Cardiac biomarkers but not measures of vascular atherosclerosis predict mortality in patients with peripheral artery disease.

BACKGROUND: Peripheral artery disease (PAD) becomes more prevalent with advancing age and is associated with elevated risk of cardiovascular events and shortened life expectancy. We investigated the prognostic performance of cardiac and vascular biomarkers in a cohort of PAD patients. METHODS: A total of 95 PAD patients were enrolled (mean age 68 years, range 47 to 86 years, 73 males). Carotid intima-media thickness (cIMT), ankle brachial index (ABI), high sensitive cardiac troponin T, and N-terminal pro-B-type Natriuretic Peptide (NT-proBNP) were measured. RESULTS: During a median follow-up time of 9.5 years, 44 patients died and 51 patients survived. Upon Kaplan-Meier survival analysis hs-TnT (P < .001) or NT-proBNP levels (P < .001) above the median but not cIMT above the median (P = .488) or ABI below the median (P < .436)were associated with reduced survival rate. Upon univariate cox regression and after adjustment for age, gender, prior cerebral artery disease, and diabetes mellitus only the association between hs-cTnT and mortality remained significant (HR 1.93, 95% CI 1.33-2.79, P < .001). In receiver operating curve analysis hs-cTnT (area under the curve [AUC]: 0.77, 95% CI: 0.67-0.87, P < .001) NT-proBNP (AUC: 0.74, 95% CI: 0.64-0.84, P < .001) as well as hs-cTnT, and NT-proBNP combined (AUC: 0.79, 95% CI: 0.69-0.88, P < .001) were superior to cIMT (AUC: 0.64, 95%, CI: 0.53-0.76, P = .022) and ABI (AUC: 0.57, 95% CI: 0.44-0.68, P = .313) in discriminating risk for mortality. CONCLUSION: hs-cTnT and NT-proBNP should be taken into account for prognosis of patients with PAD.

Vertebral and internal mammary artery steal syndrome in patients with hemodialysis access.

BACKGROUND: Increased flow in the subclavian artery feeding a vascular access for hemodialysis can induce steal phenomena in the vertebral (VA) and internal mammary artery (IMA). The aim of this study was to describe the hemodynamic effects of access flow on the VA and IMA in patients with native fistulas and grafts. PATIENTS AND METHODS: Peak systolic (PSV) and end diastolic (EDV) velocity measurements of the VA, IMA and carotid arteries, as well as flow volume measurements of the subclavian artery, were performed. Flow measurements at the side of the vascular access were compared with the contralateral side. Fifty-five patients were consecutively included, most with a radio-cephalic fistula on the left arm with a mean shunt volume of 1156 ml/min. RESULTS: Pathologic flow patterns were observed in the ipsilateral VA in four patients (7.3 %); contralateral VA flow was normal in all patients. Peak systolic velocity of the VA was significantly decreased at the side of the shunt arm with a PSV of 42.6 ± 11.8 cm/s compared to 48.4 ± 15.6 cm/s contralateral (p < 0.05). The IMA flow pattern were normal in all patients. The PSV of the IMA was significantly decreased (p < 0.01) at the side of the shunt arm (87.5 ± 29.1 cm/s) compared to the non-shunt arm (95.9 ± 27.4 cm/s). CONCLUSION: We describe significant hemodynamic effects of fistulas to the vertebral and internal mammary arteries. Doppler spectral analysis of the vertebral and internal mammary arteries should be integrated in ultrasound, especially in patients with cerebrovascular or cardiac symptoms.

Misdiagnosis of plexiform neurofibroma as venous malformation in pediatric patients.

BACKGROUND: The aim of this study was to identify Magnetic Resonance Imaging (MRI) characteristics that reliably distinguish deep plexiform neurofibromas (PNFs) from venous malformations (VMs). METHODS: A database search was conducted for patients that were referred with a vascular anomaly but had a neurofibroma instead. Clinical and imaging features of patients with venous malformations as the most common referral diagnosis were compared to those with PNFs. The imaging features of deep PNFs recorded were: anatomical location, size, morphology, margins, signal intensity and post-contrast enhancement pattern. RESULTS: Ten patients with PNFs were identified. Five patients had adequate imaging. These five patients were included in our study. There were 3 female and 2 male patients ranging in age from 10 months to 21 years. Deep PNFs were located in the cervicofacial region (N.=3), lower extremity (N.=1) and back/flank region (N.=1). The most common clinical features of all these patients were palpable mass (N.=5) and pain (N.=4). The MRI features that distinguished VMs from deep PNFs were the serpiginous morphology, relatively intermediate T-2 signal intensity and peculiar enhancement pattern without fluid-fluid levels or phleboliths and nerve root involvement. The target sign can be regularly found in PNFs, but may be also present in VMs and other vascular lesions. CONCLUSIONS: Target signs, a typical sign of PNFs may be absent and can also be found in vascular anomalies, leading to confusion in diagnosis. PNFs can be reliably distinguished from VMs on MRI based on the above mentioned features.

