The effect of standardization of insertion and removal of percutaneous left ventricular assist device.

BACKGROUND: The effect of standardizing an insertion and removal protocol for pVAD devices has not been previously described. OBJECTIVES: We sought to evaluate clinical outcomes in patients who underwent pVAD insertion pre- and post-protocol standardization. METHODS: All patients who underwent pVAD insertion that remained in place at index procedure completion between January 2017 and September 2023 at a single academic center for both high-risk PCI and cardiogenic shock indications were included in the study. The primary outcome was the incidence of limb ischemia and major bleeding before and after the protocol initiation. Secondary outcomes included in-hospital and 30-day MACCE rate (death, myocardial infarction, stroke, emergent CABG), and how often the operators followed the protocol. RESULTS: A total of 89 patients had pVAD left in place (29 pre-protocol initiation and 60 post-protocol initiation). There was a significant decrease in incidence of limb ischemia post-protocol initiation compared to pre (17.2 % vs 1.7 %, p = 0.01) but no difference in bleeding incidence (13.8 % vs 20.0 %, p = 0.47). Adherence increased in all components of the protocol except for right heart catheterization. CONCLUSION: Standardization of an insertion and removal protocol for pVAD devices led to a statistically significant decrease in limb ischemia in a high-risk patient population.

Techniques to Overcome the Pushability of Robotic-Assisted PCI.

Robotic-assisted percutaneous coronary intervention (PCI) was developed with a safety system that limits pushability as compared to manual PCI, thus preventing inadvertent deep delivery of the device and avoiding complications. This safety feature may limit robotic completion when performing intervention to more complex lesions that may require device delivery through calcified or previously stented lesions. In this article, we report three cases that highlight techniques to overcome this limited pushability, resulting in successful robotic completion of the procedures.

Implementation of Robotic-Assisted Percutaneous Coronary Intervention Into a High-Risk PCI Program.

BACKGROUND: How to implement robotic-assisted PCI safely and when to escalate to more complex cases has not been previously described. We sought to evaluate clinical outcomes in patients undergoing robotic-assisted PCI in the first year of a newly established robotic-assisted PCI program. METHODS: All patients who underwent robotic-assisted PCI in the first 12 months at a single academic center were included in the study. Lesion complexity was characterized as "PRECISE-like", "CORA-PCI-like", or "CORA-PCI excluded" based on established criteria. The primary outcome was clinical success, defined as <30% residual stenosis after stenting with a final TIMI flow grade 2-3 and no procedural complications. Secondary outcomes included robotic success, defined as clinical success with robotic completion, unintentional manual conversion rate, procedure time, and procedural complications. RESULTS: Of the 57 consecutive lesions treated, 12 (22.6%) had a PRECISE-like lesion complexity while 32 (56.1%) had a CORA- PCI-like, and 13 (22.8%) a CORA-PCI excluded lesion complexity. There was no significant difference in clinical success (100.0% vs. 96.7% vs. 100.0%, p = 1.00) among the groups but robotic success was numerically lower as complexity increased (100.0% vs. 80.0% vs. 72.7%, p = 0.15), with an increased frequency of manual conversion. There was no significant difference in procedural complication rates among the groups. The robotic completion rate improved during the study period. CONCLUSION: Robotic-assisted PCI, can be safely implemented in a moderate-sized academic center, with a rapid escalation in patient and lesion complexity.

Clinical Impact of Tricuspid Regurgitation on Transcatheter Edge-to-Edge Mitral Valve Repair for Mitral Regurgitation.

