Long-term results of simplified frozen elephant trunk technique in complicated acute type A aortic dissection: A case-control study.

AIM: To describe the long-term experience of a simplified frozen elephant trunk technique (sFETT) used in complicated acute type A aortic dissection (AAAD) treatment. METHODS AND RESULTS: Between January 2001 and December 2012, 34 patients (mean age 59.9 ± 11.0 years) with complicated AAAD (DeBakey I) underwent an emergency surgery including sFETT. sFETT consisted in gluing the dissected aortic arch wall layers with gelatine-resorcinol adhesive and video-assisted antegrade open arch aortic stent-graft deployment in the arch or proximal descending aorta. In addition to sFETT, the aortic root was addressed with standard techniques. A 30-day mortality was 14.7% (five patients) due to bleeding (1), multiple organ failure (2), and colon ischemia (2). Postoperative morbidity included neurological (2), renal (1) and cardio-pulmonary complications (4), as well as wound infection (1). Mean follow-up was 74.4 ± 45.0 months. Actual survival rates were 73.5% at 1 year, 70.2% at 5 years, and 58.5% at 13 years of follow-up. Six patients died during long-term follow-up from heart failure (1) and unknown reasons (5). Five patients required reoperation for aortic arch (3) or aorto-iliac (2) progression of aneurysm during the mid- and long-term follow-up. The remaining patients showed favorable evolution of the dissected aorta with false lumen occlusion in most cases and stable aortic diameters. CONCLUSIONS: In AAAD patients, sFETT as used in our series is an easy and safe technique to repair the aortic arch. Long-term results after sFETT showed false lumen occlusion and stable aortic diameter in up to 13 years of follow-up.

Wall shear stress in the stented superficial femoral artery in peripheral arterial disease.

OBJECTIVE: Local changes in wall shear stress (WSS) contribute to vascular wall thickening and subsequent stenosis. Restenosis after stenting is a major concern, especially in the superficial femoral artery (SFA) of patients with peripheral arterial disease (PAD). Local alterations in WSS after stenting might contribute to restenosis/reocclusion. To test the hypothesis that WSS is impaired along the stented SFA segment, we studied the profile of WSS along the femoro-popliteal axis after stent placement in a cross-sectional design. METHODS: Eighty-seven patients with PAD (89 limbs) were included one day after stenting of the SFA. Flow velocities (peak and mean) and vessel diameter were measured by duplex ultrasound in five predefined segments along the femoro-popliteal axis, at rest and after exercise (30 toe raises); WSS (peak and mean) was calculated from flow velocities, vessel diameter and whole blood viscosity. RESULTS: WSS progressively declined along the stented segment at rest (peak WSS, p < 0.0001; mean WSS, p < 0.05); after exercise, WSS increased in all segments (all p < 0.001), but, again, progressively declined along the stent (peak WSS, p < 0.0001; mean WSS, p < 0.05). The internal vessel diameter remained unchanged after exercise in the stented and in the non-stented parts of the femoro-popliteal axis (all p > 0.05). CONCLUSION: In PAD patients with SFA stenting WSS is impaired along the femoro-popliteal axis. The consequences of this finding in terms of local effects on the vessel wall that might favor restenosis/reocclusion needs further investigation.

Autocatalytic nitration of prostaglandin endoperoxide synthase-2 by nitrite inhibits prostanoid formation in rat alveolar macrophages.