Long term follow-up after endovascular brachytherapy of femoro-popliteal arteries.

To perform a long term follow-up after endovascular brachytherapy (EVBT) and balloon angioplasty (PTA) regarding vessel patency and diameter. EVBT had been successfully used to decrease restenosis in short term, but long term data are lacking. Participants of a randomized study comparing EVBT and balloon angioplasty alone were invited for follow-up examination ten years after intervention. Using a standardized protocol measurement of the patency and vessel diameter was performed of femoral and popliteal arteries. 44 patients were included, 21 had been treated with EVBT and 23 had received PTA alone. Target lesion patency was similar between the two groups (90.5% vs. 87.0%). Vessel diameter of the target lesion was significantly greater in the EVBT group (6.4 mm, range 3.9-9.9) compared to the controls (5.0 mm, range 3.1-7.4; p = 0.002). Ten years after EVBT of femoro-popliteal arteries vessel diameter is significantly increased whereas patency rate is not different compared to angioplasty alone.

Markers of arterial stiffness in peripheral arterial disease.

Increased arterial stiffness results from reduced elasticity of the arterial wall and is an independent predictor for cardiovascular risk. The gold standard for assessment of arterial stiffness is the carotid-femoral pulse wave velocity. Other parameters such as central aortic pulse pressure and aortic augmentation index are indirect, surrogate markers of arterial stiffness, but provide additional information on the characteristics of wave reflection. Peripheral arterial disease (PAD) is characterised by its association with systolic hypertension, increased arterial stiffness, disturbed wave reflexion and prognosis depending on ankle-brachial pressure index. This review summarises the physiology of pulse wave propagation and reflection and its changes due to aging and atherosclerosis. We discuss different non-invasive assessment techniques and highlight the importance of the understanding of arterial pulse wave analysis for each vascular specialist and primary care physician alike in the context of PAD.

Combined and complex vascular malformations.

The correct diagnosis of vascular malformations is obtainable by clinical assessment and patient history in the majority of cases. Nonetheless, confusion in nomenclature, existence of multiple classifications and rarity of these lesions leads to misdiagnosis and related wrong treatment. This is especially the case in combined or complex vascular malformations or vascular malformations that are part of syndromes as these have overlapping clinical and imaging features. New entities in the field of vascular anomalies have been described recently like fibro-adipose vascular anomaly or central conducting lymphatic anomalies.

Vascular malformations revisited.

Vascular malformations are congenital anomalies that can affect each part of the vasculature. Combined forms are common and they are often part of complex syndromes. Most malformations are diagnosed during infancy, but some get obvious only later in life. The field of vascular malformations is emerging with recently described new entities and treatments. Still, misdiagnosis is common in this field, leading to nosologic confusion and wrong treatment. Clinical evaluation and imaging are the gold standard for diagnostic confirmation. Sclerotherapy and embolization are the main treatment techniques but are also used preoperatively to reduce blood loss and shrink the lesion if surgery is planned. Despite new treatment options, especially if extensive in size or involving vulnerable structures, vascular malformations are still considered chronic diseases and cause significant morbidity. Common understanding and agreement on terminology and a multidisciplinary approach are the basis of successful treatment and long-term support for these patients. Continuing research in the field of vascular anomalies will improve knowledge and create further treatment options.

Carotid artery disease after head and neck radiotherapy.

Radiation induced atherosclerosis of the carotid artery is a clinically relevant late complication after head and neck radiotherapy. Improved long-term survival after multimodality therapy in neck malignancies result in an increased risk of carotid artery disease in patients after radiotherapy (RT). This review focuses on the current knowledge of occlusive carotid disease after head and neck radiotherapy and highlights the exceeding morphologic post-radiation vessel wall pathologies. More severe and extensive carotid artery atherosclerosis with plaque in all segments including the common carotid artery is a frequent finding after RT. Therefore, colour coded duplex ultrasound surveillance in patients after head and neck RT is recommended. Some histopathological studies indicate differences to “classical” atherosclerosis, and pathogenesis of chronic radiation vasculopathy is still under discussion.

Acute effects of haemodialysis on central venous and arterial pressure characteristics.

