Mechano-energetics of the asynchronous and resynchronized heart

Abstract

Abnormal electrical activation of the ventricles creates major abnormalities in cardiac mechanics. Local contraction patterns, as reflected by measurements of local strain, are not only out of phase, but often also show opposing length changes in early and late activated regions. As a consequence, the efficiency of cardiac pump function (the amount of stroke work generated by a unit of oxygen consumed) is approximately 30% lower in asynchronous than in synchronous hearts. Moreover, the amount of work performed in myocardial segments becomes considerably larger in late than in early activated regions. Cardiac Resynchronization Therapy (CRT) improves mechano-energetics of the previously asynchronous heart in various ways: it alleviates impediment of the abnormal contraction on blood flow, it increases myocardial efficiency, it recruits contraction in the previously early activated septum and it creates a more uniform distribution of myocardial blood flow. These factors act together to increase the range of cardiac work that can be delivered by the patients' heart, an effect that can explain the increased exercise tolerance and quality of life reported in several CRT trials.

Fig. 1

Three dimensional representation of ventricular electrical activation (upper panels) and strain tracings (lower panels) during normal activation (left panels) and LBBB (right panels) in a canine heart. In the LBBB heart, early activation in the septum (blue circles in right upper panel) leads to early onset of shortening (corresponding blue tracing in lower right panel) while late activated LV lateral wall regions (red tracing) are stretched during early systole, followed by pronounced shortening during the ejection phase. Gray tracings represent mean LV strain. Derived from data presented in [30] and [13]

Fig. 2

Plot of local subepicardial fiber strain during the ejection phase versus local electrical activation time during four modes of pacing: right atrial (normal activation, filled squares), LV free wall (open squares), LV apex (+) and RV outflow tract pacing (triangles). The activation time was normalized to the moment of maximum rate of rise of LV pressure. A strain value of −0.10 represents 10% shortening. Modified after [17]

Fig. 3

Definition of SRS and ISF, using strain signals from septum and LV lateral wall from a dg with LBBB (same signals as in Fig. 1). The gray part of the curves indicate the diastolic phase, not used for calculation of ISF and SRS

Fig. 4

Bulls-eye plots of the distribution of external myocardial work in the canine left ventricle during normal impulse conduction (atrial pacing) and during asynchronous activation, as induced by RV apex and LV free wall pacing. Simplified fiber stress–fiber length (S–L) relations in regions with normal (red) early (black) and late (yellow) activation are presented. Strain was measured using MRI tagging; stress was estimated from LV pressure and cavity volume and local strain. [17] External work is determined as the area of the S–L loop [40]

Fig. 5

Upper panel: Conversion of aerobic energy into stroke work and other forms of energy. Oxygen is used for aerobic metabolism resulting in ATP formation, yet in that step a certain part of the energy is lost as non-mechanical consumption. ATP is used for basal metabolism and calcium handling, still processes that do not lead to mechanical output. Contraction, energized by ATP, leads to a certain area of the LV pressure–volume loop (PVA), of which only stroke work is useful mechanical output for the body. All other energy is ultimately converted into heat. Lower panel: efficiency of conversion of oxygen into mechanical energy in dogs during normal conduction as well as during RV apex and LV apex pacing. Data derived from [30]. RV apex pacing, but not LV apex pacing, decreases the amount of stroke work achieved from a unit volume of oxygen uptake. The lower efficiency during RV pacing is associated with an increased Internal Stretch Fraction (ISF), as indicated by the numbers at the right side of the figure. PVA = pressure volume area (see text). The data provide evidence for the fact that dyssynchrony reduces cardiac efficiency by turning contractile energy into heat, presumably due to stretching of some regions by (stronger) contraction of others

Fig. 6

Strain renderings of the LV created by mapping myocardial circumferential strain (Ecc) as color on a volume reconstruction of the LV. Blue indicates contraction (negative Ecc), red indicates the reference state (Ecc = 0), and yellow indicates stretch (positive Ecc). Data are shown for late diastole, early systole, midsystole and end systole (sequential columns from left to right). Data obtained using MRI tagging during RA, BiV RV apex (RVa) and LV later wall (LV) pacing, from top to bottom. Black dot next to each heart indicates the location of the midseptum. Modified after [58]

Fig. 7

Spatial distribution of local systolic shortening amplitudes before and during CRT. Prior to CRT (gray bars), systolic shortening was highly polarized between the interventricular septum and the LV free wall. CRT homogenized distribution of systolic shortening (‘recoordination’) by strongly increasing shortening in the septal segments (Sept and AS) and slightly decreasing shortening in lateral (LAT) and posterior (Post) LV wall segments. Modified after [14]

Fig. 8

Myocardial blood flow during rest (MBF) and hyperemia (MBF stress, both ml/min/ml of myocardium) and the flow reserve, as measured with PET and H₂O¹⁵ in patients before (baseline) and after 3 months of biventricular pacing. Data derived from table 3 of [25]