Search

Background Analysis of left ventricular (LV) mechanical dyssynchrony may provide incremental prognostic information regarding cardiac resynchronization therapy (CRT) response in addition to QRS width alone. Our objective was to quantify LV dyssynchrony using feature tracking post processing of routine cardiovascular magnetic resonance (CMR) cine acquisitions (FT-CMR) in comparison to speckle tracking echocardiography. Methods We studied 72 consecutive patients who had both steady-state free precession CMR and echocardiography. Mid-LV short axis CMR cines were analyzed using FT-CMR software and compared with echocardiographic speckle tracking radial dyssynchrony (time difference between the anteroseptal and posterior wall peak strain). Results Radial dyssynchrony analysis was possible by FT-CMR in all patients, and in 67 (93%) by echocardiography. Dyssynchrony by FT-CMR and speckle tracking showed limits of agreement of strain delays of ± 84 ms. These were large (up to 100% or more) relative to the small mean delays measured in more synchronous patients, but acceptable (mainly 200 ms. Radial dyssynchrony was significantly greater in wide QRS patients than narrow QRS patients by both FT-CMR (radial strain delay 230 ± 94 vs. 77 ± 92* ms) and speckle tracking (radial strain delay 242 ± 101 vs. 75 ± 88* ms, all *p Conclusions FT-CMR delivered measurements of radial dyssynchrony from CMR cine acquisitions which, at least for the patients with more marked dyssynchrony, showed reasonable agreement with those from speckle tracking echocardiography. The clinical usefulness of the method, for example in predicting prognosis in CRT patients, remains to be investigated.

The current guidelines most strongly support cardiac resynchronization therapy (CRT) for patients with heart failure with a QRS width of ≥150 ms and left bundle branch block (LBBB). Our objective was to assess the potential benefit of echocardiographically guided left ventricular (LV) lead positioning for patients with a QRS width150 ms or non-LBBB as a substudy of the Speckle Tracking Assisted Resynchronization Therapy for Electrode Region (STARTER) prospective, randomized controlled trial. The STARTER trial randomized 187 patients with heart failure, a QRS of ≥120 ms, and ejection fraction of ≤35% to LV lead guided to the site of latest mechanical activation by speckle tracking radial strain versus routine implantation. The predefined primary end point was heart failure hospitalization or death within 2 years. This substudy included 151 CRT patients with matching echocardiographic and LV lead position data and complete follow-up data. Patients with a QRS width of 120 to 149 ms or non-LBBB and LV lead concordant or adjacent to the site of latest mechanical activation had favorable outcomes after CRT similar to those with LBBB or a QRS width of ≥150 ms. In contrast, patients with a QRS of 120 to 149 ms or non-LBBB and remote LV leads had unfavorable outcomes (hazard ratio 5.45, 95% confidence interval 2.36 to 12.6, p0.001, and hazard ratio 4.92, 95% confidence interval 2.12 to 11.39, p0.001, respectively, with significant interaction after adjusting for baseline variables, p = 0.038 and p = 0.008). In conclusion, LV lead positioning with respect to the echocardiographic site of latest activation was significantly associated with more favorable clinical outcomes in patients with a QRS duration150 ms and/or non-LBBB. Additional prospective study is warranted.

Lumped parameter models have been employed for decades to simulate important hemodynamic couplings between a left ventricular assist device (LVAD) and the native circulation. However, these studies seldom consider the pathological descending limb of the Frank-Starling response of the overloaded ventricle. This study introduces a dilated heart failure model featuring a unimodal end systolic pressure-volume relationship (ESPVR) to address this critical shortcoming. The resulting hemodynamic response to mechanical circulatory support are illustrated through numerical simulations of a rotodynamic, continuous flow ventricular assist device (cfVAD) coupled to systemic and pulmonary circulations with baroreflex control. The model further incorporated septal interaction to capture the influence of left ventricular (LV) unloading on right ventricular function. Four heart failure conditions were simulated (LV and bi-ventricular failure with/without pulmonary hypertension) in addition to normal baseline. Several metrics of LV function, including cardiac output and stroke work, exhibited a unimodal response whereby initial unloading improved function, and further unloading depleted preload reserve thereby reducing ventricular output. The concept ofextremal loading was introduced to reflect the loading condition in which the intrinsic LV stroke work is maximized. Simulation of bi-ventricular failure with pulmonary hypertension revealed inadequacy of LV support alone. These simulations motivate the implementation of an extremum tracking feedback controller to potentially optimize ventricular recovery.

Background— Mechanisms of mitral regurgitation (MR) reduction with cardiac resynchronization therapy (CRT) are complex, and their association with long-term outcome is unclear. We sought to elucidate mechanistic features of reduction in MR with CRT, which impact long-term patient survival. Methods and Results— A prospective longitudinal study of 277 patients with heart failure with QRS width ≥120 ms and ejection fraction ≤35% for CRT was performed. Quantitative echocardiography, including dyssynchrony analysis, was performed at baseline. MR was quantified by color Doppler before and 6 months after CRT. Predefined end points of death, transplant, or left ventricular assist device were tracked during 4 years. There were 114 (48%) patients with CRT with significant MR (≥moderate) at baseline; of whom 48 (42%) patients had MR improvement, and 24 (19%) patients had MR worsening after CRT. The 66 events (47 deaths, 10 transplantations, and 9 left ventricular assist devices) were strongly associated with significant MR after CRT (hazard ratio, 3.58; 95% confidence interval, 2.18–5.87; P 200 ms, lack of severe left ventricular dilatation (end-systolic dimension index 2 ), and lack of echocardiographic scar at papillary muscle insertion sites (all P P =0.0001). Conclusions— Significant MR after CRT was strongly associated with less favorable long-term survival. Echocardiographic mechanistic features were identified that were associated with improvement in MR after CRT and favorable long-term survival.

