A pilot clinical trial of cell therapy in heart failure with preserved ejection fraction

Figures

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  Figure 1. Flow‐chart of the study design. After enrolment all patients were treated with optimization of medical therapy for 6 months (Phase 1). Thereafter, all patients received transendocardial CD34+ cell therapy, and were followed for another 6 months (Phase 2). At the time of enrolment (6 months before cell therapy), at the time of cell therapy, and 6 months thereafter we performed detailed clinical evaluation, laboratory assays, echocardiography, 6‐min walk test, and measured plasma levels of N‐terminal pro‐B‐type natriuretic peptide.

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  Figure 2. Measurement of local mechanical diastolic delay and myocardial viability. (A) Exemplary electroanatomical mapping of the left ventricle with measurement of local mechanical diastolic delay. (B) Examples of mapping points with (top) and without (bottom) local mechanical diastolic delay. (C) Schematic presentation of the local mechanical diastolic delay measurements from panel B. Prior to stem cell application, we performed electroanatomical mapping of the left ventricle consisting of at least 150 mapping points. At each point we measured local movement of left ventricular wall (white lines in panels B and C). Local mechanical diastolic delay (red arrows in panel C) was defined as timing difference between maximum local diastolic time and end‐diastolic time based on left ventricular volume (yellow lines in panels B and C). In panel (A), blue and purple areas represent regions with increased local mechanical diastolic delay; red, yellow and green areas represent the regions without significant local mechanical diastolic delay. Green lines in panels (B) and (C) represent local action potential. (E) Exemplary unipolar voltage map: red and yellow areas represent regions with decreased…

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  Figure 3. Changes in E/e′. The chart displays individual changes in E/e′ between baseline (6 months before cell therapy), the time of cell therapy, and 6 months thereafter. The decrease in E/e′ was significantly more pronounced in Phase 2 than in Phase 1 (p = 0.001). SC, stem cell.

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  Figure 4. Changes in global and local longitudinal strain, N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP), and exercise capacity. In Phase 1, we found no change in global longitudinal strain (GLS); although GLS showed a trend of decrease in Phase 2, the changes did not reach statistical significance (A). Levels of NT‐proBNP remained stable throughout Phase 1 but decreased significantly in Phase 2 (B). In Phase 1, 6‐min walk test (6MWT) distance did not change; however, we found a significant improvement in 6MWT distance in Phase 2 (C). SC, stem cell.