Biomedical subjects

Richard J Cohen

Publications and source records attributed to Richard J Cohen.

At least 19 recordsLinked to original sources

PubMed2006

"Indeterminate" microvolt T-wave alternans tests predict high risk of death or sustained ventricular arrhythmias in patients with left ventricular dysfunction.

OBJECTIVES: This study tested the hypothesis that an "indeterminate" microvolt T-wave alternans (MTWA) test, when due to ectopy, unsustained MTWA, or low exercise heart rate (HR), has prognostic significance similar to a positive MTWA test. BACKGROUND: MTWA testing, used to stratify risk of sudden or total mortality in patients with structural heart disease, has been limited by a substantial number of "indeterminate" tests. Indeterminate tests are due to patient factors--excessive ventricular ectopy during exercise, unsustained MTWA, or failure to achieve a HR of 105 beats/min for 1 min--or technical factors such as a noisy recording or an exercise protocol that causes an excessively rapid rise in HR. METHODS: Patients in sinus rhythm with left ventricular ejection fraction < or =0.40 underwent MTWA exercise tests, analyzed with the spectral method and classified by a computerized interpretation algorithm. The primary end point was all-cause mortality or documented non-fatal sustained ventricular arrhythmia (SVA). "Indeterminate" tests were reviewed jointly by 2 readers blinded to subsequent events to determine the primary reason for indeterminacy. RESULTS: Participants (N = 549) were 56 +/- 13 years and 71% male; 49% had ischemic cardiomyopathy. There were 40 deaths and 11 non-fatal SVA. Most (94%) indeterminate results were due to patient factors. The 2-year rate for death or SVA was 17.8% in patients with an "indeterminate" MTWA test compared with 12.3% in those with a positive test. CONCLUSIONS: In patients with left ventricular dysfunction, an "indeterminate" MTWA test due to patient factors predicted death or SVA at least as well as a positive test.

Adult↗

PubMed2006

Continuous cardiac output monitoring by peripheral blood pressure waveform analysis.

A clinical method for monitoring cardiac output (CO) should be continuous, minimally invasive, and accurate. However, none of the conventional CO measurement methods possess all of these characteristics. On the other hand, peripheral arterial blood pressure (ABP) may be measured reliably and continuously with little or no invasiveness. We have developed a novel technique for continuously monitoring changes in CO by mathematical analysis of a peripheral ABP waveform. In contrast to the previous techniques, our technique analyzes the ABP waveform over time scales greater than a cardiac cycle in which the confounding effects of complex wave reflections are attenuated. The technique specifically analyzes 6-min intervals of ABP to estimate the pure exponential pressure decay that would eventually result if pulsatile activity abruptly ceased (i.e., after the high frequency wave reflections vanish). The technique then determines the time constant of this exponential decay, which equals the product of the total peripheral resistance and the nearly constant arterial compliance, and computes proportional CO via Ohm's law. To validate the technique, we performed six acute swine experiments in which peripheral ABP waveforms and aortic flow probe CO were simultaneously measured over a wide physiologic range. We report an overall CO error of 14.6%.

Algorithms↗

PubMed2006

A weighted-principal component regression method for the identification of physiologic systems.

We introduce a system identification method based on weighted-principal component regression (WPCR). This approach aims to identify the dynamics in a linear time-invariant (LTI) model which may represent a resting physiologic system. It tackles the time-domain system identification problem by considering, asymptotically, frequency information inherent in the given data. By including in the model only dominant frequency components of the input signal(s), this method enables construction of candidate models that are specific to the data and facilitates a reduction in parameter estimation error when the signals are colored (as are most physiologic signals). Additionally, this method allows incorporation of preknowledge about the system through a weighting scheme. We present the method in the context of single-input and multi-input single-output systems operating in open-loop and closed-loop. In each scenario, we compare the WPCR method with conventional approaches and approaches that also build data-specific candidate models. Through both simulated and experimental data, we show that the WPCR method enables more accurate identification of the system impulse response function than the other methods when the input signal(s) is colored.

Algorithms↗

PubMed2006

Why is orthostatic tolerance lower in women than in men? Renal and cardiovascular responses to simulated microgravity and the role of midodrine.

