Assessment of ICD eligibility in non-ischaemic cardiomyopathy patients: a position statement by the Task Force of the Dutch Society of Cardiology.

International guidelines recommend implantation of an implantable cardioverter-defibrillator (ICD) in non-ischaemic cardiomyopathy (NICM) patients with a left ventricular ejection fraction (LVEF) below 35% despite optimal medical therapy and a life expectancy of more than 1 year with good functional status. We propose refinement of these recommendations in patients with NICM, with careful consideration of additional risk parameters for both arrhythmic and non-arrhythmic death. These additional parameters include late gadolinium enhancement on cardiac magnetic resonance imaging and genetic testing for high-risk genetic variants to further assess arrhythmic risk, and age, comorbidities and sex for assessment of non-arrhythmic mortality risk. Moreover, several risk modifiers should be taken into account, such as concomitant arrhythmias that may affect LVEF (atrial fibrillation, premature ventricular beats) and resynchronisation therapy. Even though currently no valid cut-off values have been established, the proposed approach provides a more careful consideration of risks that may result in withholding ICD implantation in patients with low arrhythmic risk and substantial non-arrhythmic mortality risk.

Post-implantation CMR imaging to study biventricular pacing effects on the right ventricle in left bundle branch block patients.

Cardiac resynchronization therapy (CRT) is an established treatment for heart failure patients with left ventricular dysfunction and a left bundle branch block. However, its impact on right ventricular (RV) function remains uncertain. This cardiac magnetic resonance imaging study found that CRT did not improve RV volumes and function, and CRT-off during follow-up had an immediate detrimental effect on the RV, which may suggest potential unfavorable RV remodeling with RV pacing during CRT.

Dynamic prediction of malignant ventricular arrhythmias using neural networks in patients with an implantable cardioverter-defibrillator.

BACKGROUND: Risk stratification for ventricular arrhythmias currently relies on static measurements that fail to adequately capture dynamic interactions between arrhythmic substrate and triggers over time. We trained and internally validated a dynamic machine learning (ML) model and neural network that extracted features from longitudinally collected electrocardiograms (ECG), and used these to predict the risk of malignant ventricular arrhythmias. METHODS: A multicentre study in patients implanted with an implantable cardioverter-defibrillator (ICD) between 2007 and 2021 in two academic hospitals was performed. Variational autoencoders (VAEs), which combine neural networks with variational inference principles, and can learn patterns and structure in data without explicit labelling, were trained to encode the mean ECG waveforms from the limb leads into 16 variables. Supervised dynamic ML models using these latent ECG representations and clinical baseline information were trained to predict malignant ventricular arrhythmias treated by the ICD. Model performance was evaluated on a hold-out set, using time-dependent receiver operating characteristic (ROC) and calibration curves. FINDINGS: 2942 patients (61.7 ± 13.9 years, 25.5% female) were included, with a total of 32,129 ECG recordings during a mean follow-up of 43.9 ± 35.9 months. The mean time-varying area under the ROC curve for the dynamic model was 0.738 ± 0.07, compared to 0.639 ± 0.03 for a static (i.e. baseline-only model). Feature analyses indicated dynamic changes in latent ECG representations, particularly those affecting the T-wave morphology, were of highest importance for model predictions. INTERPRETATION: Dynamic ML models and neural networks effectively leverage routinely collected longitudinal ECG recordings for personalised and updated predictions of malignant ventricular arrhythmias, outperforming static models. FUNDING: This publication is part of the project DEEP RISK ICD (with project number 452019308) of the research programme Rubicon which is (partly) financed by the Dutch Research Council (NWO). This research is partly funded by the Amsterdam Cardiovascular Sciences (personal grant F.V.Y.T).

Optimizing patient selection for primary prevention implantable cardioverter-defibrillator implantation: utilizing multimodal machine learning to assess risk of implantable cardioverter-defibrillator non-benefit.

