Measuring mechanical function in the failing heart

Abstract

A common pathology in heart failure is a detrimental change in the mechanics of both contraction and filling. In familial hypertrophic cardiomyopathy, a genetic disease characterized by left ventricular hypertrophy and myofiber disarray, left ventricular diastolic dysfunction is common and contributes to congestive heart failure. In dilated cardiomyopathy, a common correlate to reduced wall thickening and increased chamber volume is an asynchronous activation of the left ventricle due to left bundle branch block. Local measures of the timing and magnitude of myocardial shortening and relaxation can be obtained with magnetic resonance (MR) tissue tagging, MR cine phase contrast, or MR cine displacement encoding. In familial hypertrophic cardiomyopathy, these methods have been shown to quantify the restrictive filling of the ventricle. Characterizing the regions of the failing heart which are activated late has allowed investigators to measure the change in protein expression in those regions compared to normal myocardium. Also, these MR imaging methods have led to a better quantification of the asynchronous activation in dilated cardiomyopathy, which can be used to predict response to resynchronization therapy with pacing.

Introduction

Heart failure is the leading cause of hospitalizations among the elderly. It is estimated that just less than 5 million people in the US have heart failure. Heart failure comprises a broad spectrum of pathologies in which the heart undergoes changes in its geometrical dimensions and its pump function is reduced. This can involve myocardium, which is too thick and stiff in the case of hypertrophic cardiomyopathy (HCM) or is too thin in the case of dilated cardiomyopathy (DCM). In both cases, the heart experiences a reduction in pump function due to a poor geometry and/or asynchronous activation of the myocardium. The myocardium itself may be compromised by the infiltration of fibrous tissue secondary to previous infarct, or due to idiopathic etiology.

When evaluating the patient with heart failure, it is necessary to measure the geometry of the heart, the mechanics of the contracting ventricles, hemodynamics, and the classification of the myocardium as viable or nonviable. Magnetic resonance imaging (MRI) can fill all of these needs. Methods currently exist for the precise measurement of local 3-dimensional myocardial motion noninvasively with MRI tagging.¹ From these motion estimates, strain images representing the local deformation of the myocardium can be formed to show local myocardial contraction.^2,3 These images clearly show the sequence of mechanical events during the activation and relaxation of the heart, making them ideal to visualize abnormalities caused by asynchronous electrical activation or ischemia. Flow imaging can be used for measuring hemodynamics⁵ and late enhancement Gd-diethylenetriamine pentaacetic acid imaging can be used to highlight nonviable myocardium.^6-8

In this article, we will focus our attention on the ability of MRI to measure the mechanical properties of the failing heart.

Measuring mechanics with MRI

Magnetic resonance imaging has made significant contributions to the understanding of myocardial mechanics through the use of numerous “tagging” methods for tracking myocardial motion noninvasively.¹ In MRI tagging, a set of saturation pulses placed in the tissue provide a spatially varying signal intensity pattern that is an intrinsic part of the tissue; the change in shape of the intensity pattern in the image reflects the change in shape of the underlying body containing the intensity pattern.^9-11 Although these methods were initially difficult to perform in large patient populations, they are now available on almost all commercial MRI scanners, and the advent of new processing algorithms has made it possible to analyze the data in a reasonable time.¹² This has led to the use of tagging in large clinical trials.^13,14 Recent work on alternative motion-tracking methods has also opened up opportunities of high-resolution imaging of myocardial motion,^15,16 but these have yet to be used in large clinical trials. Reviews of these techniques exist,^17,18 so we will not cover the details here. Fig. 1 shows a short axis slice of the heart at 2 time points in the heart cycle: just after the electrocardiogram trigger and at end-systole. The ability to measure local mechanics from the deformation of the tagging pattern is very clear.

Fig. 1.

Two images of a short axis slice in a heart that has been tagged with a grid pattern. The left image shows the heart just after electrocardiogram detection and tag pattern application. The right picture shows the mechanical deformation of the myocardium close to end-systole. Note the severe deformation of the thinned septum away from the center of the left ventricle indicating “paradoxical” systolic stretching in this region of myocardium. These lines can be tracked and the regional circumferential shortening calculated.

