Reported mortality with rotating sheaths vs. laser sheaths for transvenous lead extraction.

AIMS: Rotating sheaths and laser sheaths are commonly used for transvenous lead extraction. This study aims to compare observed mortality between both approaches. METHODS AND RESULTS: The Manufacturer and User Facility Device Experience database was searched from 2011 to 2016 to determine number of deaths associated with each sheath. An independent analytics firm provided estimates for number of cases done, allowing calculation of market share. A sensitivity analysis was performed to determine relative risk (RR) of mortality at the calculated market share (36% rotating/64% laser) and two others. Additional sensitivity analyses assumed underreporting of deaths associated with rotating sheaths. An estimated 50 545 extractions were performed. Thirteen deaths were associated with rotating sheaths compared to 167 with laser sheaths. Of these, 92% (rotating) and 95% (laser) were due to cardiovascular injury. At the calculated market share, the RR of death was 7.2 times greater with laser sheaths [95% confidence interval (CI) 4.1-12.7, P < 0.0001]. At market share estimates of 25% rotating/75% laser and 45% rotating/55% laser, the RR of death with laser sheaths was 4.3 (95% CI 2.4-7.5, P < 0.0001) and 10.5 times greater (95% CI 6.0-18.5, P < 0.0001), respectively. The RR of death remained significant when assuming deaths with rotating sheaths were underreported and when deaths using both sheaths were attributed to the rotating sheath. CONCLUSIONS: Lead extraction with laser sheaths appears to be associated with a higher risk of mortality compared to rotating sheaths. Further studies are warranted to confirm this finding.

Wireless power transfer to deep-tissue microimplants.

The ability to implant electronic systems in the human body has led to many medical advances. Progress in semiconductor technology paved the way for devices at the scale of a millimeter or less ("microimplants"), but the miniaturization of the power source remains challenging. Although wireless powering has been demonstrated, energy transfer beyond superficial depths in tissue has so far been limited by large coils (at least a centimeter in diameter) unsuitable for a microimplant. Here, we show that this limitation can be overcome by a method, termed midfield powering, to create a high-energy density region deep in tissue inside of which the power-harvesting structure can be made extremely small. Unlike conventional near-field (inductively coupled) coils, for which coupling is limited by exponential field decay, a patterned metal plate is used to induce spatially confined and adaptive energy transport through propagating modes in tissue. We use this method to power a microimplant (2 mm, 70 mg) capable of closed-chest wireless control of the heart that is orders of magnitude smaller than conventional pacemakers. With exposure levels below human safety thresholds, milliwatt levels of power can be transferred to a deep-tissue (>5 cm) microimplant for both complex electronic function and physiological stimulation. The approach developed here should enable new generations of implantable systems that can be integrated into the body at minimal cost and risk.

Screening drug-induced arrhythmia [corrected] using human induced pluripotent stem cell-derived cardiomyocytes and low-impedance microelectrode arrays.

BACKGROUND: Drug-induced arrhythmia is one of the most common causes of drug development failure and withdrawal from market. This study tested whether human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) combined with a low-impedance microelectrode array (MEA) system could improve on industry-standard preclinical cardiotoxicity screening methods, identify the effects of well-characterized drugs, and elucidate underlying risk factors for drug-induced arrhythmia. hiPSC-CMs may be advantageous over immortalized cell lines because they possess similar functional characteristics as primary human cardiomyocytes and can be generated in unlimited quantities. METHODS AND RESULTS: Pharmacological responses of beating embryoid bodies exposed to a comprehensive panel of drugs at 65 to 95 days postinduction were determined. Responses of hiPSC-CMs to drugs were qualitatively and quantitatively consistent with the reported drug effects in literature. Torsadogenic hERG blockers, such as sotalol and quinidine, produced statistically and physiologically significant effects, consistent with patch-clamp studies, on human embryonic stem cell-derived cardiomyocytes hESC-CMs. False-negative and false-positive hERG blockers were identified accurately. Consistent with published studies using animal models, early afterdepolarizations and ectopic beats were observed in 33% and 40% of embryoid bodies treated with sotalol and quinidine, respectively, compared with negligible early afterdepolarizations and ectopic beats in untreated controls. CONCLUSIONS: We found that drug-induced arrhythmias can be recapitulated in hiPSC-CMs and documented with low impedance MEA. Our data indicate that the MEA/hiPSC-CM assay is a sensitive, robust, and efficient platform for testing drug effectiveness and for arrhythmia screening. This system may hold great potential for reducing drug development costs and may provide significant advantages over current industry standard assays that use immortalized cell lines or animal models.