AIMS: Prostaglandin endoperoxide H(2) synthase (PGHS) is a well-known target for peroxynitrite-mediated nitration. In several experimental macrophage models, however, the relatively late onset of nitration failed to coincide with the early peak of endogenous peroxynitrite formation. In the present work, we aimed to identify an alternative, peroxynitrite-independent mechanism, responsible for the observed nitration and inactivation of PGHS-2 in an inflammatory cell model. RESULTS: In primary rat alveolar macrophages stimulated with lipopolysaccharide (LPS), PGHS-2 activity was suppressed after 12 h, although the prostaglandin endoperoxide H(2) synthase (PGHS-2) protein was still present. This coincided with a nitration of the enzyme. Coincubation with a nitric oxide synthase-2 (NOS-2) inhibitor preserved PGHS-2 nitration and at the same time restored thromboxane A(2) (TxA(2)) synthesis in the cells. Formation of reactive oxygen species (ROS) was maximal at 4 h and then returned to baseline levels. Nitrite (NO(2)(-)) production occurred later than ROS generation. This rendered generation of peroxynitrite and the nitration of PGHS-2 unlikely. We found that the nitrating agent was formed from NO(2)(-), independent from superoxide ((•)O(2)(-)). Purified PGHS-2 treated with NO(2)(-) was selectively nitrated on the active site Tyr(371), as identified by mass spectrometry (MS). Exposure to peroxynitrite resulted in the nitration not only of Tyr(371), but also of other tyrosines (Tyr). INNOVATION AND CONCLUSION: The data presented here point to an autocatalytic nitration of PGHS-2 by NO(2)(-), catalyzed by the enzyme's endogenous peroxidase activity and indicate a potential involvement of this mechanism in the termination of prostanoid formation under inflammatory conditions.

Impact of social characteristics on the treatment of patients with ischaemic events and patent foramen ovale.

OBJECTIVE: Percutaneous closure of a patent foramen ovale (PFO) is a technically simple and safe procedure. PFO is a common finding present in up to one third of the population. Although several conditions such as stroke, migraine, and sleep apnoea have been associated with a PFO, as underlined by observational studies, no causal relationship has been documented so far. As this setting may potentially leave more space for the involved physicians for the choice of treatment, we hypothesized that social characteristics of the patient with a PFO might play a role. METHODS: We retrospectively analysed the data of 153 patients with a cerebrovascular and/or peripheral ischaemic event with the diagnosis of a PFO as documented in echocardiography from 2000 until 2005 at the University Hospital in Zurich, Switzerland. RESULTS: Forty-four patients (= 23%) underwent catheter-based PFO closure. There was no significant difference with respect to age (<40 years: P = 0.094, ns; 40-59 years: P = 0.923, ns; > or =60 years: P= 0.234, ns), gender (P = 0.356, ns) and insurance status (<40 years: P= 0.15, ns; 40-59 years: P= 0.37, ns; 60 years: P = 0.26, ns) between those who underwent percutaneous PFO closure and those who did not. CONCLUSION: We conclude from this single-centre experience that social characteristics of patients only have a marginal impact on the indication of percutaneous closure of a PFO, if at all.

High-dose atorvastatin treatment in patients with peripheral arterial disease: effects on platelet aggregation, blood rheology and plasma homocysteine.

BACKGROUND: Statins are used for the treatment of hypercholesterolemia. Although they are well known to have pleiotropic effects, their dose-dependent influence on platelet aggregation, hemorheologic properties and the plasma levels of homocysteine in patients with peripheral arterial disease (PAD) has not been thoroughly investigated so far. METHODS AND RESULTS: From a total of 100 patients with PAD 48 patients were randomized to a treatment with atorvastatin 80 mg/d for six months, and 52 patients served as controls who continued their medication including statins in lower doses. At baseline and at six months' follow up we assessed platelet aggregation upon stimulation with ADP, collagen and epinephrine using light transmission aggregometry. Furthermore, we determined major hemorheologic variables as well as the plasma levels of homocysteine, folic acid, and vitamin B6 and B12. No patient had obtained folic acid or B vitamin supplement. Platelet aggregation upon agonist-induced stimulation did not differ between patients under high-dose atorvastatin therapy and controls at baseline and after six months (p > 0.05). All hemorheologic parameters (plasma viscosity, red cell aggregation, whole blood viscosity, hematocrit, platelets, leucocytes) measured at baseline and after six months were not significantly different between both groups, too. After therapy with 80 mg atorvastatin homocysteine levels were significantly elevated as compared with baseline values (p = 0.0007), whereas levels remained unchanged in the control group. Folic acid levels were higher in the patients receiving high-dose atorvastatin as compared with controls both at baseline (p = 0.002) and at six months' follow up (p = 0.034). No significant difference in vitamin B6 and B12 levels both at baseline and after six months could be detected in either group. CONCLUSIONS: Treatment with 80 mg atorvastatin did not affect platelet aggregation and major hemorheologic parameters. The finding of an increase of homocysteine plasma levels in the presence of rather elevated levels of folic acid needs further investigation.

