The scar: the wind in the perfect storm-insights into the mysterious living tissue originating ventricular arrhythmias.

BACKGROUND: Arrhythmic death is very common among patients with structural heart disease, and it is estimated that in European countries, 1 per 1000 inhabitants yearly dies for sudden cardiac death (SCD), mainly as a result of ventricular arrhythmias (VA). The scar is the result of cardiac remodelling process that occurs in several cardiomyopathies, both ischemic and non-ischemic, and is considered the perfect substrate for re-entrant and non-re-entrant arrhythmias. METHODS: Our aim was to review published evidence on the histological and electrophysiological properties of myocardial scar and to review the central role of cardiac magnetic resonance (CMR) in assessing ventricular arrhythmias substrate and its potential implication in risk stratification of SCD. RESULTS: Scarring process affects both structural and electrical myocardial properties and paves the background for enhanced arrhythmogenicity. Non-uniform anisotropic conduction, gap junctions remodelling, source to sink mismatch and refractoriness dispersion are some of the underlining mechanisms contributing to arrhythmic potential of the scar. All these mechanisms lead to the initiation and maintenance of VA. CMR has a crucial role in the evaluation of patients suffering from VA, as it is considered the gold standard imaging test for scar characterization. Mounting evidences support the use of CMR not only for the definition of gross scar features, as size, localization and transmurality, but also for the identification of possible conducting channels suitable of discrete ablation. Moreover, several studies call out the CMR-based scar characterization as a stratification tool useful in selecting patients at risk of SCD and amenable to implantable cardioverter-defibrillator (ICD) implantation. CONCLUSIONS: Scar represents the substrate of ventricular arrhythmias. CMR, defining scar presence and its features, may be a useful tool for guiding ablation procedures and for identifying patients at risk of SCD amenable to ICD therapy.

To evaluate the efficacy of an acellular Flowable matrix in comparison with a wet dressing for the treatment of patients with diabetic foot ulcers: a randomized clinical trial.

The authors aimed to evaluate the efficacy of an advanced wound matrix (Integra Flowable Wound Matrix, Integra LifeScience Corp, Plainsboro, NJ, USA) for treating wounds with irregular geometries versus a wet dressing in patients with diabetic foot ulcers. Sixty patients with diabetic foot ulcers (Grades 3 Wagner) were included in this randomized clinical trial. The study was conducted in the General Surgery Unit and Geriatric of the Second University of Naples, Italy, in the last 12 months. Forty-six cases of diabetic foot ulcers were equally and randomly divided into control and test groups. The first group treated with Integra Flowable Wound Matrix, while the control group with a wet dressing. Both groups were evaluated once a week for 6 weeks to value the degree of epithelialization and granulation tissue of the wound. The complete healing rate in the whole study population was 69.56% (Integra Flowable Wound Matrix group, 86.95%, control group, 52.17%; p = 0.001). Amputation and rehospitalization rates were higher in the control group compared to the first group, therefore, the difference was statistically significant (p = 0.0019; p = 0.028, respectively). The Integra Flowable Wound Matrix, was significantly superior, compared to the wet dressing, by promoting the complete healing of diabetic foot ulcers. Ease of use, absence of adverse effects, and a facilitated wound healing process are among the properties of the matrix. These characteristics make it appropriate in the management of diabetic foot ulcers. Additional research will shed more light on the promising advantages of this material in healing diabetic foot ulcers.

Bleeding versus thrombosis: role of short DAPT in complex lesions.

Therapy with dual antiplatelet agents, defined as the combination of a platelet P2Y12 inhibitor and aspirin, is required to prevent thrombotic complications, after percutaneous coronary intervention (PCI) with stent implantation. Usually current guidelines recommend administration of dual antiplatelet therapy (DAPT) following percutaneous revascularization with drug-eluting stent (DES) for a period of at least 12 months or for 6 to 12 months in patients not at high risk. Nevertheless, the treatment of stable/unstable coronary artery disease with DES implantation increasing largely, the optimal duration of DAPT is still unclear. The duration of DAPT after coronary stenting has been evaluated in recent randomized studies with conflicting results. The administration of long period of DAPT is a strategy to reduce thrombosis events but largely increase the hemorrhagic ones. Otherwise, shorter DAPT period is protective about bleeds with consequently increased ischemic events. In addition, as new DES carry a lower risk of stent thrombosis (ST) compared with the first-generation DES and possibly even bare-metal stents, a shift toward better protection from ST may have an effect on the duration and the intensity of DAPT. Whether the duration of DAPT should be shorter or longer than the currently recommended 6 to 12 months is analyzed in this review, drawing on results from the most recent studies and meta-analysis.

