Iwona Cygankiewicz

Effectiveness of Cardiac Resynchronization Therapy by QRS Morphology in the Multicenter Automatic Defibrillator Implantation Trial–Cardiac Resynchronization Therapy (MADIT-CRT)

Background— This study aimed to determine whether QRS morphology identifies patients who benefit from cardiac resynchronization therapy with a defibrillator (CRT-D) and whether it influences the risk of primary and secondary end points in patients enrolled in the Multicenter Automatic Defibrillator Implantation Trial–Cardiac Resynchronization Therapy (MADIT-CRT) trial. Methods and Results— Baseline 12-lead ECGs were evaluated with regard to QRS morphology. Heart failure event or death was the primary end point of the trial. Death, heart failure event, ventricular tachycardia, and ventricular fibrillation were secondary end points. Among 1817 patients with available sinus rhythm ECGs at baseline, there were 1281 (70%) with left bundle-branch block (LBBB), 228 (13%) with right bundle-branch block, and 308 (17%) with nonspecific intraventricular conduction disturbances. The latter 2 groups were defined as non-LBBB groups. Hazard ratios for the primary end point for comparisons of CRT-D patients versus patients who only received an implantable cardioverter defibrillator (ICD) were significantly (P<0.001) lower in LBBB patients (0.47; P<0.001) than in non-LBBB patients (1.24; P=0.257). The risk of ventricular tachycardia, ventricular fibrillation, or death was decreased significantly in CRT-D patients with LBBB but not in non-LBBB patients. Echocardiographic parameters showed significantly (P<0.001) greater reduction in left ventricular volumes and increase in ejection fraction with CRT-D in LBBB than in non-LBBB patients. Conclusions— Heart failure patients with New York Heart Association class I or II and ejection fraction ⩽30% and LBBB derive substantial clinical benefit from CRT-D: a reduction in heart failure progression and a reduction in the risk of ventricular tachyarrhythmias. No clinical benefit was observed in patients with a non-LBBB QRS pattern (right bundle-branch block or intraventricular conduction disturbances). Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00180271.

Heart Rate Turbulence: Standards of Measurement, Physiological Interpretation, and Clinical Use: International Society for Holter and Noninvasive Electrophysiology Consensus

This consensus statement has been compiled on behalf of the International Society for Holter and Noninvasive Electrophysiology. It reviews the topic of heart rate turbulence (HRT) and concentrates on technologies for measurement, physiologic background and interpretation, and clinical use of HRT. It also lists suggestions for future research. The phenomenon of HRT refers to sinus rhythm cycle-length perturbations after isolated premature ventricular complexes. The physiologic pattern of HRT consists of brief heart rate acceleration (quantified by the so-called turbulence onset) followed by more gradual heart rate deceleration (quantified by the so-called turbulence slope) before the rate returns to a pre-ectopic level. Available physiologic investigations confirm that the initial heart rate acceleration is triggered by transient vagal inhibition in response to the missed baroreflex afferent input caused by hemodynamically inefficient ventricular contraction. A sympathetically mediated overshoot of arterial pressure is responsible for the subsequent heart rate deceleration through vagal recruitment. Hence, the HRT pattern is blunted in patients with reduced baroreflex. The HRT pattern is influenced by a number of factors, provocations, treatments, and pathologies reviewed in this consensus. As HRT measurement provides an indirect assessment of baroreflex, it is useful in those clinical situations that benefit from baroreflex evaluation. The HRT evaluation has thus been found appropriate in risk stratification after acute myocardial infarction, risk prediction, and monitoring of disease progression in heart failure, as well as in several other pathologies.

Long-Term Benefit of Primary Prevention With an Implantable Cardioverter-Defibrillator An Extended 8-Year Follow-Up Study of the Multicenter Automatic Defibrillator Implantation Trial II

Background— The Multicenter Automatic Defibrillator Implantation Trial II (MADIT-II) showed a significant 31% reduction in the risk of death with primary implantable cardioverter-defibrillator (ICD) therapy during a median follow-up of 1.5 years. However, currently there are no data on the long-term efficacy of primary defibrillator therapy. Methods and Results— MADIT-II enrolled 1232 patients with ischemic left ventricular dysfunction who were randomized to ICD and non-ICD medical therapy and were followed up through November 2001. For the present long-term study, we acquired posttrial mortality data through March 2009 for all study participants (median follow-up, 7.6 years). Multivariate Cox proportional hazards regression modeling was performed to calculate the hazard ratio for ICD versus non-ICD therapy during long-term follow-up. At 8 years of follow-up, the cumulative probability of all-cause mortality was 49% among patients treated with an ICD compared with 62% among non-ICD patients (P<0.001). Multivariate analysis demonstrated that ICD therapy was associated with a significant long-term survival benefit (hazard ratio for 0- through 8-year mortality=0.66 [95% confidence interval, 0.56 to 0.78]; P<0.001). Treatment with an ICD was shown to be associated with a significant reduction in the risk of death during the early phase of the extended follow-up period (0 through 4 years: hazard ratio=0.61 [95% confidence interval, 0.50 to 0.76]; P<0.001) and with continued life-saving benefit during the late phase of follow-up (5 through 8 years: hazard ratio=0.74 [95% confidence interval, 0.57 to 0.96]; P=0.02). Conclusions— Our findings demonstrate a sustained 8-year survival benefit with primary ICD therapy in the MADIT-II population.

