Prophylactic Implantable Cardioverter-defibrillator Therapy Research Articles

Long-term prognosis and prognostic factors after primary prophylactic implantable cardioverter-defibrillator therapy

BackgroundLittle is known regarding which patients with ischemic cardiomyopathy (ICM) should be considered for prophylactic therapies, such as an implantable cardioverter-defibrillator (ICD), in the primary percutaneous intervention era. The aim of this study was to investigate the influence of non-sustained ventricular tachycardia (NSVT) on major adverse cardiac events (MACE) in heart failure with reduced ejection fraction (HFrEF) patients. MethodsWe retrospectively analyzed patients of ICM and non-ICM who underwent ICD implantation at our institute from October 2006 to August 2020. MACE were defined as composite outcome of cardiovascular death, heart failure hospitalization, and appropriate ICD therapies. ResultsA total of 167 patients were enrolled [male, 138 (83 %); age, 62.1 ± 11.7 years; left ventricular ejection fraction, 23.5 ± 6.1 %; left ventricular diastolic diameter, 67.4 ± 9.0 mm; atrial fibrillation, 47 (28 %); NSVT, 124 (74 %); use of class III antiarrhythmic drugs, 55 (33 %); ischemic cardiomyopathy, 56 (34 %); cardiac resynchronization therapy, 73 (44 %)]. The median follow-up duration was 61 months. MACE occurred with 71 patients (43 %). When comparing baseline characteristics of the patients, left ventricular ejection fraction (p = 0.02) and atrial fibrillation (p = 0.04) were significantly associated with MACE. The multivariable Cox analysis for the target variable MACE identified atrial fibrillation (hazard ratio 2.00; 95 % confidence index 1.18–3.37; p = 0.01) as an independent predictor for MACE. ConclusionsPrior NSVT before ICD implantation was not an independent predictor of future MACE in patients with HFrEF with primary prophylactic ICD. In contrast, atrial fibrillation was associated with worse prognosis. To predict the prognosis of patients with primary prophylactic ICD, these factors should be assessed as comprehensive risk stratification factors for MACE.

Prognostic value of cardiac magnetic resonance - LGE distribution in non-ischemic dilated cardiomyopathy for prophylactic implantable-cardioverter defibrillator therapy

Abstract Background/Introduction International guidelines recommend implantable cardioverter-defibrillator (ICD) implantation when patients with nonischemic dilated cardiomyopathy (NICM) have left ventricular ejection fraction (LVEF) of 35% or less. Tissue characterization obtained by cardiac magnetic resonance (CMR) has emerged as a promising tool for better identification of patients at high arrhythmic risk and thus worthy of prophylactic ICD therapy. Purpose Current analysis has the scope to assess the prognostic value of fibrosis as evaluated by late gadolinium enhancement sequences (LGE) specifically regarding its LV wall distribution. The primary endpoint was all-cause mortality. The secondary end-point consisted of major adverse arrhythmic cardiac events (MAACE), defined as combination of SCD, aborted SCD, and sustained ventricular tachycardia. Methods Study population is part of DERIVATE Study, an international, multicenter, prospective, observational registry including consecutive patients from 21 sites across Europe and US referred for heart failure (HF) work-up including transthoracic echocardiography (TTE) and CMR without a history of previous major ventricular arrhythmias. Inclusion criteria were: (i) aged 18 or older, (ii) chronic HF according to the ESC Task force definition, and (iii) LV-EF<50% at initial TTE. All patients underwent TTE and CMR within 3 months. Patients with (i) decompensated within 3 months of enrollment, (ii) recent myocardial infarction (<40 days), (iii) unstable angina, (iv) severe valvular disease, (v) primary or secondary cardiomyopathies other than NICM, (vi) cardiac amyloidosis, and (vii) congenital heart disease were excluded. Results The entire cohort consisted of 1384 subjects [mean age: 56±14 years, male: 948 (68.4%)]. The median follow-up time was 959 days. Mortality and MAACE occurred in 92 (6.6%) and 125 (9%) patients, respectively. SCD, aborted SCD, and sustained VT occurred in 15 (1.1%), 80 (5.8%), and 104 (7.5%), respectively. In the multivariate analyses for all-cause mortality, only the number of segments with LGE at the level of the septum was an independent predictor (p=0.002), while in the analyses for MAACE the only independent predictors were male gender, LVEDVi by CMR, and the number of segments with LGE at the level of septum inferior. Based on the multivariate analysis, the DERIVATE score (including all 1384 patients) ranging from 0 to 8 (Cox regression analysis HR=1.35, 95%CI 1.24-1.46, p< 0.001) was built up. The redistribution of patients according to the CMR composite DERIVATE risk/year MAACE was of 44%, 37% and 32% for the low, intermediate and high risk groups, respectively. Conclusions The arrhythmic risk of patients with NICM is also dependent on the different distribution of fibrosis in the LV. The redistribution of the event rate according to the CMR composite risk score indicates the potential to alter the decision on ICD implantation in a relevant portion of NICM patients.

