Variations and inequities in access to cardiac diagnostic services in Ontario Canada.

OBJECTIVES: Echocardiography is an essential diagnostic modality known to have wide regional utilization variations. This study's objectives were to quantify regional variations and to examine the extent to which they are explained by differences in population age, sex, cardiac disease prevalence (CDP), and social determinants of health (SDH) risk. METHODS: This is an observational study of all echocardiography exams performed in Ontario in 2019/20 (n = 695,622). We measured regional variations in echocardiography crude rates and progressively standardized rates for population age, sex, CDP, and SDH risk. RESULTS: After controlling for differences in population age, sex, and CDP, Ontario's highest rate regions had echocardiography rates 57% higher than its lowest rate regions. Forty eight percent of total variation was not explained by differences in age, sex, and CDP. CDP increased with SDH risk. Access to most cardiac diagnostics was negatively correlated with SDH risk, while cardiac catheterization rates were positively correlated with SDH risk. CONCLUSION: Variations analysis that adjusts for age and sex only without including clinical measures of need are likely to overestimate the unwarranted portion of total variation. Substantial variations persisted despite a mandatory provider accreditation policy aimed at curtailing them. The associations between variations and SDH risks imply a need to redress access and outcome inequities.

Trends in the Use of Cardiac Imaging for Patients With Heart Failure in Canada.

Importance: Cardiac imaging is a component of the provision of medical care for patients with heart failure that has experienced a broad expansion in past decades. However, there is a paucity of studies examining the patterns of use of cardiac imaging modalities in real-world clinical practice. Objectives: To investigate temporal trends in the use and costs of cardiac imaging for the examination of patients with heart failure in Canada and to examine the association between the institution of an accreditation program and the use of echocardiography. Design, Setting, and Participants: A repeated cross-sectional study based on population-based administrative databases in Ontario, Canada, of individuals with heart failure identified using a validated algorithm based on hospital admissions and ambulatory physician claims was conducted between April 1, 2002, and March 31, 2017. Main Outcomes and Measures: The incidence and prevalence of heart failure and the age- and sex-adjusted rate of use and costs of cardiac imaging, including resting and stress echocardiography, myocardial perfusion scintigraphy, invasive coronary angiography, computed tomography, magnetic resonance imaging, and positron emission tomography. Results: A total of 882 355 adults (50.1% women; median age, 76 years [interquartile range, 66-83 years]) with prevalent heart failure were identified. The age- and sex-standardized prevalence of heart failure remained stable during the study (2.4% [95% CI, 2.4%-2.4%] in 2002 and 2.0% [95% CI, 2.0%-2.0%] in 2016). There was an increase in the rate of use of resting echocardiography, from 386 tests (95% CI, 373-398) per 1000 patients with heart failure in 2002 to 533 (95% CI, 519-547) per 1000 patients in 2011. Coinciding with the initiation of an accreditation program for echocardiography in 2012, there was an immediate reduction in the rate of use (-59.5 tests per 1000 patients with heart failure; P < .001), which was followed by a plateau in subsequent years. At the same time, there was a 10.8% relative reduction in the use of myocardial perfusion scintigraphy and an 11.2% relative reduction in the use of invasive coronary angiography from 2011 to 2016 and the incorporation of newer modalities after they became publicly insured health services. Conclusions and Relevance: These findings suggest that resting echocardiography remains the most used imaging technique for patients with heart failure, exceeding the use of and the cost spent on other modalities. Stabilization in the use of traditional imaging modalities coincided temporally with the emergence of advanced techniques and provincewide quality improvement policy initiatives.

Echocardiographic Assessment of Young Male Draft-Eligible Elite Hockey Players Invited to the Medical and Fitness Combine by the National Hockey League.

