6. What is the cost-benefit ratio of screening for asymptomatic cardiac systolic dysfunction in adult non-oncology populations?
First Author Year	Study Design	Participants	Diagnostic tests	Main outcomes	Addt’l remarks
Heidenreich51 2004	Cost-benefit analysis using published data from community cohorts (gender-specific BNP test characteristics, prevalence of depressed LVEF) and randomized trials (benefit from treatment).	Men and women age 60 years with no history of heart failure (hypothetical cohorts). Prevalence of depressed LVEF: 3.5% in men; 0.45% in women.	Four screening strategies: BNP testing and, if abnormal, echocardiography. Patients with an LVEF<40% are treated (ACE inhibitors) to prevent the development of heart failure. BNP only, with treatment based on the results. Echocardiography for all patients (treatment based on the results). Not to screen for depressed left ventricular function. Threshold BNP: 21ng/dl for men; 34 ng/dl for women.	Screening 1,000 asymptomatic patients with BNP followed by echocardiography in those with an abnormal test increased the lifetime cost of care (176,000 US dollars for men, 101,000 US dollars for women) and improved outcome (7.9 QALYs for men, 1.3 QALYs for women), resulting in a cost per QALY of 22,300 US dollars for men and 77,700 US dollars for women. The number of men needed to screen with BNP was 44 to identify one with depressed LVEF, 133 to gain one year of life, and 127 to gain one QALY. The number of women needed to screen with BNP was 278 to identify one with depressed LVEF, 909 to gain one year of life, and 769 to gain one QALY. Screening with BNP followed by echocardiography in those with an abnormal test was economically attractive for 60-year-old men and possibly for women. Screening all patients with echocardiography was expensive, and relying on BNP alone to decide treatment led to higher cost and worse outcome compared to the sequential BNP-echocardiography strategy. In general, screening with BNP followed by echocardiography is likely to be economically attractive for patient groups with at least a 1% prevalence of moderate or greater LV systolic dysfunction (i.e. increased outcome at a cost < 50,000 US dollars per QALY gained). Screening would not be attractive if a diagnosis of left ventricular dysfunction led to significant decreases in quality of life or income	Possible limitations as reported in the article: the absence of data on the effect of ACE inhibitors in patients with no known cardiac disease. Patients in the used SOLVD prevention trial are likely to have a higher event rate and the effect of ACE inhibitors greater than for patients with unsuspected left ventricular dysfunction. However, if beta-blockers are shown to prevent heart failure then the potential value of screening might be underestimated. Although a quality-of-life decrement for patients receiving a positive test was accounted for, the repercussions of a diagnosis of LV dysfunction may be underestimated. In addition, there are financial consequences if the ability to obtain insurance and employment is limited. These issues will be most significant for young patients, where many positive test results will be false positives because of the low prevalence of disease. Potential screening benefits of identifying diastolic dysfunction or significant valvular disease that may be found with BNP screening were not included. These patients may benefit from more aggressive treatment of hypertension or fluid overload. Including these benefits would make screening more economically attractive. A recent meta-analysis suggests that ACE inhibitors may be more effective for asymptomatic men than women with reduced LV function post myocardial infarction. If true for all patients with depressed EF, this would further support screening for men, but in women only at high-risk for heart disease.

BNP: B-type natriuretic peptide; LVEF: left ventricular ejection fraction; QALY: quality-adjusted life years.