Why traumatic leg amputees are at increased risk for cardiovascular diseases.

BACKGROUND: Post-traumatic lower limb amputees have an increased morbidity and mortality from cardiovascular disease. Risk factors for this amplified morbidity and the involved pathophysiologic mechanisms have not been comprehensively studied. METHODS: The MEDLINE database was reviewed, with case-controlled studies and nested in cohort studies eligible for inclusion in this analysis. RESULTS: Insulin resistance, psychological stress and patients' deviant behaviors are prevalent in traumatic lower limb amputees. Each of these factors may have systemic consequences on the arterial system and may contribute to the increased cardiovascular morbidity in traumatic amputees. Abnormalities of arterial flow proximal to the amputation site may hold the explanation for the linkage between the extent of leg amputation and the magnitude of the cardiovascular risk: proximal leg amputation is associated with greater risk than distal amputation and bilateral amputation with greater risk than unilateral amputation. This review focuses on hemodynamic culprits (shear stress, circumferential strain, reflected waves), hemodynamic consequences in proximity to the occluded femoral artery and hemodynamic consequences at a distance. CONCLUSION: Coronary risk in lower limb amputees may be substantially greater than predicted by available algorithms, given that neither hemodynamic nor psychological factors concern the current prediction models. It seems reasonable to take early prophylactic measures in lower limb amputees by discouraging smoking, excessive alcohol consumption and adherence to a low fat diet. Studies are needed to evaluate the optimal intensity of physical exercise effects on reflected pulse waves and their possible long-term consequences. Guidelines for optimal blood pressure, blood glucose and lipid control in amputees need to be convened.

Aortic involvement in rheumatic diseases.

OBJECTIVE: To review the prevalence, mechanisms, presentations and clinical significance of aortic involvement in rheumatic inflammatory diseases. METHODS: The medical literature, available through a PUBMED search was reviewed and the relevant information was summarized. In addition, selected articles related to aortic involvement in rheumatic diseases were included in this review. RESULTS: Rheumatic disorders may be categorized by their propensity to involve the aorta: conditions with a prevalence of 10% and more (Takayasu's arteritis, temporal arteritis, long-standing ankylosing spondylitis, Cogan's syndrome and relapsing polychondritis), disorders with uncommon but well documented aortic involvement and rheumatic conditions with rare case reports of such involvement. Clinical presentation of aortic disease is dependent on the part of aorta involved and may manifest by aortic pain and/or other symptoms caused by aortic dilatation, narrowing or aneurysm. The histopathology of inflammatory aortitis is characterized by lymphoplasmacytic infiltration with or without giant cells or granulomas. On the other hand, non-inflammatory aortic damage in rheumatic diseases may include Marfan-like cystic disintegration of the aortic media as well as accelerated atherosclerosis. Awareness of rheumatic conditions with a high potential for clinically significant aortic involvement may promote referral of such patients for aortic imaging and sometimes surgery before fatal complications intervene. CONCLUSION: Early diagnosis of aortic involvement can be advanced by informed consideration of such a complication in a rheumatic patient.

The patient with supine hypertension and orthostatic hypotension: a clinical dilemma.

Coexistent supine hypertension and orthostatic hypotension (SH-OH) pose a particular therapeutic dilemma, as treatment of one aspect of the condition may worsen the other. Studies of SH-OH are to be found by and large on patients with autonomic nervous disorders as well as patients with chronic arterial hypertension. In medical practice, however, the aetiologies and clinical presentation of the syndrome seem to be more varied. In the most typical cases the diagnosis is straightforward and the responsible mechanism evident. In those patients with mild or non-specific symptoms, the diagnosis is more demanding and the investigation may benefit from results of the tilt test, bedside autonomic tests as well as haemodynamic assessment. Discrete patterns of SH-OH may be recognisable. This review focuses on the management of the patient with coexistent SH-OH.

Amiodarone toxicity presenting as pulmonary mass and peripheral neuropathy: the continuing diagnostic challenge.

A 64 year old man receiving long term amiodarone treatment presented with dyspnea, cough, and weight loss. Radiographs and computed tomography showed a lung mass with associated multiple pulmonary nodules. Biopsies of the pulmonary mass showed foamy histiocytes without malignant cells. However, findings on FDG-PET scan were consistent with a malignant tumour. These findings on computed tomography and PET scan and the unusually late resolution of the pulmonary lesions after withdrawal of amiodarone treatment posed a challenging diagnostic problem.

