Predictors Of Appropriate Therapy Research Articles

Long-term outcome of implantable cardioverter–defibrillator implantation in secondary prevention of sudden cardiac death

Little is known about the long-term outcomes of patients who receive an implantable cardioverter-defibrillator (ICD) for purely secondary prevention indications. To assess the rates and predictors of appropriate therapies over a very long-term follow-up period in this population. Between June 2003 and August 2006, 239 consecutive patients with structural left ventricular disease and a secondary prophylaxis indication for ICD therapy (survivors of life-threatening ventricular tachyarrhythmias) were prospectively enrolled. An extended follow-up of these patients was carried out. The primary endpoint was the occurrence of appropriate device therapy. Secondary endpoints were all-cause death, electrical storm and inappropriate therapy. The study population consisted of 239 patients (90% men; mean age 64±12 years; 72% ischaemic cardiomyopathy; left ventricular ejection fraction 37±12%). During a median follow-up of 7.8 (3.5-9.3) years, appropriate device therapy occurred in 139 (58.2%) patients. Death occurred in 141 patients (59%), electrical storm in 73 (30.5%) and inappropriate therapy in 42 (17.6%). Multivariable analysis identified patients whose presenting arrhythmia was ventricular fibrillation as being less likely to require appropriate device therapy than those whose presenting arrhythmia was ventricular tachycardia (sub-hazard ratio 0.62, 95% confidence interval 0.40-0.97; P=0.04). Independent predictors of all-cause death were age at implantation (P<0.0001), wide QRS complexes (P=0.024), creatinine concentration (P=0.0002) and B-type natriuretic peptide at implantation (P=0.0001). Secondary prevention ICD recipients exhibit a high risk of appropriate device therapy and death over prolonged follow-up. Patients who presented initially with ventricular fibrillation were less likely to require the delivery of appropriate device therapy.

Analysis of ECG Measures of Cardiac Repolarization in Relation to Arrhythmic Events in an Implantable Cardioverter Defibrillator Population

ECG-derived measures of cardiac repolarization may have utility in risk prediction of future ventricular arrhythmia, and a range of different measures have been proposed. We compared time-based, vectorcardiographic, and singular value decomposition (SVD) derived measures of repolarization to determine which was most predictive of appropriate therapy in an ICD population. We examined the independent prognostic value of a range of repolarization measures derived from 60 second 12-lead ECG recordings in 150 patients receiving new ICD implants in relation to the occurrence of appropriate therapy during follow-up. Over an average follow-up of 2.15 ± 0.87 years, male gender, presence of premature ventricular complex (PVC), relative T wave residuum (TWR-rel, measures regional repolarization heterogeneity), and TCRT (the total cosine R-to-T, describes the global angle between repolarization and depolarization wavefronts) were the only independent predictors of appropriate therapy. With every 0.01% increase in TWR-rel, there was 2% increased risk of appropriate therapy (HR = 1.02, 95% CI 1.006-1.034, P < 0.001). With every 1° decrease in TCRT, there was an increase in arrhythmic risk of 0.9% (HR 1.009, 95% CI 1.003-1.015, P = 0.003). The use of advanced analytic ECG techniques to derive measures of repolarization abnormality might shave utility in risk stratification in an ICD population.

0470: Implantable cardioverter defibrillator in primary prevention for chronic heart failure: incidence and predictors of appropriate therapy

Implantable cardioverter defibrillator (ICD) has been shown to be associated with a significant reduction in the risk of sudden cardiac death. The aim of this study was to assess the prevalence and to identify the clinical predictors of appropriate ICD therapy in patients with chronic heart failure following implantation of an ICD for primary prevention. A monocenter retrospective analysis was performed and all consecutive patients undergoing implantation of ICD for primary prevention were included. Device interrogations were performed and appropriate therapies were recorded. The endpoint follow-up was the last available device interrogation in our center. Of 317 primary prevention patients undergoing ICD implantation, 203 (64%) had ischemic cardiomyopathy (ICM) and 114 had non-ischemic dilated cardiomyopathy (NIDCM). After a mean follow-up time 760±599 days, 56 (17.7%) had received appropriate ICD therapies. Mean LVEF was 26±6%. By univariate comparison, LVDD≥65mm (p=0.035) and lack of diuretic (p=0.024) were predictors for ICD therapy. Absence of cardiac resynchronization therapy device (CRTD) was close to be significant (p=0.055). ICM and NIDCM patients benefit from ICD implantation did not differ (p=0.941). By multivariate analysis, elderly patients ≥65y (HR 1.92, p=0.032), LVDD≥65mm (HR 2.01, p=0.022) and lack of diuretic (HR 0.31, p<0.001) were all significant independent predictors for ICD therapy. Overall, the absence of CRTD device was close to be significant (H 0.53, p=0.062), but was significant in NIDCM population (p=0.007). During follow-up, the onset of atrial fibrillation (p=0.027) and hospitalization for acute heart failure (p=0.002) were significantly associated with ICD-delivered therapy. ICD therapy occurred in 17.7% of primary prevention patients without any difference between ICM and NIDCM. Older age, LV dilatation and absence of diuretic were predictive factors for ICD therapy. Presence of CRTD was close to be significant (figure next page). Abstract 0470 – Figure

