Imaging in patients with cardiovascular implantable electronic devices: part 1-imaging before and during device implantation. A clinical consensus statement of the European Association of Cardiovascular Imaging (EACVI) and the European Heart Rhythm Association (EHRA) of the ESC.

More than 500 000 cardiovascular implantable electronic devices (CIEDs) are implanted in the European Society of Cardiology countries each year. The role of cardiovascular imaging in patients being considered for CIED is distinctly different from imaging in CIED recipients. In the former group, imaging can help identify specific or potentially reversible causes of heart block, the underlying tissue characteristics associated with malignant arrhythmias, and the mechanical consequences of conduction delays and can also aid challenging lead placements. On the other hand, cardiovascular imaging is required in CIED recipients for standard indications and to assess the response to device implantation, to diagnose immediate and delayed complications after implantation, and to guide device optimization. The present clinical consensus statement (Part 1) from the European Association of Cardiovascular Imaging, in collaboration with the European Heart Rhythm Association, provides comprehensive, up-to-date, and evidence-based guidance to cardiologists, cardiac imagers, and pacing specialists regarding the use of imaging in patients undergoing implantation of conventional pacemakers, cardioverter defibrillators, and resynchronization therapy devices. The document summarizes the existing evidence regarding the use of imaging in patient selection and during the implantation procedure and also underlines gaps in evidence in the field. The role of imaging after CIED implantation is discussed in the second document (Part 2).

Monitoring of Myocardial Involvement in Early Arrhythmogenic Right Ventricular Cardiomyopathy Across the Age Spectrum.

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by fibrofatty replacement of primarily the right ventricular myocardium, a substrate for life-threatening ventricular arrhythmias (VAs). Repeated cardiac imaging of at-risk relatives is important for early disease detection. However, it is not known whether screening should be age-tailored. OBJECTIVES: The goal of this study was to assess the need for age-tailoring of follow-up protocols in early ARVC by evaluating myocardial disease progression in different age groups. METHODS: We divided patients with early-stage ARVC and genotype-positive relatives without overt structural disease and VA at first evaluation into 3 groups: age <30 years, 30 to 50 years, and ≥50 years. Longitudinal biventricular deformation characteristics were used to monitor disease progression. To link deformation abnormalities to underlying myocardial disease substrates, Digital Twins were created using an imaging-based computational modeling framework. RESULTS: We included 313 echocardiographic assessments from 82 subjects (57% female, age 39 ± 17 years, 10% probands) during 6.7 ± 3.3 years of follow-up. Left ventricular global longitudinal strain slightly deteriorated similarly in all age groups (0.1%-point per year [95% CI: 0.05-0.15]). Disease progression in all age groups was more pronounced in the right ventricular lateral wall, expressed by worsening in longitudinal strain (0.6%-point per year [95% CI: 0.46-0.70]) and local differences in myocardial contractility, compliance, and activation delay in the Digital Twin. Six patients experienced VA during follow-up. CONCLUSIONS: Disease progression was similar in all age groups, and sustained VA also occurred in patients aged >50 years without overt ARVC phenotype at first evaluation. Unlike recommended by current guidelines, our study suggests that follow-up of ARVC patients and relatives should not stop at older age.

The added value of abnormal regional myocardial function for risk prediction in arrhythmogenic right ventricular cardiomyopathy.

AIMS: A risk calculator for individualized prediction of first-time sustained ventricular arrhythmia (VA) in arrhythmogenic right ventricular cardiomyopathy (ARVC) patients has recently been developed and validated (www.ARVCrisk.com). This study aimed to investigate whether regional functional abnormalities, measured by echocardiographic deformation imaging, can provide additional prognostic value. METHODS AND RESULTS: From two referral centres, 150 consecutive patients with a definite ARVC diagnosis, no prior sustained VA, and an echocardiogram suitable for deformation analysis were included (aged 41 ± 17 years, 50% female). During a median follow-up of 6.3 (interquartile range 3.1-9.8) years, 37 (25%) experienced a first-time sustained VA. All tested left and right ventricular (LV and RV) deformation parameters were univariate predictors for first-time VA. While LV function did not add predictive value in multivariate analysis, two RV deformation parameters did; RV free wall longitudinal strain and regional RV deformation patterns remained independent predictors after adjusting for the calculator-predicted risk [hazard ratio 1.07 (95% CI 1.02-1.11); P = 0.004 and 4.45 (95% CI 1.07-18.57); P = 0.040, respectively] and improved its discriminative value (from C-statistic 0.78 to 0.82 in both; Akaike information criterion change > 2). Importantly, all patients who experienced VA within 5 years from the echocardiographic assessment had abnormal regional RV deformation patterns at baseline. CONCLUSIONS: This study showed that regional functional abnormalities measured by echocardiographic deformation imaging can further refine personalized arrhythmic risk prediction when added to the ARVC risk calculator. The excellent negative predictive value of normal RV deformation could support clinicians considering the timing of implantable cardioverter defibrillator implantation in patients with intermediate arrhythmic risk.

