ContextCardiac resynchronization therapy (CRT) through biventricular pacing
is an effective treatment for heart failure (HF) with a wide QRS; however,
the outcomes of patients requiring CRT and implantable cardioverter defibrillator
(ICD) therapy are unknown.ObjectiveTo examine the efficacy and safety of combined CRT and ICD therapy in
patients with New York Heart Association (NYHA) class III or IV congestive
HF despite appropriate medical management.Design, Setting, and ParticipantsRandomized, double-blind, parallel-controlled trial conducted from October
1, 1999, to August 31, 2001, of 369 patients with left ventricular ejection
fraction of 35% or less, QRS duration of 130 ms, at high risk of life-threatening
ventricular arrhythmias, and in NYHA class III (n = 328) or IV (n = 41) despite
optimized medical treatment.InterventionsOf 369 randomized patients who received devices with combined CRT and
ICD capabilities, 182 were controls (ICD activated, CRT off) and 187 were
in the CRT group (ICD activated, CRT on).Main Outcome MeasuresThe primary double-blind study end points were changes between baseline
and 6 months in quality of life, functional class, and distance covered during
a 6-minute walk. Additional outcome measures included changes in exercise
capacity, plasma neurohormones, left ventricular function, and overall HF
status. Survival, incidence of ventricular arrhythmias, and rates of hospitalization
were also compared.ResultsAt 6 months, patients assigned to CRT had a greater improvement in median
(95% confidence interval) quality of life score (–17.5 [–21 to
–14] vs –11.0 [–16 to –7], P =
.02) and functional class (–1 [–1 to –1] vs 0 [–1
to 0], P = .007) than controls but were no different
in the change in distance walked in 6 minutes (55 m [44-79] vs 53 m [43-75], P = .36). Peak oxygen consumption increased by 1.1 mL/kg
per minute (0.7-1.6) in the CRT group vs 0.1 mL/kg per minute (–0.1
to 0.8) in controls (P = .04), although treadmill
exercise duration increased by 56 seconds (30-79) in the CRT group and decreased
by 11 seconds (–55 to 12) in controls (P<.001).
No significant differences were observed in changes in left ventricular size
or function, overall HF status, survival, and rates of hospitalization. No
proarrhythmia was observed and arrhythmia termination capabilities were not
impaired.ConclusionsCardiac resynchronization improved quality of life, functional status,
and exercise capacity in patients with moderate to severe HF, a wide QRS interval,
and life-threatening arrhythmias. These improvements occurred in the context
of underlying appropriate medical management without proarrhythmia or compromised
ICD function.

https://jamanetwork.com/journals/jama/articlepdf/1108361/JOC30332.pdf

Combined cardiac resynchronization and implantable cardioversion defibrillation in advanced chronic heart failure: the MIRACLE ICD Trial.

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— Left ventricular (LV) mechanical dyssynchrony (LVMD) has emerged as a therapeutic target using cardiac resynchronization therapy (CRT) in selected patients with chronic heart failure. Current methods used to evaluate LVMD are technically difficult and do not assess LVMD of the whole LV simultaneously. We developed and validated real-time 3D echocardiography (RT3DE) as a novel method to assess global LVMD. Methods and Results— Eighty-nine healthy volunteers and 174 unselected patients referred for routine echocardiography underwent 2D echocardiography and RT3DE. RT3DE data sets provided time-volume analysis for global and segmental LV volumes. A systolic dyssynchrony index (SDI) was derived from the dispersion of time to minimum regional volume for all 16 LV segments. Healthy subjects and patients with normal LV systolic function had highly synchronized segmental function (SDI, 3.5±1.8% and 4.5±2.4%; P=0.7). SDI increased with worsening LV systolic function regardless of QRS duration (mild, 5.4...

Real-Time Three-Dimensional Echocardiography A Novel Technique to Quantify Global Left Ventricular Mechanical Dyssynchrony

https://www.heartrhythmjournal.com/pb/assets/raw/Health%20Advance/journals/hrthm/hrt00912001524.pdf

2012 EHRA/HRS expert consensus statement on cardiac resynchronization therapy in heart failure : implant and follow-up recommendations and management

Significance of QRS Complex Duration in Patients With Heart Failure

Acute effects of cardiac resynchronization therapy on left ventricular Doppler indices in patients with congestive heart failure.

Treatment of congestive heart failure (CHF) aims for symptomatic relief and reduction of mortality both from sudden death and pump failure. The implantable cardioverter defibrillator (ICD) is highly effective in the prevention of sudden death, but no mortality benefit in advanced CHF has yet been shown. Biventricular pacing may lead to functional improvement in selected patients with CHF. Thus, a biventricular pacemaker with defibrillation capabilities may be ideal for patients with advanced CHF. We retrospectively analyzed the data from 384 patients (age 59 +/- 12 years, 322 male and 62 female) with regard to New York Heart Association (NYHA) CHF class, mean QRS duration, mean PR interval, presence of a QRS > 120 msec and incidence of atrial fibrillation at the time of ICD implantation. Based on eligibility criteria from studies in biventricular pacing, we analyzed how many patients may benefit from biventricular pacing. Patients with CHF were older (NYHA class III: 60.9 +/- 9.7, class II: 61.3 +/- 10 versus class I: 50.8 +/- 13.6 years, p < 0.001 each) and mean QRS duration was longer with advanced CHF (NYHA class III 127.8 +/- 30 msec; class II 119.4 +/- 27.7 msec; class 0-1: 103.9 +/- 17.7 msec, p < 0.001, analysis of variance) as was the mean PR interval (NYHA class III 189.9 +/- 33.5 msec; class II 176.1 +/- 29.3 msec; class 0-1 162.7 +/- 45.9 msec, p < 0.001, analysis of variance). The incidence of atrial fibrillation was higher in class III (25.5%) compared with class 0-1 (16.9%) and class II patients (14.1%, p = 0.043, chi-square test). A total of 28 patients (7.3%) fulfilled eligibility criteria for biventricular pacing if NYHA class III patients were considered candidates and 48 (12.5%) if patients with NYHA II CHF and ejection fraction < or = 30% were included. Thus, biventricular pacing may offer a promising therapeutic approach for a significant proportion of patients with CHF at risk for ventricular tachyarrhythmia.

