John Gorcsan

Results of the Predictors of Response to CRT (PROSPECT) Trial

Background— Data from single-center studies suggest that echocardiographic parameters of mechanical dyssynchrony may improve patient selection for cardiac resynchronization therapy (CRT). In a prospective, multicenter setting, the Predictors of Response to CRT (PROSPECT) study tested the performance of these parameters to predict CRT response. Methods and Results— Fifty-three centers in Europe, Hong Kong, and the United States enrolled 498 patients with standard CRT indications (New York Heart Association class III or IV heart failure, left ventricular ejection fraction ≤35%, QRS ≥130 ms, stable medical regimen). Twelve echocardiographic parameters of dyssynchrony, based on both conventional and tissue Doppler–based methods, were evaluated after site training in acquisition methods and blinded core laboratory analysis. Indicators of positive CRT response were improved clinical composite score and ≥15% reduction in left ventricular end-systolic volume at 6 months. Clinical composite score was improved in 69% of 426 patients, whereas left ventricular end-systolic volume decreased ≥15% in 56% of 286 patients with paired data. The ability of the 12 echocardiographic parameters to predict clinical composite score response varied widely, with sensitivity ranging from 6% to 74% and specificity ranging from 35% to 91%; for predicting left ventricular end-systolic volume response, sensitivity ranged from 9% to 77% and specificity from 31% to 93%. For all the parameters, the area under the receiver-operating characteristics curve for positive clinical or volume response to CRT was ≤0.62. There was large variability in the analysis of the dyssynchrony parameters. Conclusion— Given the modest sensitivity and specificity in this multicenter setting despite training and central analysis, no single echocardiographic measure of dyssynchrony may be recommended to improve patient selection for CRT beyond current guidelines. Efforts aimed at reducing variability arising from technical and interpretative factors may improve the predictive power of these echocardiographic parameters in a broad clinical setting.

Novel Speckle-Tracking Radial Strain From Routine Black-and-White Echocardiographic Images to Quantify Dyssynchrony and Predict Response to Cardiac Resynchronization Therapy

Background— Mechanical dyssynchrony is a potential means to predict response to cardiac resynchronization therapy (CRT). We hypothesized that novel echocardiographic image speckle tracking can quantify dyssynchrony and predict response to CRT. Methods and Results— Seventy-four subjects were studied: 64 heart failure patients undergoing CRT (aged 64±12 years, ejection fraction 26±6%, QRS duration 157±28 ms) and 10 normal controls. Speckle tracking applied to routine midventricular short-axis images calculated radial strain from multiple circumferential points averaged to 6 standard segments. Dyssynchrony from timing of speckle-tracking peak radial strain was correlated with tissue Doppler measures in 47 subjects (r=0.94, P<0.001; 95% CI 0.90 to 0.96). The ability of baseline speckle-tracking radial dyssynchrony (time difference in peak septal wall–to–posterior wall strain ≥130 ms) to predict response to CRT was then tested. It predicted an immediate increase in stroke volume in 48 patients studied the day after CRT with 91% sensitivity and 75% specificity. In 50 patients with long-term follow-up 8±5 months after CRT, baseline speckle-tracking radial dyssynchrony predicted a significant increase in ejection fraction with 89% sensitivity and 83% specificity. Patients in whom left ventricular lead position was concordant with the site of latest mechanical activation by speckle-tracking radial strain had an increase in ejection fraction from baseline to a greater degree (10±5%) than patients with discordant lead position (6±5%; P<0.05). Conclusions— Speckle-tracking radial strain can quantify dyssynchrony and predict immediate and long-term response to CRT and has potential for clinical application.

Echocardiography for cardiac resynchronization therapy: recommendations for performance and reporting--a report from the American Society of Echocardiography Dyssynchrony Writing Group endorsed by the Heart Rhythm Society.