Association between comorbidities and left and right atrial dysfunction in patients with paroxysmal atrial fibrillation: Analysis of AF-RISK.

BACKGROUND: To identify the association between comorbidities and left atrial (LA) and right atrial (RA) function in patients with paroxysmal atrial fibrillation (AF). METHODS: This is a cross-sectional study. Speckle-tracking echocardiography was performed in 344 patients with paroxysmal AF at baseline, and available in 298 patients after 1-year follow-up. The number of comorbidities (hypertension, diabetes mellitus, coronary artery disease, body mass index > 25 kg/m2, age > 65 years, moderate to severe mitral valve regurgitation and kidney dysfunction (estimated glomerular filtration rate < 60 ml/min/1.73 m2)) was determined and the association with atrial strain was tested. RESULTS: Mean age of the patients was 58 (SD 12) years and 137 patients were women (40%). Patients with a higher number of comorbidities had larger LA volumes (p for trend <0.001), and had a decrease in all strain phases from the LA and RA, except for the RA contraction phase (p for trend 0.47). A higher number of comorbidities was associated with LA reservoir and conduit strain decrease independently of LA volume (p < 0.001, p < 0.001 respectively). Patients with 1-2 comorbidities, but not patients with 3 or more comorbidities, showed a further progression of impaired LA and RA function in almost all atrial strain phases at 14 [13-17] months follow-up. CONCLUSIONS: In patients with paroxysmal AF, individual and combined comorbidities are related to lower LA and RA strain. In patients with few comorbidities, impairment in atrial function progresses during one year of follow-up. Whether comorbidity management prevents or reverses decrease in atrial function warrants further study.

Parameter subset reduction for patient-specific modelling of arrhythmogenic cardiomyopathy-related mutation carriers in the CircAdapt model.

Arrhythmogenic cardiomyopathy (AC) is an inherited cardiac disease, clinically characterized by life-threatening ventricular arrhythmias and progressive cardiac dysfunction. Patient-specific computational models could help understand the disease progression and may help in clinical decision-making. We propose an inverse modelling approach using the CircAdapt model to estimate patient-specific regional abnormalities in tissue properties in AC subjects. However, the number of parameters (n = 110) and their complex interactions make personalized parameter estimation challenging. The goal of this study is to develop a framework for parameter reduction and estimation combining Morris screening, quasi-Monte Carlo (qMC) simulations and particle swarm optimization (PSO). This framework identifies the best subset of tissue properties based on clinical measurements allowing patient-specific identification of right ventricular tissue abnormalities. We applied this framework on 15 AC genotype-positive subjects with varying degrees of myocardial disease. Cohort studies have shown that atypical regional right ventricular (RV) deformation patterns reveal an early-stage AC disease. The CircAdapt model of cardiovascular mechanics and haemodynamics has already demonstrated its ability to capture typical deformation patterns of AC subjects. We, therefore, use clinically measured cardiac deformation patterns to estimate model parameters describing myocardial disease substrates underlying these AC-related RV deformation abnormalities. Morris screening reduced the subset to 48 parameters. qMC and PSO further reduced the subset to a final selection of 16 parameters, including regional tissue contractility, passive stiffness, activation delay and wall reference area. This article is part of the theme issue 'Uncertainty quantification in cardiac and cardiovascular modelling and simulation'.

The Prognostic Value of Right Ventricular Deformation Imaging in Early Arrhythmogenic Right Ventricular Cardiomyopathy.

OBJECTIVES: The aim of this study was to investigate the prognostic value of echocardiographic deformation imaging in arrhythmogenic right ventricular cardiomyopathy (ARVC) to optimize family screening protocols. BACKGROUND: ARVC is characterized by variable disease expressivity among family members, which complicates family screening protocols. Previous reports have shown that echocardiographic deformation imaging detects abnormal right ventricular (RV) deformation in the absence of established disease expression in ARVC. METHODS: First-degree relatives of patients with ARVC were evaluated according to 2010 task force criteria, including RV deformation imaging (n = 128). Relatives fulfilling structural task force criteria were excluded for further analysis. At baseline, deformation patterns of the subtricuspid region were scored as type I (normal deformation), type II (delayed onset, decreased systolic peak, and post-systolic shortening), or type III (systolic stretching and large post-systolic shortening). The final study population comprised relatives who underwent a second evaluation during follow-up. Disease progression was defined as the development of a new 2010 task force criterion during follow-up that was absent at baseline. RESULTS: Sixty-five relatives underwent a second evaluation after a mean follow-up period of 3.7 ± 2.1 years. At baseline, 28 relatives (43%) had normal deformation (type I), and 37 relatives (57%) had abnormal deformation (type II or III) in the subtricuspid region. Disease progression occurred in 4% of the relatives with normal deformation at baseline and in 43% of the relatives with abnormal deformation at baseline (p < 0.001). Positive and negative predictive values of abnormal deformation were, respectively, 43% (95% confidence interval: 27% to 61%) and 96% (95% confidence interval: 82% to 100%). CONCLUSIONS: Normal RV deformation in the subtricuspid region is associated with absence of disease progression during nearly 4-year follow-up in relatives of patients with ARVC. Abnormal RV deformation seems to precede the established signs of ARVC. RV deformation imaging may potentially play an important role in ARVC family screening protocols.

