Cardiac Function – Page 6 – American ME and CFS Society

Prevalence of abnormal cardiac wall motion in the cardiomyopathy associated with incomplete multiplication of Epstein-barr Virus and/or cytomegalovirus in patients with chronic fatigue syndrome

Abstract:

We reported unique incomplete herpesvirus (Epstein-Barr Virus (EBV) and/or nonstructural (HCMV) cytomegalovirus) multiplication in 2 distinct subsets of CFS patients. The CFS subsets were identified by: a) presence of IgM serum antibodies to HCMV nonstructural gene products p52 and CM2 (UL44 and UL57), and/or b) IgM serum antibodies to Epstein-Barr virus viral capsid antigen (EBV, VCA IgM).

Diagnostic IgM serum antibodies were found in two independent blinded studies involving 49 CFS patients, but the same antibodies were absent in 170 control patients (p<0.05). Abnormal 24 Hr-electrocardiographic monitoring, tachycardias at rest and, in severe chronic cases, abnormal cardiac wall motion (ACWM) were seen in these same CFS patients.

We now report a prospective consecutive case control study from 1987–1999 of cardiac dynamics as measured by radionuclide ventriculography in 98 CFS patients from 1987–1999. Controls were patients with various malignancies who were evaluated in protocols requiring radionuclide ventriculography before initiation of cardiotoxic chemotherapeutic agents.

The prevalence of abnormal cardiac wall motion (ACWM) at rest in CFS patients was 10 out of 87 patients (11.5%). With stress exercise, 21 patients (24.1%) demonstrated ACWM. Cardiac biopsies in 3 of these CFS patients with ACWM showed a cardiomyopathy. Among the controls, ACWM at rest was present in 4 out of 191 patients (2%) (p=0.0018). A progressive cardiomyopathy caused by incomplete virus multiplication of EBV and/or HCMV in CFS patients is present.

Source: Lerner AM, Dworkin HJ, Sayyed T, Chang CH, Fitzgerald JT, Beqaj S, Deeter RG, Goldstein J, Gottipolu P, O’Neill W. Prevalence of abnormal cardiac wall motion in the cardiomyopathy associated with incomplete multiplication of Epstein-barr Virus and/or cytomegalovirus in patients with chronic fatigue syndrome. In Vivo. 2004 Jul-Aug;18(4):417-24. http://iv.iiarjournals.org/content/18/4/417.long (Full article)

Use of time-frequency analysis to investigate temporal patterns of cardiac autonomic response during head-up tilt in chronic fatigue syndrome

Abstract:

Although a number of studies have reported alterations in cardiac autonomic nervous system function in chronic fatigue syndrome (CFS), the results are not consistent across studies. Reasons for these discrepancies include (1) the use of a heterogeneous patient sample that included those with orthostatic postural tachycardia (POTS), a condition with an autonomic changes, and (2) the use of frequency domain techniques which require a stationary signal and averaging data across relatively long epochs.

To deal with these shortcomings, we used the smoothed pseudo-Wigner-Ville transform (SPWVT) to analyze heart rate variability (HRV) and blood pressure variability (BPV) during head-up tilt (HUT) by separating CFS patients into those with and without POTS. SPWVT has the advantage of providing instantaneous information about autonomic function under nonstable physiological conditions. We studied 18 CFS patients without POTS, eight CFS patients with POTS and 25 sedentary healthy controls during supine rest and during the first 10 min after HUT.

While we found significant effects of postural change in both groups for all autonomic variables, there were significant group x time interactions between CFS without POTS and controls for only instant center frequency (ICF) within the low frequency region both from HRV (p=0.02) and from BPV (p=0.01). Although the physiological meaning of ICF still remains unknown, the data suggest that even CFS patients without POTS may have a subtle underlying disturbance in autonomic function.

