cardiac diseases. The impor...
Prevention of sudden cardiac death (SCD) has become an important issue in today's cardiovascular field, together with various developments in secondary prevention of basic cardiac diseases. The importance of the implantable cardioverter defibrillator (ICD) is now widely accepted because it has exhibited significant improvement in patients' prognoses in ischemic and non-ischemic cardiovascular diseases. However, there is an unignorable gap between the ICD indication in the guidelines and real-world high-risk patients for SCD, especially in the acute recovery phase of cardiac injury. Although various studies have demonstrated a clinical benefit of defibrillation devices, the studies of immediate ICD use in the acute recovery phase have failed to exhibit a benefit in patients from the point of the view of a decrease in total deaths. To bridge this gap, the wearable cardioverter defibrillator (WCD) provides a safer observation period in the acute phase and eliminates inappropriate overuse of ICD in the subacute phase. Here, we discuss the usefulness of the WCD and current understanding of its indications based on various clinical data. In conclusion, WCD is a feasible bridge to therapy and/or safe observation for patients at high risk of SCD, especially in the acute recovery phase of cardiac diseases.
New Search Next
- An Inappropriate Shock Case Early after Implantation of a Subcutaneous Cardiac Defibrillator by Subcutaneous Entrapped Air. [Journal Article]
- IHInt Heart J 2018 Feb 14
- A 17-year-old woman was resuscitated from cardiac arrest due to ventricular fibrillation and was diagnosed with concealed long QT syndrome. She underwent subcutaneous implantable cardiac defibrillato...
A 17-year-old woman was resuscitated from cardiac arrest due to ventricular fibrillation and was diagnosed with concealed long QT syndrome. She underwent subcutaneous implantable cardiac defibrillator (S-ICD) implantation at our hospital. The device electrogram immediately after implantation was normal. Four days after implantation, she received an inappropriate shock. The device interrogation revealed a continuous baseline shift and frequent oversensing for low amplitude signals, followed by a shock. A chest radiograph in the orthogonal view showed entrapped subcutaneous air surrounding the distal electrode. Entrapped subcutaneous air can cause inappropriate shocks in the early period after S-ICD implantation.