Effects of incremental beta-blocker dosing on myocardial mechanics of the human left ventricle: MRI 3D-tagging insight into pharmacodynamics supports theory of inner antagonism.

Beta-blockers contribute to treatment of heart failure. Their mechanism of action, however, is incompletely understood. Gradients in beta-blocker sensitivity of helically aligned cardiomyocytes compared with counteracting transversely intruding cardiomyocytes seem crucial. We hypothesize that selective blockade of transversely intruding cardiomyocytes by low-dose beta-blockade unloads ventricular performance. Cardiac magnetic resonance imaging (MRI) 3D tagging delivers parameters of myocardial performance. We studied 13 healthy volunteers by MRI 3D tagging during escalated intravenous administration of esmolol. The circumferential, longitudinal, and radial myocardial shortening was determined for each dose. The curves were analyzed for peak value, time-to-peak, upslope, and area-under-the-curve. At low doses, from 5 to 25 µg·kg(-1)·min(-1), peak contraction increased while time-to-peak decreased yielding a steeper upslope. Combining the values revealed a left shift of the curves at low doses compared with baseline without esmolol. At doses of 50 to 150 µg·kg(-1)·min(-1), a right shift with flattening occurred. In healthy volunteers we found more pronounced myocardial shortening at low compared with clinical dosage of beta-blockers. In patients with ventricular hypertrophy and higher prevalence of transversely intruding cardiomyocytes selective low-dose beta-blockade could be even more effective. MRI 3D tagging could help to determine optimal individual beta-blocker dosing avoiding undesirable side effects.

Flow-sensitive four-dimensional cine magnetic resonance imaging for offline blood flow quantification in multiple vessels: a validation study.

PURPOSE: To further validate the quantitative use of flow-sensitive four-dimensional velocity encoded cine magnetic resonance imaging (4D VEC MRI) for simultaneously acquired venous and arterial blood flow in healthy volunteers and for abnormal flow in patients with congenital heart disease. MATERIALS AND METHODS: Stroke volumes (SV) obtained in arterial and venous thoracic vessels were compared between standard two-dimensional (2D), 4D VEC MRI with and without respiratory navigator gating (gated/nongated) in volunteers (n = 7). In addition, SV and regurgitation fractions (RF) measured in aorta or pulmonary trunk of patients with malformed and/or insufficient valves (n = 10) were compared between 2D and nongated 4D VEC MRI methods. RESULTS: In volunteers and patients, Bland-Altman tests showed excellent agreement between 2D, gated, and nongated 4D VEC MRI obtained quantitative blood flow measurements. The bias between 2D and gated 4D VEC MRI was <0.5 mL for SV; between 2D and nongated 4D VEC MRI the bias was <0.7 mL for SV and <1% for RF. CONCLUSION: Blood flow can be quantified accurately in arterial, venous, and pathological flow conditions using 4D VEC MRI. Nongated 4D VEC MRI has the potential to be suited for clinical use in patients with congenital heart disease who require flow acquisitions in multiple vessels.