Diagnostic Value of Right Ventricular Dysfunction in Tachycardia-Induced Cardiomyopathy Using Cardiac Magnetic Resonance Imaging

Abstract

Background: Predicting tachycardia-induced cardiomyopathy (TIC) in patients presenting with left ventricular (LV) dysfunction and tachyarrhythmias remains challenging. We assessed the diagnostic value of early right ventricular (RV) dysfunction to predict TIC using cardiac magnetic resonance (CMR) imaging.

Methods and Results: A total of 102 consecutive patients with newly diagnosed LV dysfunction and atrial tachyarrhythmias were examined. Patients whose LV ejection fraction (EF) improved to ≥50% during a 1-year follow-up were diagnosed with TIC, and with dilated cardiomyopathy (DCM) in those whose did not improve. CMR was performed at a median of 23 days after admission, and the TIC and DCM patients exhibited different distributions of EF and end-diastolic volume (EDV) between the LV and RV (both P<0.001, ANCOVA). TIC patients had significantly lower RVEF/LVEF ratio (1.01±0.23 vs. 1.36±0.31, P<0.001) and higher RVEDV/LVEDV ratio (0.96±0.21 vs. 0.73±0.19, P<0.001) compared with DCM patients, suggesting that RV systolic dysfunction and RV dilatation were observed in TIC. In the multivariate analysis, age, RVEF/LVEF ratio, and RVEDV/LVEDV ratio were significant predictors of TIC, and RVEF/LVEF ratio of <1.05 most highly predicted TIC with a sensitivity of 69.1% and specificity of 91.5% (area under the curve 0.860).

Conclusions: Among patients with newly diagnosed LV dysfunction and atrial tachyarrhythmias, age and coexistence of RV dysfunction was a strong predictor of TIC. (Circ J 2016; 80: 2141–2148)

Tachycardia-induced cardiomyopathy (TIC, or tachycardia-mediated cardiomyopathy and arrhythmia-induced cardiomyopathy) is a reversible form of ventricular systolic dysfunction, which is caused primarily by a rapid ventricular response to tachyarrhythmias.¹ Although its incidence is unclear, its prevalence is reported to be 18–37% among patients referred for atrial fibrillation (AF) ablation² or 10% in patients with focal atrial tachycardia.³

Although atrial arrhythmias and heart failure are known to often coexist,^4–6 differentiating TIC from other non-ischemic cardiomyopathies such as dilated cardiomyopathy (DCM) remains a challenging clinical issue in patients presenting with newly diagnosed left ventricular (LV) systolic dysfunction and uncontrolled tachycardia. The echocardiographic LV chamber dimension,^7,8 or an early decline in the N-terminal pro B-type natriuretic peptide,⁹ has been suggested as a predictive variable but either of these is still insufficient.

In animal models of heart failure, sustained rapid ventricular pacing is known to produce biventricular systolic dysfunction and chamber dilatation.^10–13 On the other hand, right ventricular (RV) dysfunction in LV-originating heart failure such as DCM has been considered to develop in the advanced stages.^14,15 Therefore, we hypothesized that RV dysfunction may be present in TIC patients at an early stage, and may be predictive of TIC.

The aim of this study was to use cardiac magnetic resonance (CMR) to assess the diagnostic value of RV dysfunction for predicting TIC in patients presenting with newly diagnosed LV systolic dysfunction and atrial tachyarrhythmia.

Methods

Study Population

Among the patients admitted to the National Cerebral and Cardiovascular Center for newly diagnosed LV systolic dysfunction and concomitant atrial tachyarrhythmias, we retrospectively analyzed 102 consecutive patients who underwent CMR to evaluate their cardiac function. The first screening was performed with echocardiography and 12-lead ECG on admission. The patients with an LV ejection fraction (LVEF) of ≤45% on echocardiography and concomitant atrial tachyarrhythmias defined as a resting heart rate >100 beats/min were included. Heart failure therapies were based on the clinical practice of each physician. CMR was performed after controlling the heart rate and compensation of the heart failure. Patients with ischemic, valvular or congenital heart diseases, history of hypertrophic cardiomyopathy, or other secondary cardiomyopathies were excluded. This study was approved by the Institutional Research Board of the National Cerebral and Cardiovascular Center (M27-088).

