Review of intravascular lithotripsy for treating coronary, peripheral artery, and valve calcifications.

Management of intracoronary calcium (ICC) continues to be a challenge for interventional cardiologists. There have been significant advances in calcium treatment devices. However, there still exists a knowledge gap regarding which devices to choose for the treatment of ICC. The purpose of this manuscript is to review the principles of intravascular lithotripsy (IVL) and clinical data. The technique of IVL will then be compared to alternative calcium treatment devices. Clinical data will be reviewed concerning the treatment of coronary, peripheral artery and valvular calcifications. Controversies to be discussed include how to incorporate IVL into your practice, what is the best approach for treating calcium subtypes, how to approach under-expanded stents, what is the ideal technique for performing IVL, how safe is IVL, whether imaging adds value when performing IVL, and how IVL fits into a treatment program for peripheral arteries and calcified valves.

Mechanical circulatory support versus vasopressors alone in patients with acute myocardial infarction and cardiogenic shock undergoing percutaneous coronary intervention.

BACKGROUND: Previous studies have compared Impella use to intra-aortic balloon pump (IABP) use in patients with acute myocardial infarction and cardiogenic shock (AMI-CS) undergoing percutaneous coronary intervention (PCI). Our objective was to compare clinical outcomes in patients with AMI-CS undergoing PCI who received Impella (percutaneous left ventricular assist device) without vasopressors, IABP without vasopressors, and vasopressors without mechanical circulatory support (MCS). METHODS: We queried the National Inpatient Sample (NIS) using ICD-10 codes (2015-2018) to identify patients with AMI-CS undergoing PCI. We created three propensity-matched cohorts to examine clinical outcomes in patients receiving Impella versus IABP, Impella versus vasopressors without MCS, and IABP versus vasopressors without MCS. RESULTS: Among 17,762 patients, Impella use was associated with significantly higher in-hospital major bleeding (31.4% vs. 13.6%; p < 0.001) and hospital charges (p < 0.001) compared to IABP use, with no benefit in mortality (34.1% vs. 26.9%; p = 0.06). Impella use was associated with significantly higher mortality (42.3% vs. 35.7%; p = 0.02), major bleeding (33.9% vs. 22.7%; p = 0.001), and hospital charges (p < 0.001), when compared to the use of vasopressors without MCS. There were no significant differences in clinical outcomes between IABP use and the use of vasopressor without MCS. CONCLUSIONS: In this analysis of retrospective data of patients with AMI-CS undergoing PCI, Impella use was associated with higher mortality, major bleeding, and in-hospital charges when compared to vasopressor therapy without MCS. When compared to IABP use, Impella was associated with no mortality benefit, along with higher major bleeding events and in-hospital charges. A vasopressor-only strategy suggested no difference in clinical outcomes when compared to IABP. This study uses the NIS for the first time to highlight outcomes in AMI-CS patients undergoing PCI when treated with vasopressor support without MCS, compared to Impella and IABP use.

Modification of a Transvalvular Microaxial Flow Pump for Instantaneous Determination of Native Cardiac Output and Volume.

BACKGROUND: The current Impella cardiopulmonary (CP) pump, used for mechanical circulatory support in patients with cardiogenic shock (CS), cannot assess native cardiac output (CO) and left ventricular (LV) volumes. These data are valuable in facilitating device management and weaning. Admittance technology allows for accurate assessment of cardiac chamber volumes. OBJECTIVES: This study tested the ability to engineer admittance electrodes onto an existing Impella CP pump to assess total and native CO as well as LV chamber volumes in an instantaneous manner. METHODS: Impella CP pumps were fitted with 4 admittance electrodes and were placed in the LVs of adult swine (n = 9) that were subjected to 3 different hemodynamic conditions, including Impella CP speed adjustments, administration of escalating doses of dobutamine and microsphere injections into the left main artery to result in cardiac injury. CO, according to admittance electrodes, was calculated from LV volumes and heart rate. In addition, CO was calculated in each instance via thermodilution, continuous CO measurement, the Fick principle, and aortic velocity-time integral by means of echocardiography. RESULTS: Modified Impella CP pumps were placed in swine LVs successfully. CO, as determined by admittance electrodes, was similar by trend to other methods of CO assessment. It was corrected for pump speed to calculate native CO, and calculated LV chamber volumes trended as expected in each experimental protocol. CONCLUSIONS: We report, for the first time, that an Impella CP pump can be fitted with admittance electrodes and used to determine total and native CO in various hemodynamic situations. CONDENSED ABSTRACT: Transvalvular mechanical circulatory support devices such as the Impella CP do not have the ability to provide real-time information on native cardiac output (CO) and left ventricular (LV) volumes. This information is critical in device management and in weaning in patients with cardiogenic shock. We demonstrate, for the first time, that Impella CP pumps coupled with admittance electrodes are able to determine native CO and LV chamber volumes in multiple hemodynamic situations such as Impella pump speed adjustments, escalating dobutamine administration and cardiac injury from microsphere injection.

