Defining Normal Cardiac Structure and Function in German Adults: Age- and Sex-Specific CMR Reference Values from the NAKO

Presenting Author(s)

• 

  Christopher L. Schlett, MD, MPH

  Deputy Director
  Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
  Freiburg, Baden-Wurttemberg, Germany

Primary Author(s)

• 

  Christopher L. Schlett, MD, MPH

  Deputy Director
  Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
  Freiburg, Baden-Wurttemberg, Germany

Co-Author(s)

• CS

  Christopher Schuppert, MD

  Attending Physician
  Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
  Freiburg, Baden-Wurttemberg, Germany
• PF

  Peter M. Full, MD

  Clinical Researcher
  German Cancer Research Center (DKFZ), Heidelberg, Germany, Germany
• RS

  Robin T. Schirrmeister, PhD

  Researcher
  Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany, Germany
• MH

  Manuel Hein, MD

  Clinical Researcher
  University Heart Center Freiburg – Bad Krozingen, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany, Germany
• MR

  Maximilian Russe

  Senior Physician
  University Medical Center Freiburg, Germany
• MR

  Marco Reisert, PhD

  Researcher
  Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany, Germany
• JG

  Jan Gröschel, MD

  MD
  Charite
  Berlin, Berlin, Germany
• 

  Clemens Ammann, MD

  Physician
  Charité – Universitätsmedizin Berlin
  Berlin, Berlin, Germany
• KM

  Klaus H. Maier-Hein, PhD

  Head of Division
  German Cancer Research Center (DKFZ), Heidelberg, Germany, Germany
• FB

  Fabian Bamberg, MD, MPH

  Clinical Director
  Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany, Germany
• SR

  Susanne Rospleszcz, PhD

  Principal Investigator
  Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany, Germany
• 

  Jeanette Schulz-Menger, MD

  Head Working Group Cardiac MRI
  Charité/ University Medicine Berlin and Helios
  Berlin, Berlin, Germany

Background: Cardiovascular magnetic resonance (CMR) represents the benchmark imaging technique for evaluating cardiac structure and function. Its clinical utility depends on robust reference ranges, yet current datasets commonly lack population-wide validity. This study provides age- and sex-specific reference ranges for ventricular structure and function based on data from the population-based German National Cohort (NAKO).

Methods: Short-axis cine CMR data from 29,908 participants in the NAKO baseline examination were previously processed using a 2D/3D deep learning algorithm paired with extensive quality control for image quality and contour accuracy [1]. Standard structural and functional measures were derived for the left and right ventricles (LV and RV), including end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV), and ejection fraction (EF). Left ventricular myocardial mass at end-diastole and regional wall thickening were additionally assessed. Measurements were normalized to height and body surface area (BSA). To establish reference ranges from a healthy subgroup, we excluded participants with documented cardiovascular disease, hypertension, or cancer. A stricter ‘super-healthy’ subgroup was defined by further excluding individuals with diabetes, hypercholesterolemia, obesity, or any history of smoking. Reference intervals (mean as well as 5th and 95th percentiles) were estimated using generalized additive models and additive quantile regression to accommodate nonlinear age associations, with all analyses stratified by sex. Sex differences were further explored through visualization and formal interaction testing.

Results: The reference subgroup comprised 14,712 participants (mean age 43.8 ± 11.8 years; 48.3% women). Ventricular end-diastolic volumes (LVEDV, RVEDV) and end-systolic volumes (LVESV, RVESV) all declined progressively with age; for example, in women aged 20–25 years versus 65–72 years, LVEDV decreased from 78 [59–94] to 64 [46–83] ml/m², and LVESV from 28 [20–37] to 23 [15–31] ml/m² (Figure 1). In contrast, left ventricular ejection fraction (LVEF) remained largely unchanged across age groups, while right ventricular ejection fraction (RVEF) showed a modest increase with age (e.g., 55 [45–65] vs. 59 [49–69] in women aged 20–25 vs. 65–72 years; Figure 1). These patterns were consistent in both sexes, with significant age–sex interaction effects (p< 0.001). The ‘super-healthy’ subgroup included 5,335 participants (mean age 40.4 ± 11.9 years; 50.4% women). Measures of cardiac structure and function in this subgroup were consistent with those observed in the broader reference subgroup, without clinically relevant variation.

Conclusion: This study establishes age- and sex-specific reference values for cardiac structure and function in a large, population-based German cohort. Through stringent quality control and standardized analysis, it provides a robust resource for CMR-based assessment.

Figure 1. Age- and sex-specific reference values for cardiac structure and function by cardiac magnetic resonance (CMR), normalized to body surface area (BSA). EDV, end-dystolic volume; EF, ejection fraction; ESV, end-systolic volume; SV, stroke volume.