Definition of TIC

Patients in whom the LVEF improved to ≥50% within a 1-year follow-up period were defined as having TIC,¹⁶ and those who had persistent LV dysfunction (LVEF <50%) were defined as having DCM. The LVEF during the follow-up period was assessed by echocardiography.

CMR Image Acquisition and Analysis

After informed consent was given, CMR was performed with a standardized clinical protocol on a 1.5-T system (Magnetom Sonata; Siemens, Erlangen, Germany). We acquired the cine images using a true-FISP sequence (echo time 1.3 ms, repetitive time 2.6 ms, flip angle 90 degrees, slice thickness 6 mm, gaps 4 mm, matrix 128×128 and field of view 200 mm with multiple breath-holds in contiguous short-axis slices that encompassed both ventricles, and 3 standard long-axis slices). Prospective ECG gating was performed using the R-wave as the trigger. To quantify the end-diastolic volume (EDV), end-systolic volume (ESV), EF and mass, 2 experienced radiologists manually traced the LV and RV endocardial and epicardial contours on the end-systolic and end-diastolic frames of the short-axis slices using dedicated software (Argus; Siemens). Because of the complex RV anatomy, accurate RV wall tracing is occasionally difficult, especially at the base. In cases of doubtful accurate delineation on the short-axial slices only, RV wall contours were determined by reference to long-axial slices (eg, 4-chamber view or RV outflow tract view). This procedure is time consuming and requires significant operator expertise, but cine magnetic resonance imaging is currently considered the standard method for assessing RV volume and function compared with other modalities. Previous study in a cardiac porcine model of known volume showed that cine magnetic resonance imaging yielded the most precise volumetry using methods similar to those employed in our study.¹⁷ In patients with AF, the measurements were obtained over an average of 3 ventricular beats. Gadopentetate dimeglumine (0.15 mmol/kg; Magnevist; Bayer Healthcare Pharmaceuticals, Berlin, Germany) was administered at a rate of 3–4 ml/s using a power injector. Late gadolinium enhancement (LGE) images were acquired 20 min after the injection of contrast, with an inversion-recovery prepared true-FISP sequence and an inversion time of 300 ms. The parameters used in the true-FISP for the LGE were a repetition time of 3.5 ms; echo time, 1.7 ms; flip angle, 60°; matrix, 256×129; field of view, 340 mm; section thickness, 8 mm, and gaps of 2 mm. The presence and location of the LGE were determined using a standard 17-segment LV model by 2 trained radiologists without clinical information.

Echocardiography

All patients underwent echocardiography on admission (as a first screening) and follow-up at 12 months after the first screening by experienced technicians with commercially available ultrasonography systems. Assessments were performed according to the guidelines of the American Society of Echocardiography.^18–20

Statistical Analysis

The values are expressed as the mean±standard deviation if the variable was normally distributed, or median (interquartile range) if not. Groups were compared for categorical data using Chi-square tests, and Student’s t-test or Wilcoxon test was used for continuous values as appropriate. All tests were 2-sided, and P<0.05 was considered statistically significant. The differences in the distribution of the EF and EDV between TIC and DCM groups were performed by an analysis of covariance (ANCOVA). A logistic regression analysis was performed to determine the significant variables associated with the prediction of TIC. Only variables that proved to have P<0.10 in the univariate analysis were candidates for the final multivariate model, which was determined using a forward stepwise variable selection procedure. Multicollinearity among the variables in the model was assessed by calculation of the variance inflation factor. No variable in the prediction model had an associated variance inflation factor greater than 4.0, demonstrating that there was no significant multicollinearity in the model. A receiver-operating characteristics analysis was performed to evaluate the optimal cutoff value and to assess the predictive values for TIC. All statistical analyses were performed with JMP 12 (SAS Institute, Inc, Cary, NC, USA) and SPSS version 22 (SPSS Inc, Chicago, IL, USA) software.

