Background— Cardiac resynchronization therapy (CRT) has recently emerged as an effective treatment for patients with moderate to severe systolic heart failure and ventricular dyssynchrony. The purpose of the present study was to determine whether improvements in left ventricular (LV) size and function were associated with CRT. Methods and Results— Doppler echocardiograms were obtained at baseline and at 3 and 6 months after therapy in 323 patients enrolled in the Multicenter InSync Randomized Clinical Evaluation (MIRACLE) trial. Of these, 172 patients were randomized to CRT on and 151 patients to CRT off. Measurements were made of LV end-diastolic and end-systolic volumes, ejection fraction, LV mass, severity of mitral regurgitation (MR), peak transmitral velocities during early (E-wave) and late (A-wave) diastolic filling, and the myocardial performance index. At 6 months, CRT was associated with reduced end-diastolic and end-systolic volumes (both P<0.001), reduced LV mass (P<0.01), increased ejection f...

Effect of Cardiac Resynchronization Therapy on Left Ventricular Size and Function in Chronic Heart Failure

Guidelines and Expert Consensus Documents summarize and evaluate all currently available evidence on a particular issue with the aim to assist physicians in selecting the best management strategies for a typical patient, suffering from a given condition, taking into account the impact on outcome, as well as the risk–benefit ratio of particular diagnostic or therapeutic means. Guidelines are no substitutes for textbooks. The legal implications of medical guidelines have been discussed previously.

A great number of Guidelines and Expert Consensus Documents have been issued in recent years by the European Society of Cardiology (ESC) as well as by other societies and organizations. Because of the impact on clinical practice, quality criteria for development of guidelines have been established in order to make all decisions transparent to the user. The recommendations for formulating and issuing ESC Guidelines and Expert Consensus Documents can be found on the ESC website (http://www.escardio.org/knowledge/guidelines/rules).

In brief, experts in the field are selected and undertake a comprehensive review of the published evidence for management and/or prevention of a given condition. A critical evaluation of diagnostic and therapeutic procedures is performed including the assessment of the risk/benefit ratio. Estimates of expected health outcomes for larger societies are included, where data exist. The level of evidence and the strength of recommendation of particular treatment options are weighed and graded according to pre-defined scales, as outlined in Tables 1 and  2 .

View this table:

 Table 1 
Classes of recommendations



View this table:

 Table 2 
Levels of evidence



The experts of the writing panels have provided disclosure statements of all relationships they may have which might be perceived as real or potential sources of conflicts of interest. These disclosure forms are kept on file at the European Heart House, headquarters of the ESC. Any changes in conflict of interest that arise during the writing period must be notified …

/pdf/guidelines-for-cardiac-pacing-and-cardiac-resynchronization-e8x9bszgsr.pdf

Guidelines for cardiac pacing and cardiac resynchronization therapy: The Task Force for Cardiac Pacing and Cardiac Resynchronization Therapy of the European Society of Cardiology. Developed in collaboration with the European Heart Rhythm Association.

ContextProgressive heart failure is the most common mechanism of death among
patients with advanced heart failure. Cardiac resynchronization, a pacemaker-based
therapy for heart failure, enhances cardiac performance and quality of life,
but its effect on mortality is uncertain.ObjectiveTo determine whether cardiac resynchronization reduces mortality from
progressive heart failure.Data SourcesMEDLINE (1966-2002), EMBASE (1980-2002), the Cochrane Controlled Trials
Register (Second Quarter, 2002), The National Institutes of Health ClinicalTrials.gov
database, the US Food and Drug Administration Web site, and reports presented
at scientific meetings (1994-2002). Search terms included pacemaker, pacing, heart
failure, dual-site, multisite, biventricular, resynchronization, and left ventricular preexcitation.Study SelectionEligible studies were randomized controlled trials of cardiac resynchronization
for the treatment of chronic symptomatic left ventricular dysfunction. Eligible
studies reported death, hospitalization for heart failure, or ventricular
arrhythmia as outcomes. Of the 6883 potentially relevant reports initially
identified, 11 reports of 4 randomized trials with 1634 total patients were
included in the meta-analysis.Data ExtractionTrial reports were reviewed independently by 2 investigators in an unblinded
standardized manner.Data SynthesisFollow-up in the included trials ranged from 3 to 6 months. Pooled data
from the 4 selected studies showed that cardiac resynchronization reduced
death from progressive heart failure by 51% relative to controls (odds ratio
[OR], 0.49; 95% confidence interval [CI], 0.25-0.93). Progressive heart failure
mortality was 1.7% for cardiac resynchronization patients and 3.5% for controls.
Cardiac resynchronization also reduced heart failure hospitalization by 29%
(OR, 0.71; 95% CI, 0.53-0.96) and showed a trend toward reducing all-cause
mortality (OR, 0.77; 95% CI, 0.51-1.18). Cardiac resynchronization was not
associated with a statistically significant effect on non–heart failure
mortality (OR, 1.15; 95% CI, 0.65-2.02). Among patients with implantable cardioverter
defibrillators, cardiac resynchronization had no clear impact on ventricular
tachycardia or ventricular fibrillation (OR, 0.92; 95% CI, 0.67-1.27).ConclusionsCardiac resynchronization reduces mortality from progressive heart failure
in patients with symptomatic left ventricular dysfunction. This finding suggests
that cardiac resynchronization may have a substantial impact on the most common
mechanism of death among patients with advanced heart failure. Cardiac resynchronization
also reduces heart failure hospitalization and shows a trend toward reducing
all-cause mortality.

Cardiac resynchronization and death from progressive heart failure: a meta-analysis of randomized controlled trials.