AIMS: Left ventricular ejection fraction (LVEF) is suboptimal as a sole marker for predicting sudden cardiac death (SCD). Machine learning (ML) provides new opportunities for personalized predictions using complex, multimodal data. This study aimed to determine if risk stratification for implantable cardioverter-defibrillator (ICD) implantation can be improved by ML models that combine clinical variables with 12-lead electrocardiograms (ECG) time-series features. METHODS AND RESULTS: A multicentre study of 1010 patients (64.9 ± 10.8 years, 26.8% female) with ischaemic, dilated, or non-ischaemic cardiomyopathy, and LVEF ≤ 35% implanted with an ICD between 2007 and 2021 for primary prevention of SCD in two academic hospitals was performed. For each patient, a raw 12-lead, 10-s ECG was obtained within 90 days before ICD implantation, and clinical details were collected. Supervised ML models were trained and validated on a development cohort (n = 550) from Hospital A to predict ICD non-arrhythmic mortality at three-year follow-up (i.e. mortality without prior appropriate ICD-therapy). Model performance was evaluated on an external patient cohort from Hospital B (n = 460). At three-year follow-up, 16.0% of patients had died, with 72.8% meeting criteria for non-arrhythmic mortality. Extreme gradient boosting models identified patients with non-arrhythmic mortality with an area under the receiver operating characteristic curve (AUROC) of 0.90 [95% confidence intervals (CI) 0.80-1.00] during internal validation. In the external cohort, the AUROC was 0.79 (95% CI 0.75-0.84). CONCLUSIONS: ML models combining ECG time-series features and clinical variables were able to predict non-arrhythmic mortality within three years after device implantation in a primary prevention population, with robust performance in an independent cohort.

Septal Midwall Late Gadolinium Enhancement in Ischemic Cardiomyopathy and Nonischemic Dilated Cardiomyopathy-Characteristics and Prognosis.

Septal midwall late gadolinium enhancement (LGE) is a characteristic finding on cardiac magnetic resonance imaging (CMR) in nonischemic dilated cardiomyopathy (DCM) and is associated with adverse events. Its significance in ischemic cardiomyopathy (ICM) is unknown. With this multicenter observational study, we aimed to study the characteristics of septal midwall LGE and evaluate its prognostic value in ICM. A total of 1,084 patients with an impaired left ventricular (LV) ejection fraction (<50%) on LGE-CMR, either because of ICM (53%) or DCM, were included retrospectively. Septal midwall LGE was defined as midmyocardial stripe-like or patchy LGE in septal segments and was present in 10% of patients with ICM compared with 34% of patients with DCM (p <0.001). It was significantly associated with larger LV volumes and lower LV ejection fraction, irrespective of etiology. The primary endpoint was all-cause mortality and secondary endpoint was ventricular arrhythmias (VAs), including resuscitated cardiac arrest, sustained VA, and appropriate implantable cardioverter-defibrillator (ICD) therapy. During a median follow-up of 2.7 years, we found a significant association between septal midwall LGE and mortality in patients with DCM (hazard ratio [HR] 1.92, p = 0.03), but not in patients with ICM (HR 1.35, p = 0.39). Risk of VAs was significantly higher in patients with septal midwall LGE on CMR, both in DCM (HR 2.80, p <0.01) and in ICM (HR 2.70, p <0.01). In conclusion, septal midwall LGE, typically seen in DCM, was also present in 10% of patients with ICM and was associated with increased LV dilation and worse function, irrespective of etiology. When present, septal midwall LGE was associated with adverse outcome.

Cardiac Magnetic Resonance Imaging-Derived Left Atrial Characteristics in Relation to Atrial Fibrillation Detection in Patients With an Implantable Cardioverter-Defibrillator.

