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Hemodynamic consequences of premature ventricular contractions: Association of mechanical and postextrasystolic potentiation with premature ventricular contraction-induced cardiomyopathy

Sophie Billet, MD,* Anne Rollin, MD,* Pierre Mondoly, MD,* Benjamin Monteil, MD,* Pauline Fournier, MD,* Eve Cariou, MD,* Marie Sadron Blaye-Felice, MD,* Michel Galinier, MD,* Didier Carrié, MD,* Olivier Lairez, MD,* Clément Delmas, MD,* Philippe Maury, MD*†

From the *Department of , University Hospital Rangueil, Toulouse, France, and †Unité Inserm U 1048, Toulouse, France.

BACKGROUND The relationships between hemodynamic conse- potentiation index (PEPi 5 number of PVCs with PEP/total PVC) quences of premature ventricular contractions (PVCs) and develop- were calculated. ment of premature ventricular contraction-induced cardiomyopathy 6 6 (PVC-CM) have not been investigated. RESULTS EMi was 29% 31% in PVC-CM and 78% 20% in con- trols (P ,.0001). PEPi was 41% 6 28% in PVC-CM and 14% 6 10% OBJECTIVE The purpose of this study was to correlate concealed in controls (P 5 .001). There was no control in groups of low EMi or mechanical bradycardia and/or postextrasystolic potentiation high PEPi. EMi and PEPi were not significantly correlated to left ven- (PEP) to PVC-CM. tricular dimensions or function in PVC-CM patients. PVC coupling in- terval was related to both ejecting PVCs and PEP. METHODS Invasive arterial pressure measurements from 17 pa- tients with PVC-CM and 16 controls with frequent PVCs were retro- CONCLUSION Patients with PVC-CM more often display noneject- spectively analyzed. PVCs were considered efficient (ejecting ing PVCs and PEP compared to controls. PVCs) when generating a measurable systolic arterial pressure. PEP was defined by a systolic arterial pressure of the post-PVC beat 5 KEYWORDS ; Cardiomyopathy; Mechanical bradycardia; mm Hg higher than the preceding sinus beat. Every PVC was analyzed Postextrasystolic potentiation; Premature ventricular contraction for 10 minutes before ablation, and the electromechanical index ( Rhythm 2019;16:853–860) 2018 Heart Rhythm Society. 5 © (EMi number of ejecting PVCs/total PVC) and postextrasystolic All rights reserved.

Introduction PVCs carry some hemodynamic consequences that have Although premature ventricular contractions (PVCs) are not been investigated so far. For example, the lack of commonly considered as benign findings in the absence of mechanical efficiency of PVCs may lead to concealed mechan- 13,14 structural heart disease, some patients with frequent PVCs ical bradycardia. Postextrasystolic potentiation (PEP) is a will develop premature ventricular contraction-induced cardio- well-known physiological cardiac property defined by a tran- 15 (PVC-CM), which is reversible after elimination of sient increase in inotropism after a premature beat. Although the PVCs.1–5 However, only 5% of patients with frequent potential relationships between these features and severe left PVCs will present with PVC-CM,6 and reliable prediction of ventricular (LV) dysfunction or development of PVC-CM the late occurrence of PVC-CM remains elusive. Even if have been evoked,16 they have not been investigated to date. some parameters have been found independently associated The aim of this study was to assess potential relationships with PVC-CM in patients with frequent PVCs, mechanisms between hemodynamic consequences of PVCs and the pres- leading to PVC-CM are still hypothetical.2,4,5,7–12 ence of PVC-CM.

Methods fl All authors have reported that they have no con icts relevant to the con- Thirty-three successive patients referred for radiofrequency tents of this paper to disclose. Address reprint requests and correspon- dence: Dr Philippe Maury, Cardiology, University Hospital Rangueil, (RF) ablation of frequent PVCs in whom invasive monitoring 31059 Toulouse Cedex 09, France. E-mail address: mauryjphil@hotmail. of the arterial pressure was available were retrospectively com. included. These patients presented with frequent PVCs

