The value of ultrasound enhancing agents in the echocardiographic acquisition of pulmonary artery systolic pressure: An invasive to non-invasive correlation study.

PURPOSE: Right heart catheterization (RHC) is the gold standard for the assessment of pulmonary artery systolic pressures (PASP). Despite high utilization of echocardiography for the non-invasive assessment of PASP, the data comparing real-time non-invasive echocardiographic PASP with invasive PASP is limited. Furthermore, evidence regarding the utility and diagnostic accuracy of ultrasound enhancing agents (UEA) for non-invasive PASP assessment is lacking. To evaluate the accuracy of non-invasive PASP assessment with real-time invasive measures and the incremental benefit of UEA in this setting. METHODS: This was a prospective cohort study of 90 patients, undergoing clinically indicated RHC for hemodynamic assessment. All patients underwent a limited echocardiogram during RHC. Tricuspid regurgitant velocity (TRV) was measured on unenhanced echo, in the setting of centrally administrated agitated saline, then as either centrally administered or peripherally administered UEA. RESULTS: Of the 90 patients enrolled in our study, 41% had pulmonary hypertension. The overall mean PASP measured by RHC was 32.8 mmHg (+/- 11.3 mmHg). Unenhanced echocardiograms had a moderate correlation with invasive PASP (r = 0.57; p = < 0.001) which improved to a strong correlation with administration of agitated saline (r = 0.75; p = < 0.001) or centrally administered UEA (r = 0.77; p = < 0.001), with the best correlation noted with peripherally administered UEA (r = 0.83; p = < 0.001). Against invasive PASP, agitated saline enhanced PASP had the lowest bias (0.12mmHg; -15.6 to 15.8mmHg) when compared with all other non-invasive measures of PASP. CONCLUSIONS: Unenhanced echocardiographic estimation of TRV was found to have a poorer correlation with invasively measured PASP when compared to agitated saline and centrally administered UEA. Agitated saline enhanced PASP demonstrated the lowest bias with invasive PASP when compared to other non-invasive measures of PASP.

Corrigendum: Rationale and Design of a Pharmacist-led Intervention for the Risk-Based Prevention of Heart Failure: The FIT-HF Pilot Study.

[This corrects the article DOI: 10.3389/fcvm.2021.785109.].

Rationale and Design of a Pharmacist-led Intervention for the Risk-Based Prevention of Heart Failure: The FIT-HF Pilot Study.

Background: Given rising morbidity, mortality, and costs due to heart failure (HF), new approaches for prevention are needed. A quantitative risk-based strategy, in line with established guidelines for atherosclerotic cardiovascular disease prevention, may efficiently select patients most likely to benefit from intensification of preventive care, but a risk-based strategy has not yet been applied to HF prevention. Methods and Results: The Feasibility of the Implementation of Tools for Heart Failure Risk Prediction (FIT-HF) pilot study will enroll 100 participants free of cardiovascular disease who receive primary care at a single integrated health system and have a 10-year predicted risk of HF of ≥5% based on the previously validated Pooled Cohort equations to Prevent Heart Failure. All participants will complete a health and lifestyle questionnaire and undergo cardiac biomarker (B-type natriuretic peptide [BNP] and high-sensitivity cardiac troponin I [hs-cTn]) and echocardiography screening at baseline and 1-year follow-up. Participants will be randomized 1:1 to either a pharmacist-led intervention or usual care for 1 year. Participants in the intervention arm will undergo consultation with a pharmacist operating under a collaborative practice agreement with a supervising cardiologist. The pharmacist will perform lifestyle counseling and recommend initiation or intensification of therapies to optimize risk factor (hypertension, diabetes, and cholesterol) management according to the most recent clinical practice guidelines. The primary outcome is change in BNP at 1-year, and secondary and exploratory outcomes include changes in hs-cTn, risk factor levels, and cardiac mechanics at follow-up. Feasibility will be examined by monitoring retention rates. Conclusions: The FIT-HF pilot study will offer insight into the feasibility of a strategy of quantitative risk-based enrollment into a pharmacist-led prevention program to reduce heart failure risk. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT04684264.