The "athletic heart" is characterized by hypertrophy and dilation of the heart, in addition to functional and electrical remodeling. The aim of this study was to provide reference 2-dimensional (2DE) and 3-dimensional (3DE) echocardiographic measurements in a large database on draft-eligible elite ice hockey players and to determine the frequency of occult cardiac anomalies in this cohort of athletes. In this prospective cohort study, we performed a comprehensive cardiac assessment of the 100 top draft picks selected by the National Hockey League. Complete 2DE and 3DE examinations were performed to obtain comprehensive measurements of cardiac structure and function at rest, which were compared with nonathlete controls. A total of 592 athletes were evaluated (mean age 18 ± 0.5 years) from 2009 to 2014 at the National Hockey League combine. 2DE and 3DE ventricular, atrial dimensions, and left ventricular mass were significantly greater in the athletes compared with controls. Abnormalities were identified in 15 hockey players (2.5%) consisting of a bicuspid aortic valve in 10 (1.7%), patent ductus arteriosus in 1 (0.2%), low normal left ventricular systolic function in 2 (0.3%), an idiopathic pericardial effusion in 1 (0.2%), and posterior mitral valve prolapse in 1 (0.2%). In conclusion, intense ice hockey training is associated with typical myocardial adaptations and the frequency of cardiac anomalies found in this cohort of young elite hockey players is low and does not differ significantly from the reported incidences in the general population.

Routine versus selective cardiac magnetic resonance in non-ischemic heart failure - OUTSMART-HF: study protocol for a randomized controlled trial (IMAGE-HF (heart failure) project 1-B).

BACKGROUND: Imaging has become a routine part of heart failure (HF) investigation. Echocardiography is a first-line test in HF given its availability and it provides valuable diagnostic and prognostic information. Cardiac magnetic resonance (CMR) is an emerging clinical tool in the management of patients with non-ischemic heart failure. Current ACC/AHA/CCS/ESC guidelines advocate its role in the detection of a variety of cardiomyopathies but there is a paucity of high quality evidence to support these recommendations.The primary objective of this study is to compare the diagnostic yield of routine cardiac magnetic resonance versus standard care (that is, echocardiography with only selective use of CMR) in patients with non-ischemic heart failure. The primary hypothesisis that the routine use of CMR will lead to a more specific diagnostic characterization of the underlying etiology of non-ischemic heart failure. This will lead to a reduction in the non-specific diagnoses of idiopathic dilated cardiomyopathy and HF with preserved ejection fraction. DESIGN: Tertiary care sites in Canada and Finland, with dedicated HF and CMR programs, will randomize consecutive patients with new or deteriorating HF to routine CMR or selective CMR. All patients will undergo a standard clinical echocardiogram and the interpreter will assign the most likely HF etiology. Those undergoing CMR will also have a standard examination and will be assigned a HF etiology based upon the findings. The treating physician's impression about non-ischemic HF etiology will be collected following all baseline testing (including echo ± CMR). Patients will be followed annually for 4 years to ascertain clinical outcomes, quality of life and cost. The expected outcome is that the routine CMR arm will have a significantly higher rate of infiltrative, inflammatory, hypertrophic, ischemic and 'other' cardiomyopathy than the selective CMR group. DISCUSSION: This study will be the first multicenter randomized, controlled trial evaluating the role of CMR in non-ischemic HF. Non-ischemic HF patients will be randomized to routine CMR in order to determine whether there are any gains over management strategies employing selective CMR utilization. The insight gained from this study should improve appropriate CMR use in HF. TRIAL REGISTRATION: NCT01281384.

Comparative assessment of 2-dimensional echocardiography vs cardiac magnetic resonance imaging in measuring left ventricular mass in patients with and without end-stage renal disease.