Munchausen by internet and false perinatal crises.

BACKGROUND: In representative cases of Munchausen by internet (MBI), an individual (or "poser") goes online to falsely report or exaggerate illnesses or life crises. The principal goal, as in factitious disorder imposed on self or another, is to garner emotional satisfaction. We provide the first evidence that MBI can target a specific type of health care provider-in this case, birthing doulas. METHODS: We describe 5 cases in which individuals have utilized social media platforms to report factitious perinatal illnesses and crises, including neonatal death, in real time. Current health headlines, such as those involving the COVID-19 pandemic, can be relevant to the ruses. Posers can engage in deceptions with several health care professionals concurrently or serially, and may portray multiple people ("sock puppets") at the same time. RESULTS: MBI has consequences that can be highly disruptive. In the cases highlighted in this report, many hours of support were given to individuals who had fabricated their pregnancies, infants, and perinatal complications. The doulas experienced feelings ranging from resignation to anger and betrayal. CONCLUSIONS: Health care professionals of all types who offer services online should be vigilant to the risks of potential MBI.

Physiologic Assessment of Coronary Stenosis: Current Status and Future Directions.

PURPOSE OF REVIEW: Percutaneous coronary intervention (PCI) is a commonly used treatment option in coronary artery disease (CAD). Reduced major adverse cardiovascular events (MACE) in those randomized to PCI compared to optimal medical therapy have been demonstrated only if it is performed for physiologically significant coronary lesions. Despite data demonstrating improved outcomes primarily in stable CAD and then acute settings, physiology-guided PCI remains underutilized. This review summarizes the evidence and commonly used methods for physiologic assessment of coronary stenosis. RECENT FINDINGS: Fractional flow reserve (FFR) is the gold standard for the analysis of lesion severity. Its use is limited by the need for adenosine, which adds time, complexity, and potential adverse effects. Non-hyperemic instantaneous wave-free ratio-guided revascularization and quantitative flow reserve ratio assessment both have shown safety and effectiveness with improved patient outcomes. Coronary physiological assessment solves the ambiguity of coronary angiography. Detecting physiologically significant stenoses is crucial to decide which lesion needs to be treated. Technological advances have led to the development of new assessment indices in addition to FFR.

Chronic total occlusions-Is true lumen wire passage preferred to subintimal dissection re-entry?

True lumen crossing is superior to subintimal crossing. Subintimal versus true lumen crossing may only be apparent if IVUS is performed. Newer techniques for true lumen crossing need to be developed.

Comparison of Biomechanical Properties and Microstructure of Trabeculae Carneae, Papillary Muscles, and Myocardium in the Human Heart.

Trabeculae carneae account for a significant portion of human ventricular mass, despite being considered embryologic remnants. Recent studies have found trabeculae hypertrophy and fibrosis in hypertrophied left ventricles with various pathological conditions. The objective of this study was to investigate the passive mechanical properties and microstructural characteristics of trabeculae carneae and papillary muscles compared to the myocardium in human hearts. Uniaxial tensile tests were performed on samples of trabeculae carneae and myocardium strips, while biaxial tensile tests were performed on samples of papillary muscles and myocardium sheets. The experimental data were fitted with a Fung-type strain energy function and material coefficients were determined. The secant moduli at given diastolic stress and strain levels were determined and compared among the tissues. Following the mechanical testing, histology examinations were performed to investigate the microstructural characteristics of the tissues. Our results demonstrated that the trabeculae carneae were significantly stiffer (Secant modulus SM2 = 80.06 ± 10.04 KPa) and had higher collagen content (16.10 ± 3.80%) than the myocardium (SM2 = 55.14 ± 20.49 KPa, collagen content = 10.06 ± 4.15%) in the left ventricle. The results of this study improve our understanding of the contribution of trabeculae carneae to left ventricular compliance and will be useful for building accurate computational models of the human heart.