Aortic arch vessel geometries and deformations in patients with thoracic aortic aneurysms and dissections.

PURPOSE: To quantify aortic arch geometry and in vivo cardiac-induced and respiratory-induced arch translations and arch branch angulations using three-dimensional geometric modeling techniques. MATERIALS AND METHODS: Scanning with electrocardiogram-gated computed tomography angiography during inspiratory and expiratory breath holds was performed in 15 patients (age, 64 y ± 14) with thoracic aortic aneurysms or dissections. From the lumen models, centerlines of the thoracic aorta, brachiocephalic artery, left common carotid artery, and left subclavian artery and their branching ostia positions were quantified. Three-dimensional translation of vessel ostia, branching angles, and their changes secondary to cardiac pulsation and respiration were computed. RESULTS: During expiration, all ostia translated rightward from systole to diastole (P < .035). Regardless of cardiac phase, all ostia translated posteriorly and superiorly from inspiration to expiration (P < .05). Respiration induced greater posterior and superior translations than cardiac pulsation (P < .03). The left common carotid artery branch angled significantly more toward the aortic arch compared with the brachiocephalic artery and left subclavian artery (P < .03). No significant changes in branching angle were found from systole to diastole or inspiration to expiration. CONCLUSIONS: In patients with thoracic aortic aneurysms or dissections, the thoracic aortic arch translated significantly secondary to inspiration and expiration and to a lesser extent secondary to cardiac pulsation. Insignificant branching angle changes suggest that the aortic arch and its branch origins move predominantly in unison.

Congenital anomalies of the aortic arch in acute type-a aortic dissection: implications for monitoring, perfusion strategy, and surgical repair.

OBJECTIVE: To assess whether management of acute Stanford type-A aortic dissection differs in patients with congenital anomalies of the aortic arch compared with standard institutional practice. DESIGN: Retrospective analysis of all consecutive patients from 2001 through 2011. SETTING: Quaternary referral center for surgical management of thoracic aortic disease. PARTICIPANTS: All patients with arch anomalies who underwent surgery for acute Stanford type-A aortic dissection during the study period (n = 43). INTERVENTIONS: Surgical management, anesthetic monitoring, and perfusion strategy were analyzed in a retrospective fashion. No new interventions were undertaken as part of this study. MEASUREMENTS AND MAIN RESULTS: Management differed most in patients with an aberrant right subclavian artery (n = 5), because the institutional standard of right axillary artery cannulation with left upper extremity arterial pressure monitoring was not possible. In patients with one of two "bovine" arch patterns (n = 32), management differed in the conduct of selective antegrade cerebral perfusion, which could include clamping above or below the takeoff of the left common carotid artery (and, therefore, produced unilateral or bilateral antegrade cerebral perfusion). All patients with a connective tissue disorder exhibited a bovine arch pattern. Management of patients with a right arch (n = 3) reflected the opposite of management for normal anatomy (for patients with traditional mirror-image branching) or opposite that of the aberrant right subclavian group (for patients who had a corresponding aberrant left subclavian artery). CONCLUSIONS: Rational management reflected the anatomic variations observed. These results support the importance of interdisciplinary planning, especially in an emergency, to optimize outcome.

Thrombectomy using AlphaVac for left atrial thrombus causing mechanical mitral valve obstruction and cardiogenic shock.

We present a 73-year-old female with history of rheumatic heart disease status post-mechanical mitral valve on warfarin, valvular atrial fibrillation, and alpha thalassemia who was admitted to an outside hospital with anterior ST-segment myocardial infarction. Coronary angiogram showed occluded left anterior descending artery (LAD) with acute thrombus status post-thrombectomy and balloon angioplasty.

Protein-polymer hybrid nanoparticles for drug delivery.

Amphiphilic bovine serum albumin-poly(methyl methacrylate) conjugate forms nanoparticles with the uniform size of ~100 nm by self-assembling. Loaded with the hydrophobic anti-tumor drug camptothecin, the nanoparticle efficiently delivers drugs into cancer cells, and thus inhibits ~79% of tumor growth in animals compared with free drug.

Data Analytics of Electronic Medical Record to Study Racial Diversities in Cardiovascular Diagnosis and Treatment.

The study of precision medicine that measures the effects of social, cultural, and environmental influences on health is essential to improve health outcomes. Race is a social concept used historically to divide, track, control populations, and reinforce social hierarchies. Beyond genetics, race is also a surrogate for other socioeconomic factors affecting patient outcomes. Our data analytics study aims to analyze the Electronic Medical Record (EMR) to study patients of different races in diagnosing and treating Coronary Artery Disease (CAD). We found no race discrepancies at the University of California San Francisco Medical Centers. This study opens several new hypotheses for further research in this crucial field.