Pulmonary Right Ventricular Resynchronization in Congenital Heart Disease: Acute Improvement in Right Ventricular Mechanics and Contraction Efficiency.

BACKGROUND: Electromechanical discoordination may contribute to long-term pulmonary right ventricular (RV) dysfunction in patients after surgery for congenital heart disease. We sought to evaluate changes in RV function after temporary RV cardiac resynchronization therapy. METHODS AND RESULTS: Twenty-five patients aged median 12.0 years after repair of tetralogy of Fallot and similar lesions were studied echocardiographically (n=23) and by cardiac catheterization (n=5) after primary repair (n=4) or after surgical RV revalvulation for significant pulmonary regurgitation (n=21). Temporary RV cardiac resynchronization therapy was applied in the presence of complete right bundle branch block by atrial-synchronized RV free wall pacing in complete fusion with spontaneous ventricular depolarization using temporary electrodes. The q-RV interval at the RV free wall pacing site (mean 77.2% of baseline QRS duration) confirmed pacing from a late activated RV area. RV cardiac resynchronization therapy carried significant decrease in QRS duration (P<0.001) along with elimination of the right bundle branch block QRS morphology, increase in RV filling time (P=0.002), pulmonary artery velocity time integral (P=0.006), and RV maximum +dP/dt (P<0.001), and decrease in RV index of myocardial performance (P=0.006). RV mechanical synchrony improved: septal-to-lateral RV mechanical delay decreased (P<0.001) and signs of RV dyssynchrony pattern were significantly abolished. RV systolic stretch fraction reflecting the ratio of myocardial stretching and contraction during systole diminished (P=0.001). CONCLUSIONS: In patients with congenital heart disease and right bundle branch block, RV cardiac resynchronization therapy carried multiple positive effects on RV mechanics, synchrony, and contraction efficiency.

Combining computer modelling and cardiac imaging to understand right ventricular pump function.

Right ventricular (RV) dysfunction is a strong predictor of outcome in heart failure and is a key determinant of exercise capacity. Despite these crucial findings, the RV remains understudied in the clinical, experimental, and computer modelling literature. This review outlines how recent advances in using computer modelling and cardiac imaging synergistically help to understand RV function in health and disease. We begin by highlighting the complexity of interactions that make modelling the RV both challenging and necessary, and then summarize the multiscale modelling approaches used to date to simulate RV pump function in the context of these interactions. We go on to demonstrate how these modelling approaches in combination with cardiac imaging have improved understanding of RV pump function in pulmonary arterial hypertension, arrhythmogenic right ventricular cardiomyopathy, dyssynchronous heart failure and cardiac resynchronization therapy, hypoplastic left heart syndrome, and repaired tetralogy of Fallot. We conclude with a perspective on key issues to be addressed by computational models of the RV in the near future.

Right Ventricular Imaging and Computer Simulation for Electromechanical Substrate Characterization in Arrhythmogenic Right Ventricular Cardiomyopathy.

BACKGROUND: Previous studies suggested that electrical abnormalities precede overt structural disease in arrhythmogenic right ventricular cardiomyopathy (ARVC). Abnormal RV deformation has been reported in early ARVC without structural abnormalities. The pathophysiological mechanisms underlying these abnormalities remain unknown. OBJECTIVES: The authors used imaging and computer simulation to differentiate electrical from mechanical tissue substrates among ARVC clinical stages. METHODS: ARVC desmosomal mutation carriers (n = 84) were evaluated by electrocardiography (ECG), Holter monitoring, late-enhancement cardiac magnetic resonance imaging, and echocardiographic RV deformation imaging. Subjects were categorized based on the presence of 2010 International Task Force criteria: 1) subclinical stage (n = 21); 2) electrical stage (n = 15); and 3) structural stage (n = 48). Late enhancement was not present in any subclinical or electrical stage subjects. RESULTS: Three distinctive characteristic RV longitudinal deformation patterns were identified: type I: normal deformation (n = 12); type II: delayed onset of shortening, reduced systolic peak strain, and mild post-systolic shortening (n = 35); and type III: systolic stretching with large post-systolic shortening (n = 37). A majority (69%) of structural staged mutation carriers were type III, whereas a large proportion of both electrical and subclinical stage subjects (67% and 48%, respectively) were type II. Computer simulations demonstrated that the type II pattern can be explained by a combination of reduced contractility and mildly increased passive myocardial stiffness. This evolved into type III by aggravating both mechanical substrates. Electrical activation delay alone explained none of the patterns. CONCLUSIONS: Different ARVC stages were characterized by distinct RV deformation patterns, all of which could be reproduced by simulating different degrees of mechanical substrates. Subclinical and electrical staged ARVC subjects already showed signs of local mechanical abnormalities. Our novel approach could lead to earlier disease detection and, thereby, influence current definitions of electrical and subclinical ARVC stages.

