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Article

Comparison of Cardiac Magnetic Resonance and Advanced Echocardiography in Evaluation of Patients with High Burden of Premature Ventricular Contractions and Normal Standard Echocardiography

Karolinska Institutet, Department for Clinical Science and Education, Södersjukhuset, 118 83 Stockholm, Sweden
*
Author to whom correspondence should be addressed.
Hearts 2024, 5(3), 365-374; https://doi.org/10.3390/hearts5030026
Submission received: 26 June 2024 / Revised: 14 August 2024 / Accepted: 22 August 2024 / Published: 28 August 2024

Abstract

:
Echocardiography is recommended as a first-line diagnostic tool in patients with premature ventricular contractions (PVCs). However, standard echocardiography is not always able to identify early signs of myocardial dysfunction and cardiac magnetic resonance (CMR) may offer additional information. Since CMR has lower accessibility and higher cost compared to echocardiography, we wanted to evaluate how additional echocardiographic parameters, not included in routine examinations, perform compared to CMR in detecting signs of cardiomyopathy in PVC patients with normal findings at a standard echocardiogram. We compared CMR findings and results from an extended echocardiographic examination in thirty-nine patients who had a high PVC burden. The additional echocardiographic parameters were global longitudinal strain, mechanical dispersion, ventricular–arterial coupling, integrated backscatter and left atrial activation time. Eleven patients had pathological findings at CMR. The additional echocardiographic parameters did not significantly differ between patients with or without CMR findings. However, several patients with normal CMR findings showed signs of ventricular dysfunction when evaluated with the additional echocardiographic parameters, which suggests that these could possibly offer supplementary information in the assessment of PVC patients.

1. Introduction

Premature ventricular contractions (PVCs) are common in both individuals with and without structural heart disease [1,2,3]. It is currently unclear whether frequent PVCs may have a prognostic impact in apparently healthy individuals [4,5], since some studies show a relation between PVCs and poor prognosis [6,7,8,9], while others do not show such a link [10,11,12]. A thorough evaluation is recommended in PVC patients [13] and examination with transthoracic echocardiography is a class I recommendation in both European and American guidelines [14,15]. However, there is evidence that standard echocardiography may not be sufficient to identify early signs of PVC-induced cardiomyopathy [16,17,18,19], and cardiovascular magnetic resonance imaging (CMR) is suggested in some patients, in spite of a normal echocardiogram [14]. Moreover, PVC patients with pathologic CMR findings have been shown to have a worse prognostic outcome than PVC patients with normal CMR [20]. However, CMR is an expensive and resource-demanding procedure and far from all PVC patients undergo CMR.
The evidence for advanced echocardiography as a tool for identification of early myocardial dysfunction in PVC patients is currently limited. However, some studies have shown that advanced echocardiographic techniques are able to detect pathology even in the case of a normal standard examination [16,17,21,22]. How pathological findings at CMR relate to signs of myocardial dysfunction at advanced echocardiography has not been studied in this patient group. It would be beneficial for both patients and healthcare providers if echocardiography could more reliably be used to identify, or rule out, underlying structural heart disease, in terms of time, costs and availability.
We have previously published separate comparisons for CMR and advanced echocardiography with standard echocardiography [17,18]. Since several patients were enrolled in both these two previous studies, we wanted to compare their findings at CMR with advanced echocardiography, and to assess whether additional echocardiographic parameters differed among patients with or without findings at CMR.