AIM: Haemodynamic stability of patients during haemodialysis (HD) sessions is of pivotal importance and accurate determination of dry weight remains a challenge. Little information is available about central venous and aortic pressure during dialysis. In this pilot study we used a non-invasive technique to describe the changes in central venous pressure (CVP) during dialysis. METHODS: An ultrasound-assisted pressure-manometer was used at the cephalic vein during haemodialysis to quantify CVP. Central aortic pressure changes were assessed as aortic augmentation index and subendocardial viability ratio. Bioimpedance was applied to measure total body water, as well as extracellular and intracellular water before and after HD. Measurements were performed prior during and after 1 and 2 h on HD. RESULTS: Ten patients were included with a median age of 72 years (23-82). Haemodialysis reduced the weight by 2.0 kg, corresponding to a measured decrease in total body water of 1.9 L. The mean CVP showed a significant decrease (9.0-0.8 cmH2O; P = 0.0005) during dialysis. The significant drop in CVP was found during the first hour (9-2.8 cmH2O). Starting and stopping dialysis was reflected by a reduction of 2.6 cmH2O and a rise of 2.8 cmH2O (n.s.). Aortic augmentation index decreased from 26.1% to 21.0% (n.s.). Subendocardial viability ratio increased from 126% to 156% (P < 0.05) during HD, and decreased to 139% direct after HD (n.s.). CONCLUSION: This is the first study that illustrates a prominent reduction of CVP during the first hour of haemodialysis. Non-invasive CVP measurement is feasible during haemodialysis and adds another piece in the puzzle of factors involved in haemodynamic stability.

Small dense low density lipoprotein particles are associated with poor outcome after angioplasty in peripheral artery disease.

PURPOSE: In patients suffering from symptomatic peripheral artery disease (PAD), percutaneous revascularization is the treatment of choice. However, restenosis may occur in 10 to 60% in the first year depending on a variety of factors. Small dense low density lipoprotein (sdLDL) particles are associated with an increased risk for cardiovascular events, but their role in the process of restenosis is not known. We conducted a prospective study to analyze the association of sdLDL particles with the outcome of balloon angioplasty in PAD. The composite primary endpoint was defined as improved walking distance and absence of restenosis. METHODS: Patients with angiographically documented PAD of the lower extremities who were scheduled for lower limb revascularization were consecutively recruited for the study. At baseline and at three month follow-up triglyceride, total cholesterol, LDL size and subclasses and HDL cholesterol and ankle-brachial index (ABI) were measured. Three months after the intervention duplex sonography was performed to detect restenosis. RESULTS: Sixty-four patients (53% male) with a mean age of 68.6±9.9 years were included. The proportion of small- dense LDL particles (class III and IV) was significantly lower (33.1±11.0% vs. 39.4±12.1%, p = 0.038) in patients who reached the primary end-point compared with those who did not. Patients with improved walking distance and without restenosis had a significantly higher LDL size at baseline (26.6±1.1 nm vs. 26.1±1.1 nm, p = 0.046) and at follow-up (26.7±1.1 nm vs. 26.2±0.9 nm, p = 0.044) than patients without improvement. CONCLUSIONS: Small-dense LDL particles are associated with worse early outcome in patients undergoing percutaneous revascularization for symptomatic PAD.

Increased permeability of cutaneous lymphatic capillaries and enhanced blood flow in psoriatic plaques.

INTRODUCTION: Morphological abnormalities of microvessels are described in psoriasis. However, there are conflicting data as to whether their function is also altered. OBJECTIVE: Our aim was to study the morphology and function of the lymphatic capillaries of psoriatic skin. METHODS: Morphology and permeability of initial lymphatics were studied by microlymphography and densitometry in 20 patients. Perfusion was studied by laser Doppler fluxmetry. RESULTS: Permeability of lymphatics in plaques was increased by 7.6% compared to unafflicted skin (p < 0.001). Lymphatic vessel density and the extension of dye in lymphatic networks were not significantly different between involved and uninvolved areas. Both sites showed a wide range of diameters of lymphatics. The median laser Doppler flux in plaques was increased by 144% (91-380%) compared to unaffected skin (p < 0.001). CONCLUSIONS: Increased permeability of lymphatics and increased blood flow was demonstrated in vivo in psoriatic skin lesions. These findings may reflect the local inflammatory process and may be used as markers when studying new therapeutic approaches for psoriasis.

Predictive value of auscultation of femoropopliteal arteries.