Measuring mechanics in HCM

Hypertrophic cardiomyopathy is a condition in which the myocardium becomes too thick, thereby impairing function and sometimes obstructing the outflow tract in the left ventricle. Hypertrophic cardiomyopathy was investigated early in the development of tagging techniques.¹⁹ Young et al²⁰ found increased twist in HCM, decreased excursion of valve plane toward the apex, and reduced shortening especially in the basal septum. Kramer et al²¹ found that circumferential shortening was less in patients with HCM than in control subjects in the septal (13% ± 5% vs 24% ± 6%, P = .0002), inferior (13% ± 5% vs 21% ± 4%, P = .001), and anterior (17% ± 5% vs 21% ± 3%, P < .03) regions, but not in the lateral region. Circumferential end-systolic shortening was reduced in patients with HCM compared with control subjects at all levels from apex to base.

Recent work by Ennis et al²² that focused on creating tag patterns that could be tracked throughout the entire cardiac cycle has shown some interesting differences in the temporal characteristics of strain in HCM vs normals. Using complementary spatial modulation of magnetization²³ and extended temporal sampling with cardiac phase to order reconstruction,²⁴ we compared the slow relaxation of the HCM ventricle with normals as shown in Fig. 2.

Fig. 2.

The circumferential strain vs time in a normal volunteer and in a patient with HCM.²² The primary feature that is different is the rapid relaxation of the normal left ventricle during early diastole vs the slow relaxation of the left ventricle with HCM. This feature is quantified in the figure with percentage circumferential strain per second (% Ecc/s). The mean value of this strain rate from 8 patients and 6 normals is shown in the bar graph on the right (normals are the dark gray bars; patients with HCM, light gray bars). Figure adapted from the PhD thesis of Daniel Ennis, Johns Hopkins University, with permission.

Measuring mechanics in DCM (asynchronous activation)

The relationship between asynchronous electrical excitation and the onset of mechanical contraction has been investigated with MRI tagging.^4,25-28 These MRI methods are ideal for measuring the nature of mechanical asynchrony found in some patients with DCM, especially those who are candidates for resynchronization therapy.^29-31 Fig. 3 shows an example of the evolution of strain in a normal left ventricle vs a patient in end-stage DCM with left bundle branch block (LBBB).

Fig. 3.

These colorized surfaces show the circumferential stretch (yellow) and contraction (blue) of the midwall of a normal human left ventricle (top) and a left ventricle of a patient with DCM (bottom). The apex is toward the viewer and the free wall is on the right side. Four time frames are shown from the beginning of systole through end-systole. Note the early contraction of the septum and late contraction of the free wall in the patient.

Pacing the left ventricle with either single site or biventricular (BiV) pacing has been shown to improve cardiac function in some patients with DCM.³²However, establishing the criteria for which patients will respond best to this therapy is ongoing. Mechanical imaging with magnetic resonance has offered some insight into this problem³³ as shown in Fig. 3. Nelson et al³⁴ showed that a mechanical dyssynchrony index which quantified the strain variance at the time of maximal shortening did correlate with response to pacing much better than QRS duration.

The relative efficacy of BiV and left ventricular (LV) pacing has also been studied using MRI tagging techniques by Leclerq et al.³⁵ A similar degree of systolic function improvement was found in a canine model of LBBB-failing hearts, despite radically different electrical activation pattern from the 2 pacing protocols. Epicardial electrical mapping, tagged MRI, and hemodynamics were obtained in dogs with LBBB-failing hearts during right atrial, LV, and BiV stimulation. Biventricular and LV stimulation both significantly improved chamber hemodynamics (eg, 25% increase in dP/dt_max and aortic pulse pressure) compared with atrial pacing-LBBB. The functional improvement correlated with mechanical resynchronization as quantified by MRI tagging techniques. Paradoxically, the electrical dispersion decreased 13% with BiV but increased 23% with LV pacing (P < .01). It was concluded that improved mechanical synchrony and function do not require electrical synchrony. Mechanical coordination was the most important factor for systolic improvement with either BiV- or LV-only pacing.

Discussion

Precise measurements of cardiac mechanics in heart failure have shown that knowledge of the mechanics can predict the efficacy of resynchronization therapy, whereas the QRS interval does not seem to be useful. It should be noted that beyond mechanics, late Gd enhancement is able to accurately differentiate coronary artery disease from non-coronary artery disease etiology of heart failure.³⁶ Also, chronic mechanical asynchrony will have an effect on the myocardial substrate, possibly increasing the probability of lethal arrhythmias.³⁷ Magnetic resonance imaging is an excellent imaging modality to understand heart failure and help guide appropriate therapy.