Efficacy of cilostazol for the treatment of Raynaud's phenomenon in systemic sclerosis patients.

Cilostazol is a selective inhibitor of phosphodiesterase-III with antiplatelet, antithrombotic and vasodilating properties. The aim of our study was to evaluate the effect of the drug on vasculopathy and Raynaud's phenomenon (RP), in a series of patients with systemic sclerosis (SSc), before and after cilostazol treatment. Twenty-one consecutive SSc patients with moderate or severe RP were enrolled in an open-label study. Cilostazol was administered at the dose of 100 mg twice a day, for 12 months. Evaluations included: daily RP attack diary documenting the frequency and duration of RP episodes, Health Assessment Questionnaire-Disability Index, scleroderma visual analogue scales (VAS), flow-mediated dilation and immunological status, including endothelin 1 and interleukin 6 plasma levels. Thirteen patients completed the study. RP duration and daily number episodes recorded over a 3-week period significantly decreased after cilostazol treatment (p = 0.0049 and p = 0.0067, respectively). VAS score indicated a significant amelioration of the patients' perception of RP (p = 0.0117), and both baseline and post-ischemic brachial artery diameters were significantly increased after cilostazol treatment, as compared with basal values (p = 0.0119 and p = 0.0076, respectively). None of the patients developed digital ulcers during the study. A significant clinical improvement of RP was recorded in SSc patients undergoing cilostazol treatment. Study results indicate a potential role of cilostazol as oral maintenance therapy in SSc patients with RP.

Recurrent and Residual Shunts After Patent Foramen Ovale Closure: Results From a Long-Term Transcranial Doppler Study.

OBJECTIVES: Assess the evolution of right-to-left shunt (RLS) after transcatheter patent foramen ovale (PFO) closure. BACKGROUND: Despite the high number of interventional procedures performed worldwide, limited systematic data on the long-term abolition of RLS after percutaneous closure are available. METHODS: All patients treated at our Institution between February 2001 and July 2009 were included in this single center, prospective study, and were asked to repeat late contrast transcranial Doppler (cTCD). Rate of complete closure, residual RLS (i.e., a shunt that persists after closure), and recurrent RLS (i.e., a shunt that reappears after a previous negative cTCD) was assessed. RESULTS: Long-term follow-up was completed in 120 patients (56% male). RLS was still detectable 4.9 ± 2.3 years (range 1.3-10.3) after the procedure in 55 patients; 20 (17%) had residual RLS and 35 (29%) had recurrent RLS. Multivariate analysis revealed that significant predictors of residual RLS included post-procedural shunt at transesophageal echocardiography (OR 3.07, 95%CI 0.97-9.7), use of a bigger device (35 vs 25 mm, OR 3.85, 95%CI 1.22-12.2) and length of follow-up (OR 0.75, 95%CI 0.57-0.98), while only length of follow-up (OR 0.77, 95%CI 0.62-0.95) was associated with recurrent RLS. Neurological recurrences (1 stroke, 6 transient ischemic attacks) were equally distributed between the groups. CONCLUSION: A significant number of recurrent and residual shunts may be observed by cTCD up to 5 years after PFO closure. Management of late RLSs includes periodic re-evaluation, exclusion of device-induced complications or secondary sources of RLS, and optimization of antithrombotic treatment with or without a second intervention.

Symptom onset-to-balloon time and mortality in the first seven years after STEMI treated with primary percutaneous coronary intervention.

OBJECTIVE: To evaluate the consequence of treatment delay of primary percutaneous coronary intervention (PPCI) on long-term survival. BACKGROUND: Network organisation based on early recognition, shortening prehospital time delays and procedural delays is the cornerstone of optimal clinical results in the acute phase of ST-segment elevation myocardial infarction (STEMI). Nevertheless, the evidence of a relationship between symptom onset-to-balloon time and mortality is weak, and few long-term data are available. SETTING AND MEASURES: In this single-centre observational follow-up study, we evaluated the long-term survival of 790 consecutive STEMI patients (mean age 68 ± 13 years; 73% males) undergoing PPCI ≤ 12 h from symptom onset, or 12-36 h in the case of persistence of symptoms or hemodynamic instability. RESULTS: The median (IQR) treatment delay, defined as the time from symptom onset to reperfusion, was 180 min (120;310), fairly balanced between patient delay (80 min (40;140)) and system delay (80 min (60-114)). Patients with a treatment delay <180 min displayed lower mortality at 1, 3, 5 and 7 years (12%, 17%, 22% and 26%, respectively) than those with a treatment delay >180 min (15%, 24%, 28% and 37%, respectively). The HR was 0.7 (95% CI 0.5 to 0.9). On univariate and stepwise multiple regression analysis, field triage and transportation (p=0.0001), shorter distance from hospital (p=0.02) and male gender (p=0.02), but not clinical variables, were independent predictors of shorter treatment delay. CONCLUSIONS: Shorter symptom onset-to-balloon time predicts long-term lower mortality in STEMI patients treated with PPCI. Our findings emphasise the need to minimise any component of treatment delay.