Formation of pseudoaneurysm after aortic valve replacement without previous endocarditis: a case-control study.

BACKGROUND: The aim of this study was to identify the predisposing factors for pseudoaneurysm formation after aortic valve replacement without previous endocarditis. METHODS: Echocardiography was used to identify patients. Parameters with influence on the occurrence of pseudoaneurysms were analyzed, and the odds ratio for the influence of the type of valve was estimated. The chi2 goodness-of-fit test was used to analyze whether location or underlying etiology was associated with an accumulated occurrence of a pseudoaneurysm. Fisher's exact test was used to assess a possible relation between the occurrence of a pseudoaneurysm after composite graft implantation and etiology or location. RESULTS: Patients treated with composite grafts had a 27-fold increased risk for developing pseudoaneurysms (psiMH=27; 95% confidence interval, 1.61-454.19) in comparison with aortic valve replacement only. There was a significant difference for the probability of different etiologies to occur (P=.032), with Stanford type A aortic dissection and aortic regurgitation being the most often occurring pathologies. Significant associations between the use of a composite graft and both the underlying etiology (P=.002) and the location of the pseudoaneurysm (P=.04) was found. Furthermore, patients with composite grafts had larger diameters of the aortic root compared with patients with aortic valve replacement only (P=.03). Neither the diameter of the annulus of the aortic valve (95% confidence interval, 0.89-1.32; P=.41) nor the diameter of the ascending aorta (95% confidence interval, 0.27-1.97; P=.54) had any influence on pseudoaneurysm formation. CONCLUSIONS: The underlying disorder, determining the surgical procedure, influences the risk for the development of pseudoaneurysms in patients without previous endocarditis. The location of most pseudoaneurysms at the level of the aortic root may be a consequence of its larger diameter.

A novel operator-independent algorithm for cardiac output measurements based on three-dimensional transoesophageal colour Doppler echocardiography.

AIMS: Cardiac output (CO) measurements from three-dimensional (3D) trans-mitral Doppler echocardiography are prone to error as manual selection of the region of interest (i.e. the site of measurement) is required. We newly developed an automated, user-independent algorithm to select the site of colour Doppler CO measurement. We aimed to validate this new method by benchmarking it against thermodilution, the current gold standard for CO measurements. METHODS AND RESULTS: Transoesophageal colour 3D Doppler echocardiographic studies were obtained from 15 patients who also had received a pulmonary catheter for invasive CO measurements. Trans-mitral flow was determined using a novel operator-independent algorithm to automatically select the optimal site of measurement. The operator-independent CO measurements were referenced against thermodilution. A good correlation was found between operator-independent Doppler flow computations and thermodilution with a mean bias of 0.09 L/min, standard deviation of bias 1.3 L/min, and a 26% error (2 SD/mean CO). Mean CO was 4.94 L/min (range 3.10-7.10 L/min). CONCLUSION: Our findings demonstrate that CO computation from transoesophageal colour 3D Doppler echo can be automated concerning the site of velocity measurement. Our operator-independent algorithm provides an objective and reproducible alternative to thermodilution.

Isolated cleft in the posterior mitral valve leaflet: a congenital form of mitral regurgitation.

BACKGROUND: Isolated congenital cleft of the posterior leaflet of the mitral valve is a rare cause of mitral regurgitation (MR). This study describes the clinical, echocardiographic, and intraoperative findings as well as treatment options. METHODS: Adults with an isolated cleft of the posterior mitral valve leaflet diagnosed by transthoracic echocardiography were evaluated with respect to clinical, echocardiographic, preoperative and intraoperative findings, and different surgical strategies. RESULTS: The prevalence of isolated cleft of the posterior mitral valve leaflet in all patients examined was 0.11% (n = 22 out of 19 320 evaluated echocardiograms); male gender was predominant (73%). Dyspnea on exertion was present in almost all patients with at least moderate regurgitation. The predominant localization of the cleft was within segment P2 (59%), followed by a cleft between P1/P2 (18%). An isolated cleft in segment P3 or segment P1 occurred twice in each segment (n = 2; 9%) and between P2/P3 once (n = 1; 5%). Regurgitation was severe in 50% (n = 11), moderate in 9% (n = 2), mild in 27% (n = 6), and only trivial in 14% (n = 3) of the patients. Surgical treatment involved reconstruction with ring annuloplasty in 45% (n = 10) and replacement in 4.5% (n = 1). A total of 11 patients (50%) with mostly mild or trivial mitral regurgitation were treated medically only. CONCLUSION: Two-dimensional high-resolution cross-sectional echocardiography allows the distinct diagnosis of a clefted posterior leaflet, whereas clinical presentation, electrocardiogram, chest x-ray, and angiography are failing to identify the correct etiology of MR in patients with isolated posterior leaflet cleft mitral valve (IPLCMV). Patients with moderate to severe MR were treated surgically with excellent outcome.