1547-5271/$-see front matter © 2018 Heart Rhythm Society. All rights reserved. https://doi.org/10.1016/j.hrthm.2018.12.008 854 Heart Rhythm, Vol 16, No 6, June 2019 associated with unexplained CM (PVC-CM group) or with normal heart (control group). Patients with frequent nonsus- tained ventricular (.1% QRS complexes) were excluded. In the PVC-CM group (n 5 17), alteration of LV systolic function (left ventricular [LVEF] ,50%) and LV dilation could not be linked to an underlying structural heart disease after usual complete investigations (radionuclide or coronary angiography), persisted after 3 months of optimal drug therapy, and regressed after ablation in every case (.10% increase in LVEF).17 In the control group (n 5 16), patients with preserved LVEF and normal LV dimensions were ablated for symptomatic PVCs after failure of antiarrhythmic therapy. Twenty-four–hour ambulatory recordings were per- Figure 1 Example of premature ventricular contraction without formed before the procedure in every patient. PVC burden any significant aortic ejection, as can be seen on the arterial pressure curve. and polymorphism were noted, as well as the presence of interpolated beats or episodes of bigeminy/trigeminy defined PEP by uninterrupted episode(s) of .5 minutes’ duration. PEP was considered present when the systolic arterial pres- LVEF and end-diastolic LV diameter and volumes were sure of the sinus beat following a PVC was 5 mm Hg higher evaluated at baseline in each patient by than that of the sinus beat preceding the PVC (Figure 2). This after at least 3 successive sinus cardiac beats. threshold was based on the value of the SD of systolic pres- sure of sinus beats. Ablation procedure Because of the variability in PEP, PEP was also evaluated Antiarrhythmic drugs were discontinued at least 5 half-lives for every PVC over the same 10-minute period. The ratio before the procedure except for amiodarone. Isoproterenol between the number of PVCs with PEP and the total number was perfused when PVCs were absent at the beginning of of PVCs was calculated and termed the postextrasystolic the procedure. Activation mapping was used combined with potentiation index (PEPi). PEP was not evaluated during pace-mapping. Epicardial foci were defined by PVCs ablated periods of bigeminy (1 patient with PVC-CM and permanent inside the coronary sinus. RF energy was delivered with bigeminy could not be included in these measurements). irrigated-tip catheters using power of 30–50 W. Acute success was defined by elimination of the targeted PVC after 30 mi- Correlations of PVC hemodynamics to ECG nutes of observation with and without isoproterenol infusion. parameters In a second set of measurements, different time intervals were Hemodynamic measurements retrieved from 6 ejecting and 6 nonejecting PVCs and from 6 Invasive arterial pressure was constantly monitored during PVCs with and 6 PVCs without PEP in each patient, avoiding the whole procedure by a pressure transducer connected to periods of bigeminy. Previous cycle length, PVC coupling the 5F to 8F short or long sheath introduced into the femoral interval, and duration of post-PVC pause were determined, artery. Air bubbles were flushed from the system, and the zero as well as electromechanical delay (EMD) (between QRS level for arterial blood pressure was taken at the level of the onset and onset of ejection) and peak electromechanical right atrium. Arterial pressure curve was stored together delay (pEMD) (between QRS onset and peak of ejection) with 12-lead ECG on the electrophysiological recording sys- of both sinus beats and PVCs. tem. Measurements were performed retrospectively on screen All measurements were performed with calipers on screen before insertion of any catheter inside the sheath. at 50 mm/s speed. Intraobserver variability in such measure- ments has been already shown to be acceptable7 and was not Mechanical efficiency tested again in this study. PVCs were considered hemodynamically efficient when generating a visible systolic arterial pressure (ie, 5mm Follow-up Hg) on the descending slope of the diastolic pressure of the Antiarrhythmic drugs were stopped, whereas beta-blockers and previous beat (ejecting PVC) (Figure 1). medications were discontinued only after normal- Because of the variability in PVC-generated arterial pres- ization of LV function and dimensions. In the PVC-CM group, sure, mechanical efficiency was evaluated for every PVC all patients underwent repeat echocardiography at 3 months for over a 10-minute period. The ratio between the number of confirmation of the diagnosis. Twenty-four–hour ambulatory ejecting PVCs and the total number of PVCs was calculated recordings at 3 months were performed in every patient from and termed the electromechanical index (EMi). In case of both groups. A .80% decrease of PVC burden compared to sustained bigeminy, EMi was calculated over 5 minutes of baseline was defined as long-term success of the ablation bigeminy and 5 minutes of nonbigeminy rhythms. procedure.17 Billet et al Hemodynamic Consequences of Premature Ventricular Contractions 855

Figure 2 Example of postextrasystolic potentiation after premature ventricular contraction (PVC). Systolic arterial pressure is significantly increased compared to the beat before PVC.