Brachial artery endothelial-dependent flow-mediated dilation identifies early-stage endothelial dysfunction in systemic sclerosis and correlates with nailfold microvascular impairment.

OBJECTIVE: To assess possible correlations between endothelial-dependent flow-mediated dilation (FMD) of the brachial artery and nailfold videocapillaroscopy (NVC) in patients with systemic sclerosis (SSc). Evidence has shown that vascular impairment in SSc may be a sign of endothelial dysfunction involving both microvascular and macrovascular systems, although the pathological mechanisms of the dysfunction are poorly understood. METHODS: Forty-three consecutive patients (mean age 51 +/- 11 yrs) with SSc were studied. Thirty patients had limited cutaneous SSc, 13 had diffuse cutaneous SSc. Twenty-seven healthy subjects (mean age 48 +/- 8 yrs) were recruited as controls. Ultrasound assessment of FMD was performed on all subjects in order to evaluate macrovascular function. Patients were divided into 3 patterns of microvascular damage on the basis of NVC (early, active, and late), and the microangiopathy evolution score was calculated, as reported elsewhere. RESULTS: FMD was significantly reduced in patients with SSc compared to healthy subjects [median 8.0% (3.0%-9.0%) vs 15.0% (12.0%-16.0%), respectively; p < 0.0001]. Patients with an early pattern of microangiopathy showed reduced FMD values compared to controls (p = 0.0001). FMD was significantly reduced in patients with SSc who had the late NVC pattern of microangiopathy compared to active and early patterns (p = 0.003 and p = 0.001, respectively). FMD was inversely correlated with the microvascular damage rate in patients with SSc (p < 0.0001). CONCLUSION: We demonstrated the simultaneous presence of macrovascular and microvascular impairment in patients with SSc, which was already present in the early phase of the vascular disease.

Guide wire fracture during percutaneous transluminal coronary angioplasty: possible causes and management.

A 46-year-old woman underwent diagnostic coronary angiography in our institution due to a myocardial ischemia following a dobutamine echo-stress test. The patient showed critical stenosis of the left anterior descending (LAD) artery involving the ostium of a large diagonal branch. The planned treatment of coronary bifurcation by percutaneous coronary intervention (PCI) was direct stenting of the main branch with 'jailed' wire technique to protect the side branch, provisional T stenting of the side branch, and final kissing balloon inflation. After successful stent implantation in the LAD, the 'jailed' wire fractured during withdrawal: the distal part of the fragment was trapped in the side branch, and the proximal one was knotted in the LAD, left main coronary and the aortic bulb. We decided not to retrieve the fragment by snare, and we planned heart surgery to safely retrieve the fragment and bypass the side branch not treated by percutaneous coronary interventions. Angiographic control nine months after surgery showed non in-stent restenosis; patient is alive and event-free at 18 months' clinical follow-up. In conclusion, percutaneous management of particularly complex bifurcational lesions may be associated with procedural risks; accordingly, it is important to consider and be ready for a rescue surgical revascularization.

Optimization of flow reserve measurement using SPECT technology to evaluate the determinants of coronary microvascular dysfunction in diabetes.

