European Heart Journal Advance Access published online on August 28, 2008
European Heart Journal, doi:10.1093/eurheartj/ehn380
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
How should we optimize cardiac resynchronization therapy?
1 Department of Medicine, University of Queensland Princess Alexandra Hospital, Ipswich Road, Brisbane Q4102, Australia
2 University Hospital Aintree, Liverpool, UK
3 Stobhill Hospital, Glasgow, UK
4 Golden Jubilee National Hospital, Glasgow, UK
5 Western Infirmary, Glasgow, UK
Received 26 November 2008; revised 26 June 2008; accepted 25 July 2008.
* Corresponding author. Tel: +61 732407857, Fax: +61 732405399, Email: t.stanton{at}uq.edu.au
 |
Abstract |
|---|
Top
Abstract
IntroductionOptimization of cardiac resynchronization therapy is increasingly performed. Numerous methods have been proposed, many being echocardiographic. Both the technique and the timing of optimization are contentious. Whether acute haemodynamic benefits translate into long-term improvements in remodelling, symptoms, or prognosis is unknown. Recent guidelines from the American Society of Echocardiography advocate routine optimization. Here, we objectively review the principles, methods, timing, and evidence supporting optimization. Despite limited validation, optimization was included in landmark clinical trials and is inherent in evidence-based practice. Randomized controlled trials comparing methods are needed, with long-term clinical endpoints. For now, optimization should be performed using the iterative method, according to the CARE-HF protocol.
Key Words: Optimization • Cardiac resynchronization therapy • Atrioventricular delay • Interventricular delay
|
Introduction |
|---|
Cardiac resynchronization therapy (CRT) improves morbidity and mortality in patients with heart failure (HF).1–3 There are two important adjustable pacing parameters—the interventricular (VV) and atrioventricular (AV) delay. Although included in landmark clinical trials,1,3–6 the role of optimization remains uncertain. Recent guidelines from the American Society of Echocardiography advocate routine optimization of AV delay.7 Here, we objectively review the evidence supporting this statement. Why do we optimize CRT? How do we optimize CRT? When should we optimize CRT? And most importantly, does optimizing CRT benefit patients?
|
Search strategy |
|---|
Databases including MEDLINE, EMBASE, PubMed, and the Cochrane Library were searched up to November 2007. The search strategy included both Medical Subject Heading (MeSH) terms (‘cardiac resynchronization’, ‘pacemaker’, ‘HF’, ‘optimization’, ‘delay’) and key words (‘atrioventricular’, ‘interventricular’, ‘dyssynchrony’), restricted to humans. Combinations of terms were used depending on the requirements of the database. No language restriction was initially employed. Clinical trial registers approved by the International Committee of Medical Journal Editors were examined for information regarding current or recently completed trials, including the US National Institutes of Health register (ClinicalTrials.gov). Bibliographies of all papers and review articles identified by the initial strategy were systematically hand-searched. Two reviewers independently scanned all the abstracts and identified potentially relevant articles. Disagreement was resolved by consensus and full text copies retrieved in the event of uncertainty. International conference proceedings were examined from 2000 to 2007 (American College of Cardiology, American Heart Association, European Society of Cardiology). Finally, websites of companies producing biventricular devices were examined for additional data. Of the 108 trials initially identified, 19 were excluded (five non-English language, eight pilot studies or case reports, and six by consensus opinion owing to inapplicable study population or design).
|
What is interventricular delay? |
|---|
The VV delay signifies the delay between contraction of the right and left ventricles. In normal subjects right ventricular depolarization precedes left by a few milliseconds. Interventricular conduction times vary widely in patients with HF.8 By convention, a negative value indicates that LV activation precedes RV.
|
Why do we optimize interventricular delay? |
|---|
CRT aims to restore synchronous ventricular contraction. This is impeded by suboptimal LV lead position, abnormal global activation, and regional conduction delays across infarcted myocardium. Tailored ventricular timing aims to compensate for these delays.9,10 None of the landmark CRT trials included VV optimization.1–6
|
How do we optimize interventricular delay? |
|---|
VV delay is optimized using device-based algorithms,9 echocardiographic cardiac output,10–14 tissue Doppler synchrony,15–17 invasive dP/dtmax,18–21 blood pressure,22 surface electrocardiogram,23 and intracardiac electrogram (IEGM) methods (QuickOpt®).24,25
Invasive left ventricular dP/dtmax
A pressure sensor-tipped wire is inserted into the LV through a cardiac catheter. The maximal pressure change per unit of time (dP/dtmax) is considered a reliable method of assessing LV systolic function.26 Disadvantages include the invasive nature of the procedure, limited repeatability, time required, and cost of equipment. Four small, non-randomized studies demonstrated only a modest improvement in invasive dP/dtmax immediately after VV optimization (maximum 8%).18–21 No long-term follow-up or clinical outcomes were included (Table 1).
|
Left ventricular outflow tract velocity time integral
Interventricular delay is adjusted to maximize echocardiographic cardiac output. Left ventricular outflow tract velocity time integral (LVOT VTI) is measured beneath the aortic valve cusps using pulsed-wave (PW) Doppler, then multiplied by the cross-sectional area of the LVOT to estimate stroke volume (SV).27–30 Cardiac output is calculated by multiplying SV with heart rate. This technique has been validated in patients with advanced HF against the Fick oxygen reference standard (n = 73, r = 0.90, P = 0.00002).29 Several limitations apply. Small changes in the angle between the incident ultrasound beam and outflow jet introduce significant error. Echocardiographic-derived cardiac output varies with cardiac medications,31 exercise,32,33 and posture.34 Short-term intra- and inter-observer variability in the measurement of cardiac output ranges from 4% to 10%.28,30 Obtaining a good quality signal in the LVOT may be difficult.30,35 Some authors have substituted maximal aortic valve VTI using continuous wave Doppler.35–38 This approach is inadvisable as both cardiac output and aortic valve morphology contribute to the signal.
Three small, non-randomized studies optimized VV delay using LVOT VTI.12–14 Echocardiographic measures including cardiac output improved with optimized rather than simultaneous VV pacing. Improvement in clinical variables was however negligible [0.1 NYHA class, 7 m on 6-min walk distance (6MWT)].13
Two large multicentre trials optimized VV delay using LVOT VTI.10,11 The non-randomized InSync III study examined 359 patients. Pre-discharge optimization increased stroke volume by 8.6%. Clinical outcomes at 6 months were compared against the historical treatment arm of the MIRACLE study.10 Results were mixed. Quality-of-life (QOL) score and NYHA class failed to improve when compared with the MIRACLE treatment group. However, median 6MWT increased by 15.1 m [53.0 (range –314.0 to 613.0) vs. 37.9 (range –437.0 to 248.8), P < 0.0001]. The RHYTHM II ICD study randomized 121 patients in a 1:3 ratio to simultaneous vs. optimized biventricular (BiV) pacing.11 Optimization conferred no benefit in 6MWT, QOL, NYHA class or hospitalizations.
Tissue Doppler synchrony
Two studies have optimized VV delay using tissue Doppler measures of synchrony.16,17 The first concurrently optimized AV delay in 51 patients, but failed to improve NYHA class, QOL score, or change in 6MWT.16 In the second report, optimization of interventricular synchrony using strain rate imaging was associated with increased cardiac output (4.6 ± 0.3 vs. 4.3 ± 0.3 L/min).17
Expert Ease for Heart FailureTM algorithm
Expert Ease for Heart FailureTM (EEHF) algorithm calculates the VV delay based on the intrinsic interventricular delay measured by the device during implantation. The algorithm was derived from unpublished acute haemodynamic data in the PATH-CHF II studies: optimal VV delay = –0.333 x (RV – LV electrical delay) – 20 ms.9
The DECREASE-HF trial randomized 306 patients to simultaneous BiV, sequential BiV, or LV pacing.9 Sequential pacing was equivalent, but not superior, to simultaneous pacing for the composite primary endpoint of peak oxygen consumption and LV end-systolic dimension. The secondary echocardiographic endpoints are published. A trend towards greater improvement in LV dimensions and volumes was observed with simultaneous pacing, while measures of systolic function were similar between the two groups.