Machine Learning-Based Phenomapping in Patients with Heart Failure and Secondary Prevention Implantable Cardioverter-Defibrillator Implantation: A Proof-of-Concept Study.

Previous studies have failed to implement risk stratification in patients with heart failure (HF) who are eligible for secondary implantable cardioverter-defibrillator (ICD) implantation. We aimed to evaluate whether machine learning-based phenomapping using routinely available clinical data can identify subgroups that differ in characteristics and prognoses. A total of 389 patients with chronic HF implanted with an ICD were included, and forty-four baseline variables were collected. Phenomapping was performed using hierarchical k-means clustering based on factor analysis of mixed data (FAMD). The utility of phenomapping was validated by comparing the baseline features and outcomes of the first appropriate shock and all-cause death among the phenogroups. During a median follow-up of 2.7 years for device interrogation and 5.1 years for survival status, 142 (36.5%) first appropriate shocks and 113 (29.0%) all-cause deaths occurred. The first 12 principal components extracted using the FAMD, explaining 60.5% of the total variability, were left for phenomapping. Three mutually exclusive phenogroups were identified. Phenogroup 1 comprised the oldest patients with ischemic cardiomyopathy; had the highest proportion of diabetes mellitus, hypertension, and hyperlipidemia; and had the most favorable cardiac structure and function among the phenogroups. Phenogroup 2 included the youngest patients, mostly those with non-ischemic cardiomyopathy, who had intermediate heart dimensions and function, and the fewest comorbidities. Phenogroup 3 had the worst HF progression. Kaplan-Meier curves revealed significant differences in the first appropriate shock (p = 0.002) and all-cause death (p 0.001) across the phenogroups. After adjusting for medications in Cox regression, phenogroups 2 and 3 displayed a graded increase in appropriate shock risk (hazard ratio [HR] 1.54, 95% confidence interval [CI] 1.03-2.28, p = 0.033; HR 2.21, 95% CI 1.42-3.43, p 0.001, respectively; p for trend 0.001) compared to phenogroup 1. Regarding mortality risk, phenogroup 3 was associated with an increased risk (HR 2.25, 95% CI 1.45-3.49, p 0.001). In contrast, phenogroup 2 had a risk (p = 0.124) comparable with phenogroup 1. Machine-learning-based phenomapping can identify distinct phenotype subgroups in patients with clinically heterogeneous HF with secondary prophylactic ICD therapy. This novel strategy may aid personalized medicine for these patients.

Assessment of absolute risk of life-threatening cardiac events in long QT syndrome patients.

