Significance of prolonged QTc in acute exacerbations of COPD requiring hospitalization

Figures & data

Table 1 COPD comorbidity index*

Cardiovascular disease	0/1	Musculoskeletal disease	0/1
Ischemic heart disease		Anemia
Heart failure		Osteoporosis
Stroke		Muscle weakness
Peripheral vascular disease		Cachexia
Metabolic disease	0/1	Psychological disease	0/1
Diabetes		Anxiety
Obstructive sleep apnea syndrome		Depression
Metabolic syndrome		Oncologic disease	0/1

Note:

* The COPD comorbidity index score (maximum 5) is the sum of the scores accounted to each category, which is 1 if the patient is diagnosed with at least one of the diseases belonging to that category.

Table 2 Characteristics of patients hospitalized for an AECOPD, according to prolonged QTc status on the admission ECG*

	Patients with prolonged QTc		Patients without prolonged QTc		OR (95% CI)	p-value
	n=70		n=70
Demographics
Age (years)	77	[12]	68	[16]		<0.001
Sex (F)	17	(12)	40	(28)	0.31 (0.13–0.72)	0.005
BMI (kg/m^2)	26	[8]	24	[8]		0.039
Obesity (BMI ≥30 kg/m^2)	27	(19)	17	(12)	1.79 (0.74–4.48)	0.222
Lung disease
GOLD stage (A/B/C/D)	(6–12–15–37)		(3–9–9–49)			0.212
FEV1(%)	45	[19]	40	[20]		0.088
mMRC (0–4)	2	[2]	2	[1]		0.137
Current smoker	33	(23)	34	(24)	0.94 (0.44–2.01)	1
Number of pack-years (years)	40	[30]	41	[29]		0.503
O2 dependent	20	(14)	15	(11)	1.34 (0.51–3.56)	0.660
Comorbidity
History of sudden death	0	(0)	4	(3)	0.00 (0.00–2.40)	0.245
Cardiovascular disease	66	(46)	47	(33)	2.14 (1.03–4.50)	0.040
Charlson comorbidity index	3	[2]	2	[2]		0.034
COPD comorbidity index	2	[2]	2	[1]		0.021
Concomitant medication
Cardiovascular medication	81	(57)	77	(54)	1.30 (0.53–3.23)	0.677
QT-prolonging medication	34	(24)	43	(30)	0.70 (0.33–1.46)	0.385
Blood values
Hypokalemia	9	(6)	2	(1)	6.40 (0.75–301.32)	0.116
Hypomagnesemia	7	(1/14)	0	(0/15)	+∞ (0.03−+∞)	0.483
Cardiac troponin T (ng/mL)	(11–35–11)		(28–14–4)			<0.001
(≤0.014/0.014–0.052/≥0.052)	(57/70)		(46/70)
Elevated CRP	77	(54)	66	(46)	1.75 (0.79–4.00)	0.190
Hypoxemia	33	(23)	51	(34/67)	0.48 (0.22–1.00)	0.039
Respiratory acidosis	7	(5)	12	(5/67)	0.57 (0.14–2.10)	0.392
ECG
Heart rate (bpm)	95	[27]	84	[21]		0.009
QTc duration (msec)	472	[25]	428	[26]		<0.001
QTc >500 msec	17	(12)		–	–	–
QTcF duration (msec)	444	[25]	406	[16]		<0.001
Prolonged QTcF	36	(25)		–	–	–
QTcF >500 msec	9	(6)		–	–	–
ECG normal rhythm	81	(57)	94	(66)	0.27 (0.06–0.93)	0.036
ECG normal conductance	44	(31)	86	(60)	0.13 (0.05–0.32)	<0.001
ECG normal repolarization	77	(54)	86	(60)	0.56 (0.21–1.46)	0.277
ECG infarction signs	20	(14)	19	(13)	1.10 (0.43–2.78)	1
2nd ECG taken	46	(32)	93	(65)	0.07 (0.02–0.19)	<0.001
2nd ECG heart rate (bpm)	88	[32]	84	[23]		0.583
2nd ECG QTc duration (msec)	464	[33]	423	[28]		<0.001
2nd ECG normal rhythm	78	(25/32)	97	(63/65)	0.12 (0.01–0.67)	0.005
2nd ECG normal conductance	28	(9/32)	85	(55/65)	0.07 (0.02–0.22)	<0.001
2nd ECG normal repolarization	75	(24/32)	83	(54/65)	0.61 (0.20–2.00)	0.417
2nd ECG infarction signs	16	(5/32)	22	(14/65)	0.68 (0.17–2.26)	0.593
CXR
CXR abnormal	76	(53)	66	(46)	1.62 (0.73–3.65)	0.265
CXR cardiomegaly	51	(27/53)	24	(11/46)	3.26 (1.29–8.71)	0.007
CXR consolidation	30	(16/53)	33	(15/46)	0.89 (0.35–2.29)	0.831
CXR pleural fluid	30	(16/53)	7	(3/46)	6.10 (1.57–35.16)	0.004
CXR other	34	(18/53)	70	(32/46)	0.23 (0.09–0.57)	0.001
Outcome
Length of stay (days)	8	[6]	9	[4]		0.417
Mortality	20	(14)	9	(6)	2.65 (0.88–9.00)	0.089
Mortality for QTc >500 msec	17	(2)		–	–	–

Note:

* Values are presented as percentage (n) or median [interquartile range].