BACKGROUND: Exposure to microgravity induces cardiovascular deconditioning, manifested by orthostatic intolerance (OI). We assessed the renal, cardioendocrine, and cardiovascular responses of women and men to simulated microgravity to examine the impact of gender on OI. METHODS: Fifteen healthy female and 14 healthy male subjects were given a constant diet for 3 to 5 days, after which they underwent a tilt-stand test (pre-TST) and began 14 to 16 days of head-down tilt bed rest (HDTB), followed by a repeat tilt-stand test (post-TST). Female subjects began HDTB so that the post-TST was at the same time in their menstrual cycle as their pre-TST. Twenty-four-hour urine collections (daily), hormonal measurements, plethysmography, and cardiovascular system identification were performed. RESULTS: The times to presyncope were significantly different for men and women before (p= .005) and after HDTB (p= .001), with all of the women but only 50% of the men experiencing presyncope during the pre-TST (p= .002) and all of the women but only 64% of the men experiencing presyncope during the post-TST. At baseline, the following differences between women and men were observed: women had higher serum aldosterone levels (p = .02), higher parasympathetic responsiveness (p = .01), lower sympathetic responsiveness (p = .05), and lower venous compliance (p = .05). Several parameters changed with HDTB in both men and women. In a double-blinded randomized trial, midodrine (5 mg orally) or placebo given to female subjects 1 hour before post-TST was ineffective in preventing 01. CONCLUSION: In conclusion, the frequency of OI is higher in women than in men and is not modified by midodrine at the dose used. This increased susceptibility is likely secondary to intrinsic basal differences in the activity of volume-mediated parasympathetic and adrenergic systems and in venous tone. Thus, approaches to reduce OI in women are likely to differ from those effective in men.

Adaptation, Physiological↗

PubMed2005

Can microvolt T-wave alternans testing reduce unnecessary defibrillator implantation?

The Multicenter Automatic Defibrillator Implantation Trial II (MADIT II) and the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) have established that patients with a reduced ejection fraction gain an overall mortality benefit from prophylactic implantable cardioverter-defibrillator therapy. Only a small proportion of the patients in these studies, however, have received life-saving therapy from the defibrillator. Because defibrillator therapy is invasive and expensive, patients with a low ejection fraction would benefit from effective risk stratification so that defibrillator therapy was used only in those at significant risk. In this review, we analyze prospective clinical trials that have evaluated microvolt T-wave alternans (MTWA) testing as a predictor of ventricular tachyarrhythmic events in populations of patients similar to those studied in MADIT II or SCD-HeFT; that is, patients with a reduced ejection fraction who were not selected on the basis of a history of ventricular tachyarrhythmias. In these studies, the average annual rate of fatal and nonfatal ventricular tachyarrhythmic events among the patients who tested negative for MTWA was around 1%. This rate is so low that it is unlikely that such patients would benefit from implantable cardioverter-defibrillator therapy. The mortality, moreover, was lower among MTWA-negative patients who did not receive implantable defibrillators than that observed in the MADIT II and SCD-HeFT patients who received implantable cardioverter-defibrillators. In response, patients with a low ejection fraction who are being considered for implantable cardioverter-defibrillator therapy should undergo MTWA testing as part of their evaluation.

Clinical Trials as Topic↗

PubMed2005

Simulated microgravity induces microvolt T wave alternans.

BACKGROUND: There are numerous anecdotal reports of ventricular arrhythmias during spaceflight; however, it is not known whether spaceflight or microgravity systematically increases the risk of cardiac dysrhythmias. Microvolt T wave alternans (MTWA) testing compares favorably with other noninvasive risk stratifiers and invasive electrophysiological testing in patients as a predictor of sudden cardiac death, ventricular tachycardia, and ventricular fibrillation. We hypothesized that simulated microgravity leads to an increase in MTWA. METHODS: Twenty-four healthy male subjects underwent 9 to 16 days of head-down tilt bed rest (HDTB). MTWA was measured before and after the bed rest period during bicycle exercise stress. For the purposes of this study, we defined MTWA outcome to be positive if sustained MTWA was present with an onset heart rate<or=125 bpm. During various phases of HDTB, the following were also performed: daily 24-hour urine collections, serum electrolytes and catecholamines, and cardiovascular system identification (measure of autonomic function). RESULTS: Before HDTB, 17% of the subjects were MTWA positive [95%CI: (0.6%, 37%)]; after HDTB, 42% of the subjects were MTWA positive [95%CI: (23%, 63%)] (P=0.03). The subjects who were MTWA positive after HDTB compared with MTWA negative subjects had an increased versus decreased sympathetic responsiveness (P=0.03) and serum norepinephrine levels (P=0.05), and a trend toward higher potassium excretion (P=0.06) after bed rest compared to baseline. CONCLUSIONS: HDTB leads to an increase in MTWA, providing the first evidence that simulated microgravity has a measurable effect on electrical repolarization processes. Possible contributing factors include loss in potassium and changes in sympathetic function.

