Meta-Analysis of Normal Reference Values for Right and Left Ventricular Quantification by Cardiovascular Magnetic Resonance

Abstract

BACKGROUND: Cardiovascular magnetic resonance (CMR) reference values are relied upon to accurately diagnose left ventricular (LV) and right ventricular (RV) pathologies. To date, reference values have been derived from modest sample sizes with limited patient diversity and attention to 1 but not both commonly used tracing techniques for papillary muscles and trabeculations. We sought to overcome these limitations by meta-analyzing normal reference values for CMR parameters stemming from multiple countries, vendors, analysts, and patient populations. METHODS: We comprehensively extracted published and unpublished data from studies reporting CMR parameters in healthy adults. A steady-state free-precession short-axis stack at 1.5T or 3T was used to trace either counting the papillary muscles and trabeculations in the LV volume or mass. We used a novel Bayesian hierarchical meta-analysis model to derive the pooled lower and upper reference values for each CMR parameter. Our model accounted for the expected differences between tracing techniques by including informative prior distributions from a large external data set. RESULTS: A total of 254 studies from 25 different countries were systematically reviewed, representing 12 812 healthy adults, of which 52 were meta-analyzed. For LV parameters counting papillary muscles and trabeculations in the LV volume, pooled normative reference ranges in men and women, respectively, were as follows: LV ejection fraction of 52% to 73% and 54% to 75%, LV end-diastolic volume index of 60 to 109 and 56 to 96 mL/m 2 , LV end-systolic volume index of 18 to 45 and 16 to 38 mL/m 2 , and LV mass index of 41 to 76 and 33 to 57 g/m 2 . For LV parameters counting papillary muscles and trabeculations in the LV mass, pooled normative reference ranges in men and women, respectively, were as follows: LV ejection fraction of 57% to 74% and 57% to 75%, LV end-diastolic volume index of 60 to 97 and 55 to 88 mL/m 2 , LV end-systolic volume index of 18 to 37 and 15 to 34 mL/m 2 , and LV mass index of 50 to 83 and 38 to 65 g/m 2 . For RV parameters, pooled normative reference ranges in men and women, respectively, were as follows: RV ejection fraction of 47% to 68% and 49% to 71%, RV end-diastolic volume index of 64 to 115 and 57 to 99 mL/m 2 , RV end-systolic volume index of 23 to 52 and 18 to 42 mL/m 2 , and RV mass index of 14 to 29 and 13 to 25 g/m 2 . CONCLUSIONS: Our Bayesian hierarchical meta-analysis provides normative reference values for CMR parameters of LV and RV size, systolic function, and mass, encompassing both tracing techniques across a diverse multinational sample of healthy men and women.

Nuances in Defining Normal Ranges for Chamber Quantification With Cardiovascular Magnetic Resonance

“…6 The LV and RV volumes, masses, and ejection fraction reference ranges are reasonably similar between those guidelines and Zhan et al, with LRVs and URVs mostly within 10 units of each other, which is reassuring and partly explained by many overlapping studies that were analyzed. 2,6 As observed in prior studies, CMR reference ranges identified were significantly higher for indexed volumes, significantly lower for indexed mass, and similar for ejection fraction compared with echocardiography guidelines, because of differences in imaging techniques, so volumes and mass between modalities cannot be directly compared. 1,2,6 Finally, are separate reference ranges necessary for LV and RV quantification depending on patient or imaging factors?…”

“…2,6 As observed in prior studies, CMR reference ranges identified were significantly higher for indexed volumes, significantly lower for indexed mass, and similar for ejection fraction compared with echocardiography guidelines, because of differences in imaging techniques, so volumes and mass between modalities cannot be directly compared. 1,2,6 Finally, are separate reference ranges necessary for LV and RV quantification depending on patient or imaging factors? For example, there are significant differences in chamber size parameters (end-diastolic volume, end-systolic volume, and mass) between men and women; hence, sex-specific thresholds are reported although ejection fraction and indexed stroke volume are similar.…”

“…For instance, the LRV (95% CI) of LV ejection fraction in men was reported as 52% (47%, 56%) in Table S2. 2 The more accurate interpretation would then be values above 56%, between 47% and 56%, and below 47% are considered normal, borderline, and abnormal, respectively. How the normal ranges reported in this meta-analysis compare with other contemporary cardiac guidelines are summarized in the Table.…”

“…How the normal ranges reported in this meta-analysis compare with other contemporary cardiac guidelines are summarized in the Table. 1,2,6 The current Society for Cardiovascular Magnetic Resonance guidelines reported their reference ranges for quantifying cardiac chambers, valves, major vessels, parametric mapping, and myocardial perfusion using traditional meta-analysis techniques of healthy patient studies in the literature. 6 The LV and RV volumes, masses, and ejection fraction reference ranges are reasonably similar between those guidelines and Zhan et al, with LRVs and URVs mostly within 10 units of each other, which is reassuring and partly explained by many overlapping studies that were analyzed.…”

“…For example, there are significant differences in chamber size parameters (end-diastolic volume, end-systolic volume, and mass) between men and women; hence, sex-specific thresholds are reported although ejection fraction and indexed stroke volume are similar. 1,2,6 Both Zhan et al and the Society for Cardiovascular Magnetic Resonance guidelines highlighted differences in whether PMT is included in tracing methodologies to report separate thresholds, especially for LV, 2,6 and of course, CMR and echocardiography reference ranges also differ. 1,6 The Society for Cardiovascular Magnetic Resonance guidelines actually reported age-group-specific reference ranges for LV and RV parameters, which were relatively small, but not ethnicspecific reference ranges.…”