Source: Yoshiuchi K, Quigley KS, Ohashi K, Yamamoto Y, Natelson BH. Use of time-frequency analysis to investigate temporal patterns of cardiac autonomic response during head-up tilt in chronic fatigue syndrome. Auton Neurosci. 2004 Jun 30;113(1-2):55-62. http://www.ncbi.nlm.nih.gov/pubmed/15296795

Plasma endothelin-1 levels in chronic fatigue syndrome

Comment on: Increased plasma endothelin-1 levels in fibromyalgia syndrome. [Rheumatology (Oxford). 2003]

SIR, We read with interest the report by Pache et al. [1] showing increased endothelin-1 (ET-1) levels in patients with a diagnosis of fibromyalgia syndrome (FMS) and their conclusion that elevated ET-1 levels might contribute to some of the apparent vascular disturbances that characterize the syndrome. Pache et al. also point to the overlap between the clinical presentation of FMS and other ‘stress-associated disorders including chronic fatigue syndrome (CFS) and depression’. Whether FMS or CFS is stress-induced is a contentious issue in itself, but of equal concern is the view that FMS should be considered to be part of the spectrum of illness under the generic name ‘chronic fatigue syndrome’. Clearly, the symptoms of FMS and CFS have much in common [2, 3] but it has been said that FMS represents an additional burden of suffering among those with CFS [4], those patients meeting the case definitions for both FMS and CFS having a worse course, worse overall health and greater disease impact [2]. Furthermore, while many FMS patients experience fatigue, it has been estimated that only about one-fifth fulfil the specific criteria required for CFS [5]. Clinical similarities apart, there are biological differences between the two; for example, cerebrospinal fluid levels of substance P are elevated in FMS but not in CFS patients [6], and cardiovascular responses to postural challenge are characteristic of many CFS patients but are not apparent in those with FMS [7].

You can read the rest of this comment here: http://rheumatology.oxfordjournals.org/content/43/2/252.long

Source: Kennedy G, Spence V, Khan F, Belch JJ. Plasma endothelin-1 levels in chronic fatigue syndrome. Rheumatology (Oxford). 2004 Feb;43(2):252-3; author reply 253-4. http://rheumatology.oxfordjournals.org/content/43/2/252.long (Full article)

Prolonged acetylcholine-induced vasodilatation in the peripheral microcirculation of patients with chronic fatigue syndrome

Abstract:

Although the aetiology of chronic fatigue syndrome (CFS) is unknown, there have been a number of reports of blood flow abnormalities within the cerebral circulation and systemic blood pressure defects manifesting as orthostatic intolerance. Neither of these phenomena has been explained adequately, but recent reports have linked cerebral hypoperfusion to abnormalities in cholinergic metabolism.

Our group has previously reported enhanced skin vasodilatation in response to cumulative doses of transdermally applied acetylcholine (ACh), implying an alteration of peripheral cholinergic function. To investigate this further, we studied the time course of ACh-induced vasodilatation following a single dose of ACh in 30 patients with CFS and 30 age- and gender-matched healthy control subjects.

No differences in peak blood flow was seen between patients and controls, but the time taken for the ACh response to recover to baseline was significantly longer in the CFS patients than in control subjects. The time taken to decay to 75% of the peak response in patients and controls was 13.7 +/- 11.3 versus 8.9 +/- 3.7 min (P = 0.03), respectively, and time taken to decay to 50% of the peak response was 24.5 +/- 18.8 versus 15.1 +/- 8.9 min (P = 0.03), respectively.

Prolongation of ACh-induced vasodilatation is suggestive of a disturbance to cholinergic pathways, perhaps within the vascular endothelium of patients with CFS, and might be related to some of the unusual vascular symptoms, such as hypotension and orthostatic intolerance, which are characteristic of the condition.

Source: Khan F, Spence V, Kennedy G, Belch JJ. Prolonged acetylcholine-induced vasodilatation in the peripheral microcirculation of patients with chronic fatigue syndrome. Clin Physiol Funct Imaging. 2003 Sep;23(5):282-5. http://www.ncbi.nlm.nih.gov/pubmed/12950326

Abnormal impedance cardiography predicts symptom severity in chronic fatigue syndrome

Abstract:

BACKGROUND: Findings indicative of a problem with circulation have been reported in patients with chronic fatigue syndrome (CFS). We examined this possibility by measuring the patient’s cardiac output and assessing its relation to presenting symptoms.

METHODS: Impedance cardiography and symptom data were collected from 38 patients with CFS grouped into cases with severe (n = 18) and less severe (n = 20) illness and compared with those from 27 matched, sedentary control subjects.

RESULTS: The patients with severe CFS had significantly lower stroke volume and cardiac output than the controls and less ill patients. Postexertional fatigue and flu-like symptoms of infection differentiated the patients with severe CFS from those with less severe CFS (88.5% concordance) and were predictive (R2 = 0.46, P < 0.0002) of lower cardiac output. In contrast, neuropsychiatric symptoms showed no specific association with cardiac output.