Adult↗

PubMed2005

Readaptation from simulated microgravity as a stimulus for improved orthostatic tolerance: role of the renal, cardioendocrine, and cardiovascular systems.

BACKGROUND: Microgravity and simulated microgravity (SM) lead to important changes in orthostatic tolerance (OT), the autonomic nervous system (ANS), and the volume-regulating systems. After one is exposed to microgravity or SM, a period of readaptation to gravity is known to take place, but it is not certain if orthostatic function returns to baseline within the initial recovery and what mechanisms are involved. We hypothesized that after a period of recovery, OT, ANS, and volume-regulating systems would return to pre-SM levels. METHODS: To test this hypothesis, 24 healthy men were placed on a constant diet for 3 to 5 days, after which a tilt-stand test (pre-TST) was performed. The TST was repeated after 14 to 16 days of head-down tilt bed rest (HDTB) (post-TST) and a 3-day period of recovery (rec-TST), at which times measurements of renal, cardioendocrine, and cardiovascular systems were conducted. RESULTS: Presyncope occurred in 46% of subjects pre-TST, in 72% post-TST, and in 23% during rec-TST. OT was significantly better during the recovery period than at baseline (p = .03). There was a significant decrease in urinary sodium and potassium excretion, along with a decrease in plasma renin activity and serum and urine aldosterone compared with baseline. Serum norepinephrine and sympathetic responsiveness remained below baseline values. CONCLUSION: In summary, OT improved compared with baseline after a period of readaptation. Retention of electrolytes (sodium, potassium) could be involved. These findings indicate that recovery after SM is not simply a gradual return to baseline values but is instead a dynamic process reflecting interaction of multiple regulatory systems.

Adaptation, Physiological↗

PubMed2005

Bed rest effects on human calf hemodynamics and orthostatic intolerance: a model-based analysis.

INTRODUCTION: Microgravity-induced orthostatic intolerance continues to be a primary problem after space missions. Its etiology remains uncertain despite significant research efforts over the past years. We hypothesized that calf hemodynamic parameters (compliance and resistance) are significantly affected by 14 to 16-d head-down bed rest (simulated microgravity), and their alterations play a role in the pathogenesis of orthostatic intolerance (OI) following bed rest. METHODS: To estimate these parameters, we developed a model-based approach to quantitatively simulate calf vascular response to venous occlusion, which only necessitates measurement of plethysmography data. In this study, plethysmography data were obtained from 29 subjects before and after 14-16 d of head-down bed rest. The subjects also underwent a tilt/stand test before and after bed rest. RESULTS: Statistical analyses demonstrated an increase in calf compliance (1.87 +/- 0.08, mean +/- SE, pre-bed rest; 2.16 +/- 0.10, end-bed rest) but no significant change in vascular resistance following bed rest. Compared with the tilt-intolerant subjects, those who were tilt-tolerant before bed rest had significantly higher calf compliance [2.00 +/- 0.09 (tolerant); 1.58 +/- 0.09 (intolerant)] and higher vascular resistance [7.79 +/- 0.18 (tolerant); 6.91 +/- 0.40 (intolerant)]. After bed rest, no such difference was detected. DISCUSSION: Based on these results, we validated the hypothesis that, instead of causing orthostatic intolerance, higher calf compliance before bed rest leads to recruitment of compensatory mechanisms (validated by the enhanced vascular resistance during venous occlusion) for a better toleration of orthostatic stress. With the absence of orthostatic challenge during bed rest, the difference in calf hemodynamic parameters is attenuated between the tilt-tolerant and tilt-intolerant groups.

Adaptation, Physiological↗

PubMed2004

Sleep restriction does not affect orthostatic tolerance in the simulated microgravity environment.