Acute studies have suggested that left ventricular pacing (LVP) may have benefits over biventricular pacing (BVP). The adaptive cardiac resynchronization therapy (aCRT) algorithm provides LVP synchronized to produce fusion with the intrinsic activation when the intrinsic atrioventricular (AV) interval is normal. The randomized double-blind adaptive cardiac resynchronization therapy trial demonstrated noninferiority of the aCRT algorithm compared to echocardiography-optimized BVP (control).To examine whether synchronized LVP (sLVP) resulted in better clinical outcomes.First, stratification by percent sLVP (%sLVP) and multivariate Cox proportional hazards model was used to assess the relationship between %sLVP and clinical outcomes. Second, outcomes were compared between patients in the aCRT arm (n = 318) and control patients (n = 160) stratified by intrinsic AV interval at randomization.In the aCRT arm, %sLVP ≥50% (n = 142) was independently associated with a decreased risk of death or heart failure hospitalization (hazard ratio 0.49; 95% confidence interval 0.28-0.85; P = .012) compared with %sLVP50% (n = 172). A greater proportion of patients with %sLVP ≥50% improved in Packer's clinical composite score at 6-month (82% vs. 68%; P = .002) and 12-month (80% vs. 62%; P = .0006) follow-ups compared to controls. In the subgroup with normal AV (n = 241), there was a lower risk of death or heart failure hospitalization (hazard ratio 0.52; 95% confidence interval 0.27-0.98; P = .044) with the aCRT algorithm. A greater proportion of patients in the aCRT arm improved in the clinical composite score at 6-month (81% vs. 69%; P = .041) and 12-month (77% vs. 66%; P = .076) follow-ups compared to controls.Higher %sLVP was independently associated with superior clinical outcomes. In patients with normal AV conduction, the aCRT algorithm provided mostly sLVP and demonstrated better clinical outcomes compared to echocardiography-optimized BVP.

Background— Cardiac resynchronization therapy improves mortality and morbidity in patients with heart failure (HF) with wide QRS complex and diminished left ventricular (LV) function, but response is variable. Methods and Results— The Speckle Tracking Assisted Resynchronization Therapy for Electrode Region (STARTER) was a prospective, double-blind, randomized controlled trial testing the hypothesis that an incremental benefit to cardiac resynchronization therapy would be gained by echo-guided (EG) transvenous LV lead placement versus a routine fluoroscopic approach. EG LV lead placement was attempted at the site of latest time to peak radial strain by speckle tracking echocardiography. The prespecified primary end point was first HF hospitalization or death. Of 187 New York Heart Association class II to IV patients with HF (62% ischemic; ejection fraction 26±6%; QRS 159±27 ms), 110 were randomized to EG and 77 to routine strategies. Primary events included 30 deaths and 37 HF hospitalizations over 1.8 years. Using intention-to-treat, patients randomized to an EG strategy had a significantly more favorable event-free survival (hazard ratio, 0.48; 95% confidence interval, 0.28–0.82; P =0.006). Exact or adjacent concordance of LV lead with latest site could be achieved in 85% of the EG group and occurred fortuitously in 66% of controls ( P =0.010) and was associated with an improvement in event-free survival (hazard ratio, 0.40; 95% confidence interval, 0.22–0.71; P =0.002). Conclusions— A strategy of EG LV lead placement for cardiac resynchronization therapy improved patient outcomes by reducing the combined risk of death or HF hospitalizations and has implications for delivery of cardiac resynchronization therapy. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00156390.

Prediction of prognosis in patients with systolic heart failure (HF) is of clinical importance. To test the hypothesis that global circumferential strain (GCS) as a new measure of left ventricular (LV) function may predict prognosis using novel cardiac magnetic resonance (CMR) Feature Tracking

Background Right ventricular (RV) performance appears to be important in patients with severe heart failure. Although clinical assessments of RV function previously have been limited to load-dependent ejection phase indices, a new method has been developed using the relatively load-insensitive concepts of pressure-volume relations with automated echocardiographic measures of RV cross-sectional area as a surrogate for volume. Methods and Results Sixteen patients with New York Heart Association functional class IV heart failure and group mean left ventricular ejection fraction of 20±5% were studied. RV pressure-area loops were recorded on-line from echocardiographic measures of RV area and high-fidelity pressure during transient inferior vena caval balloon occlusions. RV contractile reserve was assessed as its functional response to an increase in dobutamine from 5.7±4.1 to 13.1±4.7 μg/kg per minute. Complete data sets were available in 13 patients. Group mean RV end-systolic elastance (E'es) and maximal elastance (E'max) increased with augmented dobutamine infusion (2.9±1.5 to 5.5±3.3 mm Hg/cm 2 and 3.3±1.6 to 6.4±3.9 mm Hg/cm 2 , respectively; P P Conclusions RV performance can be assessed by pressure-area relations in patients with heart failure. RV contractile reserve in response to increases in dobutamine was associated with a good short-term outcome and may be of prognostic value in patients with severe heart failure.

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 (P0.05) 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.

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.

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.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.The patients had significant improvement in the transitional-dyspnea index after surgery (P0.001). 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, P0.001). 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 (P0.001). Forced expiratory volume in one second increased (from 0.87+/-0.36 to 1.11+/-0.45 liters, P0.001). 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).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.