Signalling processes in endothelial ageing in relation to chronic oxidative stress and their potential therapeutic implications in humans.

Ageing is an important risk factor for the development of cardiovascular diseases. Vascular ageing is mainly characterized by endothelial dysfunction, an alteration of endothelium-dependent signalling processes and vascular remodelling. The underlying mechanisms comprise increased production of reactive oxygen species (ROS), inactivation of nitric oxide (.NO) and subsequent formation of peroxynitrite (ONOO(-)). Elevated ONOO(-) may exhibit new messenger functions by post-translational oxidative modification of intracellular regulatory proteins. Mitochondria are a major source of age-associated superoxide formation, as electrons are misdirected from the respiratory chain. Manganese superoxide dismutase (MnSOD), a mitochondrial antioxidant enzyme, is an integral part of the nucleoids and may protect mitochondrial DNA from ROS. A model linking .NO, mitochondria, MnSOD and its acetylation/deacetylation by sirtuins (NAD+-dependent class III histone deacetylases) may be the basis for a potentially new powerful therapeutic intervention in the ageing process.

Serological evidence for the association of Bartonella henselae infection with arrhythmogenic right ventricular cardiomyopathy.

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an important cause of sudden death in young adults. On the basis of histopathological findings its pathogenesis may involve both a genetic origin and an inflammatory process. Bartonella henselae may cause endomyocarditis and was detected in myocardium from a young male who succumbed to sudden cardiac death. HYPOTHESIS: We hypothesized that chronic infection with Bartonella henselae could contribute to the pathogenesis of ARVC. METHODS: We investigated sera from 49 patients with ARVC for IgG antibodies to Bartonella henselae. In this study, 58 Swiss blood donors tested by the same method served as controls. RESULTS: Six patients with ARVC (12%) had positive (>1:256) IgG titres in the immunofluorescence test with Bartonella henselae. In contrast, only 1 elevated titre was found in 58 controls (p < or = 0.05). Interestingly, all patients with increased titres had no familial occurrence of ARVC. CONCLUSIONS: Further studies in larger patient cohorts seem justified to investigate a possible causal link between chronic Bartonella henselae and ARVC, in particular its sporadic (nonfamilial) form.

Endogenous peroxynitrite modulates PGHS-1-dependent thromboxane A2 formation and aggregation in human platelets.

Aggregation of activated platelets is considerably mediated by the autocrine action of thromboxane A2 (TxA2) which is formed in a prostaglandin endoperoxide H2 synthase-1 (PGHS-1 or COX-1)-dependent manner. The activity of PGHS-1 can be stimulated by peroxides, an effect termed "peroxide tone", that renders PGHS-1 the key regulatory enzyme in the formation of TxA2. Activated platelets release nitric oxide (*NO) and superoxide (O*2) but their interactions with the prostanoid pathway have been controversially discussed in platelet physiology and pathophysiology. The current study demonstrates that endogenously formed peroxynitrite at nanomolar concentrations, originating from the interaction of *NO and *O2, potently activated PGHS-1, which parallels TxA2 formation and aggregation in human platelets. Inhibition of the endogenous formation of either *NO or O*2 resulted in a concentration-dependent decline of PGHS-1 activity, TxA2 release, and aggregation. The concept of peroxynitrite as modulator of TxA2 formation and aggregation explains the interaction of *NO and O*2 with the PGHS pathway and suggests a mechanism by which antioxidants can regulate PGHS-1-dependent platelet aggregation. This may provide a molecular explanation for the clinically observed hyperreactivity of platelets in high-risk patients and serve as a basis for novel therapeutic interventions.

