Potential Underestimation of Left Ventricular Mechanical Dyssynchrony in Dyssynchrony and Outcomes Assessment

Figures & data

Table 1 The Clinical Characteristics and Ultrasonic Parameters of the Three QRS Groups. P: Level of Significance

	LBBB(n=68)	RBBB(n=106)	Normal(n=103)	p(Overall)
Age(years) median (IQR)	63(14.5)	63.5(15)	54(18)	<0.01
Male/female (n)	38/30	74/32	76/27	0.042
HF/NHF (n)	20/48	30/76	26/77	0.81
NT-proBNP(pg/mL) median (IQR)	164.35(130.1)	175.35(402.8)	115(982)	0.061
Hypertension n (%)	19(27.94%)	33(31.32%)	12(11.65%)	<0.01
Diabetes n (%)	11(16.18%)	20(18.87%)	13(12.62%)	0.467
QRS duration (ms)median (IQR)	138(16)	135(18)	107(9)	<0.01
Medications used
Digitalis n (%)	7(10.3%)	5(4.72%)	4(3.83%)	0.178
Loop diuretics n (%)	12(17.6%)	18(17%)	15(14.6%)	0.838
Spironolactone n (%)	19(27.9%)	27(25.5%)	26(25.2%)	0.914
ACEI/ARB n (%)	23(33.82%)	42(39.62%)	39(37.86%)	0.74
ARNI	8(11.76%)	12(11.32%)	11(10.68%)	0.975
β-Blocker	43(63.24%)	65(61.32%)	71(68.93%)	0.497
Calcium channel blocker	18(26.47%)	48(45.28%)	33(32.04%)	0.025
Nitrate	13(19.11%)	17(16.04%)	14(13.6%)	0.625
2D echocardiographic parameter
LVEDD (mm) median (IQR)	56(12)	52(10)	52(15)	0.119
LVEF (%) median (IQR)	50(16)	58(23)	56.4(16.9)	0.017
LVEDV(mL) median (IQR)	91.05(48.65)	86.95(41.5)	94.1(45.36)	0.026
E/e’	8.45(2.08)	8.84(2.78)	9.21(2.96)	0.709
Synchrony indices
Tmsv16-SD (%) median (IQR)	2.33(4.63)	2.645(3.5)	2.7(3.08)	0.961
Tmsv12-SD (%) median (IQR)	2.135(4.655)	2.085(3.4)	2.56(2.81)	0.413
Tmsv6-SD (%) median (IQR)	2.54(3.09)	1.96(3.21)	3.19(4.55)	<0.01
Tmsv16-Dif (%) median (IQR)	8.49(7.625)	7.015(9.25)	8.85(7.99)	0.175
Tmsv12-Dif (%) median (IQR)	6.67(6.47)	5.5750(8.2)	7.67(7.5)	0.028
Tmsv6-Dif (%) median (IQR)	5.685(5.865)	4.6(6.81)	6.13(6.08)	0.667
LVMD n (%)	21(30.88%)	30(28.30%)	26(25.24%)	0.715

Notes: Table 1 displays the stratification of participant characteristics based on QRS morphology. There is no significant difference between the three QRS groups in the distribution of HF and diabetes, uses of Digitalis, Loop diuretics, Spironolactone, ACEI/ARB, ARNI, β-Blocker and Nitrate, and 2D echocardiographic parameter including LVEDD, E/e’, Tmsv16-SD, Tmsv12-SD, Tmsv16-Dif, Tmsv6-Dif and LVMD.

Abbreviations: HF, heart failure; IQR, interquartile range; LBBB, left Bundle branch block; LVMD, left ventricular intra-ventricular mechanical dyssynchrony; NHF, non-heart failure; RBBB, right bundle branch block.

Table 2 LVSDI in Multivariable Logistic Regression of BBB. Other Included Variables: Age, Hypertension, Diabetes, QRS Duration, LVEF. RR: Risk Ratio; P: Level of Significance

	Tmsv16-SD		Tmsv12-SD		Tmsv6-SD		Tmsv16-Dif		Tmsv12-Dif		Tmsv6-Dif
	RR	p	RR	p	RR	p	RR	p	RR	p	RR	p
LBBB VS Normal	1.08	0.62	1.21	0.35	1.01	0.96	1.04	0.48	1.03	0.60	1.17	0.06
RBBB VS Normal	1.10	0.55	1.18	0.43	1.01	0.93	1.05	0.27	1.04	0.44	1.20	0.03

Notes: In Table 2, multivariable logistic regression shows that the majority of LVSDIs have no correlation with either LBBB or RBBB after adjusting for age, hypertension, diabetes, QRS width, and LVEF. But Tmsv6-Dif have a correlation with LBBB and RBBB.