Purpose: Although pyruvate supplementation enhances endurance in humans and increases cardiac output in dogs, its effects on cardiac and peripheral vascular function are not known. Thus, we assessed the cardiovascular effects of pyruvate infusion. Materials and Methods: Aortic, left ventricular (LV), and pulmonary (Ppa) pressures and LV stroke volume (Svlv; derived from aortic flow probe) were measured after thoracotomy in eight anesthetized dogs. LV area or volume changes were measured using either an epicardial echocardiography (n = 6) or a conductance catheter (n = 2). LV end-systolic elastance (Eeslv) and preload recruitable stroke force (PRSFlv) relations, as estimates of contractility, were generated by transient inferior vena cave occlusion. Simultaneous stroke volume to arterial pressure relations during the occlusions were used to measure arterial elastance (Ea), and steady-state systemic and pulmonary vascular resistances were used as measures of arterial tone. Graded doses of pyruvate (8, 16, and 32 mg/kg/min), dobutamine (positive control) and propranolol (negative control) and placebo (volume control) were sequentially given. Results: Dobutamine increased Eeslv PRSFlv, whereas propranolol had the opposite effect on Eeslv and PRSFlv. Pyruvate at 32 mg/kg/min increased heart rate, Ppa, and SVlv and decreased LV end-diastolic area, and systemic vascular resistance without changing arterial pressure, Eeslv PRSFlv. or Ea. Conclusions: We conclude that pyruvate infusion in normal dogs induces venodilation but does not alter either cardiac contractility or arterial tone.

We examined the relation between changes in R-to-T wave amplitude ratios (R:T) and left ventricular (LV) performance as cardiac output was rapidly varied by inferior vena caval occlusion in 6 subjects prior to cardiopulmonary bypass. To assess the influence of contractility, paired studies before and after bypass were performed in 4 subjects. Stroke volume and cardiac output were assessed by aortic flow probe, and transesophageal echocardiographic LV area measures using the automated border-detection method were used to give LV stroke area, stroke force, maximal LV area, fractional area change, end-systolic elastance, and preload recruitable stroke force. Data were collected on computer and analyzed by linear regression. Significant changes in R:T and measured LV variables during the inferior vena caval occlusion were stroke volume (r = 0.81), LV stroke area (r = 0.77), LV stroke force (r = 0.81), maximal LV area (r = 0.78), and cardiac output (r = 0.80). However, R:T varied inconsistently in relation to fractional area change. After cardiopulmonary bypass, the linear relation between R:T with LV stroke force, LV stroke volume, and maximal LV area persisted, but at a lesser slope. Although absolute pre-inferior vena caval occlusion R:T did not correlate with end-systolic elastance or preload recruitable stroke force, the change in the slope of these linear relations correlated well with the change in end-systolic elastance after surgery (r = 0.92). Instantaneous changes in electrocardiographic morphology reflect changes in LV preload-dependent variables, whereas long-term changes in electrocardiographic morphology may also reflect changes in contractile state.

Aim: Left ventricular (LV) global longitudinal strain (GLS) reflects LV systolic function and correlates inversely with the extent of LV myocardial scar and fibrosis. The present subanalysis of the Echocardiography Guided CRT trial investigated the prognostic value of LV GLS in patients with narrow QRS complex.Methods and results: Left ventricular (LV) global longitudinal strain (GLS) was measured on the apical 2-, 4- and 3-chamber views using speckle tracking analysis. Measurement of baseline LV GLS was feasible in 755 patients (374 with cardiac resynchronization therapy (CRT)-ON and 381 with CRT-OFF). The median value of LV GLS in the overall population was 7.9%, interquartile range 6.2-10.1%. After a mean follow-up period of 19.4 months, 95 patients in the CRT-OFF group and 111 in the CRT-ON group reached the combined primary endpoint of all-cause mortality and heart failure hospitalization. Each 1% absolute unit decrease in LV GLS was independently associated with 11% increase in the risk to reach the primary endpoint (Hazard ratio 1.11; 95% confidence interval 95% 1.04-1.17, P Conclusion: Low LV GLS is associated with poor outcome in heart failure patients with QRS width

Background On-line determination of right ventricular (RV) volume to assess its function is clinically difficult. Echocardiographic automated border detection measures of left ventricular (LV) cavity area have been shown to reflect changes in volume, and pressure-area relations have been used to estimate LV contractility. The potential for RV cavity area to estimate changes in volume and to assess RV function, however, has not been evaluated. Accordingly, the objective of this study was to determine the relation between echocardiographic automated border-detected RV cross-sectional area and true volume and to assess the potential for end-systolic pressure-area relations to estimate RV function in an isovolumically contracting isolated canine heart preparation. Methods and Results Eight excised dog hearts with both right and left intraventricular balloons were perfused in an ex vivo apparatus in which both ventricular volumes were controlled independently. RV area data from the level of the left midventricular short-axis plane and pressure data were recorded on a computer through a customized hardware and software interface with the ultrasound system. RV volumes were varied from 9.4±3.9 to 43.8±6.9 mL at each of three different LV volume ranges (low range, 12.5±3.8 mL; medium range, 23.9±5.6 mL; and high range, 37.5±5.4 mL). The variation of RV area during isovolumic contraction, which we called deformational area change, was considerable (1.49±0.68 cm 2 mean±SD) but did not change significantly with changing RV and LV volumes. Linear regression analysis correlated the maximum, minimum, and mean automated border-detected RV area during isovolumic contraction with absolute volume. A predominantly linear relation was observed, with the group mean r =.98 ( y =0.16 x +0.97; SEE=0.21 cm 2 ). The effect of LV volume on RV area-volume relation was a significant parallel downward shift ( P Conclusions Echocardiographic automated border-detected RV area reflects changes in RV volume under a constant LV volume, and the derived end-systolic pressure-area relation has potential for on-line assessment of RV function.