0334 : Implantable cardioverter defibrillator in primary prevention for chronic heart failure: incidence and predictors of appropriate therapy

Considering morbidity and financial impact on the health care system, it may be helpful to stratify patients who would most benefit from primary ICD treatment. The aim of this study was to assess the prevalence and identify the clinical predictors of appropriate ICD therapy in patients following implantation of an ICD in primary prevention for chronic heart failure. A monocenter retrospective analysis was performed and all patients undergoing implantation of ICD in primary prevention were included. Device interrogations were performed and appropriate therapies, either ATP or shock, were noticed. Over the 317 primary prevention patients undergoing ICD implantation, 203 had ischemic cardiomyopathy (ICM) and 114 had nonischemic dilated cardiomyopathy (NIDCM). At the median follow-up time 760±599 days, 56 (17,7%) had received appropriate ICD therapies. Average Figure: Predictors of appropriate ICD therapy LVEF was 26±6%. By univariate comparison, LVDD≥65mm (p=0,035) and lack of diuretic (p=0,024) were significant predictors for ICD therapy. ICM and NIDCM patients benefit equivalently from ICD implantation (p=0,941). By multivariate analysis, elderly patients ≥65y (HR 1,92, p=0,032), LVDD≥65mm (HR 2,01, p=0,022) and lack of diuretic (HR 0,31, p<0,001) were all significant independent predictors for ICD therapy. Absence of CRT device was closed to be significant (HR 0,53, p=0,062), but was significant in NIDCM population (p=0,007). Onset atrial fibrillation (p=0,027) and hospitalization for acute heart failure (p=0,002) were significantly associated with ICD-delivered therapy. ICD therapy occurred in 17,7% of primary prevention patients with both ICM and NIDCM. In multivariate analysis, age ≥65y, LVDD≥65mm and absence of diuretic were predictive factors for ICD therapy. Presence of CRT device was closed to be significant. There was no difference by considering heart failure etiology, ICM and NIDCM patients benefited from ICD equivalently.

Incidence and predictors of appropriate therapies delivered by the implantable cardioverter defibrillator in patients with ischemic cardiomyopathy: A systematic review

BackgroundAlthough the implantable cardioverter defibrillator (ICD) improves the survival of patients at increased risk of sudden cardiac death due to systolic heart failure, ICD shocks have been associated with both worse survival and quality of life. We performed a systematic review of primary prevention ICD studies to evaluate the incidence and clinical predictors of appropriate ICD shocks or anti-tachycardia pacing (ATP) in patients with ischemic cardiomyopathy. MethodsWe performed a literature search in MEDLINE. Eligible studies had to be full text, written in the English language, performed in adults aged ≥19, and published from 1999 through April 2014. ResultsOf 289 identified studies, 9 met all our inclusion criteria. The mean length of follow up ranged from 17 to 45.5months. The incidence of appropriate ICD therapy varied from 17% to 31%. Among those studies, only 4 included data on the clinical characteristics of appropriate ICD therapy recipients. Characteristics associated with appropriate ICD therapy included male sex, advanced New York Heart Association class, non-sustained ventricular tachycardia, and lower serum creatinine. Patients who received appropriate therapy were also less likely to be on a beta-blocker. Left ventricular ejection fraction was not significantly different between patients who received appropriate ICD therapy and those who did not. ConclusionThe incidence of appropriate ICD therapy is not trivial in patients with ischemic cardiomyopathy and a primary prevention ICD. Predictors of appropriate ICD therapy have not been adequately assessed in large patient populations. As such, large prospective studies of predictors of appropriate ICD therapies are needed.