OBJECTIVES: This study aimed to evaluate whether baseline tricuspid regurgitation (TR) impacted clinical outcomes after mitral valve transcatheter edge-to-edge repair (M-TEER) for severe secondary mitral regurgitation (MR). BACKGROUND: Baseline TR is common among patients undergoing M-TEER for secondary MR, although its impact on clinical outcomes is unclear. METHODS: The Cochrane Library, PubMed/MEDLINE, and Google Scholar were searched according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines from January 1, 2011 through January 31, 2021. Randomized controlled trials and nonrandomized prospective studies that evaluated baseline TR by echocardiography before M-TEER for MR were included. The primary outcome was a composite of mortality and heart failure hospitalization (HFH) at 1-year. RESULTS: A total of 5 studies (n = 1395 patients) were included in the primary analysis. Concurrent moderate/severe TR was associated with a worse 1 year composite of all-cause mortality and HFH (OR: 2.13; 95% CI: 1.12-4.05; p = 0.02) after M-TEER for severe MR. In studies that reported TR grade pre- and post-M-TEER for severe MR, 32% of patients with moderate-to-severe baseline TR had a reduction in TR severity after the intervention. CONCLUSIONS: Baseline moderate-to-severe TR was associated with increased 1-year mortality and heart failure hospitalizations among patients undergoing M-TEER. Further randomized studies are needed to assess the interaction of TR among patients undergoing M-TEER.

Totally Robotic Three-Vessel Percutaneous Coronary Intervention With Total Occlusion Using Robotic Automation.

Robotic-assisted percutaneous coronary intervention (PCI) has emerged as an alternative to manual PCI to mitigate the risk of occupational hazards for operators, and to increase precision of device placement. Previous studies have reported the safety and efficacy of robotic-assisted PCI in simpler lesions, and recently the safety and efficacy of robotic-assisted chronic total occlusion PCI have been reported. Herein, we report two cases with three-vessel disease, including total occlusions, successfully treated robotically utilizing newer guidewire and device automation.

Siddha fasting in obese acute decompensated heart failure may improve hospital outcomes through empowerment and natural ketosis.

BACKGROUND: Morbid obesity (BMI > 35 kg/m2 with comorbid conditions) is present in 25 - 35% of acute decompensated heart failure (AHF) patients. Prevalence of HF increases with duration of morbid obesity from 30% at 15 years to over 90% at 30 years. There is a need to develop pragmatic therapies that address the unique physical and mental challenges faced by obese AHF patients. Siddha is 5,000 year old Tamil Medicine using yoga and mind-body methods towards higher consciousness. Hunger gratitude Experience (HUGE) is intuitive Siddha fasting method which may improve in-hospital AHF outcomes independent of weight reduction. CASE SUMMARY: We present 5 cases of morbidly obese patients with cardiorenal syndrome (CRS) that began intermittent fasting either during their AHF hospitalization or in the outpatient setting for refractory symptoms despite hospitalization. Initiation of fasting correlated with reduction of respiratory distress and edema as well as improvements in psychological wellbeing and functional capacity. DISCUSSION: Siddha fasting mediates hemodynamic and anti-inflammatory effects through natural ketosis and psychological benefits through empowerment in AHF. Potential role of fasting in reducing myocardial workload, coronary steal, angina, volume overload, and CRS needs further study in cardiac patients.

Radial versus femoral access for left main percutaneous coronary intervention: An analysis from the Veterans Affairs Clinical, Reporting, and Tracking Program.

OBJECTIVES: We aimed to compare clinical characteristics and procedural outcomes of left main percutaneous interventions (LM-PCI) by transradial (TRA) versus transfemoral (TFA) approach in the VA healthcare system. BACKGROUND: TRA for percutaneous coronary intervention (PCI) is steadily increasing. However, the frequency and efficacy of TRA for LM-PCI remain less studied. METHODS: All LM-PCIs performed in the VA healthcare system were identified for fiscal year 2008 through 2018. Patients' baseline characteristics and procedure-related variables were compared by access site. Both short- and long-term clinical outcomes were analyzed using propensity score matching. RESULTS: A total of 4004 LM-PCI were performed in the VA via either radial or femoral access from 2008 to 2018. Among these, 596 (14.9%) LM PCIs were performed via TRA. Use of TRA for LM-PCI increased from 2.2% to 31.5% over the study period. Propensity matched outcome analysis, comparing TRA versus TFA, showed a similar procedural success (98.4% for TRA vs. 97.8% for TFA; RR: 1.01 [0.98, 1.03]) and 1-year major adverse cardiovascular events (MACE) (25.9% for TRA vs. 26.8% TFA; RR: 0.96 [0.74, 1.25]). There were no statistically significant differences among secondary outcomes analyses including major bleeding. CONCLUSION: Use of TRA for LM-PCI has been steadily increasing in the VA healthcare system. These findings demonstrate similar procedural success and 1-year MACE across access strategies, suggesting an opportunity to continue increasing TRA use for LM-PCI.

