Raul D. Mitrani

Fractal analysis and time- and frequency-domain measures of heart rate variability as predictors of mortality in patients with heart failure

Time-domain measures of heart rate (HR) variability provide prognostic information among patients with congestive heart failure (CHF). The prognostic power of spectral and fractal analytic methods of HR variability has not been studied in the patients with chronic CHF. The aim of this study was to assess whether traditional and fractal analytic methods of HR variability predict mortality among a population of patients with CHF. The standard deviation of RR intervals, HR variability index, frequency-domain indexes, and the short-term fractal scaling exponent of RR intervals were studied from 24-hour Holter recordings in 499 patients with CHF and left ventricular ejection fraction < or =35%. During a mean follow-up of 665 +/- 374 days, 210 deaths (42%) occurred in this population. Conventional and fractal HR variability indexes predicted mortality by univariate analysis. For example, a short-term fractal scaling exponent <0.90 had a risk ratio (RR) of 1.9 (95% confidence interval [CI] 1.4 to 2.5) and the SD of all RR intervals <80 ms had an RR of 1.7 (95% CI 1.2 to 2.1). After adjusting for age, functional class, medication, and left ventricular ejection fraction in the multivariate proportional-hazards analysis, the reduced short-term fractal exponent remained the independent predictor of mortality, RR 1.4 (95% CI 1.0 to 1.9; p <0.05). All HR variability indexes were more significant univariate predictors of mortality in functional class II than in class III or IV. Among patients with moderate heart failure, HR variability measurements provide prognostic information, but all HR variability indexes fail to provide independent prognostic information in patients with the most severe functional impairment.

Prediction of sudden cardiac death by fractal analysis of heart rate variability in elderly subjects.

OBJECTIVES The aim of this study was to test the hypothesis that abnormal scaling characteristics of heart rate (HR) predict sudden cardiac death in a random population of elderly subjects. BACKGROUND An abnormality in the short-term fractal scaling properties of HR has been observed to be related to a risk of life-threatening arrhythmias among patients with advanced heart diseases. The predictive power of altered short-term scaling properties of HR in general populations is unknown. METHODS A random sample of 325 subjects, age 65 years or older, who had a comprehensive risk profiling from clinical evaluation, laboratory tests and 24-h Holter recordings were followed up for 10 years. Heart rate dynamics, including conventional and fractal scaling measures of HR variability, were analyzed. RESULTS At 10 years of follow-up, 164 subjects had died. Seventy-one subjects had died of a cardiac cause, and 29 deaths were defined as sudden cardiac deaths. By univariate analysis, a reduced short-term fractal scaling exponent predicted the occurrence of cardiac death (relative risk [RR] 2.5, 95% confidence interval [CI], 1.9 to 3.2, p < 0.001) and provided even stronger prediction of sudden cardiac death (RR 4.1, 95% CI, 2.5 to 6.6, p < 0.001). After adjusting for other predictive variables in a multivariate analysis, reduced exponent value remained as an independent predictor of sudden cardiac death (RR 4.3, 95% CI, 2.0 to 9.2, p < 0.001). CONCLUSIONS Altered short-term fractal scaling properties of HR indicate an increased risk for cardiac mortality, particularly sudden cardiac death, in the random population of elderly subjects.

Contemporary Trends of Hospitalization for Atrial Fibrillation in the United States, 2000 Through 2010 Implications for Healthcare Planning

Background— Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. The associated morbidity and mortality make AF a major public health burden. Hospitalizations account for the majority of the economic cost burden associated with AF. The main objective of this study is to examine the trends of AF-related hospitalizations in the United States and to compare patient characteristics, outcomes, and comorbid diagnoses. Methods and Results— With the use of the Nationwide Inpatient Sample from 2000 through 2010, we identified AF-related hospitalizations using International Classification of Diseases, 9th Revision, Clinical Modification code 427.31 as the principal discharge diagnosis. Overall AF hospitalizations increased by 23% from 2000 to 2010, particularly in patients ≥65 years of age. The most frequent coexisting conditions were hypertension (60.0%), diabetes mellitus (21.5%), and chronic pulmonary disease (20.0%). Overall in-hospital mortality was 1%. The mortality rate was highest in the group of patients ≥80 years of age (1.9%) and in the group of patients with concomitant heart failure (8.2%). In-hospital mortality rate decreased significantly from 1.2% in 2000 to 0.9% in 2010 (29.2% decrease; P<0.001). Although there was no significant change in mean length of stay, mean cost of AF hospitalization increased significantly from

Clinical utility of intraatrial pacemaker stored electrograms to diagnose atrial fibrillation and flutter.