Fragmented Surface ECG Was a Poor Predictor of Appropriate Therapies in Patients with Chagas’ Cardiomyopathy and ICD Implantation (Fragmented ECG in CHAgas’ Cardiomyopathy Study)

Main causes of death in chronic Chagas' cardiomyopathy (CChC) are progressive congestive heart failure and sudden cardiac death. Implantable cardioverter defibrillators (ICD) have been proved an effective therapy to prevent sudden death in patients with CChC. Identification of predictors of sudden death remains a challenge. To determine whether surface fragmented ECG (fQRS) helps identifying patients with CChC and ICDs at higher risk of presenting appropriate ICD therapies. Multicenter retrospective study. All patients with CChC and ICDs were analyzed. Clinical demographics, surface ECG, and ICD therapies were collected. A total of 98 patients were analyzed. Another four cases were excluded due to pacing dependency. Mean age was 55.5 ± 10.4 years, male gender 65%, heart failure New York Heart Association class I 47% and II 38%. Mean left ventricular ejection fraction (LVEF) 39.6 ± 11.8%. The indication for ICD was secondary prevention in 70% of patients. fQRS was found in 56 patients (59.6%). Location of fragmentation was inferior (57.1%), lateral (35.7%), and anterior (44.6%). Rsr pattern was the more prevalent (57.1%). Predictors of appropriate therapy in the multivariate model were: increased age (P = 0.01), secondary prevention indication (P = 0.01), ventricular pacing >50% of the time (P = 0.004), and LVEF <30% (P = 0.01). The presence of fQRS did not identify patients at higher risk of presenting appropriate therapies delivered by the ICD (P = 0.87); regardless of QRS interval duration. fQRS is highly prevalent among patients with CChC. It has been found a poor predictor of appropriate therapies delivered by the ICD in this population.

Fragmented QRS as a predictor of arrhythmic events in patients with hypertrophic obstructive cardiomyopathy

This study aims to determine whether fragmented QRS (fQRS) in the surface electrocardiogram (ECG) at implantable cardioverter defibrillator (ICD) implant can predict arrhythmic events using appropriate therapy delivered by the ICD as a surrogate. Hypertrophic obstructive cardiomyopathy (HOCM) is a genetic disorder associated with life-threatening arrhythmias frequently requiring an ICD. Seeking a noninvasive method of risk stratification remains a challenge. This paper is a retrospective, multicenter study of patients with HOCM and ICD. Surface 12-lead ECGs were analyzed. Appropriate therapy was validated by a blinded Core Lab. Univariate and multivariate analyses were performed. A p value of <0.05 was considered significant. We included 102 patients from 13 centers. Mean age at implant was 41.16 ± 18.25 years, 52% were male. Mean left ventricular ejection fraction was 61.56 ± 9.46% and two thirds had heart failure according to the New York Heart Association class I. Secondary prophylaxis ICD implantation was the indication for implant in 40.2% of cases. About half received a single-chamber ICD. fQRS was present at the time of diagnosis in 21 and in 54% at ICD implant. At a mean follow-up of 47.8 ± 39.3 months, 41 patients (40.2%) presented with appropriate therapy. In a multivariate logistic regression, predictors of appropriate therapy included fQRS at implant (odds ratio [OR], 16.4; 95% confidence interval [CI], 3.6-74.0; p = 0.0003), history of combined ventricular tachycardia/fibrillation/sudden death (OR, 14.3; 95% CI, 3.2-69.3; p = 0.001) and history of syncope (OR, 5.5; 95% CI, 1.5-20.4; p = 0.009). Ten deaths (9.8%) occurred during the follow-up. fQRS in the lateral location increased the risk of appropriate therapy (p < 0.0001). fQRS predicts arrhythmic events in patients with HOCM and should be considered in a model of risk stratification.

Predictors of Sustained Ventricular Arrhythmias in Cardiac Resynchronization Therapy

Patients undergoing cardiac resynchronization therapy (CRT) are at high risk for ventricular arrhythmias (VAs), and risk stratification in this population remains poor. This study followed 269 patients (left ventricular ejection fraction <35%; QRS >120 ms; New York Heart Association class III/IV) undergoing CRT with a defibrillator for 553±464 days after CRT with defibrillator implantation to assess for independent predictors of appropriate device therapy for VAs. Baseline medication use, medical comorbidities, and echocardiographic parameters were considered. The 4-year incidence of appropriate device therapy was 36%. A Cox proportional hazard model identified left ventricular end-systolic diameter >61 mm as an independent predictor in the entire population (hazard ratio [HR], 2.66; P=0.001). Those with left ventricular end-systolic diameter >61 mm had a 51% 3-year incidence of VA compared with a 26% incidence among those with a less dilated ventricle (P=0.001). Among patients with left ventricular end-systolic diameter ≤61 mm, multivariate predictors of appropriate therapy were absence of β-blocker therapy (HR, 6.34; P<0.001), left ventricular ejection fraction <20% (HR, 4.22; P<0.001), and history of sustained VA (HR, 2.97; P=0.013). Early (<180 days after implant) shock therapy was found to be a robust predictor of hospitalization for heart failure (HR, 3.41; P<0.004) and mortality (HR, 5.16; P<0.001.) Among patients with CRT and a defibrillator, left ventricular end-systolic diameter >61 mm is a powerful predictor of VAs, and further risk stratification of those with less dilated ventricles can be achieved based on assessment of ejection fraction, history of sustained VA, and absence of β-blocker therapy.