Orthostatic intolerance (OI) is a major problem following spaceflight, and, during flight, astronauts also experience sleep restriction. We hypothesized that sleep restriction will compound the risk and severity of OI following simulated microgravity and exaggerate the renal, cardioendocrine, and cardiovascular adaptive responses to it. Nineteen healthy men were equilibrated on a constant diet, after which they underwent a tilt-stand test. They then completed 14-16 days of simulated microgravity [head-down tilt bed rest (HDTB)], followed by repeat tilt-stand test. During HDTB, 11 subjects were assigned to an 8-h sleep protocol (non-sleep restricted), and 8 were assigned to a sleep-restricted protocol with 6 h of sleep per night. During various phases, the following were performed: 24-h urine collections, hormonal measurements, and cardiovascular system identification. Development of presyncope or syncope defined OI. There was a significant decrease in time free of OI (P = 0.02) and an increase in OI occurrence (P = 0.06) after HDTB among all subjects. However, the increase in OI occurrence did not differ significantly between the two groups (P = 0.60). The two groups also experienced similar physiological changes with HDTB (initial increase in sodium excretion; increased excretion of potassium at the end of HDTB; increase in plasma renin activity secretion without a change in serum or urine aldosterone). No significant change in autonomic function or catecholamines was noted. Simulated microgravity leads to increased OI, and sleep restriction does not additively worsen OI in simulated microgravity. Furthermore, conditions of sleep restriction and nonsleep restriction are similar with respect to renal, cardioendocrine, and cardiovascular responses to simulated microgravity.

Adult↗

PubMed2004

Theoretical considerations in the dynamic closed-loop baroreflex and autoregulatory control of total peripheral resistance.

The most important goal of this study is to enhance our understanding of the crucial functional relationships that determine the behavior of the systemic circulation and its underlying physiological regulatory mechanisms with minimal modeling. To the present day, much has been said about the indirect hydraulic effects of right atrial pressure (PRA) via cardiac output (CO) on arterial pressure (Pa) through the heart and pulmonary circulation or the direct regulatory effects of PRA on Pa through the cardiopulmonary baroreflex; however, very little attention has been given to the hydraulic influence that PRA exerts directly through the systemic circulation. The experimental data reported by Guyton et al. in 1957 demonstrated that steady-state PRA and the rate at which blood passes through the systemic circulation are locked in a functional relationship independent of any consequence of altered PRA on cardiac function. With this in mind, we emphasize the analytic algebraic analysis of the systemic circulation composed of arteries, veins, and its underlying physiological regulatory mechanisms of baroreflex and autoregulatory modulation of total peripheral resistance (TPR), where the behavior of the system can be analytically synthesized from an understanding of its minimal elements. As a result of this analysis, we present a novel mathematical method to determine short-term TPR fluctuations, which accounts for the entirety of observed Pa fluctuations, and propose a new cardiovascular system identification method to delineate the actual actions of the physiological mechanisms responsible for the dynamic couplings between CO, Pa, PRA, and TPR in an individual subject.

Atrial Function, Right↗

PubMed2004

Test of dynamic closed-loop baroreflex and autoregulatory control of total peripheral resistance in intact and conscious sheep.

This is the first study able to examine and delineate the actual actions of the physiological mechanisms responsible for the dynamic couplings between cardiac output (CO), arterial pressure (Pa), right atrial pressure (PRA), and total peripheral resistance (TPR) in an individual subject without altering the underlying regulatory mechanisms. Eight conscious male sheep were used, where both types of baroreceptors were independently exposed to simultaneous beat-to-beat pressure perturbations under intact closed-loop conditions while CO, Pa, PRA, and TPR were measured. We applied the cardiovascular system identification method proposed in a companion paper (4) to quantitatively characterize the dynamic closed-loop transfer relations CO-->Pa, PRA-->Pa, Pa-->TPR, and PRA-->TPR from the measured signals. To validate the dynamic properties of the estimated transfer relations, the essential parts of the linear dynamics of the model were independently and comprehensively evaluated via error model cross-validation, and the overall model's steady-state behavior was compared with a separate random effects regression approach. In addition to numerous physiological findings, we found that the cardiovascular system identification results were exceptionally consistent with the analytically derived solutions previously discussed in Ref. 4. In conclusion, this study presents the first time validation of a cardiovascular system identification method by means of experimentally acquired animal data in the intact and conscious animal and offers a set of powerful quantitative tools essential to advancing our knowledge of cardiovascular regulatory physiology.

Animals↗

PubMed2004

A novel and highly efficient synthetic route to unsymmetrical organoselenides using cesium bases.

A new and convenient one-pot method for the preparation of unsymmetrical selenides has been developed. In the presence of cesium hydroxide, molecular sieves, and DMF, benzeneselenol undergoes direct alkylation with various alkyl halides for the synthesis of alkyl phenyl selenides in moderate to excellent yields. Another method to prepare unsymmetrical organoselenides was also completed by coupling terminal alkynes with benzeneselenyl bromide. As an application, the synthesis of a selenopeptide was also accomplished. Furthermore, this methodology was extended to the synthesis of an organoselenide on solid support.