Results of the self-expandable BA9 stent for treatment of large angle coronary bifurcation.

Since the advent of coronary angioplasty the treatment of bifurcation lesions has always proved a complex issue resulting in lower angiographic success rates, increased risk of restenosis, higher rates of dissection, myocardial infarction, and acute vessel closure. The advent of coronary stenting reduced the risks, but in-stent restenosis was noted to be frequent at the ostium of the side branch; for this reasons two-stent techniques were developed to try to combat this phenomenon. Novel dedicated stents have recently been developed to provide easier access to the SB and to scaffold more effectively its ostium, matching the stent configuration more closely to the anatomy of the bifurcation. Most of bifurcation lesions that require treatment and which have a wide angle involving the left main coronary artery (LMCA). The impact of the angle and the asymmetry of bifurcation on flow dynamic are very important and may influence clinical outcome. More recently, percutaneous coronary intervention (PCI) to treat wide angle disease has increased in frequency, and is associated with improvements in interventional techniques and adjunctive drug therapy. Several studies have shown that stenting in LMCA, especially using drug-eluting stents (DES), is a safe and effective treatment strategy both at mid- and long-term follow-up. The AXXESS System is a self-expanding, conically-shaped stent from nitinol (nickel-titanium alloy) with strut thickness, specifically designed to conform to the anatomy at the level of the bifurcation carina. A special version of the AXXESS System has been designed for left main bifurcation lesions, allowing for larger diameters (up to 4.75 mm) and distinct bifurcation angles (flare-end diameters of 8, 10 and 12 mm). The AXXENT trial is the first study to evaluate the vascular response of the self-expanding biolimus-eluting AXXESS stent for the treatment of LMCA bifurcation lesions. It was designed to evaluate the safety and efficacy of the AXXESS biolimus-eluting stent for the treatment of LMCA bifurcation lesions, that showed good results in terms of stent thrombosis and TLR at 6 months follow-up. Technical modifications and stent innovations may further improve both the angiographic and clinical outcomes for patients with wide angle bifurcation disease treated by PCI. Moreover a long term follow-up is needful to demonstrate better safety and efficacy of these new dedicated bifurcation devices.

Early, intermediate and late infectious complications after transcatheter or surgical aortic-valve replacement: a prospective cohort study.

Transcatheter aortic valve implantation (TAVI) has been proposed to treat older surgical high-risk patients with severe symptomatic aortic stenosis. There are no data regarding short-term and long-term infectious complications in these patients. The objective of this study was to define the incidence, aetiology and outcome of early and late infectious complications following TAVI compared with patients >65 years old undergoing traditional surgical aortic replacement (SAR). This was a prospective observational study evaluating all consecutive patients who underwent TAVI or SAR. Follow up was performed up to 1 year after the procedure of valve implantation. Fifty-one patients underwent TAVI and were compared with 102 patients who underwent SAR. Compared with SAR patients, those who underwent TAVI had lower incidence of early post-operative (11.7% vs 26.4%, p 0.04), intermediate (5.9% vs 17.6%, p 0.01) and late (7.8% vs 11.7%, p 0.03) infections. Among SAR patients the most common infections were bloodstream infections, pneumonias, urinary tract infections and sternal wound infections. Patients who underwent TAVI had a longer survival without infection (358 days vs 312.9, p 0.006). There were no significant differences in 12-month crude survival between the two study populations. Despite a high frequency of coexisting illnesses, patients undergoing TAVI develop few infectious complications. TAVI appears to be a reasonable and safe option in high-risk patients with severe symptomatic aortic stenosis.

Do angle and anatomy influence outcomes in bifurcation stenting?

Coronary bifurcation lesions are regarded as complex and their treatment is still the subject of substantial debate. Important elements to consider before approaching a bifurcation include angle and anatomy, in particular the take off angle (proximal angle, A) that is between the proximal MB and SB and the carina angle (distal angle, B) that is between distal main branch (MB) and side branch (SB) and also the extent and distribution of disease on the side branch and its size. Many techniques have been used to treat coronary bifurcation lesions such as provisional stenting or double stenting but no consensus technique has been accepted primarily due to variation of disease severity, angle and anatomy. Angle B is the unique statistically significant independent predictor factor influencing outcomes. Bifurcation angle and anatomy are important predictors of short and long-term outcomes after bifurcation treatment. Moreover we should evaluate it after wiring MB and SB so as after pre-dilatation because of side branch access and carina area angle anatomy variation and plaque shift. Should be investigated if the developing of new dedicated devices for bifurcation lesions could mix the advantages of one and two-stent techniques.