Informed consent was obtained from all patients. The study Logistic regression was performed to determine parameters was performed in accordance with ethical standards and associated with the presence of PVC-CM. Parameters signifi- declared to the CNIL (Commission Nationale de l’Informa- cantly related to PVC-CM in univariate analysis (P ,.1) tique et des Libertés) according to French law (no. 2205320). were considered eligible explanatory variables in a multivar- iate logistic model. Statistical analysis Analysis and calculations were performed using the Stat- View program (1992–1996, version 5.0; Abacus Concepts Categorical variables are given as number and percentage Inc, Berkeley, CA). P ,.05 was considered significant for and were compared using c2 test or the Fisher exact test as each analysis. appropriate. Continuous variables are expressed as mean 6 SD and were compared using unpaired t test or analysis of variance for comparison between several groups. Paired Results t test was used for comparison of parameters between Patients from the PVC-CM group had lower LVEF and higher different PVC groups for each patient. Correlations between LV dimensions compared to controls (P ,.0001). In the PVC- numerical values were assessed by nonparametric Spearman CM group, patients presented less frequently with , test. had higher baseline New York Heart Association functional 856 Heart Rhythm, Vol 16, No 6, June 2019

Table 1 Clinical and echocardiographic parameters of the study population Whole population (n 5 33) PVC-CM (n 5 17) Controls (n 5 16) P value Age (y) 60 6 16 61 6 14 59 6 18 NS Male (%) 17 (52) 11 (65) 6 (37) NS Smokers (%) 11 (33) 6 (35) 5 (31) NS (%) 4 (12) 3 (18) 1 (6) NS Hypercholesterolemia (%) 10 (30) 4 (24) 6 (37) NS (%) 12 (36) 6 (35) 6 (37) NS PVC history (years) 3.6 6 4.3 5.5 6 6 2.1 6 1.5 .07 Palpitations (%) 16 (48) 4 (24) 12 (75) .003 New York Heart Association functional 10/18/5 2/11/4 8/7/1 .04 class (II/III/IV) Antiarrhythmic drug before ablation (%) 33 (100) 17 (100) 16 (100) NS Antiarrhythmic drug after ablation (%) 23 (67) 15 (88) 8 (50) .01 LVEF (%) 47 6 15 35 6 9616 5 ,.0001 End-diastolic LV diameter (mm) 55 6 10 62 6 7486 7 ,.0001 End-diastolic LV volume (mL/m2)776 27 101 6 21 56 6 9 ,.0001 Values are given as mean 6 SD or n (%) unless otherwise indicated. LV 5 left ; LVEF 5 left ventricular ejection fraction; PVC 5 premature ventricular contraction; PVC-CM 5 premature ventricular contraction-induced cardiomyopathy. class, and were more often prescribed with antiarrhythmic was 122 6 42 minutes, with a mean of 17 6 11 minutes of drugs after ablation compared to controls. Both groups were fluoroscopy and 8 6 6 minutes of RF application (P 5 NS similar for other parameters (Table 1). Five patients in the between groups). PVC-CM group and 2 controls had additional structural heart Mean follow-up duration was 20 6 12 months (P 5 NS disease (P 5 NS), which was not considered to be linked to the between groups). Long-term success was achieved in all patients alteration of LVEF and LV dilation in the PVC-CM group. from the PVC-CM group and in 13 controls (81%) (P 5 NS). In Baseline PVC burden was not significantly higher in the the PVC-CM group, ablation led to a significant increase in PVC-CM group (23% 6 7% vs 18% 6 11%; P 50.2). PVC LVEF (35% 6 9% to 53% 6 9%; P ,.0001) and decrease in burden at 3 months was low and did not differ between groups. end-diastolic LV diameter (62 6 7mmto566 7mm; Mean heart rates and presence of bi/trigeminy were not P ,.0001) and volume (101 6 21 mL/m2 to 78 6 16 mL/m2; different between groups, either at baseline or during follow- P ,.0001). Based on LVEF increase, all patients in this group up. PVC origin, morphology, or presence of polymorphism were considered to have PVC-CM. or interpolation were not significantly different between groups (Table 2). Because coupling intervals, post-PVC Mechanical efficiency of PVCs pauses, cycle lengths, or EMDs were variable and not evalu- ated for every PVC, they could not be directly compared Ejecting PVCs and EMi between groups. Over a 10-minute period, 157 6 121 PVCs and 90 6 72 PVCs A mean of 1.2 6 0.4 procedures was performed for each were analyzed in the PVC-CM and control groups, respectively patient (2 procedures in 9 patients). Mean procedure duration (P 5 .06). The number of hemodynamically efficient PVCs was