BACKGROUND: Femoropopliteal bruits indicate flow turbulences and increased blood flow velocity, usually caused by an atherosclerotic plaque or stenosis. No data exist on the quality of bruits as a means for quantifying the degree of stenosis. We therefore conducted a prospective observational study to investigate the sensitivity and specificity of femoropopliteal auscultation, differentiated on the basis of bruit quality, to detect and quantify clinically relevant stenoses in patients with symptomatic and asymptomatic peripheral arterial disease (PAD). METHODS: Patients with known chronic and stable PAD were recruited in the outpatient clinic. We included patients with known PAD and an ankle-brachial index (ABI) <0.90 and/or an ABI ≥0.90 with a history of lower limb revascularisation. Auscultation was performed independently by three investigators with varied clinical experience after a 10-minute period of rest. Femoropopliteal lesions were classified as follows: normal vessel wall or slight wall thickening (<20%), atherosclerotic plaque with below 50% reduction of the vessel lumen, prestenotic/intrastenotic ratio over 2.5 (<70%), over 3.5 (<99%) and complete occlusion (100%). RESULTS: Weighted Cohen's κ coefficients for differentiated auscultation were low in all vascular regions and did not differ between investigators. Sensitivity was low in most areas with an increase after exercise. The highest sensitivity in detecting relevant (>50%) stenosis was found in the common femoral artery (86%). CONCLUSION: Vascular auscultation is known to be of great use in routine clinical practice in recognising arterial abnormalities. Diagnosis of PAD is based on various diagnostic tools (pulse palpation, ABI measurement) and auscultation can localise relevant stenosis. However, auscultation alone is of limited sensitivity and specificity in grading stenosis in femoropopliteal arteries. Where PAD is clinically suspected further diagnostic tools, especially colour-coded duplex ultrasound, should be employed to quantify the underlying lesion.

Pressure indices in peripheral arterial disease assessed by infrared photosensors.

Ankle-brachial index (ABI) assessment by Doppler is operator dependent and limited in calcified arteries. For the detection of peripheral arterial disease (PAD), we evaluated ABI and toe-finger (ToFi) pressures by infrared (IR) sensors at the digits and compared with standard Doppler (Doppler-ABI) in 100 patients with PAD and in 15 controls. Pressure indices were obtained in 86% for Doppler-ABI, 82% for IR-ABI, and 94% for IR-ToFi (P < .01). According to Bland-Altmann analysis, IR-ABI and Doppler-ABI are exchangeable (limits of agreement [loa] -0.30; 0.30, bias -0.003, 95% confidence interval [CI] -0.02; 0.02), whereas IR-ToFi was not (loa -0.23; 0.61, bias of 0.2, 95% CI 0.16; 0.23). The IR-ToFi revealed the best inter- and intrarater agreement (0.92/0.98) followed by IR-ABI (0.74/0.98) and Doppler-ABI (0.66/0.89). Ankle-brachial arterial pressure index can be assessed by IR photosensors. Although toe-finger index is not exchangeable with standard Doppler, it will need further exploration to define its value for the diagnosis of PAD due to its excellent inter- and intrarater agreement.

Associated vascular lesions in patients with spontaneous coronary artery dissection.

AIM: To identify vascular abnormalities in patients presenting with spontaneous coronary artery dissection (SCAD). METHODS: We performed a whole-body MR angiography and a duplex sonography of the renal and carotid arteries in 12 patients (9 women, 3 men) with SCAD to identify vascular abnormalities. RESULTS: MR angiography revealed abnormalities of the renal arteries in 3/12 patients (25%). All 3 patients were women, 2 presented with changes suggesting fibromuscular dysplasia (FMD), 1 had a spontaneous renal artery dissection. No other vascular abnormalities were identified in any of the patients. Duplex sonography confirmed MR findings and showed non-significant renal artery stenoses in both patients with FMD. CONCLUSIONS: Abnormalities of the renal arteries were found in 3/12 (25%) of the patients with SCAD. No other vascular abnormalities were identified. Additional diagnostic tests of the renal arteries such as renal artery angiography or duplex sonography may be considered in patients presenting with SCAD.

Predictive value of duplex ultrasound for restenosis after renal artery stenting.

PURPOSE: Factors predicting renal function and recurrent stenosis following percutaneous renal revascularization are poorly identified. The predictive value of hemodynamic duplex ultrasound (DUS) parameters was evaluated. METHODS: In a prospective observational study patients undergoing stenting of renal artery stenosis (RAS) were included. Renal resistance index (RI) and peak systolic velocity (PSV) were measured at baseline, one day, and six months after intervention. RESULTS: At 6-months follow-up 16 (16.8%) restenosis of 105 treated renal arteries were detected. Baseline RI was 0.69 +/- 0.12 and increased significantly to 0.72 +/- 0.09 after 6 months (p < 0.0001), however, RI did not predict restenosis. PSV at baseline and age were independent predictors for increased RI at 6 months (p = 0.0078 and p = 0.0019). Diabetics had a significant higher RI before revascularization (0.74 +/- 0.08) than non-diabetics (0.68 +/- 0.12, p = 0.04). PSV after stenting was higher in patients with restenosis (1.4 +/- 0.4 m/sec vs. 1.0 +/- 0.3 m/sec, p = 0.002) and was an independent predictor for restenosis. CONCLUSIONS: Increased PSV within the stent one day after the procedure is predictive for restenosis. Patients with high grade RAS and older patients have a worse outcome. DUS is recommended to detect patients at risk for restenosis after percutaneous renal revascularization.