Nonspecific dizziness: frequency of supine hypertension associated with hypotensive reactions on head-up tilt.

The clinical syndrome of supine hypertension associated with orthostatic hypotension (OH) in given individuals is recognized by specialists, but is underdiagnosed in the community. The objective of this study was to assess supine hypertension associated with hypotensive reactions on head-up tilt (SH-HRT) among patients evaluated for nonspecific dizziness. Consecutive patients with nonspecific dizziness were studied with a 10-min supine 30-min head-up tilt test. Supine hypertension (SH) was diagnosed when supine systolic blood pressure (SBP) was > or = 140 mmHg and/or supine diastolic blood pressure (DBP) was > or = 90 mmHg. Hypotensive reactions on tilt (HRT) were diagnosed when SBP decreased by > or = 30 mmHg on tilt and/or DBP decreased by > or = 15 mmHg. Of 430 patients tested, 42 (9.8%) had SH-HRT. The median age was 67 years; 37 had a pretest diagnosis of hypertension, with treatment. The median supine BP was 162/90 mmHg; the median nadir BP on tilt was 118/78 mmHg. Four SH-HRT patterns were recognized: (I) SH with typical neurogenic OH (n = 6), (II) SH with vasovagal reaction on tilt (n = 4), (III) SH with sustained HRT (n = 28), and (IV) SH with mixed orthostatic-vasovagal reaction on tilt (n = 4). Dizziness on tilt occurred in 25% of patients category III (SH with sustained HRT), while appearing universally in other SH-HRT patterns. In conclusion, nonspecific dizziness may be the chief complaint in patients with SH-HRT, a disorder often unrecognized by clinicians. Different patterns of SH-HRT on HUTT may reflect different aberrations in cardiovascular homeostasis and may require differentiated management strategies.

Hyperventilation and amplified blood pressure response: is there a link?

Based on prior studies, the hypothesis that hyperventilation (HV) may have a pressor effect and play a causal role in hypertension has been suggested. The objective of this study was to correlate HV with blood pressure (BP)-change during a postural challenge. Consecutive subjects referred for evaluation of syncope, dizziness, chronic fatigue syndrome (CFS), fibromyalgia, or non-CFS fatigue were assessed with a 10-min supine 30-min head-up tilt test combined with capnography. We selected for analysis the records of patients aged 17-70 years, not taking vasoactive medications, having sitting systolic BP (SBP) < 140 mmHg, sitting diastolic BP (DBP) < 90 mmHg, and who completed 30 min of tilt. HV was diagnosed when end-tidal pressure of CO2 < 30 mmHg was recorded consecutively for > or = 10 min. Postural hypertension (PHT) was diagnosed when DBP on tilt > or = 90 mmHg was recorded consecutively for > or = 10 min. DBP-change was computed as (median DBP on tilt) -(median DBP supine). PHT and DBP-change were correlated with HV. A total of 320 patient charts were reviewed. PHT was present in 30 cases. The mean DBP-change in patients with PHT was +9.9 mmHg (s.d. 5.8), with three patients manifesting HV. Of the remaining 290 patients, 56 had HV, their mean DBP-change was -0.3 mmHg (s.d. 7.2). The other 234 patients without HV had a mean DBP-change +0.95 mmHg (s.d. 5.7), comparable to the DBP-change in patients with HV. In, conclusion, posturally induced HV was not associated with an increase in BP, nor was PHT associated with HV, except in a small minority of cases.

Patterns of cardiovascular reactivity in disease diagnosis.