Identification of prolapsing mitral valve scallops by a three-dimensional multiplanar reconstruction method.

BACKGROUND: The objectives of this study were twofold: to assess the diagnostic utility of three-dimensional (3D) multiplanar reconstruction (MPR) in identifying prolapsing mitral valve (MV) scallops, and (2) to compare two-dimensional (2D) transthoracic echocardiography (TTE) and 3DMPR to (2D) transesophageal echocardiography (TEE) approaches among patients with mitral valve prolapse (MVP). METHODS: Fifty-five patients with MVP who underwent MV repair or replacement were retrospectively analyzed using 3 types of echocardiographic studies (2DTEE, 2DTTE, 3DMPR). The operative (OR) findings were considered the gold standard. RESULTS: When 3DMPR was combined with 2DTTE, the agreement with the OR findings was moderately strong for the A2 scallop (P < 0.001) and strong for the A3 scallop (P = 0.001), entire anterior leaflet (P < 0.001), P2 scallop (P < 0.001) and the entire posterior leaflet (P < 0.001). In comparison to the OR findings, 2DTEE demonstrated moderately strong agreement for the A2 scallop (P = 0.010) and the entire anterior leaflet (P < 0.001), and strong agreement for the P2 scallop (P < 0.001) and entire posterior leaflet (P < 0.001). CONCLUSIONS: Three-dimensional MPR should be added to the armamentarium of complementary echo techniques in the evaluation of MVP. There is increased benefit in combining 3DMPR with 2DTTE findings as part of the preoperative evaluation of patients with MVP.

Ultrastructural and cellular basis for the development of abnormal myocardial mechanics during the transition from hypertension to heart failure.

Although the development of abnormal myocardial mechanics represents a key step during the transition from hypertension to overt heart failure (HF), the underlying ultrastructural and cellular basis of abnormal myocardial mechanics remains unclear. We therefore investigated how changes in transverse (T)-tubule organization and the resulting altered intracellular Ca(2+) cycling in large cell populations underlie the development of abnormal myocardial mechanics in a model of chronic hypertension. Hearts from spontaneously hypertensive rats (SHRs; n = 72) were studied at different ages and stages of hypertensive heart disease and early HF and were compared with age-matched control (Wistar-Kyoto) rats (n = 34). Echocardiography, including tissue Doppler and speckle-tracking analysis, was performed just before euthanization, after which T-tubule organization and Ca(2+) transients were studied using confocal microscopy. In SHRs, abnormalities in myocardial mechanics occurred early in response to hypertension, before the development of overt systolic dysfunction and HF. Reduced longitudinal, circumferential, and radial strain as well as reduced tissue Doppler early diastolic tissue velocities occurred in concert with T-tubule disorganization and impaired Ca(2+) cycling, all of which preceded the development of cardiac fibrosis. The time to peak of intracellular Ca(2+) transients was slowed due to T-tubule disruption, providing a link between declining cell ultrastructure and abnormal myocardial mechanics. In conclusion, subclinical abnormalities in myocardial mechanics occur early in response to hypertension and coincide with the development of T-tubule disorganization and impaired intracellular Ca(2+) cycling. These changes occur before the development of significant cardiac fibrosis and precede the development of overt cardiac dysfunction and HF.

Ten-year echo/doppler determination of the benefits of aerobic exercise after the age of 65 years.