Table 2 Results of ambulatory recordings and PVC origin and morphology in the study population Whole population (n 5 33) PVC-CM (n 5 17) Controls (n 5 16) P value Baseline PVC burden (%) 20 6 9236 7186 11 NS Baseline bi/trigeminy (%) 17 (51) 9 (53) 8 (50) NS Baseline mean heart rate (bpm) 72 6 7706 6746 7NS PVC burden at 3 months (%) 1.9 6 2.9 2.3 6 2.7 1.5 6 3.1 NS Bi/trigeminy at 3 months (%) 4 (12) 2 (12) 2 (16) NS Mean heart rate at 3 months (bpm) 70 6 8696 7726 9NS Left pattern (%) 20 (60) 9 (53) 11 (79) NS Left axis (%) 12 (36) 9 (53) 3 (21) NS Right ventricular origin (%) 5 (15) 1 (6) 4 (25) NS Epicardial location (%) 6 (18) 3 (18) 3 (19) NS Polymorphism (%) 8 (24) 5 (29) 3 (19) NS No. of different PVC morphologies 1.27 6 0.5 1.3 6 0.5 1.25 6 0.6 NS PVC QRS duration (ms) 139 6 18 138 6 23 139 6 13 NS PVC QRS amplitude (mV) 2.05 6 0.6 2.1 6 0.8 2.0 6 0.4 NS Interpolation 8/33 5/17 3/16 NS Values are given as mean 6 SD or n (%) unless otherwise indicated. PVC 5 premature ventricular contraction; PVC-CM 5 premature ventricular contraction-induced cardiomyopathy. Billet et al Hemodynamic Consequences of Premature Ventricular Contractions 857

Figure 3 Proportion of premature ventricular contraction-induced cardiomyopathy (PVC-CM) and controls according to the electromechanical index (EMi).

36 6 55 in the PVC-CM group and 66 6 51 in controls Parameters linked to PVC hemodynamics (P 5 NS). Thus, EMi was 29% 6 31% in PVC-CM patients When comparing 6 ejecting PVCs with and 6 nonejecting (0%–100%) and 78% 6 20% in controls (37%–100%) PVCs in each patient, only coupling interval was signifi- (P ,. 0001). cantly longer in ejecting PVCs (with more borderline differ- No cutoff value for EMi can be found for differentiating ences in cycle length, systolic pressure, EMD, and pEMD of PVC-CM patients and controls, but classification of patients the preceding sinus beat) (Table 4). into 3 groups according to EMi (.75%, between 25% and 75%, and ,25%) yielded significant difference in the propor- PEP 5 tion of PVC-CM patients and controls (P .001) (Figure 3). Over 10 minutes, 129 6 117 PVCs and 88 6 80 PVCs were LVEF and end-diastolic LV volumes and diameters were analyzed in the PVC-CM and control groups, respectively fi signi cantly related to EMi group (Table 3), but none of the (P 5 NS). The number of PVCs with PEP was 33 6 29 in fi other clinical or ECG parameters were signi cantly corre- the PVC-CM group and 13 6 16 in controls (P 5 .02). 5 lated to EMi group, except smoker habits (P .04) and dia- Thus, PEPi was 41% 6 28% in the PVC-CM group (3–90) 5 fi betes (P .06) were borderline signi cant. and 14% 6 10% in controls (0–44) (P 5 .001). fi 5 EMi was signi cantly correlated to LVEF (R 0.66; No cutoff value for PEPi can be found for differentiating 5 5 P .0002) and inversely to end-diastolic LV diameter (R PVC-CM patients and controls, but classification of patients 2 5 52 5 0.5; P .004) and volume (R 0.7; P .0001) in the in 3 groups according to PEPi (.70%, between 30% and fi whole group, but this was no more signi cant when only 70%, and ,30%) yielded borderline differences in the propor- PVC-CM patients were studied. tion of PVC-CM patients and controls (P 5 .06) (Figure 4).