Results

Patients Characteristics

The patient characteristics are shown in Table 1. There were no differences in the LVEF on admission but it significantly improved after the follow-up period (TIC vs. DCM: 29.5±8.4 to 55.1±4.4% vs. 28.4±7.9 to 38.0±8.4%, P<0.001 at follow-up). The LV and LA dimensions were consistently smaller in the TIC compared with the DCM group during the course of this study. The severities of mitral and tricuspid regurgitation, inferior vena cava diameter, tricuspid regurgitation pressure gradient, and end-diastolic pulmonary regurgitation gradient were similar between the groups; however, the TIC group tended to have larger RV diastolic dimension. Tricuspid annular plane systolic excursion (TAPSE) values were equally reduced in both groups at first screening, however, they were significantly increased in the TIC group (15.8±5.2 to 20.4±3.4 mm, P<0.05) at follow-up. The TIC patients more frequently received rhythm control therapy, and sinus rhythm was more commonly observed after the follow-up period. Beta-blockers were prescribed in over 96% of the patients in both groups (P=NS), and there were no differences in the other medications.

Table 1. Characteristics of the TIC and DCM Patients

	TIC group (n=55)	DCM group (n=47)	P value
Age, years	58 (45–68)	64 (52–72)	0.046
Male, n (%)	41 (75)	40 (85)	0.23
Atrial tachyarrhythmias			0.62
Atrial fibrillation, n (%)	51 (93)	41 (87)
Atrial flutter, n (%)	1 (2)	2 (4)
Focal atrial tachycardia, n (%)	3 (5)	4 (9)
Heart rate
At first screening, beats/min	126.1±24.0	124.5±22.9	0.76
At follow-up, beats/min	65.5±15.5	64.9±11.4	0.88
Echocardiography at first screening
LVEF, %	29.5±8.4	28.4±7.9	0.54
LVDd, mm	54.5±8.5	59.9±7.5	0.001
LVDs, mm	44.8±8.9	50.7±9.3	0.002
LA dimension, mm	42.4±8.5	45.8±7.2	0.04
TMF E wave, cm/s	77 (61–93)	77 (56–88)	0.57
TMF DcT, ms	157 (129–191)	144 (119–182)	0.36
E/e’	9.0 (5.8–12.9)	10.0 (7.4–13.1)	0.34
MR moderate/severe, %	7 (13)	7 (15)	0.76
TR moderate/severe, %	3 (5)	1 (2)	0.38
IVC diameter, mm	18.6±5.7	18.5±5.5	0.97
TR pressure gradient, mmHg	22 (17–31)	26 (20–37)	0.06
End-diastolic pulmonary regurgitation gradient, mmHg	6.5±2.9	7.3±3.7	0.50
RVDd, mm	31.2±7.7	26.4±7.5	0.16
TAPSE, mm	15.8±5.2	15.7±4.3	0.92
Echocardiography at follow-up
LVEF, %	55.1±4.4*	38.0±8.4*	<0.001
LVDd, mm	50.2±5.3*	56.0±7.3*	<0.001
LVDs, mm	33.9±4.6*	42.8±9.0*	<0.001
LA dimension, mm	39.6±7.7	43.0±8.0	0.07
TMF E wave, cm/s	66 (52–85)	66 (48–83)	0.56
TMF DcT, ms	213 (175–247)*	184 (150–219)*	0.06
E/e’	7.6 (5.9–8.8)*	7.6 (6.5–9.7)*	0.39
MR moderate/severe, %	1 (2)	3 (6)	0.24
TR moderate/severe, %	2 (4)	1 (2)	0.64
IVC diameter, mm	15.8±3.9*	16.6±4.5	0.32
TR pressure gradient, mmHg	21.4±6.5	21.1±5.6*	0.84
End-diastolic pulmonary regurgitation gradient, mmHg	3.9±1.8*	5.3±2.9	0.11
RVDd, mm	30.1±8.9	27.6±5.9	0.44
TAPSE, mm	20.4±3.4*	17.7±4.2	0.044
Rhythm control
Radiofrequency catheter ablation, n (%)	19 (35)	4 (9)	0.001
Cardioversion, n (%)	24 (44)	12 (26)	0.06
Rhythm at follow-up			0.02
Sinus, n (%)	34 (62)	18 (38)
Atrial fibrillation, n (%)	21 (38)	29 (62)
Medications during the follow-up period
β-blockers, n (%)	54 (98)	45 (96)	0.48
ACEI/ARB, n (%)	39 (70)	35 (75)	0.65
Aldosterone receptor antagonists, n (%)	13 (24)	18 (38)	0.12
Anti-arrhythmic drugs, n (%)	11 (20)	11 (23)	0.71