As the human lifespan becomes progressively extended, potential health-related effects of intense aerobic exercise after age 65 need evaluation. This study evaluates the cardiovascular (CV), pulmonary, and metabolic effects of competitive distance running on age-related deterioration in men between 69 (+/-3) and 77 (+/-2) years (mean +/- SD). Twelve elderly competitive distance runners (ER) underwent oxygen consumption and echo/Doppler treadmill stress testing (Balke protocol) for up to 10 years. Twelve age-matched sedentary controls (SC) with no history of CV disease were similarly tested and the results compared for the initial three series of the study. CV data clearly separated the ER from SC. At entry, resting and maximal heart rate, systolic/diastolic blood pressure, peak oxygen consumption (VO(2max)), and E/A ratio of mitral inflow were better in the ER (P < 0.05 vs. SC). With aging, ER had a less deterioration of multiple health parameters. Exceptions were VO(2max) and left ventricular diastolic function (E/A, AFF, IVRT) that decreased (P < 0.05, Year 10 vs. Year 1). Health advantages of high-level aerobic exercise were demonstrated in the ER when compared to SC. Importantly, data collected in ER over 10 years confirm the benefit of intensive exercise for slowing several negative effects of aging. However, the normative drop of exercise capacity in the seventh and eighth decades reduces the potential athleticism plays in prevention of CV events.

Physical activity during daily life and brachial artery flow-mediated dilation in peripheral arterial disease.

We determined whether higher levels of physical activity in daily life are associated with better brachial artery flow-mediated dilation (FMD) among individuals with lower extremity peripheral arterial disease (PAD). Participants were 111 men and women with PAD (ankle-brachial index (ABI)

A reproducible porcine ePTFE arterial bypass model for neointimal hyperplasia.

BACKGROUND: Late failure of prosthetic vascular bypass grafting using expanded polytetrafluoroethylene (ePTFE) is secondary to the development of neointimal hyperplasia, most commonly at the distal anastomosis. To develop therapies that can improve upon current prosthetic vascular bypass grafting, a large animal model of prosthetic bypass grafting that results in reproducible neointimal hyperplasia is necessary. METHODS: We performed bilateral end-to-side carotid artery bypasses with 6 mm ePTFE in a porcine model (n = 11). We studied graft patency using magnetic resonance angiography (MRA, 3 wk), duplex ultrasonography (4 wk), and digital-subtraction contrast angiography (4 wk). Animals were sacrificed at 4 wk and morphometric analysis was performed. RESULTS: Of the 11 animals that underwent surgery, one pig died from respiratory compromise; of the remaining 10, graft patency was 90% at 4 wk. Peak systolic and end diastolic velocities were established for this model using ultrasonography. MRA, ultrasonography, and angiography confirmed graft patency and were complimentary tools to evaluate the grafts. Development of neointimal hyperplasia was reproducible at 4 wk in both the proximal and distal anastomoses (2.5 to 3 mm(2)) of the ePTFE bypass grafts. CONCLUSION: We developed a reproducible porcine ePTFE carotid artery bypass model for studying neointimal hyperplasia. Not only does this model allow for the manipulation and evaluation of potential therapies, but patency and neointimal hyperplasia can be easily evaluated by traditional means, such as MRA, ultrasonography, and angiography. This preclinical model is ideal for evaluation of novel therapies in vivo designed to inhibit neointimal hyperplasia following arterial reconstruction with prosthetic bypass grafting.

Brachial arterial dynamics during staged lower extremity exercise: utility and comparison in physically active versus sedentary subjects.

Constriction and relaxation of peripheral conduit arteries in response to exercise and recovery are amenable to noninvasive imaging. Diameter changes in the brachial artery during stationary bicycle pedaling are paradoxical to those in the lower extremities. When exercise is confined to the legs, arteries in the upper extremities constrict while leg arteries dilate. The magnitude of vasoconstriction in the upper extremities reflects the integrity of exercise mediated vascular responses. In the current study, young and old men with various levels of physical activity and cardiovascular histories exercised on a stationary bicycle while brachial artery diameter and flow velocity were continuously obtained. Results suggest that normal aging blunts arterial reactivity in seniors even if they exercise regularly. However, arterial dysfunction is greater when associated with sedentary lifestyle. This methodology of imaging brachial artery diameter changes during bicycle pedaling appears to be an effective tool for assessing the physiologic integrity of the vascular bed.