ORAL PRESENTATION

ORAL PRESENTATION

Genetic polymorphisms of the adrenergic system and implantable cardioverter-defibrillator therapies in patients with heart failure

We investigated whether the combination of beta(1)-Gly389Arg and GNB3 C825T, two genetic polymorphisms strictly related to adrenergic system modulation, could act as predictors of appropriate therapies in patients with heart failure (HF) using implantable cardioverter-defibrillators (ICDs). Patients with HF and ICD implantation for primary and secondary prevention were studied. All ICD therapies were registered and classified as appropriate (secondary to ventricular tachycardia) or inappropriate (others). Genetic analysis was performed by polymerase chain reaction and restriction fragment length polymorphism methods. Seventy-three patients with mean left ventricular ejection fraction of 35 +/- 11% were evaluated. Overall, 35 ICD therapies occurred during follow-up in 31 (42.5%) patients. Twenty-four therapies (33%) were appropriate, and 11 (15%) were inappropriate. Individual analysis of each polymorphism only identified T825 carriers of GNB3 C825T as predictor of appropriate shocks. The combined presence of risk genotypes (Arg389 of the beta(1)-Gly389Arg and T825 of the GNB3 C825T) identified patients with higher risk of appropriate shocks. Patients with two at-risk genotypes had a survival rate free of appropriate shocks lower than those with none or only one of these markers (87 vs. 54%, respectively; log-rank statistic = 0.006). Using a Cox regression model, each at-risk genotype was associated with an increment of risk of appropriate ICD shocks (odds ratio = 3.9, 95% confidence interval of 1.3-12.0; P = 0.02). Genetic polymorphisms of the adrenergic system may help to identify HF patients who are more likely to receive appropriate ICD therapies. Further studies are necessary to determine the clinical applicability of these polymorphisms as predictors of arrhythmias.

Predictors of appropriate therapy in patients with implantable cardioverter-defibrillator for primary prevention of sudden cardiac death

The purpose of this study was to evaluate predictors of appropriate therapy in patients with implantable cardioverter-defibrillators (ICD) for primary prevention of sudden cardiac death. A retrospective cohort of 321 patients with systolic heart failure undergoing ICD placement for primary prevention of sudden cardiac death was queried with a mean follow-up period of 2.6 years. Appropriate ICD therapy was defined as therapy delivered for termination of a ventricular tachyarrhythmia. Appropriate ICD therapy was delivered in 142 (44%) of the patients. In a multivariate model, body mass index ≥28.8 kg/m2, chronic kidney disease, left ventricular ejection fraction ≤20% and metabolic syndrome were found to be independent predictors of appropriate ICD therapy. Appropriate ICD therapy was associated with higher cardiovascular mortality. These findings show the importance of identification of risk factors, especially metabolic syndrome, in patients following ICD implantation as aggressive treatment of these co-morbidities may decrease appropriate ICD therapy and cardiovascular mortality.

Abstract 4124: Polymorphisms can Predict Appropriate Therapies in Patients with Heart Failure and Implantable Cardioverter Defibrillators

Introduction: The use of implantable cardioverter defibrillators (ICD) reduces mortality in patients with heart failure (HF). However, given its elevated cost, an adequate selection of individuals with higher risk is warranted. Yet, known predictors of risk of sudden cardiac death have shown limited value to select use of ICD. More recently, genetic polymorphisms have been considered as potentially interesting tools to guide therapeutic strategies. Objective: To study the role of three genetic polymorphisms (β1 Arg389Gly, GNB3 C825T and GP IIb/IIIa Pl A1 /Pl A2 ) as predictors of appropriate ICD therapies in patients with heart failure (HF) who received an ICD implant for primary or secondary prevention. Patients and Methods: Retrospective cohort study of patients with ICD use during at least 6 months for primary and secondary prevention, followed at our HF outpatient clinic. Clinical data were registered and ICD analyses were made by telemetry. ICD therapies were defined as appropriate or inappropriate by a cardiac electrophysiologist. Twenty mL of blood were collected for polymorphism analysis by the PCR-RFLP technique. For univariate analysis, Student’s t-test and the χ 2 (chi-square) test were used; logistic regression was used for multivariate analysis. Results: The sample included 73 patients (75% male, 89% white and 56% ischemic etiology). The mean ejection fraction was 34.9 ± 9.8%. Individually, the Arg389 allele of the β1 Arg389Gly polymorphism, the T825 allele of the GNB3 C825T polymorphism, and the Pl A2 allele of the GP IIb/IIIa Pl A1 /Pl A2 polymorphism were not associated with appropriate ICD therapy. Nevertheless, the combined presence of these alleles identified patients with higher risk for appropriate shocks (p=0.03). Survival rate free of appropriate shocks was significantly lower in patients with 2 or 3 risk genotypes when compared with others (p=0.03). Conclusions: When analyzed in combination, the presence of the β1 Arg389Gly, GNB3 C825T, and GP IIb/IIIa Pl A1 /Pl A2 polymorphisms possibly act as predictors of appropriate therapies in ICD recipients with HF. Further studies are needed to determine the clinical applicability of these genetic markers.