Background Among patients with an implantable cardioverter-defibrillator, a high prevalence of atrial fibrillation (AF) is present. Identification of AF predictors in this patient group is of clinical importance to initiate appropriate preventive therapeutic measures to reduce the risk of AF-related complications. This study assesses whether cardiac magnetic resonance imaging-derived atrial characteristics are associated with AF development in patients with a dual-chamber implantable cardioverter-defibrillator or cardiac resynchronization therapy defibrillator, as detected by the cardiac implantable electronic device. Methods and Results This single-center retrospective study included 233 patients without documented AF history at the moment of device implantation (dual-chamber implantable cardioverter-defibrillator [63.5%] or cardiac resynchronization therapy defibrillator [36.5%]). All patients underwent cardiac magnetic resonance imaging before device implantation. Cardiac magnetic resonance-derived features of left atrial (LA) remodeling were evaluated in all patients. Detection of AF episodes was based on cardiac implantable electronic device interrogation. During a median follow-up of 6.1 years, a newly diagnosed AF episode was detected in 88 of the 233 (37.8%) patients with an ICD. In these patients, increased LA volumes and impaired LA function (LA emptying fraction and LA strain) were found as compared with patients without AF during follow-up. However, a significant association was only found in patients with dilated cardiomyopathy and not in patients with ischemic cardiomyopathy. Conclusions LA remodeling characteristics were associated with development of AF in patients with dilated cardiomyopathy but not patients with ischemic cardiomyopathy, suggesting different mechanisms of AF development in ischemic cardiomyopathy and dilated cardiomyopathy. Assessment of LA remodeling before device implantation might identify high-risk patients for AF.

Feasibility of CMR Imaging during Biventricular Pacing: Comparison with Invasive Measurement as a Pathway towards a Novel Optimization Strategy.

OBJECTIVES: This prospective pilot study assessed the feasibility of cardiovascular magnetic resonance (CMR) imaging during biventricular (BIV) pacing in patients with a CMR conditional cardiac resynchronization therapy defibrillator (CRT-D) and compared the results with invasive volume measurements. METHODS: Ten CRT-D patients underwent CMR imaging prior to device implantation (baseline) and six weeks after device implantation, including CRT-on and CRT-off modes. Left ventricular (LV) function, volumes, and strain measurements of LV dyssynchrony and dyscoordination were assessed. Invasive pressure-volume measurements were performed, matching the CRT settings used during CMR. RESULTS: Post-implantation imaging enabled reliable cine assessment, but showed artefacts on late gadolinium enhancement images. After six weeks of CRT, significant reverse remodeling was observed, with a 22.7 ± 11% reduction in LV end-systolic volume during intrinsic rhythm (CRT-off). During CRT-on, the LV ejection fraction significantly improved from 27.4 ± 5.9% to 32.2 ± 8.7% (p < 0.01), and the strain assessment showed the abolition of the left bundle branch block contraction pattern. Invasively measured and CMR-assessed LV hemodynamics during BIV pacing were significantly associated. CONCLUSIONS: Post-CRT implantation CMR assessing acute LV pump function is feasible and provides important insights into the effects of BIV pacing on cardiac function and contraction patterns. LV assessment during CMR may constitute a future CRT optimization strategy.

The link between cardiac status and depression and anxiety in implantable cardioverter defibrillator patients: Design and first results of the PSYCHE-ICD study.

OBJECTIVE: Depression and anxiety in patients with an implantable cardioverter-defibrillator (ICD) are associated with adverse outcomes. This study describes the design of the PSYCHE-ICD study and evaluates the correlation between cardiac status and depression and anxiety in ICD patients. METHODS: We included 178 patients. Prior to implantation, patients completed validated psychological questionnaires for depression, anxiety and personality traits. Cardiac status was evaluated by means of left ventricular ejection fraction assessment (LVEF), New York Heart Association (NYHA) functional class, 6-minute walk test (6MWT), and 24-h Holter monitoring for heart rate variability (HRV). A cross-sectional analysis was performed. Follow-up with annual study visits, including repeated full cardiac evaluation, will continue 36 months after ICD implantation. RESULTS: Depressive symptoms were present in 62 (35%) and anxiety in 56 (32%) patients. Values of depression and anxiety significantly increased with higher NYHA class (P < 0.001). Depression symptoms were correlated with a reduced 6MWT (411 ± 128 vs. 488 ± 89, P < 0.001), higher heart rate (74 ± 13 vs. 70 ± 13, P = 0.02), higher thyroid stimulation hormone levels (1.8 [1.3-2.8] vs 1.5 [1.0-2.2], P = 0.03) and multiple HRV parameters. Anxiety symptoms were correlated with higher NYHA class and a reduced 6MWT (433 ± 112 vs 477 ± 102, P = 0.02). CONCLUSION: A substantial part of patients receiving an ICD have symptoms of depression and anxiety at time of ICD implantation. Depression and anxiety were correlated with multiple cardiac parameters, suggesting a possible biological links between psychological distress and cardiac disease in ICD patients.