Anemia Among Patients Undergoing Transcatheter Mitral Valve Repair: From the National Inpatient Sample in the United States.

Background The prevalence and impact of anemia on the outcomes of transcatheter mitral valve repair (TMVr) have not been well-studied. Anemia is a commonly encountered comorbidity among patients with cardiovascular disorders and is frequently under-recognized. The study aimed to analyze the prevalence of anemia and its impact on post-TMVr in-hospital outcomes. Methods The National Inpatient Sample (NIS) was queried to identify all patients who underwent TMVr from 2011-2015 in the United States by utilizing suitable International Classification of Diseases, Ninth Revision (ICD-9) codes. The baseline characteristics and in-hospital outcomes were compared among patients with and without anemia. Results A total of 4,382 patients were identified. Out of these, 978 (22.3%) patients had baseline anemia. Anemic patients were noted to have a higher burden of co-morbidities, including chronic kidney disease, hypertension, and diabetes mellitus. The in-hospital mortality was higher but not statistically significant between anemic and non-anemic patients (3.6% vs 2.6%; odds ratio (OR): 1.44; confidence interval (CI): 0.85-2.46, p=0.179). The other adverse outcomes, including the length of stay, the requirement for blood transfusions, the incidence of post-implant acute kidney injury, hemodialysis, and the cost of hospitalization, were higher in anemic patients. Conclusion Anemia was present in one out of five patients undergoing TMVr in this nationally representative cohort. Baseline anemia showed numerically higher but not statistically significant in-hospital mortality and was associated with other in-hospital adverse outcomes. Further larger studies are needed to highlight the importance of anemia in the TMVr procedure.

Novel Assessment of Ischemia in Patients With Anomalous Right Coronary Artery.

Anomalous right coronary arteries are usually benign; however, sudden death owing to myocardial ischemia, especially during exertion, have been reported in patients with intramural or interarterial course, which is likely due to dynamic obstruction. We propose a novel method of physiological evaluation with instantaneous wave-free ratio with dobutamine infusion to simulate controlled dynamic obstruction in anomalous right coronary arteries. (Level of Difficulty: Intermediate.).

A novel nonpharmacologic technique to remove entrapped radial sheath.

Radial artery access for performance of coronary and peripheral diagnostic as well as interventional procedures is on the rise. With increasing adoption comes the expected increase in procedural complications. We describe a novel, simple, and effective nonpharmacologic solution for sheath entrapment related to pharmaco-resistant radial artery spasm. © 2014 Wiley Periodicals, Inc.

Ultrastructure Study of Transgenic Ren2 Rat Aorta - Part 1: Endothelium and Intima.

BACKGROUND: The renin-angiotensin-aldosterone system plays an important role in the development and progression of hypertension and accelerated atherosclerosis (atheroscleropathy) associated with the cardiorenal metabolic syndrome and type 2 diabetes mellitus. Additionally, the renin-angiotensin-aldosterone system plays an important role in vascular-endothelial-intimal cellular and extracellular remodeling. METHODS: Thoracic aortas of young male transgenic heterozygous (mRen2)27 (Ren2) rats were utilized for this ultrastructural study. This lean model of hypertension, insulin resistance and oxidative stress harbors the mouse renin gene with increased local tissue (aortic) levels of angiotensin II and angiotensin type 1 receptors and elevated plasma aldosterone levels. RESULTS: The ultrastructural observations included marked endothelial cell retraction, separation, terminal nuclear lifting, adjacent duplication, apoptosis and a suggestion of endothelial progenitor cell attachment. The endothelium demonstrated increased caveolae, microparticles, depletion of Weibel-Palade bodies, loss of cell-cell and basal adhesion hemidesmosome-like structures, platelet adhesion and genesis of subendothelial neointima. CONCLUSION: These observational ultrastructural studies of the transgenic Ren2 vasculature provide an in-depth evaluation of early abnormal remodeling changes within conduit-elastic arteries under conditions of increased local levels of angiotensin II, oxidative stress, insulin resistance and hypertension.

