Cardiac PET Myocardial Blood Flow Quantification Assessment of Early Cardiac Allograft Vasculopathy.

BACKGROUND: Positron emission tomography (PET) has demonstrated utility for diagnostic and prognostic assessment of cardiac allograft vasculopathy (CAV) but has not been evaluated in the first year after transplant. OBJECTIVES: The authors sought to evaluate CAV at 1 year by PET myocardial blood flow (MBF) quantification. METHODS: Adults at 2 institutions enrolled between January 2018 and March 2021 underwent prospective 3-month (baseline) and 12-month (follow-up) post-transplant PET, endomyocardial biopsy, and intravascular ultrasound examination. Epicardial CAV was assessed by intravascular ultrasound percent intimal volume (PIV) and microvascular CAV by endomyocardial biopsy. RESULTS: A total of 136 PET studies from 74 patients were analyzed. At 12 months, median PIV increased 5.6% (95% CI: 3.6%-7.1%) with no change in microvascular CAV incidence (baseline: 31% vs follow-up: 38%; P = 0.406) and persistent microvascular disease in 13% of patients. Median capillary density increased 30 capillaries/mm2 (95% CI: -6 to 79 capillaries/mm2). PET myocardial flow reserve (2.5 ± 0.7 vs 2.9 ± 0.8; P = 0.001) and stress MBF (2.7 ± 0.6 vs 2.9 ± 0.6; P = 0.008) increased, and coronary vascular resistance (CVR) (49 ± 13 vs 47 ± 11; P = 0.214) was unchanged. At 12 months, PET and PIV had modest correlation (stress MBF: r = -0.35; CVR: r = 0.33), with lower stress MBF and higher CVR across increasing PIV tertiles (all P < 0.05). Receiver-operating characteristic curves for CAV defined by upper-tertile PIV showed areas under the curve of 0.74 for stress MBF and 0.73 for CVR. CONCLUSIONS: The 1-year post-transplant PET MBF is associated with epicardial CAV, supporting potential use for early noninvasive CAV assessment. (Early Post Transplant Cardiac Allograft Vasculopahty [ECAV]; NCT03217786).

Automated Assessment of Cardiac Systolic Function From Coronary Angiograms With Video-Based Artificial Intelligence Algorithms.

Importance: Understanding left ventricular ejection fraction (LVEF) during coronary angiography can assist in disease management. Objective: To develop an automated approach to predict LVEF from left coronary angiograms. Design, Setting, and Participants: This was a cross-sectional study with external validation using patient data from December 12, 2012, to December 31, 2019, from the University of California, San Francisco (UCSF). Data were randomly split into training, development, and test data sets. External validation data were obtained from the University of Ottawa Heart Institute. Included in the analysis were all patients 18 years or older who received a coronary angiogram and transthoracic echocardiogram (TTE) within 3 months before or 1 month after the angiogram. Exposure: A video-based deep neural network (DNN) called CathEF was used to discriminate (binary) reduced LVEF (≤40%) and to predict (continuous) LVEF percentage from standard angiogram videos of the left coronary artery. Guided class-discriminative gradient class activation mapping (GradCAM) was applied to visualize pixels in angiograms that contributed most to DNN LVEF prediction. Results: A total of 4042 adult angiograms with corresponding TTE LVEF from 3679 UCSF patients were included in the analysis. Mean (SD) patient age was 64.3 (13.3) years, and 2212 patients were male (65%). In the UCSF test data set (n = 813), the video-based DNN discriminated (binary) reduced LVEF (≤40%) with an area under the receiver operating characteristic curve (AUROC) of 0.911 (95% CI, 0.887-0.934); diagnostic odds ratio for reduced LVEF was 22.7 (95% CI, 14.0-37.0). DNN-predicted continuous LVEF had a mean absolute error (MAE) of 8.5% (95% CI, 8.1%-9.0%) compared with TTE LVEF. Although DNN-predicted continuous LVEF differed 5% or less compared with TTE LVEF in 38.0% (309 of 813) of test data set studies, differences greater than 15% were observed in 15.2% (124 of 813). In external validation (n = 776), video-based DNN discriminated (binary) reduced LVEF (≤40%) with an AUROC of 0.906 (95% CI, 0.881-0.931), and DNN-predicted continuous LVEF had an MAE of 7.0% (95% CI, 6.6%-7.4%). Video-based DNN tended to overestimate low LVEFs and underestimate high LVEFs. Video-based DNN performance was consistent across sex, body mass index, low estimated glomerular filtration rate (≤45), presence of acute coronary syndromes, obstructive coronary artery disease, and left ventricular hypertrophy. Conclusion and relevance: This cross-sectional study represents an early demonstration of estimating LVEF from standard angiogram videos of the left coronary artery using video-based DNNs. Further research can improve accuracy and reduce the variability of DNNs to maximize their clinical utility.

