Recurrence of cryptogenic stroke or TIA in patients with patent foramen ovale successfully treated by using different kind of percutaneous occluder devices: five-year follow-up.

AIM: Cryptogenic stroke remains the final diagnosis in 40% of ischemic acute cerebrovascular events. Until now there are no clinical evidences that the percutaneous closure of PFO is able to prevent the recurrence of stroke or transient ischemic attack (TIA). The aim of this study was to evaluate the incidence of recurrence in patients successfully treated by percutaneous closure of PFO with different occluder devices by using TCD, TTE and clinical evaluation. METHODS: From February 2004 to November 2009, 72 pts, (40 females and 32 males; average age 46 yrs, range 14-66), admitted with diagnosis of recurrent ischemic neurologic events (58 stroke and 14 TIA) underwent percutaneous closure of PFO. Thirty-one (43%) of the 72 patients had a concomitant history of migraine, 16 (52%) of whom with aura. Five different occluder devices were used, with a total amount of 74 implants. All pts were studied during the follow-up by clinical evaluation (Rankin modified scale), TCD and TTE. RESULTS: Successful device deployment is achieved in 100% of pts without any periprocedural major complication. Only in two pts atrial arrhythmia have occurred. All pts was discharged within 3 days in good overall conditions. In all pts a double antiplatelet regimen was adopted. The follow-up was complete in 100% of the cases (median 30, range 3-58 months ). At five years, there was no recurrent stroke or TIA, and no new cerebral lesions developed by MRI in those patients with residual shunt. Moreover, in 65 (90%) of them the Rankin scale significantly (P<0.0001) reduced to 0 whereas only in 2 pts score 1 was reached. In 19 (61%) of the 31pts with concomitant migraine, the intensity and the frequency of the attacks significantly (P<0.0001) decreased over time. At the TCD, 5 pts (7%) resulted positive for microembolic signals but, only 1 of them, was successfully treated for an associate defect. The TTE evaluation showed however an optimal sealing of all the devices without signs of erosion, incomplete closure and thrombus formation around the device. CONCLUSION: Our experience suggests that percutaneous treatment of PFO is safe and beneficial at the medium term follow-up for secondary prevention since able to prevent the clinical recurrence of acute cerebrovascular events irrespective of the device used.

Endovascular treatment of pulmonary and cerebral arteriovenous malformations in patients affected by hereditary haemorrhagic teleangiectasia.

Hereditary Haemorrhagic Teleangiectasia (HHT) is a vascular disorder of angiogenesis transmitted in an autosomal dominant pattern, characterised by heterogeneity in clinical manifestations. One of the most important organ involved is lung, including pulmonary arteriovenous malformations (PAVM). PAVM occur in 20 to 30% of the HHT population and recently are considered a marker of disease. PAVM are direct artery-to-vein connections with low pressure and without an interveining capillary bed. PAVM are classified as simple (supplied by one feeding artery) or complex (receiving blood supply from two or more feeding artery). According to the international reports, treatment it's recommendable for all PAVM with feeding vessels 3mm or larger, in order to reduce the risk of cerebral ischaemia and neurologic manifestations frequently attributed to paradoxical embolisation. Transcatheter embolotherapy of PAVM is a form of treatment based on occlusion of the feeding artery to a PAVM by using platinum coils or detachable balloons. The technique of coil embolisation involves the exact localisation of PAVM by pulmonary angiography followed by superselective percutaneous caheterisation of feeding artery obtained by using a dedicated 7F guiding catheter, which coaxially allocates a 5F hydrophilic catheter advanced in order to perform both superselective angiography of feeding artery and embolisation itself. Inside the 5F catheter the platinum coils are advanced using a .035'' guide-wire and released until an optimal occlusion of feeding artery is achieved. At the end of the procedure angiographic control is performed in order to verify the occlusion of feeding artery. The use of platinum coils is preferable over detachable balloons when feeding artery are greater than 7 mm in diameter and have irregular anatomical configuration. On the other hand, the principal advantage of using detachable balloons is that the balloon itself can be deflated and repositioned if necessary. Transcatheter embolotherapy is technically safe and clinically effective and may represent the primary choice of treatment in HHT patients. On the other hand the most common complications of this treatment (pleurisy and air embolism) can be prevented by using some tips during the embolisation procedure like "anchor technique," "scaffold technique" and "balloon assisted technique." Cerebral arteriovenous malformations (CAVM) are present in 10-20% of patients with HHT and multiple in 50% of cases. Cortical surface is the most frequent localisation. Angiography is needed to diagnose all CAVM and to clarify the angioarchitecture of the lesion. In HHT CAVM are usually either micro-AVM, with a nidus not bigger than 1 cm, or small AVM, with a nidus between 1 and 3 cm. Quite frequently there are lesions characterised by arteriovenous fistulas. In the three patterns of CAVM usually found in HHT, small AVM are the most risky for bleeding although the risk is lower than that associated with sporadic ones. It is estimated from 0.38 to 0.69% per year in spite of the general incidence of bleeding in sporadic CAVM that ranges from 2 to 4% per year. In HHT patients, at present, the precise indications and timing of treatment are not established. Trend is to treat small AVM and AVF and to follow-up micro-AVM with MRI and angiography. As for sporadic CAVM, treatment of small AVM is usually referred to stereotactic radiosurgery. Endovascular embolisation is proposable if the lesion is easily reachable by microcatheterism and the position of the microcatheter is safe. Glue is used for embolisation and the technique is briefly discussed.