Data Analytics of Electronic Health Records to Enhance Care of Coronary Artery Disease in Younger Women with Avoiding Possible Delay in Treatment.

Early detection plays a key role to enhance the outcome for Coronary Artery Disease. We utilized a big data analytics platform on ∼32,000 patients to trace patients from the first encounter to CAD treatment. There are significant gender-based differences in patients younger than 60 from the time of the first encounter to Coronary Artery Bypass Grafting with a p-value=0.03. This recognition makes significant changes in outcome by avoiding delay in treatment.

An Ontology for Cardiothoracic Surgical Education and Clinical Data Analytics.

The development of an ontology facilitates the organization of the variety of concepts used to describe different terms in different resources. The proposed ontology will facilitate the study of cardiothoracic surgical education and data analytics in electronic medical records (EMR) with the standard vocabulary.

Gender-based time discrepancy in diagnosis of coronary artery disease based on data analytics of electronic medical records.

Background: Women continue to have worse Coronary Artery Disease (CAD) outcomes than men. The causes of this discrepancy have yet to be fully elucidated. The main objective of this study is to detect gender discrepancies in the diagnosis and treatment of CAD. Methods: We used data analytics to risk stratify ~32,000 patients with CAD of the total 960,129 patients treated at the UCSF Medical Center over an 8 year period. We implemented a multidimensional data analytics framework to trace patients from admission through treatment to create a path of events. Events are any medications or noninvasive and invasive procedures. The time between events for a similar set of paths was calculated. Then, the average waiting time for each step of the treatment was calculated. Finally, we applied statistical analysis to determine differences in time between diagnosis and treatment steps for men and women. Results: There is a significant time difference from the first time of admission to diagnostic Cardiac Catheterization between genders (p-value = 0.000119), while the time difference from diagnostic Cardiac Catheterization to CABG is not statistically significant. Conclusion: Women had a significantly longer interval between their first physician encounter indicative of CAD and their first diagnostic cardiac catheterization compared to men. Avoiding this delay in diagnosis may provide more timely treatment and a better outcome for patients at risk. Finally, we conclude by discussing the impact of the study on improving patient care with early detection and managing individual patients at risk of rapid progression of CAD.

Coronary artery disease detection using artificial intelligence techniques: A survey of trends, geographical differences and diagnostic features 1991-2020.

While coronary angiography is the gold standard diagnostic tool for coronary artery disease (CAD), but it is associated with procedural risk, it is an invasive technique requiring arterial puncture, and it subjects the patient to radiation and iodinated contrast exposure. Artificial intelligence (AI) can provide a pretest probability of disease that can be used to triage patients for angiography. This review comprehensively investigates published papers in the domain of CAD detection using different AI techniques from 1991 to 2020, in order to discern broad trends and geographical differences. Moreover, key decision factors affecting CAD diagnosis are identified for different parts of the world by aggregating the results from different studies. In this study, all datasets that have been used for the studies for CAD detection, their properties, and achieved performances using various AI techniques, are presented, compared, and analyzed. In particular, the effectiveness of machine learning (ML) and deep learning (DL) techniques to diagnose and predict CAD are reviewed. From PubMed, Scopus, Ovid MEDLINE, and Google Scholar search, 500 papers were selected to be investigated. Among these selected papers, 256 papers met our criteria and hence were included in this study. Our findings demonstrate that AI-based techniques have been increasingly applied for the detection of CAD since 2008. AI-based techniques that utilized electrocardiography (ECG), demographic characteristics, symptoms, physical examination findings, and heart rate signals, reported high accuracy for the detection of CAD. In these papers, the authors ranked the features based on their assessed clinical importance with ML techniques. The results demonstrate that the attribution of the relative importance of ML features for CAD diagnosis is different among countries. More recently, DL methods have yielded high CAD detection performance using ECG signals, which drives its burgeoning adoption.

Three-dimensional electrospun ECM-based hybrid scaffolds for cardiovascular tissue engineering.

Electrospinning using natural proteins or synthetic polymers is a promising technique for the fabrication of fibrous scaffolds for various tissue engineering applications. However, one limitation of scaffolds electrospun from natural proteins is the need to cross-link with glutaraldehyde for stability, which has been postulated to lead to many complications in vivo including graft failure. In this study, we determined the characteristics of hybrid scaffolds composed of natural proteins including collagen and elastin, as well as gelatin, and the synthetic polymer poly(epsilon-caprolactone) (PCL), so to avoid chemical cross-linking. Fiber size increased proportionally with increasing protein and polymer concentrations, whereas pore size decreased. Electrospun gelatin/PCL scaffolds showed a higher tensile strength when compared to collagen/elastin/PCL constructs. To determine the effects of pore size on cell attachment and migration, both hybrid scaffolds were seeded with adipose-derived stem cells. Scanning electron microscopy and nuclei staining of cell-seeded scaffolds demonstrated the complete cell attachment to the surfaces of both hybrid scaffolds, although cell migration into the scaffold was predominantly seen in the gelatin/PCL hybrid. The combination of natural proteins and synthetic polymers to create electrospun fibrous structures resulted in scaffolds with favorable mechanical and biological properties.

