Diagnostic accuracy, clinical characteristics, and prognostic differences of patients with acute myocarditis according to inclusion criteria.

INTRODUCTION: The diagnosis of acute myocarditis (AM) is complex due to its heterogeneity and typically is defined by either Electronic Healthcare Records (EHRs) or advanced imaging and endomyocardial biopsy, but there is no consensus. We aimed to investigate the diagnostic accuracy of these approaches for AM. METHODS: Data on ICD 10th Revision(ICD-10) codes corresponding to AM were collected from two hospitals and compared to CMR-confirmed or clinically suspected(CS) AM cases with respect to diagnostic accuracy, clinical characteristics, and all-cause mortality. Next, we performed a review of published AM studies according to inclusion criteria. RESULTS: We identified 291 unique admissions with ICD-10 codes corresponding to AM in the first three diagnostic positions. The positive predictive value(PPV) of ICD-10 codes for CMR-confirmed or CS-AM was 36%, and patients with CMR-confirmed or CS AM had a lower all-cause mortality than those with a refuted diagnosis (P = 0.019). Using an unstructured approach, patients with CMR-confirmed and CS AM had similar demographics, comorbidity profiles and survival over a median follow-up of 52 months (P = 0.72). Our review of the literature confirmed our findings. Outcomes for patients included in studies using CMR-confirmed criteria were favourable compared to studies with EMB-confirmed AM cases. CONCLUSION: ICD-10 codes have poor accuracy in identification of AM cases and should be used with caution in clinical research. There are important differences in management and outcomes of patients according to the selection criteria used to diagnose AM. Potential selection biases must be considered when interpreting AM cohorts and requires standardisation of inclusion criteria for AM studies.

The prognostic impact of specialist cardiology input in patients admitted for heart failure and normal ejection fraction.

AIMS: Specialist cardiology care is associated with a prognostic benefit in patients with heart failure (HF) with reduced ejection fraction (HFrEF) admitted with decompensated HF. However, up to one third of patients admitted with HF and normal ejection fraction (HFnEF) do not receive specialist cardiology input. Whether this has prognostic implications is unknown. METHODS AND RESULTS: Data on patients hospitalized with HFnEF from two tertiary centres were analysed. The primary outcome measure was all-cause mortality during follow-up. The secondary outcome was in-hospital mortality. A total of 1413 patients were included in the study. Of these, 23% (n = 322) did not receive in-hospital specialist cardiology input. Patients seen by a cardiologist were less likely to have hypertension (73% vs. 79%, P = 0.03) and respiratory co-morbidities (25% vs. 31%, P = 0.02) compared with those who did not receive specialist input. Similarly, clinical presentation was more severe for those who received specialist input (New York Heart Association III/IV 83% vs. 75% respectively, P = 0.003; moderate-to-severe peripheral oedema 65% vs. 54%, P < 0.001). Medical management was similar, except for a higher use of diuretics (90% vs. 86%, P = 0.04) and a longer length of stay for patients who received specialist input (9 vs. 4 days, P < 0.001). Long-term outcomes were comparable between patients who received specialist input and those who did not. However, specialist input was independently associated with lower in-hospital mortality (hazard ratio 0.19, confidence interval 0.09-0.43, P < 0.001). CONCLUSIONS: In-hospital cardiology specialist input has no long-term prognostic advantage in patients with HFnEF but is independently associated with reduced in-hospital mortality.

Syncope in ICD recipients: a single centre experience.

AIMS: There is little evidence of the impact of syncope in implantable cardioverter-defibrillator (ICD) patients in routine community hospital care. This single-centre retrospective study sought to evaluate the incidence and prognostic significance of syncope in consecutive ICD patients. METHODS AND RESULTS: Data were collected on consecutive patients undergoing first ICD implantation between January 2009 and December 2019. The primary endpoints were the first occurrence of all-cause syncope, all-cause mortality, and all-cause hospitalization. Multivariate Cox proportional hazard models were used to identify risk factors associated with syncope and to analyse the subsequent risk of mortality and hospitalization. 1003 patients (58% primary prevention) were included in the final analysis. During a mean follow-up of 1519 ± 1055 days, 106 (10.6%) experienced syncope, 304 died (30.3%), and 477 (47.5%) were hospitalized for any cause. In an analysis adjusted for baseline variables, the first occurrence of syncope was associated with a significantly increased risk of mortality (HR 2.82, P < 0.001) and the first occurrence of hospitalization (HR 2.46, P = 0.002). CONCLUSION: Syncope in ICD recipients is common and associated with a poor prognosis irrespective of baseline variables and ICD programming. The occurrence of syncope is associated with a significant increase in the risk of mortality and hospitalization.