Computational Modeling of Human Left Ventricle to Assess the Effects of Trabeculae Carneae on the Diastolic and Systolic Functions.

Trabeculae carneae are irregular structures that cover the endocardial surfaces of both ventricles and account for a significant portion of human ventricular mass. The role of trabeculae carneae in diastolic and systolic functions of the left ventricle (LV) is not well understood. Thus, the objective of this study was to investigate the functional role of trabeculae carneae in the LV. Finite element (FE) analyses of ventricular functions were conducted for three different models of human LV derived from high-resolution magnetic resonance imaging (MRI). The first model comprised trabeculae carneae and papillary muscles, while the second model had papillary muscles and partial trabeculae carneae, and the third model had a smooth endocardial surface. We customized these patient-specific models with myofiber architecture generated with a rule-based algorithm, diastolic material parameters of Fung strain energy function derived from biaxial tests and adjusted with the empirical Klotz relationship, and myocardial contractility constants optimized for average normal ejection fraction (EF) of the human LV. Results showed that the partial trabeculae cutting model had enlarged end-diastolic volume (EDV), reduced wall stiffness, and even increased end-systolic function, indicating that the absence of trabeculae carneae increased the compliance of the LV during diastole, while maintaining systolic function.

The Effect of Trabeculae Carneae on Left Ventricular Diastolic Compliance: Improvement in Compliance With Trabecular Cutting.

The role of trabeculae carneae in modulating left ventricular (LV) diastolic compliance remains unclear. The objective of this study was to determine the contribution of trabeculae carneae to the LV diastolic compliance. LV pressure-volume compliance curves were measured in six human heart explants from patients with LV hypertrophy at baseline and following trabecular cutting. The effect of trabecular cutting was also analyzed with finite-element model (FEM) simulations. Our results demonstrated that LV compliance improved after trabecular cutting (p < 0.001). Finite-element simulations further demonstrated that stiffer trabeculae reduce LV compliance further, and that the presence of trabeculae reduced the wall stress in the apex. In conclusion, we demonstrate that integrity of the LV and trabeculae is important to maintain LV stiffness and loss in trabeculae leads to more LV compliance.

Fourier optics analysis of phase-mask-based path-length-multiplexed optical coherence tomography.

Optical coherence tomography (OCT) is an imaging technique that constructs a depth-resolved image by measuring the optical path-length difference between broadband light backscattered from a sample and a reference surface. For many OCT sample arm optical configurations, sample illumination and backscattered light detection share a common path. When a phase mask is placed in the sample path, features in the detected signal are observed, which suggests that an analysis of a generic common path OCT imaging system is warranted. In this study, we present a Fourier optics analysis using a Fresnel diffraction approximation of an OCT system with a path-length-multiplexing element (PME) inserted in the sample arm optics. The analysis may be generalized for most phase-mask-based OCT systems. A radial-angle-diverse PME is analyzed in detail, and the point spread function, coherent transfer function, sensitivity of backscattering angular diversity detection, and signal formation in terms of sample spatial frequency are simulated and discussed. The analysis reveals important imaging features and application limitations of OCT imaging systems with a phase mask in the sample path optics.

Detection of plaque structure and composition using OCT combined with two-photon luminescence (TPL) imaging.