Stent-graft treatment of complete acute aortic transection complicated by intussusception and pseudo-coartaction.

Aim of the study was to validate the use of endoluminal stent-graft treatment as an alternative to conventional surgery in patients affected by blunt chest trauma and aortic disruption with multiple associated lesions. We report the case of a young female admitted with diagnosis of descending thoracic aortic transection and multiple traumas following a car accident. Spiral computed tomography revealed circular disruption of thoracic aorta immediately after isthmus region with intussusception of leaflets and pseudo-coartation. Doppler analysis showed a 70 mmHg transaortic gradient. The hemodynamic evaluation confirmed the existence of severe transaortic gradient. A Gore-TAG endoprosthesis (26 x 100 mm) was selected. Intraoper-ative transesophageal echocardiography assessment was performed to monitoring the entire procedure. The final arteriogram showed an optimal sealing at proximal and distal site without endoleak with complete readjustment of intimal leaflets to the aortic wall and disappearance of transaortic gradient related to the pseudo-coartation. No complication was observed in the early postoperative and patient was discharged one month later once complete rehabilitation of associated lesion was obtained. Computed tomography scan performed before discharge revealed persistency of patent lumen of aorta with fibrosis of readjusted circumferential intimal flap. In conclusion endovascular repair of complete aortic transection may result safe and effective particularly in patients with extensive associated injuries. Indeed the severity of coexisting non-aortic lesions could be adversely affected by conventional surgery in consideration of high surgical morbidity due to open thoracotomy. Stent-graft repair allows the patient to timely undergo medical or surgical management of associated lesions and a prompt rehabilitation with shorter hospital stay.

Endovascular stent-graft treatment for diseases of the descending thoracic aorta.

OBJECTIVE: Assessment of endovascular stent-graft treatment for diseases of the descending thoracic aorta as a valid and effective alternative to surgery. METHODS: From March 1999 to August 2000, a total of 16 patients underwent deployment of endovascular stent-grafts in the descending thoracic aorta. Patients were divided into three groups according to the type of lesion. Group A (n=8) included five patients with atherosclerotic aneurysm and three with chronic post-traumatic pseudoaneurysm. Patients with acute post-traumatic pseudoaneurysm (n=3) and type B aortic dissection (n=5) were included in Groups B and C, respectively. All patients underwent 5-mm chest spiral angio-computerized tomography (CT) scan and angiography as preoperative assessment. The deployed stent-graft systems were Talent-Medtronic and Excluder-Gore. RESULTS: A total of 20 stent-grafts were placed. Two patients required deployment of two grafts, while three grafts were juxtaposed in a third patient in order to treat larger lesions. There was no mortality related to the procedure, although one patient (6.2%) died because of multiorgan failure 24h post-operatively. The placement of the graft was successful in all cases except one affected with type B dissection and characterized by a very large intimal flap, which was eventually fenestrated by graft guidewire. Therefore, an optimal sealing of the grafts was achieved in 15 patients. However, in one patient the descending aorta had to be surgically replaced because of the calcified pseudoaneurysm still compressing the trachea and left bronchus. Two patients required a left carotid-subclavian by-pass in order to achieve a sufficient neck for the proximal placement of the graft. No spinal cord injuries were observed. At the follow-up, performed with chest spiral angio-CT scan within 72 h and scheduled at 6 and 12 months and once a year, no stent-graft related complications have been detected. CONCLUSIONS: Endoluminal stent-graft treatment may represent a valid option in well-selected cases of descending thoracic aorta diseases. A longer follow-up in a larger series of patients is desirable to confirm these initial positive results.

