Kristoffer Russell

Echocardiographic Evaluation of Hemodynamics in Patients With Decompensated Systolic Heart Failure

Background— Doppler echocardiography is currently applied for the assessment of left ventricular and right ventricular hemodynamics in patients with cardiovascular disease. However, there are conflicting reports about its accuracy in patients with unstable decompensated heart failure. The objective of this study was to evaluate the accuracy of the technique in patients with unstable heart failure. Methods and Results— Consecutive patients with decompensated heart failure had simultaneous assessment of left ventricular and right ventricular hemodynamics invasively and by Doppler echocardiography. In 79 patients, the noninvasive measurements of stroke volume (r=0.83, P<0.001), pulmonary artery systolic (r=0.83, P<0.001) and diastolic pressure (r=0.51, P=0.009), and mean right atrial pressure (r=0.85, P<0.001) all had significant correlations with invasively acquired measurements. Several Doppler indices had good accuracy in identifying patients with pulmonary capillary wedge pressure >15 mm Hg (area under the curve, 0.86 to 0.92). The recent American Society of Echocardiography/European Association of Echocardiography guidelines were highly accurate (sensitivity, 98%; specificity, 91%) in identifying patients with increased wedge pressure. In 12 repeat studies, Doppler echocardiography readily detected the changes in mean wedge pressure (r=0.75, P=0.005) as well as changes in pulmonary artery systolic pressure and mean right atrial pressure. Conclusions— Doppler echocardiography provides reliable assessment of right and left ventricular hemodynamics in patients with decompensated heart failure.

Mechanisms of Abnormal Systolic Motion of the Interventricular Septum During Left Bundle-Branch Block

Background— In a majority of patients with left bundle-branch block (LBBB), there is abnormal leftward motion of the interventricular septum during the preejection phase. This motion was considered to be passive, caused by early rise in right ventricular (RV) pressure, and has therefore been excluded from most indices of left ventricular (LV) dyssynchrony. If considered active, however, the leftward motion reflects onset of septal activation and should be included. We therefore investigated if the motion was a passive response to pressure changes or caused by active contraction. Methods and Results— LBBB was induced in 8 anesthetized dogs with micromanometers. Cardiac dimensions were measured by sonomicrometry and echocardiography. Induction of LBBB resulted in preejection leftward motion of the septum, simultaneously with shortening of septal segments (P<0.01). In each experiment, preejection septal shortening occurred against rising LV pressure, consistent with active contraction. Furthermore, the LV pressure–segment length relationships were shifted upward (P<0.01) relative to the passive elastic curve, indicating stiffening of septal myocardium, confirming an active mechanism. Initially, RV pressure increased faster than LV pressure, suggesting that the leftward septal motion may have a passive pressure component. However, the passive component appeared to play a minor role. The magnitude of preejection septal shortening was modified by load alterations. Conclusions— Leftward preejection motion of the septum during LBBB is mainly a result of active septal contraction, whereas alterations in diastolic ventricular pressures modulate the amplitude of this motion. The findings imply that the preejection phase should be included when assessing LV dyssynchrony.

A novel clinical method for quantification of regional left ventricular pressure-strain loop area: a non-invasive index of myocardial work.

Aims Left ventricular (LV) pressure–strain loop area reflects regional myocardial work and metabolic demand, but the clinical use of this index is limited by the need for invasive pressure. In this study, we introduce a non-invasive method to measure LV pressure–strain loop area. Methods and results Left ventricular pressure was estimated by utilizing the profile of an empiric, normalized reference curve which was adjusted according to the duration of LV isovolumic and ejection phases, as defined by timing of aortic and mitral valve events by echocardiography. Absolute LV systolic pressure was set equal to arterial pressure measured invasively in dogs (n = 12) and non-invasively in patients (n = 18). In six patients, myocardial glucose metabolism was measured by positron emission tomography (PET). First, we studied anaesthetized dogs and observed an excellent correlation (r = 0.96) and a good agreement between estimated LV pressure–strain loop area and loop area by LV micromanometer and sonomicrometry. Secondly, we validated the method in patients with various cardiac disorders, including LV dyssynchrony, and confirmed an excellent correlation (r = 0.99) and a good agreement between pressure–strain loop areas using non-invasive and invasive LV pressure. Non-invasive pressure–strain loop area reflected work when incorporating changes in local LV geometry (r = 0.97) and showed a strong correlation with regional myocardial glucose metabolism by PET (r = 0.81). Conclusions The novel non-invasive method for regional LV pressure–strain loop area corresponded well with invasive measurements and with directly measured myocardial work and it reflected myocardial metabolism. This method for assessment of regional work may be of clinical interest for several patients groups, including LV dyssynchrony and ischaemia.