|
What is atrioventricular delay? |
|---|
Atrial contraction contributes 20–30% to stroke volume at rest in patients with HF and left ventricular systolic dysfunction (LVSD).39–43 This contribution increases with higher heart rates.44 Impaired AV conduction reduces cardiac output and systolic blood pressure.45
A long AV delay causes late ventricular contraction. Diastolic filling time (DFT) is reduced, causing fusion of the E- and A-waves of the mitral inflow Doppler (Figure 1). The atrial contribution to filling terminates significantly before depolarization of the ventricle, resulting in wasted diastole and suboptimal preload for ventricular contraction. Patients with HF often exhibit diastolic mitral regurgitation (MR). A left ventricular–atrial pressure gradient develops owing to high LV end-diastolic pressure and incomplete mitral valve closure.39 This further reduces preload and LV filling.46 AV programming of CRT can eliminate diastolic MR.47
|
A short AV delay causes early ventricular contraction. DFT is increased, separating the E- and A-waves of the mitral inflow Doppler. However, end-diastolic filling is interrupted by the onset of ventricular contraction and early mitral valve closure, manifested as A-wave truncation (Figure 2).
|
The goal of optimizing AV delay is two-fold. First, to maximize DFT (i.e. separation of the E- and A-waves). Secondly, to allow complete end-diastolic filling (marked by the end of the A-wave) before the onset of LV contraction. AV delay is programmed during CRT implantation, and may be set empirically to 120 ms.36,48,49 The exact number of patients receiving optimization or empirical settings in clinical practice is unknown.
|
Why do we optimize atrioventricular delay? |
|---|
The evidence supporting optimization of AV delay originates from dual-chamber pacing studies (Table 2). All were small, short-term studies of echocardiographic or invasive haemodynamic measures. Only one trial involved more than 25 patients, included randomization or blinding, or recruited consecutive patients. None demonstrated an improvement in clinical outcome. Disparate optimization techniques and outcome measures were employed. Intra- and inter-observer variability were rarely documented.
|
In total, the studies included only 64 patients with HF. Extrapolating results from these historic studies to CRT candidates with severe HF is unwise without rigorous validation. Clearly, such patients have major structural and haemodynamic differences when compared with conventional recipients of brady-pacemakers.
|
How do we optimize atrioventricular delay? |
|---|
Many echocardiographic and non-echocardiographic optimization methods have been proposed. These aim to optimize either DFT or markers of systolic function.
|
Echocardiographic optimization methods |
|---|
As with dual-chamber pacing, the evidence derives mainly from small, single centre, non-randomized studies (Table 3). Many different optimization methods were assessed with diverse definitions of response. Few studies included clinical outcomes.16,36,49–52 The timing of optimization after implant varied greatly, or was not documented. Many studies lacked or included only limited follow-up. Only three of these included a control group.16,36,49 Without controls, inferring long-term benefit from AV optimization is impossible. The results may simply reflect the effects of CRT alone.
|
Some studies compared the ‘optimal’ AV delay with selected short or long comparator AV delays.50,53–55 This exaggerates the purported benefit. Few compared optimization with standard ‘out of box’ settings.16,36,49 All but one study performed optimization at rest in the supine position.56 Extrapolation to standing or exercising patients is unfounded. Most techniques require validation in unselected HF patients beyond the research environment. Intra- and inter-observer variability were rarely documented.
|
Optimization of diastolic filling time |
|---|
Iterative method
This method uses mitral valve PW Doppler.1 DFT is measured from the start of the E-wave until the end of the A-wave. A long AV delay is programmed and reduced in 20 ms steps until the A-wave truncates. The interval is then increased in 10 ms increments. The shortest AV delay without A-wave truncation is selected to maximize DFT.
A retrospective study examined 215 patients who underwent AV optimization within 30 days of CRT implantation.57 The majority were optimized using Ritter's method (see below), the remainder using the iterative method. Over a mean follow-up period of 23 months, NYHA class and LVEF improved significantly. With no control group, as alluded to earlier, it is impossible to quantify the effects of AV optimization alone. The only direct benefit attributable to optimization was in ‘diastolic function stage’, which improved only in 9% of patients. Remarkably, the authors concluded that assessment of DFT was useful in all patients undergoing CRT.
The iterative method was recently compared against no optimization in a non-randomized observational cohort study of 100 patients.16 AV delay was optimized in 38 patients in conjunction with optimization of VV delay using tissue Doppler imaging. No significant improvement occurred in any clinical endpoint, including NYHA class, QOL score, change in 6MWT, death, or cardiac transplantation. Although Doppler-derived cardiac output increased at 6-month follow-up, LV dimensions and EF were unchanged.
Ritter's method
This method is derived from dual-chamber pacing studies,58–60 with only limited validation in patients with HF.61 Two extreme AV delays are programmed. A short interval (AVshort) with clear A-wave truncation and a long interval (AVlong) without A-wave attenuation (e.g. 30 ms and 200 ms).59,62 For each, the time between QRS onset and completion of the A-wave is measured. The optimal AV delay is calculated using the formula: AVopt = AVshort + [(AVlong + QAlong) – (AVshort + QAshort)].35,62 This is simplified to AVopt = AVlong – (QAshort – QAlong).59,62 Essentially, this calculates the longest DFT without interruption of the A-wave. Calculation rather than testing multiple AV delays reduces the procedure time to around 5 min.61,62
Whether or not the derived AV delay is ‘optimal’ in patients with HF is unclear. Major haemodynamic and structural differences exist compared to patients with preserved EF and high-degree AV block. In particular, calculation based on shifts in the mitral valve closure point may be inaccurate in the presence of high LV end-diastolic pressure.35,59 Only one small study (n = 10) validated Ritter's method in patients with LVSD requiring DDD pacing.61 The ‘optimal’ AV interval was unusually defined by maximal LVEF as measured by radionuclide ventriculography. A good correlation was observed with Ritter's method (intra-class quotient 0.92).
Ritter's method, aortic valve VTI, and a device-based algorithm were compared in a prospective study involving 28 patients.38 The algorithm most accurately predicted optimal AV delay defined by invasive dP/dtmax in both atrial-sensed and atrial-paced modes. Ritter's method was the least accurate technique.
Mitral inflow velocity time integral
The mitral inflow VTI theoretically represents the LV filling volume, assuming a constant mitral valve area. The AV delay is adjusted to maximize the mitral inflow VTI.35 Four methods of AV optimization were compared in 30 patients against invasive dP/dtmax (mitral inflow VTI, DFT, aortic valve VTI, and Ritter's method).35 The ‘optimal’ AV delay was predicted in 97% of patients by mitral inflow VTI, in 67% by DFT, and in 43% by aortic valve VTI. Ritter's method was correct in none.
Simplified (Meluzin) mitral inflow method
Meluzin et al.53 proposed a method to align the end of ventricular filling and onset of ventricular contraction, using a single recording of transmitral flow lasting 5–10 s. The maximum AV delay allowing full ventricular capture, lowered by 5–10 ms, is designated the ‘long AV delay’. The time between the end of the A-wave and onset of systolic MR is measured (termed ‘t1’). The optimal AV delay is obtained by subtracting ‘t1’ from the ‘long AV delay’. This technique is again limited by the need for detectable MR.
Only one study optimized CRT using the Meluzin method.53 Eighteen patients were studied 3 months after CRT implantation. No follow-up or randomization was included. The ‘optimal’ AV delay was simply compared with optimal AV delay –50 ms and +28 ms at this single timepoint. Cardiac output calculated by right heart catheterization was significantly higher (4.5 ± 0.7 L/min) at the mean optimal AV delay of 149 ± 17 ms, compared with 4.3 ± 0.7 L/min and 4.4 ± 0.8 L/min at optimal AV delay –50 ms and +28 ms, respectively.
Diastolic mitral regurgitation (Ishikawa) method
Diastolic MR is observed in many patients with HF, as a consequence of elevated LV end-diastolic pressure. This method aims to minimize diastolic MR.63,64 A long AV delay is selected to induce diastolic MR. The optimal AV delay is calculated by subtracting the duration of diastolic MR from the initial long AV delay.
A single study examined the Ishikawa method in just five consecutive patients.50 The ‘optimal’ delay was compared with selected longer and shorter delays (±25 ms). The reason for choosing these comparators is unclear. Echocardiographic cardiac output and DFT were greatest at the optimal AV delay. With no control group, the improvement in NYHA class over a mean of 2.3 years (1.4 ± 0.5 vs. 3.6 ± 0.5, P < 0.001) may simply reflect the effect of CRT alone.
Ismer method
A bipolar oesophageal electrode is passed to provide a left atrial electrogram.55 A mitral valve PW Doppler trace and real-time pacemaker markers from the oesophageal electrode are obtained. A complex formula involving these measurements is used to estimate the optimal AV delay.
