Does gabapentin provide benefit for patients with knee OA? A benefit-harm and cost-effectiveness analysis.

OBJECTIVE: Gabapentin can treat neuropathic pain syndromes and has increasingly been prescribed to treat nociplastic pain. Some patients with knee osteoarthritis (OA) suffer from both nociceptive and nociplastic pain. We examined the cost-effectiveness of adding gabapentin to knee OA care. METHOD: We used the Osteoarthritis Policy Model, a validated Monte Carlo simulation of knee OA, to examine the value of gabapentin in treating knee OA by comparing three strategies: 1) usual care, gabapentin sparing (UC-GS); 2) targeted gabapentin (TG), which provides gabapentin plus usual care for those who screen positive for nociplastic pain on the modified PainDETECT questionnaire (mPD-Q) and usual care only for those who screen negative; and 3) universal gabapentin plus usual care (UG). Outcomes included cumulative quality-adjusted life years (QALYs), lifetime direct medical costs, and incremental cost-effectiveness ratios (ICERs), discounted at 3% annually. We derived model inputs from published literature and national databases and varied key input parameters in sensitivity analyses. RESULTS: UC-GS dominated both gabapentin-containing strategies, as it led to lower costs and more QALYs. TG resulted in a cost increase of $689 and a cumulative QALY reduction of 0.012 QALYs. UG resulted in a further $1,868 cost increase and 0.036 QALY decrease. The results were robust to plausible changes in input parameters. The lowest TG strategy ICER of $53,000/QALY was reported when mPD-Q specificity was increased to 100% and AE rate was reduced to 0%. CONCLUSION: Incorporating gabapentin into care for patients with knee OA does not appear to offer good value.

The neuroinflammatory component of negative affect in patients with chronic pain.

Negative affect (NA) is a significant cause of disability for chronic pain patients. While little is known about the mechanism underlying pain-comorbid NA, previous studies have implicated neuroinflammation in the pathophysiology of both depression and chronic pain. Here, we tested the hypothesis that NA in pain patients is linked to elevations in the brain levels of the glial marker 18 kDa translocator protein (TSPO), and changes in functional connectivity. 25 cLBP patients (42.4 ± 13 years old; 13F, 12M) with chronic low back pain (cLBP) and 27 healthy control subjects (48.9 ± 13 years old; 14F, 13M) received an integrated (i.e., simultaneous) positron emission tomography (PET)/magnetic resonance imaging (MRI) brain scan with the second-generation TSPO ligand [11C]PBR28. The relationship between [11C]PBR28 signal and NA was assessed first with regression analyses against Beck Depression Inventory (BDI) scores in patients, and then by comparing cLBP patients with little-to-no, or mild-to-moderate depression against healthy controls. Further, the relationship between PET signal, BDI and frontolimbic functional connectivity was evaluated in patients with mediation models. PET signal was positively associated with BDI scores in patients, and significantly elevated in patients with mild-to-moderate (but not low) depression compared with controls, in anterior middle and pregenual anterior cingulate cortices (aMCC, pgACC). In the pgACC, PET signal was also associated with this region's functional connectivity to the dorsolateral PFC (pgACC-dlPFC), and mediated of the association between pgACC-dlPFC connectivity and BDI. These observations support a role for glial activation in pain-comorbid NA, identifying in neuroinflammation a potential therapeutic target for this condition.

Cost-effectiveness of duloxetine for knee OA subjects: the role of pain severity.

OBJECTIVE: Establish the impact of pain severity on the cost-effectiveness of generic duloxetine for knee osteoarthritis (OA) in the United States. DESIGN: We used a validated computer simulation of knee OA to compare usual care (UC) - intra-articular injections, opioids, and total knee replacement (TKR) - to UC preceded by duloxetine in those no longer achieving pain relief from non-steroidal anti-inflammatory drugs (NSAIDs). Outcomes included quality-adjusted life years (QALYs), lifetime medical costs, and incremental cost-effectiveness ratios (ICERs). We considered cohorts with mean ages 57-75 years and Western Ontario and McMaster Osteoarthritis Index (WOMAC) pain 25-55 (0-100, 100-worst). We derived inputs from published data. We discounted costs and benefits 3% annually. We conducted sensitivity analyses of duloxetine efficacy, duration of pain relief, toxicity, and costs. RESULTS: Among younger subjects with severe pain (WOMAC pain = 55), duloxetine led to an additional 9.6 QALYs per 1,000 subjects (ICER = $88,500/QALY). The likelihood of duloxetine being cost-effective at willingness-to-pay (WTP) thresholds of $50,000/QALY and $100,000/QALY was 40% and 54%. Offering duloxetine to older patients with severe pain led to ICERs >$150,000/QALY. Offering duloxetine to subjects with moderate pain (pain = 25) led to ICERs <$50,000/QALY, regardless of age. Among knee OA subjects with severe pain (pain = 55) who are unwilling or unable to undergo TKR, ICERs were <$50,600/QALY, regardless of age. CONCLUSIONS: Duloxetine is a cost-effective addition to knee OA UC for subjects with moderate pain or those with severe pain unable or unwilling to undergo TKR. Among younger subjects with severe pain, duloxetine is cost-effective at WTP thresholds >$88,500/QALY.