Instrumental validation of percutaneous transmyocardial revascularization: follow-up data at one year.

BACKGROUND: Despite the clinical efficacy of percutaneous transmyocardial revascularization (PTMR), up to date there are still no instrumental validations to demonstrate both the improved perfusion of treated areas and cardiac function. METHODS: During the first year of follow-up after PTMR, 27 patients (group A) underwent 99mTc MIBI exercise-single photon emission tomography (SPET), while 30 patients (group B) underwent serial transthoracic echocardiography (TTE) evaluations with analysis of cardiac volumes and subendocardial layer thickness in systole. RESULTS: All 57 patients had a significant angina Canadian Cardiovascular Society (CCS) class improvement. Group A patients (75%) had improved exercise-SPET perfusion in treated areas at 12 weeks after PTMR, and at the next follow-up. Group B patients had non-significant reduction in global volume and no significant change in ejection fraction. However, there was an improvement in thickness of the subendocardial-treated areas in systole that persisted during follow-up. CONCLUSIONS: The use of SPET and TTE validates the clinical efficacy of PTMR.

Inflammatory response and angiogenesis after percutaneous transmyocardial laser revascularization.

BACKGROUND: The aim of our study was to investigate the inflammatory response immediately after percutaneous transmyocardial laser revascularization (PTMR) along with the underlying mechanism of angiogenesis. METHODS: Patients with angina pectoris underwent coronary angiography and were divided into two groups. Group A (n = 10) included patients with obstructed vessels who received PTMR, whereas group B (n = 5) comprised patients who had normal coronary arteries. Blood levels of neutrophils, procalcitonin, troponin-I, myoglobin, and creatine kinase (CK) mass were evaluated in each patient before angiography and monitored up to 48 hours after the procedure. Six patients were injected with 99mTc-leukoscan approximately 60 to 90 minutes after PTMR. During the 240 to 300 minutes after the radionuclide administration, single photon emission tomography (SPET) was performed and compared with conventional 99mTc-sestamibi-SPET. RESULTS: A significant increase in blood levels of neutrophils and procalcitonin was observed in group A only (p < 0.005). A slight but significant increase of troponin-I was evident in the same group (p < 0.05), and a distinct myocardial uptake of 99mTc-Leukoscan-SPET was observed in each patient along homologous regions treated by PTMR. CONCLUSIONS: The increased amount of neutrophils (both circulating and inside the treated myocardial areas) along with the raised levels of procalcitonin were the immediate reactions to PTMR. This systemic and intramyocardial inflammatory response is the underlying mechanism that gives rise to angiogenesis.

Effect of intravenous propranolol on coronary vasomotion at rest and during dynamic exercise in patients with coronary artery disease.

