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.

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.

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.

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.).

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.

Mineralocorticoid receptor blockade attenuates chronic overexpression of the renin-angiotensin-aldosterone system stimulation of reduced nicotinamide adenine dinucleotide phosphate oxidase and cardiac remodeling.

The renin-angiotensin-aldosterone system contributes to cardiac remodeling, hypertrophy, and left ventricular dysfunction. Angiotensin II and aldosterone (corticosterone in rodents) together generate reactive oxygen species (ROS) via reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, which likely facilitate this hypertrophy and remodeling. This investigation sought to determine whether cardiac oxidative stress and cellular remodeling could be attenuated by in vivo mineralocorticoid receptor (MR) blockade in a rodent model of the chronically elevated tissue renin-angiotensin-aldosterone system, the transgenic TG (mRen2) 27 rat (Ren2). The Ren2 overexpresses the mouse renin transgene with resultant hypertension, insulin resistance, proteinuria, and cardiovascular damage. Young (6- to 7-wk-old) male Ren2 and age-matched Sprague-Dawley rats were treated with spironolactone or placebo for 3 wk. Heart tissue ROS, immunohistochemical analysis of 3-nitrotyrosine, and NADPH oxidase (NOX) subunits (gp91(phox) recently renamed NOX2, p22(phox), Rac1, NOX1, and NOX4) were measured. Structural changes were assessed with cine-magnetic resonance imaging, transmission electron microscopy, and light microscopy. Significant increases in Ren2 septal wall thickness (cine-magnetic resonance imaging) were accompanied by perivascular fibrosis, increased mitochondria, and other ultrastructural changes visible by light microscopy and transmission electron microscopy. Although there was no significant reduction in systolic blood pressure, significant improvements were seen with MR blockade on ROS formation and NOX subunits (each P < 0.05). Collectively, these data suggest that MR blockade, independent of systolic blood pressure reduction, improves cardiac oxidative stress-induced structural and functional changes, which are driven, in part, by angiotensin type 1 receptor-mediated increases in NOX.

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.

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.

Detecting microalbuminuria and taking action in the cardiometabolic syndrome and type 2 diabetes mellitus.

Microalbuminuria is an early indicator of cardiac and renal vascular endothelial damage in individuals with diabetes mellitus, impaired glucose tolerance, hypertension, and the CardioMetabolic Syndrome. This simple, inexpensive dipstick screening test is not only associated with an increased risk of progressive renal insufficiency but also with an increased risk of cardiovascular disease and events. Regular screening for microalbuminuria will allow for early detection and intervention to prevent renal and vascular complications of these disease states.

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.

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.

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.

Understanding essential hypertension from the perspective of the cardiometabolic syndrome.

Hypertension (HTN) is an important modifiable risk factor for major health problems such as coronary heart disease, stroke, congestive heart failure, end-stage renal disease, and peripheral vascular disease. Because of the associated morbidity and mortality, and the cost to society, HTN is an important public health challenge. HTN is frequently associated with other cardiovascular disease risk factors constituting the cardiometabolic syndrome, which individually and synergistically influence the pathophysiology of HTN, and the resultant increased redox stress contributes to the remodeling changes in key organs such as the heart and kidney. Remodeling at the subcellular level, and extracellular matrix in the heart and kidney of the hypertensive Ren2 transgenic rat model of tissue angiotensin II overexpression (TG(mREN-2)27), compared with the Sprague Dawley control rat model, has been observed by light and electron microscopy and are discussed. A better understanding of the pathophysiology of HTN may provide clinician and researcher, tools to effectively investigate and manage this complicated disease process.

Chronic kidney disease and cardiovascular risk.

Chronic kidney disease (CKD) is a global public health concern, and there is emerging a strong relationship between CKD and increased cardiovascular disease (CVD) risk. CKD in the presence of other co-morbidities such as type 2 diabetes mellitus (T2DM) and hypertension (HTN) can lead to early progression to end-stage renal disease (ESRD/stage V CKD) and confer a greater risk for CVD morbidity and mortality. CVD events are the leading cause of premature death in patients with CKD, even before their progression to ESRD, with the rate of CVD progression being twice as common compared with the general population. The higher mortality from CVD persists even after adjusting for most of the traditional risk factors, suggesting the possible contributions of uremia-related, nontraditional risk factors. This has led to the current understanding that the pathophysiology of CVD in CKD involves a complex interplay of both the traditional as well as nontraditional, uremia-related risk factors. This review will elaborate on the pathophysiology of CVD in CKD and will discuss the role of microalbuminuria (MAU)-proteinuria as a potential diagnostic and prognostic tool for CVD in CKD risk assessment.

Angiotensin II-mediated oxidative stress promotes myocardial tissue remodeling in the transgenic (mRen2) 27 Ren2 rat.

Angiotensin II (ANG II) contributes to cardiac remodeling, hypertrophy, and left ventricular dysfunction. ANG II stimulation of the ANG type 1 receptor (AT(1)R) generates reactive oxygen species via NADPH oxidase, which facilitates this hypertrophy and remodeling. This investigation sought to determine whether cardiac oxidative stress and cellular remodeling could be attenuated by in vivo AT(1)R blockade (AT(1)B) (valsartan) or superoxide dismutase/catalase mimetic (tempol) treatment in a rodent model of chronically elevated tissue levels of ANG II, the transgenic (mRen2) 27 rat (Ren2). Ren2 rats overexpress the mouse renin transgene with resultant hypertension, insulin resistance, proteinuria, and cardiovascular damage. Young (6-7 wk old) male Ren2 and age-matched Sprague-Dawley rats were treated with valsartan (30 mg/kg), tempol (1 mmol/l), or placebo for 3 wk. Heart tissue NADPH oxidase (NOX) activity and immunohistochemical analysis of subunits NOX2, Rac1, and p22(phox), heart tissue malondialdehyde, and insulin-stimulated protein kinase B (Akt) activation were measured. Structural changes were assessed with cine MRI, transmission electron microscopy, and light microscopy. Increases in septal wall thickness and altered systolic function (cine MRI) were associated with perivascular fibrosis and increased mitochondria in Ren2 on light and transmission electron microscopy (P < 0.05). AT(1)B, but not tempol, reduced blood pressure (P < 0.05); significant improvements were seen with both AT(1)B and tempol on NOX activity, subunit expression, malondialdehyde, and insulin-mediated activation/phosphorylation of Akt (each P < 0.05). Collectively, these data suggest cardiac oxidative stress-induced structural and functional changes are driven, in part, by AT(1)R-mediated increases in NADPH oxidase activity.

Myocardial myocyte remodeling and fibrosis in the cardiometabolic syndrome.

Myocardial cellular and extracellular matrix remodeling are important in the development of left ventricular hypertrophy and are essential for the adaptive and maladaptive changes associated with the cardiometabolic syndrome. This brief review of myocyte remodeling also presents preliminary observational findings regarding myocardial adaptive hypertrophy remodeling, including an increase in mitochondria and capillaries, convolutions and lengthening of intercalated discs, the addition of sarcomeres, thickened Z lines, and the novel presence of pericapillary fibrosis (in addition to perivascular arteriolar fibrosis). The 11-week-old TG(mREN-2)27 transgene rat model of tissue angiotensin II overexpression, which develops hypertension and insulin resistance, was chosen to examine both myocyte hypertrophy and extracellular matrix fibrosis. This review and the preliminary observational findings may provide the clinician and researcher a better understanding of remodeling changes in the myocardium and ultimately foster earlier recognition and therapeutic interventions.