High-dose atorvastatin in peripheral arterial disease (PAD): effect on endothelial function, intima-media-thickness and local progression of PAD. An open randomized controlled pilot trial.

Beneficial effects of aggressive lipid-lowering with high-dose atorvastatin (80 mg/day) have been demonstrated in patients with coronary and cerebrovascular disease. The impact of such a therapy in patients with peripheral arterial disease (PAD) is less known so far. Here we studied the effects of high-dose atorvastatin on brachial artery endothelial function, common carotid intima-media thickness (IMT) and local progression of PAD in these patients. One hundred of 500 patients screened with documented PAD were randomly assigned to receive 80 mg of atorvastatin daily for six months or to continue on conventional medical treatment. Ninety-six percent of patients in the control group were on standard statin treatment. High resolution B-mode ultrasonography was used to study brachial artery flow-mediated dilation (FMD), IMT and ankle-brachial index (ABI) at baseline and at six months. FMD and IMT at baseline and at six months were 4.1 (0.06-8.6) versus 5.0 (0.76 vs. 8.1) %, p = 0.96, and 0.76 (0.66-0.82) versus 0.73 (0.63-0.81) mm, p = 0.41, respectively, in the atorvastatin group, and 2.66 (-1.9-6.9) versus 3.65 (0.0-8.6)%, p = 0.02, and 0.78 (0.71-0.90) versus 0.77 (0.70-0.90) mm, p = 0.48, in the control group. ABI at baseline and at six months was not different in either group. LDL cholesterol was reduced from 2.53 (2.21-3.28) to 1.86 (1.38-2.29) mM (p < 0.0001) in the atorvastatin group, whereas levels remained stable in the control group [2.38 (1.94-3.16) vs. 2.33 (1.82-2.84) mM, p = 0.61]. Major adverse cardiovascular events occurred in 2.1% in the atorvastatin group and 1.9% in the control group (p = 0.61). In conclusion, in this pilot trial aggressive lipid-lowering with 80 mg of atorvastatin daily for six months had no effect on brachial artery FMD in patients with PAD. IMT and ABI were also similar in patients with and without high-dose atorvastatin at six months.

Inactivity of nitric oxide synthase gene in the atherosclerotic human carotid artery.

OBJECTIVE: Nitric oxide (NO) inhibits thrombus formation, vascular contraction, and smooth muscle cell proliferation. We investigated whether NO release is enhanced after endothelial NO synthase (eNOS) gene transfer in atherosclerotic human carotid artery ex vivo. METHODS AND RESULTS: Western blotting and immunohistochemistry revealed that transduction enhanced eNOS expression; however, neither nitrite production nor NO release measured by porphyrinic microsensor was altered. In contrast, transduction enhanced NO production in non-atherosclerotic rat aorta and human internal mammary artery. In transduced carotid artery, calcium-dependent eNOS activity was minimal and did not differ from control conditions. Vascular tetrahydrobiopterin concentrations did not differ between the experimental groups. Treatment of transduced carotid artery with FAD, FMN, NADPH, L-arginine, and either sepiapterin or tetrahydrobiopterin did not alter NO release. Superoxide formation was similar in transduced carotid artery and control. Treatment of transduced carotid artery with superoxide dismutase (SOD), PEG-SOD, PEG-catalase did not affect NO release. CONCLUSIONS: eNOS transduction in atherosclerotic human carotid artery results in high expression without any measurable activity of the recombinant protein. The defect in the atherosclerotic vessels is neither caused by cofactor deficiency nor enhanced NO breakdown. Since angioplasty is performed in atherosclerotic arteries,eNOS gene therapy is unlikely to provide clinical benefit.

Low-molecular-weight heparin for prevention of restenosis after femoropopliteal percutaneous transluminal angioplasty: a randomized controlled trial.