Evaluating psychosocial contributions to chronic pain outcomes.

The biopsychosocial model of pain dominates the scientific community's understanding of chronic pain. Indeed, the biopsychosocial approach describes pain and disability as a multidimensional, dynamic integration among physiological, psychological, and social factors that reciprocally influence one another. In this article, we review two categories of studies that evaluate the contributions of psychosocial factors to the experience of chronic pain. First, we consider general psychosocial variables including distress, trauma, and interpersonal factors. Additionally, we discuss pain-specific psychosocial variables including catastrophizing, expectations, and pain-related coping. Together, we present a diverse array of psychological, social, and contextual factors and highlight the need to consider their roles in the development, maintenance, and treatment of chronic pain conditions.

Changes in Pain Sensitivity and Pain Modulation During Oral Opioid Treatment: The Impact of Negative Affect.

OBJECTIVE: Opioids are frequently prescribed for chronic low back pain (CLBP), but there are broad individual differences in the benefits and risks of opioid therapy, including the development opioid-induced hyperalgesia. This study examined quantitative sensory testing (QST) data among a group of CLBP patients undergoing sustained oral opioid treatment. We investigated whether individual differences in psychological characteristics were related to opioid-induced changes in pain perception and pain modulation. DESIGN: The six-month, open-label trial evaluated patients with low to high levels of negative affect (e.g., symptoms of distress, depression and anxiety); participants underwent QST at baseline (prior to initiating treatment) and during oral opioid treatment. SETTING: A chronic pain management center. PATIENTS: The 31 study participants had chronic discogenic back pain, with a pain intensity rating >3/10. Participants were divided into groups with high vs. low levels of Negative Affect (NA). RESULTS: In the previously-published manuscript describing the clinical outcomes of the trial, high NA patients achieved only about half of the analgesic effect observed in the low NA group (Wasan AD, Michna E, Edwards RR, et al. Psychiatric comorbidity is associated prospectively with diminished opioid analgesia and increased opioid misuse in patients with chronic low back pain. Anesthesiology 2015;123:861-72). The QST findings reported here suggested that tolerance to experimental (cold pressor) pain and conditioned pain modulation tended to decrease in the high NA group over the course of opioid treatment, while temporal summation of mechanical pain declined in the low NA group. CONCLUSIONS: These results reveal that while the low NA group seemed to exhibit a generally adaptive, analgesic pattern of changes during opioid management, the high NA group showed a pattern more consistent with opioid-induced hyperalgesic processes. A greater susceptibility to hyperalgesia-promoting changes in pain modulation among patients with high levels of distress may contribute to a lower degree of benefit from opioid treatment in high NA patients.

Does catastrophic thinking enhance oesophageal pain sensitivity? An experimental investigation.