Abbreviations: BBB, bundle branch block; LVSDI, left ventricular systolic dyssynchrony index; LBBB, left Bundle branch block; RBBB, right bundle branch block.

Table 3 Partial Correlation Analyses of LVSDIs, LVEF and QRS Duration. R: Correlation Coefficient; P: Level of Significance

LVSDIs	LVSDIs with QRS Duration		LVSDIs with LVEF		QRS Duration with LVEF
	R	p	R	p	R	p
Tmsv16-SD (%)	0.036	0.554	−0.426	<0.01	0.114	0.059
Tmsv12-SD (%)	0.045	0.454	−0.436	<0.01	0.118	0.051
Tmsv6-SD (%)	−0.089	0.142	−0.368	<0.01	0.068	0.257
Tmsv16-Dif (%)	−0.033	0.583	−0.484	<0.01	0.079	0.189
Tmsv12-Dif (%)	−0.04	0.506	−0.451	<0.01	0.079	0.190
Tmsv6-Dif (%)	0.006	0.922	−0.365	<0.01	0.104	0.086

Notes: As shown in Table 3, after applying the QRS adjustment, all LVSDIs were significantly and negatively correlated with LVEF. There was no independent correlation between LVSDI and QRS width. Correlation between QRS width and LVEF was not significant.

Abbreviations: LVSDI, left ventricular systolic dyssynchrony index; LVEF, left ventricular ejection fraction.

Figure 1 Comparison of LVSDIs between the HF and NHF groups. Nonparametric tests of two independent samples with the Mann–Whitney test are used for the difference examination.

Abbreviations: LVSDI, left ventricular systolic dyssynchrony index; P, level of significance.

Figure 2 The ROC curve analysis of LVSDIs between patients with dilated cardiomyopathy (HF) and non-heart failure (NHF) participants.

Abbreviations: LVSDI, left ventricular systolic dyssynchrony index; AUC, area under the curve; P, level of significance.

Figure 3 Comparison of ROC curve using the DeLong method between the LVSDI with the maximum AUC and NT-proBNP to differentiate patients with dilated cardiomyopathy (HF) in the three QRS subgroups and the overall participants.

Abbreviations: LVSDI, left ventricular systolic dyssynchrony index; LBBB, left bundle branch block; RBBB, right bundle branch block; AUC, area under the curve; P, level of significance.

Table 4 Multivariable Logistic Binomial Regression of Factors Associated with Heart Failure (DCM) in Three QRS Subgroups and Overall Subjects. RR: Risk Ratio; P: Level of Significance

Factor	LBBB		RBBB		Normal		Overall
	RR	p	RR	p	RR	p	RR	p
Age	1.0	0.92	1.01	0.63	1.05	0.01	1.03	0.04
Gender(male)	2.67	0.12	1.35	0.63	2.24	0.24	1.80	0.07
Hypertension	1.43	0.58	0.33	0.12	1.25	0.78	0.64	0.23
Diabetes	4.64	0.04	5.59	0.01	2.23	0.26	2.60	0.01
QRS duration	0.99	0.75	0.88	<0.01	1.02	0.52	0.99	0.09
LVMD	0.63	0.50	3.40	0.03	3.58	0.02	2.48	<0.01

Notes: As displayed in Table 4, multivariable logistic binomial regression analysis shows: (1) LVMD is independently linked with HF in the overall study participants, RBBB, and Normal groups, while it is not independently linked in the LBBB group. (2) QRS duration has no correlation with HF in the overall patient population and each subgroup. (3) Diabetes is a strong risk factor for HF, regardless of QRS morphology and duration.

Abbreviations: LVMD, left ventricular intra-ventricular mechanical dyssynchrony; LBBB, left Bundle branch block; RBBB, right bundle branch block.