Collateral presence and extent do not predict myocardial viability and ischemia in chronic total occlusions: A stress-CMR study.

BACKGROUND: Well-developed collaterals are assumed as a marker of viability and ischemia in chronic total occlusions (CTO). We aim to correlate viability and ischemia with collateral presence and extent in CTO patients by cardiac magnetic resonance (CMR). METHODS: Multicentre study of 150 CTO patients undergoing stress-CMR, including adenosine if normal systolic function, high-dose-dobutamine for patients with akinetic/>2 hypokinetic segments and EF ≥35%, otherwise low-dose-dobutamine (LDD); all patients underwent late gadolinium enhancement (LGE) imaging. Viability was defined as mean LGE transmurality ≤50% for adenosine, as functional improvement for dobutamine-stress-test, ischemia as ≥1.5 segments with perfusion defects outside the scar zone. RESULTS: Rentrop 3/CC 2 defined well-developed (WD, n = 74) vs poorly-developed collaterals (PD, n = 76). Viability was equally prevalent in WD vs PD: normo-functional myocardium with ≤50% LGE in 52% vs 58% segments, p = 0.76, functional improvement by LDD in 48% vs 52%, p = 0.12. Segments with none, 1-25%,26-50%,51-75% LGE showed viability by LDD in 90%,84%,81%,61% of cases, whilst in 12% if 76-100% LGE (p < 0.01). There was no difference in WD vs PD for ischemia presence (74% vs 75%, p = 0.99) and extent (2.7 vs 2.8 segments, p = 0.77). CONCLUSIONS: In a large cohort of CTO patients, presence and extent of collaterals did not predict viability and ischemia by stress-CMR. Scar extent up to 75% LGE was still associated with viability, whereas ischemia was undetectable in 25% of patients, suggesting that the assessment of CTO patients with CMR would lead to a more comprehensive evaluation of viability and ischemia to guide revascularization.

Anti-inflammatory effects of diet and caloric restriction in metabolic syndrome.

BACKGROUND: Weight loss in patients with metabolic syndrome has positive effects on cardiovascular and type 2 diabetes risks, but its effects on peripheral cytokines and lipid profiles in patients are still unclear. AIM: To determine the effects of diet-induced weight loss on metabolic parameters, lipids and cytokine profiles. METHODS: Eighteen adult males with metabolic syndrome (defined according to IDF 2009) and Body Mass Index (BMI) between 25 and 35 kg/m2 were subjected to a balanced hypocaloric diet for 6 months to reach at least a 5% body weight loss. RESULTS: After weight loss, a significant improvement in BMI, waist circumference, insulin, fasting blood glucose and HOMA-IR (homeostasis model assessment of insulin resistance) was observed. The analysis of LDL (low-density lipoprotein cholesterol) and HDL (high-density lipoprotein cholesterol) lipoproteins showed a change in their composition with a massive transfer of triacylglycerols from HDL to LDL. This was associated with a significant reduction in peripheral pro-inflammatory cytokines such as IL-6, TNF-α, IL-8 and MIP-1ß, leading to an overall decreased inflammatory score. An interesting positive correlation was also observed among peripheral cytokines levels after diet and peripheral levels of CETP (cholesteryl ester transfer protein), an enzyme with a key role in lipid change. CONCLUSION: Weight loss through caloric restriction is associated with an improvement in peripheral lipid and cytokine profiles that may play a major role in improving cardiovascular risk.

Cardiac magnetic resonance for ischaemia and viability detection. Guiding patient selection to revascularization in coronary chronic total occlusions: The CARISMA_CTO study design.