Recurrent ventricular arrhythmias and mortality in cardiac arrest survivors with a reversible cause with and without an implantable cardioverter defibrillator: A systematic review.

BACKGROUND: Sudden cardiac arrest survivors with a reversible cause are not eligible for implantable cardioverter defibrillator (ICD) implantation. This study aims to evaluate the risk of recurrent ventricular arrhythmia in sudden cardiac arrest survivors with a reversible cause and evaluate if ICD implantation increases survival. METHODS: We conducted a systematic review to identify studies evaluating ICD implantation in sudden cardiac arrest survivors with a reversible cause. Outcomes were mortality and appropriate device therapy. Sudden cardiac arrest patients were divided into 4 subgroups: due to acute myocardial infarction; due to coronary artery spasm; due to takotsubo cardiomyopathy; and studies with various reversible causes of cardiac arrest. RESULTS: 27 studies were included, evaluating 11,402 patients. A total of 2570 patients received an ICD. Studies evaluating coronary artery spasm and with various reversible causes showed a relatively high rate of appropriate device therapy (17% and 20%) and described an increased survival in ICD patients. Takotsubo cardiomyopathy was associated with a low mortality and none of the ICD patients received appropriate device therapy. Studies evaluating acute myocardial infarction survivors reported inconsistent results, with high numbers of appropriate device therapy (12-66%), but the mortality-rate of patients with and without an ICD varied. CONCLUSION: This study shows that the recurrence risk of ventricular arrhythmia varies between different reversible causes of sudden cardiac arrest and should not be evaluated as one entity. Cardiac arrest survivors with a reversible cause can be at risk of recurrent ventricular arrhythmia and selected patients may benefit from ICD implantation.

Sex-specific differences in outcome and risk stratification of ventricular arrhythmias in implantable cardioverter defibrillator patients.

AIMS: Risk stratification models of sudden cardiac death (SCD) are based on the assumption that risk factors of SCD affect risk to a similar extent in both sexes. The aim of the study is to evaluate differences in clinical outcomes between sexes and evaluate whether risk factors associated with appropriate device therapy (ADT) differ between men and women. METHODS AND RESULTS: We performed a cohort study of implantable cardioverter defibrillator (ICD) patients referred for primary or secondary prevention of SCD between 2009 and 2018. Multivariable Cox regression models for prediction of ADT were constructed for men and women separately. Of 2300 included patients, 571 (25%) were women. Median follow-up was 4.6 (inter-quartile range: 4.4-4.9) years. Time to ADT was shorter for men compared with women [hazard ratio (HR) 1.71, P < 0.001], as was time to mortality (HR 1.37, P = 0.003). In women, only secondary prevention ICD therapy (HR 1.82, P < 0.01) was associated with ADT, whereas higher age (HR 1.20, P < 0.001), absence of left bundle branch block (HR 0.72, P = 0.01), and secondary prevention therapy (HR 1.80, P < 0.001) were independently associated with ADT in men. None of the observed parameters showed a distinctive sex-specific pattern in ADT. CONCLUSIONS: Male ICD patients were at higher risk of ADT and death compared with female ICD patients, irrespective of an ischaemic or non-ischaemic underlying cardiomyopathy. Our study highlights the importance to stratify outcomes of ICD trials by sex, as study results differ between men and women. However, none of the available clinical parameters showed a clear sex-specific relation to ventricular arrhythmias. As a consequence, sex-specific risk stratification models of SCD using commonly available clinical parameters could not be derived.

Reversible Cause of Cardiac Arrest and Secondary Prevention Implantable Cardioverter Defibrillators in Patients With Coronary Artery Disease: Value of Complete Revascularization and LGE-CMR.

