Individual corrected QT interval (QTc) may vary widely among carriers of the same long QT syndrome (LQTS) mutation. Currently, neither the mechanism nor the implications of this variable penetrance ...are well understood.
To hypothesize that the assessment of QTc variance in patients with congenital LQTS who carry the same mutation provides incremental prognostic information on the patient-specific QTc.
The study population comprised 1206 patients with LQTS with 95 different mutations and ≥ 5 individuals who carry the same mutation. Multivariate Cox proportional hazards regression analysis was used to assess the effect of mutation-specific standard deviation of QTc (QTcSD) on the risk of cardiac events (comprising syncope, aborted cardiac arrest, and sudden cardiac death) from birth through age 40 years in the total population and by genotype.
Assessment of mutation-specific QTcSD showed large differences among carriers of the same mutations (median QTcSD 45 ms). Multivariate analysis showed that each 20 ms increment in QTcSD was associated with a significant 33% (P = .002) increase in the risk of cardiac events after adjustment for the patient-specific QTc duration and the family effect on QTc. The risk associated with QTcSD was pronounced among patients with long QT syndrome type 1 (hazard ratio 1.55 per 20 ms increment; P<.001), whereas among patients with long QT syndrome type 2, the risk associated with QTcSD was not statistically significant (hazard ratio 0.99; P = .95; P value for QTcSD-by-genotype interaction = .002).
Our findings suggest that mutations with a wider variation in QTc duration are associated with increased risk of cardiac events. These findings appear to be genotype-specific, with a pronounced effect among patients with the long QT syndrome type 1 genotype.
Abstract Background Cardiac resynchronization with defibrillators (CRT-D) reduces heart failure and mortality compared with defibrillators alone. Whether this applies to all ages is unclear. Methods ...and Results We assessed the association of age on heart failure and death as a post hoc analysis of the MADIT-CRT follow-up study, in which 1,281 patients with class I/II heart failure (HF) were randomized to CRT-D or implantable cardioverter-defibrillators alone. Different age groups (<60, 60–74, and ≥75 years) were evaluated over 7 years for mortality and HF events. Among the 3 age groups, there were 399, 651, and 231 patients, respectively. We compared events with the use of a multivariate regression model. CRT-D compared with defibrillators alone significantly reduced the composite of HF or death across all age groups: <60 years: relative risk reduction (RRR) = 36%; 60–74 years: RRR = 61%; ≥75 years: RRR = 56%. CRT-D significantly reduced HF in all age groups: <60 years: RRR = 49%; 60–74 years: RRR = 62%; ≥75 years: RRR = 74%. CRT-D was associated with significant mortality reduction only in the 60–74 year age group: RRR = 59%. Conclusions CRT-D reduced HF events and the composite of mortality or HF events during long-term follow-up in all age groups. CRT-D reduced mortality only in the 60–74 year age group.
The optimal atrioventricular pacing delay (AVD) in cardiac resynchronization therapy (CRT) remains to be determined.
To determine whether programming CRT devices to short AVD (S-AVD) will improve ...clinical response secondary to greater reductions in dyssynchrony.
The study population comprised 1235 patients with left bundle branch block enrolled in Multicenter Automatic Defibrillator Implantation Trial in Cardiac Resynchronization Therapy (MADIT-CRT). We assessed the relationship between AVD and outcomes. Patients programmed to S-AVD (median value of <120 ms; n = 337) vs long AVD (L-AVD; ≥120 ms; n = 390) were assessed for the end points of heart failure (HF) or death, death alone, and echocardiographic response to the CRT at 1-year follow-up. Outcomes were also compared to the left bundle branch block implantable cardioverter-defibrillator-only group (n = 508).
Multivariate analysis showed that patients programmed to S-AVD experienced a significant 33% (hazard ratio HR 0.67; 95% confidence interval CI 0.44-0.85; P = .037) reduction in the risk of HF or death and a 47% (HR 0.53; 95% CI 0.29-0.94; P = .031) reduction in death alone as compared with those programmed to L-AVD. Patients with CRT-programmed S-AVD and L-AVD experienced 63% (HR 0.37; 95% CI 0.26-0.53; P < .001) and 46% (HR 0.54; 95% CI 0.31-0.96; P < .001) reduction, respectively, in the risk of HF or death compared to patients with implantable cardioverter-defibrillator alone. At 1 year of follow-up, S-AVD vs L-AVD was associated with a greater reduction in left ventricular end-systolic volume (34.2% vs 30.8%; P = .002) along with a significantly greater improvement in dyssynchrony (22.3% vs 9.4%; P = .036).