Coronary vasomotion was studied at rest and during bicycle exercise with biplane quantitative coronary arteriography in 28 patients with coronary artery disease. Patients were divided into two groups; the first 18 patients served as controls (group 1), and the next 10 patients were treated with propranolol 0.1 mg/kg, which was infused intravenously before exercise (group 2). Luminal area of a normal and a stenotic vessel segment was determined at rest, during supine bicycle exercise, and 5 minutes after sublingual administration of 1.6 mg nitroglycerin after exercise. In group 1, the normal vessel showed vasodilation (+16%, p less than 0.001) during exercise, whereas the stenotic vessel segment showed vasoconstriction (-31%, p less than 0.001). After sublingual administration of nitroglycerin, there was coronary vasodilation of both normal (+36%, p less than 0.001 vs. rest) and stenotic (+20%, p less than 0.001) vessel segments. Patients with angina pectoris during supine exercise (n = 10) had significantly (p less than 0.05) more vasoconstriction (-36%) than patients without angina (-23%). In group 2, intravenous administration of propranolol at rest was associated with a decrease in luminal area of both normal (-24%, p less than 0.001) and stenotic (-43%, p less than 0.001) vessel segments; however, during subsequent exercise, both normal (-2%, p = NS vs. rest) and stenotic (-3%, p = NS vs. rest) vessel segments dilated when compared with the measurements after propranolol. Administration of nitroglycerin further increased luminal area of both vessel segments (normal segment, +23%, p less than 0.001; stenotic segment, +46%, p less than 0.001 vs. rest). It is concluded that dynamic exercise in patients with coronary artery disease is associated with coronary vasodilation of the normal and vasoconstriction of the stenotic coronary arteries. Patients with exercise-induced angina had significantly more stenosis vasoconstriction than patients without angina although minimal luminal area at rest was similar. Intravenous administration of propranolol is accompanied by a significant decrease in coronary luminal area of both normal and stenotic vessel segments at rest, which is overridden by dynamic exercise and sublingual nitroglycerin. The reduction in myocardial oxygen consumption and the prevention of exercise-induced stenosis vasoconstriction might explain the beneficial effect of beta-blocker treatment in most patients with coronary artery disease.

Functional and structural abnormalities in patients with dilated cardiomyopathy.

Passive diastolic properties of the left ventricle were determined in 10 control subjects and 12 patients with dilated cardiomyopathy. Simultaneous left ventricular angiography and high fidelity pressure measurements were performed in all patients. Left ventricular chamber stiffness was calculated from left ventricular pressure-volume and myocardial stiffness from left ventricular stress-strain relations with use of a viscoelastic model. Patients with dilated cardiomyopathy were classified into two groups according to the diastolic constant of myocardial stiffness (beta). Group 1 consisted of seven patients with a normal constant of myocardial stiffness less than or equal to 9.6 (normal range 2.2 to 9.6) and group 2 of 5 patients with a beta greater than 9.6. Structural abnormalities (percent interstitial fibrosis, fibrous content) in patients with dilated cardiomyopathy were assessed by morphometry from right ventricular endomyocardial biopsies. Heart rate was similar in the three groups. Left ventricular end-diastolic pressure was significantly greater in patients with cardiomyopathy (18 mm Hg in group 1 and 22 mm Hg in group 2) than in the control patients (10 mm Hg). Left ventricular ejection fraction was significantly lower in groups 1 (37%) and 2 (36%) than in the control patients (66%). Left ventricular muscle mass index was significantly increased in both groups with cardiomyopathy. The constant of chamber stiffness (beta*) was slightly although not significantly greater in groups 1 and 2 (0.58 and 0.58, respectively) than in the control group (0.35). The constant of myocardial stiffness beta was normal in group 1 (7.0; control group 6.9, p = NS) but was significantly increased in group 2 (23.5). Interstitial fibrosis was 19% in group 1 and 43% (p less than 0.001) in group 2 (normal less than or equal to 10%). There was an exponential relation between both diastolic constant of myocardial stiffness (beta) and interstitial fibrosis (IF) (r = 0.95; p less than 0.001) and beta and fibrous content divided by end-diastolic volume index (r = 0.93; p less than 0.001). It is concluded that myocardial stiffness can be normal in patients with dilated cardiomyopathy despite severely depressed systolic function. Structural alterations of the myocardium with increased amounts of fibrous tissues are probably responsible for the observed changes in passive elastic properties of the myocardium in patients with dilated cardiomyopathy. The constant of myocardial stiffness (beta) helps to identify patients with severe structural alterations (group 2), representing possibly a more advanced stage of the disease.