Background In survivors of sudden cardiac arrest with obstructive coronary artery disease, it remains challenging to distinguish ischemia as a reversible cause from irreversible scar-related ventricular arrhythmias. We aimed to evaluate the value of implantable cardioverter-defibrillator (ICD) implantation in sudden cardiac arrest survivors with presumably reversible ischemia and complete revascularization. Methods and Results This multicenter retrospective cohort study included 276 patients (80% men, age 67±10 years) receiving ICD implantation for secondary prevention. Angiography was performed before ICD implantation. A subgroup of 166 (60%) patients underwent cardiac magnetic resonance imaging with late gadolinium enhancement before implantation. Patients were divided in 2 groups, (1) ICD-per-guideline, including 228 patients with incomplete revascularization or left ventricular ejection fraction ≤35%, and (2) ICD-off-label, including 48 patients with complete revascularization and left ventricular ejection fraction >35%. The primary outcome was time to appropriate device therapy (ADT). During 4.0 years (interquartile range, 3.5-4.6) of follow-up, ADT developed in 15% of the ICD-off-label group versus 43% of the ICD-per-guideline group. Time to ADT was comparable in the ICD-off-label and ICD-per-guideline groups (hazard ratio (HR), 0.46; P=0.08). No difference in mortality was observed (HR, 0.95; P=0.93). Independent predictors of ADT included age (HR, 1.03; P=0.01), left ventricular end-diastolic volume HR, (1.05 per 10 mL increase; P<0.01) and extent of transmural late gadolinium enhancement (HR, 1.12; P=0.04). Conclusions This study demonstrates that sudden cardiac arrest survivors with coronary artery disease remain at high risk of recurrent ventricular arrhythmia, even after complete revascularization and with preserved left ventricular function. Late gadolinium enhancement-cardiac magnetic resonance imaging derived left ventricular volumes and extent of myocardial scar were independently associated with.

Characteristics and prognostic value of right ventricular (dys)function in patients with non-ischaemic dilated cardiomyopathy assessed with cardiac magnetic resonance imaging.

AIMS: In non-ischaemic dilated cardiomyopathy (DCM), concomitant right ventricular (RV) dysfunction is frequently observed. This study sought to determine the correlation of RV dysfunction with several cardiac magnetic resonance (CMR) imaging characteristics in patients with DCM, and the prognostic value of RV dysfunction on all-cause mortality and ventricular arrhythmias (VA) was evaluated. METHODS AND RESULTS: Consecutive patients with DCM and left ventricular (LV) dysfunction (ejection fraction < 50%) on CMR were included retrospectively. Left atrial (LA), LV, and RV volumes and function were quantified. RV systolic dysfunction was defined as RVEF<45%. The presence and pattern of late gadolinium enhancement (LGE) on CMR were assessed visually. Septal midwall LGE was defined as midmyocardial stripe-like or patchy hyperenhancement in the septal segments, and the extent was quantified using the full width at half maximum method. Primary endpoint was a composite of all-cause mortality and VA, including resuscitated cardiac arrest, sustained VA, and appropriate implantable cardioverter defibrillator therapy. Secondary endpoints were time to all-cause mortality alone and time to VA alone. A total of 216 DCM patients were included (42% female, age 58 ± 14 years). Mean RVEF was 46 ± 12%, and RV dysfunction was present in 38%. RVEF was moderately correlated with LA dilation (LA minimal volume ρ = -0.38, P < 0.001) and strongly correlated with LA and LV dysfunction (LA emptying fraction r = 0.58, P < 0.001 and LVEF ρ = 0.52, P < 0.001). Septal midwall LGE was more often observed in patients with RV dysfunction compared with patients with preserved RV function (respectively 40% vs. 26%, P = 0.04). No correlation was found between RVEF and the extent of septal midwall LGE (ρ = -0.12, P = 0.34). During a median follow-up of 2.2 years [IQR 1.6-2.8], 30 patients experienced the primary endpoint. RV dysfunction was significantly associated with shorter time to the composite primary endpoint (HR 3.19 [95% CI 1.49-6.84], P < 0.01) and to the secondary endpoint of VA alone (HR 6.48 [95% CI 1.83-22.98], P < 0.01). There was a trend towards increased mortality when RV dysfunction was present (HR 2.54 [95% CI 0.99-6.57], P = 0.05). CONCLUSIONS: Right ventricular dysfunction was predominantly observed in patients with DCM with advanced heart failure and pronounced myocardial remodelling, defined as increased LV and LA dilation and dysfunction and the presence of septal midwall LGE on CMR. During follow-up, RV dysfunction was associated with shorter time to all-cause mortality and ventricular arrhythmic events.