Journal Article↗

PubMed2004

Utility of implantable cardioverter defibrillator electrograms to estimate repolarization alternans preceding a tachyarrhythmic event.

Electrical alternans is a pattern of variation in the shape of the ECG waveform that appears on an every-other-beat basis. In humans, alternation in ventricular repolarization, namely, repolarization alternans, has been associated with increased vulnerability to ventricular tachycardia/ventricular fibrillation and sudden cardiac death. This study investigates the utility of implantable cardioverter defibrillator electrograms to estimate repolarization alternans preceding a tachyarrhythmic event. It is demonstrated that microvolt-level repolarization alternans is present prior to an arrhythmic event, and one can record low-amplitude-noise signals that can be used to obtain reliable estimates of repolarization alternans. This study eventually may lead to new methods that would prevent the onset of malignant tachyarrhythmias.

Algorithms↗

PubMed2004

Renal, endocrine, and cardiovascular responses to bed rest in male subjects on a constant diet.

BACKGROUND: Exposure to actual and simulated microgravity induces cardiovascular deconditioning through a variety of factors. Although the mechanisms involved remain uncertain, one involves alterations in volume-regulating systems--the hypothesis being tested in this study. To maximize our ability to detect subtle changes in the volume-regulating systems, subjects were studied on a high-average salt intake to maximally suppress these systems basally. METHODS: Fourteen healthy male subjects underwent 14-day head-down tilt bed rest (HDTB) during which a constant 200 mEq sodium, 100 mEq potassium diet was maintained. Daily 24-hour urine collection was performed; plasma renin activity, serum aldosterone, plethysmography, and cardiovascular system identification were performed during a control period (pre-HDTB) and at the end of HDTB (end HDTB). RESULTS: Sodium excretion increased initially (pre-HDTB = 182.8 +/- 10.4 mEq/total volume; early HDTB = 236.4 +/- 13.0; p = .002) and then returned to baseline values. Potassium excretion increased 4 days after the initiation of HDTB and remained elevated thereafter (pre-HDTB = 82.2 +/- 2.4/total volume; mid- to late HDTB = 89.4 +/- 2.1; p = .02). Plasma renin activity increased significantly with HDTB (pre-HDTB = 1.28 +/- 0.21 ng/mL/h; end HDTB = 1.69 +/- 0.18; p = .01), but serum aldosterone did not change. A significant decrease in autonomic responsiveness and an increase in leg compliance were observed. CONCLUSIONS: We conclude that even in the presence of a high-average salt intake diet, simulated microgravity leads to renal, cardioendocrine, and cardiovascular system alterations that likely contribute to cardiovascular deconditioning.

Adult↗

PubMed2003

Diurnal variation of aldosterone and plasma renin activity: timing relation to melatonin and cortisol and consistency after prolonged bed rest.

Exposure to prolonged bed rest is known to induce changes in the renin-angiotensin-aldosterone system (RAAS) by way of posture, sodium and potassium balance, and stress, which may have serious consequences for patients. We focused on the diurnal variation of the RAAS by investigating changes in the levels of plasma renin activity (PRA) and aldosterone; for comparison to markers of the intrinsic pacemaker and to stress, we measured melatonin and cortisol. PRA, aldosterone, melatonin, and cortisol were measured hourly in 10 normal subjects with standardized sleep patterns, posture, and diet at baseline and after 11 days of prolonged bed rest conducted under a light-dark cycle. Circadian characteristics of hormone secretion patterns were estimated by multiple harmonic regression with excellent goodness-of-fit measures. Variability in the melatonin and cortisol patterns across subjects was minimal. Even for pulsatile hormones, this technique successfully estimated the acrophase, which was the salient feature. Baseline hormone peak times started with melatonin near the middle of the sleep period, followed by PRA, then aldosterone, and then cortisol around wake time. Prolonged bed rest did not induce significant changes in any timing characteristic of the secretion patterns. Baseline and prolonged bed rest peak times for melatonin and cortisol and amplitude characteristics for all hormones were highly correlated, indicating consistency within individuals. These data provide strong evidence that prolonged bed rest of 11 days' duration does not disrupt either the timing characteristics of the RAAS or the intrinsic pacemaker.

Adult↗

PubMed2003

Medium perfusion enables engineering of compact and contractile cardiac tissue.