BACKGROUND AND OBJECTIVES: Atherosclerosis and plaque rupture leads to myocardial infarction and stroke. A novel hybrid optical coherence tomography (OCT) and two-photon luminescence (TPL) fiber-based imaging system was developed to characterize tissue constituents in the context of plaque morphology. STUDY DESIGN/MATERIALS AND METHODS: Ex vivo coronary arteries (34 regions of interest) from three human hearts with atherosclerotic plaques were examined by OCT-TPL imaging. Histological sections (4 µm in thickness) were stained with Oil Red O for lipid, Von Kossa for calcium, and Verhoeff-Masson Tri-Elastic for collagen/elastin fibers and compared with imaging results. RESULTS: Biochemical components in plaques including lipid, oxidized-LDL, and calcium, as well as a non-tissue component (metal) are distinguished by multi-channel TPL images with statistical significance (P < 0.001). TPL imaging provides complementary optical contrast to OCT (two-photon absorption/emission vs scattering). Merged OCT-TPL images demonstrate the distribution of lipid deposits in registration with detailed plaque surface profile. CONCLUSIONS: Results suggest that multi-channel TPL imaging can effectively identify lipid sub-types and different plaque components. Furthermore, fiber-based hybrid OCT-TPL imaging simultaneously detects plaque structure and composition, improving the efficacy of vulnerable plaque detection and characterization.

Open Radial Artery Study.

Radial artery occlusion (RAO) has been the most common postprocedural complication of transradial artery access. The optimal method of prevention of RAO is still lacking. In our study, we aimed to evaluate the effect of patent hemostasis on early (24 hours) and late (2 weeks) RAO prevention. The Open Radial Artery Study was a single-arm, prospective, and multicenter study. The primary end points were early and late RAO at the vascular access site after transradial coronary procedures. Secondary end points were access site hematoma, pseudoaneurysm formation, arteriovenous fistula, and nerve injury. A total of 2,181 patients were analyzed (67% male, mean age 68 years). The mean interventional duration and hemostatic times were 75.6 ± 55.6 and 60 ± 5.6 minutes, respectively. Radial artery spasm occurred in 10% of patients (n = 218). Catheter kinking, radial artery rupture, or dissection were not observed during the procedure. RAO, hematoma, pseudoaneurysm, arteriovenous fistula, or nerve damage was not observed in any of the patients in the early or late period. In patients who undergo coronary diagnostic or interventional procedures through transradial artery access, the patent hemostasis method seems a critical step in the prevention of early and late RAO.

Somatoform, factitious, and related diagnoses in the national hospital discharge survey: addressing the proposed DSM-5 revision.

BACKGROUND: The DSM-5 working group on the somatoform (SFD) and factitious (FD) disorders has recommended substantial revisions of these categories. The recommendations are based, in part, on anecdotal evidence that the diagnoses are infrequently used. OBJECTIVE: To assess the assignment rates for SFD, FD, and related diagnoses among general medical inpatients. METHOD: The National Hospital Discharge Survey was queried for instances of SFD and FD, along with related diagnoses identifying medical cases in which psychological factors play a role. Diagnoses of major depression and generalized anxiety disorder were queried for comparison purposes. RESULTS: The target diagnoses were assigned far less frequently than published prevalence and recognition rates suggest. Nearly half of the assigned target diagnoses were generic diagnoses (esp. physiological malfunction due to psychological factors) other than SFD or FD. However, the apparent degree of underassignment of the target diagnoses was not dramatically greater than the underassignment observed for major depression and generalized anxiety disorder. CONCLUSION: The results provide empirical support for the impression that physicians do not assign SFD and FD diagnoses in recognized cases, but do not strongly support the assertion that these diagnoses are uniquely problematic.

Excretion and toxicity of gold-iron nanoparticles.

Though gold nanoparticles have been considered bio-inert, recent studies have questioned their safety. To reduce the potential for toxicity, we developed a nanoclustering of gold and iron oxide as a nanoparticle (nanorose) which biodegrades into subunits to facilitate rapid excretion. In this present study, we demonstrate acid and macrophage lysosomal degradation of nanorose via loss of the near-infrared optical shift, and clearance of the nanorose in vivo following i.v. administration in C57BL/6 mice by showing gold concentration is significantly reduced in 11 murine tissues in as little as 31 days (P < 0.01). Hematology and chemistry show no toxicity of nanorose injected mice up to 14 days after administration. We conclude that the clustering design of nanorose does enhance the excretion of these nanoparticles, and that this could be a viable strategy to limit the potential toxicity of gold nanoparticles for clinical applications. FROM THE CLINICAL EDITOR: The potential toxicity of nanomaterials is a critically important limiting factor in their more widespread clinical application. Gold nanoparticles have been classically considered bio-inert, but recent studies have questioned their safety. The authors of this study have developed a clustering gold and iron oxide nanoparticle (nanorose), which biodegrades into subunits to facilitate rapid excretion, resulting in reduced toxicity.