Prognostic relevance of demographic factors in cardiac magnetic resonance-proven acute myocarditis: A cohort study.

Aim: Acute myocarditis (AM) is a heterogeneous condition with variable estimates of survival. Contemporary criteria for the diagnosis of clinically suspected AM enable non-invasive assessment, resulting in greater sensitivity and more representative cohorts. We aimed to describe the demographic characteristics and long-term outcomes of patients with AM diagnosed using non-invasive criteria. Methods and results: A total of 199 patients with cardiac magnetic resonance (CMR)-confirmed AM were included. The majority (n = 130, 65%) were male, and the average age was 39 ± 16 years. Half of the patients were White (n = 99, 52%), with the remainder from Black and Minority Ethnic (BAME) groups. The most common clinical presentation was chest pain (n = 156, 78%), with smaller numbers presenting with breathlessness (n = 25, 13%) and arrhythmias (n = 18, 9%). Patients admitted with breathlessness were sicker and more often required inotropes, steroids, and renal replacement therapy (p < 0.001, p < 0.001, and p = 0.01, respectively). Over a median follow-up of 53 (IQR 34-76) months, 11 patients (6%) experienced an adverse outcome, defined as a composite of all-cause mortality, resuscitated cardiac arrest, and appropriate implantable cardioverter defibrillator (ICD) therapy. Patients in the arrhythmia group had a worse prognosis, with a nearly sevenfold risk of adverse events [hazard ratio (HR) 6.97; 95% confidence interval (CI) 1.87-26.00, p = 0.004]. Sex and ethnicity were not significantly associated with the outcome. Conclusion: AM is highly heterogeneous with an overall favourable prognosis. Three-quarters of patients with AM present with chest pain, which is associated with a benign prognosis. AM presenting with life-threatening arrhythmias is associated with a higher risk of adverse events.

Cardiovascular Damage in COVID-19: What We Know Two Years Later.

PURPOSE OF THE REVIEW: The Coronavirus disease 2019 (COVID-19) pandemic has profoundly influenced cardiological clinical and basic research in the past two years. In the present review, we summarize the current knowledge on myocardial involvement in COVID-19, providing an overview on the incidence, the pathogenetic mechanisms, and the clinical implications of cardiac injury in this setting. RECENT FINDINGS: The possibility of heart involvement in patients with COVID-19 has received great attention since the beginning of the pandemic. After more than two years, several steps have been taken in understanding the mechanisms and the incidence of cardiac injury during COVID-19 infection. Similarly, studies globally have clarified the implications of co-existing heart disease and COVID-19. Severe COVID-19 infection may be complicated by myocardial injury. To date, a direct damage from the virus has not been demonstrated. The presence of myocardial injury should be systematically assessed for a prognostication purpose and for possible therapeutic implications.

Impact of the COVID-19 pandemic on in-hospital mortality in cardiovascular disease: a meta-analysis.

AIMS: The COVID-19 pandemic has resulted in excess mortality due to both COVID-19 directly and other conditions, including cardiovascular (CV) disease. We aimed to explore the excess in-hospital mortality, unrelated to COVID-19 infection, across a range of CV diseases. METHODS AND RESULTS: A systematic search was performed for studies investigating in-hospital mortality among patients admitted with CV disease without SARS-CoV-2 infection compared with a period outside the COVID-19 pandemic. Fifteen studies on 27 421 patients with CV disease were included in the analysis. The average in-hospital mortality rate was 10.4% (n = 974) in the COVID-19 group and 5.7% (n = 1026) in the comparator group. Compared with periods outside the COVID-19 pandemic, the pooled risk ratio (RR) demonstrated increased in-hospital mortality by 62% during COVID-19 [95% confidence interval (CI) 1.20-2.20, P = 0.002]. Studies with a decline in admission rate >50% during the COVID-19 pandemic observed the greatest increase in mortality compared with those with <50% reduction [RR 2.74 (95% CI 2.43-3.10) vs. 1.21 (95% CI 1.07-1.37), P < 0.001]. The observed increased mortality was consistent across different CV conditions (P = 0.74 for interaction). CONCLUSIONS: In-hospital mortality among patients admitted with CV diseases was increased relative to periods outside the pandemic, independent of co-infection with COVID-19. This effect was larger in studies with the biggest decline in admission rates, suggesting a sicker cohort of patients in this period. However, studies were generally poorly conducted, and there is a need for further well-designed studies to establish the full extent of mortality not directly related to COVID-19 infection.