2. Materials and Methods

The findings from CMR investigations and advanced echocardiographic examinations of PVC patients and a control group have previously been published separately [17,18]. For these studies, we prospectively included consecutive patients between 2016 and 2018 with a high PVC burden, defined as at least 10,000 PVCs/day on Holter recording. All patients were referred to and evaluated at an arrythmia outpatient clinic. Exclusion criteria were previous history of ischemic heart disease, heart failure, moderate or severe valvular dysfunction, sustained ventricular tachycardia, pathological findings at exercise testing or standard echocardiography. A normal exercise test was defined as an absence of test-induced ventricular arrhythmia, ST segment depression, and chest pain. Standard echocardiography was assessed as normal if the left ventricular ejection fraction (LVEF) was at least 55%, the left ventricular diastolic function assessed according to current recommendations [23] was normal, the right ventricular systolic function was normal with a tricuspid annular plane systolic excursion (TAPSE) of at least 17 mm, ventricular dimensions and wall thickness were within conventional limits [24] and moderate-to-severe valvular disease and regional wall motion abnormalities were absent.
All patients were in sinus rhythm during echocardiographic and CMR investigations. A 1.5 T Signa HDxt scanner (GE, Milwaukee, WI, USA) was used for CMR procedure and a dedicated software (Segment CMR, Medviso, Lund, Sweden) for postprocessing. Functional parameters were obtained from the short-axis images. Values for ventricular volumes and ejection fractions were compared to the respective reference values for class age and sex [23]. Late gadolinium enhancement (LGE) was performed using a gadolinium dose of 0.2 mmol/kg bodyweight. Two expert investigators who were blinded to each other’s opinions evaluated each examination; consensus was sought in case of different evaluations. Pathological findings on CMR were defined as regional wall motion anomalies, impaired ventricular ejection fraction (EF) < 55%, presence of fibrosis or edema, or abnormal ventricular dimensions. Patients without any of these pathological findings were considered to have no CMR findings.
Echocardiographic examinations were performed with a Vivid E9 machine (GE Vingmed, Horten, Norway) with an M5S phased-array transducer. Analysis was performed using EchoPAC version 204 (GE Vingmed, Horten, Norway). Each exam was performed by an EACVI (European Association of Cardiovascular Imaging)-certified sonographer and reviewed by a blinded additional examiner. Global longitudinal strain (GLS) was measured with the speckle tracking technique, with manual tracing of the endocardium and exclusion of the papillary muscles and pericardium. Mechanical dispersion was measured as the standard deviation of the time in milliseconds from the onset of the R-wave on the ECG to the time point of peak systolic strain in 17 left ventricular segments. Ventricular–arterial (VA) coupling was assessed as the ratio of end-systolic left ventricular volume and stroke volume, measured with the Doppler technique. Left atrial activation time was measured from the onset of the P-wave on the ECG to the peak of the A-wave on the tissue Doppler tracing [25]. Integrated backscatter (IBS) calculation was based on curves acquired in parasternal long-axis view at framerates of 50–70 frames/s. Average pericardial IBS intensity was subtracted from average myocardial IBS intensity from the septum and the inferolateral wall.
The aim of this study was to assess differences in additional echocardiographic parameters comparing PVC patients with and without pathological CMR findings.

Statistical Analysis

Continuous values were compared with a t-test if normally distributed and with a Mann–Whitney U test if non-normally distributed. Normal distribution was verified with the Shapiro–Wilk test. p-values < 0.05 were considered statistically significant. Statistical analysis was performed in R version 4.0.3 (R Foundation, Vienna, Austria). To determine interobserver variability of the advanced echocardiographic parameters, six patients were measured by two different investigators, and interclass correlation coefficients for absolute agreement and coefficient of variation were calculated.

3. Results

Thirty-nine patients were included; their characteristics are summarized in Table 1. Following inclusion criteria, standard echocardiographic parameters were normal in all participants. During echocardiographic examinations, measurements for the five additional parameters of interest were performed. The echocardiographic parameters are summarized in Table 2.
Anatomical and functional CMR parameters are summarized in Table 3. Eleven patients (28%) had at least one pathologic finding at CMR, of which eight had left ventricular and three right ventricular localizations. Regional wall motion anomalies were found in three patients, all of which located in the right ventricle. We also found three cases of myocardial fibrosis, all located in the left ventricle. No fibrosis finding had characteristics pointing to previous ischemia. Three patients had sub-normal LVEF and four had a dilated left ventricle. CMR findings are summarized in Figure 1.
The additional echocardiographic parameters did not statistically differ between the patients with or without pathologic CMR findings (Table 4). Patients with CMR findings had a mean PVC burden of 22,800 PVCs per day compared to 17,900 in patients without CMR findings. However, this difference was not statistically significant, with a p-value of 0.05. Nine patients (23%) showed VA-coupling values between 0.75 and 1. Thirteen patients (33.3%) had signs of impaired global longitudinal strain, with values higher than −18%, and in ten patients (26%), we found values for mechanical dispersion longer than 60 milliseconds. The results for the additional echocardiographic parameters in patients with and without CMR findings are summarized with jitter plots in Figure 2.