BackgroundRisk stratification in long QT syndrome (LQTS) patients is important for optimizing patient care and informing clinical decision making. We developed a risk prediction algorithm with prediction of 5-year absolute risk of the first life-threatening arrhythmic event [defined as aborted cardiac arrest, sudden cardiac death, or appropriate implantable cardioverter defibrillator (ICD) shock] in LQTS patients, accounting for individual risk factors and their changes over time.MethodsRochester-based LQTS Registry included the phenotypic cohort consisting of 1,509 LQTS patients with a QTc ≥ 470 ms, and the genotypic cohort including 1,288 patients with single LQT1, LQT2, or LQT3 mutation. We developed two separate risk prediction models which included pre-specified time-dependent covariates of beta-blocker use, syncope (never, syncope while off beta blockers, and syncope while on beta blockers), and sex by age < and ≥13 years, baseline QTc, and genotype (for the genotypic cohort only). Follow-up started from enrollment in the registry and was censored at patients’ 50s birthday, date of death due to reasons other than sudden cardiac death, or last contact, whichever occurred first. The predictive models were externally validated in an independent cohort of 1,481 LQTS patients from Pavia, Italy.ResultsIn Rochester dataset, there were 77 endpoints in the phenotypic cohort during a median follow-up of 9.0 years, and 47 endpoints in the genotypic cohort during a median follow-up of 9.8 years. The time-dependent extension of Harrell’s generalized C-statistics for the phenotypic model and genotypic model were 0.784 (95% CI: 0.740–0.827) and 0.785 (95% CI: 0.721–0.849), respectively, in the Rochester cohort. The C-statistics obtained from external validation in the Pavia cohort were 0.700 (95% CI: 0.610–0.790) and 0.711 (95% CI: 0.631–0.792) for the two models, respectively. Based on the above models, an online risk calculator estimating a 5-year risk of life-threatening arrhythmic events was developed.ConclusionThis study developed two risk prediction algorithms for phenotype and genotype positive LQTS patients separately. The estimated 5-year absolute risk can be used to quantify a LQTS patient’s risk of developing life-threatening arrhythmic events and thus assisting in clinical decision making regarding prophylactic ICD therapy.

Association of Left Ventricular Systolic Dysfunction Among Carriers of Truncating Variants in Filamin C With Frequent Ventricular Arrhythmia and End-stage Heart Failure

Truncating variants in the gene encoding filamin C (FLNCtv) are associated with arrhythmogenic and dilated cardiomyopathies with a reportedly high risk of ventricular arrhythmia. To determine the frequency of and risk factors associated with adverse events among FLNCtv carriers compared with individuals carrying TTN truncating variants (TTNtv). This cohort study recruited 167 consecutive FLNCtv carriers and a control cohort of 244 patients with TTNtv matched for left ventricular ejection fraction (LVEF) from 19 European cardiomyopathy referral units between 1990 and 2018. Data analyses were conducted between June and October, 2020. The primary end point was a composite of malignant ventricular arrhythmia (MVA) (sudden cardiac death, aborted sudden cardiac death, appropriate implantable cardioverter-defibrillator shock, and sustained ventricular tachycardia) and end-stage heart failure (heart transplant or mortality associated with end-stage heart failure). The secondary end point comprised MVA events only. In total, 167 patients with FLNCtv were studied (55 probands [33%]; 89 men [53%]; mean [SD] age at baseline evaluation, 43 [18] years). For a median follow-up of 20 months (interquartile range, 7-60 months), 29 patients (17.4%) reached the primary end point (19 patients with MVA and 10 patients with end-stage heart failure). Eight (44%) arrhythmic events occurred among individuals with baseline mild to moderate left ventricular systolic dysfunction (LVSD) (LVEF = 36%-49%). Univariable risk factors associated with the primary end point included proband status, LVEF decrement per 10%, ventricular ectopy (≥500 in 24 hours) and myocardial fibrosis detected on cardiac magnetic resonance imaging. The LVEF decrement (hazard ratio [HR] per 10%, 1.83 [95% CI, 1.30-2.57]; P < .001) and proband status (HR, 3.18 [95% CI, 1.12-9.04]; P = .03) remained independent risk factors on multivariable analysis (excluding myocardial fibrosis and ventricular ectopy owing to case censoring). There was no difference in freedom from MVA between FLNCtv carriers with mild to moderate or severe (LVEF ≤35%) LVSD (HR, 1.29 [95% CI, 0.45-3.72]; P = .64). Carriers of FLNCtv with impaired LVEF at baseline evaluation (n = 69) had reduced freedom from MVA compared with 244 TTNtv carriers with similar baseline LVEF (for mild to moderate LVSD: HR, 16.41 [95% CI, 3.45-78.11]; P < .001; for severe LVSD: HR, 2.47 [95% CI, 1.04-5.87]; P = .03). The high frequency of MVA among patients with FLNCtv with mild to moderate LVSD suggests that higher LVEF values than those currently recommended should be considered for prophylactic implantable cardioverter-defibrillator therapy in FLNCtv carriers.