BACKGROUND: Gastro-oesophageal reflux disease (GORD) is a major health problem that is frequently accompanied by debilitating oesophageal pain symptoms. OBJECTIVES: The first objective of the study was to examine the association between catastrophizing and oesophageal pain sensitivity. The second objective was to examine whether catastrophizing was associated with the magnitude of acid-induced oesophageal sensitization. METHODS: Twenty-five healthy volunteers (median age: 24.0 years; range: 22-31) were recruited and were asked to complete the Pain Catastrophizing Scale (PCS). During two subsequent study visits, mechanical, thermal, and electrical pain sensitivity in the oesophagus was assessed before and after inducing oesophageal sensitization using a 30-min intraluminal oesophageal acid perfusion procedure. RESULTS: Analyses were conducted based on data averaged across the two study visits. At baseline, catastrophizing was significantly associated with mechanical (r = -0.42, p < 0.05) and electrical (r = -0.60, p < 0.01) pain thresholds. After acid perfusion, catastrophizing was also significantly associated with mechanical (r = -0.58, p < 0.01) and electrical (r = -0.50, p < 0.05) pain thresholds. Catastrophizing was not significantly associated with thermal pain thresholds. Subsequent analyses revealed that catastrophizing was not significantly associated with the magnitude of acid-induced oesophageal sensitization. CONCLUSION: Taken together, findings from the present study suggest that catastrophic thinking exerts an influence on oesophageal pain sensitivity, but not necessarily on the magnitude of acid-induced oesophageal sensitization. WHAT DOES THIS STUDY ADD?: Catastrophizing is associated with heightened pain sensitivity in the oesophagus. This was substantiated by assessing responses to noxious stimulation of the oesophagus using an experimental paradigm mimicking features and symptoms experienced by patients with gastro-oesophageal reflux disease (GORD).

Catastrophic thinking and increased risk for prescription opioid misuse in patients with chronic pain.

BACKGROUND: As a consequence of the substantial rise in the prescription of opioids for the treatment of chronic noncancer pain, greater attention has been paid to the factors that may be associated with an increased risk for prescription opioid misuse. Recently, a growing number of studies have shown that patients with high levels of catastrophizing are at increased risk for prescription opioid misuse. OBJECTIVE: The primary objective of this study was to examine the variables that might underlie the association between catastrophizing and risk for prescription opioid misuse in patients with chronic pain. METHODS: Patients with chronic musculoskeletal pain (n=115) were asked to complete the SOAPP-R, a validated self-report questionnaire designed to identify patients at risk for prescription opioid misuse. Patients were also asked to complete self-report measures of pain intensity, catastrophizing, anxiety, and depression. RESULTS: Consistent with previous research, we found that catastrophizing was associated with an increased risk for prescription opioid misuse. Results also revealed that the association between catastrophizing and risk for opioid misuse was partially mediated by patients' levels of anxiety. Follow-up analyses, however, indicated that catastrophizing remained a significant 'unique' predictor of risk for opioid misuse even when controlling for patients' levels of pain severity, anxiety and depressive symptoms. DISCUSSION: Discussion addresses the factors that might place patients with high levels of catastrophizing at increased risk for prescription opioid misuse. The implications of our findings for the management of patients considered for opioid therapy are also discussed.

The association of the cortisol awakening response with experimental pain ratings.

Cortisol is a key stress hormone that is implicated in a variety of physiological responses. Attenuated Cortisol Awakening Response (CAR) is associated with many negative health outcomes, but little research has investigated CAR and pain. The current study examines the association of CAR with experimental acute-pain ratings in healthy men and women. Attenuated CAR was related to greater pain intensity and unpleasantness ratings. Future research should examine this association across various pain populations.

Sleep continuity and architecture: associations with pain-inhibitory processes in patients with temporomandibular joint disorder.

Recent research suggests bi-directional interactions between the experience of pain and the process of sleep; pain interferes with the ability to obtain sleep, and disrupted sleep contributes to enhanced pain perception. Our group recently reported, in a controlled experimental study, that sleep fragmentation among healthy adults resulted in subsequent decrements in endogenous pain inhibition. The present report follows up that observation by extending this line of research to a sample of patients experiencing persistent pain. Patients with chronic temporomandibular joint disorder (TMD) pain were studied using polysomnography and psychophysical evaluation of pain responses. We assessed whether individual differences in sleep continuity and/or architecture were related to diffuse noxious inhibitory controls (DNIC), a measure of central nervous system pain inhibition. Among 53 TMD patients, higher sleep efficiency and longer total sleep time were positively associated with better functioning of DNIC (r=0.42-0.44, p<0.01; ps<0.05 for the multivariate analyses). These results suggest the possibility that disrupted sleep may serve as a risk factor for inadequate pain-inhibitory processing and hint that aggressive efforts to treat sleep disturbance early in the course of a pain condition might be beneficial in reducing the severity or impact of clinical pain.

Ethnic differences in pain tolerance: clinical implications in a chronic pain population.