Assessment of wasted myocardial work: a novel method to quantify energy loss due to uncoordinated left ventricular contractions

Left ventricular (LV) dyssynchrony reduces myocardial efficiency because work performed by one segment is wasted by stretching other segments. In the present study, we introduce a novel noninvasive clinical method that quantifies wasted energy as the ratio between work consumed during segmental lengthening (wasted work) divided by work during segmental shortening. The wasted work ratio (WWR) principle was studied in 6 anesthetized dogs with left bundle branch block (LBBB) and in 28 patients with cardiomyopathy, including 12 patients with LBBB and 10 patients with cardiac resynchronization therapy. Twenty healthy individuals served as controls. Myocardial strain was measured by speckle tracking echocardiography, and LV pressure (LVP) was measured by micromanometer and a previously validated noninvasive method. Segmental work was calculated by multiplying strain rate and LVP to get instantaneous power, which was integrated to give work as a function of time. A global WWR was also calculated. In dogs, WWR by estimated LVP and strain showed a strong correlation (r = 0.94) and good agreement with WWR by the LV micromanometer and myocardial segment length by sonomicrometry. In patients, noninvasive WWR showed a strong correlation (r = 0.96) and good agreement with WWR using the LV micromanometer. Global WWR was 0.09 ± 0.03 in healthy control subjects, 0.36 ± 0.16 in patients with LBBB, and 0.21 ± 0.09 in cardiomyopathy patients without LBBB. Cardiac resynchronization therapy reduced global WWR from 0.36 ± 0.16 to 0.17 ± 0.07 (P < 0.001). In conclusion, energy loss due to incoordinated contractions can be quantified noninvasively as the LV WWR. This method may be applied to evaluate the mechanical impact of dyssynchrony.

Evaluation of Left Ventricular Dyssynchrony by Onset of Active Myocardial Force Generation A Novel Method That Differentiates Between Electrical and Mechanical Etiologies

Background— Better clinical tools for measuring left ventricular electrical dyssynchrony are needed. The present study investigates if onset of active myocardial force generation (AFG) may serve as a measure of electrical dyssynchrony. Methods and Results— In anesthetized dogs, we evaluated left ventricular mechanical dyssynchrony by 2 different approaches. First, we measured timing of peak myocardial shortening velocity and strain. Second, we measured the first sign of tension development by onset AFG as defined by the myocardial pressure-segment length loop upward shift from its passive-elastic state. Electrical dyssynchrony was measured by intramyocardial electromyograms (IM-EMG). Dyssynchrony was quantified as peak intersegment time difference and as standard deviation of timing for 6 to 8 myocardial segments. During baseline, reduced preload and myocardial ischemia shortening velocity and strain indicated segmental mechanical heterogeneity, whereas onset AFG and onset R in IM-EMG indicated synchronous activation of all segments. After induction of left bundle-branch block, all methods indicated dyssynchrony. Peak intersegment time difference for shortening velocity and strain showed weak correlations ( r =0.17 and 0.16) and weak agreements (mean differences, −48±27 ms and −28±27 ms, respectively) with IM-EMG. Onset AFG by pressure-segment length loops, however, correlated well with IM-EMG ( r =0.93), and agreement was good (mean difference, −0.6±6.8 ms). Results were similar for standard deviation of timing. Onset AFG from pressure-strain analysis by echocardiography showed accuracy similar to sonomicrometry. Conclusions— Onset AFG was an accurate marker of myocardial electrical activation and was superior to shortening velocity and strain. Identification of electrical dyssynchrony by onset AFG may be feasible clinically using left ventricular pressure-strain analysis.Background—Better clinical tools for measuring left ventricular electrical dyssynchrony are needed. The present study investigates if onset of active myocardial force generation (AFG) may serve as a measure of electrical dyssynchrony. Methods and Results—In anesthetized dogs, we evaluated left ventricular mechanical dyssynchrony by 2 different approaches. First, we measured timing of peak myocardial shortening velocity and strain. Second, we measured the first sign of tension development by onset AFG as defined by the myocardial pressure-segment length loop upward shift from its passive-elastic state. Electrical dyssynchrony was measured by intramyocardial electromyograms (IM-EMG). Dyssynchrony was quantified as peak intersegment time difference and as standard deviation of timing for 6 to 8 myocardial segments. During baseline, reduced preload and myocardial ischemia shortening velocity and strain indicated segmental mechanical heterogeneity, whereas onset AFG and onset R in IM-EMG indicated synchronous activation of all segments. After induction of left bundle-branch block, all methods indicated dyssynchrony. Peak intersegment time difference for shortening velocity and strain showed weak correlations (r=0.17 and 0.16) and weak agreements (mean differences, −48±27 ms and −28±27 ms, respectively) with IM-EMG. Onset AFG by pressure-segment length loops, however, correlated well with IM-EMG (r=0.93), and agreement was good (mean difference, −0.6±6.8 ms). Results were similar for standard deviation of timing. Onset AFG from pressure-strain analysis by echocardiography showed accuracy similar to sonomicrometry. Conclusions—Onset AFG was an accurate marker of myocardial electrical activation and was superior to shortening velocity and strain. Identification of electrical dyssynchrony by onset AFG may be feasible clinically using left ventricular pressure-strain analysis.