Fluid overload and acute kidney injury.

Acute kidney injury is commonly encountered in critically ill patients, and is associated with worse outcomes. Fluid therapy is a key component in the management of these patients, often leading to fluid overload, especially in the setting of septic acute kidney injury. Emerging data overwhelmingly suggest that fluid overload in these patients may be associated with adverse outcomes. Management of such patients should include a strategy of early guided resuscitation, followed by careful assessment of fluid status, and early initiation of renal replacement therapy as soon as it is deemed safe, aiming for a neutral or negative fluid balance. This review will focus on the pathophysiological link between fluid overload and acute kidney injury, mechanisms of organ dysfunction in fluid overload, and strategies for management.

Effects of endothelial growth media on proepicardial cell gene expression and morphogenesis in 3D collagen matrices.

Proepicardial cells (PE) contribute to embryonic coronary vessel and epicardial development. Cells from the PE region can differentiate into coronary vascular smooth muscle cells and fibroblasts in vitro, but the endothelial specification capability of these cells is controversial. We sought to examine the effects of endothelial cell growth media on gene expression and the morphogenic properties of proepicardial cells in three-dimensional (3D) matrices. A primary culture of avian PE cells was subjected to molecular characterization with selected endothelial specific markers. Morphogenic properties of PE cells were assessed by in vitro assays of coronary vasculogenesis and invasion, which utilized highly defined, serum free, three-dimensional matrix conditions. PE cells maintained mixed cell population properties in the culture based on morphogenic features, immunohistochemistry, and the gene expression data. When suspended in a 3D vasculogenesis in vitro assay, PE cells formed intracellular vacuoles and assembled into multicellular tubes. Further, ultrastructural analysis revealed the presence of pinocytic vacuoles, intercellular junctions, and endothelial specific Weibel Palade bodies. In the invasion assay, PE cells spontaneously invaded control matrices. This invasion was markedly enhanced by lysophosphatidic acid (94±9.6 vs. 285.6±54.9, p<0.05) and was completely blocked with synthetic broad-spectrum metalloproteinase inhibitor GM6001. Isolated PE cells grown in endothelial cell media represent mixed-cell population, characterized by both smooth muscle and endothelial gene expression. When placed in 3D in vitro assays, PE cells manifest morphogenic properties, including multicellular tube assembly and invasion.

Renin inhibition attenuates insulin resistance, oxidative stress, and pancreatic remodeling in the transgenic Ren2 rat.

Emerging evidence indicates that pancreatic tissue expresses all components of the renin-angiotensin system. However, the functional role is not well understood. This investigation examined renin inhibition on pancreas structure/function in the transgenic Ren2 rat harboring the mouse renin gene, a model of tissue renin overexpression. Renin is the rate-limiting step in the generation of angiotensin II (Ang II), which stimulates the generation of reactive oxygen species in a variety of tissues. Overexpression of renin in Ren2 rats results in hypertension, insulin resistance, and cardiovascular and renal damage. Young (6-7 wk old) insulin-resistant male Ren2 and age-matched insulin sensitive Sprague Dawley rats were treated with the renin inhibitor, aliskiren (50 mg/kg.d by ip injection), or placebo for 21 d. At 21 d, the Ren2 demonstrated insulin resistance with increased islet insulin, Ang II, and reduced total insulin receptor substrate (IRS)-1, IRS-2, and Akt immunostaining. There was increased islet nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity and subunits (p47(phox) and Rac1) as well as increased nitrotyrosine immunostaining (each P < 0.05). These functional abnormalities were associated with a disordered islet architecture; increased islet-exocrine interface, pericapillary fibrosis, and structurally abnormal mitochondria and content in endocrine and exocrine pancreas. In vivo treatment with aliskiren normalized systemic insulin resistance and islet insulin, Ang II, NADPH oxidase activity/subunits, and nitrotyrosine and improved total IRS-1 and Akt phosphorylation (each P < 0.05) as well as islet/exocrine structural abnormalities. Collectively, these data suggest that pancreatic functional/structural changes are driven, in part, by tissue renin-angiotensin system-mediated increases in NADPH oxidase and reactive oxygen species generation, abnormalities attenuated with direct renin inhibition.