Thrombosis and myocardial infarction: the role of bioresorbable scaffolds.

Coronary stents have dramatically improved the treatment of coronary artery stenosis. In-stent-restenosis (ISR) and stent thrombosis (ST) pose major obstacles to the success of coronary stenting. Drug-eluting stents (DES) emerged as a major breakthrough in stenting and significantly reduced ISR. Despite taking dual antiplatelet therapy (DAPT), very late ST has remained a major obstacle in the success of DES. This occurs regardless of the type of polymer or antiproliferative agent in the contemporary stents. Such adverse events occur at a rate of approximately 2% to 3% per year after first year, which have been attributed to the strut fractures, loss of vessel compliance and vasomotion, and neoatherosclerosis. Fully bioresorbable scaffolds (BRS) have emerged in an effort to overcome these limitations leading to a "leave nothing behind" approach. While appealing, the initial experience with BRS technology was hampered by increased rates of BRS thrombosis compared with DES. In this review, we summarized underlying mechanisms leading to BRS failure and provided insights into optimizing BRS deployment with intravascular imaging. In addition, we outlined the perspectives of new generations BRS with thinner struts and new designs as well as alternative materials to improve outcome.

Intravascular laser lithotripsy for calcium fracture in human coronary arteries.

BACKGROUND: Electrical intravascular lithotripsy (E-IVL) uses shock waves to fracture calcified plaque. AIMS: We aimed to demonstrate the ability of laser IVL (L-IVL) to fracture calcified plaques in ex vivo human coronary arteries and to identify and evaluate the mechanisms for increased vessel compliance. METHODS: Shock waves were generated by a Ho:YAG (Holmium: yttrium-aluminium-garnet) laser (2 J, 5 Hz) and recorded by a high-speed camera and pressure sensor. Tests were conducted on phantoms and 19 fresh human coronary arteries. Before and after L-IVL, arterial compliance and optical coherence tomography (OCT) pullbacks were recorded, followed by histology. Additionally, microcomputed tomography (micro-CT) and scanning electron microscopy (SEM) were performed. Finite element models (FEM) were utilised to examine the mechanism of L-IVL. RESULTS: Phantom cracks were obtained using 230 µm and 400 µm fibres with shock-wave pressures of 84±5.0 atm and 62±0.4 atm, respectively. Post-lithotripsy, calcium plaque modifications, including fractures and debonding, were identified by OCT in 78% of the ex vivo calcified arteries (n=19). Histological analysis revealed calcium microfractures (38.7±10.4 µm width) in 57% of the arteries which were not visible by OCT. Calcium microfractures were verified by micro-CT and SEM. The lumen area increased from 2.9±0.4 to 4.3±0.8 mm2 (p<0.01). Arterial compliance increased by 2.3±0.6 atm/ml (p<0.05). FEM simulations suggest that debonding and intimal tears are additional mechanisms for increased arterial compliance. CONCLUSIONS: L-IVL has the capability to increase calcified coronary artery compliance by multiple mechanisms.

Combined two-photon luminescence microscopy and OCT for macrophage detection in the hypercholesterolemic rabbit aorta using plasmonic gold nanorose.

BACKGROUND AND OBJECTIVES: The macrophage is an important early cellular marker related to risk of future rupture of atherosclerotic plaques. Two-channel two-photon luminescence (TPL) microscopy combined with optical coherence tomography (OCT) was used to detect, and further characterize the distribution of aorta-based macrophages using plasmonic gold nanorose as an imaging contrast agent. STUDY DESIGN/MATERIALS AND METHODS: Nanorose uptake by macrophages was identified by TPL microscopy in macrophage cell culture. Ex vivo aorta segments (8 × 8 × 2 mm(3) ) rich in macrophages from a rabbit model of aorta inflammation were imaged by TPL microscopy in combination with OCT. Aorta histological sections (5 µm in thickness) were also imaged by TPL microscopy. RESULTS: Merged two-channel TPL images showed the lateral and depth distribution of nanorose-loaded macrophages (confirmed by RAM-11 stain) and other aorta components (e.g., elastin fiber and lipid droplet), suggesting that nanorose-loaded macrophages are diffusively distributed and mostly detected superficially within 20 µm from the luminal surface of the aorta. Moreover, OCT images depicted detailed surface structure of the diseased aorta. CONCLUSIONS: Results suggest that TPL microscopy combined with OCT can simultaneously reveal macrophage distribution with respect to aorta surface structure, which has the potential to detect vulnerable plaques and monitor plaque-based macrophages overtime during cardiovascular interventions.