Abbreviations: AECOPD, acute exacerbation of COPD; QTc, QT interval corrected according to Bazett’s formula; ECG, electrocardiogram; BMI, body mass index; GOLD, Global Initiative for Chronic Obstructive Lung Disease; FEV₁, forced expiratory volume in 1 second; mMRC, modified Medical Research Council; CRP, C-reactive protein; QTcF, QT interval corrected according to Fridericia’s formula; CXR, chest X-ray.

Figure 1 Distribution of (cardiovascular) comorbidity according to prolonged QTc status in COPD patients hospitalized for an acute exacerbation, assessed by the (A) Charlson comorbidity index (p=0.034), (B) COPD comorbidity index (p=0.021) and (C) presence of cardiovascular disease (p=0.040).

Abbreviation: QTc, QT interval corrected according to Bazett’s formula.

Figure 2 Distribution of cardiac troponin T value according to prolonged QTc status in COPD patients hospitalized for an acute exacerbation (p<0.001). Cutoff values: negative, ≤0.014 ng/mL; intermediate, 0.014–0.052 ng/mL; high, ≥0.052 ng/mL.

Abbreviation: QTc, QT interval corrected according to Bazett’s formula.

Table 3 Multivariate logistic regression model: determinants for prolonged QTc in patients hospitalized for an AECOPD*

Variable	OR	(95% CI)	p-value
Age (years)	1.02	(0.97–1.07)	0.502
Sex (male vs female)	1.22	(0.39–3.82)	0.727
BMI (kg/m^2)	1.05	(0.96–1.15)	0.263
FEV1 (% pred)	1.03	(1.00–1.07)	0.078
Hypokalemia (yes vs no)	2.34	(2.16–603.81)	0.019
cTnT (>0.014 vs ≤0.014 ng/mL)	6.28	(2.28–19.03)	<0.001
Hypoxemia (yes vs no)	5.05	(0.19–1.29)	0.155
Heart rate (bpm)	1.02	(0.99–1.05)	0.124
ECG abnormal conductance (yes vs no)	5.17	(1.89–15.28)	0.002
CXR pleural fluid (yes vs no)	4.29	(1.01–26.07)	0.071

Notes:

* Multiple imputation was performed for cardiac troponin T (cTnT). Significant p-values are highlighted in bold.

Abbreviations: QTc, QT interval corrected according to Bazett’s formula; AECOPD, acute exacerbation of COPD; BMI, body mass index; FEV₁, forced expiratory volume in 1 second; ECG, electrocardiogram; CXR, chest X-ray.

Figure 3 Influence of prolonged QTc on overall survival in COPD patients hospitalized for an acute exacerbation (log rank test, p=0.035).

Abbreviation: QTc, QT interval corrected according to Bazett’s formula.

Table 4 Characteristics of pulmonary patients hospitalized for acute respiratory problems, according to the main admission diagnosis*