Value of CMR and PET in Predicting Ventricular Arrhythmias in Ischemic Cardiomyopathy Patients Eligible for ICD.

OBJECTIVES: This study presents a head-to-head comparison of the value of cardiac magnetic resonance (CMR)-derived left-ventricular (LV) function and scar burden and positron emission tomography (PET)-derived perfusion and innervation in predicting ventricular arrhythmias (VAs). BACKGROUND: Improved risk stratification of VA is important to identify patients who should benefit of prophylactic implantable cardioverter-defibrillator (ICD) implantation. Perfusion abnormalities, sympathetic denervation, and scar burden have all been linked to VA, although comparative studies are lacking. METHODS: Seventy-four patients with ischemic cardiomyopathy and left-ventricular ejection fraction (LVEF) ≤35%, referred for primary prevention ICD placement were enrolled prospectively. Late gadolinium-enhanced (LGE) CMR was performed to assess LV function and scar characteristics. [15O]H2O and [11C]hydroxyephedrine positron emission tomography (PET) were performed to quantify resting and hyperemic myocardial blood flow (MBF), coronary flow reserve (CFR), and sympathetic innervation. During follow-up of 5.4 ± 1.9 years, the occurrence of sustained VA, appropriate ICD therapy, and mortality were evaluated. RESULTS: In total, 20 (26%) patients experienced VA. CMR and PET parameters showed considerable overlap between patients with VA and patients without VA, caused by substantial heterogeneity within groups. Univariable analyses showed that lower LVEF (hazard ratio [HR]: 0.92; p = 0.03), higher left-ventricular end-diastolic volume index (LVEDVi) (HR 1.02; p < 0.01), and larger scar border zone (HR 1.11; p = 0.03) were related to VA. Scar core size, resting MBF, hyperemic MBF, perfusion defect size, innervation defect size, and the innervation-perfusion mismatch were not found to be associated with VA. CONCLUSIONS: In patients with ischemic cardiomyopathy, lower LVEF, higher LVEDVi, and larger scar border zone were related to VA. PET-derived perfusion and sympathetic innervation, as well as CMR-derived scar core size were not associated with VA. These results suggest that improved prediction of VA by advanced imaging remains challenging for the individual patient.

The Benefit of Prophylactic Implantable Cardioverter Defibrillator Implantation in Asymptomatic Heart Failure Patients With a Reduced Ejection Fraction.

Recommendations for prophylactic implantable cardioverter defibrillator (ICD) implantation in asymptomatic heart failure patients with a reduced left ventricular ejection fraction (LVEF) differ between guidelines. Evidence on the risk of appropriate device therapy (ADT) and death in New York Heart Association (NYHA) class I patients is scarce. Aim of this study is to evaluate ADT and mortality in NYHA-I primary prevention ICD patients with a LVEF ≤35%. A retrospective cohort was studied, including 572 patients with LVEF ≤35% who received a prophylactic ICD with or without resynchronization therapy (CRT-D). To evaluate the incidence of ADT and mortality, NYHA-I was compared with NYHA-II-III using Cox regression analysis. During a follow-up of 4.1 ± 2.4 years, 33% of the NYHA-I patients received ADT compared with 20% of the NYHA-II-III patients (hazard ratio 1.5, 95% confidence interval 1.04 to 2.31, p = 0.03). No differences in mortality were observed (hazard ratio 0.70, 95% confidence interval 0.49 to 1.07, p = 0.10). Additional analyses showed no difference in time to ADT excluding CRT patients (ICD-NYHA-I patients vs ICD-NYHA-II-III patients, p = 0.17) and comparing ischemic and nonischemic cardiomyopathy NYHA-I patients (p = 0.13). Multivariable Cox regression analyses showed that NYHA class was the strongest independent predictor of ADT. In conclusion, primary prevention NYHA-I ICD patients showed a higher incidence of ADT compared with NYHA-II-III ICD patients. These results strongly suggest that primary prevention NYHA-I patients with a LVEF ≤35% are likely to benefit from ICD therapy and should not be excluded from a potentially life-saving therapy.