Recovering from spontaneous coronary artery dissection: Patient-reported challenges and rehabilitative intervention needs.

BACKGROUND: Spontaneous coronary artery dissection (SCAD) is an increasingly recognized cause of acute coronary syndrome that disproportionally affects younger women. The underlying etiology is incompletely understood, postmorbid psychological distress is high, and treatment plans are predominantly based on clinician experience. There remains uncertainty on how to adequately address the needs of patients with SCAD as part of secondary prevention. METHOD: As a Define and Refine phase of the ORBIT model (Phase 1), this study investigated SCAD patients' challenges and rehabilitative intervention needs using a qualitative research design. Patients with SCAD were purposively recruited to participate in structured interviews that were analyzed using inductive thematic coding techniques. RESULTS: Patients with SCAD (n = 15; 86.7% female; mean age = 47.5 years; data saturation reached with patient sample) expressed challenges in (a) navigating uncertainty associated with the disease; (b) living with anxiety; (c) reconciling pre and post-SCAD identities; (d) accurately identifying symptoms and experiencing a sense of isolation in recovery due to gender and young age; and (e) managing changing family dynamics and family members' stress. Intervention needs included (a) addressing unique demographic and cardiovascular profiles when designing programs for cardiac rehabilitation; (b) providing more psychological and peer support resources to address anxiety and sense of isolation; (c) disseminating information on rapidly evolving SCAD research; and (d) acknowledging and providing support to the family system. CONCLUSIONS: The results signal curricula to be included in tailored SCAD programming and underscore the need for further study and dissemination of optimal secondary preventative care for this patient population. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Contrast-free optical coherence tomography:Systematic evaluation of non-contrast media for intravascular assessment.

BACKGROUND: Coronary revascularization using imaging guidance is rapidly becoming the standard of care. Intravascular optical coherence tomography uses near-infrared light to obtain high resolution intravascular images. Standard optical coherence tomography imaging technique employs iodinated contrast dye to achieve the required blood clearance during acquisition. We sought to systematically evaluate the technical performance of saline as an alternative to iodinated contrast for intravascular optical coherence tomography assessment. METHODS AND RESULTS: We performed bench top optical coherence tomography analysis on nylon tubing with sequential contrast/saline dilutions to empirically derive adjustment coefficients. We then applied these coefficients in vivo in an established rabbit abdominal stenting model with both saline and contrast optical coherence tomography imaging. In this model, we assessed the impact of saline on both quantitative and qualitative vessel assessment. Nylon tubing assessment demonstrated a linear relationship between saline and contrast for both area and diameter. We then derived adjustment coefficients, allowing for accurate calculation of area and diameter when converting saline into both contrast and reference dimensions. In vivo studies confirmed reduced area with saline versus contrast [7.43 (5.67-8.36) mm2 versus 8.2 (6.34-9.39) mm2, p = 0.001] and diameter [3.08 mm versus 3.23 mm, p = 0.001]. Following correction, a strong relationship was achieved in vivo between saline and contrast in both area and diameter without compromising image quality, artefact, or strut assessment. CONCLUSION: Saline generates reduced dimensions compared to contrast during intravascular optical coherence tomography imaging. The relationship across physiologic coronary diameters is linear and can be corrected with high fidelity. Saline does not adversely impact image quality, artefact, or strut assessment.