The surgical approach to lung transplantation for patients with severe pulmonary hypertension will be dependent on the primary disease and specific cardiac anatomy. To determine the safety and utility of transesophageal echocardiography in the management of patients with severe pulmonary hypertension who are being evaluated for lung transplantation, we studied 48 consecutive patients, aged 38 +/- 11 years, with pulmonary artery systolic pressure of 70 mm Hg or greater. All patients previously underwent left and right heart catheterization, transthoracic echocardiography, and radionuclide ventriculography. Transesophageal echocardiography was tolerated well by all patients. Additional data that significantly altered surgical therapy was found in 12 of 48 patients (25%): proximal pulmonary artery thrombi (3), patent foramen ovale with significant right to left shunting (2), atrial septal defect (2), double-outlet right ventricle (2), ventricular septal defect (2), and exclusion of atrial septal defect (1). These findings were confirmed surgically in all patients except 3, who died awaiting transplantation. Transesophageal echocardiography is useful in the evaluation of patients with severe pulmonary hypertension.

Consequences of conduction abnormalities requiring a permanent pacemaker (PPM) after transcatheter aortic valve replacement (TAVR) are still unclear. Our aim was to determine risk factors for PPM after TAVR and associated effects on LV function over time. Of 389 consecutive TAVR patients, we

Right ventricular (RV) remodeling is important to humans with pulmonary hypertension (PH). Small animal models of PH are used to investigate novel therapies, but assessment of RV remodeling is difficult. The aim was to compare a new RV remodeling index (echo RV to LV area ratio) to invasive

Pulmonary hypertension (PH) is a progressive disease with variable prognosis and expanding treatment options. Guidelines have supported individual echocardiographic prognostic markers, but their ability to predict mortality remain unclear. The aim was to assess the prognostic significance of

Peripartum cardiomyopathy (PPCM) has a variable clinical course. The aim was to test the hypothesis that global longitudinal strain (GLS) at presentation has prognostic value for left ventricular (LV) recovery and clinical outcomes. Of 100 PPCM patients in the multicenter Investigation in Pregnancy

Aneurysmal subarachnoid hemorrhage (SAH) may be associated with acute cardiac dysfunction which is variable. The aim was to test the hypothesis that neurocardiac injury in SAH is associated with left ventricular (LV) regional discoordination. We prospectively studied 151 patients with SAH (

LVEF and abnormalities of electrical activation, in particular left bundle branch block (LBBB). The dyssynchronous pattern typically associated with LBBB is early septal activation and delayed free-wall activation, with mechanical activation terminating in the LV posterolateral region. Accordingly, CRT, consisting of LV pacing from the delayed LV posterolateral region and septal activation from a right ventricular (RV) lead, results in mechanical resynchronization coupled with associated improvements in LV ejection effectiveness and reverse remodeling. The challenge has been that patients selected for CRT based on widening of the QRS interval alone have a variable response to resynchronization therapy, with approximately one-third of patients apparently failing to benefit. This substantial treatment failure rate provides a real motivation to increase our understanding of the biological substrates of the dyssynchronous heart, in order to improve the delivery of therapy, with a goal toward developing an individualized therapy delivery algorithm so that CRT is delivered optimally.

Mixed cohorts of patients with ischemic and nonischemic end-stage heart failure (HF) with a QRS duration of ≥120 ms and requiring intravenous inotropes do not appear to benefit from cardiac resynchronization therapy (CRT). However, CRT does provide greater benefit to patients with nonischemic cardiomyopathy and might, therefore, be able to reverse the HF syndrome in such patients who are inotrope dependent. To address this question, 226 patients with nonischemic cardiomyopathy who received a CRT-defibrillator and who had a left ventricular ejection fraction of ≤35% and QRS of ≥120 ms were followed up for the outcomes of death, transplantation, and ventricular assist device placement. Follow-up echocardiograms were performed in patients with ≥6 months of transplant- and ventricular assist device-free survival after CRT. The patients were divided into 3 groups: (1) never took inotropes (n = 180), (2) weaned from inotropes before CRT (n = 30), and (3) dependent on inotropes at CRT implantation (n = 16). At 47 ± 30 months of follow-up, the patients who had never taken inotropes had had the longest transplant- and ventricular assist device-free survival. The inotrope-dependent patients had the worst outcomes, and the patients weaned from inotropes experienced intermediate outcomes (p

Aims Because benefits of cardiac resynchronization therapy (CRT) appear to be less favourable in non-left bundle branch block (LBBB) patients, this prospective longitudinal study tested the hypothesis that QRS morphology and echocardiographic mechanical dyssynchrony were associated with long-term outcome after CRT. Methods and results Two-hundred and seventy-eight consecutive New York Heart Association class III and IV CRT patients with QRS ≥120 ms and ejection fraction ≤35% were studied. The pre-specified primary endpoint was death, heart transplant, or left ventricular assist device over 4 years. Dyssynchrony assessed before CRT included interventricular mechanical delay (IVMD) and speckle-tracking radial strain using pre-specified cut-offs for each. Of 254 with baseline quantitative echocardiographic data available, 128 had LBBB, 81 had intraventricular conduction delay (IVCD), and 45 had right bundle branch block (RBBB). Radial dyssynchrony was observed in 85% of the patients with LBBB, 59% with IVCD*, and 40% with RBBB* (* P < 0.01 vs. LBBB). Of 248 (98%) with follow-up, LBBB patients had a significantly more favourable long-term survival than non-LBBB patients. However, non-LBBB patients with dyssynchrony had a more favourable event-free survival than those without dyssynchrony: radial dyssynchrony hazard ratio 2.6, 95% confidence interval (CI) 1.47–4.53 ( P = 0.0008) and IVMD hazard ratio 4.9, 95% CI 2.60–9.16 ( P = 0.0007). Right bundle branch block patients who lacked dyssynchrony had the least favourable outcome. Conclusion Non-LBBB patients with dyssynchrony had a more favourable long-term survival than non-LBBB patients who lacked dyssynchrony. Mechanical dyssynchrony and QRS morphology are associated with outcome following CRT.