4. Discussion

In recent decades, many scientific studies exploring the potential prognostic importance of PVCs have been published. Whether frequent PVCs may have a negative effect on individuals without structural heart disease is still up for debate. Moreover, it is not clear whether PVCs may cause disease themselves or are rather markers of an ongoing pathologic process. There is evidence of the ability to reverse PVC-induced cardiomyopathy with catheter ablation, which could suggest a direct pathogenic effect from PVCs [13,26]. Different mechanisms have been suggested: electromechanical dyssynchrony, coupling interval dispersion, extrasystolic potentiation and myocardial remodeling being some of them [26]. On the other hand, trials focusing on PVC suppression have not shown any positive effect on clinical endpoints, suggesting that PVCs may be a risk marker and not per se be the primus motor of disease [26,27]. However, it is very important and strongly recommended to offer PVC patients a thorough evaluation aiming to identify or exclude underlying structural heart disease [13,14].
There is growing evidence suggesting that more advanced cardiac imaging methods can identify signs of myocardial dysfunction when standard echocardiography is normal. As early as 1997, CMR was shown to be a valuable diagnostic tool in the work-up of PVCs, and in recent decades, this has been confirmed by several studies. Pathological findings at CMR have also been linked to worse prognosis [20,28]. The presence of myocardial scars has especially been identified as an important prognostic marker [29]. While CMR is a cornerstone of diagnostic work-up in specific conditions such as arrhythmogenic right ventricular cardiomyopathy, it also has a class II recommendation in evaluation of idiopathic PVCs, according to current guidelines [14]. However, CMR is an expensive and somewhat scarce method. Which PVC patients should be further evaluated with CMR remains unclear, and some studies trying to address this question have recently been published [30].
The role of advanced echocardiography has not been as well explored as CMR and it is not used in everyday practice. Its higher availability and cost-effectiveness make it appealing in the assessment of PVC patients. It has been shown that speckle tracking can identify signs of ventricular dysfunction in PVC patients despite normal results at standard echocardiography [16]. One study also indicated that PVC burden correlated with mechanical dispersion and GLS, but not with ejection fraction in 52 patients referred for PVC ablation [21].
We have previously shown that PVC patients with normal findings at standard echocardiography show signs of myocardial dysfunction when evaluated with additional parameters [17]. With this study, we aimed to compare findings at CMR with those obtained when measuring global longitudinal strain, mechanical dispersion, VA coupling, integrated backscatter and left atrial activation time. We did not find any statistically significant difference in the echocardiographic parameters between participants with and without CMR findings, possibly because of the limited sample size. However, several participants with normal CMR showed signs of ventricular dysfunction, such as high VA-coupling values and low absolute GLS values, or fibrosis, such as prolonged LA activation time or reduced myocardial elasticity measured by integrated backscatter. Whether these results are due to false-negative CMR findings or false-positive echo findings is hard to determine from the present study due to the small sample size and lack of long-term follow-up. Genetic testing for underlying cardiomyopathies would be interesting as a potential discriminator between the two imaging methods.
The role of VA coupling in overall myocardial performance has long been recognized. In our study, we measured VA coupling as the ratio of arterial elastance to end-systolic ventricular elastance [31]. While a VA-coupling value of about 0.5 is considered optimal, the normal cutoff is set at 1.0 ± 0.36 [32]. Thirteen study participants had a value above 0.7, suggesting some degree of myocardial dysfunction. Interestingly, six of these patients had no pathological findings at CMR. This is potentially relevant since VA coupling has an independent prognostic value [32]. VA coupling has been quantified in hypertension [33,34], diabetes [35] and inflammatory diseases [36,37]. However, we have previously shown it to be higher in otherwise healthy PVC patients, when compared to controls [17]. Thirteen patients had a GLS value higher than −18%, nine of them without showing any pathologic CMR finding. GLS has recently gained ground as a robust method for the evaluation of ventricular function and has in this regard even been proven to be more sensitive than ejection fraction, but is still not included in all standard echocardiographic exams [38,39,40].
Mechanical dispersion has previously been linked to PVC burden [21], clinical outcomes after myocardial infarction, hypertrophic cardiomyopathy, and heart failure [41,42,43], and a cutoff value of 63.5 milliseconds has been suggested [42]. In our study, five patients had a higher value than this cutoff, and two of these had normal CMR findings. We also evaluated parameters relating to myocardial rigidity and fibrosis. Integrated backscatter is a measure of ultrasonic reflectance and elasticity [44,45,46]. Although no widely accepted cutoff exists for myocardial tissue evaluation with integrated backscatter, we have previously shown that PVC patients have higher values (lower absolute values) than controls [17]. In the present study, there was no significant difference in this parameter between patients with and without pathology at CMR, suggesting that impaired myocardial elasticity can exist in the absence of fibrosis detectable by CMR. Similarly, signs of slow electrical conduction through the atria were shown in patients with normal CMR [25].
CMR is still gold standard when it comes to assessing structural heart disease, but if robust examination protocols for advanced echocardiography were identified, it would be beneficial for both patients and healthcare providers in terms of costs, time and availability.