Smart Drain for Post-Cardiac Surgery Left Ventricular Volumes Evaluated in Large Animal Models.

BACKGROUND: Open heart surgeries for coronary arterial bypass graft and valve replacements are performed on 400,000 Americans each year. Unexplained hypotension during recovery causes morbidity and mortality through cerebral, kidney, and coronary hypoperfusion. An early detection method that distinguishes between hypovolemia and decreased myocardial function before onset of hypotension is desirable. We hypothesized that admittance measured from a modified pericardial drain can detect changes in left ventricular end-systolic, end-diastolic, and stroke volumes. METHODS: Admittance was measured from 2 modified pericardial drains placed in 7 adult female dogs using an open chest preparation, each with 8 electrodes. The resistive and capacitive components of the measured admittance signal were used to distinguish blood and muscle components. Admittance measurements were taken from 12 electrode configurations in each experiment. Left ventricular preload was reduced by inferior vena cava occlusion. Physiologic response to vena cava occlusion was measured by aortic pressure, aortic flow, left ventricle diameter, left ventricular wall thickness, and electrocardiogram. RESULTS: Admittance successfully detected a drop in left ventricular end-diastolic volume (P < .001), end-systolic volume (P < .001), and stroke volume (P < .001). Measured left ventricular muscle resistance correlated with crystal-derived left ventricular wall thickness (R2 = 0.96), validating the method's ability to distinguish blood from muscle components. CONCLUSIONS: Admittance measured from chest tubes can detect changes in left ventricular end-systolic, end-diastolic, and stroke volumes and may therefore have diagnostic value for unexplained hypotension.

DIAMondback Atherectomy With OCT Visualization for Calcified PAD Lesions (DIAMOCT-PAD Study).

OBJECTIVE: In this study, we aimed to describe the immediate and long-term vascular effects of OAS in patients with peripheral arterial disease (PAD) and moderate to severely calcified lesions. BACKGROUND: Debulking the calcified atherosclerotic plaque with the orbital atherectomy system (OAS) can potentially enhance vessel compliance and increase the chance of reaching a desirable angioplasty result. METHODS: A total of 7 patients were evaluated both at baseline and at 6-month follow-up. Following a diagnostic peripheral angiogram, patients with significant SFA disease had a baseline intravascular optical coherence tomography (IV-OCT) and the lesion was treated with OAS. Repeat IV-OCT was performed after atherectomy and after drug-coated balloon, if used. Patients were also evaluated with angiography and IV-OCT imaging at their 6-month follow-up. RESULTS: The majority of tissue removed was fibrous tissue. During follow-up, luminal volume increased for 4 of the 7 patients from baseline to 6-month follow-up and decreased in 3 patients. On average there was a 6% increase of luminal volume (P<.01 compared with baseline). A recent virtual histology algorithm was used for automatic classification of IV-OCT images unaided by any reader. The algorithm used convolutional neural networks to identify regions as either calcium, fibrous, or lipid plaque, and it agreed with an expert reader 82% of the time. CONCLUSION: To the best of our knowledge, the current report is the first to describe vascular effects of OAS in medial calcified lesions immediately after and at follow-up using IV-OCT in patients with severe PAD.

Growth of high-aspect ratio horizontally-aligned ZnO nanowire arrays.

A method of fabricating horizontally-aligned zinc-oxide (ZnO) nanowire (NW) arrays with full control over the width and length is demonstrated. SEM images reveal the hexagonal structure typical of zinc oxide NWs. Arrays of high-aspect ratio horizontal ZnO NWs are fabricated by making use of the lateral overgrowth from dot patterns created by electron beam lithography (EBL). An array of patterned wires are lifted off and transferred to a flexible PDMS substrate with possible applications in several key nanotechnology areas.