Our findings indicate that in MADIT-CRT programming, the CRT AVD <120 ms was associated with a greater clinical and echocardiographic response to CRT.
We hypothesized that the response to cardiac resynchronization therapy with a defibrillator (CRT-D) in patients with mildly symptomatic heart failure (HF) is more favorable than the commonly ...referenced figure of 70%. This study involves the Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy (MADIT-CRT) study population in which paired echocardiograms from baseline and 1-year follow-up were available in 621 implantable cardioverter-defibrillator–treated patients and 749 patients treated with CRT-D. We prespecified CRT-D responders as the patients who at 1-year follow-up had a reduction in left ventricular end-systolic volume (LVESV) that corresponded to the top (best) quintile of LVESV reduction in the implantable cardioverter-defibrillator–treated patients, that is, a ≥17% reduction in LVESV. Using this metric, 88% of patients treated with CRT-D and 91% of the patients treated with CRT-D with left bundle branch block (LBBB) were identified as cardiac resynchronization therapy responders. Landmark multivariate Cox model analyses revealed a significant interaction (p = 0.038) involving LVESV (responders vs nonresponders) and LBBB (present vs not present) in risk reduction for HF or death. The interaction finding indicates that cardiac resynchronization therapy responders with LBBB have a significantly lower risk for HF or death (hazard ratio HR 0.24) than patients without LBBB (HR 0.62). In the patients treated with CRT-D, LVESV response was associated with reduction in the risk of death (HR 0.20, p <0.001). An increasing percent reduction in LVESV was associated with progressively lower rates of HF or death, a finding consistent with a dose-response relation. In conclusion, approximately 90% of CRT-D–treated patients in MADIT-CRT had a significant and meaningful reduction in LVESV, and these LVESV responders had reduced rates of cardiac events during long-term follow-up.
The temporal effect of heart failure (HF) hospitalization occurring at different time periods before implantation has not yet been studied in detail. The aim of the present study was to investigate ...the potential association between time from last HF hospitalization to device implantation and effects on subsequent outcomes and benefit from cardiac resynchronization therapy with a defibrillator (CRT-D). Multivariate Cox models were used to determine the temporal influence of previous HF hospitalization on the end point of HF or death within all left bundle branch block implantable cardioverter-defibrillator (ICD) and CRT-D patients enrolled in the Multicenter Automatic Defibrillator Implantation Trial–Cardiac Resynchronization Therapy (MADIT-CRT) trial (n = 1,250) and to evaluate the clinical benefit of CRT-D implantation, comparing CRT-D patients with ICD patients within each previous HF hospitalization group. The patients with previous HF hospitalization ≤12 months before device implantation had the greatest incidence of HF or death during 4-year follow-up (31%), while those with previous HF hospitalization >12 months and those with no previous HF hospitalization had similar lower rates of HF or death (22% and 24%, respectively). All patients treated with CRT-D derived significant clinical benefit compared with their ICD counterparts, regardless of time of previous hospitalization (hazard ratios 0.38 no previous hospitalization, 0.49 (≤12 months), and 0.45 (>12 months); p for interaction = 0.67). In conclusion, in the present study of patients with mild HF with prolonged QRS intervals and LBBB, a previous HF hospitalization ≤12 months was associated with increased risk for HF or death compared with >12 months and no previous HF hospitalizations. The clinical benefit of CRT-D was evident in all patients regardless of time from last HF hospitalization to implantation compared with ICD only.
Sudden death of a sibling is thought to be associated with greater risk of death in long QT syndrome (LQTS). However, there is no evidence of such an association.
This study sought to test the ...hypothesis that sudden death of a sibling is a risk factor for death or aborted cardiac arrest (ACA) in patients with LQTS.
We examined all probands and first-degree and second-degree relatives in the International Long QT Registry from birth to age 40 years with QTc >/= 0.45 s. Covariates included sibling death, QTc, gender by age, syncope, and implantable cardioverter-defibrillator (ICD) and beta-blocker treatment. End points were (1) severe events (ACA, LQTS-related death) and (2) any cardiac event (syncope, ACA, or LQTS-related death).