BACKGROUND: Restenosis after angioplasty is essentially due to intimal hyperplasia. Low-molecular-weight heparins (LMWHs) have experimentally been shown to have antiproliferative effects in addition to their antithrombotic properties. Their potential in reducing restenosis remains to be established. Therefore, we wanted to test the hypothesis that LMWH plus aspirin is more effective than aspirin alone in reducing the incidence of restenosis/reocclusion in patients undergoing percutaneous transluminal angioplasty (PTA) of femoropopliteal arteries. Further, different effects of LMWH in patients treated for critical limb ischemia (CLI) or claudication only should be investigated. METHODS: After successful PTA, 275 patients with symptomatic peripheral arterial disease (claudication or critical limb ischemia) and femoropopliteal obstructions were randomized to receive either 2500 IU of dalteparin subcutaneously for 3 months plus 100 mg of aspirin daily (n = 137), or 100 mg aspirin daily alone (n = 138). The primary end point was restenosis or reocclusion documented by duplex ultrasonography imaging at 12 months. RESULTS: Restenosis/reocclusion occurred in 58 patients (44%) in the dalteparin group and in 62 patients (50%) in the control group (P = .30). In a subgroup analysis according to the severity of peripheral arterial disease, we found that in patients treated for claudication, restenosis/reocclusion developed in 43 (43%) in the dalteparin group, and in 35 (41%) in the control group (P = .70); in patients treated for CLI, restenosis/reocclusion was significantly lower in the dalteparin group (15, 45%) than in the control group (27, 72%; P = .01). No major bleeding events occurred in either group. CONCLUSIONS: Treatment with 2500 IU dalteparin subcutaneously given for 3 months after femoropopliteal PTA failed to reduce restenosis/reocclusion at 12 months. However, dalteparin may be beneficial in the subgroup of patients with CLI at 12 months follow-up.

Age-associated cellular relocation of Sod 1 as a self-defense is a futile mechanism to prevent vascular aging.

Vascular aging is characterized by the presence of chronic oxidative stress. Although cytosolic Sod 1 has a key role in the detoxification of superoxide ((*)O(2)(-)), little is known about its importance in vascular aging. We found that inhibition of Sod 1 had no effect on (*)O2- generation. Furthermore, its expression decreased in an age-dependent manner. Interestingly, Sod 1 loses its membrane-association and is also lost from the caveolae with increasing age. Instead, a relocation of Sod 1 to the mitochondria takes place, presumably in an attempt to maintain mitochondrial integrity and to counter-balance age-associated oxidative stress. Unlike Sod 2, which is constitutively expressed in mitochondria to control (*)O2- radical fluxes, Sod 1 is not inactivated by peroxynitrite and is not nitrated as a function of age. These novel insights into oxidative stress-associated vascular aging and the understanding about how redox-systems are regulated in old age may identify new targets to ameliorate aging as the greatest cardiovascular risk factor.

Decreased wall shear stress in the common carotid artery of patients with peripheral arterial disease or abdominal aortic aneurysm: relation to blood rheology, vascular risk factors, and intima-media thickness.

BACKGROUND: Wall shear stress, a local risk factor of atherosclerosis, is decreased in the common carotid artery of patients with vascular risk factors. We evaluated wall shear stress in the common carotid artery of patients with symptomatic peripheral arterial occlusive disease (PAD) and abdominal aortic aneurysm (AAA). As blood viscosity is a determinant of wall shear stress, we further investigated the impact of rheologic variables on wall shear stress in relation to vascular risk factors and intima-media thickness. METHODS: High-resolution ultrasonography scans were used to study intima-media thickness, internal diameter, and blood velocity in the common carotid artery of 31 patients with PAD, 36 patients with AAA, and 37 controls. Furthermore, major hemorheologic variables and vascular risk factors were evaluated, and wall shear stress was calculated. RESULTS: Wall shear stress was lower in patients with PAD (median [IQR], dynes/cm(2): 14.4 [10 to 19]) and with AAA (12.1 [9 to 15]) than in healthy controls (20.6 [17 to 24]; P < .0001). Wall shear stress was inversely related to red cell aggregation (P = .01), fibrinogen (P = .003), leucocyte count (P = .001), plasma viscosity (P = .04), and intima-media thickness (P < .0001). Furthermore, wall shear stress was negatively associated with age, smoking, and triglycerides, but positively correlated with high-density lipoprotein cholesterol (all P < .001). When the influence of all these predictors were simultaneously taken into account in a multiple regression model, only age (P < .0001), smoking (P = .005), and triglycerides (P = .003) remained significantly associated with wall shear stress. CONCLUSIONS: This is the first report, to our knowledge, showing that wall shear stress of the common carotid artery is decreased in patients with symptomatic PAD and in patients with AAA. Rheologic variables are less important in predicting wall shear stress than age, triglycerides, and smoking.