A single study compared the Ismer method against greatly longer and shorter AV delays (±50 ms) in 11 patients.55 There was no randomization, follow-up, or clinical outcomes. Despite conducting 26 tests for significance, only one was positive; LVEF at optimal AV delay (28 ± 12%) was significantly higher than that at optimal AV delay, –50 ms (20 ± 7%). However, LVEF failed to improve when compared with baseline (27.3 ± 11.9%).
|
Optimization of markers of systolic function |
|---|
Left ventricular outflow tract velocity time integral
Atrioventricular delay is incrementally adjusted to maximize echocardiographic cardiac output. Three small studies have employed LVOT VTI to optimize CRT.51,52,56 The first included 36 patients.56 There was no randomization, follow-up, or clinical outcomes. The so-called ‘optimal’ AV delay was defined solely by the greatest LVOT VTI. The limitations are highlighted by the marked variation in optimal delay during exercise, and even between supine and seated positions (99 ± 19 ms vs. 84 ± 22 ms, P = 0.052). At peak heart rate, the optimal AV delay increased by over 100 ms.
The second study included just 19 patients.51 Again the ‘optimal’ AV delay was defined by the greatest LVOT VTI. Again there was no randomization. Although NYHA class improved at 6 months, the benefit (if any) attributable to optimization is impossible to discern. The simultaneous optimization of AV and VV delay, coupled with the lack of control group, precludes conclusions regarding AV delay alone.
A third study included 33 patients but was again neither randomized nor blinded.52 EF, myocardial performance index (MPI), and E/Ea (a marker of diastolic function) all improved significantly immediately post-optimization. Results after 43 ± 5 days follow-up were mixed. While 6MWT and N-terminal pro B type natriuretic peptide significantly improved, EF and QOL were unchanged. Once again the absence of controls hinders interpretation.
Aortic valve velocity time integral
A single blind study randomized 40 patients to aortic VTI-optimized AV delay (mean 119 ± 34 ms) or an empirical 120 ms.36 Those optimized had an improvement in the subjective variables of QOL and NYHA class at 3 months, but not the objective variables measured (6MWT, LVEF, or LV volumes). The lack of a primary endpoint must raise concerns regarding multiple hypothesis testing. Subsequently, the same group found significantly different optimal AV delays when comparing the aortic valve VTI and Ritter methods (119 ± 34 ms vs. 95 ± 24 ms, respectively).37 It is unclear whether results originate from the same cohort, given the discrepancies but also similarities in baseline characteristics (both n = 40, mean optimal AV delay 119 ± 34 ms, mean NYHA class 3.1).36,37 The aortic valve VTI method, acting as both outcome measure and comparator, exhibited the highest increase from baseline.
Doppler-derived dP/dtmax
The AV delay is adjusted to produce the greatest dP/dt.49 The MR CW Doppler velocity curve represents the instantaneous pressure difference between the LV and atrium in systole. The normally steep downward gradient is reduced in LVSD.65,66 Time (dt) is measured between two points on the MR jet (1 m/s and 3 m/s).49,65 These points correspond to LV–LA gradients of 4 mmHg and 36 mmHg, respectively, according to the modified Bernoulli equation (pressure gradient = 4v2). Thus, dP is a constant at 32 mmHg. This approach is limited by the need for detectable MR. The technique has been validated against cardiac catheterization in patients with HF.67
A recent study allocated 41 consecutive patients on a 2:1 basis to optimization using Doppler-derived dP/dtmax or an empirical AV delay of 120 ms.49 Adequate images were obtained in 23 of 26 patients. Intra- and inter-observer repeatability were excellent (r = 0.99 and 0.98, respectively). At 6 months, the optimized group had a significantly lower NYHA class (2.1 ± 0.1 vs. 3.0 ± 0.2, P < 0.01) and higher echocardiographic LVEF (32.1 ± 1.0 vs. 27.5 ± 1.6, P < 0.05).
Myocardial performance index
MPI is calculated as the sum of isovolumic contraction and relaxation times divided by ejection time.68,69 It is considered a measure of global cardiac function.70,71 In 170 patients, MPI differentiated between those with normal LV function, moderate HF (NYHA class II, LVEF 30–50%), and severe HF (NYHA class III–IV, awaiting cardiac transplantation).70 MPI also correlated with invasive dP/dtmax in 34 subjects with varying degrees of LV dysfunction (r = 0.82, P < 0.0001).71 Ejection time is the interval between the start and end of aortic flow. Isovolumic contraction is measured from the mitral A-wave terminus to the onset of aortic flow. Isovolumic relaxation is measured from the aortic flow terminus to the onset of the mitral E-wave. Improvement in MPI is signified by a lower numerical value.
Two small studies have ‘optimized CRT’ using MPI.54,69 Neither included any randomization or clinical outcomes. Optimization reduced MPI by 0.49 in 21 patients.69 No other outcome measure was assessed. In the second study of 26 patients, one of three pre-specified AV delays was selected based on agreement between three additional echocardiographic measures (LV pre-ejection interval, VV delay, and the filling fraction of the cardiac cycle).54 Thirteen patients were considered optimal at 90 ms, 10 at 120 ms, and three at 150 ms. Whether AV optimization contributed to subsequent remodelling is unknown, given the lack of control group.
|
Do different echocardiographic methods produce different atrioventricular delays? |
|---|
The evidence calls into question the entire concept of the so-called ‘optimal’ AV delay (Table 3). The supposedly optimal mean delay ranged from 97 ms to 148 ms, despite recruitment of similar patients. In accordance with international guidelines,72 patients typically had symptomatic HF (NYHA III/IV) with prolonged QRS duration
120 ms and EF 
35%. Direct comparison of methods raise similar doubts. In 40 patients, the optimal AV delay was 119 ± 34 ms using AV VTI, but only 95 ± 24 ms using Ritter's method.37 Another study compared AV VTI and Ritter's method in 28 patients.38 The optimal AV delays were comparable in atrial-sensed mode (121 ± 28 ms vs. 122 ± 28 ms), but not in atrial-paced mode (160 ± 35 ms vs. 118 ± 33 ms). ‘Optimal’ appears to be defined largely by the methods of optimization and measures of response. |
Non-echocardiographic optimization methods |
|---|
Studies of non-echocardiographic optimization of AV delay are summarized in Table 4.
|
Invasive left ventricular dP/dtmax
PATH-CHF and PATH-CHF II trials optimized AV delay at implantation using invasive LV dP/dtmax (Table 4).73,74 Short-term follow-up demonstrated improvements in exercise capacity and QOL. Three other studies totalling 100 patients optimized AV delay at implantation using invasive LV dP/dtmax (Table 4).75–77 No follow-up was undertaken. Invasive dP/dtmax increased acutely by up to 22%.75
Impedance cardiography
Impedance cardiography (ICG) was initially used to ‘optimize’ AV delay in patients with dual-chamber pacemakers.59,78 Cardiac output is evaluated non-invasively by measuring changes in impedance of an alternating current applied across the patient's thorax. The correlation with invasive measurements is highly variable, particularly in patients with HF.79,80
Four studies totalling 83 patients have optimized AV delay using ICG (Table 4).81–84 Again, all were acute studies with no follow-up. Correlations between AV delay determined by echocardiography and ICG were good (r = 0.84,81 r = 0.7483). However, the actual benefit of AV optimization was either negligible (+2% cardiac output)81 or impossible to determine.82–84 Two studies failed to document baseline measurements prior to optimization.82,83 The third study adjusted AV and VV delay concurrently, increasing mean cardiac output by 11.2%.84
Finger photoplethysmography
Finger photoplethysmography (FPPG) non-invasively measures change in blood pressure. Measurement is possible using a conventional pulse oximetry probe with appropriate software and correction algorithms.85 Signal variations owing to pacing and random errors may confound results.62 Alternatively, dedicated equipment is commercially available.22,86 A rapidly responding inflatable finger cuff maintains the volume of the finger constant during the cardiac cycle. A photoelectric plethysmograph and a volume-clamp circuit determines beat-to-beat blood pressure changes.
Three studies have demonstrated acute improvement in blood pressure following AV optimization using FPPG.22,85,86 Optimal AV delay was defined by invasive aortic pulse pressure in 57 patients. FPPG successfully identified this optimal delay in 78% of cases.85 In two smaller studies optimization using FPPG increased non-invasive systolic blood pressure by 17 mmHg and 21 mmHg.22,86 No clinical outcomes were assessed.
Expert Ease for Heart FailureTM algorithm
Expert Ease for Heart FailureTM (EEHF) algorithm calculates both sensed and paced AV delays by measuring the intrinsic-sensed and -paced AV intervals (from the device) and QRS duration (from surface ECG). Calculation includes coefficients that vary depending on the pacing chamber (LV or BiV) and LV lead location.38
When compared with Ritter's method and AV VTI, the EEHF algorithm was superior in predicting optimal AV delay as determined by invasive LV dP/dtmax.38 Results correlated closely with the maximum achievable LV dP/dtmax (R2 = 0.99, P < 0.0001).