Angiogenic pretreatment to enhance myocardial function after cellular cardiomyoplasty with skeletal myoblasts.

OBJECTIVE: Improvements in ventricular function after cellular cardiomyoplasty appear to be limited by the poor survival of the cellular implants. Angiogenic pretreatment of infarcted myocardium may improve implanted cell survival and consequently myocardial function. METHODS: Fischer 344 rats underwent coronary artery ligation and injection of an adenovirus encoding vascular endothelial growth factor 121 or of saline solution at increasing intervals after ligation. Myocardial perfusion and mass preservation were assessed. On the basis of these data, four groups of animals underwent coronary ligation and adenovirus with or without syngeneic skeletal myoblast administration: (1) adenovirus at ligation and myoblasts 3 weeks later (n = 7), (2) saline solution at ligation and myoblasts 3 weeks later (n = 8), (3) saline solution at ligation and 3 weeks later (n = 8), and (4) saline solution at ligation and adenovirus with myoblasts 3 weeks later (n = 5). Left ventricular ejection fraction was analyzed by echocardiography before coronary ligation and 3 and 5 weeks later, after which cell survival was assessed in harvested tissues. RESULTS: Myocardial infarct perfusion was at least 50% greater in animals treated with adenoviral vector than with saline solution immediately after ligation (P < .02). In comparison, delayed adenovirus administration did not significantly diminish infarct perfusion but resulted in decreased myocardial preservation (P < .05). Accordingly, adenovirus administration nearly tripled implanted myoblast survival relative to saline solution-treated animals (P = .004). Left ventricular ejection fraction was improved, however, only after cell implantation with adenovirus pretreatment (P = .027). CONCLUSION: Angiogenic strategies can help to preserve myocardium jeopardized by acute coronary occlusions. Angiogenic pretreatment enhances the efficacy of cellular cardiomyoplasty.

Gadofluorine-enhanced magnetic resonance imaging of carotid atherosclerosis in Yucatan miniswine.

OBJECTIVE: The aim of this study was to determine whether gadofluorine, a paramagnetic magnetic resonance imaging (MRI) contrast agent, selectively enhances carotid atherosclerotic plaques in Yucatan miniswine. METHODS: Atherosclerotic plaques were induced in the left carotid arteries (LCA) of Yucatan miniswine (n=3) by balloon denudation and high cholesterol diet. T1-weighted MRI was performed before and 24 hours after gadofluorine injection (at a dose of 100 micromol/kg) to assess the enhancement of the balloon-injured LCA wall relative to healthy, uninjured right carotid artery (RCA) wall. Histopathology was performed to verify the presence and composition of the atherosclerotic plaques imaged with MRI. RESULTS: Gadofluorine was found to enhance LCA atherosclerotic lesions relative to RCA wall by 21% (P<0.025) 24 hours after contrast injection. Enhancement of healthy LCA wall relative to healthy RCA wall was not observed. CONCLUSION: Gadofluorine selectively enhances carotid atherosclerotic plaques in Yucatan miniswine. Gadofluorine appears to be a promising MR contrast agent for detection of atherosclerotic plaques in vivo.

Porcine carotid arterial material property alterations with induced atheroma: an in vivo study.

OBJECTIVE: A novel methodology has been developed to evaluate regional alterations in arterial wall material properties with induced atheroma in an animal model. METHODS: Atheromatous lesions (fatty, fibro-fatty, and fibrous) were induced in the carotid arteries of a Yucatan miniswine model by endothelial cell denudation and high cholesterol diet. The images at base line and 8 weeks after denudation were obtained using intravascular ultrasound (IVUS) imaging along with hemodynamic data. Finite element analysis (FEA) along with optimization was employed to assess regional alterations in elastic modulus in the presence of atheroma confirmed by histology. RESULTS: In animals with 8 weeks of induced atherosclerosis, the elastic modulus increased-(elastic modulus-all values x 10(4) Pa, mean+/-S.D.) normal elements (9.34+/-0.36) compared to abnormal elements (9.52+/-0.36) (p<0.05 versus normal elements). Wall thickness increased with atheroma formation. These data demonstrate stiffening vascular wall elastic modulus with lesion progression. This is different from the behavior of femoral arteries, where the elastic modulus decreases with early stages of atheroma development followed by an increase as lesions progress. CONCLUSIONS: This methodology permits determination of areas with early atheroma development, follow atheroma progression, and potentially evaluate interventions aimed at decreasing atheroma load and normalizing vascular material properties.