Evaluation of an in vitro coronary stent thrombosis model for preclinical assessment.

Stent thrombosis remains an infrequent but significant complication following percutaneous coronary intervention. Preclinical models to rapidly screen and validate therapeutic compounds for efficacy are lacking. Herein, we describe a reproducible, high throughput and cost-effective method to evaluate candidate therapeutics and devices for either treatment or propensity to develop stent thrombosis in an in vitro bench-top model. Increasing degree of stent malapposition (0.00 mm, 0.10 mm, 0.25 mm and 0.50 mm) was associated with increasing thrombosis and luminal area occlusion (4.1 ± 0.5%, 6.3 ± 0.5%, 19.7 ± 4.5%, and 92.6 ± 7.4%, p < 0.0001, respectively). Differences in stent design in the form of bare-metal, drug-eluting, and bioresorbable vascular scaffolds demonstrated differences in stent thrombus burden (14.7 ± 3.8% vs. 20.5 ± 3.1% vs. 86.8 ± 5.3%, p < 0.01, respectively). Finally, thrombus burden was significantly reduced when healthy blood samples were incubated with Heparin, ASA/Ticagrelor (DAPT), and Heparin+DAPT compared to control (DMSO) at 4.1 ± 0.6%, 6.9 ± 1.7%, 4.5 ± 1.2%, and 12.1 ± 1.8%, respectively (p < 0.01). The reported model produces high throughput reproducible thrombosis results across a spectrum of antithrombotic agents, stent design, and degrees of apposition. Importantly, performance recapitulates clinical observations of antiplatelet/antithrombotic regimens as well as device and deployment characteristics. Accordingly, this model may serve as a screening tool for candidate therapies in preclinical evaluation.

Photoplethysmography using a smartphone application for assessment of ulnar artery patency: a randomized clinical trial.

BACKGROUND: Radial artery access is commonly performed for coronary angiography and invasive hemodynamic monitoring. Despite limitations in diagnostic accuracy, the modified Allen test (manual occlusion of radial and ulnar arteries followed by release of the latter and assessment of palmar blush) is used routinely to evaluate the collateral circulation to the hand and, therefore, to determine patient eligibility for radial artery access. We sought to evaluate whether a smartphone application may provide a superior alternative to the modified Allen test. METHODS: We compared the modified Allen test with a smartphone heart rate-monitoring application (photoplethysmography readings detected using a smartphone camera lens placed on the patient's index finger) in patients undergoing a planned cardiac catheterization. Test order was randomly assigned in a 1:1 fashion. All patients then underwent conventional plethysmography of the index finger, followed by Doppler ultrasonography of the radial and ulnar arteries (the diagnostic standard). The primary outcome was diagnostic accuracy of the heart rate-monitoring application. RESULTS: Among 438 patients who were included in the study, we found that the heart rate-monitoring application had a superior diagnostic accuracy compared with the modified Allen test (91.8% v. 81.7%, p = 0.002), attributable to its greater specificity (93.0% v. 82.8%, p = 0.001). We also found that this application had greater diagnostic accuracy for assessment of radial or ulnar artery patency in the ipsilateral and contralateral wrist (94.0% v. 84.0%, p < 0.001). INTERPRETATION: A smartphone application used at the bedside was diagnostically superior to traditional physical examination for confirming ulnar patency before radial artery access. This study highlights the potential for smartphone-based diagnostics to aid in clinical decision-making at the patient's bedside. Trial registration: Clinicaltrials.gov, no. NCT02519491.

PET Assessment of Epicardial Intimal Disease and Microvascular Dysfunction in Cardiac Allograft Vasculopathy.