Ultrastructure of islet microcirculation, pericytes and the islet exocrine interface in the HIP rat model of diabetes.

CONTEXT: The transgenic human islet amyloid polypeptide (HIP) rat model of type 2 diabetes mellitus (T2DM) parallels the functional and structural changes in human islets with T2DM. OBJECTIVE: The transmission electron microscope (TEM) was utilized to observe the ultrastructural changes in islet microcirculation. METHODS: Pancreatic tissue from male Sprague Dawley rats (2, 4, 8, 14 months) were used as controls (SDC) and compared to the 2-, 4-, 8- and 14-month-old HIP rat models. RESULTS: The 2-month-old HIP model demonstrated no islet or microcirculation remodeling changes when compared to the SDC models. The 4-month-old HIP model demonstrated significant pericapillary amyloid deposition and diminution of pericyte foot processes as compared to the SDC models. The 8-month-old model demonstrated extensive islet amyloid deposition associated with pericyte and beta-cell apoptosis when compared with SDC. The 14-month-old HIP model demonstrated a marked reduction of beta-cells and intra-islet capillaries with near complete replacement of islets by amyloidoses. Increased cellularity in the region of the islet exocrine interface was noted in the 4- to 14-month-old HIP models as compared to SDC. In contrast to intra-islet capillary rarefaction there was noticeable angiogenesis in the islet exocrine interface. Pericytes seemed to be closely associated with collagenosis, intra-islet adipogenesis and angiogenesis in the islet exocrine interface. CONCLUSION: The above novel findings regarding the microcirculation and pericytes could assist researchers and clinicians in a better morphological understanding of T2DM and lead to new strategies for prevention and treatment of T2DM.

Attenuation of NADPH oxidase activation and glomerular filtration barrier remodeling with statin treatment.

Activation of reduced nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase by angiotensin II is integral to the formation of oxidative stress in the vasculature and the kidney. 3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibition is associated with reductions of oxidative stress in the vasculature and kidney and associated decreases in albuminuria. Effects of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibition on oxidative stress in the kidney and filtration barrier integrity are poorly understood. To investigate, we used transgenic TG(mRen2)27 (Ren2) rats, which harbor the mouse renin transgene and renin-angiotensin system activation, and an immortalized murine podocyte cell line. We treated young, male Ren2 and Sprague-Dawley rats with rosuvastatin (20 mg/kg IP) or placebo for 21 days. Compared with controls, we observed increases in systolic blood pressure, albuminuria, renal NADPH oxidase activity, and 3-nitrotryosine staining, with reductions in the rosuvastatin-treated Ren2. Structural changes on light and transmission electron microscopy, consistent with periarteriolar fibrosis and podocyte foot-process effacement, were attenuated with statin treatment. Nephrin expression was diminished in the Ren2 kidney and trended to normalize with statin treatment. Angiotensin II-dependent increases in podocyte NADPH oxidase activity and subunit expression (NOX2, NOX4, Rac, and p22(phox)) and reactive oxygen species generation were decreased after in vitro statin treatment. These data support a role for increased NADPH oxidase activity and subunit expression with resultant reactive oxygen species formation in the kidney and podocyte. Furthermore, statin attenuation of NADPH oxidase activation and reactive oxygen species formation in the kidney/podocyte seems to play roles in the abrogation of oxidative stress-induced filtration barrier injury and consequent albuminuria.