*P<0.05 compared with first screening. Numeric values are expressed as the mean±standard deviation or median (interquartile range). ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin II receptor blocker; DCM, dilated cardiomyopathy; DcT, deceleration time; Dd, diastolic dimension; Ds, systolic dimension; E/e’, ratio of early transmitral velocity to tissue Doppler mitral annular velocity during early diastole; EF, ejection fraction; IVC, inferior vena cava; LA, left atrium; LV, left ventricle; MR, mitral regurgitation; RV, right ventricle; TAPSE, tricuspid annular plane systolic excursion; TIC, tachycardia-induced cardiomyopathy; TMF, transmitral flow; TR, tricuspid regurgitation.

Results of CMR Imaging

Because the CMR was performed at a median of 23 days after the first screening by echocardiography in both groups, the LVEF in the TIC group had slightly improved by the time of CMR imaging (29.5±8.4 vs. 36.3±11.1%, P<0.001). Further, the LV EDV, ESV, and LV mass were significantly smaller in the TIC group (P<0.05, respectively, Table 2A). Accordingly, we re-evaluated the CMR results using LVEF-matched TIC and DCM patients. Table 2B shows that the patients in the TIC group had a significantly lower RVEF, and larger RVEDV and RVESV, resulting in a significantly lower RVEF/LVEF ratio and higher RVEDV/LVEDV (P=0.015 and 0.013, respectively, vs. DCM group).

Table 2. CMR Results of the Study Patients (A) and LVEF-Matched Groups (B)

	(A) All patients			(B) LVEF-matched
	TIC group (n=55)	DCM group (n=47)	P value	TIC group (n=21)	DCM group (n=21)	P value
Time from admission to CMR, days	23 (10–48)	24 (16–92)	0.15	18 (11–41)	21 (18–129)	0.09
Body surface area, m2	1.75±0.20	1.74±0.17	0.96	1.74±0.22	1.76±0.15	0.83
Heart rate at CMR, beats/min	70 (60–75)	70 (62–76)	0.38	70 (65–78)	67 (59–75)	0.45
Rhythm at CMR			0.29			0.27
Sinus, n (%)	18 (33)	10 (22)		6 (29)	3 (14)
Atrial arrhythmia, n (%)	37 (67)	37 (78)		15 (71)	18 (86)
LVEF, %	36.3±11.1	27.1±8.1	<0.001	30.4±7.8	30.5±7.8	0.97
LVEDV, ml	150 (122–189)	200 (176–257)	<0.001	174 (144–217)	186 (148–240)	0.63
LVESV, ml	94 (66–131)	152 (118–199)	<0.001	119 (99–157)	128 (98–178)	0.74
LV mass, g/m2	60.4 (50.3–74.6)	69.7 (59.8–86.3)	0.03	71.9 (57.5–85.9)	65.9 (57.5–77.0)	0.47
LV LGE, n (%)	13 (24)	20 (43)	0.04	7 (33)	11 (52)	0.21
LV LGE location
Mid-myocardium, n (%)	5 (38)	13 (65)	0.13	2 (29)	7 (63)	0.14
Insertion points, n (%)	7 (54)	11 (55)	0.95	5 (71)	8 (73)	0.95
Subendocardium, n (%)	2 (15)	5 (25)	0.50	1 (14)	2 (18)	0.83
Transmural, n (%)	0 (0)	1 (5)	0.31	0 (0)	0 (0)	NA
Epicardium, n (%)	1 (8)	0 (0)	0.17	0 (0)	0 (0)	NA
RVEF, %	35.0±7.9	35.1±7.1	0.91	31.9±8.0	36.9±7.1	0.039
RVEDV, ml	152 (127–176)	141 (125–167)	0.54	165 (135–194)	140 (118–164)	0.042
RVESV, ml	92 (77–117)	93 (77–112)	0.82	111 (85–136)	92 (67–110)	0.037
RVEF/LVEF ratio	1.01±0.23	1.36±0.31	<0.001	1.06±0.20	1.25±0.28	0.015
RVEDV/LVEDV ratio	0.96±0.21	0.73±0.19	<0.001	0.92±0.17	0.77±0.19	0.013

Numeric values are expressed as the mean±standard deviation or median (interquartile range). CMR, cardiac magnetic resonance; EDV, end-diastolic volume; ESV, end-systolic volume; LGE, late gadolinium enhancement. Other abbreviations as in Table 1.

