Long-term clinical effects of programmer-guided atrioventricular and interventricular delay optimization: Intracardiac electrography versus echocardiography for cardiac resynchronization therapy in patients with heart failure

Abstract

Objectives

To compare the haemodynamic results and long-term clinical outcomes of intracardiac electrography (QuickOpt®; St Jude Medical, St Paul, MN, USA) and echocardiography for optimization of atrioventricular (AV) and interventricular (VV) delays in cardiac resynchronization therapy (CRT).

Methods

Patients with CRT devices were prospectively enrolled; AV/VV delays were optimized by either QuickOpt® or echocardiography. Patients in the QuickOpt® group underwent both echocardiography and QuickOpt® optimization, and QuickOpt® AV/VV delays were used to program the CRT. All patients were followed-up for 12 months.

Results

In total, 44 patients were enrolled. There was good correlation between AV/VV delays determined by QuickOpt® (n = 20) and echocardiography (n = 24). QuickOpt® was significantly faster than echocardiography-guided optimization. Cardiac function, 6-min walking distance and left ventricular ejection fraction were significantly and similarly improved in both groups at 6 and 12 months compared with baseline. In the QuickOpt® group, left ventricular end diastolic diameters were significantly smaller at 6 and 12 months compared with baseline.

Conclusions

QuickOpt® is a quick, convenient and easy to perform method for optimization of AV and VV delays, with a similar long-term clinical outcome to echocardiography-guided optimization.

Keywords

Atrioventricular delay cardiac resynchronization therapy echocardiography heart failure interventricular delay intracardiac electrography QuickOpt®

Introduction

The optimization of atrioventricular (AV) and interventricular (VV) delays is a key strategy for ensuring a beneficial clinical outcome in cardiac resynchronization therapy (CRT).¹ Optimization is usually performed via standard Doppler echocardiography, but this is expensive and time consuming (taking 1–1.5 h), and requires skilled physicians and a high level of patient co-operation. QuickOpt® Timing Cycle Optimization (St Jude Medical; St Paul, MN, USA) is an intracardiac electrography-guided timing cycle optimization algorithm, incorporated within St Jude Medical devices and programs.^2–5 It allows rapid (1–2 min), simple, cost-effective and automatic determination of optimal AV/VV delays, with good patient compliance.⁶ To our knowledge, there have been no prospective studies comparing the long-term clinical effectiveness of intracardiac electrography and standard echocardiography in AV/VV delay optimization. The aims of this study were to compare the haemodynamic results of intracardiac electrography (using QuickOpt®) and echocardiography in AV/VV delay optimization, and to observe the long-term clinical outcomes of the two methods.

Patients and methods

Study Population

This prospective, comparative study recruited patients who were hospitalized at the Department of Cardiology, Shenyang Northern Hospital, Shenyang, China, for implantation of St Jude Medical CRT devices, between February 2007 and May 2009. All patients met the following standard criteria for CRT:⁷ (i) left ventricular ejection fraction (LVEF) ≤35%; (ii) New York Heart Association (NYHA) class III–IV heart failure;⁸ (iii) QRS complex duration ≥120 ms; (iv) ≥6 months’ history of heart failure; (v) repeated episodes of heart failure, despite optimal medical treatment. Patients with persistent atrial fibrillation, high-grade atrioventricular block or QRS complex duration <120 ms were excluded. All patients continued to receive heart failure medication after CRT implantation.

The study protocol was approved by the Ethics Committee of Shenyang Northern Hospital, Shenyang, China. All participants provided written informed consent prior to enrolling in the study.

AV/VV Delay Optimization

Patients were randomly divided into two groups (using a computer-generated randomization schedule) to undergo AV/VV delay optimization, with either QuickOpt® or echocardiography.

Echocardiographic optimization was performed as follows. For AV delay optimization, the apical four-chamber view was used to measure the mitral inflow velocity profile at the mitral valve. AV delay was initially programmed at 60–200 ms, and adjusted in 20 ms increments. EA duration was measured at each AV interval, and optimal AV delay was defined as the maximal EA duration without truncating the A wave. For VV delay optimization, the apical five-chamber view was used to obtain the velocity-time integral (VTI) of left ventricular outflow tract. VV delay was programmed between −40 and +40 ms, with adjustment in 20-ms increments. Optimal VV delay resulted in maximal VTI.^9,10

In intracardiac electrography, the QuickOpt^TM algorithm was used to determine optimal delays. AV/VV delay optimization was performed within the first week following CRT implantation. Patients in the QuickOpt® group first underwent echocardiography-guided optimization to determine the maximum aortic velocity time interval (AVTI), followed by QuickOpt® optimization to test the AVTI. The QuickOpt® AV/VV delays were used to program the CRT. At 6 months after CRT implantation, patients underwent a second QuickOpt® optimization. Patients in the echocardiography group underwent optimization within the first week following CRT implantation, and again at 6 months after implantation.

Study Endpoints

Patients were followed-up by telephone once per month, for 12 months. In addition, patients attended hospital follow-up appointments at 6 and 12 months, and underwent examinations including NYHA cardiac functional classification,⁸ 6-min walking distance, and echocardiography (left ventricular end diastolic diameter [LVEDD] and left ventricular ejection fraction [LVEF]).