Of 1915 subjects, 270 had a sibling who died. There were 213 severe events and 829 total cardiac events. More subjects with history of sibling death received beta-blocker therapy. Sibling death was not significantly associated with risk of ACA or LQTS-related death, but was associated with increased risk of syncope. QTc >/= 0.53 s (hazard ratio 2.5, P <.01), history of syncope (hazard ratio 6.1, P <.01), and gender were strongly associated with risk of ACA or LQTS-related death.
Sudden death of a sibling prompted more aggressive treatment but did not predict risk of death or ACA, whereas QTc >/= 0.53 s, gender, and syncope predicted this risk. All subjects should receive appropriate beta-blocker therapy. The decision to implant an ICD should be based on an individual's own risk characteristics (QTc, gender, and history of syncope).
Abstract Background Arrhythmogenic right ventricular cardiomyopathy (ARVC) is associated with sudden cardiac death. However, the selection of patients for implanted cardioverter-defibrillators ...(ICDs), as well as programming of the ICD, is unclear. Objectives The objective of this study was to identify predictors, characteristics, and treatment of ventricular arrhythmias in patients with ARVC. Methods The Multidisciplinary Study of Right Ventricular Cardiomyopathy established the North American ARVC Registry and enrolled patients with a diagnosis of ARVC. Patients were followed prospectively. Results Of 137 patients enrolled, 108 received ICDs. Forty-eight patients had 502 sustained episodes of ventricular arrhythmias, including 489 that were monomorphic and 13 that were polymorphic. In the patients with ICDs, independent predictors of ventricular arrhythmias in follow-up included spontaneous sustained ventricular arrhythmias before ICD implantation and T-wave inversions inferiorly. The only independent predictor for life-threatening arrhythmias, defined as sustained ventricular tachycardia (VT) ≥240 beats/min or ventricular fibrillation, was a younger age at enrollment. Anti-tachycardia pacing (ATP), independent of the cycle length of the VT, was successful in terminating 92% of VT episodes. Conclusions In the North American ARVC Registry, the majority of ventricular arrhythmias in follow-up are monomorphic. Risk factors for ventricular arrhythmias were spontaneous ventricular arrhythmias before enrollment and a younger age at ICD implantation. ATP is highly successful in terminating VT, and all ICDs should be programmed for ATP, even for rapid VT.
Abstract The electrocardiogram (ECG) provides important information to aid in the diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D). The ECG changes may be explained by ...the pathophysiology of the disease. The proximity of the right ventricle (RV) to the anterior chest leads (V1 to V4 ) explains why the characteristic ECG abnormalities are most prominent in those lends. The specific ECG abnormalities reflect the pathophysiology of the disease including T-wave inversion due to scarring of the free wall of the RV, prolonged S-wave duration due to slow depolarization of the terminal part of the QRS because the RV is the last part of the heart to undergo depolatization, and epsilon waves due to slow conduction in the RV. The extent of ECG abnormalities correlate with the degree of structural change in the RV.
The population of patients with heart failure (HF) and mild to moderate left ventricular (LV) dysfunction is growing, and mortality remains high. There is a need for better risk stratification of ...patients who might benefit from primary prevention of mortality. This study aimed to evaluate the prognostic value of Holter-based parameters for predicting mortality in patients with HF with LV ejection fraction (EF) >35%. The study involved 294 patients (199 men, mean age 66 years) with HF of ischemic and nonischemic causes, New York Heart Association classes II to III, and LVEF >35%. Surface electrocardiogram and 24-hour Holter monitoring were performed at enrollment to assess traditional electrocardiographic variables, as well as heart rate variability, heart rate turbulence, and repolarization dynamics (QT/RR). Total mortality and sudden death were the primary and secondary end points. During a median 44-month follow-up, there were 43 deaths (15%). None of the traditional electrocardiographic risk parameters significantly predicted mortality. A standard deviation of all normal-to-normal RR intervals ≤86 ms, turbulence slope ≤2.5 ms/RR, and QT end/RR >0.21 at daytime were found to be independent risk predictors of mortality in multivariate analyses. The predictive score based on these 3 variables showed that patients with ≥2 abnormal risk markers were at risk of death (30% 3-year mortality rate) and sudden death (12%), similar to death rates observed in patients with LVEF ≤35%. In conclusion, increased risk of mortality and sudden death could be predicted in patients with HF with LVEF >35% by evaluating the combination of standard deviation of all normal-to-normal RR intervals, turbulence slope, and QT/RR, parameters reflecting autonomic control of the heart, baroreflex sensitivity, and repolarization dynamics.
PDF
