Kevin V. Burns

Results of the PROspective MInnesota Study of ECHO/TDI in Cardiac Resynchronization Therapy (PROMISE-CRT) Study

BACKGROUND Retrospective single-center studies have shown that measures of mechanical dyssynchrony before cardiac resynchronization therapy (CRT), or acute changes after CRT, predict response better than QRS duration. The Prospective Minnesota Study of Echocardiographic/TDI in Cardiac Resynchronization Therapy (PROMISE-CRT) study was a prospective multicenter study designed to determine whether acute (1 week) changes in mechanical dyssynchrony were associated with response to CRT. METHODS AND RESULTS Nine Minnesota Heart Failure Consortium centers enrolled 71 patients with standard indications for CRT. Left ventricular (LV) size, function, and mechanical dyssynchrony (echocardiography [ECHO], tissue Doppler imaging [TDI], speckle-tracking echocardiography [STE]) as well as 6-minute walk distance and Minnesota Living with Heart Failure Questionnaire scores were measured at baseline and 3 and 6 months after CRT. Acute change in mechanical dyssynchrony was not associated with clinical response to CRT. Acute change in STE radial dyssynchrony explained 73% of the individual variation in reverse remodeling. Baseline measures of mechanical dyssynchrony were associated with reverse remodeling (but not clinical) response, with 4 measures each explaining 12% to 30% of individual variation. CONCLUSIONS Acute changes in radial mechanical dyssynchrony, as measured by STE, and other baseline mechanical dyssynchrony measures were associated with CRT reverse remodeling. These data support the hypothesis that acute improvement in LV mechanical dyssynchrony is an important mechanism contributing to LV reverse remodeling with CRT.

Intramural dyssynchrony from acute right ventricular apical pacing in human subjects with normal left ventricular function.

Ventricular pacing causes early myocardial shortening at the pacing site and pre-stretch at the opposing ventricular wall. This contraction pattern is energetically inefficient and may lead to decreased cardiac function. This study was designed to describe the acute effects of right ventricular apical (RVa) pacing on dyssynchrony and systolic function in human subjects with normal left ventricular (LV) function and compare these effects to pacing from alternate ventricular sites. Patients (n = 26) undergoing an electrophysiology evaluation were studied during atrial pacing (AAI) and dual chamber pacing from the RVa, left ventricular free wall (LVfw), and the combination of RVa and LVfw (BiV). Tissue Doppler imaging was used to measure intramural dyssynchrony by utilizing an integrated cross-correlation synchrony index (CCSI) from the apical 4-chamber view. RVa and BiV pacing significantly reduced systolic function as measured by longitudinal systolic contraction amplitude (SCAlong) (p < 0.05) and LV velocity time integral (VTI) (p < 0.05) compared to AAI and LVfw pacing. RVa (and to a lesser extent BiV) pacing resulted in septal and lateral intramural dyssynchrony as indicated by significantly (p < 0.05) lower CCSI values as compared to AAI. CCSI was significantly (p < 0.05) worse during RVa than LVfw pacing. In patients with normal LV function, acute ventricular pacing in the RVa alone, or in conjunction with LVfw pacing (BiV), results in impaired regional and global LV systolic function and intramural dyssynchrony as compared to LVfw pacing alone.

Echocardiographic and clinical response to cardiac resynchronization therapy in heart failure patients with and without previous right ventricular pacing

Right ventricular pacing (RVp) results in an electrocardiographic left bundle branch block pattern and can lead to heart failure. This study aimed to evaluate echocardiographic and clinical outcomes of heart failure patients with RVp upgraded to cardiac resynchronization therapy (CRT), as they are frequently excluded from multicentre studies.

Intramural dyssynchrony and response to cardiac resynchronization therapy in patients with and without previous right ventricular pacing

Right ventricular (RV) pacing is an iatrogenic cause of heart failure (HF) that has not been well studied. We assessed whether HF patients paced from the right ventricle (RVp) adversely remodel and respond to cardiac resynchronization therapy (CRT) in a similar way to HF patients without right ventricular pacing (nRVp).

Echocardiographic Improvements with Pacemaker Optimization in the Chronic Post Cardiac Resynchronization Therapy Setting

The current study assessed the acute effects of pacemaker optimization (PMO) on cardiac function using echocardiographic (ECHO) tissue Doppler imaging (TDI) in the post CRT setting. Data were analyzed from 50 consecutive patients clinically referred for PMO. Patients underwent a sequential ECHO/TDI-guided PMO study to determine optimal pacemaker settings. In 34 of 50 patients a change in pacemaker settings was made because of an objective improvement in ECHO/TDI findings. Overall, significant improvements were observed for ECHO/TDI measures of systolic function (global systolic contraction score, p < 0.001; ejection time, p < 0.05), diastolic function (diastolic filling period, p < 0.01; mitral velocity-time integral, p < 0.05) and left ventricular (LV) dyssynchrony (standard deviation of time to peak displacement, p < 0.05). In most patients referred for chronic PMO, ECHO/TDI-guided PMO can be used to objectively improve cardiac systolic function, diastolic function and/or LV dyssynchrony.