Chronotropic Incompetence in Chronic Heart Failure.

Chronotropic incompetence (CI) is generally defined as the inability to increase the heart rate (HR) adequately during exercise to match cardiac output to metabolic demands. In patients with heart failure (HF), however, this definition is unsuitable because metabolic demands are unmatched to cardiac output in both conditions. Moreover, HR dynamics in patients with HF differ from those in healthy subjects and may be affected by ß-blocking medication. Nevertheless, it has been demonstrated that CI in HF is associated with reduced functional capacity and poor survival. During exercise, the normal heart increases both stroke volume and HR, whereas in the failing heart, contractility reserve is lost, thus rendering increases in cardiac output primarily dependent on cardioacceleration. Consequently, insufficient cardioacceleration because of CI may be considered a major limiting factor in the exercise capacity of patients with HF. Despite the profound effects of CI in this specific population, the issue has drawn limited attention during the past years and is often overlooked in clinical practice. This might partly be caused by a lack of standardized approach to diagnose the disease, further complicated by changes in HR dynamics in the HF population, which render reference values derived from a normal population invalid. Cardiac implantable electronic devices (implantable cardioverter defibrillator; cardiac resynchronization therapy) now offer a unique opportunity to study HR dynamics and provide treatment options for CI by rate-adaptive pacing using an incorporated sensor that measures physical activity. This review provides an overview of disease mechanisms, diagnostic strategies, clinical consequences, and state-of-the-art device therapy for CI in HF.

Clinical Impact of Cardiac Magnetic Resonance Imaging Versus Echocardiography-Guided Patient Selection for Primary Prevention Implantable Cardioverter Defibrillator Therapy.

The main eligibility criterion for primary prevention implantable cardioverter defibrillator (ICD) therapy, that is, left ventricular ejection fraction (LVEF), is based on large clinical trials using primarily 2-dimensional echocardiography (2DE). Presently, cardiac magnetic resonance imaging (MRI) is considered the gold standard for LVEF assessment. It has been demonstrated that cardiac MRI assessment results in lower LVEFs compared with 2DE. Consequently, cardiac MRI-LVEF assessment may lead to more patients eligible for ICD implantation with potential clinical consequences. The aim of this study was to evaluate the clinical impact of cardiac MRI-LVEF versus 2DE-LVEF assessment for ICD eligibility. A total of 149 patients with cardiac MRI-LVEF ≤35% referred for primary prevention ICD implantation who underwent both 2DE and cardiac MRI-LVEF assessment were retrospectively included. 2DE-LVEF was computed by Simpson's biplane method. Cardiac MRI-LVEF was computed after outlining the endocardial contours in short-axis cine images. Appropriate device therapy (ADT) and all-cause mortality were evaluated during 2.9 ± 1.7 years of follow-up. The present study found that cardiac MRI-LVEF was significantly lower compared with 2DE-LVEF (23 ± 8% vs 30 ± 8%, respectively, p <0.001), resulting in 29 (19%) more patients eligible for ICD implantation according to the current guidelines (LVEF ≤35%). Patients with 2DE-LVEF >35% but cardiac MRI-LVEF ≤35% experienced a lower ADT rate compared with patients having 2DE-LVEF ≤35% (2.1% vs 10.4% per year, respectively, p = 0.02). Application of cardiac MRI-LVEF cutoff of 30% resulted in 119 eligible patients experiencing 9.9% per year ADT, comparable with 2DE-LVEF cut-off value of 35%. In conclusion, cardiac MRI-LVEF assessment resulted in more patients eligible for ICD implantation compared with 2DE who showed a relatively low event rate during follow-up. The event rate in patients with cardiac MRI-LVEF ≤30% was comparable with patients having a 2DE-LVEF ≤35%. This study suggests the need for re-evaluation of cardiac MRI-based LVEF cut-off values for ICD eligibility.