Long term effects of bosentan treatment in adult patients with pulmonary arterial hypertension related to congenital heart disease (Eisenmenger physiology): safety, tolerability, clinical, and haemodynamic effect.

BACKGROUND: Oral bosentan is an established treatment for pulmonary arterial hypertension (PAH). OBJECTIVE: To evaluate safety, tolerability, and clinical and haemodynamic effects of bosentan in patients with PAH related to congenital heart disease (CHD). PATIENTS: 22 patients with CHD related PAH (8 men, 14 women, mean (SD) age 38 (10) years) were treated with oral bosentan (62.5 mg x 2/day for the first 4 weeks and then 125 mg x 2/day). MAIN OUTCOME MEASURES: Clinical status, liver enzymes, World Health Organisation (WHO) functional class, resting oxygen saturations and 6-min walk test (6MWT) were assessed at baseline and at 1, 3, 6, and 12 months. Haemodynamic evaluation with cardiac catheterisation was performed at baseline and at 12 month follow-up. RESULTS: 12 patients had ventricular septal defect, 5 atrioventricular canal, 4 single ventricle, and 1 atrial septal defect. All patients tolerated bosentan well. No major side effects were seen. After a year of treatment, an improvement was seen in WHO functional class (2.5 (0.7) v 3.1 (0.7); p<0.05), oxygen saturation at rest (87 (6%) v 81 (9); p<0.001), heart rate at rest (81 (10) v 87 (14) bpm; p<0.05), distance travelled in the 6MWT (394 (73) v 320 (108) m; p<0.001), oxygen saturation at the end of the 6MWT (71 (14) v 63 (17%); p<0.05), Borg index (5.3 (1.8) v 6.5 (1.3); p<0.001), pulmonary vascular resistances index (14 (9) v 22 (12) WU m(2); p<0.001), systemic vascular resistances index (23 (11) v 27 (10) WU.m(2); p<0.01), pulmonary vascular resistances index/systemic vascular resistances index (0.6 (0.5) v 0.9 (0.6); p<0.05); pulmonary (4.0 (1.3) v 2.8 (0.9) l/min/m2; p<0.001) and systemic cardiac output (4.2 (1.4) v 3.4 (1.1) l/min/m2; p<0.05). CONCLUSIONS: Bosentan was safe and well tolerated in adults with CHD related PAH during 12 months of treatment. Clinical status, exercise tolerance, and pulmonary haemodynamics improved considerably.

Effect of coronary percutaneous revascularization on interferon-gamma and interleukin-10 producing CD4+ T cells during acute myocardial infarction.

T lymphocytes play an important role in the induction and progression of acute coronary syndromes (ACS). To gain insight into how different T cell subsets can influence ACS, we analyzed the frequencies of circulating CD4+ T cells producing either pro-inflammatory interferon(IFN)-gamma or anti-inflammatory interleukin (IL)-10 in subjects presenting with ST-elevation myocardial infarction (STEMI). The effect of coronary bare metal (BS) and paclitaxel-eluting stent (PES) on the balance between CD4+IFN-gamma+ and CD4+IL-10+ lymphocytes was also investigated. Peripheral blood mononuclear cells (PBMC) were isolated from 38 consecutive patients with STEMI before and 48 hrs or 6 days after implantation of either BS or PES. Twenty patients with no history of coronary artery disease were included as basal controls. PBMC were stimulated in vitro with anti-CD3/anti-CD28 monoclonal antibodies, and CD4+IFN- gamma+ or CD4+IL-10+ T cells were detected by flow cytometry intracellular staining. The frequency of peripheral CD4+IL-10+ T cells was significantly higher in STEMI patients as compared with controls. Conversely, the frequency of CD4+IFN-gamma+ T lymphocytes did not differ between STEMI and subjects without history of coronary artery disease. Six days after the revascularization procedure, the percentage of CD4+IL-10+ T cells was significantly decreased in BS but not in the PES group, whereas the relative percentage of CD4+IFN-gamma+ T lymphocytes were diminished in both groups as compared with baseline levels. Our data indicate that STEMI is associated with a peripheral expansion of CD4+IL-10+ T lymphocytes, and that primary coronary revascularization with implantation of either BS or PES is followed by a reduction in circulating CD4+IFN-gamma+ T lymphocytes. PES implantation, however, appears to inhibit the relative decrease of the IL-10 producing lymphocyte as observed in BS implanted patients, shifting the balance between pro-inflammatory and anti-inflammatory T cell populations in favor of the latter.