Patients hospitalised with heart failure across different waves of the COVID-19 pandemic show consistent clinical characteristics and outcomes.

BACKGROUND: During the first wave of the COVID-19 pandemic, admissions for cardiovascular disease, including Heart Failure (HF), were reduced. Patients hospitalised for HF were sicker and with increased in-hospital mortality. So far, whether following waves had a different impact on HF patients is unknown. METHODS: All consecutive patients hospitalised for acute heart failure during three different COVID-19 related national lockdowns were analysed. The lockdown periods were defined according to Government guidelines as 23/3/2020 to 4/7/2020 (First Lockdown), 4/11/2020 to 2/12/2020 (Second Lockdown) and 5/1/2021 to 28/2/2021 (Third Lockdown). RESULTS: Overall, 184 patients hospitalised for HF were included in the study, 95 during the 1st lockdown, 30 during the 2nd lockdown and 59 during the 3rd lockdown. Across the three groups had comparable clinical characteristics, comorbidities and cardiovascular risk factors. Specialist in-hospital care was uninterrupted during the pandemic showing comparable mortality rates (p = 0.10). Although medical therapy for HF was comparable between the three lockdowns, a significantly higher proportion of patients received Angiotensin Receptor-Neprilysin Inhibitors (ARNI) in the second and third lockdowns (p < 0.001). CONCLUSIONS: Although public health approaches changed throughout the pandemic, the clinical characteristics and outcomes of HF patients were consistent across different waves. For patients hospitalised in the subsequent waves, a more rapid optimization of medical therapy was observed during hospitalization. Particular attention should be devoted to prevent collateral cardiovascular damage during public health emergencies.

Generic ICD programming and outcomes.

INTRODUCTION: Generic ICD programming, where shock-reduction programming is extrapolated from trials of one manufacturer to another, may reduce non-essential ICD therapies beyond that seen in randomized trials. However, the benefits and risks are unknown. The purpose of this retrospective cohort study was to evaluate the impact of a standardized programming protocol, based on generic programming, across manufacturers. METHODS: We included all new ICDs in a single center (2009-2019). In 2013 a standardized programming protocol based on generic programming was introduced, incorporating high detection rates (200 bpm for primary prevention) and long detection (30/40 or equivalent in VF zone) for all patients. Patients were classified into three groups based on implant programming: pre-guideline (PS), post-guideline and guideline compliant (GC) and post-guideline but not guideline compliant (NGC). The end-points were the first occurrence of any device therapy (ATP or shock), ICD shock, syncope and all-cause mortality. Survival analysis was used to evaluate outcomes. RESULTS: 1003 patients were included (mean follow-up 1519 ± 1005 days). In primary prevention patients (n = 583) freedom from ICD therapy (91.5% vs. 73.6%, p < .001) or shock (94.7% vs 84.8%, p = .02) were significantly higher in GC compared to PS patients, without significant increase in syncope or mortality. In secondary prevention patients (n = 420) freedom from any ICD therapy or any shock were non-significantly higher in GC compared to PS patients, without an increase in syncope or mortality. CONCLUSIONS: In primary prevention patients a standardized programming protocol, incorporating generic programming, reduced the burden of ICD therapy without an increase in adverse outcomes.

Tissue Doppler-Derived Left Ventricular Systolic Velocity Is Associated with Lethal Arrhythmias in Cardiac Device Recipients Irrespective of Left Ventricular Ejection Fraction.