BACKGROUND: Cardiac allograft vasculopathy (CAV) is a leading cause of graft failure and death after heart transplantation. Absolute myocardial blood flow (MBF) quantification using rubidium 82 (Rb-82) positron emission tomography (PET) could enable evaluation of diagnostically challenging diffuse epicardial and microvascular disease in CAV. OBJECTIVES: The authors aimed to evaluate Rb-82 PET detection of CAV. METHODS: Consecutive transplant recipients undergoing coronary angiography were prospectively evaluated with PET, multivessel intravascular ultrasound (IVUS), and intracoronary hemodynamics. CAV was defined as International Society of Heart and Lung Transplantation CAV1-3 on angiography and maximal intimal thickness ≥0.5 mm on IVUS. RESULTS: Forty patients (mean age 56 years, 4.8 years post-transplant) completed evaluation. CAV was detected in 32 patients (80%) by IVUS and 14 (35%) by angiography. PET correlated significantly with invasive coronary flow indices: r = 0.29, rate-pressure product-adjusted myocardial flow reserve (cMFR) versus coronary flow reserve; r = 0.28, relative flow reserve versus fractional flow reserve; and r = 0.37, coronary vascular resistance (CVR) versus index of microcirculatory resistance. Patients with CAV or microvascular dysfunction had reduced cMFR and stress MBF and increased CVR. Receiver operator characteristic curves demonstrated good accuracy of PET for CAV on IVUS (area under the curve 0.77 to 0.81) and optimal diagnostic cutoffs of cMFR <2.9, stress MBF <2.3, and CVR >55. Combined PET assessment for CAV yielded excellent >93% sensitivity (>65% specificity) for 1 abnormal parameter and >96% specificity (>55% sensitivity) for 2 abnormal parameters. CONCLUSIONS: Rb-82 PET flow quantification has high diagnostic accuracy for CAV, with potential for noninvasive evaluation after heart transplantation.

Safety and Efficacy of a Pharmacoinvasive Strategy in ST-Segment Elevation Myocardial Infarction: A Patient Population Study Comparing a Pharmacoinvasive Strategy With a Primary Percutaneous Coronary Intervention Strategy Within a Regional System.

OBJECTIVES: This study investigated the safety and efficacy of a pharmacoinvasive strategy compared with a primary percutaneous coronary intervention (PCI) strategy for ST-segment elevation myocardial infarction (STEMI) in the context of a real-world system. BACKGROUND: Primary PCI continues to be the optimal reperfusion therapy; however, in areas where PCI centers are not readily available, a pharmacoinvasive strategy has been proposed. METHODS: The University of Ottawa Heart Institute regional STEMI system provides a primary PCI strategy for patients presenting within a 90-km radius from the PCI center, and a pharmacoinvasive strategy for patients outside this limit. We included all confirmed STEMI patients between April 2009 and May 2011. The primary efficacy outcome was a composite of mortality, reinfarction, or stroke and the primary safety outcome was major bleeding. RESULTS: We identified 236 and 980 consecutive patients enrolled in pharmacoinvasive and primary PCI strategies, respectively. The median door-to-needle time was 31 min in the pharmacoinvasive group and the median door-to-balloon time was 95 min in the primary PCI group. In a multivariable model, there was no significant difference in the primary efficacy outcome (odds ratio: 1.54; p = 0.21); however, the propensity for more bleeding with a pharmacoinvasive strategy approached statistical significance (odds ratio: 2.02; p = 0.08). CONCLUSIONS: Within the context of a STEMI system, a pharmacoinvasive strategy was associated with similar rates of the composite of mortality, reinfarction, or stroke as compared with a primary PCI strategy; however, there was a propensity for more bleeding with a pharmacoinvasive strategy.

Bivalirudin for primary percutaneous coronary interventions: outcome assessment in the Ottawa STEMI registry.