Table 3 LV characteristics according to EMi and PEPi EMi 75% 25%EMi,75% EMi ,25% P value Preserved LVEF 8/10 8/14 0/9 .001 LVEF (%) 57 6 8506 14 32 6 10 .0001 ED LVD (mm) 46 6 7536 8646 8 .0002 ED LVV (mL/m2)556 8736 25 104 6 22 .0003

PEPi 70% 70%.PEPi30% PEPi ,30% P value Preserved LVEF 0/4 4/9 12/9 .06 LVEF (%) 30 6 4466 16 54 6 13 .01 ED LVD (mm) 64 6 5566 7516 10 .04 ED LVV (mL/m2) 112 6 14 79 6 35 61 6 20 .01 Values are given as mean 6 SD unless otherwise indicated. ED LVD 5 end-diastolic left ventricular diameter; ED LVV 5 end-diastolic left ventricular volume; EMi 5 electromechanical index; LV 5 left ventricle; LVEF 5 left ventricular ejection fraction; PEPi 5 postextrasystolic potentiation index. 858 Heart Rhythm, Vol 16, No 6, June 2019

Table 4 Parameters linked to significant PVC ejection and to PEP Ejecting PVCs Nonejecting PVCs P value Coupling interval (ms) 540 6 98 455 6 42 ,.0001 Previous cycle length (ms) 870 6 194 936 6 403 .02 Preceding sinus beat EMD (ms) 177 6 33 167 6 35 .03 Preceding sinus beat peak EMD (ms) 337 6 40 322 6 45 .05

PVCs with PEP PVCs without PEP P value Coupling interval (ms) 514 6 102 537 6 101 .02 Preceding sinus beat systolic pressure 131 6 20 143 6 20 ,.0001 (mm Hg) Preceding sinus beat peak EMD (ms) 334 6 44 344 6 52 .04 EMD 5 electromechanical delay; PVC 5 premature ventricular contraction; PEP 5 postextrasystolic potentiation.

LVEF and end-diastolic LV volumes and diameters were Correlations between PVC hemodynamics and PEP significantly related to PEPi group (Table 3), but none of the No significant correlation was noted between PEPi and EMi, other clinical or ECG parameters was significantly correlated although a trend was present (P 5 .06; R 520.34). Two to PEPi group (except borderline more PEP in males; patients with PVC-CM had PEPi 70% and EMi ,25% vs P 5 .08). none in controls (P 5 NS). PEPi was significantly correlated to end-diastolic LV diam- 5 5 5 5 eter (R 0.37 ; P .03) and volume (R 0.56 ; P .003) and Multivariate analysis inversely correlated to LVEF (R 520.5 ; P 5 .006) in the fi fi Signi cant explanatory parameters in univariate analysis whole group, but this was only of borderline signi cance (PEPi, EMi, and lack of palpitations) were included in logistic P 5 when only PVC-CM patients were studied ( .09, NS, regression. EMi (odd ratio [OR] 1.05; 95% confidence interval and .04, respectively). [CI] 1.005–1.02; P 5 .03) and lack of palpitations (OR 12.6; 95% CI 0.9–176; P 5 .06) were more closely and indepen- dently associated with PVC-CM than PEPi (OR 1.1; 95% CI Parameters linked to PEP 0.98–1.2; P 5 .1) in multivariate analysis. When comparing 6 PVCs with and 6 PVCs without PEP in each patient, only systolic pressure of sinus beats preceding PVCs and more marginally PVC coupling interval and Discussion pEMD of the preceding sinus beat differed significantly Many risk factors have been proposed to explain the occur- (Table 4). rence of PVC-CM, such as PVC burden, lack of symptoms,