The MUSIC Risk score: a simple method for predicting mortality in ambulatory patients with chronic heart failure.

AIMS The prognosis of chronic heart failure (CHF) is extremely variable, although generally poor. The purpose of this study was to develop prognostic models for CHF patients. METHODS AND RESULTS A cohort of 992 consecutive ambulatory CHF patients was prospectively followed for a median of 44 months. Multivariable Cox models were developed to predict all-cause mortality (n = 267), cardiac mortality (primary end-point, n = 213), pump-failure death (n = 123), and sudden death (n = 90). The four final models included several combinations of the same 10 independent predictors: prior atherosclerotic vascular event, left atrial size >26 mm/m(2), ejection fraction < or =35%, atrial fibrillation, left bundle-branch block or intraventricular conduction delay, non-sustained ventricular tachycardia and frequent ventricular premature beats, estimated glomerular filtration rate <60 mL/min/1.73 m(2), hyponatremia < or =138 mEq/L, NT-proBNP >1.000 ng/L, and troponin-positive. On the basis of Cox models, the MUSIC Risk scores were calculated. A cardiac mortality score >20 points identified a high-risk subgroup with a four-fold cardiac mortality risk. CONCLUSION A simple score with a limited number of non-invasive variables successfully predicted cardiac mortality in a real-life cohort of CHF patients. The use of this model in clinical practice identifies a subgroup of high-risk patients that should be closely managed.

Interatrial blocks. A separate entity from left atrial enlargement: a consensus report

Impaired interatrial conduction or interatrial block is well documented but is not described as an individual electrocardiographic (ECG) pattern in most of ECG books, although the term atrial abnormalities to encompass both concepts, left atrial enlargement (LAE) and interatrial block, has been coined. In fact, LAE and interatrial block are often associated, similarly to what happens with ventricular enlargement and ventricular block. The interatrial blocks, that is, the presence of delay of conduction between the right and left atria, are the most frequent atrial blocks. These may be of first degree (P-wave duration >120 milliseconds), third degree (longer P wave with biphasic [±] morphology in inferior leads), and second degree when these patterns appear transiently in the same ECG recording (atrial aberrancy). There are evidences that these electrocardiographic P-wave patterns are due to a block because they may (a) appear transiently, (b) be without associated atrial enlargement, and (c) may be reproduced experimentally. The presence of interatrial blocks may be seen in the absence of atrial enlargement but often are present in case of LAE. The most important clinical implications of interatrial block are the following: (a) the first degree interatrial blocks are very common, and their relation with atrial fibrillation and an increased risk for global and cardiovascular mortality has been demonstrated; (b) the third degree interatrial blocks are less frequent but are strong markers of LAE and paroxysmal supraventricular tachyarrhythmias. Their presence has been considered a true arrhythmological syndrome.

Bridging a Temporary High Risk of Sudden Arrhythmic Death. Experience with the Wearable Cardioverter Defibrillator (WCD)

The implantable cardioverter defibrillator (ICD) is able to reduce sudden arrhythmic death in patients who are considered to be at high risk. However, the arrhythmic risk may be increased only temporarily as long as the proarrhythmic conditions persist, left ventricular ejection fraction remains low, or heart failure prevails. The wearable cardioverter defibrillator (WCD) represents an alternative approach to prevent sudden arrhythmic death until either ICD implantation is clearly indicated or the arrhythmic risk is considered significantly lower or even absent. The WCD is also indicated for interrupted protection by an already implanted ICD, temporary inability to implant an ICD, and lastly refusal of an indicated ICD by the patient. The WCD is not an alternative to the ICD, but a device that may contribute to better selection of patients for ICD therapy. The WCD has the characteristics of an ICD, but does not need to be implanted, and it has similarities with an external defibrillator, but does not require a bystander to apply lifesaving shocks when necessary.