	AECOPD		Lung cancer		Pulmonary infections		Miscellaneous		p-value
	n=55		n=34		n=32		n=41
Demographics
Age (years)	72	[17]	69	[11]	76	[17]	66	[16]	0.084
Sex (F)	36	(20)	32	(11)	47	(15)	44	(18)	0.562
BMI (kg/m^2)	23	[8.52]	24	[5.24]	25	[12]	23	[7]	0.506
Obesity (BMI ≥30 kg/m^2)	17	(9/54)	6	(2)	32	(10/31)	12	(5)	0.032
Lung disease
FEV1 (%)	37	[15]	70	[43]	62	[39]	73	[37]	<0.001
FEV1/FVC (%)	41	[14]	70	[17]	74	[19]	77	[23]	<0.001
Current smoker	18	(10)	27	(9/33)	13	(4)	2	(1)	0.011
Number of pack-years (years)	35	[27]	30	[20]	9	[25]	18	[30]	<0.001
O2 dependent	11	(6)	6	(2/33)	6	(2)	17	(7)	0.434
Comorbidity
Cardiovascular disease	64	(35)	47	(16)	53	(17)	68	(28)	0.223
Charlson comorbidity index	3	[3]	9	[5]	2	[2]	4	[3]	<0.001
COPD comorbidity index	2	[2]	3	[1]	2	[2]	2	[2]	0.015
Concomitant medication
Cardiovascular medication	80	(44)	77	(26)	88	(28)	95	(39)	0.081
QT-prolonging medication	64	(35)	27	(9)	44	(14)	56	(23)	0.004
Blood values
Hypokalemia	2	(1)	6	(2)	9	(3)	2	(1)	0.323
Hypomagnesemia	15	(2/13)	5	(1/22)	0	(0/8)	23	(3/13)	0.198
Cardiac troponin T (ng/mL)	(15–16–3)		(6–11–2)		(5–10–3)		(7–15–5)		0.749
(≤0.014/0.014–0.052/≥0.052)	(34/55)		(19/34)		(18/32)		(27/41)
Elevated CRP	67	(37)	100	(34)	84	(27)	83	(34)	0.001
Hypoxemia	49	(25/51)	37	(7/19)	67	(18/27)	61	(17/28)	0.171
Respiratory acidosis	4	(2/51)	0	(0/19)	0	(0/27)	4	(1/28)	0.874
ECG
Heart rate (bpm)	94	[26]	93	[26]	85	[19]	82	[18]	0.012
QTc duration (msec)	441	[35]	444	[36]	440	[55]	442	[43]	0.923
Prolonged QTc	35	(19)	32	(11)	28	(9)	27	(11)	0.858
QTcF duration (msec)	412	[39]	409	[29]	411	[52]	418	[50]	0.837
Prolonged QTcF	11	(6)	6	(2)	19	(6)	15	(6)	0.409
ECG normal rhythm	86	(47)	74	(25)	81	(26)	88	(36)	0.389
ECG normal conductance	60	(33)	82	(28)	66	(21)	68	(28)	0.164
ECG normal repolarization	60	(33)	62	(21)	72	(23)	59	(24)	0.667
ECG infarction signs	18	(10)	12	(4)	13	(4)	5	(2)	0.272
2nd ECG taken	47	(26)	32	(11)	35	(11)	37	(15)	0.472
2nd ECG heart rate (bpm)	89	[18]	95	[23]	79	[15]	76	[28]	0.028
2nd ECG QTc duration (msec)	429	[45]	447	[24]	466	[67]	436	[92]	0.236
2nd ECG normal rhythm	89	(23/26)	91	(10/11)	73	(8/11)	73	(11/15)	0.491
2nd ECG normal cond	62	(16/26)	55	(6/11)	46	(5/11)	67	(10/15)	0.751
2nd ECG normal repol	54	(14/26)	55	(6/11)	64	(7/11)	47	(7/15)	0.872
2nd ECG infarction signs	8	(2/26)	0	(0/11)	18	(2/11)	7	(1/15)	0.568
CXR
CXR abnormal	42	(23)	97	(33)	72	(23)	66	(27)	<0.001
CXR cardiomegaly	13	(7)	9	(3)	28	(9)	27	(11)	0.062
CXR consolidation	15	(8)	32	(11)	31	(10)	20	(8)	0.136
CXR pleural fluid	7	(4)	29	(10)	19	(6)	24	(10)	0.027
CXR other	15	(8)	88	(30)	34	(11)	46	(19)	<0.001
Outcome
Length of stay (days)	9	[8]	11	[6]	9	[6]	8	[7]	0.559
Mortality	6	(3)	21	(7)	3	(1)	12	(5)	0.072

Note:

* Values are presented as percentage (n) or median [interquartile range].

Abbreviations: AECOPD, acute exacerbation of COPD; BMI, body mass index; FEV₁, forced expiratory volume in 1 second; FEV₁/FVC, Tiffeneau index; CRP, C-reactive protein; ECG, electrocardiogram; QTc, QT interval corrected according to Bazett’s formula; QTcF, QT interval corrected according to Fridericia’s formula; CXR, chest X-ray.

Figure 4 Distribution of the (A) concomitant use of QT-prolonging medication (p=0.004) and the (B) prevalence of prolonged QTc (p=0.858) among pulmonary patients hospitalized for acute respiratory problems according to the admission diagnosis.

Abbreviations: AECOPD, acute exacerbation of COPD; QTc, QT interval corrected according to Bazett’s formula.

Figure 5 The median QTc duration, evaluated in (A) all pulmonary patients hospitalized for acute respiratory problems (n=160) and more specifically (B) COPD patients hospitalized for an acute exacerbation (n=123), decreases significantly during hospitalization.

Notes: This is illustrated by the leftward shift of the density curve of the control ECG towards lower QTc values when compared with the admission ECG. Only patients for whom at least two ECGs were available were used for analysis. The median is indicated by the dotted line.
Abbreviations: QTc, QT interval corrected according to Bazett’s formula; ECG, electrocardiogram.