CONCLUSIONS: These results provide a preliminary indication of reduced circulation in patients with severe CFS. Further research is needed to confirm this finding and to define its clinical implications and pathogenetic mechanisms.

Source: Peckerman A, LaManca JJ, Dahl KA, Chemitiganti R, Qureishi B, Natelson BH. Abnormal impedance cardiography predicts symptom severity in chronic fatigue syndrome. Am J Med Sci. 2003 Aug;326(2):55-60. http://www.ncbi.nlm.nih.gov/pubmed/12920435

A six-month trial of valacyclovir in the Epstein-Barr virus subset of chronic fatigue syndrome: improvement in left ventricular function

Abstract:

This study was designed to determine safety and efficacy of a 6-month trial of valacyclovir in single-virus Epstein-Barr virus (EBV) persistent infection. Phase I of this study used four specific criteria to define a subset of patients with chronic fatigue syndrome (CFS). In the second phase, myocardial dynamics were measured by MUGA rest/stress radionuclide ventriculographic (RVG) examinations pre- and posttreatment with valacyclovir.

In phase I, a trial was performed in 19 consecutive CFS patients with the following diagnostic conditions: patients met criteria for diagnosis of CFS; they had had CFS for less than 1 year. They demonstrated repetitively abnormal oscillating T waves (ischemic or flat) at 24-h Holter monitoring; and they had elevated serum IgM antibody titers to EBV viral capsid antigen and/or total diffuse early antigen as measured by the enzyme-linked immunosorbent assay method.

The treatment group comprised 10 CFS patients with no serum antibodies to human cytomegalovirus, but the control group (nine CFS patients) had, additionally, high titers of serum antibodies (IgG) to conformational structural antigens of human cytomegalovirus. Both the parallel treatment and control CFS groups received valacyclovir 1.0-1.5 gm q.6.h. for 6 months.

This valacyclovir dose achieved serum acyclovir C(max) of > 7 microm and high antiviral activity versus EBV (IC(50) of 4.4-13.3 m). In phase II, six additional CFS patients met the same four criteria as the 19 CFS patients in phase I. They had, however, been ill for a mean of 55.8 months. Thus, 25 CFS patients comprise this study.

The studies were carried out at a single outpatient practice in Birmingham, MI, U.S.A. Before initiating valacyclovir, and after 6 months of treatment, clinical and laboratory observations were made. The CFS Energy Index point score (Table I) was used to record each CFS patient’s functional capacity at baseline and after 1, 3 and 6 months of valacyclovir. Energy Index point scores, as well as EBV and human cytomegalovirus serum antibody titers were assessed.

In the second phase, left ventricular dynamics were repeated after 6 months of treatment with valacyclovir. We concluded that the 16 CFS patients (included in both phases of this study) with EBV-persistent infection (EBV single-virus subset) are improved after 6 months of continuous pharmacokinetic dosing with valacyclovir. Nine CFS patients with EBV/human cytomegalovirus co-infection did not benefit from 6 months of similar treatment. Valacyclovir is not an effective anti-human cytomegalovirus antiviral drug. Unimproved CFS patients with co-infections EBV and human cytomegalovirus may require combined treatment with valacyclovir and another drug more active against human cytomegalovirus.

This preliminary trial, with a small number of patients, may be critical to an appropriately designed larger, double-blind, placebo-controlled trial.

Source: Lerner AM, Beqaj SH, Deeter RG, Dworkin HJ, Zervos M, Chang CH, Fitzgerald JT, Goldstein J, O’Neill W. A six-month trial of valacyclovir in the Epstein-Barr virus subset of chronic fatigue syndrome: improvement in left ventricular function. Drugs Today (Barc). 2002 Aug;38(8):549-61. http://www.ncbi.nlm.nih.gov/pubmed/12582420

Assessment of cardiovascular reactivity by fractal and recurrence quantification analysis of heart rate and pulse transit time

Abstract:

Methods used for the assessment of cardiovascular reactivity are flawed by nonlinear dynamics of the cardiovascular responses to stimuli. In an attempt to address this issue, we utilized a short postural challenge, recorded beat-to-beat heart rate (HR) and pulse transit time (PTT), assessed the data by fractal and recurrence quantification analysis, and processed the obtained variables by multivariate statistics. A 10-min supine phase of the head-up tilt test was followed by recording 600 cardiac cycles on tilt, that is, 5-10 min.