Substrate Spatial Complexity Analysis for the Prediction of Ventricular Arrhythmias in Patients With Ischemic Cardiomyopathy.

Transition zones between healthy myocardium and scar form a spatially complex substrate that may give rise to reentrant ventricular arrhythmias (VAs). We sought to assess the utility of a novel machine learning approach for quantifying 3-dimensional spatial complexity of grayscale patterns on late gadolinium enhanced cardiac magnetic resonance images to predict VAs in patients with ischemic cardiomyopathy. One hundred twenty-two consecutive ischemic cardiomyopathy patients with left ventricular ejection fraction ≤35% without prior history of VAs underwent late gadolinium enhanced cardiac magnetic resonance images. From raw grayscale data, we generated graphs encoding the 3-dimensional geometry of the left ventricle. A novel technique, adapted to these graphs, assessed global regularity of signal intensity patterns using Fourier-like analysis and generated a substrate spatial complexity profile for each patient. A machine learning statistical algorithm was employed to discern which substrate spatial complexity profiles correlated with VA events (appropriate implantable cardioverter-defibrillator firings and arrhythmic sudden cardiac death) at 5 years of follow-up. From the statistical machine learning results, a complexity score ranging from 0 to 1 was calculated for each patient and tested using multivariable Cox regression models. At 5 years of follow-up, 40 patients had VA events. The machine learning algorithm classified with 81% overall accuracy and correctly classified 86% of those without VAs. Overall negative predictive value was 91%. Average complexity score was significantly higher in patients with VA events versus those without (0.5±0.5 versus 0.1±0.2; P<0.0001) and was independently associated with VA events in a multivariable model (hazard ratio, 1.5 [1.2-2.0]; P=0.002). Substrate spatial complexity analysis of late gadolinium enhanced cardiac magnetic resonance images may be helpful in refining VA risk in patients with ischemic cardiomyopathy, particularly to identify low-risk patients who may not benefit from prophylactic implantable cardioverter-defibrillator therapy. Visual Overview: A visual overview is available for this article.

Appropriate Shocks and Mortality in Patients With Versus Without Diabetes With Prophylactic Implantable Cardioverter Defibrillators.

Diabetes increases the risk of all-cause mortality and sudden cardiac death (SCD). The exact mechanisms leading to sudden death in diabetes are not well known. We compared the incidence of appropriate shocks and mortality in patients with versus without diabetes with a prophylactic implantable cardioverter defibrillator (ICD) included in the retrospective EU-CERT-ICD registry. A total of 3,535 patients from 12 European EU-CERT-ICD centers with a mean age of 63.7 ± 11.2 years (82% males) at the time of ICD implantation were included in the analysis. A total of 995 patients (28%) had a history of diabetes. All patients had an ICD implanted for primary SCD prevention. End points were appropriate shock and all-cause mortality. Mean follow-up time was 3.2 ± 2.3 years. Diabetes was associated with a lower risk of appropriate shocks (adjusted hazard ratio [HR] 0.77 [95% CI 0.62-0.96], P = 0.02). However, patients with diabetes had significantly higher mortality (adjusted HR 1.30 [95% CI 1.11-1.53], P = 0.001). All-cause mortality is higher in patients with diabetes than in patients without diabetes with primary prophylactic ICDs. Subsequently, patients with diabetes have a lower incidence of appropriate ICD shocks, indicating that the excess mortality might not be caused primarily by ventricular tachyarrhythmias. These findings suggest a limitation of the potential of prophylactic ICD therapy to improve survival in patients with diabetes with impaired left ventricular function.

Prophylactic Use of Implantable Cardioverter-Defibrillators in the Prevention of Sudden Cardiac Death in Dialysis Patients.