OBJECTIVE: Although numerous studies have independently examined ethnic differences in clinical and experimental pain, few have investigated differences in both sensitivity to controlled noxious stimuli and clinical pain reports in the same sample. The present experiment examined the effects of ethnicity (African American vs. white) on experimental pain tolerance and adjustment to chronic pain. METHODS: Three hundred thirty-seven (68 African American and 269 white) patients with chronic pain referred to a multidisciplinary treatment center participated in the study. In addition to completing a number of standardized questionnaires assessing adjustment to chronic pain, participants underwent a submaximal effort tourniquet procedure. This experimental pain procedure yields a measure of tolerance for a controlled noxious stimulus (ie, arm ischemia). RESULTS: African American subjects reported higher levels of clinical pain as well as greater pain-related disability than white participants. In addition, substantial group differences were observed for ischemic pain tolerance, with African Americans demonstrating less tolerance than whites. Correlational analyses revealed a small but significant inverse relationship between ischemic pain tolerance and the reported severity of chronic pain. CONCLUSIONS: Collectively these findings support previous research revealing ethnic differences in responses to both clinical and experimental pain. Moreover, the present results suggest that enhanced sensitivity to noxious stimuli on the part of African Americans may be associated with ethnic differences in reported clinical pain, although the magnitude of ethnic differences was much greater for ischemic pain tolerance than for clinical pain measures.

The association of hormone replacement therapy with experimental pain responses in postmenopausal women.

Considerable experimental research suggests that ovarian hormones can influence pain perception, and recent epidemiologic and clinical research suggests that exogenous hormone use may influence the prevalence and severity of clinical pain among women. However, to date no studies have examined the influence of hormone replacement therapy (HRT) on experimental pain responses and recent pain complaints among postmenopausal women. In this study, self-reported recent pain and general health were obtained, and thermal pain responses were assessed in three groups of healthy older adults: (1) women on HRT, (2) women not on HRT (No-HRT), and (3) men. Results indicated no group differences in recent pain complaints or self-reported health, but differences emerged for measures of thermal pain perception. Specifically, HRT women showed lower pain thresholds and tolerances than No-HRT women and men, and the latter two groups did not differ from each other. The potential explanations and limitations of the observed findings are discussed.

Age-associated differences in responses to noxious stimuli.

BACKGROUND: Although population-based studies typically report age-associated increases in clinical pain, laboratory-based pain assessment procedures generally indicate diminished pain sensitivity with age. The majority of these studies have utilized noxious thermal stimuli as the method of pain induction. However, other pain assessment methodologies, including ischemic pain induction, may have a more meaningful relationship to clinical pain. The present study examined the effects of age on responses to a variety of experimental noxious stimuli. In addition, relationships between cardiovascular measures and pain responses were investigated in both older and younger subjects. METHODS: Responses to thermal, mechanical, and ischemic pain were assessed in 34 younger (mean age, 22.4 years) and 34 older adults (mean age, 62.2 years). In addition, relationships between resting blood pressure and pain responses were assessed separately for older and younger participants. RESULTS: Although group differences in thermal and mechanical pain responses did not achieve statistical significance, older individuals demonstrated substantially lower ischemic pain thresholds and tolerances assessed via the modified submaximal effort tourniquet procedure (ps < .01). Overall, higher resting arterial blood pressures were associated with increased pain thresholds and tolerances, although relationships between blood pressure and ischemic pain variables were evident only for the younger group. CONCLUSIONS: These findings indicate that age-related differences in responses to experimental noxious stimuli vary as a function of the pain induction task, with older individuals showing greater sensitivity to clinically relevant stimuli. In addition, the absence of a relationship between blood pressure and ischemic pain responses in older adults may suggest potential functional decrements in at least one endogenous pain-modulatory system.

Effects of age on temporal summation and habituation of thermal pain: clinical relevance in healthy older and younger adults.