Echocardiography plays an evolving and important role in the care of heart failure patients treated with biventricular pacing, or cardiac resynchronization therapy (CRT). Numerous recent published reports have utilized echocardiographic techniques to potentially aide in patient selection for CRT prior to implantation and to optimized device settings afterwards. However, no ideal approach has yet been found. This consensus report evaluates the contemporary applications of echocardiography for CRT including relative strengths and technical limitations of several techniques and proposes guidelines regarding current and possible future clinical applications. Principal methods advised to qualify abnormalities in regional ventricular activation, known as dyssynchrony, include longitudinal velocities by color-coded tissue Doppler and the difference in left ventricular to right ventricular ejection using routine pulsed Doppler, or interventricular mechanical delay. Supplemental measures of radial dynamics which may be of additive value include septal-to-posterior wall delay using M-mode in patients with non-ischemic disease with technically high quality data, or using speckle tracking radial strain. A simplified post-CRT screening for atrioventricular optimization using Doppler mitral inflow velocities is also proposed. Since this is rapidly changing field with new information being added frequently, future modification and refinements in approach are anticipated to continue.

Improvement in pulmonary function and elastic recoil after Lung reduction surgery for diffuse emphysema

BACKGROUND Pulmonary function may improve after surgical resection of the most severely affected lung tissue (lung-reduction surgery) in patients with diffuse emphysema. The basic mechanisms responsible for the improvement, however, are not known. METHODS We studied 20 patients with diffuse emphysema before and at least three months after either a unilateral or a bilateral lung-reduction procedure. Clinical benefit was assessed by measurement of the six-minute walking distance and the transitional-dyspnea index, which is a subjective rating of the change from base line in functional impairment and the threshold for effort- and task- dependent dyspnea. Pressure-volume relations in the lungs were measured with static expiratory esophageal-balloon techniques, and right ventricular systolic function was assessed by echocardiography. RESULTS The patients had significant improvement in the transitional-dyspnea index after surgery (P<0.001). The mean (+/-SD) coefficient of retraction, an indicator of elastic recoil of the lung, improved (from 1.3+/-0.6 cm of water per liter before surgery to 1.8+/-0.8 after, P<0.001). Sixteen patients with increased elastic recoil had a greater increase in the distance walked in six minutes than the other four patients, in whom recoil did not increase (P=0.02). The improved lung recoil led to disproportionate decreases in residual volume as compared with total lung capacity (16 percent vs. 6 percent), but the decreases in both values were significant (P<0.001). Forced expiratory volume in one second increased (from 0.87+/-0.36 to 1.11+/-0.45 liters, P<0.001). End-expiratory esophageal pressure also decreased (P=0.002). These improvements in lung mechanics led to a decrease in arterial partial pressure of carbon dioxide form 42+/-6 to 38+/-5 mm Hg (P=0.006). Furthermore, the fractional change in right ventricular area, an indicator of systolic function, increased from 0.33+/-0.11 to 0.38+/-0.010 (P=0.02). CONCLUSIONS Lung-reduction surgery can produce increases in the elastic recoil of the lung in patients with diffuse emphysema, leading to short-term improvement in dyspnea and exercise tolerance.

Mitral annular descent velocity by tissue Doppler echocardiography as an index of global left ventricular function

Mitral annular descent has been described as an index of left ventricular (LV) systolic function, which is independent of endocardial definition. Echocardiographic tissue Doppler imaging is a new technique that calculates and displays color-coded cardiac tissue velocities on-line. To evaluate mitral annular descent velocity as a rapid index of global LV function, we performed tissue Doppler imaging studies in 55 patients, aged 56 +/-15 years, within 3 hours of radionuclide ventriculographic ejection fraction. Tissue Doppler M-mode studies were obtained from each of 6 mitral annular sites, as follows: inferoseptal and lateral from apical 4-chamber views, anterior and inferior from apical 2-chamber views, and anteroseptal and posterior from apical long-axis views. Only 1 patient with severe mitral annular calcification was excluded. The group mean 6-site average peak mitral annular descent velocity was 5.5 +/- 1.9 cm/s (range 2.4 to 10.5), and the group mean ejection fraction was 49 +/- 18% (range 17 to 80%). The 6-site average peak annular descent velocity correlated linearly with LV ejection fraction (r = 0.86, SEE = 1.02 cm/s): LV ejection fraction = 8.2 (average peak mitral annular descent velocity) + 3%. The 6-site peak mitral annular descent velocity average >5.4 cm/s was 88% sensitive and 97% specific for ejection fraction >50%. The peak mitral annular descent velocity from the apical 4-chamber view (average from inferoseptal and lateral sites) correlated most closely with the LV ejection fraction (r = 0.85) as an individual view. Peak mitral annular descent velocity by tissue Doppler imaging has the potential to estimate rapidly the global LV function.