Intracardiac electrogram (IEGM) (QuickOpt®)
Optimization of both AV and VV delays using an IEGM method has recently been described.24 The optimal delays correlated closely with those derived using echocardiographic aortic VTI methods (all correlation coefficients >96%, P < 0.05). The same IEGM optimization method has been shown to reduce LV dyssynchrony and improve systolic function as measured by three-dimensional echo.25 A prospective, multicentre trial investigating this method is currently recruiting patients.87
Peak endocardial acceleration
Peak endocardial acceleration (PEA) detects mechanical acceleration of the heart through a microaccelerometer located at the distal end of the ventricular lead. The amplitude of the PEA signal varies with myocardial contractility.88 In 15 patients with dual-chamber pacemakers, optimal AV delays determined by PEA analysis correlated with those obtained using Ritter's method (r = 0.79, P = 0.0012).60
The ongoing CLEAR (Clinical Evaluation of Advanced Resynchronization) study is a multicentre randomized, single-blind, controlled trial in patients with NYHA Class III or IV HF. PEA-based optimization will be compared with optimization according to the investigating centre's standard clinical practice.89
|
How was atrioventricular delay optimized in clinical trials of cardiac resynchronization therapy? |
|---|
Most of the landmark clinical trials included AV optimization (Table 5). The COMPANION trial employed the device-based Expert Ease for Heart FailureTM algorithm to optimize AV delay but not VV delay.2 The MUSTIC trial specified Ritter's formula for optimizing AV delay.4 The methods described in the MIRACLE and CARE-HF design publications are unclear.90,91 Both involve Doppler echocardiography of transmitral flow. Both advise that ‘the AV delay is set at a value which provides maximum separation of the E and A waves, representing passive ventricular filling and atrial contraction, respectively’. Subsequent publications by the MIRACLE study group refer to Ritter's method.92,93 In contrast, Appendix 8 of the CARE-HF Investigational Plan describes the iterative method. On the basis of these trials, recent guidelines from the American Society of Echocardiography recommend AV optimization using either the iterative or the Ritter method.7 None of the landmark clinical trials included any pre-specified comparisons of optimization methods.
|
|
How often should we optimize atrioventricular delay? |
|---|
The timing of optimization poses many questions. When should initial optimization be performed? Does the optimal AV delay change over time? Who requires repeat optimization? When should re-optimization occur? Optimization was performed within days of implantation in almost all studies and clinical trials (Tables 2 and 4). The schedule of re-assessment was similar in the MIRACLE and CARE-HF trials. Optimization was performed pre-discharge, and after 3, 6, and 9 months in the MIRACLE trial.90 In CARE-HF, optimization occurred pre-discharge, and after 3, 9, and 18 months. The results of optimization in these clinical trials are not yet reported.
Several small studies have documented variation of AV delay over time.36,50,94–96 Although no significant change occurred in mean optimal AV delay, change in individual patients was common.50,94–96 Temporal variations were specifically examined in three studies involving between 22 and 40 patients.94–96 About 56–82% of patients required re-optimization during follow-up ranging from 3 months to a mean of 16 months. Such changes are to be expected, given the effects of CRT on remodelling and systolic function.92 Analysis of clinical trial data would improve our understanding of temporal variation in AV delay.
|
Should we optimize only the so-called ‘non-responders’? |
|---|
Some have advocated optimizing only the so-called ‘non-responders’. No published evidence supports this standpoint. The entire concept of ‘response’ is questionable.97 Although numerous clinical and volumetric measurements have been proposed, there is no agreed definition of response. To restrict optimization to ‘non-responders’ may deny ‘responders’ additional benefit. Recent analysis of the CARE-HF trial revealed the prognostic benefits of CRT to be independent of symptom severity.98
|
Conclusion |
|---|
Optimizing CRT has major financial implications in clinical practice. The cost of echocardiographic equipment, staff, training, and patient transport are all significant. Many questions remain unanswered. Sequential BiV pacing fails to improve clinical outcomes. Routine optimization of VV delay cannot be recommended. The physiological basis and acute haemodynamic benefit of optimizing AV delay are undeniable. Whether this translates into long-term improvements in remodelling, symptoms, or prognosis is unknown. Randomized controlled trials comparing methods are needed, with long-term clinical endpoints.
Despite limited validation, optimization was included in landmark clinical trials and is inherent to evidence-based practice. Patients in the landmark clinical trials were optimized using transmitral Doppler. It is impossible to separate the benefits of CRT with optimization from that of CRT alone. Nor should we try. Evidence-based medicine is not ‘pick and mix’. Death and major cardiovascular events were reduced in the CARE-HF trial,1 while MUSTIC and MIRACLE showed improvements in exercise capacity and QOL.3,4 For now, best evidence-based practice is to follow the CARE-HF protocol and optimize AV delay using the iterative method at baseline, 3 months, and every 6 months thereafter.
Conflict of interest: none declared.
|
References |
|---|
- Cleland JG, Daubert JC, Erdmann E, Freemantle N, Gras D, Kappenberger L, Tavazzi L. The effect of cardiac resynchronization on morbidity and mortality in heart failure. N Engl J Med (2005) 352:1539–1549.
[Abstract/Free Full Text] - Bristow MR, Saxon LA, Boehmer J, Krueger S, Kass DA, De Marco T, Carson P, DiCarlo L, DeMets D, White BG, DeVries DW, Feldman AM. Cardiac-resynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure. N Engl J Med (2004) 350:2140–2150.
[Abstract/Free Full Text] - Abraham WT, Fisher WG, Smith AL, DeLurgio DB, Leon AR, Loh E, Kocovic DZ, Packer M, Clavell AL, Hayes DL, Ellestad M, Trupp RJ, Underwood J, Pickering F, Truex C, McAtee P, Messenger J. Cardiac resynchronization in chronic heart failure. N Engl J Med (2002) 346:1845–1853.
[Abstract/Free Full Text] - Cazeau S, Leclercq C, Lavergne T, Walker S, Varma C, Linde C, Garrigue S, Kappenberger L, Haywood GA, Santini M, Bailleul C, Daubert JC. Effects of multisite biventricular pacing in patients with heart failure and intraventricular conduction delay. N Engl J Med (2001) 344:873–880.
[Abstract/Free Full Text] - Young JB, Abraham WT, Smith AL, Leon AR, Lieberman R, Wilkoff B, Canby RC, Schroeder JS, Liem LB, Hall S, Wheelan K. Combined cardiac resynchronization and implantable cardioversion defibrillation in advanced chronic heart failure: the MIRACLE ICD Trial. JAMA (2003) 289:2685–2694.
[Abstract/Free Full Text] - Abraham WT, Young JB, Leon AR, Adler S, Bank AJ, Hall SA, Lieberman R, Liem LB, O'Connell JB, Schroeder JS, Wheelan KR. Effects of cardiac resynchronization on disease progression in patients with left ventricular systolic dysfunction, an indication for an implantable cardioverter-defibrillator, and mildly symptomatic chronic heart failure. Circulation (2004) 110:2864–2868.
[Abstract/Free Full Text] - Gorcsan J III, Abraham T, Agler DA, Bax JJ, Derumeaux G, Grimm RA, Martin R, Steinberg JS, Sutton MS, Yu CM. Echocardiography for cardiac resynchronization therapy: recommendations for performance and reporting–a report from the American Society of Echocardiography Dyssynchrony Writing Group endorsed by the Heart Rhythm Society. J Am Soc Echocardiogr (2008) 21:191–213.[CrossRef][Web of Science][Medline]
- Auricchio A, Salo RW. Acute hemodynamic improvement by pacing in patients with severe congestive heart failure. Pacing Clin Electrophysiol (1997) 20:313–324.[CrossRef][Medline]
- Rao RK, Kumar UN, Schafer J, Viloria E, De Lurgio D, Foster E. Reduced ventricular volumes and improved systolic function with cardiac resynchronization therapy: a randomized trial comparing simultaneous biventricular pacing, sequential biventricular pacing, and left ventricular pacing. Circulation (2007) 115:2136–2144.
[Abstract/Free Full Text] - Leon AR, Abraham WT, Brozena S, Daubert JP, Fisher WG, Gurley JC, Liang CS, Wong G. Cardiac resynchronization with sequential biventricular pacing for the treatment of moderate-to-severe heart failure. J Am Coll Cardiol (2005) 46:2298–2304.