Potential benefit of biventricular pacing in patients with congestive heart failure and ventricular tachyarrhythmia

Ventricular tachycardias in coronary artery disease arise mostly from endocardial sites However, little is known about the site of origin in other diseases We present the case of an incessant, adenosine-sensitive ventricular tachycardia arising from the lateral wall of the left ventricle in a patient with mildly reduced left ventricular function Intracardiac mapping suggested an epicardial origin, and the tachycardia was successfully ablated from a coronary sinus branch After ablation, left ventricular function returned to normal Transcoronary venous radiofrequency catheter ablation is a new approach for the treatment of ventricular tachycardia Its value in the management of other types of ventricular tachycardia has yet to be determined

Transcoronary venous radiofrequency catheter ablation of ventricular tachycardia.

Background: Radiofrequency ablation of the “slow pathway” in atrioventricular nodal reentrant tachycardia (AVNRT) relies on tachycardia non-inducibility after ablation as success criterion However, AVNRT is frequently non-inducible at baseline Thus, autonomic enhancement using either atropine or isoproterenol is frequently used for arrhythmia induction before ablation 
Methods: 80 patients (57 women, 23 men, age 50±14 years) undergoing slow pathway ablation for recurrent AVNRT were randomized to receive either 001mg/kg atropine or 05-10μg/kg/min isoproterenol before ablation after baseline assessment of AV conduction The effects of either drug on ante- and retrograde conduction was assessed by measuring sinus cycle length, PR and AH interval, antegrade and retrograde Wenckebach cycle length (WBCL), antegrade effective refractory period (ERP) of slow and fast pathway and maximal stimulus-to-H interval during slow and fast pathway conduction 
Results: Inducibility of AVNRT at baseline was not different between patients randomized to atropine (73%) and isoproterenol (58%) but was reduced after atropine (45%) compared to isoproterenol (93%, P<0001) Of the 28 patients non-inducible at baseline isoproterenol rendered AVNRT inducible in 21, atropine in 4 patients Dual AV nodal pathway physiology was present in 88% before and 50% after atropine compared to 83% before and 73% after isoproterenol Whereas both drugs exerted similar effects on ante- and retrograde fast pathway conduction maximal SH interval during slow pathway conduction was significantly shorter after isoproterenol (300±48ms vs 374±113ms, P=0012) 
Conclusion: Isoproterenol yields higher AVNRT inducibility than atropine in patients non-inducible at baseline This may be caused by a more pronounced effect on antegrade slow pathway conduction

Differential effects of atropine and isoproterenol on inducibility of atrioventricular nodal reentrant tachycardia.

An increase in sinus rate prior to ventricular tachyarrhythmias has been demonstrated in previous studies. There is no clear data available concerning changes in ventricular de- and repolarization prior to ventricular tachyarrhythmias, especially in patients with structural heart disease. Therefore, the aim of this study was to analyze the QT and QTc interval (Bazett's formula immediately before the onset of ventricular tachyarrhythmias in stored electrograms of patients with ICDs. The study analyzed 228 spontaneous ventricular tachyarrhythmia episodes in 52 patients (mean age 64 +/- 10 years, 49 men, 3 women) and compared them with 146 electrograms of baseline rhythm recorded during regular ICD follow-up. Mean ventricular cycle length (CL), QT interval, and QTc were measured before the onset of ventricular tachyarrhythmia and during baseline rhythm. Prior to ventricular tachyarrhythmias onset, CL was significantly shorter than during baseline rhythm (714 +/- 139 vs 828 +/- 149 ms, P < 0.0001). By contrast, the QT interval (430 +/- 67 ms) and QTc interval (518 +/- 67 ms) were significantly prolonged before the onset of ventricular tachyarrhythmias as compared to baseline rhythm (QT 406 +/- 67 ms, QTc 450 +/- 61 ms; P < 0.0001). CL, QT, and QTc changes were independent of concomitant treatment with antiarrhythmic drugs. Ventricular tachyarrhythmias are preceded by a significant prolongation of the QT and QTc intervals. This phenomenon may represent a greater than normal disparity of repolarization recovery times possibly facilitating the development of ventricular tachyarrhythmias.

Björn Diem

Papers

Acute effects of cardiac resynchronization therapy on left ventricular Doppler indices in patients with congestive heart failure.

Potential benefit of biventricular pacing in patients with congestive heart failure and ventricular tachyarrhythmia

Transcoronary venous radiofrequency catheter ablation of ventricular tachycardia.

Differential effects of atropine and isoproterenol on inducibility of atrioventricular nodal reentrant tachycardia.

Temporary disturbances of the QT interval precede the onset of ventricular tachyarrhythmias in patients with structural heart diseases.