Health Economic Analysis of CMR: A Systematic Review.

INTRODUCTION: Uptake of cardiac magnetic resonance (CMR) in Australia has been limited by issues of cost and access. There is a need to inform future application of CMR by evaluating pertinent health economic literature. We sought to perform a systematic review on the health economic data as it pertains to CMR. METHODS: Eight databases (biomedical/health economic) were searched for relevant articles highlighting economic evaluations of CMR. Following screening, studies that reported health economic outcomes (e.g., dollars saved, quality adjusted life years [QALY] and cost effectiveness ratios) were included. Data on cost effectiveness, clinical/disease characteristics, type of modelling were extracted and summarised. RESULTS: Thirty-eight (38) articles informed the systematic review. Health economic models used to determine cost effectiveness included both trial-based studies (n=14) and Markov modelling (n=24). Comparative strategies ranged from nuclear imaging, stress echocardiography and invasive angiography. The disease states examined included coronary artery disease (23/38), acute coronary syndrome (3/38), heart failure (5/38) and miscellaneous (7/38). The majority of studies (n=29/38) demonstrated CMR as a strategy which is either economically dominant, cost-effective or cost-saving. CONCLUSION: This systematic review demonstrates that CMR is cost-effective depending on diagnostic strategy, population and disease state. The lack of standardised protocols for application of CMR, economic models used and outcomes reported limits the ability to meta-analyse the available health economic data.

Echocardiographic Risk Assessment to Guide Screening for Atrial Fibrillation.

BACKGROUND: Although atrial fibrillation (AF) is a significant population health burden, and an avoidable cause of stroke, AF screening remains controversial. The aim of this study was to investigate whether coincidental echocardiography could provide information about patients at risk for AF. METHODS: Asymptomatic participants ≥65 years of age with more than one AF risk factor (N = 445) undergoing echocardiography for risk evaluation were followed over a median of 15 months for incident AF. Left atrial volume index (LAVi), left ventricular (LV) global longitudinal strain (GLS; absolute value), left atrial (LA) strain, and LV mass were measured. During the follow-up period, AF was diagnosed clinically by primary care physicians or by using a single-lead portable electrocardiographic monitoring device (five 60-sec recordings performed by participants over 1 week). RESULTS: AF was diagnosed in 45 patients (10%; mean age, 70.5 ± 4.2 years; 55% women). AF detection was higher in those with LV hypertrophy, GLS < 16%, LAVi > 34 mL/m2, and LA reservoir strain < 34%. GLS, LAVi, and LA reservoir strain were independently associated with AF (P < .05). Those with AF had reduced GLS, higher LAVi, and higher LV mass (P < .05), but LA strain was similar in both groups (P > .05). GLS and LAVi were the strongest predictors, and cut points of 14.3% for GLS and 39 mL/m2 were associated with increased risk for developing AF. Those with all four risk parameters (LV hypertrophy, GLS < 16%, LA reservoir strain < 34%, and LAVi > 34 mL/m2) had a 60% AF detection rate, compared with 7% without these features (P = .004). CONCLUSION: Echocardiography is widely used in patients at risk for AF, and simple LV and LA measurements may be used to enrich the process of AF screening.

Echocardiography-based pressure-volume loop assessment in the evaluation for the effects of indoxyl sulfate on cardiovascular function.

BACKGROUND: Indoxyl sulfate (IS), a uremic toxin, has been reported to have hypertrophic effects on the heart. Previous studies, however, have shown no association between elevated IS levels and cardiovascular outcomes in hemodialysis patients. We hypothesized that, despite left ventricular (LV) hypertrophy, myocardial contractility and ventricular-arterial coupling would remain preserved, and that this would explain the reason for the absence of prognostic impact of IS. METHODS: We evaluated the association of IS with LV structure, contractility, vascular function, and mechanical efficiency (ventricular-arterial coupling and stroke work/pressure volume area) in 154 patients on hemodialysis, using echocardiography-based pressure-volume loop assessment. RESULTS: As expected, subjects in the high IS group (IS ≥ 33.8 µg/mL) had greater LV mass index and end-diastolic volume index compared to subjects in the low IS group (IS < 33.8 µg/mL). These differences remained significant after adjusting for age, sex, body mass index, diabetic nephropathy, duration of hemodialysis, and NT-proBNP levels, suggesting a potential role of elevated IS levels in LV remodeling. However, no differences in LV contractility (preload recruitable stroke work, peak power index, and systolic mitral annular velocity) and mechanical efficiency (ventricular-arterial coupling and stroke work/pressure volume area) were observed between the groups. CONCLUSIONS: Deleterious effects of IS on LV remodeling are not accompanied by impaired LV contractility or mechanical efficiency, which could contribute to the absence of cardiovascular prognostic impact observed in previous studies performed on hemodialysis patients.

Relationships of high cardiac output with ventricular morphology, myocardial energetics, and energy costs in hemodialysis patients with preserved ejection fraction.