[Abstract/Free Full Text] - Boriani G, Muller CP, Seidl KH, Grove R, Vogt J, Danschel W, Schuchert A, Djiane P, Biffi M, Becker T, Bailleul C, Trappe HJ. Randomized comparison of simultaneous biventricular stimulation versus optimized interventricular delay in cardiac resynchronization therapy. The Resynchronization for the HemodYnamic Treatment for Heart Failure Management II implantable cardioverter defibrillator (RHYTHM II ICD) study. Am Heart J (2006) 151:1050–1058.[CrossRef][Web of Science][Medline]
- Bordachar P, Lafitte S, Reuter S, Sanders P, Jais P, Haissaguerre M, Roudaut R, Garrigue S, Clementy J. Echocardiographic parameters of ventricular dyssynchrony validation in patients with heart failure using sequential biventricular pacing. J Am Coll Cardiol (2004) 44:2157–2165.
[Abstract/Free Full Text] - Mortensen PT, Sogaard P, Mansour H, Ponsonaille J, Gras D, Lazarus A, Reiser W, Alonso C, Linde CM, Lunati M, Kramm B, Harrison EM. Sequential biventricular pacing: evaluation of safety and efficacy. Pacing Clin Electrophysiol (2004) 27:339–345.[CrossRef][Medline]
- Vanderheyden M, De Backer T, Rivero-Ayerza M, Geelen P, Bartunek J, Verstreken S, De Zutter M, Goethals M. Tailored echocardiographic interventricular delay programming further optimizes left ventricular performance after cardiac resynchronization therapy. Heart Rhythm (2005) 2:1066–1072.[CrossRef][Web of Science][Medline]
- Sogaard P, Egeblad H, Pedersen AK, Kim WY, Kristensen BO, Hansen PS, Mortensen PT. Sequential versus simultaneous biventricular resynchronization for severe heart failure: evaluation by tissue Doppler imaging. Circulation (2002) 106:2078–2084.
[Abstract/Free Full Text] - Vidal B, Sitges M, Marigliano A, Delgado V, Diaz-Infante E, Azqueta M, Tamborero D, Tolosana JM, Berruezo A, Perez-Villa F, Pare C, Mont L, Brugada J. Optimizing the programation of cardiac resynchronization therapy devices in patients with heart failure and left bundle branch block. Am J Cardiol (2007) 100:1002–1006.[CrossRef][Web of Science][Medline]
- Novak M, Lipoldova J, Meluzin J, Krejci J, Hude P, Feitova V, Dusek L, Kamaryt P, Vitovec J. Contribution to the V-V interval optimization in patients with cardiac resynchronization therapy. Physiol Res (2007) Epub 11 October.
- Perego GB, Chianca R, Facchini M, Frattola A, Balla E, Zucchi S, Cavaglia S, Vicini I, Negretto M, Osculati G. Simultaneous vs. sequential biventricular pacing in dilated cardiomyopathy: an acute hemodynamic study. Eur J Heart Fail (2003) 5:305–313.
[Abstract/Free Full Text] - Hay I, Melenovsky V, Fetics BJ, Judge DP, Kramer A, Spinelli J, Reister C, Kass DA, Berger RD. Short-term effects of right-left heart sequential cardiac resynchronization in patients with heart failure, chronic atrial fibrillation, and atrioventricular nodal block. Circulation (2004) 110:3404–3410.
[Abstract/Free Full Text] - van Gelder BM, Bracke FA, Meijer A, Lakerveld LJ, Pijls NH. Effect of optimizing the VV interval on left ventricular contractility in cardiac resynchronization therapy. Am J Cardiol (2004) 93:1500–1503.[CrossRef][Web of Science][Medline]
- Kurzidim K, Reinke H, Sperzel J, Schneider HJ, Danilovic D, Siemon G, Neumann T, Hamm CW, Pitschner HF. Invasive optimization of cardiac resynchronization therapy: role of sequential biventricular and left ventricular pacing. Pacing Clin Electrophysiol (2005) 28:754–761.[CrossRef][Medline]
- Whinnett ZI, Davies JE, Willson K, Manisty CH, Chow AW, Foale RA, Davies DW, Hughes AD, Mayet J, Francis DP. Haemodynamic effects of changes in atrioventricular and interventricular delay in cardiac resynchronisation therapy show a consistent pattern: analysis of shape, magnitude and relative importance of atrioventricular and interventricular delay. Heart (2006) 92:1628–1634.
[Abstract/Free Full Text] - Vidal B, Tamborero D, Mont L, Sitges M, Delgado V, Berruezo A, Diaz-Infante E, Tolosana JM, Pare C, Brugada J. Electrocardiographic optimization of interventricular delay in cardiac resynchronization therapy: a simple method to optimize the device. J Cardiovasc Electrophysiol (2007) 18:1252–1257.[CrossRef][Web of Science][Medline]
- Baker JH, McKenzie J III, Beau S, Greer GS, Porterfield J, Fedor M, Greenberg S, Daoud EG, Corbisiero R, Bailey JR, Porterfield L. Acute evaluation of programmer-guided AV/PV and VV delay optimization comparing an IEGM method and echocardiogram for cardiac resynchronization therapy in heart failure patients and dual-chamber ICD implants. J Cardiovasc Electrophysiol (2007) 18:185–191.[CrossRef][Web of Science][Medline]
- Porciani MC, Rao CM, Mochi M, Cappelli F, Bongiorno G, Perini AP, Lilli A, Ricciardi G, Hashtroudi L, Silvestri P, Barold SS, Padeletti L. A real-time three-dimensional echocardiographic validation of an intracardiac electrogram-based method for optimizing cardiac resynchronization therapy. Pacing Clin Electrophysiol (2008) 31:56–63.[Medline]
- Pak PH, Kass DA. Assessment of ventricular function in dilated cardiomyopathies. Curr Opin Cardiol (1995) 10:339–344.[CrossRef][Web of Science][Medline]
- Dubin J, Wallerson DC, Cody RJ, Devereux RB. Comparative accuracy of Doppler echocardiographic methods for clinical stroke volume determination. Am Heart J (1990) 120:116–123.[CrossRef][Web of Science][Medline]
- Pozzoli M, Capomolla S, Cobelli F, Tavazzi L. Reproducibility of Doppler indices of left ventricular systolic and diastolic function in patients with severe chronic heart failure. Eur Heart J (1995) 16:194–200.
[Abstract/Free Full Text] - Gola A, Pozzoli M, Capomolla S, Traversi E, Sanarico M, Cobelli F, Tavazzi L. Comparison of Doppler echocardiography with thermodilution for assessing cardiac output in advanced congestive heart failure. Am J Cardiol (1996) 78:708–712.[CrossRef][Web of Science][Medline]
- Coats AJ. Doppler ultrasonic measurement of cardiac output: reproducibility and validation. Eur Heart J (1990) 11(Suppl. I):49–61.
[Abstract/Free Full Text] - Harrison MR, Smith MD, Nissen SE, Grayburn PA, DeMaria AN. Use of exercise Doppler echocardiography to evaluate cardiac drugs: effects of propranolol and verapamil on aortic blood flow velocity and acceleration. J Am Coll Cardiol (1988) 11:1002–1009.[Abstract]
- Christie J, Sheldahl LM, Tristani FE, Sagar KB, Ptacin MJ, Wann S. Determination of stroke volume and cardiac output during exercise: comparison of two-dimensional and Doppler echocardiography, Fick oximetry, and thermodilution. Circulation (1987) 76:539–547.