Patients with end-stage renal disease who are undergoing dialysis are reported to be at high risk of sudden cardiac death (SCD), and to date, no therapy has been shown to be effective in reducing this risk. The feasibility and value of prophylactic implantable cardioverter-defibrillator (ICD) implantation to prevent SCD is uncertain. We conducted the ICD2 trial (Implantable Cardioverter-Defibrillator in Dialysis Patients), a prospective, randomized, controlled study investigating the value and safety of ICD implantation to prevent SCD in 200 patients on dialysis with a left ventricular ejection fraction ≥35%, after adequate screening and optimization of other treatments. The primary end point was SCD. Secondary end points were all-cause mortality and ICD-related complications. The trial was stopped as per the recommendation of the data and safety monitoring board for futility reasons after inclusion of 188 patients, 97 in the ICD group and 91 in the control group. The median duration of follow-up was 6.8 years (interquartile range, 3.8-8.8 years). SCD occurred in 19 of 188 cases (10.1%), 11 of 97 in the ICD group and 8 of 91 in the control group. The cumulative SCD incidence at 5 years was 9.7% (95% CI, 3.3%-16.2%) in the ICD group and 7.9% (95% CI, 1.7-14.0%) in the control group, resulting in a hazard ratio of 1.32 (95% CI, 0.53-3.29; P=0.55). Overall, 99 of 188 patients died (52.7%), 52 in the ICD group and 47 in the control group. Five-year survival probability was 50.6% (95% CI, 39.8%-61.5%) in the ICD group and 54.5% (95% CI, 43.0-66.0%) in the control group, resulting in a hazard ratio of 1.02 (95% CI, 0.69-1.52; P=0.92). Among 80 patients who received an ICD, 25 adverse events related to ICD implantation occurred. In a well-screened and well-treated population undergoing dialysis, prophylactic ICD therapy did not reduce the rate of SCD or all-cause mortality, which remained high. URL: http://www.controlled-trials.com . Unique identifier: ISRCTN20479861.

Cardiac magnetic resonance imaging and primary prevention implantable cardioverter defibrillator therapy: current recommendations and future directions.

: Implantable cardioverter defibrillators (ICDs) have proven to be the most effective preventive therapy of sudden cardiac death (SCD). Based on current guidelines, the indication for prophylactic ICD therapy is primarily based on a left ventricular ejection fraction (LVEF) less than 35%. However, patients with low LVEF may never have an arrhythmic event while patients with normal to moderately reduced LVEF, who are traditionally felt to be at lower risk, can experience SCD. Therefore, LVEF alone is not an ideal risk stratification parameter to determine ICD therapy. The arrhythmic risk depends mainly on myocardial histopathologic features and electrical properties, which are largely not reflected by left ventricular systolic performance. In addition, several studies demonstrated that the presence of myocardial fibrosis represents a substrate for malignant ventricular arrhythmias and SCD. Cardiac MRI with late gadolinium enhancement is a refined technique able to accurately identify and quantify ventricular myocardial fibrosis and numerous studies demonstrated its ability to better stratify arrhythmic risk compared with LVEF. Recently, the combination of conventional clinical risk factors and biomarkers, namely N-terminal pro-B-type natriuretic peptide and high-sensitivity C-reactive protein, with cardiac MRI (CMR) findings is proving to more effectively predict arrhythmic risk. Moreover, the application of strain technique to CMR and new tissue characterization indices such as T1 mapping represents an attractive possibility to predict the occurrence of tachyarrhythmia. The aim of this review is to provide state-of-the-art evidence and future perspectives on the use of CMR for primary prevention ICD therapy.

Moral negotiations in the clinic: Navigating the purgatorial pressure in prophylactic implantable cardioverter defibrillator therapy

Who should be offered prophylactic implantable cardioverter defibrillator (ICD) therapy, which is lifesaving but costly, has side effects and only benefits some of the patients treated with the therapy? In Denmark, cardiologists play key roles in making decisions about who to include in the target group for prophylactic ICD therapy. In this paper, we explore what is at stake for Danish cardiologists making these decisions in a welfare state context. Based on fieldwork in ICD clinics and the device industry, we identify three different imperatives that cardiologists juggle in the process of identifying the target group. We conceptualise the cardiologists’ negotiations as ways of groping through a moral landscape and illuminate how cardiologists walk the path of including as many people as possible in the target group for ICD therapy, thereby also supporting the elite clinic. However, in expanding the target group, the cardiologists experience ‘purgatorial pressure’ and seek indulgence for placing the future of the welfare society at risk by implanting more ICDs than is financially sustainable.