BACKGROUND: While echocardiography (ECHO)-measured left ventricular mass (LVM) predicts adverse cardiovascular events that are common in hemodialysis (HD) recipients, cardiac magnetic resonance imaging (CMR) is now considered the reference standard for determination of LVM. This study aimed to evaluate concordance between LVM measurements across ECHO and CMR among chronic HD recipients and matched controls. METHODS: A single-centre, cross-sectional study of 41 chronic HD patients and 41 matched controls with normal kidney function was performed to compare LVM measurements and left ventricular hypertrophy (LVH) designation by ECHO and CMR. RESULTS: In both groups, ECHO, compared with CMR, overestimated LVM. Bland-Altman analysis demonstrated wider agreement limits in LVM measurements by ECHO and CMR in the chronic HD group (mean difference, 60.8 g; limits -23 g to 144.6 g) than in the group with normal renal function (mean difference, 51.4 g; limits -10.5 g to 113.3 g). LVH prevalence by ECHO and CMR in the chronic HD group was 37.5% and 22.5%, respectively, while 17.5% and 12.5% had LVH by ECHO and CMR, respectively, in the normal kidney function group. Intermodality agreement in the designation of LVH was modest in the chronic HD patients (κ = 0.42, P = 0.005) but strong (κ = 0.81, P < 0.001) in the patients with preserved kidney function. Agreement was strong in assessing LVH by ECHO and CMR only in those with normal kidney function. CONCLUSIONS: Our results suggest that the limitations of LVM measurement by ECHO may be more pronounced in patients receiving HD, and provide additional support for the use of CMR in research and clinical practice when rigourous assessment of LVM is essential.

Potential clinical impact of cardiovascular magnetic resonance assessment of ejection fraction on eligibility for cardioverter defibrillator implantation.

BACKGROUND: For the primary prevention of sudden cardiac death, guidelines provide left ventricular ejection fraction (EF) criteria for implantable cardioverter defibrillator (ICD) placement without specifying the technique by which it should be measured. We sought to investigate the potential impact of performing cardiovascular magnetic resonance (CMR) for EF on ICD eligibility. METHODS: The study population consisted of patients being considered for ICD implantation who were referred for EF assessment by CMR. Patients who underwent CMR within 30 days of echocardiography were included. Echocardiographic EF was determined by Simpson's biplane method and CMR EF was measured by Simpson's summation of discs method. RESULTS: Fifty-two patients (age 62±15 years, 81% male) had a mean EF of 38 ± 14% by echocardiography and 35 ± 14% by CMR. CMR had greater reproducibility than echocardiography for both intra-observer (ICC, 0.98 vs 0.94) and inter-observer comparisons (ICC 0.99 vs 0.93). The limits of agreement comparing CMR and echocardiographic EF were - 16 to +10 percentage points. CMR resulted in 11 of 52 (21%) and 5 of 52 (10%) of patients being reclassified regarding ICD eligibility at the EF thresholds of 35 and 30% respectively. Among patients with an echocardiographic EF of between 25 and 40%, 9 of 22 (41%) were reclassified by CMR at either the 35 or 30% threshold. Echocardiography identified only 1 of the 6 patients with left ventricular thrombus noted incidentally on CMR. CONCLUSIONS: CMR resulted in 21% of patients being reclassified regarding ICD eligibility when strict EF criteria were used. In addition, CMR detected unexpected left ventricular thrombus in almost 10% of patients. Our findings suggest that the use of CMR for EF assessment may have a substantial impact on management in patients being considered for ICD implantation.

Assessment of ischemia-induced microvascular remodeling using contrast-enhanced ultrasound vascular anatomic mapping.

Our aim was to apply novel contrast-enhanced ultrasound (CEU) techniques to characterize remodeling in different vascular compartments during ischemia-mediated angiogenesis. Hind limb ischemia was produced by ligation of an external iliac artery in 60 rats, half of which were treated with intramuscular fibroblast growth factor (FGF)-2 (5 microg). The proximal adductor muscles of the ischemic and control hind limb were studied immediately after ligation and at days 4, 7, or 14. Low-power maximum intensity projection imaging was performed to assess large intramuscular vessels to the fourth branch order. CEU data were analyzed to measure capillary perfusion and functional noncapillary microvascular blood volume. Resting capillary perfusion was reduced by 30% after arterial ligation and recovered earlier in FGF-2-treated versus nontreated rats (day 4 vs. 14). Changes in perfusion were temporally related to expansion of noncapillary microvascular blood volume on CEU, which was associated with an arteriogenic response on histology. Expansion of and organization (fractal distribution) of large collateral vessels occurred gradually over 2 weeks and was slightly more rapid with FGF-2 treatment. We conclude that CEU can separately assess collateral development, more distal arteriogenesis, and secondary changes in capillary perfusion that occur differentially with ischemia and growth factor therapy.