Although the effects of aging on the experience of clinical pain seem relatively clear, investigations of age-related changes in pain perception using laboratory-based pain assessment procedures have yielded contradictory findings. One potential source of variability in this literature is the type of experimental noxious stimulus that is used. Although thermal pain thresholds are the most commonly reported measure of pain sensitivity, use of suprathreshold stimuli in pain assessment procedures may yield additional, more clinically relevant information concerning the effects of aging on the experience of pain. The present study examined the effects of age on temporal summation of both the intensity and unpleasantness of thermal pain at multiple stimulus temperatures. Specifically, responses to repetitive thermal stimuli delivered to the volar forearm at 47 degrees C, 50 degrees C, and 53 degrees C were assessed in 34 younger (mean age, 22.4 years) and 34 older (mean age, 62.2 years) healthy volunteers. Results suggested that for the 47 degrees C and 50 degrees C stimulus trains, older adults exhibited higher ratings of the intensity and unpleasantness of thermal pain and enhanced temporal summation of thermal pain relative to younger adults. Moreover, thermal pain sensitivity was inversely related to perceptions of general health and to reports of recent clinical pain among younger, but not older, subjects. Collectively these findings may indicate small, although potentially significant, age-related alterations in the plasticity of the central nervous system or endogenous pain-modulatory capacities.

Sex-dependent effects of reported familial pain history on recent pain complaints and experimental pain responses.

Previous research has demonstrated that both sex and familial pain history can influence clinical pain, and sex is known to affect experimental pain responses. However, the potential interactive effects of sex and family history on pain-related symptoms and experimental pain have not been investigated. This experiment examined recent pain complaints and laboratory pain responses as a function of sex and reported family history of pain in 212 (122 female, 90 male) young adults. All subjects completed questionnaires regarding family history of pain, recent pain experiences, and psychological measures of hypervigilance. Then, warmth detection thresholds, heat pain thresholds and heat pain tolerances were determined. Results revealed sex-dependent influences of familial pain history on recent pain complaints and experimental pain responses. Specifically, a positive family history of pain was associated with increased reports of pain over the previous month and poorer general health as well as enhanced sensitivity to thermal stimuli among females but not males. Higher levels of hypervigilance accounted for some of the family history effects on recent pain complaints but not experimental pain measures. Potential mechanisms underlying these effects of family history among females are discussed.

Effects of gender and acute dental pain on thermal pain responses.

OBJECTIVE: Considerable research suggests that females exhibit greater sensitivity to laboratory pain procedures than do males; however, whether the presence of acute clinical pain influences this sex difference in pain sensitivity has not been investigated. The present experiment investigated the effects of sex and acute dental pain on laboratory pain responses. DESIGN: Thermal pain onset and tolerance were determined in 46 dental patients (15 male, 31 female) experiencing pain due to acute irreversible pulpitis and in 33 healthy controls (13 male, 20 female). In addition, measures of mood and coping were obtained in all participants. All subjects participated in two experimental sessions. The first session took place immediately before the patients underwent endodontic treatment for relief of pulpal pain. The second session took place approximately 1-2 weeks later, when pulpitis patients were pain free after treatment. During each session, thermal pain onset and tolerance were assessed with a 1-cm2 contact thermode applied to the right volar forearm using an ascending method of limits. RESULTS: During both sessions, thermal pain onset and tolerance were lower in control females than in control males; however, male and female pulpitis patients did not differ in their thermal pain responses during either session. Pulpitis patients also showed greater affective distress than controls. CONCLUSIONS: These data suggest that the sex difference in thermal pain sensitivity frequently reported in pain-free subjects appears to be absent in patients presenting with acute dental pain. However, this effect cannot be explained solely based on the presence of clinical pain because the effect on pain threshold and tolerance persisted into session 2, when pulpitis patients were pain free. Potential explanations for these results are discussed.

Ethnic differences in thermal pain responses.

OBJECTIVE: Although numerous studies have reported ethnic differences in the prevalence and severity of clinical pain, little is known about how these differences affect the perception of experimental pain. The present experiment examined the effects of ethnicity (African American vs. white) on thermal pain responses in a healthy undergraduate population. METHODS: Thirty white subjects (16 women and 14 men) and 18 African Americans (10 women and 8 men) participated in the study. Thermal testing included evaluation of the following: warmth thresholds, thermal pain thresholds, thermal pain tolerances, and magnitude estimates of both the intensity and unpleasantness of thermal pain (at 46 degrees, 47 degrees, 48 degrees, and 49 degrees C). RESULTS: Although no group differences emerged for warmth thresholds, thermal pain thresholds, or pain intensity ratings, African Americans demonstrated lower thermal pain tolerances than whites. In addition, African Americans had smaller slopes and larger intercepts than whites for ratings of pain unpleasantness. Additional analyses suggested that these findings were a consequence of group differences in thermal pain unpleasantness ratings at the lowest temperatures assessed (46 degrees and 47 degrees C); at these temperatures, African Americans rated the stimuli as more unpleasant than whites. Finally, group differences in thermal pain tolerance and thermal pain unpleasantness ratings seemed to partially account for greater self-reported daily pain symptoms among African Americans. CONCLUSIONS: Collectively, these findings seem to suggest ethnic differences in the perception of the affective-motivational dimension of thermal pain.