5. Conclusions

There were no statistically significant differences in any of the additional echocardiographic parameters comparing PVC patients with and without pathological CMR findings. Interestingly, several patients showed signs of minor ventricular dysfunction when assessed with advanced echocardiography despite normal CMR findings. This suggests that advanced echocardiography could possibly add valuable diagnostic information, but further research is needed to determine its potential role in the assessment of PVC patients, where CMR still is the recommended modality. Longitudinal studies of PVC patients with pathological findings at advanced echocardiography but normal CMR could help determine if these findings are in fact early signs of underlying myocardial disease. Repeated echocardiographic assessments and long-term outcomes would be interesting topics for future studies.

Author Contributions

Conceptualization, M.S. and R.S.; formal analysis, O.W. and R.S.; resources, M.S. and R.S.; data curation, O.W. and R.S.; writing, review and editing, O.W., M.S. and R.S.; visualization, O.W., M.S. and R.S.; supervision, M.S. and R.S.; funding acquisition, R.S. All authors have read and agreed to the published version of the manuscript.

Funding

The study was funded by Stockholm Region’s Fund for Clinical Research as part of previous applications. Grant numbers 2014/670-31/4 (20140429), 2016/199-31/2 (20160405), 2018/912-32 (20180502), 2019-03079 (20190603).

Institutional Review Board Statement

The study is registered as a part of a larger project at ClinicalTrials.org, available online: https://clinicaltrials.gov/study/NCT03370679?a=1 (accessed on 26 August 2024) with identifier NCT03370679. The study was approved by the Regional Ethics Committee in Stockholm (approved codes: 2014/670-31/4 (20140429); 2016/199-31/2 (20160405); 2018/912-32 (20180502); 2019-03079 (20190603)) and complied with the declaration of Helsinki.

Informed Consent Statement

All patients were given oral and written information and signed an informed consent form.

Data Availability Statement

The datasets presented in this article are not readily available because of patient secrecy.

Conflicts of Interest

The authors declare no conflicts of interest.