Living With Prophylactic ICD Therapy and the Risk of Sudden Cardiac Death: How Patients Negotiate Solutions and Problems.

Prophylactic implantable cardioverter defibrillator (ICD) therapy treats potentially lethal cardiac arrhythmias in patients who have not previously experienced such but are at considerable risk due to underlying heart disease. Most patients are unaware of their risk of sudden cardiac death (SCD) until the ICD is introduced to them. Thus, the problem of risk of death and the solution of ICD therapy are presented simultaneously. Based on ethnographic fieldwork in Danish hospitals, this article illustrates how clinicians narrate prophylactic ICD therapy as a benign therapy preventing risk of death and providing the good life. However, risk of SCD is not the most pressing problem for the patients. The article argues that the solution of ICD therapy ignores patients' experience of living with severe heart disease and introduces the risk of shock therapy. For patients, a good life does not equal absence of risk of death but a life without heart disease.

Automated Quantification of Low-Amplitude Abnormal QRS Peaks From High-Resolution ECG Recordings Predicts Arrhythmic Events in Patients With Cardiomyopathy.

Cardiomyopathy patients are at risk of sudden death, typically from scar-related abnormalities of electrical activation that promote ventricular tachyarrhythmias. Abnormal intra-QRS peaks may provide a measure of altered activation. We hypothesized that quantification of such QRS peaks (QRSp) in high-resolution ECGs would predict arrhythmic events in implantable cardioverter-defibrillator (ICD)-eligible cardiomyopathy patients. Ninety-nine patients with ischemic or non-ischemic dilated cardiomyopathy undergoing prophylactic ICD implantation were prospectively enrolled (age 62±11 years, left ventricular ejection fraction 27±7%). High-resolution (1024 Hz) digital 12-lead ECGs were recorded during intrinsic rhythm. QRSp was quantified for each precordial lead as the total number of low-amplitude deflections that deviated from their respective naive QRS template. The primary end point of arrhythmic events was defined as appropriate ICD therapy or sustained ventricular tachyarrhythmias. After a median follow-up of 24 (15-43) months, 20 (20%) patients had arrhythmic events. Both QRSp and QRS duration were greater in those with arrhythmic events (both P<0.001) and this was consistent for QRSp for both cardiomyopathy types. In a multivariable Cox regression model that included age, left ventricular ejection fraction, QRS duration, and QRSp, only QRSp was an independent predictor of arrhythmic events (hazard ratio, 2.1; P<0.001). Receiver operating characteristic analysis revealed that a QRSp ≥2.25 identified arrhythmic events with greater sensitivity (100% versus 70%, P<0.05) and negative predictive value (100% versus 89%, P<0.05) than QRS duration ≥120 ms. QRSp measured from high-resolution digital 12-lead ECGs independently predicts ventricular tachyarrhythmias in ICD-eligible cardiomyopathy patients. This novel QRS morphology index has the potential to improve sudden death risk stratification and patient selection for prophylactic ICD therapy.

"There are days I wish it wasn't there, and there's days I realize I'm lucky": A qualitative study of psychological sequelae to the implantable cardioverter defibrillator as a treatment for the prevention of sudden cardiac death in arrhythmogenic right ventricular cardiomyopathy.