Intravascular ultrasound molecular imaging of atheroma components in vivo.

OBJECTIVES: Our purpose was to quantitate and confirm specific echogenic immunoliposome (ELIP) atheroma component enhancement in vivo. BACKGROUND: Targeted ELIPs for ultrasonic detection and staging of active molecular components of endothelium and atheroma have been developed. METHODS: In Yucatan miniswine, the endothelium was injured from one femoral and one carotid artery, and animals were fed a high-cholesterol diet for two months to create various stages of atheroma. Arteries were imaged with intravascular ultrasound (IVUS) 5 and 10 min after ELIP injection (5-mg dose). Anti-intercellular adhesion molecule-1 (ICAM-1), anti-vascular cell adhesion molecule-1 (VCAM-1), anti-fibrin, anti-fibrinogen, and anti-tissue factor (TF) conjugated ELIPs were used, and immunohistochemistry (IHC) confirmed the presence or absence of molecular expression. Two blinded observers determined if each segment was enhanced by ELIP. Three-dimensional image reconstruction and videodensitometric analysis determined the mean gray-scale (MGS) change of the luminal border. RESULTS: To determine endothelial injury component enhancement, anti-fibrinogen ELIP enhanced exposed fibrin in all arteries (MGS increased 22 +/- 5%; 6 arteries; 2 animals). To determine enhancement of molecular components in atherosclerotic arteries, observers detected enhancement 5 min after anti-VCAM, anti-ICAM, anti-TF, anti-fibrin, and anti-fibrinogen conjugated ELIPs. Furthermore, ELIP enhanced atheroma MGS by 39 +/- 18% (n = 8). The IHC staining confirmed the expression of respective molecular targets in all enhanced segments. CONCLUSIONS: It was shown that ELIPs specifically enhance endothelial injury/atheroma components. This allows better characterization of the type and extent of active atheroma components and may allow more directed therapy.

Left ventricular thrombus enhancement after intravenous injection of echogenic immunoliposomes: studies in a new experimental model.

BACKGROUND: Targeted echogenic immunoliposomes (ELIPs) for ultrasound enhancement of atheroma components have been developed. To date, ELIP delivery has been intra-arterial. To determine whether ELIPs can be given intravenously with enhancement of systemic structures, a left ventricular thrombus (LVT) model was developed. METHODS AND RESULTS: In 6 animals plus 1 dose-ranging animal, the apical coronary arteries were ligated, and an LVT was produced by injecting Hemaseel fibrin adhesive through the apical myocardium. The thrombus was imaged epicardially and transthoracically at 0, 1, 5, and 10 minutes after anti-fibrinogen ELIP injections. The dose of ELIPs was varied. PBS and unconjugated ELIPs were controls. The apical thrombi were easily reproduced and clearly visible with epicardial and transthoracic ultrasound. Enhancement occurred with 2 mg anti-fibrinogen ELIPs and increased with dose. With 8 mg ELIPs, enhancement was different from control within 10 minutes (P<0.05). Rhodamine-labeled anti-fibrinogen ELIPs were seen with fluorescence microscopy of the LVT. Blinded viewing detected enhancement by 10 minutes in all animals after anti-fibrinogen ELIPs. CONCLUSIONS: We describe an easily reproducible LVT model. Anti-fibrinogen ELIPs delivered intravenously, as a single-step process, rapidly enhance the ultrasound image of a systemic target. This allows for future development of ELIPs as a targeted ultrasound contrast agent.