BACKGROUND: It is debated whether percutaneous revascularization (PCI) of total coronary chronic occlusion (CTO) is superior to optimal medical therapy (OMT) in improving symptoms, left ventricular (LV) function and major adverse cardiac/cerebrovascular events (MACCE). Furthermore, CTO-PCI is a challenging technique, with lower success rate than in other settings. A systematic analysis of baseline LV function, infarction extent and ischaemic burden to predict response to revascularization has never been performed. PURPOSES: To establish a CMR protocol to identify patients (pts) who can benefit most from CTO-PCI. Myocardial viability/ischaemia retains high biological plausibility as predictors of response to revascularization. Therefore, baseline viability (necrotic tissue extent, response to inotropic stimulation) and ischaemia (perfusion defect, wall motion abnormality during stress) will be studied as potential predictors of mechanical LV segmental improvement and ischaemic burden reduction in CTO territory (primary endpoint), LV remodelling and global function, Seattle Angina Questionnaire, and MACCE improvement (secondary endpoints) in the follow-up. METHODS: Pts with CTO suitable for PCI undergo stress-CMR for viability/ischaemia assessment. Pts with normal LV function undergo adenosine, those with moderately-reduced ejection fraction (EF) and wall motion abnormalities high-dose dobutamine, pts with EF <35% low-dose dobutamine. All pts undergo late gadolinium enhancement and repeat the same scan at 12 ±â€¯3 months, regardless of PCI success or decision for OMT. CONCLUSIONS: A multi-parameter CMR protocol tailored on pts characteristics to study viability/ischaemia could help in identifying responders in terms of LV function, ischaemic burden and clinical outcome among pts suitable for CTO-PCI, improving selection of best candidates to percutaneous revascularization.

A spontaneous decrease of blood pressure occurs in acute ischemic stroke with favourable neurological course.

BACKGROUND: In the acute phase of ischemic stroke the relationship between blood pressure (BP) and clinical outcome remains not clear. The aim of our study was to evaluate the association of stroke severity and BP measurements in the acute phase of stroke, and whether early variation of neurological status affects BP profiles. METHODS: BP on admission was obtained with mercurial sphygmomanometer and 24h-ambulatory BP monitoring (ABPM) was performed on days 1(st) and 6(th). Enrolled patient were grouped according to the neurological deficit at onset (graded by the NIHSS) in group A, (NIHSS score ≤ 10, mild/moderate) and group B (NIHSS score > 10, moderate/severe) and according to the occurrence of early neurological improvement, defined as a NIHSS score reduction of at least 4 points at the 6(th) day in group C (improved) and in group D (not improved). RESULTS: A total of 57 patients were enrolled. On admission sphygmomanometric systolic BP values were higher in group A with respect to group B (158,5 mmHg ± 26,9 vs 147,7 mmHg ± 15,5 respectively; p = 0.6) whereas no difference was found in ABPM. On admission sphygmomanometric BP and ABPM were similar in group C and group D. At the 6(th) day ABPM, both systolic BP and diastolic BP values were significantly reduced in clinically improved patients (Δ systolic BP 1(st) to 6(th) day = 9,9±13,3 in group C vs 0,5±17,6 in group D, p < 0,05; Δ diastolic BP 1(st) to 6(th) day = 5,1± 8,4 mmHg in group C vs 1,3 ± 9,7 mmHg in group D, p = ns) whereas no change in the 24-h BP profile was observed in patients without early improvement. CONCLUSION: BP on admission in not related to the stroke severity and does not predict early neurological outcome and patients that show an early neurological improvement show also a reduction of the BP profile.

Improved function of circulating angiogenic cells is evident in type 1 diabetic islet-transplanted patients.

