Minimally invasive methods for creating models of focal coronary narrowing in large animals are challenging. Rapid prototyping using three-dimensionally (3D) printed coronary implants can be employed to percutaneously create a focal coronary stenosis. However, reliable delivery of the implants can be difficult without the use of ancillary equipment. We describe the use of a mother-and-child coronary guide catheter for stabilization of the implant and for effective delivery of the 3D printed implant to any desired location along the length of the coronary vessel. The focal coronary narrowing was confirmed under coronary cineangiography and the functional significance of the coronary stenosis was assessed using gadolinium-enhanced first-pass cardiac perfusion MRI. We showed that reliable delivery of 3D printed coronary implants in swine models (n = 11) of ischemic heart disease can be achieved through repurposing mother-and-child coronary guide catheters. Our technique simplifies the percutaneous delivery of coronary implants to create closed-chest swine models of focal coronary artery stenosis and can be performed expeditiously, with a low procedural failure rate.

Cross-sectional studies by intravascular ultrasound (IVUS) in heart transplant recipients have suggested that vascular remodeling occurs in coronary arteries years after transplant. However, no reports describe vascular remodeling in the same cohort of patients studied prospectively using morphometric analysis (10 evenly spaced images obtained from a slow pullback from the left anterior descending coronary artery). Morphometric analysis better reflects total vessel anatomy compared with previously reported site (2 to 3 images) analysis. We reviewed 20 patients studied by IVUS at 2 months, 1 year, 2 years, and 3 years after heart transplant.Over time, the coronary artery luminal area decreased from baseline level of 12.0 mm(2) to a 3-year mark of 9.7 mm(2) (p = 0.02). Vessel shrinkage was seen in 16/20 patients. After an initial rise in intimal parameters (maximal intimal thickness, intimal index, and plaque area) from baseline to 1 year, we found a significant decrease in intimal parameters between Year 1 and Year 3 after transplant. For example, plaque area decreased from 2.05 mm(2) at 1 year post-transplant to 1.48 mm(2) by 3 years post-transplant (p = 0.05). In a majority of heart transplant patients, early intimal thickening in the first year post-transplant is accompanied by constrictive remodeling. Over the subsequent 2 years, further constrictive remodeling is seen despite a decrease in intimal area.

The lactoperoxidase (LPO)-hydrogen peroxide-halides reaction (LPO system) converts iodide and thiocyanate (SCN-) into hypoiodous acid (HOI) and hypothiocyanite (OSCN-), respectively. Since this system has been implicated in defense of the airways and oropharynx from microbial invasion, in this proof-of-concept study we measured the concentrations of these analytes in human saliva from a convenience clinical sample of 40 qualifying subjects before and after acute iodine administration via the iodinated contrast medium used in coronary angiography to test the hypothesis that an iodide load increases salivary iodide and HOI concentrations. Saliva was collected and salivary iodide, SCN-, HOI and OSCN- were measured using standard methodology. The large iodine load delivered by the angiographic dye, several 100-fold in excess of the U.S. Recommended Daily Allowance for iodine (150 µg/day), significantly increased salivary iodide and HOI levels compared with baseline levels, whereas there was no significant change in salivary SCN- and OSCN- levels. Iodine load and changes of salivary iodide and HOI levels were positively correlated, suggesting that higher iodide in the circulation increases iodide output and salivary HOI production. This first of its kind study suggests that a sufficient but safe iodide supplementation less than the Tolerable Upper Limit for iodine set by the U.S. Institute of Medicine (1,100 µg/day) may augment the generation of antimicrobial HOI by the salivary LPO system in concentrations sufficient to at least in theory protect the host against susceptible airborne microbial pathogens, including enveloped viruses such as coronaviruses and influenza viruses.

Objectives

The purpose of this study was to assess whether the newer stent delivery systems provide a stented lumen cross-sectional area (CSA) that is equal to the delivery balloon nominal dimensions.

Background

First generation stents were often not adequately expanded with their delivery system and frequently required higher pressure or a larger balloon after deployment. Newer stents were designed to optimize expansion with noncompliant, high-pressure balloons provided as the delivery systems.

Methods

Intravascular ultrasound (IVUS) was used to evaluate 38 stents in 32 patients after deployment at 14 to 16 atm with their delivery balloon system. Minimum stent lumen CSA and stent minimum lumen diameter (MLD) were measured by IVUS imaging. The manufacturer's expected stent diameter was defined as the balloon diameter measured by the company at the maximum pressure used. The manufacturer's expected stent area was calculated based on the manufacturer's expected stent diameter.

Results

The MLD (2.5 +/- 0.5 mm) and minimum stent CSA (6.0 +/- 1.7 mm(2)) by IVUS were significantly smaller than the manufacturer's expected stent diameter (3.5 +/- 0.4 mm) and area (9.5 +/- 1.9 mm(2)) (p < 0.0001, respectively). The mean MLD by IVUS was 72 +/- 8% of the expected stent diameter, and the mean minimum stent CSA by IVUS was 62 +/- 10% of the expected stent area.

Conclusions

Despite moderately high-pressure inflations, the mean minimum stent CSA actually achieved was, on average, only 62% of the manufacturer's expected stent area. To optimize stent deployment, these IVUS observations should be considered during coronary artery stenting.

We performed Cutting Balloon angioplasty on 20 lesions in 11 heart transplant recipients 7.5 +/- 3.8 years after transplantation. The mean percentage of diameter stenosis decreased from 88.3% +/- 13.8% to 19.6% +/- 13.7% after Cutting Balloon angioplasty without complication. Seven patients underwent follow-up angiography at 4.9 +/- 1.7 months in a total of 12 lesions, and all lesions showed restenosis with a mean diameter stenosis of 84.4% +/- 19.2%. Cutting Balloon angioplasty can be used to treat obstructions in cardiac transplant coronary arteries; however, it may cause exacerbation and produce a high restenosis rate.