Vascular injury and thrombotic potential: a note of caution about recombinant factor VIIa.

Postoperative hemorrhage following cardiac surgery increases morbidity, mortality, and costs. Several case reports have described the successful use of recombinant factor VIIa to decrease or stop bleeding in patients undergoing cardiac surgery. The mechanism of action of recombinant factor VIIa is thought to be increased site-specific thrombin generation by tissue factor-mediated activation of coagulation or from activated platelets. However, there have also been many reports of thrombotic complications after recombinant factor VIIa administration. Randomized clinical trials and further laboratory studies should help better clarify the efficacy, safety, cost-effectiveness, and optimal dosing of recombinant factor VIIa in the cardiac surgical setting.

Assessment of endogenous and therapeutic arteriogenesis by contrast ultrasound molecular imaging of integrin expression.

BACKGROUND: We hypothesized that molecular imaging with contrast-enhanced ultrasound (CEU) and microbubbles targeted to endothelial integrins could be used to noninvasively assess early angiogenic responses to ischemia and growth factor therapy. METHODS AND RESULTS: Hindlimb ischemia was produced in 48 rats by ligation of an iliac artery. Half of the animals received intramuscular sustained-release fibroblast growth factor-2 (FGF-2). Immediately after ligation and at subsequent intervals from 4 to 28 days, blood flow and oxygen tension in the proximal adductor muscles were measured by CEU perfusion imaging and phosphor quenching, respectively. Targeted CEU imaging of alpha(v)- and alpha5beta1-integrin expression was performed with microbubbles bearing the disintegrin echistatin. Iliac artery ligation produced a 65% to 70% reduction in blood flow and oxygen tension. In untreated ischemic muscle, muscle flow and oxygen tension partially recovered by days 14 to 28. In these animals, signal from integrin-targeted microbubbles was intense and peaked before flow increase (days 4 to 7). In comparison to untreated animals, FGF-2-treated muscle had a greater rate and extent of blood flow recovery and greater signal intensity from integrin-targeted microbubbles, which peaked before maximal recovery of flow. On immunohistology, arteriolar but not capillary density increased in the ischemic limb after ligation, the rate and degree of which were greater in FGF-2-treated rats. Immunofluorescence demonstrated intense staining for alpha(v) in arterioles, the temporal course of which correlated with targeted imaging. CONCLUSIONS: Targeted CEU can be used to assess endogenous and therapeutic arteriogenesis before recovery of tissue perfusion. These results suggest that molecular imaging of integrin expression may be useful for evaluating proangiogenic therapies.

Incremental value of parametric quantitative assessment of myocardial perfusion by triggered Low-Power myocardial contrast echocardiography.

OBJECTIVES: The purpose of this study was to compare the assessment of myocardial perfusion by myocardial parametric quantification (MPQ) with technetium-99m sestamibi single-photon emission computed tomographic (SPECT) imaging in humans. BACKGROUND: Accurate visual interpretation of myocardial contrast echocardiographic (MCE) images is qualitative and requires considerable experience. Current computer-assisted quantitative perfusion protocols are tedious and lack spatial resolution. Myocardial parametric quantification is a novel method that quantifies, color encodes, and displays perfusion data as a set of myocardial parametric images according to the relative degree of perfusion. METHODS: Forty-six consecutive patients underwent prospective stress/rest technetium-99m sestamibi gated-SPECT imaging and MCE using intravenous Optison or Definity. Apical two- and four-chamber cine loops at rest and after dipyridamole (0.56 mg/kg) stress were acquired. For each patient, the following assessments of myocardial perfusion were performed: 1). visual cine-loop assessment (VIS); 2). MPQ assessment; and 3). combined VIS + MPQ assessment. RESULTS: The segmental rates of agreement for myocardial perfusion with SPECT were 83%, 89%, and 92% (kappa = 0.46, 0.58, and 0.68) for VIS, MPQ, and VIS + MPQ, respectively. Similar trends were seen for the classification of the presence or absence of a moderate to severe perfusion defect, with the agreement for VIS, MPQ, and VIS + MPQ being 92%, 97%, and 97%, respectively. CONCLUSIONS: Myocardial parametric quantification demonstrates good agreement with SPECT and incremental agreement with VIS. Analysis strategies that incorporate MPQ demonstrate better agreement with SPECT than visual analysis alone.