Impact of intracoronary aspiration thrombectomy during primary angioplasty on left ventricular remodelling in patients with anterior ST elevation myocardial infarction.

OBJECTIVE: To evaluate prospectively the impact on left ventricular (LV) remodelling of an intracoronary aspiration thrombectomy device as adjunctive therapy in primary percutaneous coronary intervention (PCI) in patients with anterior ST elevation myocardial infarction (STEMI). METHODS: 76 consecutive patients with anterior STEMI (65.3 (11.2) years, 48 men) were randomly assigned to intracoronary thrombectomy and stent placement (n = 38) or to conventional stenting (n = 38) of the infarct related artery. Each patient underwent transthoracic echocardiography immediately after PCI and at six months. At the time of echocardiographic control, major adverse cardiovascular events (MACE) in terms of death, new onset of myocardial infarction, and hospitalisation for heart failure were also evaluated. RESULTS: After a successful primary PCI, patients in the thrombectomy group achieved a higher rate of post-procedure myocardial blush grade 3 (36.8% v 13.1%, p = 0.03) and effective ST segment resolution at 90 minutes (81.6% v 55.3%, p = 0.02). Six months after the index intervention, 19 patients (26.8%) developed LV dilatation, defined as an increase in end diastolic volume (EDV) >or= 20%: 15 in the conventional group and four in the thrombectomy group (p = 0.006). Accordingly, at six months patients treated conventionally had significantly higher end systolic volumes (82 (7.7) ml v 75.3 (4.9) ml, p < 0.0001) and EDV (152.5 (18.1) ml v 138.1 (10.7) ml, p < 0.0001) than patients treated with thrombectomy. No differences in cumulative MACE were observed (10.5% in the conventional group v 8.6% in the thrombectomy group, not significant). CONCLUSION: Compared with conventional stenting, adjunctive aspiration thrombectomy in successful primary PCI seems to be associated with a significantly lower incidence of LV remodelling at six months in patients with anterior STEMI.

Noninvasive assessment of coronary artery stenoses by multidetector-row spiral computed tomography: comparison with conventional angiography.

BACKGROUND: Coronary artery disease (CAD) is the most common cause of hospitalization and mortality in many industrialized countries. We analysed the diagnostic accuracy of multi-detector row spiral computed tomography (MDCT) in determining mid- to high-grade coronary artery stenoses (> 50%). METHODS: Sixty-nine patients with suspected CAD were referred to MDCT coronary angiography. Patients with a heart rate above 60 bpm received 20-40 mg propranol before the scan. The left main (LM), the left anterior descending artery (LAD), the first diagonal branch (D1), the right coronary artery (RCA) and the proximal tract of the circumflex artery (LCX) were independently evaluated by two blinded observers and screened for > 50% stenoses. The mean values of MDCT coronary narrowings assessed by two observers were compared to quantitative coronary angiography. RESULTS: MDCT correctly detected 95 of 123 coronary lesions (sensitivity 77.2%) and absence of stenoses was correctly identified in 388 of 426 segments (specificity 91%). The sensitivity for the LM, LAD, RCA and the proximal tract of LCX was 100%, 86.5%, 69.8% and 80% respectively. Classification of patients as having 1-vessel, 2-vessels, 3-vessels or left main disease was accurate in 75.4% (46/61) of patients. CONCLUSIONS: MDCT technology, combined with heart rate control, allows reliable noninvasive detection of hemodynamically significant CAD.

Age-related changes in catecholaminergic nerve fibers of rat heart and coronary vessels.

BACKGROUND: Age-related changes of catecholaminergic nerve fibers supplying the myocardium and the coronary vessels were studied in adult and in old rats. OBJECTIVE: The purpose of this study was to investigate whether there are quantitative changes in myocardial and/or coronary catecholaminergic nerve fibers and related neurotransmitters. METHODS: Samples of myocardium and/or coronary vessels were studied by means of glyoxylic acid induced fluorescence, aldehyde-induced fluorescence, and neuropeptide Y immunoreactivity. All morphological results were submitted to quantitative analysis of images. Biochemical dosage of proteins and of norepinephrine was also performed, and morphological data were compared with biochemical ones. Finally, all data were subjected to statistical analysis. RESULTS: Our findings are indicative of an age-related decrease of all types of fluorescent sympathetic nerve fibers in rat heart and coronary arteries. Moreover, our data show that aging induces a strong decrease of norepinephrine levels in tissue homogenates of rat heart and coronary vessels. The majority of the catecholaminergic nerve fibers that show strong age-related changes are not contiguous with contractile cells of myocardium and/or of vascular wall. In fact, these fibers are located in adventitial (or epicardial) and in endothelial (or endocardial) layers. CONCLUSION: The decrease of the catecholaminergic innervation of heart and coronary vessels of old rats can be in close relationships to the poor cardiac and/or coronary functions observed in old animals.