Circulating angiogenic cells (CACs) are vascular-committed bone marrow-derived cells that are dysfunctional in type 1 diabetes (T1D). Here we studied whether restoration of normoglycemia following islet transplantation is associated with better CAC function. We carried out a cross-sectional study of 18 T1D patients, 14 insulin-independent islet-transplanted patients (ITA) and 14 healthy controls (C) evaluating in vivo and in vitro CACs viability and function. We found that the percentage of CACs in vivo did not differ among the three groups while the number of CAC colonies obtained from T1D, but not from ITA, was reduced compared to C (C = 7.3 ± 1.9, T1D = 0.9 ± 0.4 and ITA = 4.7 ± 1.9; p < 0.05 T1D vs. all). In vitro CAC migration/differentiation were similar, while in vivo an improved angiogenic ability of ITA compared to T1D was shown (capillary density: C = 93.5 ± 22.1, T1D = 19.2 ± 2.8 and ITA = 44.0 ± 10.5, p < 0.05 T1D vs. all). Increased apoptosis and lesser IL-8 secretion were evident in CACs obtained from T1D compared to C and ITA. in vitro addition of anti-hIL-8 reduced the number of colonies obtained from C. Finally, T1D, but not ITA, had a lower endothelial-dependent dilatation (EDD) compared with C. These data suggest that CAC function is altered in T1D and may be improved after islet transplantation.

Effect of intravenous tirofiban and aspirin in reducing short-term and long-term neurologic deficit in patients with ischemic stroke: a double-blind randomized trial.

BACKGROUND: Thrombolysis with rt-PA is the only approved pharmacological therapy for acute ischemic stroke presently administrable in a 3-hour window (very recently extended to 4.5 h). After this time, the choice is limited to endovascular treatment and antiplatelet drugs, mainly aspirin (ASA), the efficacy of which in the acute phase of stroke has poorly been evaluated. We compared the efficacy of tirofiban, a GP-IIb/IIIa inhibitor, and ASA, with both drugs being administered within 6 h. METHODS: 150 patients were randomly assigned to treatment with tirofiban or ASA, both given for 3 days in a double-blind regimen. Major inclusion criteria were stroke onset within 6 h and a baseline National Institute of Health Stroke Scale (NIHSS) score of 5-25. Outcome variables were the proportion of patients with a NIHSS score reduction of > or =4 points after 72 h, and the proportion of patients with an mRS score of 0-1 at 3 months. RESULTS: The trial, originally planned to enroll 300 patients, was halted after enrollment of 150 patients at interim analysis due to the lack of a trend difference between the 2 treatment groups. Neurological improvement at 72 h was observed in 56% of the patients in each group. At the 3-month follow-up, minimal or absent disability was seen in 45% of the patients in the tirofiban group and 53% in the ASA group; these differences were not statistically significant. Three-month mortality was the same in both groups (10.6%); the rates of symptomatic intracranial hemorrhage were 1% (tirofiban) and 4% (ASA). CONCLUSION: In spite of the fact that the null hypothesis was not supported by our data, we found results supporting the safety (and potential efficacy) of ASA and tirofiban when used in the first hours of acute ischemic stroke. However, this needs to be confirmed by further studies.

Factors influencing delay in presentation for acute stroke in an emergency department in Milan, Italy.