BACKGROUND: Life-threatening arrhythmias (LTAs) can trigger sudden cardiac death or provoke implantable cardioverter-defibrillator (ICD) discharges that escalate morbidity and mortality. Longitudinal myofibrils predominate in the subendocardium, which is uniquely sensitive to arrhythmogenic triggers. In this study, we test the hypothesis that mitral annular systolic velocity (S'), a simple routinely obtained tissue Doppler index of LV long-axis systolic function, might predict lethal arrhythmias irrespective of left ventricular ejection fraction (LVEF). METHODS: This is a retrospective analysis of data from 302 patients (mean age, 68 years; LVEF, 32%; 77% male; 52% ischemic; 35% primary prevention; and 53% cardiac resynchronization therapy defibrillator [CRT-D]) who were followed up (median, 15 months) at two centers after receipt of an ICD or CRT-D for diverse indications. S', averaged from tissue Doppler-derived medial and lateral mitral annular velocities, was correlated with the primary outcome of time to sustained ventricular tachycardia (VT) or fibrillation (VF) needing device therapy. RESULTS: The median S' was 5.1 (interquartile range, 4.0-6.2) cm/sec and lower in CRT-D than ICD subjects (4.5 [3.8-5.6] cm/sec vs 5.5 [4.8-6.8] cm/sec, P < .001). Fifty-six (19%) subjects had LTA. Each 1 cm/sec higher S' correlated to a 30% decreased risk of LTA (hazard ratio = 0.70; 95% CI, 0.57-0.87; P = .001) independently of age, sex, ß-blocker use, center, ICD use, and LVEF. Adding S' to the baseline Cox model improved net reclassification (P = .02). An S' > 5.6 cm/sec was the best cutoff and linked to a 58% lower LTA risk than an S' ≤ 5.6 cm/sec (95% CI, 0.23-0.85; P = .02). CONCLUSIONS: A higher S' is associated with a reduced probability of LTA in cardiac device recipients irrespective of LVEF and may have the potential to be used clinically to titrate medical, device, and ablative therapies to mitigate future arrhythmic risk.

Impact of different selection policies on subcutaneous ICD implants and therapies.

BACKGROUND: Patients with existing or anticipated indications for cardiac resynchronisation therapy (CRT), bradycardia, or anti-tachycardia pacing should not be offered subcutaneous defibrillators (SQIDs) but it remains unclear how clinicians should predict future need for these therapies. METHODS: We applied three SQID selection policies to data collected retrospectively from transvenous implantable cardioverter defibrillator (TV-ICD) implants: (a) approach A, SQID used in inherited channelopathies and idiopathic ventricular fibrillation only; (b) approach B, as above, plus all hypertrophic cardiomyopathy and grown-up congenital heart disease patients; (c) approach C, as above, plus primary and secondary prevention (for ventricular fibrillation only) of SCD in patients with QRS <150 ms. Approach C reflects current ESC and AHA/ACC/HRS guidelines. RESULTS: 338 of 951 patients with TV-ICD were considered for SQID after excluding 613 patients with contraindications. Approaches A, B, and C yielded 45 (4.7%), 89 (9.4%), and 338 (35.5%) patients suitable for SQID, respectively. Use of SQID resulted in more frequent ICD shocks compared to TV-ICD with approach C only (0.43 vs 0.23 per 1000 patient-days; P = .03). Rates of CRT upgrade were comparable across selection criteria (0, 0.03, and 0.07 per 1000 patient-days for approaches A, B, and C, respectively; P = NS). Risk of early mortality was higher when more liberal inclusion criteria were used (P = .003). CONCLUSIONS: One in three patients receiving ICDs may be suitable for SQID under current ESC and AHA/ACC/HRS guidelines. This proportion is influenced significantly by the selection criteria used, and the criteria used by a physician should be informed by the estimated survival of the patient, risk of shocks for MVT, future pacing, and CRT requirements.

Semantic computational analysis of anticoagulation use in atrial fibrillation from real world data.

Atrial fibrillation (AF) is the most common arrhythmia and significantly increases stroke risk. This risk is effectively managed by oral anticoagulation. Recent studies using national registry data indicate increased use of anticoagulation resulting from changes in guidelines and the availability of newer drugs. The aim of this study is to develop and validate an open source risk scoring pipeline for free-text electronic health record data using natural language processing. AF patients discharged from 1st January 2011 to 1st October 2017 were identified from discharge summaries (N = 10,030, 64.6% male, average age 75.3 ± 12.3 years). A natural language processing pipeline was developed to identify risk factors in clinical text and calculate risk for ischaemic stroke (CHA2DS2-VASc) and bleeding (HAS-BLED). Scores were validated vs two independent experts for 40 patients. Automatic risk scores were in strong agreement with the two independent experts for CHA2DS2-VASc (average kappa 0.78 vs experts, compared to 0.85 between experts). Agreement was lower for HAS-BLED (average kappa 0.54 vs experts, compared to 0.74 between experts). In high-risk patients (CHA2DS2-VASc ≥2) OAC use has increased significantly over the last 7 years, driven by the availability of DOACs and the transitioning of patients from AP medication alone to OAC. Factors independently associated with OAC use included components of the CHA2DS2-VASc and HAS-BLED scores as well as discharging specialty and frailty. OAC use was highest in patients discharged under cardiology (69%). Electronic health record text can be used for automatic calculation of clinical risk scores at scale. Open source tools are available today for this task but require further validation. Analysis of routinely collected EHR data can replicate findings from large-scale curated registries.