ObjectivesArrhythmogenic right ventricular cardiomyopathy caused by a TMEM43 p.S358L mutation is a fully penetrant autosomal dominant cause of sudden cardiac death where prophylactic implantable cardioverter defibrillator therapy significantly reduces mortality by returning lethal cardiac rhythms to normal. This qualitative study assessed the psychological ramifications of the implantable cardioverter defibrillator on recipients, their spouses and their mutation negative siblings.DesignQualitative interview study.ParticipantsTwenty-one individuals (nine mutation positive, eight mutation negative and four spouses) from 15 families completed semi-structured interviews.ResultsNo theoretical assumptions about the data were made: inductive sub-coding was accomplished with the constant comparison method and cohesive themes across all respondent interviews were determined. All interviewees had a family history of sudden cardiac death and appropriate implantable cardioverter defibrillator therapy in themselves or family members. Average length of time with an implantable cardioverter defibrillator was 10 years. Major themes included: (1) acceptance and gratitude, (2) grudging acceptance, (3) psychological effects (on emotional and psychological well-being; functioning of the broader family unit; and relationships), and (4) practical concerns (on clothes, travel, loss of driving licence and the effects of an implantable cardioverter defibrillator discharge). These affected all family members, regardless of mutation status.ConclusionsDespite the survival advantage of implantable cardioverter defibrillator therapy, the intervention carries psychological and practical burdens for family members from kindreds manifesting p.S358L TMEM43 ARVC that does not appear to dissipate with time. A move towards integrating psychology services with the cardiac genetics clinic for the extended family may provide benefit.

In Germany too many ICD implantations are performed: pro

Implantable cardioverter defibrillators (ICD) have undoubtedly developed into one of the most successful therapies in the field of cardiology over the last decades; however, a significant number of ICD operations are carried out in patients who do not benefit from ICD therapy despite significant left ventricular dysfunction. These patients can easily be identified. An ICD therapy does not prolong life in the setting of significant chronic kidney disease. In elderly patients the benefit of prophylactic ICD therapy is very small. Simple risk scores can identify other patients who do not benefit from this treatment. The number of ICD operations can also be significantly reduced by the use of devices with an extended longevity.

Family History of Sudden Death Should Be a Primary Indication for Implantable Cardioverter Defibrillator in Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is the leading cause of sudden death in young patients. A number of noninvasive clinical markers, including family history, have formed the basis for a risk stratification strategy aimed at identifying high-risk patients with HCM. The observation that sudden death can occur in multiple relatives of the same family, and clinical studies in which a family history of HCM-related sudden death emerges as an independent predictor of sudden death, support the principle that family history should be considered a risk factor which, in the appropriate clinical scenario, can form the basis for recommending prophylactic implantable cardioverter defibrillator therapy.

A call for re-evaluation of the guidelines for prophylactic ICD implantation.

A call for re-evaluation of the guidelines for prophylactic ICD implantation.

Who benefits from implantable cardioverter defibrillator therapy, and who pays the price?

Who benefits from implantable cardioverter defibrillator therapy, and who pays the price?

How to present treatment effects of implantable defibrillators? Statistics, baseline risk, and meaningful benefit

This editorial refers to ‘Absolute risk reduction in total mortality with implantable cardioverter defibrillators: analysis of primary and secondary prevention trial data to aid risk/benefit analysis’ by T.R. Betts et al. ,o n page 813. Patients with left ventricular dysfunction are prone to sudden cardiac death, presumably from ventricular tachyarrhythmias. Randomized controlled trials (RCTs) demonstrated that prophylactic implantable cardioverter-defibrillators (ICDs) improve survival among selected patients with left ventricular dysfunction considered at high risk of sudden cardiac death. Based on these clinical trial data, the indications for ICD therapy rapidly expanded from restricted therapy of ‘last resort’ (secondary prevention) to a broad-reaching pre-emptive therapy (primary prevention). However, the survival benefit of prophylactic ICD therapy is not uniform across the population with implants. For evidence to be of value, healthcare professionals, patients, and policy makers are faced with the challenge to interpret and apply the data of RCTs in daily practice. Simplified, they need to understand whether one treatment is better than another or better than no treatment at all. Clinicians have the task to communicate risk of a particular treatment to their patients. So, do we understand the concept of risk of a particular treatment, and how do we communicate this to our patients? In recent years, the amount of medical literature has increased rapidly, and with the Internet era information on medical research has become more easily accessible. The problem is how to interpret the results of several studies and decide whether it justifies changing the current treatment. The poor presentation of medical statistics of risk associated with a particular treatment can lead to poor decision-making. There are several statistical formats to present risk and risk reductions. Formats for presenting risk include frequency, percentage, and probability. Formats for presenting risk reduction include relative risk reduction (RRR), absolute risk reduction (ARR), and numbers needed to treat (NTT). Example illustrating the statistical formats The SCD-HeFT (Sudden Cardiac Death in Heart Failure Trial) study found that the ICD reduces the risk of all-cause mortality by 23% over the 5-year follow-up. 1 Specifically, 36.1% of patients without an ICD died at 5 years, compared with 28.9% of patients who received an ICD. Thus, 7.2% (36.1 2 28.9%) fewer patients would die if they received an ICD during the 5-year follow-up. In other words, 14 patients need to receive an ICD to prevent one death over 5 years. ‘Reduces the risk of all-cause mortality by 23%’ represents a RRR. ‘Seven percent less would die’ represents the ARR. ‘Fourteen patients need to receive an ICD in order to prevent one death’ represents the NTT. The question faced by the clinicians is then ‘Which one will help me in choosing the best treatment for my patient?’ In terms of risk reduction, clinicians might be more willing to recommend, and patients are more willing to accept, an intervention when its benefits are presented in relative compared with absolute terms. In this respect, the RRR can be regarded as a more persuasive summary statistic. But what really counts in decision-making is