Human adipose stem cells: a potential cell source for cardiovascular tissue engineering.

BACKGROUND/AIMS: A crucial step in providing clinically relevant applications of cardiovascular tissue engineering involves the identification of a suitable cell source. The objective of this study was to identify the exogenous and endogenous parameters that are critical for the differentiation of human adipose stem cells (hASCs) into cardiovascular cells. METHODS: hASCs were isolated from human lipoaspirate samples, analyzed, and subjected to two differentiation protocols. RESULTS: As shown by fluorescence-activated cell sorter (FACS) analysis, a population of hASCs expressed stem cell markers including CXCR4, CD34, c-kit, and ABCG2. Further, FACS and immunofluorescence analysis of hASCs, cultured for 2 weeks in DMEM-20%-FBS, showed the expression of smooth muscle cell (SMC)-specific markers including SM alpha-actin, basic calponin, h-caldesmon and SM myosin. hASCs, cultured for 2 weeks in endothelial cell growth medium-2 (EGM-2), formed a network of branched tube-like structures positive for CD31, CD144, and von Willebrand factor. The frequency of endothelial cell (EC) marker-expressing cells was passage number-dependent. Moreover, hASCs attached and formed a confluent layer on top of electrospun collagen-elastin scaffolds. Scanning electron microscopy and DAPI staining confirmed the integration of hASCs with the fibers and formation of a cell-matrix network. CONCLUSION: Our results indicate that hASCs are a potential cell source for cardiovascular tissue engineering; however, the differentiation capacity of hASCs into SMCs and ECs is passage number- and culture condition-dependent.

The role of cytoprotective cytokines in cardiac ischemia/reperfusion injury.

The mechanism(s) underlying the beneficial effects of adult mesenchymal stem cells (MSCs) after myocardial infarction (MI) is poorly understood. One possible explanation is the ability of MSCs to secrete cytokines, which modulate cardiomyocyte survival and function. MSCs express at least two cytoprotective cytokines, hepatocyte growth factor (HGF) and stromal cell-derived factor-1 alpha (CXCL12). The aim of our study was to compare the effects of these two cytokines administered acutely post-MI. We subjected adult male Lewis rats to myocardial ischemia/reperfusion injury. Immediately upon reperfusion, polymers saturated with HGF or CXCL12 were placed onto the infarcted anterior wall and the rats were allowed to recover. Echocardiographic analysis at 4 wk post-MI to assess left ventricular (LV) function revealed that LV ejection fraction was increased in the HGF treated group compared with the phosphate-buffered saline (PBS) control group. Likewise, LV end diastolic dimension was reduced in the HGF treated group compared with the PBS control group. Similarly, invasive hemodynamics at 12 wk showed improved contractility and relaxation in the HGF treated group compared with the PBS control group. In contrast, no significant effect on LV function was seen in the CXCL12 treated group. To determine the potential mechanism for this effect, infarct size (IFS) at 72 h was determined. IFS was decreased 4.2-fold in the HGF treated group compared with the PBS control group. Thus, HGF acutely post-MI using polymer delivery reduces IFS, leading to beneficial effects on post-MI LV remodeling.

Alcohol use in donors is a protective factor on recipients' outcome after heart transplantation.