The impact of the presence of left atrial low voltage areas on outcomes from pulmonary vein isolation.

BACKGROUND: AF ablation (AFA) with pulmonary vein isolation (PVI) is highly successful for paroxysmal atrial fibrillation (PAF). However, success rates for persistent AF (PsAF) are significantly lower. In this study we evaluate the impact of left atrial (LA) low voltage areas (LVA) on response to AFA. METHODS: Consecutive patients undergoing first-time radiofrequency AFA were included (n = 160, 53% PAF). PVI was performed followed by LA voltage mapping during sinus rhythm. Patients were categorized as having LVA based on the presence of LVA (0.2-0.5 mV) in the LA assessed visually by the operator intra-procedurally. Further adjunctive LA ablation was performed at the operators' discretion. The end-point was recurrence of any sustained atrial arrhythmia (atrial fibrillation/tachycardia/flutter) during 12 months follow-up. RESULTS: All patients had PVI and 23 (14%) had adjunctive LA ablation. LVA were found in 49 (31%) patients and were an independent predictor of arrhythmia recurrence. Patients with LVA compared to those without had significantly lower 12-month arrhythmia-free survival in both PAF (38% vs 76%; P = 0.002) and PsAF (27% vs 61%; P = 0.015). PsAF patients without LVA (93% had PVI alone) had similar arrhythmia-free survival to patients with PAF (61% vs 67%, respectively; P = 0.42). Recurrence in patients with LVA compared to those without was more likely to be an organized atrial arrhythmia rather than AF (16/30 recurrences vs 2/26, P < 0.001). CONCLUSIONS: The presence of LVA predicts AFA success as well as the type of arrhythmia recurrence. The absence of LVA identifies PsAF patients that respond well to a PVI-based ablation strategy.

The impact of catheter ablation for atrial fibrillation in heart failure.

Atrial fibrillation (AF) commonly co-exists with systolic heart failure (SHF) and its presence is associated with a worse prognosis. Despite this, a rhythm control approach using antiarrhythmic drugs (AADs) to reduce AF burden has demonstrated no prognostic benefit. Catheter ablation (AFA) is more effective than AADs at reducing AF burden. We performed a meta-analysis to evaluate the impact of AFA on outcomes in SHF. Electronic databases were systematically searched. We included only randomized controlled trials that examined the impact of AFA on clinical outcomes in patients with SHF (LVEF <50%). We included studies with any ablation strategy that incorporated pulmonary vein isolation and any control group. Seven studies (n = 858) were included with a mean follow-up of 6-38 months. In comparison to controls, AFA was associated with significant reductions in all-cause mortality (relative risk [RR] 0.52, P = 0.0009) and unplanned or heart failure hospitalization (RR 0.58, P < 0.00001). Compared to controls, AFA was also associated with significant improvements in LVEF (mean difference 6.30%, P < 0.00001), Minnesota Living with Heart Failure Questionnaire score (mean difference 9.58, P = 0.0003), 6-minute walk distance (mean difference 31.78 m, P = 0.003) and VO 2 max (mean difference 3.17, P = 0.003). However, major procedure-related complications occurred in 2.4%-15% of ablation patients. In patients with AF and SHF, catheter ablation has significant benefits. Further work is needed to establish the role of ablation in the routine treatment of SHF patients with AF.

Day-case device implantation-A prospective single-center experience including patient satisfaction data.