Acute hemodynamic benefits of biventricular and single-site systemic ventricular pacing in patients with a systemic right ventricle.

BACKGROUND: Patients treated by atrial redirection surgery (Senning or Mustard procedure) for transposition of the great arteries (TGA) have an important risk for heart failure caused by dysfunction of the systemic right ventricle. Conventional nonsystemic ventricular pacing (non-systVP) may even further increase this risk. OBJECTIVE: We investigated the effects of endocardial non-systVP, biventricular pacing (BiVP), and single-site systemic ventricular pacing (systVP) on systolic cardiac pump function in patients with TGA and status post atrial redirection surgery (SenningMustardTGA). METHODS: During clinically indicated catheterization in 9 patients with SenningMustardTGA, endocardial ventricular stimulation (overdrive DDD mode; 80-90 beats/min) was applied with temporary pacing leads at the nonsystemic and the systemic ventricle. Acute changes in the maximal rate of pressure rise (dP/dtmax) and systolic pressure of the systemic ventricle, as induced by non-systVP, systVP, and BiVP compared to reference, were assessed with a pressure wire within the systemic ventricle. Reference was AAI pacing with a similar heart rate (n = 7) or non-systVP at a lower heart rate than that during stimulation at experimental sites (85 beats/min vs 90 beats/min; n = 2). RESULTS: Systemic dP/dtmax and systolic ventricular pressure were significantly higher during systVP (+15.6% and +5.1%, respectively) and BiVP (+14.3% and +4.9%, respectively, compared with non-systVP). In 6 of 7 patients, systemic dP/dtmax was higher during BiVP and systVP than during AAI pacing. CONCLUSIONS: In a population of patients with SenningMustardTGA, acute hemodynamic effects of endocardial systVP and BiVP were significantly and equally better than those of non-systVP. In some patients, systVP and BiVP might even be better than ventricular activation by the intrinsic conduction system.

Mechanistic evaluation of echocardiographic dyssynchrony indices: patient data combined with multiscale computer simulations.

BACKGROUND: The power of echocardiographic dyssynchrony indices to predict response to cardiac resynchronization therapy (CRT) appears to vary between indices and between studies. We investigated whether the variability of predictive power between the dyssynchrony indices can be explained by differences in their operational definitions. METHODS AND RESULTS: In 132 CRT-candidates (left ventricular [LV] ejection fraction, 19 ± 6%; QRS width, 170 ± 22 ms), 4 mechanical dyssynchrony indices (septal systolic rebound stretch [SRSsept], interventricular mechanical dyssynchrony [IVMD], septal-to-lateral peak shortening delay [Strain-SL], and septal-to-posterior wall motion delay [SPWMD]) were quantified at baseline. CRT response was quantified as 6-month percent change of LV end-systolic volume. Multiscale computer simulations of cardiac mechanics and hemodynamics were used to assess the relationships between dyssynchrony indices and CRT response within wide ranges of dyssynchrony of LV activation and reduced contractility. In patients, SRSsept showed best correlation with CRT response followed by IVMD, Strain-SL, and SPWMD (R=-0.56, -0.50, -0.48, and -0.39, respectively; all P<0.01). In patients and simulations, SRSsept and IVMD showed a continuous linear relationship with CRT response, whereas Strain-SL and SPWMD showed discontinuous relationships characterized by data clusters. Model simulations revealed that this data clustering originated from the complex multipeak pattern of septal strain and motion. In patients and simulations with (simulated) LV scar, SRSsept and IVMD retained their linear relationship with CRT response, whereas Strain-SL and SPWMD did not. CONCLUSIONS: The power to predict CRT response differs between indices of mechanical dyssynchrony. SRSsept and IVMD better represent LV dyssynchrony amenable to CRT and better predict CRT response than the indices assessing time-to-peak deformation or motion.