Noninvasive assessment of angiogenesis by ultrasound and microbubbles targeted to alpha(v)-integrins.

BACKGROUND: Noninvasive methods for characterizing neovessel formation during angiogenesis are currently lacking. We hypothesized that angiogenesis could be imaged with the use of contrast-enhanced ultrasound (CEU) with microbubbles targeted to alpha(v)-integrins. METHODS AND RESULTS: Microbubbles targeted to alpha(v)-integrins were prepared by conjugating echistatin (MB(E)) or monoclonal antibody against murine alpha(v) (MB(alpha)) to their surface. Control microbubbles (MB(c)) were also prepared. The microvascular behavior of these microbubbles was assessed by intravital microscopy of the cremaster muscle in mice treated for 4 days with sustained-release FGF-2. Microvascular retention was much greater (P<0.01) for MB(E) (11+/-6 mm(-3)) and MB(alpha) (10+/-7 mm(-3)) than that for MB(c) (1+/-1 mm(-3)). Retained MB(E) and MB(alpha) attached directly to the microvascular endothelial surface. Microbubble retention in 4 control mice was minimal. Subcutaneous matrigel plugs enriched with FGF-2 were created in 12 mice and studied 10 days later. Neovessels within the matrigel stained positive for alpha(v)-integrins. CEU demonstrated greater (P<0.01) acoustic intensity for MB(E) (16.0+/-5.9 U) and MB(alpha) (17.0+/-5.5 U) compared with MB(c) (5.8+/-2.6 U). The signal from targeted microbubbles (MB(E) and MB(alpha)) correlated well (r=0.90) with the matrigel blood volume determined by CEU perfusion imaging. CONCLUSIONS: CEU with microbubbles targeted for alpha(v)-integrins may provide a noninvasive method for assessing therapeutic angiogenesis.

Assessment of myocardial inflammation produced by experimental coronary occlusion and reperfusion with 99mTc-RP517, a new leukotriene B4 receptor antagonist that preferentially labels neutrophils in vivo.

BACKGROUND: 99mTc-RP517 is a new leukotriene B4 (LTB4) receptor antagonist developed for imaging acute inflammation or infection. A unique property of 99mTc-RP517 is its ability to label white blood cells in vivo after intravenous injection. The goals of this study were to determine relative 99mTc-RP517 binding to human leukocyte subtypes and the 99mTc-RP517 uptake pattern in canine myocardium where inflammation was induced by either coronary occlusion and reperfusion or tumor necrosis factor alpha (TNFalpha) injection. METHODS AND RESULTS: Fluorescence-activated cell sorter analysis was performed on whole human blood (n=2) and isolated neutrophils (n= 4) with a fluorescent analog of 99mTc-RP517, [F]-RP517. In whole blood, [F]-RP517 (500 nmol/L) preferentially labeled neutrophils. On isolated neutrophils, [F]-RP517 (10 nmol/L) binding was inhibited by 44% when LTB4 (400 nmol/L) was added. 99mTc-RP517 was injected intravenously in anesthetized, open-chest dogs before coronary occlusion (90 minutes) and reperfusion (120 minutes) (n=9) or before intramyocardial TNFalpha injection (n=3). Ex vivo images of heart slices were acquired. The left ventricle was divided into 72 segments for flow and 99mTc-RP517 uptake analysis. There was an inverse exponential relationship between 99mTc-RP517 uptake and occlusion flow (r=0.73). In the same 15 segments, 99mTc-RP517 uptake was highly correlated with the neutrophil enzyme myeloperoxidase (r=0.91). Ex vivo images revealed tracer uptake in the reperfused area (ischemic to normal count ratio=2.7+/-0.2). CONCLUSIONS: RP517 binds to the neutrophil LTB4 receptor after intravenous injection. After reperfusion, 99mTc-RP517 uptake correlated with myeloperoxidase and was observed on ex vivo images, indicating that this tracer may have potential as an inflammation-imaging agent.