Hemodialysis patients have conditions that increase cardiac output (CO), including arteriovenous fistula, fluid retention, vasodilator use, and anemia. We sought to determine the relationships between these factors and CO and to evaluate the effects of the high-output states on ventricular morphology, function, and myocardial energetics in hemodialysis patients, using noninvasive load-insensitive indices. Cardiovascular function was assessed in hemodialysis patients with high output [ejection fraction ≥ 50%, cardiac index (CI) > 3.5 L/min/m2, n = 30], those with normal output (CI < 3.0 L/min/m2, n = 161), and control subjects without hemodialysis (n = 155). As compared to control subjects and hemodialysis patients with normal CI, patients with elevated CI were anemic and displayed decreased systemic vascular resistance index (SVRI), excessive left ventricular (LV) contractility, larger LV volume, and tachycardia. Lower hemoglobin levels were correlated with decreased SVRI, excessive LV contractility, and higher heart rate, while estimated plasma volume and interdialytic weight gain were associated with larger LV volume, thus increasing CO. High output patients displayed markedly increased pressure-volume area (PVA) and PVA/stroke volume ratio, which were correlated directly with CO. The use of combination vasodilator therapy (angiotensin-converting enzyme inhibitor/angiotensin-receptor blocker and calcium channel blocker) was not associated with high-output states. In conclusion, anemia and fluid retention are correlated with increased CO in hemodialysis patients. The high-output state is also associated with excessive myocardial work and energy cost.

Single Versus Standard Multiview Assessment of Global Longitudinal Strain for the Diagnosis of Cardiotoxicity During Cancer Therapy.

OBJECTIVES: The goal of this study was to compare echocardiographic measurements of global longitudinal strain (GLS) (using 3 apical views) with single-view longitudinal strain (LS, 4- or 2-chamber [4CV_LS and 2CV_LS, respectively]) for detection of cancer-therapy related cardiotoxicity. BACKGROUND: GLS is useful for the detection of cardiotoxicity, but the need for repeated measurements poses a significant burden on busy echocardiography laboratories. A single-view LS measurement, possibly at point of care, could improve efficiency. METHODS: Seventeen international centers prospectively recruited 108 patients (mean age 54 ± 13 years) at high risk for cardiotoxicity as part of the ongoing SUCCOUR (Strain Surveillance for Improving Cardiovascular Outcomes During Chemotherapy) randomized controlled trial. Echocardiography performed at baseline and follow-up were analyzed in a core laboratory setting blinded to clinical information. Peak systolic GLS and LS were measured from raw data. Cardiotoxicity was defined by reduction in left ventricular ejection fraction >0.10 to <0.55 or a relative drop in GLS by ≥12%. RESULTS: Cardiotoxicity developed in 46 patients by either criteria. Baseline and follow-up 2-dimensional left ventricular ejection fraction were 61 ± 4% and 58 ± 5%, respectively (p < 0.001). The baseline GLS (-20.9 ± 2.4%) was not different from 4CV_LS (-20.7 ± 2.5%; p = 0.09) or 2CV_LS (-21.1 ± 3.1%; p = 0.25). The follow-up GLS (-19.5 ± 2.4%) was also similar to 4CV_LS (-19.5 ± 2.6%; p = 0.80) and 2CV_LS (-19.7 ± 3.1%; p = 0.19). There was good correlation between GLS and 4CV_LS at baseline (r = 0.86; p < 0.001) and follow-up (r = 0.89; p < 0.001) and with 2CV_LS at baseline (r = 0.87; p < 0.001) and follow-up (r = 0.88; p < 0.001). However, there was 15% to 22% disagreement between GLS and 4CV_LS or 2CV_LS for the detection of cardiotoxicity. The interobserver and intraobserver reproducibility was higher for GLS (intraclass correlation: 0.93 to 0.95; coefficient of variance: 2.9% to 3.7%) compared with either single-chamber-based LS measurement (intraclass correlation: 0.85 to 0.91; coefficient of variance: 4.1% to 4.8%). CONCLUSIONS: Although there was good correlation between GLS and single-view LS measurements, single-view LS measurement led to disagreement in the diagnosis of cardiotoxicity in up to 22% of patients. GLS measurements were more reproducible than single-view LS. GLS based on 3 apical views should remain the preferred technique for detection of cardiotoxicity. (Strain Surveillance for Improving Cardiovascular Outcomes During Chemotherapy [SUCCOUR]; ACTRN12614000341628).

Effect of Sex Differences on the Association Between Stroke Risk and Left Atrial Anatomy or Mechanics in Patients With Atrial Fibrillation.