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Figure 1. Pathological CMR findings in 39 study participants. Numbers above bars denote absolute numbers of each pathological finding. RWMA = regional wall motion anomalies. Impaired EF = ejection fraction < 55%.
Figure 1. Pathological CMR findings in 39 study participants. Numbers above bars denote absolute numbers of each pathological finding. RWMA = regional wall motion anomalies. Impaired EF = ejection fraction < 55%.
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Figure 2. Comparison of values for the additional echocardiographic parameters in patients with and without pathological findings at CMR. 1 VA = ventriculo-arterial. 2 LA = left atrial.
Figure 2. Comparison of values for the additional echocardiographic parameters in patients with and without pathological findings at CMR. 1 VA = ventriculo-arterial. 2 LA = left atrial.
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Table 1. Clinical characteristics and echocardiographic parameters of study participants.
Table 1. Clinical characteristics and echocardiographic parameters of study participants.
Clinical Characteristicsn = 39%
Women2256.4
Age, median (IQR) 164 (45–74)
Hypertension1128.2
Paroxysmal atrial fibrillation512.8
Systolic blood pressure, mmHg, mean ± SD 2136 ± 18
Body surface area, m2, mean ± SD1.91 ± 0.2
1 IQR = interquartile range, 2 SD = standard deviation.
Table 2. Echocardiographic parameters in study participants.
Table 2. Echocardiographic parameters in study participants.
Standard Echocardiographic ParametersValue
Stroke volume index (mL/m2)39.63 (36.51–45.41)
LV 1 ejection fraction (%)58.1 ± 2.4
TAPSE 2 (mm)24 ± 2.8
LV end-systolic volume (mL)46.9 ± 11
LV end-diastolic volume (mL)111.9 ± 24.7
Additional Echocardiographic ParametersValue
LV global longitudinal strain (%)−17.9 ± 2.4
Mechanical dispersion (ms)47.5 (39–59.5)
VA 3 coupling0.62 ± 0.25
Integrated backscatter (dB)−16.9 ± 5.4
Left atrial activation time (ms)133.1 ± 18.6
1 LV = left ventricular. 2 TAPSE = tricuspid annular plane systolic excursion. 3 VA = ventriculo-arterial. All values are presented as means ± SD or median (IQR).
Table 3. CMR-obtained parameters in study participants.
Table 3. CMR-obtained parameters in study participants.
CMR-Obtained ParametersValue
LV 1 ejection fraction (%)55 (53.5–59)
LV stroke volume (mL)89 ± 20
LV end-systolic volume (mL)73.2 ± 20.6
LV end-diastolic volume (mL)162.7 ± 37.8
RV 2 ejection fraction (%)56 (53–60)
RV stroke volume (mL)84 ± 22
RV end-systolic volume (mL)68 ± 22
RV end-diastolic volume (mL)155.2 ± 41.7
1 LV = left ventricular. 2 RV = right ventricular. All values are presented as means ± SD or median (IQR).
Table 4. Comparison between patient characteristics and extended echocardiographic parameters in study participants with and without pathological CMR findings.
Table 4. Comparison between patient characteristics and extended echocardiographic parameters in study participants with and without pathological CMR findings.
Clinical CharacteristicsCMR FindingsNo CMR Findingsp-Value
Age (years)57.960.50.46
Systolic blood pressure (mmHg)138.75135.20.75
Diastolic blood pressure (mmHg)77.9277.50.82
Body surface area (m2)1.831.950.35
PVC 1 burden (PVCs/day)22,80017,9000.05
Echocardiographic parameters
Septal wall thickness (mm)9.839.590.63
LV 2 mass index (g/m2)78.6771.960.3
LA 3 volume index (mL/m2)33.7530.550.22
LV global longitudinal strain (%)−17.49−18.050.15
LA activation time (ms)133.64132.880.06
Integrated backscatter (dB)−18.4−16.370.75
VA 4 coupling0.680.590.57
Mechanical dispersion (ms)66.7149.190.97
1 PVC = Premature ventricular complex. 2 LV = left ventricular. 3 LA = left atrial. 4 VA = ventriculo-arterial. All values are presented as means.
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Wickzén, O.; Sundqvist, M.; Scorza, R. Comparison of Cardiac Magnetic Resonance and Advanced Echocardiography in Evaluation of Patients with High Burden of Premature Ventricular Contractions and Normal Standard Echocardiography. Hearts 2024, 5, 365-374. https://doi.org/10.3390/hearts5030026

AMA Style

Wickzén O, Sundqvist M, Scorza R. Comparison of Cardiac Magnetic Resonance and Advanced Echocardiography in Evaluation of Patients with High Burden of Premature Ventricular Contractions and Normal Standard Echocardiography. Hearts. 2024; 5(3):365-374. https://doi.org/10.3390/hearts5030026

Chicago/Turabian Style

Wickzén, Oscar, Martin Sundqvist, and Raffaele Scorza. 2024. "Comparison of Cardiac Magnetic Resonance and Advanced Echocardiography in Evaluation of Patients with High Burden of Premature Ventricular Contractions and Normal Standard Echocardiography" Hearts 5, no. 3: 365-374. https://doi.org/10.3390/hearts5030026

APA Style

Wickzén, O., Sundqvist, M., & Scorza, R. (2024). Comparison of Cardiac Magnetic Resonance and Advanced Echocardiography in Evaluation of Patients with High Burden of Premature Ventricular Contractions and Normal Standard Echocardiography. Hearts, 5(3), 365-374. https://doi.org/10.3390/hearts5030026

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