We hypothesized that functional constructs with physiological cell densities can be engineered in vitro by mimicking convective-diffusive oxygen transport normally present in vivo. To test this hypothesis, we designed an in vitro culture system that maintains efficient oxygen supply to the cells at all times during cell seeding and construct cultivation and characterized in detail construct metabolism, structure, and function. Neonatal rat cardiomyocytes suspended in Matrigel were cultured on collagen sponges at a high initial density (1.35 x 10(8) cells/cm(3)) for 7 days with interstitial flow of medium; constructs cultured in orbitally mixed dishes, neonatal rat ventricles, and freshly isolated cardiomyocytes served as controls. Constructs were assessed at timed intervals with respect to cell number, distribution, viability, metabolic activity, cell cycle, presence of contractile proteins (sarcomeric alpha-actin, troponin I, and tropomyosin), and contractile function in response to electrical stimulation [excitation threshold (ET), maximum capture rate (MCR), response to a gap junctional blocker]. Interstitial flow of culture medium through the central 5-mm-diameter x 1.5-mm-thick region resulted in a physiological density of viable and differentiated, aerobically metabolizing cells, whereas dish culture resulted in constructs with only a 100- to 200-microm-thick surface layer containing viable and differentiated but anaerobically metabolizing cells around an acellular interior. Perfusion resulted in significantly higher numbers of live cells, higher cell viability, and significantly more cells in the S phase compared with dish-grown constructs. In response to electrical stimulation, perfused constructs contracted synchronously, had lower ETs, and recovered their baseline function levels of ET and MCR after treatment with a gap junctional blocker; dish-grown constructs exhibited arrhythmic contractile patterns and failed to recover their baseline MCR levels.

Actins↗

PubMed2003

Effects of simulated microgravity on closed-loop cardiovascular regulation and orthostatic intolerance: analysis by means of system identification.

Microgravity-induced orthostatic intolerance (OI) continues to be a primary concern for the human space program. To test the hypothesis that exposure to simulated microgravity significantly alters autonomic nervous control and, thus, contributes to increased incidence of OI, we employed the cardiovascular system identification (CSI) technique to evaluate quantitatively parasympathetic and sympathetic regulation of heart rate (HR). The CSI method analyzes second-to-second fluctuations in noninvasively measured HR, arterial blood pressure, and instantaneous lung volume. The coupling mechanisms between these signals are characterized by using a closed-loop model. Parameters reflecting parasympathetic and sympathetic responsiveness with regard to HR regulation can be extracted from the identified coupling mechanisms. We analyzed data collected from 29 human subjects before and after 16 days of head-down-tilt bed rest (simulated microgravity). Statistical analyses showed that parasympathetic and sympathetic responsiveness was impaired by bed rest. A lower sympathetic responsiveness and a higher parasympathetic responsiveness measured before bed rest identified individuals at greater risk of OI before and after bed rest. We propose an algorithm to predict OI after bed rest from measures obtained before bed rest.

Adult↗

PubMed2003

Usefulness of microvolt T-wave alternans for prediction of ventricular tachyarrhythmic events in patients with dilated cardiomyopathy: results from a prospective observational study.

OBJECTIVES: This study was designed to evaluate the ability of microvolt-level T-wave alternans (MTWA) to identify prospectively patients with idiopathic dilated cardiomyopathy (DCM) at risk of ventricular tachyarrhythmic events and to compare its predictive accuracy with that of conventional risk stratifiers. BACKGROUND: Patients with DCM are at increased risk of sudden death from ventricular tachyarrhythmias. At present, there are no established methods of assessing this risk. METHODS: A total of 137 patients with DCM underwent risk stratification through assessment of MTWA, left ventricular ejection fraction, baroreflex sensitivity (BRS), heart rate variability, presence of nonsustained ventricular tachycardia (VT), signal-averaged electrocardiogram, and presence of intraventricular conduction defect. The study end point was either sudden death, resuscitated ventricular fibrillation, or documented hemodynamically unstable VT. RESULTS: During an average follow-up of 14 +/- 6 months, MTWA and BRS were significant univariate predictors of ventricular tachyarrhythmic events (p < 0.035 and p < 0.015, respectively). Multivariate Cox regression analysis revealed that only MTWA was a significant predictor. CONCLUSIONS: Microvolt-level T-wave alternans is a powerful independent predictor of ventricular tachyarrhythmic events in patients with DCM.

Adult↗