[Abstract/Free Full Text] - Wong M, Matsumura M, Omoto R. Left and right ventricular flows by Doppler echocardiography: serial measurements in patients with aortic regurgitation during exercise, cold pressor stimulation, and vasodilation. J Am Soc Echocardiogr (1990) 3:285–293.[Medline]
- Wish M, Fletcher RD, Gottdiener JS, Cohen AI. Importance of left atrial timing in the programming of dual-chamber pacemakers. Am J Cardiol (1987) 60:566–571.[CrossRef][Web of Science][Medline]
- Jansen AH, Bracke FA, van Dantzig JM, Meijer A, van der Voort PH, Aarnoudse W, van Gelder BM, Peels KH. Correlation of echo-Doppler optimization of atrioventricular delay in cardiac resynchronization therapy with invasive hemodynamics in patients with heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. Am J Cardiol (2006) 97:552–557.[CrossRef][Web of Science][Medline]
- Sawhney NS, Waggoner AD, Garhwal S, Chawla MK, Osborn J, Faddis MN. Randomized prospective trial of atrioventricular delay programming for cardiac resynchronization therapy. Heart Rhythm (2004) 1:562–567.[CrossRef][Web of Science][Medline]
- Kerlan JE, Sawhney NS, Waggoner AD, Chawla MK, Garhwal S, Osborn JL, Faddis MN. Prospective comparison of echocardiographic atrioventricular delay optimization methods for cardiac resynchronization therapy. Heart Rhythm (2006) 3:148–154.[CrossRef][Web of Science][Medline]
- Gold MR, Niazi I, Giudici M, Leman RB, Sturdivant JL, Kim MH, Yu Y, Ding J, Waggoner AD. A prospective comparison of AV delay programming methods for hemodynamic optimization during cardiac resynchronization therapy. J Cardiovasc Electrophysiol (2007) 18:1–7.[CrossRef][Web of Science][Medline]
- Nishimura RA, Hayes DL, Holmes DR Jr, Tajik AJ. Mechanism of hemodynamic improvement by dual-chamber pacing for severe left ventricular dysfunction: an acute Doppler and catheterization hemodynamic study. J Am Coll Cardiol (1995) 25:281–288.[Abstract]
- DiCarlo LA Jr, Morady F, Krol RB, Baerman JM, de Buitleir M, Schork MA, Sereika SM, Schurig L. The hemodynamic effects of ventricular pacing with and without atrioventricular synchrony in patients with normal and diminished left ventricular function. Am Heart J (1987) 114:746–752.[CrossRef][Web of Science][Medline]
- Ovsyshcher IE. Toward physiological pacing: optimization of cardiac hemodynamics by AV delay adjustment. Pacing Clin Electrophysiol (1997) 20:861–865.[CrossRef][Medline]
- Brecker SJ, Xiao HB, Sparrow J, Gibson DG. Effects of dual-chamber pacing with short atrioventricular delay in dilated cardiomyopathy. Lancet (1992) 340:1308–1312.[CrossRef][Web of Science][Medline]
- Linde C, Gadler F, Edner M, Nordlander R, Rosenqvist M, Ryden L. Results of atrioventricular synchronous pacing with optimized delay in patients with severe congestive heart failure. Am J Cardiol (1995) 75:919–923.[CrossRef][Web of Science][Medline]
- Reiter MJ, Hindman MC. Hemodynamic effects of acute atrioventricular sequential pacing in patients with left ventricular dysfunction. Am J Cardiol (1982) 49:687–692.[CrossRef][Web of Science][Medline]
- Auricchio A, Fantoni C, Steinberg JS. Acute and chronic sequelae of ventricular dyssynchrony. Prog Cardiovasc Dis (2006) 48:227–231.[CrossRef][Web of Science][Medline]
- Xiao HB, Lee CH, Gibson DG. Effect of left bundle branch block on diastolic function in dilated cardiomyopathy. Br Heart J (1991) 66:443–447.
[Abstract/Free Full Text] - Nof E, Glikson M, Bar-Lev D, Gurevitz O, Luria D, Eldar M, Schwammenthal E. Mechanism of diastolic mitral regurgitation in candidates for cardiac resynchronization therapy. Am J Cardiol (2006) 97:1611–1614.[CrossRef][Web of Science][Medline]
- Naqvi TZ, Rafique AM. Novel insights on effect of atrioventricular programming of biventricular pacemaker in heart failure—a case series. Cardiovasc Ultrasound (2006) 4:38.[CrossRef][Medline]
- Morales MA, Startari U, Panchetti L, Rossi A, Piacenti M. Atrioventricular delay optimization by doppler-derived left ventricular dP/dt improves 6-month outcome of resynchronized patients. Pacing Clin Electrophysiol (2006) 29:564–568.[CrossRef][Medline]
- Inoue N, Ishikawa T, Sumita S, Nakagawa T, Kobayashi T, Matsushita K, Matsumoto K, Ohkusu Y, Taima M, Kosuge M, Uchino K, Kimura K, Umemura S. Long-term follow-up of atrioventricular delay optimization in patients with biventricular pacing. Circ J (2005) 69:201–204.[CrossRef][Web of Science][Medline]
- Riedlbauchova L, Kautzner J, Fridl P. Influence of different atrioventricular and interventricular delays on cardiac output during cardiac resynchronization therapy. Pacing Clin Electrophysiol (2005) 28(Suppl. 1):S19–S23.[CrossRef][Medline]
- Hardt SE, Yazdi SH, Bauer A, Filusch A, Korosoglou G, Hansen A, Bekeredjian R, Ehlermann P, Remppis A, Katus HA, Kuecherer HF. Immediate and chronic effects of AV-delay optimization in patients with cardiac resynchronization therapy. Int J Cardiol (2007) 115:318–325.[CrossRef][Web of Science][Medline]
- Meluzin J, Novak M, Mullerova J, Krejci J, Hude P, Eisenberger M, Dusek L, Dvorak I, Spinarova L. A fast and simple echocardiographic method of determination of the optimal atrioventricular delay in patients after biventricular stimulation. Pacing Clin Electrophysiol (2004) 27:58–64.[CrossRef][Medline]
- Stockburger M, Fateh-Moghadam S, Nitardy A, Langreck H, Haverkamp W, Dietz R. Optimization of cardiac resynchronization guided by Doppler echocardiography: haemodynamic improvement and intraindividual variability with different pacing configurations and atrioventricular delays. Europace (2006) 8:881–886.
[Abstract/Free Full Text] - Melzer C, Knebel F, Ismer B, Bondke H, Nienaber CA, Baumann G, Borges AC. Influence of the atrio-ventricular delay optimization on the intra left ventricular delay in cardiac resynchronization therapy. Cardiovasc Ultrasound (2006) 4:5.[CrossRef][Medline]
- Scharf C, Li P, Muntwyler J, Chugh A, Oral H, Pelosi F, Morady F, Armstrong WF. Rate-dependent AV delay optimization in cardiac resynchronization therapy. Pacing Clin Electrophysiol (2005) 28:279–284.[CrossRef][Medline]
- Kedia N, Ng K, Apperson-Hansen C, Wang C, Tchou P, Wilkoff BL, Grimm RA. Usefulness of atrioventricular delay optimization using Doppler assessment of mitral inflow in patients undergoing cardiac resynchronization therapy. Am J Cardiol (2006) 98:780–785.[CrossRef][Web of Science][Medline]
- Ritter P, Lelieve T, Lavergne T. Quick determination of the optimal AV delay at rest in patients paced in DDD mode for complete AV block. Eur J Cardiac Pacing Electrophysiol (1994) 4:P54.
- Kindermann M, Frohlig G, Doerr T, Schieffer H. Optimizing the AV delay in DDD pacemaker patients with high degree AV block: mitral valve Doppler versus impedance cardiography. Pacing Clin Electrophysiol (1997) 20:2453–2462.[CrossRef][Medline]
- Dupuis JM, Kobeissi A, Vitali L, Gaggini G, Merheb M, Rouleau F, Leftheriotis G, Ritter P, Victor J. Programming optimal atrioventricular delay in dual chamber pacing using peak endocardial acceleration: comparison with a standard echocardiographic procedure. Pacing Clin Electrophysiol (2003) 26:210–213.[CrossRef][Medline]
- Melzer C, Borges AC, Knebel F, Richter WS, Combs W, Baumann G, Theres H. Echocardiographic AV-interval optimization in patients with reduced left ventricular function. Cardiovasc Ultrasound (2004) 2:30.[CrossRef][Medline]
- Burri H, Sunthorn H, Shah D, Lerch R. Optimization of device programming for cardiac resynchronization therapy. Pacing Clin Electrophysiol (2006) 29:1416–1425.[CrossRef][Medline]
- Ishikawa T, Sumita S, Kimura K, Kuji N, Nakayama R, Nagura T, Miyazaki N, Tochikubo O, Usui T, Kashiwagi M. Critical PQ interval for the appearance of diastolic mitral regurgitation and optimal PQ interval in patients implanted with DDD pacemakers. Pacing Clin Electrophysiol (1994) 17:1989–1994.[CrossRef][Medline]
- Ishikawa T, Sumita S, Kimura K, Kikuchi M, Kosuge M, Kuji N, Endo T, Sugano T, Sigemasa T, Kobayashi I, Tochikubo O, Usui T. Prediction of optimal atrioventricular delay in patients with implanted DDD pacemakers. Pacing Clin Electrophysiol (1999) 22:1365–1371.[CrossRef][Medline]
- Bargiggia GS, Bertucci C, Recusani F, Raisaro A, de Servi S, Valdes-Cruz LM, Sahn DJ, Tronconi L. A new method for estimating left ventricular dP/dt by continuous wave Doppler-echocardiography. Validation studies at cardiac catheterization. Circulation (1989) 80:1287–1292.