Cardiac-Resynchronization Therapy in Heart Failure with a Narrow QRS Complex

BACKGROUND Cardiac-resynchronization therapy (CRT) reduces morbidity and mortality in chronic systolic heart failure with a wide QRS complex. Mechanical dyssynchrony also occurs in patients with a narrow QRS complex, which suggests the potential usefulness of CRT in such patients. METHODS We conducted a randomized trial involving 115 centers to evaluate the effect of CRT in patients with New York Heart Association class III or IV heart failure, a left ventricular ejection fraction of 35% or less, a QRS duration of less than 130 msec, and echocardiographic evidence of left ventricular dyssynchrony. All patients underwent device implantation and were randomly assigned to have CRT capability turned on or off. The primary efficacy outcome was the composite of death from any cause or first hospitalization for worsening heart failure. RESULTS On March 13, 2013, the study was stopped for futility on the recommendation of the data and safety monitoring board. At study closure, the 809 patients who had undergone randomization had been followed for a mean of 19.4 months. The primary outcome occurred in 116 of 404 patients in the CRT group, as compared with 102 of 405 in the control group (28.7% vs. 25.2%; hazard ratio, 1.20; 95% confidence interval [CI], 0.92 to 1.57; P=0.15). There were 45 deaths in the CRT group and 26 in the control group (11.1% vs. 6.4%; hazard ratio, 1.81; 95% CI, 1.11 to 2.93; P=0.02). CONCLUSIONS In patients with systolic heart failure and a QRS duration of less than 130 msec, CRT does not reduce the rate of death or hospitalization for heart failure and may increase mortality. (Funded by Biotronik and GE Healthcare; EchoCRT ClinicalTrials.gov number, NCT00683696.).

Quantitative Assessment of Alterations in Regional Left Ventricular Contractility With Color-Coded Tissue Doppler Echocardiography Comparison With Sonomicrometry and Pressure-Volume Relations

BACKGROUND Tissue Doppler imaging (TDI) is a novel method of color-coding myocardial velocity on-line. The objective of the present study was to evaluate endocardial velocity with TDI as a method of objectively quantifying alterations in regional contractility over a wide range induced by inotropic modulation. METHODS AND RESULTS Myocardial length crystals were used to simultaneously assess regional left ventricular (LV) function, and high-fidelity pressure and conductance catheters were used to assess global LV contractility by pressure-volume relations in nine open-chest dogs. Mid-LV M-mode and two-dimensional color TDI images were recorded during control and inotropic modulation stages with dobutamine and esmolol. Predicted significant increases in TDI indices occurred with dobutamine: peak systolic velocity of 4.41 +/- 1.07 to 6.67 +/- 1.07 cm/s*, systolic time-velocity integral (TVI) of 0.43 +/- 0.12 to 0.62 +/- 0.10 cm*, and diastolic TVI of 0.49 +/- 0.11 to 0.71 +/- 0.17 cm*. Opposing significant decreases occurred with esmolol: peak systolic velocity of 4.46 +/- 0.94 to 2.31 +/- 0.81 cm/s*, systolic TVI of 0.47 +/- 0.12 to 0.19 +/- 0.11 cm*, and diastolic TVI of 0.55 +/- 0.11 to 0.33 +/- 0.11 cm* (*all P < .001 versus control). Changes in TDI peak systolic velocity were correlated with changes in fractional shortening (r = .88) and shortening velocity (r = .87) by sonomicrometry. Changes in TDI peak velocity from multiple mid-LV sites also correlated significantly with maximal elastance (r = .85 +/- .04) from pressure-volume relations. CONCLUSIONS TDI measures reflect directional and incremental alterations in regional and global LV contractility and have the potential to quantify regional LV function.