Mass spectrometric inverse gas chromatography: investigation of polymeric phase transitions.

An improved inverse gas chromatographic method involving the use of a mass-specific detector for the determination of the glass transition temperature of polymeric materials is described. The new method allows the use of several probe solutes simultaneously with an automated, closed-loop injector and stepped temperature programming. The result is a single continuous chromatogram for each probe solute over a range of temperatures encompassing the glass transition temperature, T(g). Several different methods for the exact determination of T(g) from the chromatogram were investigated, including the classical van't Hoff-type plots with retention volumes calculated from both the peak maximum and first moment values of the elution peaks. Two new methods are also proposed for the evaluation of T(g) from either the temperature dependence of the second moments of the elution peaks for probe solutes or simple inspection of the variation of elution peak height (width) with temperature. All four methods for the determination of T(g) are evaluated with three probe solutes and four different polymers, viz., poly(methyl methacrylate), poly(ethylene terephthalate), polycarbonate, and two batches of polystyrene with different molecular weights and T(g) values. Three phenomenological models were used to interpret the chromatographic retention mechanisms of the solute probes in glassy and rubbery polymers. These are (i) the classical adsorption/absorption model for glass and rubber polymers, (ii) the single absorption mechanism model, and (iii) a dual-mode model previously used to explain the sorption of gases, such as CO(2), in glassy polymers. It is concluded that no single approach is adequate to interpret the experimental results for all of the systems, although each model is adequate for some individual solute/polymer combinations.

The effects of aging on information-processing channels in the sense of touch: III. Differential sensitivity to changes in stimulus intensity.

Detection thresholds and difference limens were measured for 16 subjects ranging from 19 to 91 years of age. The stimuli were 250-Hz bursts of vibration applied through a 3.0-cm2 contactor to the thenar eminence of the right hand. Detection thresholds were higher in older than in younger subjects, as were the absolute values of difference limens. When the difference limen was expressed in relative terms as the proportion by which two stimuli had to differ in amplitude to be discriminated (delta alpha/alpha), discriminative capacities were unaffected by aging except for stimuli slightly above the detection threshold, in which case the limens of older subjects were significantly higher than those of younger subjects. The results are consistent with the hypothesis that elevations in the detection thresholds of older subjects are the results of reduced afferent input to central brain centers that, with regard to their capacity to detect the presence of threshold-level stimuli and to discriminate differences among suprathreshold stimuli, are relatively unaffected by aging.

Use of the signal-averaged ECG to predict maximum ventricular tachycardia rate.

Rapid ventricular tachycardia is poorly tolerated, and estimation of maximum ventricular tachycardia rate prior to programmed ventricular stimulation is difficult. A method to estimate maximum ventricular tachycardia rate using late potential duration from the signal-averaged ECG and ventricular functional refractory period is described. Late potentials recorded in patients with ventricular tachycardia may represent delayed conduction through arrhythmogenic ventricular myocardium. This delay may be rate limiting in determining the minimum cycle length of reentrant ventricular tachycardia originating from these areas. Using the ratio of ventricular activation time (VAT), which equals QRS plus late potential duration, to unfiltered QRS duration (QRS) as estimate of this delay, the following relationship is proposed: Minimum ventricular tachycardia cycle length = (FRP 400 - 12.5 ms) (VAT/QRS). Twenty patients with late potentials who had sustained, monomorphic ventricular tachycardia at programmed stimulation were evaluated. Predicted cycle lengths ranged from 326 to 214 ms. Predicted and observed cycle lengths were significantly correlated (r = 0.91, SEE = 11.9 ms, p less than 0.0005), with predicted and observed cycle lengths differing by less than 3.5%. Predicted cycle lengths were more accurate than cycle lengths estimated using FRP alone (p less than 0.01). Accurate prediction of minimum ventricular tachycardia cycle length using this relationship suggests that late potential duration is proportional to the conduction delay occurring in arrhythmogenic ventricular myocardium.