BACKGROUND AND AIMS: Early treatment is critical for successful intervention in acute stroke. The aim of this study was to describe delays in presentation to hospital and in the emergency department (ED) management of patients with acute stroke and to identify factors influencing these delays in an Italian urban hospital. METHODS: The present series includes all patients presenting with acute stroke, in whom arrival delay was ascertainable. To describe delays into the ED, the triage-visit delay, visit-computed tomography (CT) delay and visit-CT report delay were registered. Type of stroke, severity of stroke assessed using the modified National Institute of Health Stroke Scale (mNIHSS) scale, level of consciousness, history of previous stroke or previous hospital admission, use of the emergency medical service (EMS), onset of stroke during day or night and admission during working or non-working day were registered for every patient. Univariate and multivariate analysis were performed to evaluate factors influencing early arrival. RESULTS: Over a one-year period 537 patients with acute stroke were evaluated; 375 patients in whom arrival delay was ascertainable were included in the study. Median arrival delay was 5.4 h (interquartile range (IQR) 2.7-11.6); 104 patients (28%) arrived within 3 h and 198 (53%) within 6 h. Triage-visit delay was 0.3 h (IQR 0.2-0.7), visit-CT scan delay was 1.2 h (IQR 0.8-1.9), visit-CT report delay was 2.7 h (IQR 1.7-4.5). Triage-visit delay and visit-CT delay were shorter for patients presenting within 3 h. The type of stroke was ischaemic in 240 (64%), haemorrhagic in 61 (16%) and transient ischaemic attack in 74 (20%). The median basal mNIHSS score was 5 (IQR 3-10); 64 patients (17%) had an altered level of consciousness, 103 (27%) had had a previous stroke, 223 (59%) had had a previous hospital admittance. In this series 214 patients (57%) arrived with the EMS, 323 (86%) presented with symptoms during the day, 261 (70%) were admitted during working days. Univariate analysis showed a significantly shorter arrival delay in patients calling the EMS (median 4.2 vs 7.2 h; p<0.001) and in patients with a higher basal mNIHSS score (Spearman rho = -0.204; p<0.001) or altered level of consciousness (normal 5.8 h, not alert but arousable 3.8, not alert but arousable with strong stimulation 2.5, totally unresponsive 6.0; p = 0.005). Multivariate analysis showed that use of the EMS and higher basal mNIHSS score were independent variables associated with a shorter arrival delay. CONCLUSION: A substantial proportion of patients does not arrive at the ED in a suitable time for reperfusion therapy. Patients using the EMS have a shorter arrival delay. Approximately half of the patients with stroke are sufficiently aware of the urgency of this clinical condition to activate the emergency telephone system.

Minor stroke and major vascular occlusion. A case report.

Occlusion of middle cerebral artery (MCA) is generally associated to severe stroke and poor prognosis; however a few patients with mild to moderate presentation and long-term reversibility of neurological deficits have been reported. A 66-year-old male presented with left-side weakness and dysarthria (NIHSS score 7), which progressively resolved within a few days; ischaemic lesion of the anterior arm of the right internal capsule was found at brain CT obtained 72 h after presentation. Transcranial Colour Doppler showed absence of flow of the right MCA. Cerebral angiography showed occlusion of the right MCA that was retrogradely revascularised by leptomeningeal collaterals. Non-invasive intracranial vascular examinations could identify major intracranial artery lesions in patients who present with mild to moderate stroke symptoms. These patients could be identified and followed to clarify their best treatment and prognosis.

Human osteoblast-like cell proliferation induced by calcitonin-related peptides involves PKC activity.

The calcitonin peptides [calcitonin (CT), calcitonin gene-related peptide (CGRP), amylin] share many biological actions, including activity on bone cells. In the present study, CT (10(-11) to 10(-9) M) stimulated [(3)H]thymidine incorporation in primary cultures of human osteoblasts (hOB), as already demonstrated for CGRP and amylin. RT-PCR analysis showed that the calcitonin receptor and the calcitonin receptor-like receptor are both expressed in hOB. In these cells, CT (10(-10) M) and amylin (10(-9) M), in contrast to CGRP (10(-8) M), did not increase cAMP production. All three peptides stimulated protein kinase C (PKC) activity. To evaluate PKC involvement in hOB proliferation, cells were incubated with phorbol 12,13-dibutyrate, a stimulator of PKC activity; cell proliferation was increased in a dose-dependent manner (EC(50) = 3.4 x 10(-8) M). Staurosporine (10(-9) M), a PKC inhibitor, blocked phorbol 12,13-dibutyrate-induced PKC activity and cell proliferation. Inhibition of PKC by staurosporine also counteracted the stimulatory effect of CT, CGRP, and amylin on hOB proliferation. From these data, it is deduced that the activation of PKC is important for hOB proliferation and that it is involved in the anabolic effect of CT peptides on bone.

Low Ca(2+) pump activity in diabetic nephropathy.

