Christopher L. Kaufman

Relationships of Cardiac Autonomic Function With Metabolic Abnormalities in Childhood Obesity

Objective: The objective was to examine cardiovascular autonomic (cANS) function and its potential relationships with leptin resistance, insulin resistance, oxidative stress, and inflammation in a pediatric sample with varying levels of obesity.

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.

Mechanical versus manual chest compressions in out-of-hospital cardiac arrest: a meta-analysis.

Objective:The objective of this study was to conduct a meta-analysis of literature examining rates of return of spontaneous circulation from load-distributing band and piston-driven chest compression devices as compared with manual cardiopulmonary resuscitation. Data Sources:Searches were conducted in MEDLINE, the ClinicalTrials.gov registry, and bibliographies on manufacturer websites for studies written in English. Study Selection:Selection criteria for the meta-analysis required that studies must be human controlled (randomized, historical, or case-control) investigations with confirmed out-of-hospital cases. Data Extraction:A total of 12 studies (load-distributing band cardiopulmonary resuscitation versus manual cardiopulmonary resuscitation = 8, piston-driven cardiopulmonary resuscitation versus manual cardiopulmonary resuscitation = 4), comprising a total of 6,538 subjects with 1,824 return of spontaneous circulation events, met the selection criteria. Data Synthesis:Random effects models were used to assess the relative effect of treatments on return of spontaneous circulation. Compared with manual cardiopulmonary resuscitation, load-distributing band cardiopulmonary resuscitation had significantly greater odds of return of spontaneous circulation (odds ratio, 1.62 [95% CI, 1.36, 1.92], p < 0.001). The treatment effect for piston-driven cardiopulmonary resuscitation was similar to manual cardiopulmonary resuscitation (odds ratio, 1.25 [95% CI, 0.92, 1.68];p = 0.151). The corresponding difference in percentages of return of spontaneous circulation rates from cardiopulmonary resuscitation was 8.3% for load-distributing band cardiopulmonary resuscitation and 5.2% for piston-driven cardiopulmonary resuscitation. Compared with manual cardiopulmonary resuscitation, combining both mechanical cardiopulmonary resuscitation devices produced a significant treatment effect in favor of higher odds of return of spontaneous circulation with mechanical cardiopulmonary resuscitation devices (odds ratio, 1.53 [95% CI, 1.32, 1.78], p < 0.001). Conclusion:The ability to achieve return of spontaneous circulation with mechanical chest compression devices is significantly improved when compared with manual chest compressions. In the case of load-distributing band cardiopulmonary resuscitation, it was superior to manual cardiopulmonary resuscitation as the odds of return of spontaneous circulation were over 1.6 times greater. The robustness of these findings should be tested in large randomized clinical trials.

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.

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.

Diet revision in overweight children: effect on autonomic and vascular function

In an effort to determine the effect of a 5-month dietary modification on measures of vascular and cardiac autonomic (cANS) function in overweight (OW) children, 15 OW children had standard non-invasive measures of vascular and cANS function assessed pre- and post-intervention. Body fat percentage and cANS, but not vascular, function changed significantly after the intervention. Changes in body composition in OW children due to dietary modification alone can result in modest improvements in indices of cardiac risk.

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.

Ventricular Fibrillation Waveform Changes during Controlled Coronary Perfusion Using Extracorporeal Circulation in a Swine Model

Background Several characteristics of the ventricular fibrillation (VF) waveform have been found predictive of successful defibrillation and hypothesized to reflect the myocardial energy state. In an open-chest swine model of VF, we modeled “average CPR” using extracorporeal circulation (ECC) and assessed the time course of coronary blood flow, myocardial metabolism, and myocardial structure in relation to the amplitude spectral area (AMSA) of the VF waveform without artifacts related to chest compression. Methods VF was induced and left untreated for 8 minutes in 16 swine. ECC was then started adjusting its flow to maintain a coronary perfusion pressure of 10 mmHg for 10 minutes. AMSA was calculated in the frequency domain and analyzed continuously with a 2.1 s timeframe and a Tukey window that moved ahead every 0.5 s. Results AMSA progressively declined during untreated VF. With ECC, AMSA increased from 7.0 ± 1.9 mV·Hz (at minute 8) to 12.8 ± 3.3 mV·Hz (at minute 14) (p < 0.05) without subsequent increase and showing a modest correlation with coronary blood flow of borderline statistical significance (r = 0.489, p = 0.0547). Myocardial energy measurements showed marked reduction in phosphocreatine and moderate reduction in ATP with increases in ADP, AMP, and adenosine along with myocardial lactate, all indicative of ischemia. Yet, ischemia did not resolve during ECC despite a coronary blood flow of ~ 30% of baseline. Conclusion AMSA increased upon return of coronary blood flow during ECC. However, the maximal level was reached after ~ 6 minutes without further change. The significance of the findings for determining the optimal timing for delivering an electrical shock during resuscitation from VF remains to be further explored.