BACKGROUND: Embolic stroke in atrial fibrillation is more prevalent in women than in men, yet the basis for this difference remains unclear. This study seeks to elucidate whether there are any sex differences in the relationships between stroke risk (CHADS2 score, CHA2DS2-VASc score without a sex category, and estimated stroke rate) and left atrial (LA) anatomy or mechanics in patients with atrial fibrillation. METHODS AND RESULTS: LA emptying fraction and global peak atrial longitudinal strain were assessed in 414 subjects with paroxysmal or persistent atrial fibrillation (156 women and 258 men). Linear regression models with an interaction term were performed to test the effect of sex difference on associations between the embolic risk and LA function or anatomy. Sensitivity analyses were performed in 228 age, heart rate, and rhythm-matched subjects (114 women and men). Women were older and had larger LA volumes and lower LA mechanics than men. Significant negative association between the CHADS2 score and LA emptying fraction was only demonstrated in women with a significant interaction between sexes. Similar significant interactions were found in global peak atrial longitudinal strain but not in LA volume. These findings were corroborated in the comparisons against CHA2DS2-VASc score without a sex category and the estimated stroke rate. Sensitivity analyses in the matched subgroup also confirmed the robustness of these sex differences in LA emptying fraction, but less so in global peak atrial longitudinal strain. CONCLUSIONS: Significant sex interactions on the association between global LA function and risk stratification schemes exist, which may be a reason for the higher prevalence of embolic stroke in women.

Temporal changes in appropriateness of cardiac imaging.

BACKGROUND: Appropriate use criteria (AUC) for cardiac imaging have been available for almost 10 years. The extent to which there has been a reported improvement in appropriate use is undefined. OBJECTIVES: This study systematically reviewed published evidence to identify whether the promulgation of AUC has led to an improvement in the proportion of appropriate cardiac imaging requests. METHODS: Electronic databases were systematically searched for English-language papers related to AUC and cardiovascular imaging. We found 59 reports involving 103,567 tests that were published from 2000 to 2012. The rate of appropriate testing over time was analyzed in a meta-regression. RESULTS: New AUC were associated with apparent improvements in appropriateness for transthoracic echocardiography (TTE) (80% [95% confidence interval (CI): 0.75 to 0.84] vs. 85% [95% CI: 0.81 to 0.89]), transesophageal echocardiography (TEE) (89% [95% CI: 0.81 to 0.94] vs. 95% [95% CI: 0.93 to 0.96]) and computed tomography angiography (CTA) (37% [95% CI: 0.21 to 0.55] vs. 55% [95% CI: 0.44 to 0.65]) but not stress echocardiography (53% [95% CI: 0.45 to 0.61] vs. 52% [95% CI: 0.42 to 0.61]) or single-photon emission computed tomography (72% [95% CI: 0.66 to 0.77] vs. 68% [95% CI: 0.60 to 0.74]). Although there were no correlations between the proportion of appropriate TTEs and published year (p = 0.36) for 2007 AUC, there was a positive correlation between proportion of appropriateness and the year of publication (p = 0.01) for 2011 AUC. There was a significant decrease in the proportion of appropriateness over time using the 2007 TEE AUC (p = 0.03) and 2006 CT AUC (p = 0.02). There were no meaningful associations between appropriateness and publication year for stress echocardiography, CTA, or single-photon emission computed tomography. CONCLUSIONS: Rates of reported appropriate use in imaging show improvements for TTE and CTA but not for stress imaging and TEE. The observed reductions in imaging studies are not matched by reported rates of appropriate use.

Appropriate test selection for single-photon emission computed tomography imaging: association with clinical risk, posttest management, and outcomes.

BACKGROUND: Appropriate use criteria (AUC) for stress single-photon emission computed tomography (SPECT) are only one step in appropriate use of imaging. Other steps include pretest clinical risk evaluation and optimal management responses. We sought to understand the link between AUC, risk evaluation, management, and outcome. METHODS: We used AUC to classify 1,199 consecutive patients (63.8 ± 12.5 years, 56% male) undergoing SPECT as inappropriate, uncertain, and appropriate. Framingham score for asymptomatic patients and Bethesda angina score for symptomatic patients were used to classify patients into high (≥5%/y), intermediate, and low (≤1%/y) risk. Subsequent patient management was defined as appropriate or inappropriate based on the concordance between management decisions and the SPECT result. Patients were followed up for a median of 4.8 years, and cause of death was obtained from the social security death registry. RESULTS: Overall, 62% of SPECTs were appropriate, 18% inappropriate, and 20% uncertain (only 5 were unclassified). Of 324 low-risk studies, 108 (33%) were inappropriate, compared with 94 (15%) of 621 intermediate-risk and 1 (1%) of 160 high-risk studies (P < .001). There were 79 events, with outcomes of inappropriate patients better than uncertain and appropriate patients. Management was appropriate in 986 (89%), and appropriateness of patient management was unrelated to AUC (P = .65). CONCLUSION: Pretest clinical risk evaluation may be helpful in appropriateness assessment because very few high-risk patients are inappropriate, but almost half of low-risk patients are inappropriate or uncertain. Appropriate patient management is independent of appropriateness of testing.