BACKGROUND: Data from randomized trials has demonstrated the superiority of bivalirudin to glycoprotein IIb/IIIa inhibitors plus heparin in patients undergoing primary percutaneous coronary intervention. Real-world performance of bivalirudin in primary percutaneous coronary intervention and the benefit of bivalirudin over heparin remain unknown in an era of routine dual antiplatelet therapy. METHODS AND RESULTS: From July 2004 to December 2010, 2317 consecutive patients were indexed in the University of Ottawa Heart Institute ST-segment-elevation myocardial infarction registry. During this period 748 patients received bivalirudin, 699 patients received glycoprotein IIb/IIIa inhibitors, and 676 patients received unfractionated heparin alone. The primary outcome was the rate of noncoronary artery bypass graft related thrombolysis in myocardial infarction major bleeding. Bivalirudin significantly reduced the primary outcome compared with heparin plus glycoprotein IIb/IIIa inhibitors (2.7% versus 7.3%, adjusted OR 2.96, 95% CI: 1.61-5.45, P<0.001) and the composite end point of death, stroke, reinfarction and major bleed (OR 1.66, 95% CI: 1.12-2.45, P=0.01). Compared with heparin alone, a reduction in major bleeds (OR 1.21, 95% CI: 0.60-2.44, P=0.59) or the composite end point (1.05, 95% CI: 0.68-1.63, P=0.83) with bivalirudin could not be demonstrated. Notably, major bleeding was associated with a 5-fold increase in the risk of mortality both in-hospital (3.5% versus 20.6%) and out to 180 days (5.6% versus 25.8%). CONCLUSIONS: Bivalirudin use compared with glycoprotein IIb/IIIa inhibitors plus heparin as an antithrombotic strategy in primary percutaneous coronary intervention results in less major bleeding in contemporary practice. A benefit of bivalirudin over heparin could not be established with this registry and requires additional investigations to either confirm or refute.

The potential economic impact of restricted access to angiotensin-receptor blockers.

BACKGROUND: The use of angiotensin-receptor blockers increased by more than 4000% in Canada from 1996 to 2006. The benefit of these medications over angiotensin-converting-enzyme (ACE) inhibitors has not been proven aside from a reduction in dry cough. We estimated the potential cost savings that might have been achieved had access to angiotensin-receptor blockers been restricted. METHODS: We performed a cost-minimization analysis with a decision-tree model using a societal perspective over a one-year period. Sources of data for model parameters included IMS Health Canada data collected from one-third of all retail pharmacies for the cost and use of angiotensin-receptor blockers and ACE inhibitors in each province, as well as published studies for administrative costs and incidence of dry cough. We used Monte Carlo simulations with 10 000 iterations to test the impact of several model parameters (e.g., drug prices, administrative costs and the incidence of dry cough). All data are in 2006 Canadian dollars. RESULTS: A policy that would have restricted access to angiotensin-receptor blockers might have saved more than $77 million in Canada in 2006. The simulations yielded similar savings for the year (mean $58.3 million, 95% confidence interval $29.3 million to $90.8 million). Every simulation showed a cost savings. INTERPRETATION: Had access to angiotensin-receptor blockers been restricted, the potential cost savings to the Canadian health care system might have been more than $77 million in 2006, likely without any adverse effect on cardiovascular health.

Long-term trends in use of and expenditures for cardiovascular medications in Canada.

BACKGROUND: Medication expenditures have become the fastest growing sector of costs within the Canadian health care system. Evaluation of the use of cardiovascular medications is important to determine the magnitude of the growth, to identify which medications dominate the landscape and to detect interprovincial differences in utilization. We describe long-term trends in the use of and expenditures for cardiovascular medications in Canada, by drug class and by province. METHODS: For these analyses, we used volume and expenditure data related to prescriptions for cardiovascular medications obtained from IMS Health Canada's CompuScript Audit database for the period 1996-2006. Here, we describe national and provincial patterns of utilization and expenditures for specified classes of cardiovascular medications. RESULTS: The use of cardiovascular medications increased sharply in Canada during the study period, with related costs rising by over 200% during this period to surpass $5 billion in 2006. Changes in population demographics, risk factors and inflation appeared to account for about two-thirds of the observed growth in expenditures. Use of newer medication classes (statins, angiotensin-receptor blockers, angiotensin-converting-enzyme inhibitors), for which patented brand name medications predominate, accounted for almost one-third of the cost increases. Interprovincial differences in total expenditures for cardiovascular drugs portrayed a descending gradient from east to west, with greatest variability for the newer drug classes. INTERPRETATION: Prescriptions and expenditures for cardiovascular medications in Canada escalated over the study period. Projected increases may reach potentially unsustainable levels. Greater emphasis on the use of cost-effective medications is required to limit further increases. Factors influencing interprovincial differences warrant further study.