Elevated cell Na(+)-H(+) exchange (NHE) activity characterizes diabetic nephropathy (DN), but the mechanisms of this abnormality are unclear. Recent evidence suggests that NHE and the Ca(2+) pump share similar regulatory pathways, but whether abnormalities in Ca(2+) metabolism characterize DN is not known. We investigated Ca(2+) efflux rates, NHE activity, cytosolic Ca(2+) ([Ca(2+)](i)) concentrations, and intracellular pH (pH(i)) in human skin fibroblasts from 20 patients with type 1 (insulin-dependent) diabetes and nephropathy; 20 patients with diabetes with normoalbuminuria matched for age, sex, and duration of diabetes; and 10 individuals without diabetes. Ca(2+) pump-mediated Ca(2+) efflux was significantly lower in patients with nephropathy than in patients with normoalbuminuria and individuals without diabetes (0.074 +/- 0.01 versus 0.115 +/- 0.01 versus 0.131 +/- 0.02 nmol.mg(protein)(-1).min(-1); analysis of variance [ANOVA], P = 0.015). Elevated maximal velocity of the Na(+)-H(+) exchanger was confirmed in fibroblasts from patients with nephropathy (14.4 +/- 1.2 versus 7.1 +/- 0.7 versus 8.0 +/- 1.2 mmol H(+).l cell(-1).min(-1); ANOVA, P < 0.0001). A reverse correlation between Ca(2+) pump activity and NHE rates could be shown. Adjustment for glycated hemoglobin and plasma lipid levels did not affect these findings. Finally, [Ca(2+)](i) concentrations and pH(i) were normal in all patients. Low Ca(2+) pump activity is a concomitant event of elevated NHE rates in DN; the molecular dysfunction(s) underlying these abnormalities remains to be established.

Amiloride-insensitive Na+-H+ exchange: a candidate mediator of erythrocyte Na+-Li+ countertransport.

Erythrocyte Na+-Li+ countertransport shows an increased activity in essential hypertension and diabetic nephropathy, but its nature remains unknown. This amiloride-insensitive membrane transport may not be a mode of operation of the amiloride-sensitive NHE1, the only Na+-H+ exchange isoform found in human erythrocytes. Whether an independent, although unknown, amiloride-insensitive isoform mediates Na+-Li+ countertransport is unclear. Na+-H+ exchange activity was measured in acid-loaded erythrocytes. Dimethylamiloride, a specific inhibitor of Na+-H+ exchange and phloretin, a known inhibitor of Na+-Li+ countertransport, gave a reduction in H+-driven Na+ influx (by 31 and 37%, respectively). This effect was additive, and a 66% reduction in H+-driven Na+ influx was found in the presence of both inhibitors. Internal acidification, a stimulus for Na+-H+ exchange, enhanced Na+-Li+ countertransport activity (from 287 +/- 55 to 1213 +/- 165 micromol x Lcell(-1) h(-1), mean +/- SEM, P = 0.003). This transport remained sensitive to phloretin under both conditions. Conversely, external acidification decreased Na+-Li+ countertransport activity (as expected for a Na+-H+ exchanger). Competition between internal H+ and Li+ or Na+ for a common binding site was present. Finally, similar kinetic parameters for external Na+ characterized Na+-Li+ countertransport and the phloretin-sensitive component of H+-driven Na+ influx. These findings suggest that both Na+-Li+ countertransport and the amiloride-insensitive, phloretin-sensitive component of H+-driven Na+ influx can be mediated by a previously unrecognized novel amiloride-insensitive Na+-H+ exchange isoform in human erythrocytes.

[Centenarians in Milan]. / Centenari a Milano.

Demographic analysis of the populations in Italy has confirmed that the number of old people, particularly the very old, is progressively increasing. At present, 92% of the women and 85% of the men reach the age of 60 years, and in 1990, there were 1660 centanarians in Italy. In this study we evaluated the demographic profile of the very old living in Milan. Data were collected by use of the Milan General Registry updated to January 1992. At that time there were 159 centenarians and 166 persons over 100 years (range 101-106 years). Seventy-seven percent of the centenarians were females born in northern Italy who had been living in Milan for over 50 years. Of the subjects aged 101-106 years, 79% were women. One hundred twenty-five subjects were either widows or widowers, 82% had lived in Milan for over 50 years. Only 9% of the centenarians were institutionalized. Our survey confirms previous nationwide data obtained on centenarians indicating growth of the very old population.