[Abstract/Free Full Text] - Chen C, Rodriguez L, Lethor JP, Levine RA, Semigran MS, Fifer MA, Weyman AE, Thomas JD. Continuous wave Doppler echocardiography for noninvasive assessment of left ventricular dP/dt and relaxation time constant from mitral regurgitant spectra in patients. J Am Coll Cardiol (1994) 23:970–976.[Abstract]
- Chung N, Nishimura RA, Holmes DR Jr, Tajik AJ. Measurement of left ventricular dP/dt by simultaneous Doppler echocardiography and cardiac catheterization. J Am Soc Echocardiogr (1992) 5:147–152.[Medline]
- Porciani MC, Fantini F, Musilli N, Sabini A, Michelucci A, Colella A, Pieragnoli P, Demarchi G, Padeletti L. A perspective on atrioventricular delay optimization in patients with a dual chamber pacemaker. Pacing Clin Electrophysiol (2004) 27:333–338.[CrossRef][Medline]
- Porciani MC, Dondina C, Macioce R, Demarchi G, Pieragnoli P, Musilli N, Colella A, Ricciardi G, Michelucci A, Padeletti L. Echocardiographic examination of atrioventricular and interventricular delay optimization in cardiac resynchronization therapy. Am J Cardiol (2005) 95:1108–1110.[CrossRef][Web of Science][Medline]
- Tei C, Ling LH, Hodge DO, Bailey KR, Oh JK, Rodeheffer RJ, Tajik AJ, Seward JB. New index of combined systolic and diastolic myocardial performance: a simple and reproducible measure of cardiac function—a study in normals and dilated cardiomyopathy. J Cardiol (1995) 26:357–366.[Medline]
- Tei C, Nishimura RA, Seward JB, Tajik AJ. Noninvasive Doppler-derived myocardial performance index: correlation with simultaneous measurements of cardiac catheterization measurements. J Am Soc Echocardiogr (1997) 10:169–178.[CrossRef][Web of Science][Medline]
- Swedberg K, Cleland J, Dargie H, Drexler H, Follath F, Komajda M, Tavazzi L, Smiseth OA, Gavazzi A, Haverich A, Hoes A, Jaarsma T, Korewicki J, Levy S, Linde C, Lopez-Sendon JL, Nieminen MS, Pierard L, Remme WJ. Guidelines for the diagnosis and treatment of chronic heart failure: executive summary (update 2005): The Task Force for the Diagnosis and Treatment of Chronic Heart Failure of the European Society of Cardiology. Eur Heart J (2005) 26:1115–1140.
[Free Full Text] - Auricchio A, Stellbrink C, Sack S, Block M, Vogt J, Bakker P, Huth C, Schondube F, Wolfhard U, Bocker D, Krahnefeld O, Kirkels H. Long-term clinical effect of hemodynamically optimized cardiac resynchronization therapy in patients with heart failure and ventricular conduction delay. J Am Coll Cardiol (2002) 39:2026–2033.
[Abstract/Free Full Text] - Auricchio A, Stellbrink C, Butter C, Sack S, Vogt J, Misier AR, Bocker D, Block M, Kirkels JH, Kramer A, Huvelle E. Clinical efficacy of cardiac resynchronization therapy using left ventricular pacing in heart failure patients stratified by severity of ventricular conduction delay. J Am Coll Cardiol (2003) 42:2109–2116.
[Abstract/Free Full Text] - Auricchio A, Stellbrink C, Block M, Sack S, Vogt J, Bakker P, Klein H, Kramer A, Ding J, Salo R, Tockman B, Pochet T, Spinelli J. Effect of pacing chamber and atrioventricular delay on acute systolic function of paced patients with congestive heart failure. The Pacing Therapies for Congestive Heart Failure Study Group. The Guidant Congestive Heart Failure Research Group. Circulation (1999) 99:2993–3001.
[Abstract/Free Full Text] - Auricchio A, Ding J, Spinelli JC, Kramer AP, Salo RW, Hoersch W, KenKnight BH, Klein HU. Cardiac resynchronization therapy restores optimal atrioventricular mechanical timing in heart failure patients with ventricular conduction delay. J Am Coll Cardiol (2002) 39:1163–1169.
[Abstract/Free Full Text] - van Gelder BM, Bracke FA, Meijer A, Pijls NH. The hemodynamic effect of intrinsic conduction during left ventricular pacing as compared to biventricular pacing. J Am Coll Cardiol (2005) 46:2305–2310.
[Abstract/Free Full Text] - Crystal E, Ovsyshcher IE. Cardiac output-based versus empirically programmed AV interval–how different are they? Europace (1999) 1:121–125.
[Abstract/Free Full Text] - Wang DJ, Gottlieb SS. Impedance cardiography: more questions than answers. Curr Cardiol Rep (2006) 8:180–186.[CrossRef][Medline]
- Leslie SJ, McKee S, Newby DE, Webb DJ, Denvir MA. Non-invasive measurement of cardiac output in patients with chronic heart failure. Blood Press Monit (2004) 9:277–280.[CrossRef][Web of Science][Medline]
- Santos JF, Parreira L, Madeira J, Fonseca N, Soares LN, Ines L. Non invasive hemodynamic monitorization for AV interval optimization in patients with ventricular resynchronization therapy. Rev Port Cardiol (2003) 22:1091–1098.[Medline]
- Tse HF, Yu C, Park E, Lau CP. Impedance cardiography for atrioventricular interval optimization during permanent left ventricular pacing. Pacing Clin Electrophysiol (2003) 26:189–191.[CrossRef][Medline]
- Braun MU, Schnabel A, Rauwolf T, Schulze M, Strasser RH. Impedance cardiography as a noninvasive technique for atrioventricular interval optimization in cardiac resynchronization therapy. J Interv Card Electrophysiol (2005) 13:223–229.[CrossRef][Web of Science][Medline]
- Heinroth KM, Elster M, Nuding S, Schlegel F, Christoph A, Carter J, Buerke M, Werdan K. Impedance cardiography: a useful and reliable tool in optimization of cardiac resynchronization devices. Europace (2007) 9:744–750.
[Abstract/Free Full Text] - Butter C, Stellbrink C, Belalcazar A, Villalta D, Schlegl M, Sinha A, Cuesta F, Reister C. Cardiac resynchronization therapy optimization by finger plethysmography. Heart Rhythm (2004) 1:568–575.[CrossRef][Web of Science][Medline]
- Whinnett ZI, Davies JE, Willson K, Chow AW, Foale RA, Davies DW, Hughes AD, Francis DP, Mayet J. Determination of optimal atrioventricular delay for cardiac resynchronization therapy using acute non-invasive blood pressure. Europace (2006) 8:358–366.
[Abstract/Free Full Text] - St Jude Medical. Frequent Optimization Study Using the QuickOpt Method study. www.clinicaltrials.gov/ct2/show/NCT00418314.
- Rickards AF, Bombardini T, Corbucci G, Plicchi G. An implantable intracardiac accelerometer for monitoring myocardial contractility. The Multicenter PEA Study Group. Pacing Clin Electrophysiol (1996) 19:2066–2071.[CrossRef][Medline]
- Sorin Group. Clinical Evaluation of Advanced Resynchronization study. www.clinicaltrials.gov/ct2/show/NCT00658203.
- Abraham WT. Rationale and design of a randomized clinical trial to assess the safety and efficacy of cardiac resynchronization therapy in patients with advanced heart failure: the Multicenter InSync Randomized Clinical Evaluation (MIRACLE). J Card Fail (2000) 6:369–380.[CrossRef][Web of Science][Medline]
- Cleland JG, Daubert JC, Erdmann E, Freemantle N, Gras D, Kappenberger L, Klein W, Tavazzi L. The CARE-HF study (CArdiac REsynchronisation in Heart Failure study): rationale, design and end-points. Eur J Heart Fail (2001) 3:481–489.
[Abstract/Free Full Text] - St.John Sutton MG, Plappert T, Abraham WT, Smith AL, DeLurgio DB, Leon AR, Loh E, Kocovic DZ, Fisher WG, Ellestad M, Messenger J, Kruger K, Hilpisch KE, Hill MR. Effect of cardiac resynchronization therapy on left ventricular size and function in chronic heart failure. Circulation (2003) 107:1985–1990.
[Abstract/Free Full Text] - John Sutton MG St., Plappert T, Hilpisch KE, Abraham WT, Hayes DL, Chinchoy E. Sustained reverse left ventricular structural remodeling with cardiac resynchronization at one year is a function of etiology: quantitative Doppler echocardiographic evidence from the Multicenter InSync Randomized Clinical Evaluation (MIRACLE). Circulation (2006) 113:266–272.