Statistical Analyses

Quantitative data were presented as mean ± SD, and categorical data as number (n) of patients (%). Between-group comparisons were made using Student’s t-test for continuous data and χ²-test with Yates’ correction for categorical data. The correlation between aortic VTI values obtained by echocardiography and QuickOpt® was analysed by concordance correlation coefficient. Statistical analyses were performed using SPSS® software, version 16.0 (SPSS Inc., Chicago, IL, USA) for Windows®. A P-value <0.05 was considered statistically significant.

Results

The study included 44 patients (29 males/15 females, mean age 60.34 ± 13.16 years, age range 33–85 years). The QuickOpt® group included 20 patients; the echocardiography group included 24 patients. All patients completed the 1-year follow-up period. Patients’ baseline demographic and clinical characteristics are shown in Table 1.

Table 1.

Baseline demographic and clinical characteristics of patients with cardiac resynchronization therapy (CRT) devices who were included in a study to compare QuickOpt® (St Jude Medical, St Paul, MN, USA) and echocardiography-guided optimization of atrioventricular (AV) and interventricular (VV) delays.

Characteristic	QuickOpt® group n = 20	Echocardiography group n = 24
Male	14 (70.0)	15 (62.5)
Age, years	59.35 ± 10.56	61.33 ± 10.48
PR interval, ms	187.37 ± 35.41	201.25 ± 38.48
QRS duration before CRT, ms	145.29 ± 21.88	162.06 ± 27.89
QRS duration after CRT, ms	123.00 ± 28.67	134.17 ± 24.48
Aetiology of cardiomyopathy
Ischaemic	5 (25.0)	8 (33.3)
Nonischaemic	15 (75.0)	16 (66.7)
NYHA class⁸	3.35 ± 0.49	3.38 ± 0.49
6-min walk test, m	277.15 ± 129.15	288.57 ± 115.74
LVEDD, mm	67.90 ± 5.89	71.25 ± 7.69
LVEF, %	28.60 ± 4.81	29.79 ± 5.57
Disease duration, years	4.02 ± 3.19	2.55 ± 3.75
Serum creatinine level, µmol/l	98.45 ± 17.93	117.5 ± 32.82^a
Cardioventricular pacing, %	98.16 ± 3.52	98.54 ± 4.28

Data presented as mean ± SD or n (%) of patients.

NYHA: New York Heart Association; LVEDD: left ventricular end diastolic diameter; LVEF: left ventricular ejection fraction.

P < 0.05 versus QuickOpt® group; Student’s t-test.

There was a good correlation between the optimal AV/VV delays as determined by echocardiography or QuickOpt® in the QuickOpt® group (P < 0.01 for each correlation, Table 2). Optimization was significantly faster with QuickOpt® than with echocardiography (total time 1.45 ± 0.39 min versus 63.65 ± 16.24 min; P < 0.01). Echocardiography optimizations of AV and VV delays took 27.15 ± 11.82 and 36.50 ± 12.73 min, respectively.

Table 2.

Correlations between maximum aortic velocity time intervals (maxAVTI) for optimization of atrioventricular (AV) and interventricular (VV) delays, as determined by echocardiography or QuickOpt® (St Jude Medical, St Paul, MN, USA) in patients with cardiac resynchronization therapy devices (n = 20).

Optimal delay	MaxAVTI, cm		r	Statistical significance^a
Optimal delay	Echocardiography	QuickOpt®	r	Statistical significance^a
Sensed AV	22.62 ± 5.98	20.84 ± 5.80	0.923	P < 0.01
Paced AV	21.99 ± 5.12	20.22 ± 5.44	0.894	P < 0.01
VV	22.56 ± 9.16	22.43 ± 5.24	0.948	P < 0.01

Data presented as mean ± SD.

Concordance correlation coefficient.

Data regarding cardiac function parameters at baseline, and 6 and 12 months after optimization, are shown in Table 3. There was a significant improvement in NYHA class, 6-min walking distance and LVEF in both groups at 6 and 12 months (P < 0.01 for all comparisons). There were no significant between-group differences in these parameters at any time point. QuickOpt® optimization resulted in a significant decrease in LVEDD at both 6 and 12 months (P < 0.05 and P < 0.01 versus baseline, respectively; Table 3). In addition, LVEDD was significantly lower in the QuickOpt® group than in the echocardiography group at 12 months after optimization (P < 0.01; Table 3).

Table 3.

Clinical and cardiac function parameters at baseline, and 6 and 12 months after optimization of atrioventricular (AV) and interventricular (VV) delays, using QuickOpt® (St Jude Medical, St Paul, MN, USA) or echocardiography-guided optimization in patients with cardiac resynchronization therapy devices.