Transplant vasculopathy significantly limits the survival of cardiac transplant patients and occurs in 50% of patients by 5 years posttransplant. We report our experience with six cardiac transplant patients who underwent intracoronary brachytherapy for in-stent restenosis. At four centers, six patients underwent intracoronary radiation for in-stent restenosis. All patients received extended antiplatelet therapy with clopidogrel and aspirin. Follow-up angiography was performed in all patients. Two of the six patients underwent subsequent target lesion revascularization. Patient 1 presented with total occlusion of her radiated lesion. She had a complex procedure requiring stenting for a dissection after the radiation dwell. Patient 2 had high-grade restenosis following brachytherapy. Patient 3 had a 50% restenotic lesion. Patients 4, 5, and 6 had follow-up angiography that showed no evidence of restenosis. There are few good options to treated accelerated transplant vasculopathy. Radiation therapy may be a viable option in this difficult patient population.

Diabetic patients undergoing coronary interventions have worse clinical and angiographic outcomes than do patients without diabetes. Metformin, an insulin sensitizer, may decrease the occurrence of these outcomes. Diabetic patients in the Prevention of Restenosis with Tranilast and its Outcomes Trial were identified through their medical records (n = 2,772). In this trial, 1,110 diabetic patients received nonsensitizer therapy (insulin and/or sulfonylureas) and 887 received sensitizer therapy (metformin with or without additional therapy). Logistic regression was used to obtain odds ratios (ORs) (sensitizer vs nonsensitizer therapy) of any clinical event (death, myocardial infarction, or ischemia-driven target vessel revascularization) and adjusted for multiple risk factors. Multivariate analysis showed no effect of lesion characteristics on clinical outcomes. Compared with patients on nonsensitizer therapy, those on sensitizer therapy showed an adjusted OR of 0.72 (95% confidence interval [CI] 0.57 to 0.91, p = 0.005) for any clinical event. The differences between the nonsensitizer therapy group and the sensitizer group were attributable mainly to decreased rates of death (OR 0.39, 95% CI 0.19 to 0.77, p = 0.007) and myocardial infarction (OR 0.31, 95% CI 0.15 to 0.66, p = 0.002). In our retrospective analysis, use of metformin in diabetics undergoing coronary interventions appeared to decrease adverse clinical events, especially death and myocardial infarction, compared with diabetic patients treated with nonsensitizer therapy.

Reliable, closed-chest methods for creating large animal models of acute myocardial hypoperfusion are limited. We demonstrated the feasibility and efficacy of using magnetic resonance (MR)-compatible 3D-printed coronary implants for establishing swine models of myocardial hypoperfusion. We designed, manufactured, and percutaneously deployed implants in 13 swine to selectively create focal coronary stenosis. To test the efficacy of the implants to cause hypoperfusion or ischemia in the perfused territory, we evaluated regional wall motion, myocardial perfusion, and infarction using MR imaging. The overall swine survival rate was 85% (11 of 13). The implant retrieval rate was 92% (12 of 13). Fluoroscopic angiography confirmed focal stenosis. Cine and perfusion MRI showed regional wall motion abnormalities and inducible ischemia, respectively. Late gadolinium enhancement and histopathology showed no myocardial infarction. Our minimally invasive technique has promising applications for validation of new diagnostic methods in cardiac MR. Graphical abstract Our new minimally invasive, percutaneous method for creating swine models of acute focal coronary stenosis can be used for magnetic resonance imaging studies of myocardial ischemia. Comparable to existing methods in its efficacy and reliability, this rapid prototyping technique will allow researchers to more easily conduct translational cardiac imaging studies of coronary artery disease in large animal models.

Background

Iodine and particularly its oxidated forms have long been recognized for its effective antiseptic properties. Limited in vitro and in vivo data suggest that iodine exposure may rapidly inactivate, reduce transmission, and reduce infectivity of SARS-CoV-2. We hypothesized that iodine exposure may be associated with decreased incident COVID-19 infection.

Methods

A retrospective population-level cohort analysis was performed of the U.S. Veterans Health Administration between 1 March 2020 and 31 December 2020, before the widespread availability of vaccines against SARS-CoV-2. Multivariable logistic regression models estimated the adjusted odds ratios (OR) and 95% confidence intervals (CI) of the associations between iodinated contrast exposure and incident COVID-19 infection, adjusting for age, sex, race/ethnicity, place of residence, socioeconomic status, and insurance status.

Results

530,942 COVID-19 tests from 333,841 Veterans (mean ± SD age, 62.7 ± 15.2 years; 90.2% men; 61.9% non-Hispanic Whites) were analyzed, of whom 9% had received iodinated contrast ≤60 days of a COVID-19 test. Iodine exposure was associated with decreased incident COVID-19 test positivity (OR, 0.75 95% CI, 0.71-0.78). In stratified analyses, the associations between iodinated contrast use and decreased COVID-19 infection risk did not differ by age, sex, and race/ethnicity.

Conclusion

Iodine exposure may be protective against incident COVID-19 infection. Weighed against the risks of supraphysiologic iodine intake, dietary, and supplemental iodine nutrition not to exceed its Tolerable Upper Limit may confer an antimicrobial benefit against SARS-CoV-2. A safe but antimicrobial level of iodine supplementation may be considered in susceptible individuals, particularly in geographic regions where effective COVID-19 vaccines are not yet readily available.