Comparative study on the acceptability of two modern monophasic oral contraceptive preparations: 30 microgram ethinyl estradiol combined with 150 microgram desogestrel or 75 microgram gestodene.

Cycle control and tolerability of two monophasic oral contraceptive pills containing 30 microg ethinyl estradiol (EE) with either 150 microg desogestrel (DSG) or 75 microg gestodene (GSD) were compared in women starting oral contraception. A minimum of 200 healthy women at risk for pregnancy were to be treated for a total of 6 cycles per patient in a prospective, randomized open parallel-group multicenter trial. Two hundred and forty-one subjects were randomized, 115 to DSG/EE and 126 to GSD/EE. Compliance to the study preparation was high (around 95%) in both groups and no pregnancies occurred during the study. Cycle control was excellent; there were no differences between the two groups with regard to incidence of spotting and breakthrough bleeding or duration and intensity of withdrawal bleeding. Side-effects were mild and in general comparable in the two groups. Both at baseline and during treatment, a higher proportion of women taking GSD/EE complained about breast tenderness. This resulted in more early withdrawals because of breast tenderness in the GSD/EE group. It was concluded that monophasic DSG/EE and GSD/EE are equally effective, have similar cycle control and both are generally well tolerated.

[Evaluation of some coagulation tests in women using low dosage oral contraception]. / Valutazione di alcuni test della coagulazione in donne che usano contraccettivi orali a basso dosaggio.

PIP: This study assessed the effects of 3 types of combined oral contraceptives (OCs) on blood coagulation. The OCs investigated were a monophasic (EE 30 mcg + DOG 150 mcg), another monophasic (EE 30 mcg + LNG 150 mcg), and a triphasic (EE 30 mcg + LNG 50 mcg, EE 40 mcg + LNG 75 mcg, EE 30 mcg + LNG 125 mcg). 60 women between the ages of 19-30 with no contraindications to OC use were randomly recruited and divided into 3 groups. A blood sample was collected at a baseline level, and after 3 and 6 months of use. The parameters examined were antithrombin III, prothrombin time, partial thromboplastin time, fibrinogen degradation products, and protamina sulphate testing. There were no significant changes in any of the coagulation tests during the treatment period with these 3 different OCs. Thus, these OC compounds appear to be equally safe for use. (author's modified)^ieng

[Oral contraceptives and their minor side effects: comparison of three low-dose estroprogestinic combinations]. / Contraccettivi orali ed effetti collaterali minori: confronto fra tre estroprogestinici a basso dosaggio.

PIP: 3 groups of women aged 19-25 with normal weight and in good physical health were studied. In the first group, 40 subjects received a monophasic oral contraceptive (OC) containing .15 mg of levonorgestrel (LNG) and .03 mg of ethinyl estradiol (EE). In the second group, 32 women received a triphasic OC containing LNG and EE (.05 mg of LNG + .03 mg of EE; .075 mg of LNG + .04 mg of EE; .125 mg of LNG + .03 mg of EE). In the third group, 34 women received a monophasic OC containing .15 mg of desogestrel (DSG) and .03 mg of ethinyl estradiol (EE). The observation lasted 6 month, involving 646 menstrual cycles. 3 months and 6 months later, checkups were conducted to find out about characteristics of the cycles, spotting or BTB (hemorrhagic rupture), weight change, and other minor disorders. After 3 months, spotting occurred in 4.1% of the monophasic LNG group, in 5.8% of the monophasic DSG group, and in 1% of the triphasic group (significantly higher in the DSG group). Heavy bleeding decreased from 25% in the LNG group, 25% in the triphasic group, and 17.6% in the DSG group to 0 after 6 months. Likewise, dysmenorrhea disappeared in all 3 groups. Weight change occurred in 50% of the LNG group, in 57% of the triphasic group, and in 76% of the DSG group. Premenstrual disorders, such as mastodynia, dropped from 40 to 25% in the LNG group, from 75 to 50% in the triphasic group, and from 54.5 to 36.3% in the DSG group after 6 months. Depression decreased from 20 to 8.3% in the LNG group and from 18.1 to 4.5% in the DSG group. Acne fell from 25% to 0 in the triphasic group and from 31.8 to 9 in the DSG group. These OCs were well tolerated without major differences between their minor side effects.^ieng