OBJECTIVE: The outcome of heart transplantation is highly influenced by good donor selection. Because a history of alcoholism is prevalent among potential heart donors, we sought to explore the effect of alcohol use in donors on the outcome of heart transplantation in the recipient. METHOD: A total of 437 consecutive patients underwent heart transplantation from January 2002 through September 2005. Patients' files were retrospectively studied. Mean follow-up period was 3.14+/-1.9 years (range, 3 days to 6.5 yrs). The cohort was divided into two subgroups. The alcoholic donor group (ADG) included 98 of 421 patients and the nonalcoholic donor group (NADG) included 323 of 421 patients. Mean age was 35.3+/-11.4 yrs (range, 18-66) for the ADG and 33+/-12.2 yrs (range, 18-62) for the NADG. RESULTS: Mortality among the ADG was 7 of 98 (7.1%) and for NADG was 55 of 323 (17.1%) (P=0.015). The mean interval time between transplant and mortality was, for ADG, 27.7+/-20.6 months (range, 0.07-51) and for NADG, 16.4+/-19.6 months (range, 0.14-73) (P=0.031). Survival rate was significantly higher among the ADG at 72.8+/-1.9 months compared with NADG at 66.2+/-1.5 months (P=0.019). Overall rejection rate was 22 of 421 (5.2%); rejection rate was 17 of 323 (5.2%) in NADG and 5 of 98 (5.1%) in ADG. Rejection free survival was 74.6+/-0.85 with no significant difference between the two groups (P=0.85). CONCLUSION: The chronic alcoholism of donors was found to be a protective factor regarding the outcome after heart transplantation. Significant differences were found in mortality rate and survival after heart transplantation between the ADG and NADG. These data support the fact that it is safe to use donors' hearts regardless of a history of alcoholism.

Influence of systematically varied nano-scale topography on cell morphology and adhesion.

The types of cell-matrix adhesions and the signals they transduce strongly affect the cell-phenotype. We hypothesized that cells sense and respond to the three-dimensionality of their environment, which could be modulated by nano-structures on silicon surfaces. Human foreskin fibroblasts were cultured on nano-structures with different patterns (nano-post and nano-grate) and heights for 3 days. The presence of integrin alpha(5), beta(1), beta(3), paxillin and phosphorylated FAK (pFAK) were detected by western blot and immunofluorescence. Integrin beta(3) exhibited stronger signals on nano-grates. pFAK and paxillin were observed as small dot-like patterns on the cell-periphery on nano-posts and as elongated and aligned patterns on nano-grates. Collectively, our observations highlighted the presence of focal (integrin beta(1), beta(3), pFAK, paxillin), fibrillar (integrin alpha(5), beta(1)) and 3-D matrix (integrin alpha(5), beta(1), paxillin) adhesions on nano-structures. The presented nano-structures offer interesting opportunities to study the interaction of cells with topographical features comparable to the size of extracellular matrix components.

Cell interaction with three-dimensional sharp-tip nanotopography.

Cells in their native microenvironment interact with three-dimensional (3D) nanofeatures. Despite many reports on the effects of substrate nanotopography on cells, the independent effect of 3D parameters has not been investigated. Recent advances in nanofabrication for precise control of nanostructure pattern, periodicity, shape, and height enabled this systematic study of cell interactions with 3D nanotopographies. Two distinct nanopatterns (posts and grates) with varying three-dimensionalities (50-600 nm in nanostructure height) were created, while maintaining the pattern periodicity (230 nm in pitch) and tip shape (needle- or blade-like sharp tips). Human foreskin fibroblasts exhibited significantly smaller cell size and lower proliferation on needle-like nanoposts, and enhanced elongation with alignment on blade-like nanogrates. These phenomena became more pronounced as the nanotopographical three-dimensionality (structural height) increased. The nanopost and nanograte architectures provided the distinct contact guidance for both filopodia extension and the formation of adhesion molecules complex, which was believed to lead to the unique cell behaviors observed.

Quantification of motion of the thoracic aorta after ascending aortic repair of type-A dissection.

PURPOSE: To quantify cardiac and respiratory deformations of the thoracic aorta after ascending aortic graft repair. METHODS: Eight patients were scanned with cardiac-resolved computed tomography angiography during inspiratory/expiratory breath-holds. Aortic centerlines and lumen were extracted to compute the arclength, curvature, angulation, and cross-section shape. RESULTS: From systole to diastole, the angle of graft [Formula: see text] arch increased by 2.4[Formula: see text] ± 1.8[Formula: see text] (P < 0.01) and the angle of arch [Formula: see text] descending aorta decreased by 2.4[Formula: see text] ± 2.6[Formula: see text] (P < 0.05), while the effective diameter of the proximal arch decreased by 2.4 ± 1.9% (P < 0.01), a greater change than those of the graft or distal arch (P < 0.05). From inspiration to expiration, the angle of graft [Formula: see text] arch increased by 2.8[Formula: see text] ± 2.6[Formula: see text] (P < 0.02) with the peak curvature increase (P < 0.05). Shorter graft length was correlated with greater cardiac-induced graft [Formula: see text] arch angulation, and longer graft length was correlated with greater respiratory-induced arch [Formula: see text] descending aorta angulation (R [Formula: see text] 0.50). CONCLUSION: The thoracic aorta changed curvature and angulation with cardiac and respiratory influences, driven by aortic root and arch motion. The thoracic aortic geometry and deformation are correlated with the ascending aortic graft length.