Mechanism of prolonged electromechanical delay in late activated myocardium during left bundle branch block

During left bundle branch block (LBBB), electromechanical delay (EMD), defined as time from regional electrical activation (REA) to onset shortening, is prolonged in the late-activated left ventricular lateral wall compared with the septum. This leads to greater mechanical relative to electrical dyssynchrony. The aim of this study was to determine the mechanism of the prolonged EMD. We investigated this phenomenon in an experimental LBBB dog model (n = 7), in patients (n = 9) with biventricular pacing devices, in an in vitro papillary muscle study (n = 6), and a mathematical simulation model. Pressures, myocardial deformation, and REA were assessed. In the dogs, there was a greater mechanical than electrical delay (82 ± 12 vs. 54 ± 8 ms, P = 0.002) due to prolonged EMD in the lateral wall vs. septum (39 ± 8 vs.11 ± 9 ms, P = 0.002). The prolonged EMD in later activated myocardium could not be explained by increased excitation-contraction coupling time or increased pressure at the time of REA but was strongly related to dP/dt at the time of REA (r = 0.88). Results in humans were consistent with experimental findings. The papillary muscle study and mathematical model showed that EMD was prolonged at higher dP/dt because it took longer for the segment to generate active force at a rate superior to the load rise, which is a requirement for shortening. We conclude that, during LBBB, prolonged EMD in late-activated myocardium is caused by a higher dP/dt at the time of activation, resulting in aggravated mechanical relative to electrical dyssynchrony. These findings suggest that LV contractility may modify mechanical dyssynchrony.

The role of echocardiography in quantification of left ventricular dyssynchrony: state of the art and future directions

This article discusses how echocardiography can be applied to quantify dyssynchrony in patients who are evaluated for cardiac resynchronization therapy (CRT). A number of echocardiographic indices have been proposed as markers of success of CRT. However, when tested against QRS width in prospective clinical trials, none of the echocardiographic indices are proven to give clinical benefit. One important message in this review is that future studies should focus on approaches which can differentiate between electrical and non-electrical aetiologies of dyssynchrony, since only electrical dyssynchrony is likely to respond to CRT. Just measuring velocity indices does not identify the aetiology. Myocardial strain appears more promising, but one should be aware that timing of peak systolic strain is determined not only by electrical conduction. It is proposed to use onset septal shortening during pre-ejection for timing of earliest left ventricular (LV) electrical activation. One should take into account potential ischaemia, scarring, and other structural changes as contributors to dyssynchrony. As a method to identify electrical dyssynchrony, the authors propose to use time of active force generation as defined by LV pressure-strain loops. A non-invasive method to measure segmental pressure-strain loops is also proposed as a means to quantify the impact of dyssynchrony on distribution of myocardial work. Furthermore, it is important to be aware that LV dyssynchrony may have a combination of aetiologies, not all amenable for CRT.