We further analyzed the relationship between the EF and EDV of the LV and RV between the TIC and DCM groups (Figures 1A,C), as well as their distributions between the LVEF-matched groups (Figures 1B,D). The Figures show that the distribution pattern significantly differed between the groups by ANCOVA. Figure 2A shows that the TIC patients had a significantly lower RVEF/LVEF ratio than the DCM group. Similarly, the RVEDV/LVEDV ratio was significantly higher in the TIC group (Figure 2B). These results indicated that RV systolic dysfunction and dilatation during the early phase were clearly observed in patients with TIC.

Figure 1.

Distribution of ventricular ejection fractions (EF) and end-diastolic volumes (EDV) stratified by tachycardia-induced cardiomyopathy (TIC) and dilated cardiomyopathy (DCM). (A) Distribution of the left ventricular EF (LVEF, x axis) and right ventricular EF (RVEF, y axis) with a linear regression line and 95% confidence intervals stratified by TIC (blue circles) and DCM (red circles). (B) Distribution of the EF between the LVEF-matched groups. (C) Distribution of the EDV and (D) EDV distribution between LVEF-matched groups. The differences between the groups were compared using an analysis of covariance (ANCOVA).

Figure 2.

Distribution of the right ventricular EF/left ventricular EF ratio (RVEF/LVEF ratio, A) and right ventricular EDV/left ventricular EDV ratio (RVEDV/LVEDV ratio, B), with receiver-operating characteristics (ROC) analysis (C,D) for predicting tachycardia-induced cardiomyopathy (TIC). (C) Predictive value of the RVEF/LVEF ratio for TIC in the ROC analysis. The area under the curve was 0.860, and a cutoff value of 1.05 predicted TIC with a sensitivity of 69.1% and specificity of 91.5%. Likewise, the RVEDV/LVEDV ratio had an area under the curve of 0.798, sensitivity of 72.3% and specificity of 73.4% with a cutoff value of 0.82 (D).

Predictors of TIC

Using the clinical data and CMR variables shown in Tables 1 and 2, we performed a logistic regression analysis for significant predictors of TIC (Table 3): age, sinus rhythm at follow-up, LVEF, LVEDV, LV mass, RVEF/LVEF ratio, RVEDV/LVEDV ratio, and positive LGE were all significant predictors in the univariate analysis. In the multivariate analysis, age, RVEF/LVEF ratio, and RVEDV/LVEDV ratio were independent predictors of TIC. In Table 4, the area under the curve (AUC), sensitivity, and specificity are listed with the optimal cutoff values. The results showed that RVEF/LVEF ratio <1.05 predicted TIC with an AUC of 0.860, sensitivity of 69.1%, and specificity of 91.5%, and RVEDV/LVEDV ratio >0.82 predicted TIC with an AUC of 0.798, sensitivity of 72.3% and specificity of 73.4% (Figures 2C,D); the RVEF/LVEF ratio had the most highly predictive value. Of note, the RVEF/LVEF ratio and RVEDV/LVEDV ratio had higher predictive value than the previously reported TIC predictors, the LVEDV and LV mass.

Table 3. Logistic Regression Analysis for the Predictors of TIC

	Univariate		Multivariate
	OR (95% CI)	P value	OR (95% CI)	P value
Age per 1 year	0.969 (0.940–0.997)	0.030	0.939 (0.895–0.978)	0.022
Sinus rhythm at follow-up	2.608 (1.182–5.902)	0.017
LVEF per 1%	1.101 (1.053–1.160)	<0.001
LVEDV per 10 ml	0.910 (0.850–0.966)	0.001
LV mass per 10 mg/m2	0.817 (0.664–0.988)	0.037
RVEF/LVEF per 0.1	0.585 (0.454–0.719)	<0.001	0.645 (0.483–0.819)	<0.001
RVEDV/LVEDV per 0.1	1.833 (1.431–2.467)	<0.001	1.510 (1.099–2.156)	0.006
Positive LGE	2.393 (1.034–5.703)	0.042

CI, confidence interval; OR, odds ratio. Other abbreviations as in Tables 1,2.