Echocardiographic Assessment of Myocardial Strain

Echocardiographic strain imaging, also known as deformation imaging, has been developed as a means to objectively quantify regional myocardial function. First introduced as post-processing of tissue Doppler imaging velocity converted to strain and strain rate, strain imaging has more recently also been derived from digital speckle tracking analysis. Strain imaging has been used to gain greater understanding into the pathophysiology of cardiac ischemia and infarction, primary diseases of the myocardium, and the effects of valvular disease on myocardial function, and to advance our understanding of diastolic function. Strain imaging has also been used to quantify abnormalities in the timing of mechanical activation for heart failure patients undergoing cardiac resynchronization pacing therapy. Further advances, such as 3-dimensional speckle tracking strain imaging, have emerged to provide even greater insight. Strain imaging has become established as a robust research tool and has great potential to play many roles in routine clinical practice to advance the care of the cardiovascular patient. This perspective reviews the physiology of myocardial strain, the technical features of strain imaging using tissue Doppler imaging and speckle tracking, their strengths and weaknesses, and the state-of-the-art present and potential future clinical applications.

Color-coded measures of myocardial velocity throughout the cardiac cycle by tissue Doppler imaging to quantify regional left ventricular function

TDI is a new echocardiographic technique that calculates and displays color-coded myocardial velocity on-line. To determine the feasibility of endocardial velocity throughout the cardiac cycle as a means to quantify regional function, 20 normal subjects aged 30 +/- 5 years and 12 patients with heart disease aged 62 +/- 17 years were studied with a prototype TDI system. TDI M-mode images were acquired by using a multicolored velocity map (display range, -30 to 30 mm/sec; temporal resolution, 90 Hz). Color-coded velocity data were then converted to numeric values off-line at 50 msec intervals. Posterior wall velocities throughout the cardiac cycle by TDI were closely correlated with velocity calculations from the first derivative of routine digitized M-mode tracings (group mean r = 0.88 +/- 0.03, SEE = 7.0 +/- 1.1 mm/sec). Anteroseptal TDI color-coded systolic velocity occurred 164 +/- 84 msec from the onset of the electrocardiographic QRS compared with 203 +/- 33 msec in the posterior wall (P < 0.05) in normal subjects, consistent with normal electrical activation. Significant differences in systolic and diastolic posterior wall TDI velocity data were observed in patients with hypokinetic or akinetic segments assessed by independent routine study when compared with normal controls. Calculated systolic and early diastolic posterior wall TDI indexes correlated significantly with percentage of wall thickening. Of abnormal anteroseptal segments, TDI systolic time velocity integrals were significantly different than normal and correlated with percentage of wall thickening. TDI has potential to quantitatively assess regional left ventricular function.

Dyssynchrony by speckle-tracking echocardiography and response to cardiac resynchronization therapy: results of the Speckle Tracking and Resynchronization (STAR) study

Aims The Speckle Tracking and Resynchronization (STAR) study used a prospective multi-centre design to test the hypothesis that speckle-tracking echocardiography can predict response to cardiac resynchronization therapy (CRT). Methods and results We studied 132 consecutive CRT patients with class III and IV heart failure, ejection fraction (EF) ≤35%, and QRS ≥120 ms from three international centres. Baseline dyssynchrony was evaluated by four speckle tracking strain methods; radial, circumferential, transverse, and longitudinal (≥130 ms opposing wall delay for each). Pre-specified outcome variables were EF response and three serious long-term events: death, transplant, or left ventricular assist device. Of 120 patients (91%) with baseline dyssynchrony data, both short-axis radial strain and transverse strain from apical views were associated with favourable EF response 7 ± 4 months and long-term outcome over 3.5 years (P < 0.01). Radial strain had the highest sensitivity at 86% for predicting EF response with a specificity of 67%. Serious long-term unfavourable events occurred in 20 patients after CRT, and happened three times more frequently in those who lacked baseline radial or transverse dyssynchrony than in patients with dyssynchrony (P < 0.01). Patients who lacked both radial and transverse dyssynchrony had unfavourable clinical events occur in 53%, in contrast to events occurring in 12% if baseline dyssynchrony was present (P < 0.01). Circumferential and longitudinal strains predicted response when dyssynchrony was detected, but failed to identify dyssynchrony in one-third of patients who responded to CRT. Conclusion Dyssynchrony by speckle-tracking echocardiography using radial and transverse strains is associated with EF response and long-term outcome following CRT.