Left ventricular pressure-length relation during exercise-induced ischemia.

The pressure-length relation in normal and ischemic segments was analyzed with use of left ventriculography and simultaneous micromanometry during supine exercise in 9 normal subjects and 12 patients with effort angina. Segmental analysis was done in the right anterior oblique projection using a long axis with three perpendicular, equidistant chords. The apical segment in the 12 patients with coronary artery disease represented the ischemic region. In 5 of the 12 patients with coronary artery disease, the basal segment that showed no exercise-induced deterioration in wall motion was used as an intrapatient control (nonischemic segment). In the 12 patients with coronary artery disease, left ventricular ejection fraction decreased (from 65% to 50%, p less than 0.001), end-diastolic pressure increased (from 24 to 40 mm Hg, p less than 0.001) and the lowest diastolic filling pressure increased (from 9 to 22 mm Hg, p less than 0.001) during exercise-induced ischemia. In normal subjects, ejection fraction increased (from 64% to 70%, p less than 0.01) with unchanged end-diastolic pressure, whereas the lowest diastolic filling pressure decreased during exercise (from 9 to 3 mm Hg, p less than 0.01). Global left ventricular diastolic pressure-volume curves showed an upward and rightward shift during exercise-induced ischemia. Regional pressure-length curves of both nonischemic (n = 5) and ischemic (n = 12) segments were shifted upward in early diastole, but moved to a higher portion of the rest pressure-length curve without an upward shift during mid- to end-diastole. In contrast, the apical segment in normal subjects showed a downward shift during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Abnormal coronary vasomotion during exercise in patients with normal coronary arteries and reduced coronary flow reserve.

A reduced coronary flow reserve has been reported in patients with ischemialike symptoms and normal coronary arteries. In 13 such patients, both coronary vasomotion and flow reserve were studied. The luminal area of the proximal and distal third of the left anterior descending and left circumflex artery were determined by biplane quantitative coronary arteriography using a computer-assisted system. Patients were studied at rest, during submaximal supine bicycle exercise (4.0 minutes, 116 W), and 5 minutes after sublingual administration of 1.6 mg nitroglycerin. Heart rate, mean pulmonary pressure, and mean aortic pressure as well as the percent change of both proximal and distal luminal area were determined. In 10 of the 13 patients, coronary sinus blood flow was measured by coronary sinus thermodilution technique at rest and after dipyridamole infusion (0.5 mg/kg in 15 minutes) 10 +/- 5 days after quantitative coronary arteriography. Coronary flow ratio (dipyridamole/rest) and coronary resistance ratio (rest/dipyridamole) were determined in these patients. Patients were divided into two groups according to the behavior of the coronary vessels during exercise (vasodilation, group 1; vasoconstriction, group 2). Coronary vasodilation of the proximal (luminal area +26%, p less than 0.001) and distal (+45%, p less than 0.001) artery was observed in seven patients (group 1) during exercise and after sublingual nitroglycerin (+46%, p less than 0.001; and +99%, p less than 0.001, respectively). In group 2 (n = 6), however, there was coronary vasoconstriction of the distal vessel segments (-24%, p less than 0.001) during exercise, whereas the proximal coronary artery showed vasodilation (+26%, p less than 0.001) during exercise. After sublingual nitroglycerin, both vessel segments elicited vasodilation (distal coronary, +44%, p less than 0.001; proximal coronary artery, +47%, p less than 0.001). Coronary flow ratio amounted to 2.5 in group 1 and 1.2 in group 2 (p less than 0.05) and coronary resistance ratio to 2.7 in group 1 and to 1.2 in group 2 (p less than 0.05), respectively. Thus, among patients with ischemialike symptoms and normal coronary arteries, there is a group of patients (group 2) with an abnormal dilator response of the distal coronary arteries to the physiologic dilator stimulus of exercise and a reduced dilator capacity of the resistance vessels after dipyridamole (abnormal coronary vasodilator syndrome). The nature of this exercise-induced distal coronary vasoconstriction is not clear but might be due to an abnormal neurohumoral tone that may cause or contribute to the blunted vascular response during exercise.