Novel doppler assessment of intracoronary volumetric flow reserve: validation against PET in patients with or without flow-dependent vasodilation.

UNLABELLED: Volumetric blood flow (Q) determination requires simultaneous assessment of mean blood flow velocity and vessel cross-sectional area. At present, no method provides both values. Intracoronary Doppler-based assessment of coronary flow velocity reserve (CFVR) relies on average peak velocity (APV). Because this does not account for changes in velocity profile or vessel area usually occurring with flow-dependent vasodilation, results can be misleading. The aim of this clinical study was to validate against the current gold standard (measurement of myocardial perfusion reserve [MPR] by PET) a new, Doppler-based method for calculating coronary Q and coronary flow reserve (CFR). METHODS: Doppler-based intracoronary Q was measured with a proprietary guidewire device in a nonstenotic coronary artery at baseline and during adenosine-induced hyperemic flow (140 mug/kg/min intravenously during 7 min). Three gate positions were assessed, of which 2 were lying within the vessel and 1 was intersecting the vessel. The zeroth (M(0)) and the first (M(1)) Doppler moments of the intersecting gate were used to calculate mean blood flow velocity (M(1)/M(0)) and vessel area (M(0)), and M(0) of the 2 proximal gates was used to correct for scattering and attenuation. CFR was calculated as hyperemic/resting flow with Q and compared with APV-derived CFVR and with the corresponding segmental MPR obtained with (15)O-labeled water and PET. RESULTS: Q (CFR, 2.60 +/- 1.07) correlated well with PET (MPR, 2.58 +/- 1.11) (r = 0.832, P < 0.005; Bland-Altman limits, -1.42 to 1.09), whereas CFVR did not (r = 0.09, P = not statistically significant; Bland-Altman limits, -3.36 to 2.24). However, in vessels without dilation, there was no difference between CFR, CFVR, and MPR. CONCLUSION: This procedure for intracoronary Q measurement using the proprietary Doppler guidewire system, which accounts for both changes in flow profile and changes in vessel area, allows invasive, accurate assessment of CFR even in the presence of flow-dependent vasodilation.

Blood fluidity and outcome after femoropopliteal percutaneous transluminal angioplasty (PTA): role of plasma viscosity and low platelet count in predicting restenosis.

Rheological abnormalities are well known in patients with peripheral arterial occlusive disease (PAOD). We wanted to determine whether rheological variables are related to restenosis after femoropopliteal percutaneous transluminal angioplasty (PTA). In 114 patients (62 men; median age 70 years) undergoing femoropopliteal PTA for symptomatic peripheral arterial occlusive disease (PAOD) plasma viscosity, red cell aggregation, whole blood viscosity, hematocrit, fibrinogen, platelet count, leukocytes and C-reactive protein were determined the day after the procedure and at 1, 3, and 12 months. The primary endpoint was restenosis >50% documented by duplexsonography up to 12 months. Cox proportional hazards analysis was used to assess the risk of restenosis for postinterventional values of rheological variables. Forty-eight patients (42%) developed restenosis at 12 months. Patients with restenosis had higher baseline plasma viscosity (PV) (medians, 1.71 vs. 1.65 millipascal seconds [mPa.s]; p = 0.04) and lower platelet count (224 vs. 240 x 10(3)/microl; p = 0.03) than patients without restenosis. The hazard ratio (HR; 95% CI) of incident restenosis was 9.2 (1.12-76; p = 0.03) for PV and 0.99 (0.99-1.0; p = 0.07) for PLT. When examining jointly both high PV and low platelet count (PLT), patients with PV > 1.66 mPa.s and PLT < 233 x 10(3)/microl (i.e. variables split at their respective median) had an increased risk of restenosis (log-rank test p = 0.01). Multivariate Cox proportional hazard analysis showed that plasma viscosity (p = 0.02), low platelet count (p = 0.01), lesion length (p = 0.0037) and lack of hypertension (p = 0.01) were associated with restenosis at 12 months. No associations were found between restenosis and the other rheological and inflammatory variables studied. Our data suggest that increased PV and low PLT contribute to restenosis after femoropopliteal PTA.