Three groups of patients were studied, each including 20 subjects matched for age and gender–healthy subjects, patients with essential hypertension (HT), and patients with chronic fatigue syndrome (CFS). The latter group was studied on account of the well-known dysautonomia of CFS patients, which served as contrast against the cardiovascular reactivity of the healthy population. A total of 52 variables of the HR and PTT were determined in each subject.

The multivariate model identified the best predictors for the assessment of reactivity of healthy subjects vs CFS. Based on these predictors, the “Fractal & Recurrence Analysis-based Score” (FRAS) was calculated: FRAS=76.2+0.04*HR-supine-DET -12.9*HR-tilt-R/L -0.31*HR-tilt-s.d. -19.27*PTT-tilt-R/L -9.42*PTT-tilt-WAVE. The median values and IQR of FRAS in the groups were: healthy=-1.85 (IQR 1.89), hypertensives=+0.52 (IQR 5.78), and CFS=-24.2 (5.34) (HT vs healthy subjects: P=0.0036; HT vs CFS: P<0.0001). Since the FRAS differed significantly between the three groups, it appears likely that the FRAS may recognize phenotypes of cardiovascular reactivity.

Source: Naschitz JE, Rosner I, Shaviv N, Khorshidi I, Sundick S, Isseroff H, Fields M, Priselac RM, Yeshurun D, Sabo E.Erratum in: J Hum Hypertens. 2003 Aug;17(8):585. Itzhak, R [corrected to Rosner, I]. Assessment of cardiovascular reactivity by fractal and recurrence quantification analysis of heart rate and pulse transit time. J Hum Hypertens. 2003 Feb;17(2):111-8. http://www.ncbi.nlm.nih.gov/pubmed/12574789

A measure of heart rate variability is sensitive to orthostatic challenge in women with chronic fatigue syndrome

Abstract:

The use of symptoms generated by head up tilt (HUT) is not a useful tool in identifying chronic fatigue syndrome (CFS). We investigated whether heart rate variability (HRV) assessed early during HUT might be useful. A sample of 46 female subjects (24 with CFS and 22 sedentary, age-matched healthy controls; CON) who had exhibited no difference in time to syncope during tilt was examined for HRV responses to 10 min of 70 degrees HUT after 5 min of baseline in the supine position. HRV data were analyzed by the method of coarse graining spectral analysis. Variables compared between groups included mean and standard deviation (SD(RRI)) of RR intervals (RRI), amplitudes of low- (A(LF); 0.04-0.15 Hz) and high-frequency (A(HF); >0.15 Hz) harmonic as well as aperiodic, fractal (A(FR); 1/f(beta)) spectral components, the spectral exponent beta, and the difference in these values between baseline and HUT for each subject.

In the supine baseline, only mean RRI was significantly (P < 0.01) lower in CFS than in CON. During HUT, however, mean RRI (P < 0.01), SD(RRI) (P < 0.01), A(HF) (P < 0.05), and A(FR) (P < 0.01) were significantly lower in CFS than in CON. When the difference in values between baseline and HUT for each subject was examined, only the difference for A(FR) (deltaA(FR)) was significantly (P < 0.01) lower in CFS than in CON, suggesting that A(FR)is a disease-specific response of HRV to HUT. When a cut-off level was set to deltaA(FR) = -2.7 msec, the sensitivity and the specificity in differentiating CFS from controls were 90% and 72%, respectively. The data suggest that a decrease in aperiodic fractal component of HRV in response to HUT can be used to differentiate patients with CFS from CON.

Source: Yamamoto Y, LaManca JJ, Natelson BH. A measure of heart rate variability is sensitive to orthostatic challenge in women with chronic fatigue syndrome. Exp Biol Med (Maywood). 2003 Feb;228(2):167-74. http://www.ncbi.nlm.nih.gov/pubmed/12563023

Hemodynamics instability score in chronic fatigue syndrome and in non-chronic fatigue syndrome

Erratum in: Semin Arthritis Rheum. 2003 Apr;32(5):343. Madelain, Fields [corrected to Fields, Madeline]; Hillel, Isseroff [corrected to Isseroff, Hillel].

Abstract:

OBJECTIVE: In studying patients with chronic fatigue syndrome (CFS) we developed a method that confers numerical expression to the degree of blood pressure and heart rate lability, ie, the ‘hemodynamic instability score’ (HIS). The HIS in CFS patients differed significantly from healthy subjects. The present investigation compares the HIS in CFS, non-CFS chronic fatigue and patients with recurrent syncope.