6410 in 2001 to

New-Onset Atrial Fibrillation After Aortic Valve Replacement : Comparison of Transfemoral, Transapical, Transaortic, and Surgical Approaches

8439 in 2010 (24.0% increase; P<0.001). Conclusions— Hospitalization rates for AF have increased exponentially among US adults from 2000 to 2010. The proportion of comorbid chronic diseases has also increased significantly. The last decade has witnessed an overall decline in hospital mortality; however, the hospitalization cost has significantly increased.

Heart rate variability in inappropriate sinus tachycardia

POLLAK, W.M., et al.: Clinical Utility of Intraatrial Pacemaker Stored Electrograms to Diagnose Atrial Fibrillation and Flutter. The purpose of this study was to determine if intraatrial electrograms (EGMs) are required to diagnose specific types of atrial tachyarrhythmias detected by pacemaker diagnostics. DDD pacemakers in 56 patients were programmed to store episodes of atrial tachyarrhythmias. Some episodes had a stored atrial EGM snapshot of the atrial tachyarrhythmia. The EGMs were analyzed to confirm whether the stored episodes were true atrial tachyarrhythmias or other pacemaker‐sensed events. EGM confirmation of atrial tachyarrhythmias correlated with increasing duration and rate of episodes. In particular, using EGMs, 8 (18%) of 44 episodes < 10 seconds in duration confirmed atrial tachyarrhythmias compared to 16 (89%) of 18 episodes > 5 minutes in duration (P < 0.001). Only 10 (18%) of 56 detected atrial arrhythmia episodes at rates < 250 complexes per minute were confirmed by the atrial EGM as true arrhythmias compared to 33 (57%) of 58 detected episodes at rates > 250/min (P < 0.001) Twenty‐nine (91%) of 32 EGM confirmed episodes of atrial fibrillation/flutter had an atrial rate > 250 complexes per minute and were a minimum of 10 seconds in duration. Fifteen (88%) of 17 episodes meeting the combined stored data criteria of > 250 complexes per minute and duration > 5 minutes were confirmed as atrial fibrillation or flutter by stored EGMs. Atrial EGMs identified that 71 (62%) of 114 stored high atrial rate (HAR) episodes were events other than true atrial tachyarrhythmias. Pacemaker diagnostic data with intraatrial EGMs can diagnose specific atrial tachyarrhythmias and identify other pacemaker‐sensed events. Stored episodes > 250 complexes per minute and > 5 minutes in duration had a high correlation with atrial fibrillation and flutter.

Dynamic Behavior and Autonomic Regulation of Ectopic Atrial Pacemakers

OBJECTIVES This study sought to determine the incidence of new-onset atrial fibrillation (AF) associated with different methods of isolated aortic valve replacement (AVR)-transfemoral (TF), transapical (TA), and transaortic (TAo) catheter-based valve replacement and conventional surgical approaches. BACKGROUND The relative incidences of AF associated with the various access routes for AVR have not been well characterized. METHODS In this single-center, retrospective cohort study, we evaluated a total of 231 consecutive patients who underwent AVR for degenerative aortic stenosis (AS) between March 2010 and September 2012. Patients with a history of paroxysmal, persistent, or chronic AF, with bicuspid aortic valves, and patients who died within 48 h after AVR were excluded. A total of 123 patients (53% of total group) qualified for inclusion. Data on documented episodes of new-onset AF, along with all clinical, echocardiographic, procedural, and 30-day follow-up data, were collated. RESULTS AF occurred in 52 patients (42.3%). AF incidence varied according to the procedural method. AF occurred in 60% of patients who underwent surgical AVR (SAVR), in 53% after TA-TAVR, in 33% after TAo-TAVR cases, and 14% after TF-TAVR. The episodes occurred at a median time interval of 53 (25th to 75th percentile, 41 to 87) h after completion of the procedure. Procedures without pericardiotomy had an 82% risk reduction of AF compared with those with pericardiotomy (adjusted odds ratio: 0.18; 95% confidence interval: 0.05 to 0.59). CONCLUSIONS AF was a common complication of AVR with a cumulative incidence of >40% in elderly patients with degenerative AS who underwent either SAVR or TAVR. AF was most common with SAVR and least common with TF-TAVR. Procedures without pericardiotomy were associated with a lower incidence of AF.