[Myocardial infarction caused by accidental electrocution. Apropos of a case with an 8-year follow-up]. / Infarto miocardico da elettrocuzione. A proposito di un caso seguito per 8 anni.

We report on a case of non-fatal myocardial infarction (MI) after electrocution. The diagnosis was made on the basis of electrocardiographic and enzymatic changes and was supported by the results of two-dimensional echocardiogram and radio-nuclide scans, showing segmental hypoperfusion and wall motion abnormalities. The patient was followed for over 8 years, evaluating the evolution of cardiac damage with the above tests. MI associated with electrical injury is very likely overestimated, owing to the low specificity of classical diagnostic criteria, such as ECG changes and CK-MB elevation, and the short monitoring of survivors. We suggest that non-invasive functional methods, exploring myocardial perfusion and ventricular kinesis, and a longer follow-up can reliably assess the prevalence of this complication.

[The emergency treatment of supraventricular tachyarrhythmias: the efficacy and safety of intravenous propafenone]. / II trattamento d'emergenza delle tachiaritmie sopraventricolari: efficacia e sicurezza del propafenone endovena.

One hundred patients, admitted to the Emergency Unit for paroxysmal supraventricular tachycardia (SVT) with 1:1 AV conduction, atrial fibrillation (af) and flutter (AF) of recent onset (less than 72 hours) were treated with intravenous propafenone (P). The drug was administered at the dose of 70 mg over 5 min, repeated after 10 min if sinus rhythm (SR) was not restored and eventually followed by continuous infusion (0.35-0.50 mg/min) until conversion to SR or during the next 48 hours. Exclusion criteria were ventricular rate < 100/min, R-R intervals > 1 s, clinical signs of heart failure or asthma. Termination of SVT within 30 min was obtained in 94% of the patients, while reversion to SR occurred in 79% with af and in 55% with AF. For af and AF conversion was achieved within 30 min in 49% of overall responders (R), between 30 min and 6 hours in 27% and between 6 hours and 48 hours in 24%. The efficacy of P was significantly influenced by the duration of arrhythmia and left atrial size, measured by 2D-echocardiography. On the contrary, no difference was observed between R and non-R in mean age and in the percentage of primary or relapsing arrhythmias. Adverse effects were encountered in 7 patients: in 1 case worsened arrhythmia and in 6 patients, with long-lasting arrhythmias, congestive heart failure. Neither conduction disturbance nor extra-cardiac complications occurred. In conclusion, P provides effective and safe treatment for paroxysmal atrial tachyarrhythmias, so that it can be considered among the drugs of first choice even in non-intensive care units.

Cryoglobulinemia secondary to acute viral hepatitis. Evaluation of a hospital study.

In the present study the possible relationships between cryoglobulins and acute hepatitis of different viral etiology have been investigated. In most cases, cryoglobulins represent a transient phenomenon limited to the acute phase of the disease. Conversely, in 2 cases the persistence of cryoglobulins was associated with a histological pattern of chronic persistent hepatitis.

Heart involvement in essential mixed cryoglobulinemia.

Cardiovascular involvement has been investigated in the course of essential mixed cryoglobulinemia (EMC). A direct pathogenetic role of cryoglobulins, due to coexisting coronary risk factors, is difficult to demonstrate. Nevertheless, a clear role of cryoglobulins in determining heart damage was hypothesized. A significant statistical incidence (p less than 0.05) of heart impairment was found in patients affected by EMC compared with an age- and sex-matched control group. Cryoglobulinemic coronary vasculitis found at post-mortem examination further supports this point of view.