PURPOSE: Many centers perform day-case cardiac rhythm management (CRM) device implantation. However, there is a paucity of prospective data concerning this approach. We performed a prospective single-center study of day-case device implantation, including data on patient satisfaction. METHODS: All patients scheduled for a new elective device were considered for a day-case procedure. Exclusion criteria were living alone or without a suitable carer, advancing age/frailty, a metallic valve, and persistent complete heart block. Following discharge, patients were reviewed in device clinic at 6 weeks with an anonymized questionnaire. RESULTS: During the study period (May 2014-August 2016), 797 new CRM devices were implanted. Of these, 232 were elective and included in the analysis; 101 were planned to be day-case and 131 scheduled for overnight stay. Of the 101 day-case patients, 52 had a pacemaker, 28 an implantable cardioverter defibrillator (ICD), 16 a cardiac resynchronization therapy pacemaker/defibrillator, and five a subcutaneous-ICD. Complications were similar in the day-case (n  =  12, 12%) and overnight stay (n  =  15, 11%) groups (P  =  0.92). In the day-case group, 93 (92%) patients went home the same day. An estimated 111 overnight bed days were saved, translating to a cost saving of £61,912 (euro 70,767, $79,211). Note that 99% (n  =  100) of patients returned the questionnaire. Patient satisfaction was universally high. The majority (n  =  98, 98%) felt ready to go home on discharge; only a minority (n  =  5, 5%) would have preferred an overnight stay. CONCLUSIONS: A significant proportion of elective new CRM device implants can be performed as day-case procedures. With appropriate selection patient acceptability of same-day discharge is high.

Outcomes with single-coil versus dual-coil implantable cardioverter defibrillators: a meta-analysis.

Aims: Dual-coil implantable cardioverter defibrillator (ICD) leads have traditionally been used over single-coil leads due to concerns regarding high defibrillation thresholds (DFT) and consequent poor shock efficacy. However, accumulating evidence suggests that this position may be unfounded and that dual-coil leads may also be associated with higher complication rates during lead extraction. This meta-analysis collates data comparing dual- and single-coil ICD leads. Methods and results: Electronic databases were systematically searched for randomized controlled trials (RCT) and non-randomized studies comparing single-coil and dual-coil leads. The mean differences in DFT and summary estimates of the odds-ratio (OR) for first-shock efficacy and the hazard-ratio (HR) for all-cause mortality were calculated using random effects models. Eighteen studies including a total of 138,124 patients were identified. Dual-coil leads were associated with a lower DFT compared to single coil leads (mean difference -0.83J; 95% confidence interval [CI] -1.39--0.27; P = 0.004). There was no difference in the first-shock success rate with dual-coil compared to single-coil leads (OR 0.74; 95%CI 0.45-1.21; P=0.22). There was a significantly lower risk of all-cause mortality associated with single-coil leads (HR 0.91; 95%CI 0.86-0.95; P < 0.0001). Conclusion: This meta-analysis suggests that single-coil leads have a marginally higher DFT but that this may be clinically insignificant as there appears to be no difference in first-shock efficacy when compared to dual-coil leads. The mortality benefit with single-coil leads most likely represents patient selection bias. Given the increased risk and complexity of extracting dual-coil leads, centres should strongly consider single-coil ICD leads as the lead of choice for routine new left-sided ICD implants.

Alzheimer's Disease-Related Dementias Summit 2016: National research priorities.

Goal 1 of the National Plan to Address Alzheimer's Disease is to prevent and effectively treat Alzheimer disease and Alzheimer disease-related dementias by 2025. To help inform the research agenda toward achieving this goal, the NIH hosts periodic summits that set and refine relevant research priorities for the subsequent 5 to 10 years. This proceedings article summarizes the 2016 Alzheimer's Disease-Related Dementias Summit, including discussion of scientific progress, challenges, and opportunities in major areas of dementia research, including mixed-etiology dementias, Lewy body dementia, frontotemporal degeneration, vascular contributions to cognitive impairment and dementia, dementia disparities, and dementia nomenclature.

The Significance of Shocks in Implantable Cardioverter Defibrillator Recipients.

Large-scale implantable cardioverter defibrillator (ICD) trials have unequivocally shown a reduction in mortality in appropriately selected patients with heart failure and depressed left ventricular function. However, there is a strong association between shocks and increased mortality in ICD recipients. It is unclear if shocks are merely a marker of a more severe cardiovascular disease or directly contribute to the increase in mortality. The aim of this review is to examine the relationship between ICD shocks and mortality, and explore possible mechanisms. Data examining the effect of shocks in the absence of spontaneous arrhythmias as well as studies of non-shock therapy and strategies to reduce shocks are analysed to try and disentangle the shocks versus substrate debate.