Table 4. Optimal Cutoff Points of the Significant Variables and Their Predictive Ability for TIC

	Sensitivity	Specificity	AUC
Age <58.8years	54.6	70.2	0.615
LVEF >30.2%	70.9	68.1	0.742
LVEDV <174 ml	69.1	76.6	0.736
LV mass <69.7 mg/m2	69.1	48.9	0.627
RVEF/LVEF <1.05	69.1	91.5	0.860
RVEDV/LVEDV >0.82	72.3	73.4	0.798
Positive LGE	76.4	42.6	0.595

AUC, area under the curve. Other abbreviations as in Tables 1,2.

Discussion

Based on our analysis of patients with newly diagnosed LV dysfunction and concomitant atrial tachyarrhythmias using CMR, TIC patients were found to have relatively depressed RV systolic function and RV dilatation with the first diagnosis of the LV dysfunction (from an early stage) compared with DCM patients, and pronounced bilateral ventricular systolic dysfunction was observed in the TIC patients. Hence, the RVEF/LVEF ratio during the early phase was a significant and strong predictor for TIC. These findings focused on the RV function have important clinical implications for discriminating TIC.

Mechanism of RV Dysfunction in TIC

RV dysfunction in LV-originating heart failure, as in DCM, has been considered to develop in the advanced stages as a consequence of increased RV afterload through the development of group 2 pulmonary arterial hypertension.¹⁴ Previous studies have reported that RV dysfunction is associated with worse clinical outcomes in patients with chronic systolic heart failure,¹⁴ ventricular tachycardia,²¹ implantable cardioverter defibrillators,²² acute decompensated heart failure,²³ or heart failure with preserved EF,²⁴ implying that RV dysfunction is a sign of disease progression.

On the other hand, as previously reported in animal models of rapid pacing-induced LV dysfunction, a sustained rapid ventricular response is known to produce biventricular systolic dysfunction and chamber dilatation.^10–13 Although the precise mechanism responsible for pacing-induced cardiomyopathy is unknown, myocardial energy depletion, myocardial ischemia, abnormalities of cardiac calcium regulation, and myocyte and/or extracellular matrix remodeling are candidate mechanisms of this biventricular dysfunction.¹²

Although the RV is known to poorly tolerate increased pressure compared with the LV,^25–27 we found no evidence of increased RV preload/afterload in TIC patients at first screening in our echocardiographic analysis. Therefore, we believe that RV dysfunction in TIC is a consequence of biventricular deterioration by tachycardia, unrelated to increased right-sided pressure, and that the presence of RV dysfunction may serve as a TIC predictor. Although RV dysfunction generally implies advanced heart failure, early onset of RV dysfunction in TIC may be recognized as a paradox of RV function.

Clinical Implications

Although there is no absolute parameter that can distinguish TIC from other forms of non-ischemic cardiomyopathies such as DCM, previous studies have reported that LV chamber size by echocardiography tends to be smaller in patients with TIC,^7,8 without an increase in the LV mass.^8,28 Jeong et al reported that an LV diastolic dimension ≤61 mm could predict TIC with a sensitivity of 100% and a specificity of 71.4%.⁸ Our study assessed ventricular function by CMR, which is known to be the most accurate method for assessing LV and RV functions.²⁵ Our results are consistent with the previous studies in terms of a smaller LV volume and smaller LV mass in TIC. However, the presence of RV systolic dysfunction and dilatation, particularly assessed by the RVEF/LVEF and RVEDV/LVEDV ratios, had a higher predictive value for TIC than LV volume or LV mass in our study.