BACKGROUND: Aberrations of cardiovascular reactivity (CVR), an expression of autonomic function, occur in a number of clinical conditions, but lack specificity for a particular disorder. Recently, a CVR pattern particular to chronic fatigue syndrome was observed. AIM: To assess whether specific CVR patterns can be described for other clinical conditions. METHODS: Six groups of patients, matched for age and gender, were evaluated with a shortened head-up tilt test: patients with chronic fatigue syndrome (CFS) (n = 20), non-CFS fatigue (F) (n = 15), neurally-mediated syncope (SY) (n = 21), familial Mediterranean fever (FMF) (n = 17), psoriatic arthritis (PSOR) (n = 19) and healthy subjects (H) (n = 20). A 10-min supine phase was followed by recording 600 cardiac cycles on tilt (5-10 min). Beat-to-beat heart rate (HR) and pulse transit time (PTT) were measured. Results were analysed using conventional statistics, recurrence plot analysis and fractal analysis. RESULTS: Multivariate analysis evaluated independent predictors of the CVR in each patient group vs. all other groups. Based on these predictors, equations were determined for a linear discriminant score (DS) for each group. The best sensitivities and specificities of the DS, consistent with disease-related phenotypes of CVR, were noted in the following groups: CFS, 90.0% and 60%; SY, 93.3% and 62.5%; FMF, 90.1% and 75.4%, respectively. DISCUSSION: Pathological disturbances may alter cardiovascular reactivity. Our data support the existence of disease-related CVR phenotypes, with implications for pathogenesis and differential diagnosis.

The head-up tilt test with haemodynamic instability score in diagnosing chronic fatigue syndrome.

BACKGROUND: Studying patients with chronic fatigue syndrome (CFS), we have developed a method that uses a head-up tilt test (HUTT) to estimate BP and HR instability during tilt, expressed as a 'haemodynamic instability score' (HIS). AIM: To assess HIS sensitivity and specificity in the diagnosis of CFS. DESIGN: Prospective controlled study. METHODS: Patients with CFS (n=40), non-CFS chronic fatigue (n=73), fibromyalgia (n=41), neurally mediated syncope (n=58), generalized anxiety disorder (n=28), familial Mediterranean fever (n=50), arterial hypertension (n=28), and healthy subjects (n=59) were evaluated with a standardized head-up tilt test (HUTT). The HIS was calculated from blood pressure (BP) and heart rate (HR) changes during the HUTT. RESULTS: The tilt was prematurely terminated in 22% of CFS patients when postural symptoms occurred and the HIS could not be calculated. In the remainder, the median(IQR) HIS values were: CFS +2.14(4.67), non-CFS fatigue -3.98(5.35), fibromyalgia -2.81(2.62), syncope -3.7(4.36), generalized anxiety disorder -0.21(6.05), healthy controls -2.66(3.14), FMF -5.09(6.41), hypertensives -5.35(2.74) (p<0.0001 vs. CFS in all groups, except for anxiety disorder, p=NS). The sensitivity for CFS at HIS >-0.98 cut-off was 90.3% and the overall specificity was 84.5%. DISCUSSION: There is a particular dysautonomia in CFS that differs from dysautonomia in other disorders, characterized by HIS >-0.98. The HIS can reinforce the clinician's diagnosis by providing objective criteria for the assessment of CFS, which until now, could only be subjectively inferred.

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

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.

Hemodynamic instability in chronic fatigue syndrome: indices and diagnostic significance.

OBJECTIVES: To evaluate the cardiovascular response to postural challenge in patients with chronic fatigue syndrome (CFS) and to determine whether the degree of instability of the cardiovascular response may aid in diagnosing CFS. METHODS: Patients with CFS (n = 25) and their age- and gender-matched healthy controls (n = 37), patients with fibromyalgia (n = 30), generalized anxiety disorder (n = 15), and essential hypertension (n = 20) were evaluated with the aid of a standardized tilt test. The blood pressure (BP) and heart rate (HR) were recorded during 10 minutes of recumbence and 30 minutes of head-up tilt. We designated BP changes as the differences between successive BP values and the last recumbent BP. The average and standard deviation (SD) were calculated. Time curves of BP differences were loaded into a computerized image analyzer, and their outline ratios and fractal dimensions were measured. HR changes were determined similarly. The average and SD of the parameters were calculated, and intergroup comparisons were performed. RESULTS: On multivariate analysis, the independent predictors of CFS patients versus healthy controls were the fractal dimension of absolute values of the systolic BP changes (SYST-FD.abs), the standard deviation of the current values of the systolic BP changes (SYST-SD.cur), and the standard deviation of the current values of the heart rate changes (HR-SD.cur). The following equation was deduced to calculate the hemodynamic instability score (HIS) in the individual patient: HIS = 64.3303 + (SYST-FD.abs x -68.0135) + (SYST-SD.cur x 111.3726) + (HR-SD.cur x 60.4164). The best cutoff differentiating CFS from the healthy controls was -0.98. HIS values >-0.98 were associated with CFS (sensitivity 97%, specificity 97%). The HIS differed significantly between CFS and other groups (P <.0001) except for generalized anxiety disorder. Group averages (SD) of HIS were CFS = +3.72 (5.02), healthy = -4.62 (2.26), fibromyalgia = -3.27 (2.63), hypertension = -5.53 (2.24), and generalized anxiety disorder = +1.08 (5.2). CONCLUSION: The HIS adds objective criteria confirming the diagnosis of CFS.