To assess the potential effects of coronary artery bypass surgery on left ventricular diastolic filling, 12 patients, aged 65 ± 11 years, were studied by serial transesophageal Doppler echocardiograms. Doppler measures of mitral inflow velocity were made before, immediately after, 4 h after, and 20 h after cardiopulmonary bypass (CPB). Left atrial pressure was directly measured and controlled at 10 ± 2 mm Hg for each study period. Mitral maximal early inflow velocity (E)/maximal atrial velocity (A) ratios and atrial filling fractions were calculated as indexes of diastolic function from maximal E and A velocities and their time velocity integrals, respectively. Data sets were available for serial comparison in 11 patients and were also compared with an age-matched control group of normal values. The results of E/A ratios were as follows: control group—1.4 ± 0.2; before CPB—1.7 ± 0.6; immediately after CPB—1.0 ± 0.2 (p

The rapid assessment of the response of right ventricular (RV) performance to decreasing levels of mechanical assistance may be an important adjunct in determining if a patient can tolerate the removal of such a device. This report describes the use of on-line pressure area relationships to assess RV function in a patient supported with an RV assist device (RVAD). Mid RV short axis cross-sectional area was measured on-line by transesophageal echocardiography with an automated endocardial border detection feature. RV pressure was measured with a high fidelity catheter. Pressure and area were plotted simultaneously on a computer workstation interfaced with the pressure and echo systems to yield on-line pressure area loops. The following indices of RV performance were calculated while RVAD flow was decreased in 1 L/min increments: stroke work' (SW' = integral of PdA)[mmHg*cm2], stroke area (SA = Maximum Area-Minimum Area)[cm2], and fractional area change (FAC = SA/Maximum Area*100)[%]. SW', SA, and FAC significantly increased with decreasing RVAD flow: SW'(from 32 to 61 mmHg*cm2), SA (from 2.58 to 4.37 cm2), and FAC (from 20 to 32%). In conclusion, the increase in these parameters of RV performance with decreasing mechanical assistance suggested that this patient would tolerate removal of the RVAD, which was subsequently successful. This method of on-line pressure area relationships may be useful to predict the need for further mechanical assistance.

Recent echocardiographic ABD algorithms can estimate LV volume on-line from a single long-axis plane. The objective of this study was to assess the capability and limitations of transesophageal ABD to estimate stroke volume and cardiac output in patients before and after coronary artery bypass surgery by correlating these data with simultaneous thermodilution measurements. ABD data were acquired on-line from the transverse-plane four-chamber view and the longitudinal-plane two-chamber view and calculated by automated area-length and Simpson's rule formulas for volume. Thirty-three studies were attempted in 18 patients. Technically adequate ABD data were available in all patients from at least one view. Twenty-two (67%) of 33 studies from the four-chamber view and 27 (82%) of 33 studies from the two-chamber view were technically adequate. Cardiac output by all ABD methods was significantly correlated with thermodilution values (r range 0.72 to 0.89; SEE range 0.48 to 0.55 L/min). The two-chamber view underestimated cardiac output slightly, by an average of 0.4 L/min, whereas the four-chamber view consistently underestimated cardiac output by an average of 1.9 L/min. The area-length and Simpson's rule algorithms produced similar results. Biplane transesophageal ABD is an alternative method for estimating cardiac output; the two-chamber view in particular has potential for on-line volume determination.

The end-diastolic pressure-volume relationship can be used to describe left ventricular (LV) compliance. The objective of this study was to utilize measurements of LV cavity area by echocardiographic automated border detection and pressure data to estimate the end-diastolic pressure-volume curve in an isolated heart preparation where true volume could be measured by an intraventricular balloon. Six dog hearts were excised for placement of an intraventricular balloon and a micromanometer catheter and perfused in an ex vivo circuit. Mid-ventricular short-axis images were used to measure cross-sectional area by automated border detection while LV volumes were increased from 5 ml to maximal volume (30-40 ml) in each preparation. Simultaneous area and pressure data were recorded on a computer workstation through a customized interface with the ultrasound system. Three runs of varying LV volumes at 1 ml increments were performed on each of 6 hearts for a total of 1,080 simultaneous measurements. Pressure-volume and pressure-area curves were analyzed by linear regression analyses, the slope of which was used to estimate compliance. End-diastolic pressure-area and pressure-volume relationships were significantly correlated with mean r = 0.97 +/- 0.02 (p < 0.001) from individual hearts. The slopes which served to estimate compliance of the individual pressure-area and pressure-volume curves were similar and differed by only 7 +/- 4%. A similar correlation was observed by second order regression analyses with r = 0.97 +/- 0.01 (p < 0.001) for pressure-area and r = 0.98 +/- 0.01 (p < 0.001) for pressure-volume relationships.(ABSTRACT TRUNCATED AT 250 WORDS)

Nitric oxide (NO) production by the human heart has been demonstrated in patients undergoing cardiac surgery. Similar to what has been described in other species, a basal production of NO by the human heart is seen (126 +/- 42 pmol/min per gram). Following reperfusion, at the end of the procedure, the level of NO production increases significantly reaching concentrations of 1430 +/- 330 pmol/min per gram. Increased activity for the enzyme NO synthase (NOS) (8.0 +/- 1.2 pmol/mg prebypass vs 26.4 +/- 4.8 pmol/mg postbypass) coincides with changes in NO production and occurs at a time when myocardial stunning is clinically detectable. The significance of these findings is discussed and suggest a role for NO in the pathophysiology of myocardial stunning.