Wasted septal work in left ventricular dyssynchrony: a novel principle to predict response to cardiac resynchronization therapy

Aims Cardiac resynchronization therapy (CRT) in heart failure is limited by many non-responders. This study explores whether degree of wasted left ventricular (LV) work identifies CRT responders. Methods and results Twenty-one patients who received CRT according to guidelines were studied before and after 8 ± 3 months. By definition, segments that shorten in systole perform positive work, whereas segments that lengthen do negative work. Work was calculated from non-invasive LV pressure and strain by speckle tracking echocardiography. For each myocardial segment and for the entire LV, wasted work was calculated as negative work in percentage of positive work. LV wall motion score index (WMSI) was assessed by echocardiography. Response to CRT was defined as ≥15% reduction in end-systolic volume (ESV). Responder rate to CRT was 71%. In responders, wasted work for septum was 117 ± 102%, indicating more negative than positive work, and decreased to 14 ± 12% with CRT (P < 0.01). In the LV free wall, wasted work was 19 ± 16% and showed no significant change. Global LV wasted work decreased from 39 ± 21 to 17 ± 7% with CRT (P < 0.01). In non-responders, there were no significant changes. In multiple linear regression analysis, septal wasted work and WMSI were the only significant predictors of ESV reduction (β = 0.14, P = 0.01; β = 1.25, P = 0.03). Septal wasted work together with WMSI showed an area under the curve of 0.86 (95% confidence interval 0.71–1.0) for CRT response prediction. Conclusion Wasted work in the septum together with WMSI was a strong predictor of response to CRT. This novel principle should be studied in future larger studies.

Pacing in Heart Failure Patients With Narrow QRS Is There More to Gain Than Resynchronization

Ventricular dyssynchrony is defined as uncoordinated regional myocardial contraction and relaxation and may be either interventricular or intraventricular. Most of the clinical focus has been on left ventricular (LV) intraventricular dyssynchrony, which in principle may have 3 different origins. First, dyssynchrony may have an electric origin as in left bundle-branch block, which causes nonuniform timing of electric activation. Second, there may be disturbances in excitation-contraction coupling, and this would be apparent as delay in electromechanical activation time. Presently, there are limited data on the clinical relevance of such disturbances. Third, dyssynchrony may have a primary mechanical origin and may occur in ventricles with regional impairment of function, as in myocardial ischemia when systolic shortening in different segments is out of phase. Furthermore, a primary mechanical origin may be found in ventricles with nonuniform distribution of load, and this may occur when there are regional differences in LV wall thickness or differences in local radius of curvature, including septal curvature. In these cases, segmental differences in systolic wall stress may lead to differences in timing of peak contraction. Article see p 1687 Cardiac resynchronization therapy (CRT) is established as an effective treatment option in patients with severe heart failure (HF) and LV electric dyssynchrony as indicated by a wide QRS complex.1 Because CRT corrects electric dyssynchrony, it would a priori seem less likely that patients with narrow QRS should be responders because they presumably have relatively normal electric conduction. Consistent with this notion, Beshai et al2 found no benefit of CRT in patients with severe HF with QRS <130 ms and echocardiographic evidence of mechanical dyssynchrony. In apparent contradiction to this, Williams et al,3 in this issue of Circulation , demonstrate that CRT causes marked immediate improvement in LV function in HF patients with narrow QRS and no …

Non-invasive myocardial work index identifies acute coronary occlusion in patients with non-ST-segment elevation-acute coronary syndrome

AIMS Acute coronary artery occlusion (ACO) occurs in ∼30% of patients with non-ST-segment elevation-acute coronary syndrome (NSTE-ACS). We investigated the ability of a regional non-invasive myocardial work index (MWI) to identify ACO. METHODS AND RESULTS Segmental strain analysis was performed before coronary angiography in 126 patients with NSTE-ACS. Left ventricular (LV) pressure was estimated non-invasively using a standard waveform fitted to valvular events and scaled to systolic blood pressure. MWI was calculated as the area of the LV pressure-strain loop. Empirical cut-off values were set to identify segmental systolic dysfunction for MWI (<1700 mmHg %) and strain (more than -14%). The number of dysfunctional segments was used in ROC analysis to identify ACO. The presence of ≥4 adjacent dysfunctional segments assessed by MWI was significantly better than both global strain and ejection fraction at detecting the occurrence of ACO (P < 0.05). Regional MWI had a higher sensitivity (81 vs. 78%) and especially specificity (82 vs. 65%) compared with regional strain. Logistic regression demonstrated that elevated systolic blood pressure significantly decreased the probability of actual ACO in a patient with an area of impaired regional strain. CONCLUSION The presence of a region of reduced MWI in patients with NSTE-ACS identified patients with ACO and was superior to all other parameters. The regional MWI was able to account for the influence of systolic blood pressure on regional contraction. We therefore propose that MWI may serve as an important clinical tool for selecting patients in need of prompt invasive treatment.