Predictors of Appropriate Defibrillator Therapy Among Patients with an Implantable Defibrillator That Delivers Cardiac Resynchronization Therapy

The purpose of this study was to determine predictors of appropriate implantable defibrillator (ICD) therapy among patients with heart failure who are treated with a cardiac resynchronization therapy-defibrillator (CRT-D). Patients enrolled in the Ventak CHF/Contak CD study were treated with a CRT-D device and were required to have NYHA class II-IV CHF, QRS duration > or = 120 msec, and a class I or II indication for an ICD. The study database was retrospectively analyzed during the 6-month postimplant period to identify predictors of appropriate ICD therapy. Five hundred and one of the 581 patients enrolled in the trial had successful device implantation and were included in this analysis. Patients were mostly male (83%), 66 +/- 11 years old, and had coronary artery disease (69%), a mean left ventricular ejection fraction (EF) = 0.22 +/- 0.07, and NYHA class II (33%), III (58%), or IV (9%) CHF symptoms. During 6 months of follow-up, 73 of 501 (14%) patients received an appropriate ICD therapy. Two independent predictors of appropriate therapy were identified: a history of a spontaneous, sustained ventricular arrhythmia (HR = 2.05; 95% CI = 1.31-3.20; P = 0.002) and NYHA class IV CHF (HR = 1.81; 95% CI = 1.10-2.96; P = 0.019). When patients with NYHA class II were excluded from analysis, a history of a sustained ventricular arrhythmia and the presence of NYHA class IV CHF symptoms remained as independent predictors of appropriate ICD therapy. In a select population of advanced heart failure patients receiving a CRT-D, NYHA class IV CHF was a powerful independent predictor of appropriate ICD therapy. Approximately one-quarter of the patients with NYHA class IV CHF who received a CRT-D device received an appropriate ICD therapy within 3 months after implant. Additional studies are needed to confirm an association between class IV CHF symptoms and an increased frequency of ICD shocks.

Does the abnormal signal-averaged electrocardiogram predict future appropriate therapy in patients with implantable cardioverter-defibrillators?

Background Several studies have documented the prognostic significance of the signal-averaged electrocardiogram (SAECG) both after myocardial infarction and nonischemic cardiomyopathy. However, whether the SAECG can identify patients with implantable cardioverter-defibrillator (ICD) who receive appropriate therapy has not been hitherto completely investigated. Methods Between August 2002 and August 2004, 83 consecutive ICD patients who had had SAECGs recorded were enrolled in this study. All patients were followed up in the outpatient ICD clinic, and interrogated electrograms were collected. Results Over 9.0 ± 2.8 months of follow-up, 27 (32%) patients had appropriate ICD therapy for ventricular tachycardia or fibrillation; 15 (55.6%) patients had abnormal; and the remaining 12 (44.4%) had normal SAECGs. Of the 56 patients with no appropriate therapy, 27 (48.2%) and 29 (51.8%) patients had abnormal and normal SAECGs, respectively. There were no statistically significant differences between the 2 groups in SAECG findings ( P = .41). A Cox regression analysis showed that the left ventricular ejection fraction was the only predictor of appropriate therapy ( P = .02). Subgroup analysis of the patients with coronary artery disease and spontaneous monomorphic ventricular tachycardia indicated that left ventricular ejection fraction ( P = .03) and abnormal SAECG ( P = .02) were predictors of appropriate therapy. Conclusions Our data demonstrate that except for the subgroup of patients with coronary artery disease presenting with monomorphic ventricular tachycardia, the SAECG did not predict ventricular tachyarrhythmia recurrence and, hence, appropriate ICD therapy. Thus, SAECG findings should generally not be a factor in decision for ICD implantation.