[Abstract/Free Full Text] - O'Donnell D, Nadurata V, Hamer A, Kertes P, Mohammed W. Long-term variations in optimal programming of cardiac resynchronization therapy devices. Pacing Clin Electrophysiol (2005) 28(Suppl. 1):S24–S26.[CrossRef][Medline]
- Porciani MC, Dondina C, Macioce R, Demarchi G, Cappelli F, Lilli A, Pappone A, Ricciardi G, Colombo PC, Padeletti M, Jelic S, Padeletti L. Temporal variation in optimal atrioventricular and interventricular delay during cardiac resynchronization therapy. J Card Fail (2006) 12:715–719.[CrossRef][Web of Science][Medline]
- Zhang Q, Wing-Hong FJ, Chan YS, Chi-Kin CH, Lin H, Chan S, Yu CM. The role of repeating optimization of atrioventricular interval during interim and long-term follow-up after cardiac resynchronization therapy. Int J Cardiol (2007) 124:211–217.[Web of Science][Medline]
- Hawkins NM, Petrie MC, Macdonald MR, Hogg KJ, McMurray JJ. Selecting patients for cardiac resynchronization therapy: electrical or mechanical dyssynchrony? Eur Heart J (2006) 27:1270–1281.
[Abstract/Free Full Text] - Cleland JG, Freemantle N, Daubert JC, Toff WD, Leisch F, Tavazzi L. Long-term effect of cardiac resynchronisation in patients reporting mild symptoms of heart failure: a report from the CARE-HF study. Heart (2008) 94:278–283.
[Abstract/Free Full Text] - Burri H, Sunthorn H, Somsen A, Zaza S, Fleury E, Shah D, Righetti A. Optimizing sequential biventricular pacing using radionuclide ventriculography. Heart Rhythm (2005) 2:960–965.[CrossRef][Web of Science][Medline]
- Gold MR, Feliciano Z, Gottlieb SS, Fisher ML. Dual-chamber pacing with a short atrioventricular delay in congestive heart failure: a randomized study. J Am Coll Cardiol (1995) 26:967–973.[Abstract]
- Faerestrand S, Ohm OJ. A time-related study of the hemodynamic benefit of atrioventricular synchronous pacing evaluated by Doppler echocardiography. Pacing Clin Electrophysiol (1985) 8:838–848.[CrossRef][Medline]
- Haskell RJ, French WJ. Optimum AV interval in dual chamber pacemakers. Pacing Clin Electrophysiol (1986) 9:670–675.[CrossRef][Medline]
- Forfang K, Otterstad JE, Ihlen H. Optimal atrioventricular delay in physiological pacing determined by Doppler echocardiography. Pacing Clin Electrophysiol (1986) 9:17–20.[CrossRef][Medline]
- Freedman RA, Yock PG, Echt DS, Popp RL. Effect of variation in PQ interval on patterns of atrioventricular valve motion and flow in patients with normal ventricular function. J Am Coll Cardiol (1986) 7:595–602.[Abstract]
- Iwase M, Sotobata I, Yokota M, Takagi S, Jing HX, Kawai N, Hayashi H, Murase M. Evaluation by pulsed Doppler echocardiography of the atrial contribution to left ventricular filling in patients with DDD pacemakers. Am J Cardiol (1986) 58:104–109.[CrossRef][Web of Science][Medline]
- von Bibra H, Wirtzfeld A, Hall R, Ulm K, Blomer H. Mitral valve closure and left ventricular filling time in patients with VDD pacemakers. Assessment of the onset of left ventricular systole and the end of diastole. Br Heart J (1986) 55:355–363.
[Abstract/Free Full Text] - Wish M, Gottdiener JS, Cohen AI, Fletcher RD. M-mode echocardiograms for determination of optimal left atrial timing in patients with dual chamber pacemakers. Am J Cardiol (1988) 61:317–322.[CrossRef][Web of Science][Medline]
- Pearson AC, Janosik DL, Redd RR, Buckingham TA, Blum RI, Labovitz AJ. Doppler echocardiographic assessment of the effect of varying atrioventricular delay and pacemaker mode on left ventricular filling. Am Heart J (1988) 115:611–621.[CrossRef][Web of Science][Medline]
- Janosik DL, Pearson AC, Buckingham TA, Labovitz AJ, Redd RM. The hemodynamic benefit of differential atrioventricular delay intervals for sensed and paced atrial events during physiologic pacing. J Am Coll Cardiol (1989) 14:499–507.[Abstract]
- Mehta D, Gilmour S, Ward DE, Camm AJ. Optimal atrioventricular delay at rest and during exercise in patients with dual chamber pacemakers: a non-invasive assessment by continuous wave Doppler. Br Heart J (1989) 61:161–166.
[Abstract/Free Full Text] - Occhetta E, Piccinino C, Francalacci G, Magnani A, Bolognese L, Devecchi P, Rognoni G, Rossi P. Lack of influence of atrioventricular delay on stroke volume at rest in patients with complete atrioventricular block and dual chamber pacing. Pacing Clin Electrophysiol (1990) 13:916–926.[CrossRef][Medline]
- Auricchio A, Sommariva L, Salo RW, Scafuri A, Chiariello L. Improvement of cardiac function in patients with severe congestive heart failure and coronary artery disease by dual chamber pacing with shortened AV delay. Pacing Clin Electrophysiol (1993) 16:2034–2043.[CrossRef][Medline]
- Shinbane JS, Chu E, DeMarco T, Sobol Y, Fitzpatrick AP, Lau DM, Klinski C, Schiller NB, Griffin JC, Chatterjee K. Evaluation of acute dual-chamber pacing with a range of atrioventricular delays on cardiac performance in refractory heart failure. J Am Coll Cardiol (1997) 30:1295–1300.[Abstract]
- Leonelli FM, Wang K, Youssef M, Hall R, Brown D. Systolic and diastolic effects of variable atrioventricular delay in patients with complete heart block and normal ventricular function. Am J Cardiol (1997) 80:294–298.[CrossRef][Web of Science][Medline]
- Khairy P, Talajic M, Dominguez M, Tardif JC, Juneau M, Lavoie L, Roy D, Dubuc M. Atrioventricular interval optimization and exercise tolerance. Pacing Clin Electrophysiol (2001) 24:1534–1540.[CrossRef][Medline]
- Toda N, Ishikawa T, Nozawa N, Kobayashi I, Ochiai H, Miyamoto K, Sumita S, Kimura K, Umemura S. Doppler index and plasma level of atrial natriuretic hormone are improved by optimizing atrioventricular delay in atrioventricular block patients with implanted DDD pacemakers. Pacing Clin Electrophysiol (2001) 24:1660–1663.[CrossRef][Medline]
- Leclercq C, Walker S, Linde C, Clementy J, Marshall AJ, Ritter P, Djiane P, Mabo P, Levy T, Gadler F, Bailleul C, Daubert JC. Comparative effects of permanent biventricular and right-univentricular pacing in heart failure patients with chronic atrial fibrillation. Eur Heart J (2002) 23:1780–1787.
[Abstract/Free Full Text] - Higgins SL, Hummel JD, Niazi IK, Giudici MC, Worley SJ, Saxon LA, Boehmer JP, Higginbotham MB, De Marco T, Foster E, Yong PG. Cardiac resynchronization therapy for the treatment of heart failure in patients with intraventricular conduction delay and malignant ventricular tachyarrhythmias. J Am Coll Cardiol (2003) 42:1454–1459.
[Abstract/Free Full Text]
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. Bertini, V. Delgado, J. J. Bax, and N. R.L. Van de Veire Why, how and when do we need to optimize the setting of cardiac resynchronization therapy? Europace, November 1, 2009; 11(suppl_5): v46 - v57. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. W.L. De Boeck, A. J. Teske, M. Meine, G. E. Leenders, M. J. Cramer, F. W. Prinzen, and P. A. Doevendans Septal rebound stretch reflects the functional substrate to cardiac resynchronization therapy and predicts volumetric and neurohormonal response Eur J Heart Fail, September 1, 2009; 11(9): 863 - 871. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. M. Hawkins, M. C. Petrie, M. I. Burgess, and J. J.V. McMurray Selecting patients for cardiac resynchronization therapy: the fallacy of echocardiographic dyssynchrony. J. Am. Coll. Cardiol., May 26, 2009; 53(21): 1944 - 1959. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Abraham, D. Kass, G. Tonti, G. F. Tomassoni, W. T. Abraham, J. J. Bax, and T. H. Marwick Imaging Cardiac Resynchronization Therapy J. Am. Coll. Cardiol. Img., April 1, 2009; 2(4): 486 - 497. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Ballo, A. Motto, S. Mondillo, and M. Galderisi Three-dimensional echocardiography for optimization of cardiac resynchronization therapy Eur. Heart J., February 2, 2009; 30(4): 505 - 505. [Full Text] [PDF]
|
|
|
|
 |
|
 J. McMurray, M. Petrie, K. Swedberg, M. Komajda, S. Anker, and R. Gardner CHAPTER 23 Heart Failure ESC Textbook of Cardiovascular Medicine, January 1, 2009; 2(1): med-9780199566990-chapter - med-9780199566990-chapter. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||