Figure 4 Proportion of premature ventricular contraction-induced cardiomyopathy (PVC-CM) and controls according to the postextrasystolic potentiation in- dex (PEPi). Billet et al Hemodynamic Consequences of Premature Ventricular Contractions 859 epicardial focus, QRS duration, male gender, and various other In this study, only the PVC coupling interval was strongly parameters.2,4,5,7–12 However, because only a limited number associated with PVC hemodynamics. Ejecting PVCs had a of subjects sharing these parameters will present with late longer coupling interval, which may be easily explained by CM, the reasons for frequent PVCs inducing CM remain a longer LV filling time and therefore a higher ejection largely unknown, and other parameters should be involved volume. However, even if a short coupling interval was in order to explain this uncommon evolution. Besides sometimes found associated with PVC-CM,21,22 there are ventricular dyssynchrony, PVCs may lead to some controversial data.5,9,11 hemodynamic consequences, which may represent interesting clues for explaining late CM. In this study, we tested 2 different hemodynamic conse- PEP quences of PVCs potentially involved in PVC-CM: concealed PEP is a well-known physiological phenomenon that was mechanical bradycardia due to hemodynamic inefficiency of recognized .100 years ago15,19 and may be a sign of PVCs and presence of PEP. These hemodynamic conse- failing heart.15,19,20,23 Initially thought to be simply due to quences of PVCs have already been evoked in relation to a Frank–Starling phenomenon together with baroreflex- PVC-CM16 but had never been evaluated in dedicated studies. dependent sympathetic changes or changes in afterload,19,23 We found that patients with PVC-CM more often present with PEP was then proved to be independent of loading concealed mechanical bradycardia and PEP than controls. conditions24,25 and was linked to changes in calcium homeostasis.15 Currently, PEP is best explained by the refrac- tory period of Ca21 release channels.16,26 Concealed mechanical bradycardia Some have advocated PEP as a mechanism for Some PVCs do not generate sufficient ejection volume or PVC-CM.16 PEP significantly increases myocardial oxygen pressure to allow opening of the and detect- consumption,27,28 and when frequent this increased energy able aortic pressure (mechanical systole), leading to a con- consumption may explain the occurrence of systolic cealed mechanical bradycardia. In this case, the cardiac dysfunction. However, this hypothesis has never been rate measured on ECG does not reflect the true mechanical investigated. cardiac rate. This phenomenon was first reported in In our study, patients with PVC-CM had a significantly 1988,13 then mechanical bradycardia was reported in higher proportion of PVC-inducing PEP compared to another patient with PVC-CM in 2004.14 This mechanism controls (41% 6 28% vs 14% 6 10%). as a potential cause of PVC-CM was proposed in a recent Just as for PVCs hemodynamics, although we indicated a review,16 but no study investigating this point is available significant correlation between PEP and the presence of to date. PVC-CM, determining from this study whether PEP induced In our study, PVCs in controls were more often efficient in CM or altered LV leads to PEP is difficult. We also showed ejecting into the aorta than in patients with PVC-CM, leading that PEPi was significantly correlated to LV systolic function to shorter periods of concealed mechanical bradycardia. and dimensions: the more altered EF and dilated LV, the Repeated mechanical inefficiency of PVCs leads to sus- more PEP was present. However, there were patients with tained concealed mechanical bradycardia, decreasing cardiac frequent PEP despite preserved LVEF and conversely, and output18 and increasing LV diastolic pressures, leading to vol- correlations between PEPi and LV function and dimensions ume overload, LV dilation, and LV systolic dysfunction. were of limited significance in the subgroup of patients Furthermore, repeated lack of arterial pulse can be responsible with PVC-CM. This probably means that LV function alone for neurovegetative imbalance through baroreceptor reflex,19,20 does not predict the existence of PEP, which probably is which may be deleterious to myocardial function over time. modulated by many others factors. Definitive conclusions Although we indicated a significant correlation between cannot be drawn from this study, and only prospective works poor hemodynamic performance of PVCs and the presence can resolve this issue. of PVC-CM, it is difficult to determine from this study Coupling interval was significantly lower in cases of PEP. whether inefficient PVCs induced CM or altered LV was Other studies also showed that the shorter the coupling inter- unable to allow PVCs to eject. We showed that EMi was val, the weaker the PVC and the stronger the postextrasystolic significantly correlated to LV systolic function and dimen- beat.15,19,29 Thus, coupling interval seems to be the common sions: the less frequently PVCs generated significant aortic underlying mechanistic factor for both PVC ejection and pressure, the more altered EF and dilated LV was present. PEP. However correlations between coupling interval and However, there were patients with high EMi despite altered CM-PVC are controversial.5,9,11,21,22 LVEF and conversely, and correlations between EMi and Finally, PEP and PVC mechanical efficiency were not LV function/dimensions were no more valid in the subgroup well correlated in this study and did not show synergistic of patients with PVC-CM. This probably means that LV properties. Multivariate analysis showed that EMi was inde- function alone does not predict hemodynamic consequences pendently and stronger associated with PVC-CM compared of PVCs, which are modulated by many others factors. Defin- to PEPi. Prospective studies are needed to investigate the itive conclusions cannot be drawn from this study, and only potential role of mechanical efficiency and PEP in the devel- prospective works can resolve this issue. opment of PVC-CM in normal populations. 860 Heart Rhythm, Vol 16, No 6, June 2019

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