Parameter	QuickOpt® group n = 20			Echocardiography group n = 24
Parameter	Baseline	6 months	12 months	Baseline	6 months	12 months
NYHA class⁸	3.35 ± 0.49	2.05 ± 0.69^a	1.81 ± 0.69^a	3.38 ± 0.49	2.02 ± 0.69^a	2.12 ± 0.79^a
6-min walking distance, m	227.15 ± 129.15	431.63 ± 168.21^a	430.28 ± 171.45^a	288.57 ± 115.74	391.64 ± 114.07^a	380.38 ± 117.63^a
LVEDD, mm	67.90 ± 5.89	62.47 ± 9.57^b	59.50 ± 8.35^a,c	71.25 ± 7.69	66.73 ± 9.57	66.48 ± 8.27
LVEF, %	28.60 ± 4.81	39.79 ± 7.12^a	42.33 ± 9.61^a	29.79 ± 5.57	42.41 ± 11.16^a	39.76 ± 7.93^a

P < 0.01 versus baseline, ^bP < 0.05 versus baseline, ^cP < 0.01 versus echocardiography at 12 months; Student’s t-test.

NYHA: New York Heart Association; LVEDD: left ventricular end diastolic diameter; LVEF: left ventricular ejection fraction.

Discussion

Cardiac resynchronization therapy is widely used to treat chronic congestive heart failure, and optimization of AV and VV delays reduces the nonresponse rate.^11–14 The ideal AV delay reflects co-ordinated atrioventricular contraction, and can enhance mitral blood flow and increase ventricular filling time.¹⁵ Under normal conditions, passive ventricular filling occurs during the early and mid-diastolic phases, when blood flows from the atrium to the ventricle due to atrioventricular pressure differences. The peak left atrial pressure occurs during the end-diastolic phase of the left ventricle, immediately before the start of left ventricular systole.¹⁶ Atrial contraction during the ventricular end-diastolic phase actively pushes blood to the ventricles, increasing LVEDD (preload) by 30%.¹⁷ The contribution of atrial contraction to ventricular filling enhances cardiac output, thus improving clinical symptoms, LVEF and diastolic function, and decreasing brain natriuretic peptide secretion.^18–20 Ventricular systole and diastole begin 20–30 ms earlier in the left ventricle than in the right, although both ventricles contract at the same time. Adjusting the VV interval can partially correct the inappropriate position of left ventricular CRT leads, by optimizing the stimulation timing sequence of the left and right ventricles (but not the overall activity sequence).²¹ The appropriate VV interval can effectively correct cardiac dys-synchrony.²² Greater preactivation of the left ventricle than the right has been shown to result in optimal haemodynamic benefits, with simultaneous biventricular contraction leading to the best haemodynamic response in <30% of patients.²³

Echocardiography-guided optimization of AA/VV delays is accurate and achievable, and is the first choice for postsurgery interval optimization.^24–28 Optimal delays are determined by mitral inflow velocity profile and left ventricular outflow tract velocity profile (VTI; reflecting the volume of blood ejected by the left ventricle to the aorta), which are obtained via Doppler echocardiography. The ideal AV delay shows separation of the E and A waves on transmitral inflow Doppler signals.²⁹ As left ventricular stroke volume is calculated as left ventricular outflow tract area ×VTI, and left ventricular outflow tract area is constant, left ventricular stroke volume increases with increasing VTI. Optimal AV/VV delays are therefore those intervals that maximize VTI. Echocardiography-guided optimization has several advantages, including the noninvasive nature of the procedure, reliability and good clinical outcomes.³⁰ The procedure is limited by its high cost and the length of time required to perform it, which both lead to poor compliance in some patients. In addition, accuracy and consistency are affected by the operational performance of technicians.

QuickOpt® timing cycle optimization is an algorithm that rapidly determines optimal AV and VV intervals based on heart electrical activity, as measured by intracardiac electrography.^18,31 Intracardiac electrography can accurately determine the duration of atrial activation and paced conduction properties of both ventricles, ensuring ventricle contraction begins after the mitral valve is completely closed, thereby reducing mitral regurgitation while maximizing left atrial preload.³² In addition, it ensures that both ventricular conduction waves and self-pacing stimuli arrive at the ventricular septum simultaneously, optimizing the AV/VV intervals.³³ QuickOpt® is rapid (∼1 min) and simple to perform, does not require special training and incurs no additional costs. Research has shown that QuickOpt® interval optimization is as accurate as echocardiographic optimization,³⁴ but poor correlation between QuickOpt® and echocardiography was reported elsewhere.³⁵ There was good correlation between AV/VV delays determined using these two methods in the present study, and QuickOpt® optimization was significantly faster than echocardiography. Both methods resulted in significant and similar improvements in clinical outcomes and cardiac function at 6 and 12 months after CRT implantation. QuickOpt® optimization resulted in significant decreases in LVEDD at 6 and 12 months after implantation in the present study, which was significantly different from echocardiographic optimization at 12 months.

In conclusion, QuickOpt® is a quick, convenient and easy to perform method for optimization of AV and VV delays, with a similar long-term clinical outcome to echocardiography-guided optimization. The sample size of the present study was small, and further large-scale trials are required to confirm the accuracy of QuickOpt® optimization.

Footnotes

Declaration of Conflicting Interest

The authors declare that there is no conflict of interest.

Funding

This study was supported by the Chinese Military Foundation of the Eleventh 5-year Plan (grant no. 06MB049).

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