Cardiovascular response to upright tilt in fibromyalgia differs from that in chronic fatigue syndrome.

OBJECTIVE: To compare the cardiovascular response during postural challenge of patients with fibromyalgia (FM) to those with chronic fatigue syndrome (CFS). METHODS: Age and sex matched patients were studied, 38 with FM, 30 with CFS, and 37 healthy subjects. Blood pressure (BP) and heart rate (HR) were recorded during 10 min of recumbence and 30 min of head-up tilt. Differences between successive BP values and the last recumbent BP, their average, and standard deviation (SD) were calculated. Time curves of BP differences were analyzed by computer and their outline ratios (OR) and fractal dimensions (FD) were measured. HR differences were determined similarly. Based on the latter measurements, each subject's discriminant score (DS) was computed. RESULTS: For patients and controls average DS values were: FM: -3.68 (SD 2.7), CFS: 3.72 (SD 5.02), and healthy controls: -4.62 (SD 2.24). DS values differed significantly between FM and CFS (p < 0.0001). Subgroups of FM patients with and without fatigue had comparable DS values. CONCLUSION: The DS confers numerical expression to the cardiovascular response during postural challenge. DS values in FM were significantly different from DS in CFS, suggesting that homeostatic responses in FM and CFS are dissimilar. This observation challenges the hypothesis that FM and CFS share a common derangement of the stress-response system.

The Haemodynamic Instability Score (HIS) for assessment of cardiovascular reactivity in hypertensive and normotensive patients.

The normal response to postural challenge is characterised by maintenance of relatively stable blood pressure (BP) and heart rate (HR) after 30 sec to 30 min of head-up tilt. The objective of the present study was to determine the degree of instability of cardiovascular responses to postural challenge in normotensive and hypertensive subjects. In the initial phase of the study, two groups of age and sex-matched subjects were assessed: essential hypertension (n = 20) and healthy (n = 37). The BP and HR were recorded at 5-min intervals during the course of the 10-min supine-30-min head-up tilt test (HUTT). We categorised 'BP-change' as the difference between individual BP measurements during HUTT and the last recumbent BP value, divided by latter value. The average and standard deviation (SD) of the recorded BP changes were calculated, and BP changes were plotted along a time curve. A computerised image analyser then calculated the outline ratio (OR) and fractal dimension (FD) values for each of the curves. An identical process evaluated measurements for HR-changes. BP- and HR-changes were then converted into absolute numbers, and the average, SD, OR, and FD were calculated. A multivariate analysis was conducted, evaluating independent predictors of hypertension. Finally, an equation for the calculation of 'haemodynamic instability score' (HIS) was deduced and a cut-off between HIS of hypertensive and normotensive subjects was established. Independent predictors of the cardiovascular response to postural challenge of hypertensives (Group I) vs healthy (Group II) were: a.DIAST-FD, a.HR-AVG, a.HR-SD, a.HR-FD, DIAS-SD and HR-SD and HR-SD. Based on these five predictors, a linear discriminant score was computed and called the Haemodynamic Instability Score (HIS): HIS = 59.4 + (-16.6*a.DIAST-FD) + (-29.0*a.HR-AVG) + (-82.4*a.HR-SD) + (-30.1*a.HR-FD) + (-57.9*DIAS-SD) + (73.4*HR-SD) The HIS values in Group I (hypertensives) were: avg = 3.348, SD = 2.863, and 95% CI for mean = 2.008, 4.688. The HIS values in Group II (healthy) were: avg = -3.394, SD = 2.435, 95% CI for mean = -4.206, -2.582. Values of the HIS > -2.09 were generally observed in hypertensives (sensitivity 95%) and values < or = -2.09 were usually seen in the healthy (specificity 81.1%). The HIS was cross-validated in an additional group of hypertensive patients (n = 73). In the latter group, the HIS values were: avg = -0.456, SD = 4.403, 95% CI for mean = -1.506, 0.593 and 71.4% sensitivity at the proposed cut-off point. In conclusion, the HIS confers numerical expression to the degree of lability of BP and HR during postural challenge. Based on this score, a distinction between the cardiovascular reactivity of hypertensives vs normotensives is drawn. Possible applications of HIS are discussed.