METHODS: Patients with CFS (n = 21), non-CFS chronic fatigue (n = 24), syncope of unknown cause (n = 44), and their age and sex-matched healthy controls (n = 21) were evaluated with a standardized head-up tilt test (HUTT). Abnormal reactions (endpoints) on HUTT were classified ‘clinical outcomes’ (cardioinhibitory or vasodepressor reaction, orthostatic hypotension, postural tachycardia syndrome) and ‘HIS endpoint’, i.e. HIS >-0.98.

RESULTS: The highest incidence of endpoints was noted in patients with CFS (79%), followed by patients with syncope of unknown cause (46%), non-CFS chronic fatigue (35%), and healthy subjects (14%). Presyncope or syncope during tilt occurred in 38% of CFS patients, 21% of patients with non-CFS chronic fatigue, and 43% of patients with recurrent syncope. The average HIS values were: CFS = +2.02 (SD 4.07), non-CFS chronic fatigue = -2.89 (SD 3.64), syncope = -3.2 (SD 3.0), healthy = -2.48 (4.07). The odds ratios for CFS patients to have HIS >-0.98 was 8.8 compared with non-CFS chronic fatigue patients, 14.6 compared with recurrent syncope patients, and 34.8 compared with healthy subjects.

CONCLUSION: The cardiovascular reactivity in patients with CFS has certain features in common with the reactivity in patients with recurrent syncope or non-CFS chronic fatigue, such as the frequent occurrence of vasodepressor reaction, cardioinhibitory reaction, and postural tachycardia syndrome. Apart from to these shared responses, the large majority of CFS patients exhibit a particular abnormality which is characterized by HIS values >-0.98. Thus, HIS >-0.98 lends objective criteria to the assessment of CFS.

Source: Naschitz JE, Sabo E, Naschitz S, Rosner I, Rozenbaum M, Fields M, Isseroff H, Priselac RM, Gaitini L, Eldar S, Zukerman E, Yeshurun D. Hemodynamics instability score in chronic fatigue syndrome and in non-chronic fatigue syndrome. Semin Arthritis Rheum. 2002 Dec;32(3):141-8. http://www.ncbi.nlm.nih.gov/pubmed/12528078

Fractal analysis and recurrence quantification analysis of heart rate and pulse transit time for diagnosing chronic fatigue syndrome

Abstract:

This study aimed to develop a method to distinguish between the cardiovascular reactivity in chronic fatigue syndrome (CFS) and other patient populations.

Patients with CFS (n = 23), familial Mediterranean fever (n = 15), psoriatic arthritis (n = 10), generalized anxiety disorder (n = 12), neurally mediated syncope (n = 20), and healthy subjects (n = 20) were evaluated with a shortened head-up tilt test (HUTT). A 10-minute supine phase of the HUTT was followed by recording 600 cardiac cycles on tilt, i. e., 5 to 10 minutes. Beat-to-beat heart rate (HR) and pulse transit time (PTT) were acquisitioned. Data were processed by recurrence plot and fractal analysis. Fifty-two variables were calculated in each subject.

On multivariate analysis, the best predictors of CFS were HR-tilt-R/L, PTT-tilt-R/L, HR-supine-DET, PTT-tilt-WAVE, and HR-tilt-SD. Based on these predictors, the ‘Fractal & Recurrence Analysis-based Score’ (FRAS) was calculated: FRAS = 76.2 + 0.04*HR-supine-DET – 12.9*HR-tilt-R/L – 0.31*HR-tilt-SD – 19.27*PTT-tilt-R/L – 9.42* PTT-tilt-WAVE. The best cut-off differentiating CFS from the control population was FRAS = + 0.22. FRAS > + 0.22 was associated with CFS (sensitivity 70 % and specificity 88 %). The cardiovascular reactivity received mathematical expression with the aid of the FRAS. The shortened HUTT was well tolerated. The FRAS provides objective criteria which could become valuable in the assessment of CFS.

Comment in: Chronic fatigue syndrome and hidden happenings of the heartbeat. [Clin Auton Res. 2002]

Source: Naschitz JE, Sabo E, Naschitz S, Rosner I, Rozenbaum M, Priselac RM, Gaitini L, Zukerman E, Yeshurun D. Fractal analysis and recurrence quantification analysis of heart rate and pulse transit time for diagnosing chronic fatigue syndrome. Clin Auton Res. 2002 Aug;12(4):264-72. http://www.ncbi.nlm.nih.gov/pubmed/12357280