In the clinical setting, assessment of the RV is often difficult and limited in its reproducibility compared with the LV. At first echocardiographic screening, TAPSE, a commonly used echocardiographic variable, did not differ between TIC and DCM patients. We believe this is a consequence of tachycardia and atrial arrhythmia themselves reducing the TAPSE values not only in TIC but also in DCM patients,^29,30 supporting that CMR-assessed RV function may be valuable compared with echocardiography. Furthermore, considering the ventricular interaction and pressure “mismatch” known between the left- and right-sided pressures,³¹ contrasting RV variables with LV variables, such as the RVEF/LVEF and RVEDV/LVEDV in our study, may be useful for assessing RV function, as reported in animal studies.³²

Our study also found younger age as a predictor of TIC. Although TIC has been reported to occur in any age, including children and adolescents, it appears to be present more often in younger patients.³ Fenelon et al have also reported that age is a factor that contributes to the differences in tachycardia rate and duration related to the development of TIC.³³ We found no collinearity between age and LGE; however, aging has been reported to be related with myocardial damage and higher AF incidence, so we believe that the relationship between age and TIC prediction requires further validation beyond our CMR study.

Evaluation of the Myocardial Substrate Using CMR

Previous reports of TIC recurrence,³⁴ sudden cardiac death,^35,36 and persistent LV dilatation² have suggested the presence of a persistent abnormality in the myocardial substrate in TIC.³⁷ Histological reports have shown mild myocardial hypertrophy and fibrosis in endomyocardial biopsies from TIC patients.^38–40

Although LGE and T1 mapping using CMR have emerged as novel tools to assess myocardial fibrosis,^41,42 data regarding the prevalence and characteristics of LGE in TIC are limited. Hasdemir et al reported a positive LGE prevalence of 5% in arrhythmia-induced cardiomyopathy caused by premature ventricular contractions and/or ventricular tachycardia.⁴³ However, the prevalence of LGE in atrial arrhythmia-induced cardiomyopathy is unknown. Ling et al reported that no LGE was observed in 18 TIC patients who underwent CMR 5 years after their treatment of atrial-TIC.³⁷ The same authors also reported that in 16 AF patients without LGE, all patients had normalized ventricular function following the restoration of sinus rhythm.⁴⁴ However, the prevalence of LGE in TIC caused by atrial arrhythmias was not examined in those studies.

Our study demonstrated a positive LGE in 24% of TIC and 43% of DCM patients. However, it is clinically difficult to differentiate TIC from other cases of DCM when the patient responded to heart failure therapy and had a marked improvement in systolic function. This clinical limitation makes it difficult to define the true LGE prevalence in TIC, and we cannot deny the possibility that some portion of the patients with DCM were classified into the TIC group.

Study Limitations

Our study had several limitations that need to be taken into account. First, this was a single-center, retrospective observational study with a relatively small patient cohort, which could be therefore subject to a myriad of biases, particularly selection bias and statistical power limitations. Second, we had no prior knowledge of the duration of atrial tachyarrhythmia or prior ventricular dysfunction, as the majority of the patients presented with newly diagnosed LV dysfunction and tachycardia without prior documentation. There may be a possibility that patients with pre-existing cardiomyopathy (that was exacerbated by tachyarrhythmia) or long-standing TIC with irreversible myocardial damage may have biased our results. Third, we were unable to obtain follow-up of the RV function by CMR. Thus, the reversibility of RV dysfunction could not be fully proven beyond our hypothesis. Fourth, the effect of rhythm or rate control on our results could not be evaluated because of the retrospective nature of the study. As achieving sinus rhythm by non-pharmacological rhythm control has been reported to improve the EF compared with rate control, the higher prevalence of sinus rhythm at follow-up in the TIC group may have had an effect on LV functional recovery and may have biased our results. Hence, the current data need to be confirmed in further large-scale clinical trials, and further studies are needed to elucidate the underlying pathophysiologic mechanisms and reversibility of RV dysfunction in TIC, as well as the clinical prognosis of RV dysfunction in this patient population.

Conclusions

Among patients with newly diagnosed LV dysfunction and atrial tachyarrhythmias, CMR analysis revealed depressed RV systolic function and dilatation in TIC patients, and the presence of RV dysfunction had a high predictive value for TIC. Although RV dysfunction generally implies advanced heart failure, early onset of RV dysfunction in TIC may be recognized as a paradox of RV function.

Acknowledgment

We thank Hiroko Sakai for excellent assistance with the manuscript.

Funding Sources / Disclosures

This work was supported by intramural research funds (22-1-2, 28-6-18) for cardiovascular disease from National Cerebral and Cardiovascular Center.

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