Ultrastructural islet study of early fibrosis in the Ren2 rat model of hypertension. Emerging role of the islet pancreatic pericyte-stellate cell.

CONTEXT: Type 2 diabetes mellitus is a multifactorial disease with polygenic and environmental stressors resulting in multiple metabolic toxicities and islet oxidative stress. We have integrated the role of the islet renin-angiotensin system (RAS) in the pathogenesis of early islet fibrosis utilizing the transgenic (mRen2)27 rodent model of hypertension and tissue RAS overexpression. OBJECTIVE: The Ren2 pancreatic islet tissue was evaluated with transmission electron microscopy to study both early cellular and extracellular matrix remodeling. ANIMALS: Four 9- to 10-week-old male Ren2 untreated models and four Sprague Dawley sex and age matched controls were used. DESIGN: Ultrastructural study to compare pancreatic islet tissue. MAIN OUTCOME MEASURES: Only qualitative and observational transmission electron microscopy findings are reported. RESULTS: Major remodeling differences in the Ren2 model were found to be located within the islet exocrine interface, including deposition of early fibrillar-banded collagen (fibrosis) and cellular remodeling of the pericyte suggesting proliferation, migration, hypertrophy and activation as compared to the Sprague Dawley controls. CONCLUSION: This study points to the possibility of the pericyte cell being one of many contributors to the fibrogenic pool of cells important for peri-islet fibrosis as a result of excess angiotensin II at the local tissue level in the Ren2 model. These findings suggest that the pericyte may be capable of differentiating into the pancreatic stellate cell. This islet ultrastructure study supports the notion that pericyte cells could be the link between islet vascular oxidative stress and peri-islet fibrosis. Pericyte-endothelial-pancreatic stellate cell associations and morphology are discussed.

Nephrogenic systemic fibrosis: a mysterious disease in patients with renal failure--role of gadolinium-based contrast media in causation and the beneficial effect of intravenous sodium thiosulfate.

Nephrogenic fibrosing dermopathy/nephrogenic systemic fibrosis (NSF) is an emerging scleromyxedema-like cutaneous disorder of unknown cause that is seen in patients with renal failure, and the number of reported cases has grown significantly since its first recognition. Recent case reports associated the use of gadolinium (Gd3+)-based contrast agents with the development of NSF. Herein is reported an additional patient who had NSF and had multiple previous exposures to Gd3+-based magnetic resonance imaging studies and had marked improvement in pain and skin changes after a trial of intravenous sodium thiosulfate. Discussed are the possible association of Gd3+-based contrast media with the development of NSF and potential for the use of sodium thiosulfate in the treatment of NSF.

Longitudinal ultrastructure study of islet amyloid in the HIP rat model of type 2 diabetes mellitus.

In 2004, the human islet amyloid polypeptide (HIP) rat model was created by transfecting the Sprague-Dawley rat with the human islet amyloid polypeptide (hIAPP)-amylin gene. The objective of this study is to utilize the transmission electron microscope to study the longitudinal cellular and extracellular morphological changes within the islets of this model at 4, 8, and 14 months of age. It has been previously demonstrated that the 2-, 5-, and 10-month HIP models have no diabetes, impaired fasting glucose, and diabetes, respectively. The 4-month HIP model (FBS 123 mg/dl) demonstrated an abundance of beta-cells and insulin secretory granules with significant pericapillary and inter-beta-cell islet amyloid deposition. The 8-month model (FBS 187 mg/dl) demonstrated extensive islet amyloid deposition and marked changes of beta-cell apoptosis. The 14-month-old model (FBS 244 mg/dl) demonstrated islet and beta-cell atrophy with even greater amounts of extracellular islet amyloid compared to the 4-month-old and 8-month-old models. Functional beta cells were sparse and were associated with intra islet adipose deposition. These findings of ultrastructure cellular and extracellular morphological longitudinal remodeling changes in this novel animal model of type 2 diabetes may provide investigators with a better understanding regarding the role of islet amyloid in human islet.