Incomplete ventricular septal tears are uncommon or probably underreported cardiac lesions caused by blunt chest trauma. This report describes two cases of incomplete ventricular septal tears that were not suspected clinically. Transthoracic and transesophageal echocardiography provided the diagnostic information in both of these cases. Despite associated valvular lesions, the patients' stable in-hospital course lead to the decision to treat them medically with no specific treatment to the incomplete ventricular septal tears. Accordingly, these two cases were observed for a mean period of 1.5 years with serial echocardiographic studies to track the natural history of these lesions. During the follow-up period, both of these cases did not manifest any changes in the extent of ventricular septal tear, septal structure, or any left-to-right shunting through the tear. There were no significant changes in left ventricular size, shape, or systolic function. Thus echocardiographic imaging proved to be useful both in initial diagnosis and follow-up.

Background: Left ventricular assist device (LVAD) support as bridge to recovery (BTR) is uncommon for subjects with chronic heart failure. Myocardial recovery is more evident in recent onset nonischemic cardiomyopathy (ROCM); however, the prevalence of BTR in this subset has not been addressed. Methods and Results: We examined the use of LVAD support for subjects with ROCM in the Intervention in Myocarditis and Acute Cardiomyopathy 2 (IMAC2) study. The overall cohort (n 5 373) was 38% female, 21% black, with a mean age of 45 6 14 years. LVAD support was used in 3.8% (n 5 14, 43% female, age 32 6 10). Of LVAD subjects, 57% (8/14) were BTR, including 73% (8/11) of subjects with symptoms #4 months at the time of support. Left ventricular end-diastolic diameter (LVEDD) was smaller in BTR than nonrecovered (NR) subjects (P 5 .04). Myocardial inflammation was more common in BTR (75% versus 0%, P 5 .005), whereas fibrosis was less evident (25% versus 100%, P 5 .005). Of BTR subjects, 7/8 (87.5%) were alive and free of transplant with median follow-up of 19 months. Conclusion: In a multicenter registry of ROCM, BTR was common and occurred in the majority of subjects requiring LVAD support. Histology and LVEDD may assist in predicting potential for BTR in ROCM. (J Cardiac Fail 2012;18:755e761)

Background The magnitude of benefit of cardiac resynchronization therapy (CRT) varies significantly among its recipients; approximately 30% of CRT patients do not report clinical improvement. Optimization of CRT pacing parameters can further improve cardiac function, both acutely and chronically. Echocardiographic optimization is used in clinical practice, but it is time and resource consuming. In addition, optimal settings at rest may change later with activity or cardiac remodeling. The adaptive CRT (aCRT) algorithm was designed to provide automatic ambulatory adjustment of CRT pacing configuration (left ventricular or biventricular pacing) and device delays based on periodic measurement of electrical conduction intervals. Methods The aCRT algorithm is currently undergoing evaluation in a prospective, randomized, double-blinded, worldwide clinical trial. The trial enrolled 522 patients, who satisfied standard clinical indications for a CRT device. Within 2 weeks after the implant, the patients were randomized to aCRT versus echo-optimized biventricular pacing (Echo) settings in 2:1 ratio and followed up at 1-, 3-, 6-, and 12-month postrandomization. The noninferiority primary trial objectives at 6-month postrandomization are to demonstrate that ( a ) the percentage of aCRT patients who improved in their clinical composite score is at least as high as the percentage of Echo patients; ( b ) cardiac performance as assessed by echocardiography is similar when using aCRT settings versus echo-optimized settings; and ( c ) aCRT does not result in inappropriate device settings. First and last patient enrollments occurred in November 2009 and December 2010, respectively. Conclusions The safety and efficacy of the aCRT algorithm will be evaluated in this ongoing clinical trial.

BACKGROUND: Quantification of left ventricular (LV) dyssynchrony allows for objective measures of resynchronization therapy (CRT) effectiveness. We tested the hypothesis that site of LV pacing, fusion beats and baseline contractility alter contraction synchrony as quantified by regional and global measures of LV performance. METHODS AND RESULTS: In 8 open-chested pentobarbital-anesthetized canine preparations we compared the effects of right atrial (RA), RA-high right ventricular (RV) free wall, as a model of left bundle branch block contraction pattern, RA-LV apex (LVa), RA-LV free wall (LVfw), and RA-RV-apical LV (CRTa) and RA-RV-free wall LV (CRTfw), as CRT. LV pressure-volume loops recorded using high-fidelity pressure and conductance catheters and echocardiographic angle-corrected color-coded strain imaging of mid-LV short axis views analyzed radial strain from six segments. To control for contractile state esmolol-induced beta blockage was studied, and in 5 dogs to control for RA and ventricular pacing fusion beat artifacts, repeat studies were done following AV node ablation. RA-RV pacing reduced stroke work (SW) (57±18 to 33±13* mmHg·mL,*p0.05 vs RA pacing), decreased LV end-diastolic volume and induced marked radial dyssynchrony (maximal time difference between peak segmental strain) from 31±15 to 234±60* ms. Changes in radial dyssynchrony correlated significantly with changes in SW (r=-0.53, p0.01). Dyssynchrony improved with both CRTa and CRTfw (69*±31 and 98*±63 ms, respectively) while SW only improved with CRTa (62±22* and 37±13 mmHg·mL, respectively * p0.05 vs RV pacing). CRTa also tended to increased LV end-diastolic volume over RA-RV. Esmolol slowed HR from 118±10 to 108±10 beats/min* and tended to decrease contractility (end-systolic elastance (Ees) from 12.1±7.9 to 8.9±3.9 mmHg/ml, p=0.167) but did not alter the degree of RV-pacing induced dyssynchrony. AV ablation had no effect on the observed apical and free wall contraction differences seen during baseline conditions. CONCLUSION: Although both CRTa and CRTfw reduced contraction dyssynchrony, CRTa tended to improve global LV performance more by increasing end-diastolic volume. Thus, CRT may improve global LV performance differently, depending on the LV pacing site.