Background— In patients with severe heart failure and dilated cardiomyopathy, cardiac resynchronization therapy (CRT) improves left ventricular (LV) systolic function associated with LV reverse remodeling and favorable 1-year survival. However, it is unknown whether LV reverse remodeling translates into a better long-term prognosis and what extent of reverse remodeling is clinically relevant, which were investigated in this study. Methods and Results— Patients (n=141) with advanced heart failure (mean±SD age, 64±11 years; 73% men) who received CRT were followed up for a mean (±SD) of 695±491 days. The extent of reduction in LV end-systolic volume (LVESV) at 3 to 6 months relative to baseline was examined for its predictive value on long-term clinical outcome. The cutoff value for LV reverse remodeling in predicting mortality was derived from the receiver operating characteristic curve. Then the relation between potential predictors of mortality and heart failure hospitalizations were compared by Kaplan-Me...

Left Ventricular Reverse Remodeling but Not Clinical Improvement Predicts Long-Term Survival After Cardiac Resynchronization Therapy

Biventricular pacing results in left ventricular (LV) reverse remodeling in heart failure patients with wide QRS complexes. This study examines potential predictors of reverse remodeling. Echocardiography with tissue Doppler imaging was performed at baseline and 3 months after biventricular pacing in 30 patients (21 men and 9 women, mean age 62 +/- 14 years). There were 17 responders to reverse remodeling (defined as a reduction in LV end-systolic volume by >15%) and 13 nonresponders. Responders had significant improvement in 6-minute hall-walking distance (p = 0.006), metabolic equivalents (p = 0.02), peak oxygen uptake (p = 0.02), New York Heart Association functional class (p <0.001), and quality of life (p <0.001); an increase in the sphericity index (p = 0.007), ejection fraction (p <0.001), and diastolic filling time (p = 0.03); a decrease in myocardial performance index (p = 0.02), isovolumic relaxation time (p = 0.004), and mitral regurgitation (p = 0.007); and an improvement in systolic dyssynchrony (SD of the time to peak myocardial systolic contraction of the 12 LV segments as dyssynchrony index) (45.0 +/- 8.3 vs 32.5 +/- 14.5 ms, p = 0.003). In contrast, nonresponders only had a small degree of clinical improvement in New York Heart Association class (p = 0.03) and quality-of-life scores (p = 0.03), without any change in cardiac function, and worsening of systolic dyssynchrony (24.8 +/- 4.5 vs 34.1 +/- 13.5 ms, p = 0.02). When all the above factors were put into univariate and multivariate analyses models, systolic dyssynchrony was the only independent predictor of reverse remodeling (r = -0.76, p <0.001) (beta = -1.54, p = 0.007). A preimplant dyssynchrony index of 32.6 ms (+2 SDs from mean of 88 normal controls) was able to totally segregate responders from nonresponders of biventricular pacing. Thus, responders of LV reverse remodeling were associated with improvement in clinical status, cardiac function, and systolic synchronicity. Direct assessment of systolic synchronicity by tissue Doppler imaging is highly accurate in predicting responders to therapy.

http://portal.mah.harvard.edu/cms/content/4474074C1D114E8A8917D7C36A46939C/91002CE309F041DBB87F440E9D59BDC3.pdf

Predictors of left ventricular reverse remodeling after cardiac resynchronization therapy for heart failure secondary to idiopathic dilated or ischemic cardiomyopathy

Background:

recent short-term observations have shown an improvement in cardiac function and heart failure symptoms from atrio-biventricular pacing. This study was designed to assess the safety and feasibility of an atrio-biventricular transvenous pacing system, and examine the long-term effects of cardiac resynchronization in patients with advanced heart failure and ventricular conduction abnormalities.



Methods and results:

between August, 1997 and November, 1998, 103 patients received a cardiac resynchronization system (CRS) consisting of a pulse generator interfaced with an atrio-biventricular lead system, including a lead designed for left ventricular (LV) pacing via cardiac veins. Baseline evaluation included 12-lead electrocardiogram, estimation of New York Heart Association (NYHA) functional class, assessment of quality of life (QOL), and distance covered during a 6-min walk (6-MW). Detailed echocardiographic data were also collected in a subset of 46 patients. Measurements were repeated in all surviving patients at 1, 3, 6 and 12 months after implantation of the CRS. A single, self-limiting procedure-related complication occurred. Over a follow-up of 12 months, 21 patients died. The 12-month actuarial survival was 78% (CI 70–87%). Nine surviving patients were withdrawn from the study during long-term follow-up for miscellaneous reasons. At each point of follow-up, a significant shortening of QRS duration was measured. In addition, significant improvements were observed in mean NYHA functional class, 6-MW and QOL score. In the 46 patients with complete echocardiographic data, LV ejection fraction increased from 21.7±6.4% at baseline to 26.1±9.0% at last follow-up (P-0.006), LV end diastolic dimension decreased from 72.7±9.2 to 71.6±9.1 mm (P-0.233), interventricular mechanical delay decreased from 27.5±32.1 to 20.3±25.5 ms (P-0.243), mitral regurgitation apical four-chamber area decreased from 7.66±5.5 to 6.69±5.9 cm2 (P-0.197), and left ventricular filling time increased from 363±127 to 408±111 ms (P-0.002).



Conclusions:

long-term cardiac resynchronization can be safely and reliably achieved by transvenous atrial synchronized right and left ventricular pacing. These changes were accompanied by clinically relevant improvements in functional status and QOL, as well as a measurable increase in LV performance. The outcome of randomised controlled trials is awaited.

Anders Kirstein-Pedersen

Papers

Cardiac resynchronization therapy in advanced heart failure the multicenter InSync clinical study.