Prophylactic implantable defibrillators in dilated cardiomyopathy

Arrhythmia risk stratification with regard to prophylactic implantable cardioverter-defibrillator (ICD) therapy was investigated in the Marburg Cardiomyopathy Study, which revealed left ventricular ejection fraction to be the only significant independent arrhythmia risk predictor in a relatively large dilated cardiomyopathy (DCM) patient population. Based of the favorable results of the SCD-HeFT Trial, prophylactic ICD therapy became a classI indication for patients with DCM, NYHA classII or III heart failure and a left ventricular ejection fraction ≤ 35% despite optimized medical therapy. In addition, prophylactic ICD therapy combined with cardiac resynchronization became standard treatment in DCM patients with complete left bundle branch block and an ICD indication according to SCD-HeFT criteria. Unresolved issues of prophylactic ICD therapy in DCM include a high number to treat in order to save one patient from sudden death due to difficult arrhythmia risk stratification which is largely based on reduced left ventricular ejection fraction. Second, optimal timing of prophylactic ICD implant remains difficult, because a significant but unpredictable number of DCM patients show a marked improvement of left ventricular function during follow-up, thus, averting the need prophylactic ICD therapy. Finally, prophylactic ICD therapy is associated with a considerable complication rate with painful inappropriate shocks and lead-related problems being the most frequent complications during long-term follow-up.

The cost-effectiveness of primary prophylactic implantable defibrillator therapy in patients with ischaemic or non-ischaemic heart disease: a European analysis

It remains unclear whether primary prophylactic implantable cardioverter-defibrillator (ICD) therapy is cost-effective compared with a 'no ICD strategy' in the European health care setting. We performed a cost-effectiveness analysis for a cohort of patients with a left ventricular ejection fraction <40% and ischaemic or non-ischaemic heart disease. A Markov decision analytic model was used to evaluate long-term survival, quality-adjusted life years (QALYs), and lifetime costs for a cohort of patients with a reduced left ventricular function without previous arrhythmias, managed with a prophylactic ICD. Input data on effectiveness were derived from a meta-analysis of primary prophylactic ICD-only therapy randomized trials, from a prospective cohort study of ICD patients, from a health care utilization survey, and from the literature. Input data on costs were derived from a micro-cost analysis. Data on quality-of-life were derived from the literature. Deterministic and probabilistic sensitivity analysis was performed to assess the uncertainty. Probabilistic sensitivity analysis demonstrated a mean lifetime cost of €50 685 ± €4604 and 6.26 ± 0.64 QALYs for patients in the 'no ICD strategy'. Patients in the 'ICD strategy' accumulated €86 759 ± €3343 and an effectiveness of 7.08 ± 0.71 QALYs yielding an incremental cost-effectiveness ratio of €43 993/QALY gained compared with the 'no ICD strategy'. The probability that ICD therapy is cost-effective was 65% at a willingness-to-pay threshold of €80 000/QALY. Our results suggest that primary prophylactic ICD therapy in patients with a left ventricular ejection fraction <40% and ischaemic or non-ischaemic heart disease is cost-effective in the European setting.