Cardiac resynchronization therapy (CRT) has been proven to be a major benefit to severely symptomatic heart failure patients with widened QRS duration ≥ 120 ms, and reduced ejection fraction (EF) ≤ 35%. The prevailing evidence supports that multi-site pacing improves abnormalities of left ventricular (LV) mechanical activation, known as dyssynchrony, as the principal therapeutic effect of CRT. The most common pattern of dyssynchrony is represented by left bundle branch block (LBBB), which is characterized by early septal mechanical activation followed by delayed posterior and lateral wall activation. Although several variations in abnormalities of electrical and mechanical activation may exist, the electrical dispersion manifest by QRS widening is believed to be a surrogate for mechanical dyssynchrony. Current clinical guidelines based on selection criteria used in the CRT trials use QRS widening as a marker for dyssynchrony. Unfortunately, approximately one-third of patients receiving CRT do not seem to benefit using these routine clinical selection criteria. Since CRT implantation is expensive and associated with a small but significant procedural risk of complications, efforts have been focused on improvement in patient selection. The study of echocardiographic dyssynchrony has led to the important observation that there is a subset of patients with widened QRS duration that do not have significant mechanical dyssynchrony. The reasons for the disassociation of mechanical dyssynchrony from QRS widening are unclear, but most existing information indicates that the patients with QRS widening who lack significant mechanical dyssynchrony do not respond favorably to CRT and appear to have a worse prognosis.

Cardiac resynchronization therapy (CRT) has undoubtedly been of major benefit to many patients who have heart failure with wide QRS complexes, improving symptoms and survival. Unfortunately, the CRT nonresponder rate remains at about one third with the use of the current selection criteria. An appropriate goal is to better understand the factors related to nonresponse to improve patient care. In a recent study of 229 CRT patients, we reported that the absence of echocardiographic dyssynchrony was associated with a significantly less favorable event-free survival with the use of the combined end point of death, heart transplantation, or left ventricular assist device over 4 years after CRT.1 We appreciate the commendation from Fornwalt et al in their letter and …

Objectives: To assess the impact of cardiac resynchronization therapy (CRT) with or without atrial overdrive pacing, on sleep-related breathing disorder (SRBD). Introduction: CRT may have a positive influence on SRBD in patients who qualify for the therapy. Data are inconclusive in patients with obstructive SRBD. Methods: Consenting patients eligible for CRT underwent a baseline polysomnography (PSG) 2 weeks after implantation during which pacing was withheld. Patients with an apnea hypopnea index (AHI) ≥15 but

The purpose of this study was to evaluate mechanical dyssynchrony in patients with acute onset cardiomyopathy with narrow QRS interval, and its association with improvements in left ventricular (LV) function.LV dyssynchrony has been usually studied in patients with chronic heart failure and wide QRS in the context of cardiac resynchronization therapy.We studied 201 patients enrolled in the IMAC-2 (Inflammatory Mediators in Acute Cardiomyopathy) trial with recent onset nonischemic cardiomyopathy and ejection fraction40%. Dyssynchrony was assessed using speckle-tracking velocity vector imaging. Diastolic function was assessed by mitral inflow E and mitral E' annular velocities (E/E'). A normal control group of 15 normal volunteers was studied for comparison.Although mean QRS was narrow (98 ± 21 ms), 108 (54%) acute cardiomyopathy patients had significant LV dyssynchrony at presentation: opposing wall delay 89 ± 51 ms, versus 35 ± 11 ms in controls, and 12-site standard deviation 43 ± 23, versus 24 ± 8 ms in controls (p0.001). Patients with dyssynchrony had greater degrees of diastolic dysfunction: E/E' 15 ± 8 versus 12 ± 6 (p0.05). At 6 months, group mean ejection fraction improved from 23 ± 8% to 40 ± 12% and E/E' improved from 14 ± 7 to 9 ± 5 (both p0.001). Dyssynchrony improved from 89 ± 51 ms to 52 ± 35 ms in maximum opposing wall delay, and 43 ± 23 ms to 32 ± 19 ms in 12-site standard deviation, and the prevalence of dyssynchrony decreased to 12% after 6 months (p0.001 vs. baseline).Mechanical dyssynchrony was observed in a significant number of patients with acute onset cardiomyopathy, despite having a narrow QRS interval. Resolution of dyssynchrony associated with improvements in LV function occurred in the large majority of these patients.

A new index to assess left ventricular (LV) function in patients implanted with continuous flow left-ventricular assist devices (LVADs) is proposed. Derived from the pump flow signal, this index is defined as the coefficient (k) of the semilogarithmic relationship between "pseudo-ejection" fraction (pEF) and the volume discharged by the pump in diastole, (V d). pEF is defined as the ratio of the "pseudo-stroke volume" (pSV) to V d. The pseudo-stroke volume is the difference between V d and the volume discharged by the pump in systole (V s), both obtained by integrating pump flow with respect to time in a cardiac cycle. k was compared in-vivo with others two indices: the LV pressure-based index, M(TP), and the pump flow-based index, I(Q). M(TP) is the slope of the linear regression between the "triple-product" and end-diastolic pressure, EDP. The triple-product, TP = LV SP.dP/dt(max). HR, is the product of LV systolic pressure, maximum time-derivative of LV pressure, and heart rate. I(Q) is the slope of the linear regression between maximum time-derivative of pump flow, dQ/dt(max), and pump flow peak-to-peak amplitude variation, Q(P2P). To test the response of k to contractile state changes, contractility was altered through pharmacological interventions. The absolute value of k decreased from 1.354 ± 0.25 (baseline) to 0.685 ± 0.21 after esmolol infusion. The proposed index is sensitive to changes in inotropic state, and has the potential to be used clinically to assess contractile function of patients implanted with VAD.

