Longitudinal study of vascular remodeling in coronary arteries after heart transplantation

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

Novel Percutaneous Approach for Deployment of 3D Printed Coronary Stenosis Implants in Swine Models of Ischemic Heart Disease.

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

Low molecular weight heparin (enoxaparin) reduces restenosis after iliac angioplasty in the hypercholesterolemic rabbit

AbstractSmooth muscle cell proliferation is central to the process of restenosis. Attempts to inhibit the events leading to this proliferation have met with little success. In addition to its known antithrombotic effects, heparin also has inhibitory effects on smooth muscle cell proliferation. These effects appear to be unrelated to its anticoagulant properties and are retained in low molecular weight heparin derivatives. Although the use of heparin for as long as 18 to 24 h after coronary angioplasty in humans has not prevented restenosis, longer treatment periods have not been assessed.This study examines the effect of treatment with a low molecular weight heparin (enoxaparin) in a hypercholesterolemic rabbit iliac artery model. Control rabbits had a mean iliac artery diameter of 0.70 ± 0.06 mm, which increased to 1.73 ± 0.09 mm after balloon angioplasty. At follow-up angiography 4 weeks later, the mean vessel diameter was 0.56 ± 0.12 mm. Animals treated with low dose enoxaparin (1 mg/kg per day) for 4 weeks and high dose enoxaparin (10 mg/kg per day) for either 2 or 4 weeks had similar mean luminal diameters before and immediately after angioplasty. At follow-up angiography, the mean luminal diameter was 0.82 ± 0.17 mm for low dose enoxaparin, 1.04 ± 0.20 mm for 2 week high dose enoxaparin (p = 0.03 versus control) and 1.19 ± 0.09 mm for 4 week high dose enoxaparin (p = 0.001 versus control).When defined as loss of 50% of the initial gain achieved with angioplasty, restenosis was found in all control vessels. In the 2 week high dose enoxaparin group, only two of nine vessels had restenosis and in the 4 week high dose group, three of nine vessels had restenosis (p = 0.001 versus control). These results show that antiproliferative agents such as low molecular weight heparin can inhibit restenosis in animal models and suggest that they may be useful in humans

Excess iodine exposure acutely increases salivary iodide and antimicrobial hypoiodous acid concentrations in humans

Abstract 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

Optimizing stent expansion with new stent delivery systems

AbstractOBJECTIVESThe 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.BACKGROUNDFirst 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.METHODSIntravascular 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.RESULTSThe MLD (2.5 ± 0.5 mm) and minimum stent CSA (6.0 ± 1.7 mm2) by IVUS were significantly smaller than the manufacturer’s expected stent diameter (3.5 ± 0.4 mm) and area (9.5 ± 1.9 mm2) (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.CONCLUSIONSDespite 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

Iodine‐Induced Hypothyroidism and Long‐Term Risks of Incident Heart Failure

Background Although most individuals can adapt to a large iodine load and remain euthyroid, hypothyroidism can develop after iodine exposure. Hypothyroidism is associated with adverse cardiovascular consequences, including heart failure. This study was performed to investigate the relationships between iodine‐induced hypothyroidism and incident heart failure. Methods and Results This cohort study of the US Veterans Health Administration (1998–2021) included adults aged ≥18 years with a serum thyroid‐stimulating hormone (thyrotropin) <60 days of iodine contrast administration, and <1 year of a baseline normal serum thyroid‐stimulating hormone. Cox proportional hazards regression ascertained risk of incident heart failure following iodine‐induced hypothyroidism, adjusting for age, sex, race and ethnicity, body mass index, and history of coronary heart disease, dyslipidemia, diabetes, and hypertension. Of 45 470 veterans (mean±SD age, 61.1±14.1 years; 88% men), 3361 (7.4%) developed iodine‐induced hypothyroidism. Heart failure developed in 5685 (12.5%) individuals over a median follow‐up of 3.6 years (interquartile range, 1.9–7.2 years). Adjusted for risk factors, iodine‐induced hypothyroidism was associated with increased risk of heart failure, compared with those who remained euthyroid after iodine exposure (adjusted hazard ratio [HR], 1.11 [95% CI, 1.01–1.22]). Women were at greater risk than men (adjusted HR: women, 1.65 [95% CI, 1.13–2.40]; men, 1.08 [95% CI, 0.98–1.19]; P for interaction, 0.02). Conclusions In the largest US study of this topic, hypothyroidism following iodine exposure was associated with an increased risk of incident heart failure, particularly in women. These findings support the need for further research to address the clinical significance of this issue, including the possible sex‐specific risks of incident heart failure in more diverse data sets and study populations