PURPOSE: The aim of this study was to validate a new method to measure regional myocardial perfusion reserve (MPR) with technetium-labelled tracers in patients with type 2 diabetes mellitus (DM2). METHODS: A total of 40 consecutive DM2 patients without history of coronary artery disease (CAD) and 7 control subjects were recruited. Dipyridamole myocardial blood flow index (MBF) was assessed by measuring first transit counts in the pulmonary artery and myocardial count rate from gated SPECT images using (99m)Tc-labelled tracers. The corresponding MBF index was estimated 2 h later according to the same procedure. Regional myocardial perfusion reserve (MPR) was defined as the ratio between dipyridamole and baseline MBF using a 17-segment left ventricular (LV) model. Coronary flow reserve (CFR) was estimated by transthoracic contrast echo Doppler monitoring of flow velocity in the left anterior descending coronary artery (LAD) during the same session. RESULTS: Estimated MPR was higher in control subjects than in patients (3.36 +/- 0.66 vs 1.91 +/- 0.61, respectively, p < 0.01). In patients, LAD CFR and LAD MPR were 2.01 +/- 0.78 vs 1.93 +/- 0.63, respectively (p = ns). The agreement between the two techniques was documented by their close correlation (r = 0.92, p < 0.001) and confirmed by the Bland-Altman analysis. Reversible perfusion defects occurred in 13 patients (32%) who showed similar MPR values as the remaining 27 (2.10 +/- 0.71 vs 1.83 +/- 0.71, respectively, p = ns). Finally, MPR was closely correlated with age (r = -0.50, p < 0.01) and time elapsed from the diagnosis of DM2 (r = -0.51, p < 0.01). CONCLUSION: LV regional MPR can be accurately estimated with the broadly available single photon technology. Application of this method to DM2 patients documents the presence of a microvascular dysfunction homogeneously distributed throughout the LV walls and most frequently not associated with reversible perfusion defects.

The kidney is the major site of S-adenosylhomocysteine disposal in humans.

S-adenosylhomocysteine (SAH), the metabolic precursor of homocysteine in the body, is a potent inhibitor of methylation reactions. Several methylation reactions play a major role in epigenetic regulation of protein expression, atherosclerosis, and cancer development. Here we studied the mechanisms responsible for the maintenance of circulating SAH levels by measurement of the arterio-venous differences across the kidney, splanchnic organs, and the lung in humans. The lungs did not remove or add any circulating SAH, whereas the liver released it into the hepatic veins. The kidney extracted 40% of SAH and the SAH arterio-venous difference across the kidney was directly and significantly related to its arterial levels. Thus, the kidney plays a major role in maintaining SAH levels and may, indirectly, control tissue transmethylation reactions. Our findings of a pivotal role for the human kidney in sulfur amino acid metabolism may also account for the increased plasma levels of SAH in patients with chronic kidney diseases.

Cardiac magnetic resonance imaging detects subclinical right ventricular impairment in systemic sclerosis.

OBJECTIVE: To assess myocardial involvement in patients with systemic sclerosis (SSc) with no signs or symptoms of cardiac impairment (New York Heart Association functional class I). METHODS: Fifty patients (45 women, 5 men, age 53.3 +/- 12.9 yrs) who did not complain of serious diseases other than SSc were recruited out of 119 consecutive patients with SSc. Thirty-three were found to have limited cutaneous SSc (lSSc) and 17 diffuse SSc (dSSc). All underwent cardiovascular magnetic resonance imaging (MRI) to determine right and left systolic and diastolic volumes and ventricular ejection fractions (RVEF and LVEF). Thirty-one healthy subjects matched for sex, age, and body surface area (BSA) were studied as controls. Diffusion lung capacity test (DLCO) and high resolution computed tomography were performed to evaluate lung involvement. RESULTS: Disease duration between patients with lSSc (14.1 +/- 11.4 yrs) and those with dSSc (6.9 +/-4.4yrs) was found to be significantly different (p < 0.003). lSSc patients were older than those with dSSc (54.8 +/- 13.7 yrs vs 50.4 +/- 9.9 yrs, respectively; p < 0.04). Anticentromere antibodies and Scl-70 were positive in 23 (46%) and 17 patients (34%). Except for the left and right systolic volumes, all unadjusted cardiac MRI measures were significantly reduced in SSc compared to the controls (p < 0.001 and p < 0.009). These differences persisted after adjustment for subjects' height and BSA. Raw RVEF data and RVEF data matched for height and BSA were significantly reduced in dSSc patients in comparison to lSSc (p < 0.03). CONCLUSION: Compromised RVF was found in patients with asymptomatic SSc. Unlike standard diagnostic techniques, cardiac MRI appears to be a rapid and noninvasive means of determining subclinical right myocardial involvement that is otherwise undetected in patients with SSc.