Rheumatic syndromes: clues to occult neoplasia.

Rheumatic disorders associated with cancer include a variety of conditions, most of which have no features distinguishing them from idiopathic rheumatic disorders. It is generally held that an extensive search for occult malignancy in most rheumatic syndromes is not recommended unless the case is accompanied by specific findings suggestive of malignancy. Within the past year information has accumulated on the role of long-standing rheumatic disorders as premalignant conditions and the role of autoantibodies as screening tests for occult cancer. The present article discusses cancer-associated rheumatic syndromes, calls attention to aspects that may suggest the presence of a hidden cancer, and examines the role of laboratory tests as clues of a possible neoplastic etiology of those syndromes.

The capnography head-up tilt test for evaluation of chronic fatigue syndrome.

OBJECTIVES: To compare the hemodynamic and ventilatory responses to autonomic challenge evoked by upright tilt table testing in patients with chronic fatigue syndrome (CFS) to healthy individuals. METHODS: Thirty-two consecutive patients with CFS and 32 healthy volunteers were evaluated with the aid of the recently introduced capnography head-up tilt test (CHUTT). The main outcome measures were values of blood pressure (BP), heart rate (HR), respiratory rate (RR), and end-tidal pressure of co2 (ETPco2) recorded during recumbence and tilt. In addition, the end points of vasodepressor and cardioinhibitory reactions, hyperventilation (defined by ETPco2 <25 mm Hg) and the postural tachycardia syndrome, were recorded. RESULTS: The BP, HR, RR, and ETPco2 recorded during recumbence were similar in both groups. During tilt, patients with CFS developed significantly lower systolic BP, diastolic BP, and ETPco2, and a significant rise in HR and RR (P<.01). In CFS patients, the postural tachycardia syndrome occurred in 44%, vasodepressor reaction in 41%, cardioinhibitory reaction in 13%, and hyperventilation in 31% of cases. One or more end points of the CHUTT were reached in 78% of patients with CFS but in none of the controls (P<.0001). CONCLUSIONS: In most patients with CFS, a spectrum of abnormal homeostatic reactions is diagnosed with the aid of the CHUTT. Data provided by the CHUTT may reinforce the clinical diagnosis by adding objective and unbiased criteria to the subjective assessment of CFS.

Hepatitis C virus-related arthritis: characteristics and response to therapy with interferon alpha.

OBJECTIVE: To characterize hepatitis C virus (HCV)-related arthropathy and to evaluate the response to treatment with interferon-alpha (INF-alpha). METHODS: We studied 28 HCV-infected patients with arthritis. All patients underwent complete clinical, laboratory and radiological evaluation, including assessment and follow-up by a rheumatologist. Twenty-five patients were treated with INF-alpha for a median period of 12 months. RESULTS: All patients were HCV-RNA positive (genotype 1b in 65%). The mean duration of arthropathy-related symptoms prior to the diagnosis of HCV infection was 12 months. 19 patients (68%) had symmetric polyarthritis and 19 (68%) had morning stiffness > or = 60 min. None of the patients had erosive disease or subcutaneous nodules. 12 (43%) had detectable cryoglobulin (mean cryocrit: 3.6 +/- 3.5%), 17 (61%) had rheumatoid factor (RF) (median titer: 1:80), and only 15 (54%) had elevated ESR. 14 patients (50%) had > or = 4 ACR (American College of Rheumatology) criteria for the diagnosis of rheumatoid arthritis (RA), 9 of whom were mistakenly diagnosed and previously treated as RA patients. Only 3 patients had a satisfactory response to previous treatment with anti-inflammatory or disease modifying drugs. Complete or partial response of arthritis-related symptoms in INF-alpha treated patients was observed in 44% and 32%, respectively. Cryoglobulin became undetectable in 9 of 12 patients. However, a complete biochemical and virological end-of-treatment response was achieved in only 8 (36%) and 5 patients (20%), respectively. CONCLUSION: HCV arthropathy should be considered in the differential diagnosis of any patient with arthritis, even in the absence of liver disease. Treatment with interferon-alpha may lead to substantial clinical improvement of HCV-related arthritis even without a complete biochemical or virological response.