Right Ventricular Pacing, Mechanical Dyssynchrony, and Heart Failure

Cardiac pacing is a common treatment option for patients with sick sinus syndrome or atrioventricular block, with the ventricular pacing lead often secured in the convenient right ventricular (RV) apical location. While RV pacing reduces symptoms and limitations associated with heart block, it may have detrimental effects on cardiac structure and function, leading to heart failure (HF) in some patients. RV pacing creates electrical dyssynchrony similar to a left-bundle branch block, with conduction occurring cell-by-cell rather than through the His–Purkinje network. Studies have shown that impairment of myocardial metabolism, structure, and function related to RV pacing occurs regionally (most prominently near the pacing site) and globally, within the left ventricle. Strategies being studied to prevent or treat pacing-induced intraventricular mechanical dyssynchrony and HF include: initial biventricular rather than RV pacing in selected patients, programming to avoid or minimize RV pacing, use of alternate (non-apical) RV pacing sites, echocardiographic screening for development of pacing-induced dyssynchrony and HF, and upgrade to biventricular pacing.

Torsion and Dyssynchrony Differences Between Chronically Paced and Non-Paced Heart Failure Patients

BACKGROUND Chronic right ventricular pacing may lead to left ventricular dyssynchrony, systolic dysfunction, remodeling, and heart failure. Cardiac mechanics may differ between paced and nonpaced heart failure patients, and their optimal treatment may also differ. METHODS AND RESULTS Echocardiograms were analyzed using tissue Doppler imaging and speckle tracking echocardiography in 20 patients with chronic right ventricular pacing for complete heart block (RVP group), 29 nonpaced patients with different heart failure etiologies but ejection fractions similar to the RVP group (HF group), and 25 control subjects without pacemakers or heart failure (control group). Left ventricle volumes were smaller in RVP than HF (end-diastolic volume = 93.6 ± 25.1 mL vs. 112.1 ± 22.8 mL), but intraventricular longitudinal and radial dyssynchrony were similar. Dyssynchrony within the septum was greater (number of segments lengthening during systole = 1.9 ± 1.7 vs. 0.9 ± 1.8), systolic torsion was lower (6.2 ± 7.3° vs. 10.6 ± 4.2°), untwisting was delayed (time from peak torsion to peak untwist rate = 188 ± 141 ms vs. 102 ± 73 ms), and apical rotation was reversed in more subjects (35% vs 0%) in RVP than HF groups (P < .05 for all). CONCLUSIONS Intraventricular dyssynchrony was similar between RVP and HF groups with similar ejection fraction. However, RVP subjects had smaller ventricles, greater dyssynchrony within the septum, lower torsion, altered apical rotation, and delayed untwisting.

Multi-plane mechanical dyssynchrony in cardiac resynchronization therapy

The aims of this study were to assess the ability of several echo measures of dyssynchrony to predict CRT response and to characterize the global effect of CRT.

Cardiac resynchronization therapy in the real world: comparison with the COMPANION study.

BACKGROUND Several clinical trials have confirmed that cardiac resynchronization therapy (CRT) improves outcomes in well defined patient populations. It is uncertain, however, whether outcomes are similar in real-world clinical settings. This study compared outcomes after CRT with defibrillator (CRT-D) in a large real-world private-practice cardiology setting with those in the COMPANION multicenter trial. METHODS AND RESULTS A total of 429 consecutive patients who received CRT-D for standard indications (group 1) were retrospectively compared with the 595 patients (group 3) in the COMPANION CRT-D cohort regarding survival and survival free of cardiovascular (CV) hospitalization. A subgroup of the group 1 patients who met the COMPANION entrance criteria (group 2) was also compared with the COMPANION cohort (group 3) both with and without propensity-matching statistical analysis. Survival and survival free of CV hospitalization was better in group 1 than in group 3. Survival in group 2 with and without propensity matching was similar to group 3. However, survival free of CV hospitalization was better in the real-world patients (group 2) even after adjustment for differences in baseline characteristics. CONCLUSIONS Survival and CV hospitalization outcomes in a real-world clinical setting are as good as, or better than, those demonstrated in the COMPANION research trial.

Comparison of Cardiac Resynchronization Therapy Outcomes in Patients With New York Heart Association Functional Class I/II Versus III/IV Heart Failure

BACKGROUND Several randomized trials have shown that cardiac resynchronization therapy (CRT) benefits New York Heart Association (NYHA) functional class I/II heart failure (HF) patients, but it is unknown if similar outcomes occur in the real-world. METHODS AND RESULTS All patients receiving CRT between 2003 and 2008 with ejection fraction (EF) ≤35% and QRS duration ≥120 ms were included. Outcomes assessed were subjective clinical response, echocardiographic response, and survival free of cardiovascular (CV) hospitalization. Baseline demographics in functional class I/II (n = 155) and functional class III/IV (n = 512) were similar, except for differences in age and several comorbidities. Clinical response was similar in both groups. The functional class I/II group had a greater decrease in left ventricular (LV) end-diastolic dimension (P = .031), and trended toward greater improvements in LV end-systolic dimension (P = .056) and EF (P = .059). The functional class I/II group had a better 5-year survival rate (79 vs 54%; P < .0001) and survival free of CV hospitalization (45% vs 26%; P < .0001). CONCLUSIONS In this real-world clinical scenario, NYHA functional class I/II CRT patients improved clinical status, and LV function and size as good as or better than those in NYHA functional class III/IV patients. These observations provide further support for the use of CRT in patients with mild symptoms of HF.