QRS duration on electrocardiography and cardiovascular mortality (from the National Health and Nutrition Examination Survey-III).

Analysis of heart rate variability in patients with inappropriate sinus tachycardia showed a 24-hour decrease in all temporal and spectral indexes, even after attempted correction to a rate of 75 beats/min. This may have resulted from a global decrease in parasympathetic activity or from a rapid sinus rate produced by other ill-defined mechanisms.

Differences in the activation patterns between sustained and self-terminating episodes of human ventricular fibrillation

BACKGROUND Heart rate (HR) variability reflects the neural regulation of normal pacemaker tissue, but the autonomic nervous regulation of abnormal atrial foci originating outside the sinus node has not been well characterized. We compared the HR variability of tachycardias originating from the ectopic foci and the sinus node. METHODS AND RESULTS R-R-interval variability was analyzed from 24-hour Holter recordings in 12 patients with incessant ectopic atrial tachycardia (average HR 107+/-14 bpm), 12 subjects with sinus tachycardia (average HR 106+/-9 bpm), and 24 age- and sex-matched subjects with normal sinus rhythm (average HR 72+/-8 bpm). Time- and frequency-domain HR variability measures, along with approximate entropy, short- and long-term correlation properties of R-R intervals (exponents alpha(1) and alpha(2)), and power-law scaling (exponent beta), were analyzed. Time- and frequency-domain measures of HR variability did not differ between subjects with ectopic and sinus tachycardia. Fractal scaling exponents and approximate entropy were similar in sinus tachycardia and normal sinus rhythm, but the short-term scaling exponent alpha(1) was significantly lower in ectopic atrial tachycardia (0.71+/-0.16) than in sinus tachycardia (1.16+/-0.13; P<0.001) or normal sinus rhythm (1.19+/-0.11; P<0.001). Abrupt prolongations in R-R intervals due to exit blocks from the ectopic foci or instability in beat-to-beat R-R dynamics were the major reasons for altered short-term HR behavior during ectopic tachycardias. CONCLUSIONS HR variability obtained by time- and frequency-domain methods does not differ between ectopic and sinus tachycardias, which suggests that abnormal atrial foci are under similar long-term autonomic regulation as normal pacemaker tissue. Short-term R-R-interval dynamics are altered toward more random behavior in ectopic tachycardia, which may result from a specific autonomic disturbance or an intrinsic abnormality of ectopic atrial pacemakers.

Pacemaker diagnostics: a critical appraisal of current technology.

The relation of bundle branch block (BBB) with adverse outcome is controversial. We hypothesized that increased QRS duration is an independent predictor of cardiovascular (CV) mortality in a cross-sectional US population. This is a retrospective cohort study on prospectively collected data to assess the relationship between QRS duration on routine ECG and CV mortality. Participants included 8,527 patients with ECG data available from the National Health and Nutrition Examination Survey data set, representing 74,062,796 individuals in the United States. Mean age was 60.5 ± 13.6 years. Most subjects were white (87%) and women (53%). During the follow-up period of 106,244.6 person-years, 1,433 CV deaths occurred. Multivariate analysis revealed that the highest quartile of QRS duration was associated with higher CV mortality than lowest quartile (hazard ratio [HR] 1.3, 95% confidence interval [CI] 1.01 to 1.7, p = 0.04) after adjustment for established risk factors. Both left BBB (HR 2.4, 95% CI 1.3 to 4.7, p = 0.009) and right BBB (HR 1.90, 95% CI 1.2 to 3.0, p = 0.008) were significantly associated with increased CV mortality. The addition of the QRS duration in 10-millisecond increments to the Framingham Risk Score model resulted in 4.4% overall net reclassification improvement (95% CI 0.02 to 0.04; p = 0.00006). In conclusion, increased QRS duration was found to be an independent predictor of CV mortality in this cross-sectional US population. A model including QRS duration in addition to traditional risk factors was associated with improved CV risk prediction.