Heart rate turbulence predicts all-cause mortality and sudden death in congestive heart failure patients

BACKGROUND Abnormal heart rate turbulence (HRT) has been documented as a strong predictor of total mortality and sudden death in postinfarction patients, but data in patients with congestive heart failure (CHF) are limited. OBJECTIVE The aim of this study was to evaluate the prognostic significance of HRT for predicting mortality in CHF patients in New York Heart Association (NYHA) class II-III. METHODS In 651 CHF patients with sinus rhythm enrolled into the MUSIC (Muerte Subita en Insuficiencia Cardiaca) study, the standard HRT parameters turbulence onset (TO) and slope (TS), as well as HRT categories, were assessed for predicting total mortality and sudden death. RESULTS HRT was analyzable in 607 patients, mean age 63 years (434 male), 50% of ischemic etiology. During a median follow up of 44 months, 129 patients died, 52 from sudden death. Abnormal TS and HRT category 2 (HRT2) were independently associated with increased all-cause mortality (HR: 2.10, CI: 1.41 to 3.12, P <.001 and HR: 2.52, CI: 1.56 to 4.05, P <.001; respectively), sudden death (HR: 2.25, CI: 1.13 to 4.46, P = .021 for HRT2), and death due to heart failure progression (HR: 4.11, CI: 1.84 to 9.19, P <.001 for HRT2) after adjustment for clinical covariates in multivariate analysis. The prognostic value of TS for predicting total mortality was similar in various groups dichotomized by age, gender, NYHA class, left ventricular ejection fraction, and CHF etiology. TS was found to be predictive for total mortality only in patients with QRS > 120 ms. CONCLUSION HRT is a potent risk predictor for both heart failure and arrhythmic death in patients with class II and III CHF.

Long QT Syndrome and Short QT Syndrome

The long QT syndrome (LQTS) is a genetic disorder characterized by prolongation of the QT interval in the electrocardiogram (ECG) and a propensity to torsades de pointes ventricular tachycardia frequently leading to syncope, cardiac arrest, or sudden death usually in young otherwise healthy individuals. The long QT syndrome is caused by mutations of predominantly potassium and sodium ion channel genes or channel-related proteins leading to positive overcharge of myocardial cell with consequent heterogeneous prolongation of repolarization in various layers and regions of myocardium. These conditions facilitate the early after-depolarization and reentry phenomena underlying development of polymorphic ventricular tachycardia observed in patients with LQTS. Obtaining detailed patient history regarding cardiac events in the patient and his/her family members combined with careful interpretation of standard 12-lead ECG (with precise measurement of QT interval in all available ECGs and evaluation of T-wave morphology) usually is sufficient to diagnose the LQTS. Genetic testing plays an important role and is particularly useful in cases with nondiagnostic or borderline ECG findings. The clinical course of patients with LQTS depends on the extent of QTc prolongation and history of cardiac events and is modulated by age, sex, and genotype. beta-Blockers remain the therapy of choice for LQTS, but implantation of a cardioverter defibrillator is increasingly used in high-risk patients.

Predictors of long-term mortality in Multicenter Automatic Defibrillator Implantation Trial II (MADIT II) patients with implantable cardioverter-defibrillators.

BACKGROUND Data on long-term follow-up and factors influencing mortality in implantable cardioverter-defibrillator (ICD) recipients are limited. OBJECTIVE The aim of this study was to evaluate mortality during long-term follow-up and the predictive value of several risk markers in the Multicenter Automatic Defibrillator Implantation Trial II (MADIT II) patients with implanted cardioverter-defibrillators (ICDs). METHODS The study involved U.S. patients from the MADIT II trial randomized to and receiving ICD treatment. Data regarding long-term mortality were retrieved from the National Death Registry. Several clinical, biochemical, and electrocardiogram variables were tested in a multivariate Cox model for predicting long-term mortality, and a score identifying high-, medium-, and lower risk patients was developed. RESULTS The study population consisted of 655 patients, mean age 64 +/- 10 years. During a follow-up of up to 9 years, averaging 63 months, 294 deaths occurred. The 6-year cumulative probability of death was 40%, with evidence of a constant risk of about 8.5% per year among survivors. Median survival was estimated at 8 years. Multivariate analysis identified age >65 years, New York Heart Association class 3-4, diabetes, non-sinus rhythm, and increased levels of blood urea nitrogen as independent risk predictors of mortality. Patients with three or more of these risk factors were characterized by a 6-year mortality rate of 68%, compared with 43% in those with one to two risk factors and 19% in patients with no risk factors. CONCLUSION A combination of a few readily available clinical variables indicating advanced disease and comorbid conditions identifies ICD patients at high risk of mortality during long-term follow-up.

Risk Stratification of Mortality in Patients With Heart Failure and Left Ventricular Ejection Fraction >35%

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 < or =86 ms, turbulence slope < or =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 > or =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 < or =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.