Echocardiographic automated border detection can determine the interface between blood and myocardial tissue and calculate left ventricular (LV) cavity area in real-time. The objective was to determine if on-line measurements of LV cavity area by transesophageal automated border detection could be used to determine beat-to-beat changes in stroke volume in humans. Studies were attempted on 9 consecutive patients, aged 66 +/- 8 years, undergoing coronary bypass surgery. Stroke volume was measured by electromagnetic flow from the ascending aorta, and LV cavity area was measured at the midventricular short-axis level. Simultaneous area and flow data were recorded on a computer workstation through a customized interface with the ultrasound system. Recordings were performed during baseline apnea and rapid alterations induced by inferior vena caval occlusions before and after cardiopulmonary bypass. Measurements of stroke area (maximal area-minimal area) were correlated with stroke volume for matched beats. Data were available for analysis on 8 of 9 patients before and on 5 patients after cardiopulmonary bypass for 644 beats. Stroke area was closely correlated with stroke volume both before (mean R = 0.94 +/- 0.03, SEE = 0.33 +/- 0.12 cm2) and after (mean R = 0.92 +/- 0.05, SEE = 0.59 +/- 0.81 cm2) cardiopulmonary bypass. The slopes of these stroke area-stroke volume relations were quite reproducible from before to after cardiopulmonary bypass in the same patient but varied between individual patients. Transesophageal automated border detection has potential for on-line estimation of changes in stroke volume in selected patients.

Isoflurane may precipitate ischemia in patients with coronary artery disease, presumably via "coronary steal." We sought to examine whether myocardial ischemia is more common in patients with coronary artery disease receiving isoflurane (0.7%) than in a control group receiving enflurane (0.9%). Thirty-eight patients scheduled for coronary artery bypass surgery were randomly assigned one anesthetic and monitored for ischemia. All patients had ejection fractions of at least 45%. Extraneous causes of ischemia were controlled as much as possible: arterial blood pressure was maintained within 20% of baseline (primarily with phenylephrine), heart rate was maintained below 80 bpm, effects from endotracheal intubation were monitored, and measurements were made before incision. Electrocardiogram, transthoracic echocardiography, and coronary sinus lactate measurement were used to detect ischemia. Measurements were made after insertion of vascular catheters, after intubation, and after 20 min of breathing the inhaled anesthetic. During the awake period and after induction of anesthesia with fentanyl (25 micrograms/kg), there was no significant difference detected between the two groups in incidence of ischemia: 20% in the enflurane group and 22% in the isoflurane group (P = 0.38). After 20 min of receiving the inhaled anesthetic, the incidence of ischemia in the isoflurane group increased to 50%, whereas the incidence in the enflurane group was unchanged at 20% (P = 0.02). These results show that, even with strict control of hemodynamics, isoflurane is associated with more myocardial ischemia than is enflurane.

Echocardiographic automated border detection (ABD) is a new on-line technique that can determine the interface between blood and myocardial tissue and calculate left ventricular (LV) cavity area in real time. The objective of this study was to determine whether ABD measurements of the LV cavity area could be used to estimate LV stroke volume at basal conditions and during large changes in LV stroke volume induced by inferior vena caval occlusions in an open-chest canine model. Seven dogs had LV stroke volume measured by electromagnetic flow from the ascending aorta with epicardial recordings of ABD echocardiographic area at the midventricular short-axis level. Simultaneous beats of stroke volume were recorded along with ABD echo area during baseline apnea and during IVC occlusions. Neither ABD echo stroke area nor stroke volume varied significantly during apnea baseline. Changes in stroke area were closely correlated with changes in stroke volume for 540 matched beats from 24 IVC occlusions: R = 0.93, standard error of the estimate = 5%, y = 0.92x + 0.4 (p < 0.001). Echocardiographic ABD appears to be a promising new on-line method of determining rapid alterations in LV stroke volume; it also has potential applications to multiple investigational and clinical settings.

Glycopyrrolate is an anticholinergic agent used to dry oral secretions and has been advocated for routine use with transesophageal echocardiography (TEE). To evaluate the safety and efficacy of glycopyrrolate for this unique application, a prospective double-blind placebo-controlled study of glycopyrrolate was performed in 61 patients who were awake while undergoing TEE. Thirty patients were randomized to the standard dose of glycopyrrolate (0.2 mg intravenously), and 31 patients received 1 ml of saline solution as placebo. Intravenous midazolam was used for sedation in all but one patient. Heart rate, electrocardiogram, blood pressure, and oxygen saturation were continuously monitored before, during, and after TEE. The patients scored their comfort immediately after TEE and were interviewed at 24 hours for side effects. The operator scored the ease of performing the TEE. No complications occurred in either group. Changes in vital signs and oxygen saturation were similar in both groups. The operator ease and patient comfort was similar in both groups. A significantly higher incidence of the following side effects was observed at 24 hours in patients who received glycopyrrolate versus those who received placebo: sore throat, 63% versus 19%; dry mouth, 43% versus 6%; and urinary retention, 16% versus 0% (p0.05 for all). No benefit from glycopyrrolate was noted in operator ease or patient comfort. In conclusion, glycopyrrolate is not recommended for routine use when performing TEE on patients who are awake.