Ganglionated plexi ablation in the right atrium for the treatment of cardioinhibitory syncope.

Neurocardiogenic syncope, also called vasovagal syncope, represents one of the clinical manifestations of neurally mediated syncopal syndrome. Generally, the prognosis of the cardioinhibitory form of neurocardiogenic syncope is good, but quality of life is seriously compromised in patients who experience severe forms. Drug therapy has not achieved good clinical results and very heterogeneous data come from studies regarding permanent cardiac pacing. In this scenario, the ganglionated plexi ablation has been proposed as an effective and safe method in patients with cardioinhibitory neurocardiogenic syncope, especially in young patients in order to avoid or prolong, as much as possible, the timing of definitive cardiac pacing. Certainly, making this procedure less extensive and limiting the ablation in the right atrium (avoiding the potential complications of a left atrial approach) and at level of anatomical regions of the most important ganglionated plexy, considered 'gateway' of the sino-atrial and atrio-ventricular node function (through the recognition of specific endocardial potentials), could be very advantageous in this clinical scenario. Finally, randomized, multicentre, clinical trials on a large population are needed to better understand which is the best ablation treatment (right-only or bi-atrial) and provide evidence for syncope guidelines.

Cardiac resynchronization therapy in the elderly. How much is it safe and beneficial?

Heart failure is a widespread disease in the western world whose incidence and prevalence are constantly increasing, mainly involving the more advanced age groups. Cardiac resynchronization therapy (CRT) has been shown able to reduce sudden cardiac death and all-cause mortality in patients with heart failure and reduced ejection fraction. Elderly patients are generally under-represented in the clinical trials aimed to evaluate the efficacy of CRT and, chiefly, of implantable cardiac defibrillator (ICD). The simultaneous presence of confounding factors such as co-morbidities, polypharmacy, changes in cognitive status, frailty, are the most important causes for the exclusion of subjects of advanced age from RCTs on the ICD or CRT implant. Current guidelines do not suggest any upper age limit for ICD and CRT but recommend avoiding their use in frail older patients with a life expectancy of less than 1 year. Data from the literature show that CRT has equal dignity in both the elderly and the young, in fostering effective functional and morphological improvements, also suggesting that, in older patients, CRT-D may have little practical value compared to CRT-P given the low incidence of arrhythmic death. Nevertheless, it is necessary to develop RCTs that consider aspects of the elderly patient in relation to CRT such as functional, cognitive and nutritional status.

The red blood cell as a gender-associated biomarker in metabolic syndrome: a pilot study.

In the present pilot study (56 patients), some red blood cell parameters in samples from patients with metabolic syndrome and subclinical atherosclerosis, but without any sign of coronary artery disease, have been analyzed. The main goal of this work was to determine, in this preclinical state, new peripheral gender-associated bioindicators of possible diagnostic or prognostic value. In particular, three different "indicators" of red blood cell injury and aging have been evaluated: glycophorin A, CD47, and phosphatidylserine externalization. Interestingly, all these determinants appeared significantly modified and displayed gender differences. These findings could provide novel and useful hints in the research for gender-based real-time bioindicators in the progression of metabolic syndrome towards coronary artery disease. Further, more extensive studies are, however, necessary in order to validate these findings.

Determinants of microvascular damage recovery after acute myocardial infarction: results from the acute myocardial infarction contrast imaging (AMICI) multi-centre study.

AIMS: Microvascular damage (MD) occurring soon after primary percutaneous coronary intervention (PPCI) may reverse or remain sustained within the first week after ST-elevation myocardial infarction (STEMI). We investigated the incidence, determinants, and long-term clinical relevance of MD reversal after PPCI. METHODS AND RESULTS: Serial two-dimensional echocardiograms (2DE) and a myocardial contrast study were obtained within 24 h of PPCI (T1) and at pre-discharge (T2) in 110 successfully re-perfused STEMI patients. Six months 2DE and 2-year clinical follow-up were obtained. After PPCI myocardial re-perfusion was normal at T1 only in 40 patients (36%, 'normal reflow'), recovered at T2 in 33 (30%, 'reversible MD'), and remained abnormal in 37 (34%, 'sustained MD'). At follow-up, normal reflow and reversible MD were coupled with a significant reduction in the infarct area, decrease in cardiac volumes, and a slight non-significant improvement in systolic function. Conversely, in the sustained MD group, the infarct area did not change and cardiac volumes significantly increased with a parallel worsening in systolic function. By multivariate analysis, independent predictors of reversible MD were: absence of family history of coronary artery disease (CAD), younger age, shorter time to re-perfusion, and absence of diabetes. The 2-year combined events rate was significantly lower in reversible MD (log-rank test P= 0.03) compared with sustained MD patients. CONCLUSIONS: In STEMI patients treated according to the current guidelines, MD frequently occurs soon after re-perfusion but it is reversible in ~50% of cases and it is associated with a favourable functional and clinical outcome. Family history of CAD, aging, time to re-perfusion, and diabetes are independent predictors of MD reversibility.

Update on phase II studies of erythropoietin in acute myocardial infarction. Rationale and design of Exogenous erythroPoietin in Acute Myocardial Infarction: New Outlook aNd Dose Association Study (EPAMINONDAS).

Erythropoietin (Epo) is a hematopoietic hormone produced mainly by the kidneys in response to hypoxia. Recent acquisitions in the fields of hematology, neurology, cardiology, and experimental medicine show cytoprotective, angiogenetic and antiinflammatory effects of Epo. Exogenous erythroPoietin in Acute Myocardial Infarction: New Outlook aNd Dose Association Study (EPAMINONDAS, EudraCTno. 200500485386) is one of four ongoing randomized controlled trials, each testing the effects of Epo in >or=100 patients with STEMI. EPAMINONDAS is a multicenter, prospective, double-blind, placebo-controlled, dose-finding study assessing intravenous moderate doses of human recombinant Epo (epoietin-alpha, 100 or 200 IU/kg/die) versus placebo, given on the first 3 days, in 102 patients with first ST-segment elevation myocardial infarction. Initial dosing is within 12 h of primary percutaneous coronary revascularization. The primary endpoint is infarct size, quantified by CK-MB time-concentration curve, left ventricular wall motion score index, and pattern of contrast-enhanced magnetic resonance imaging. Secondary endpoints are ischemic recurrences, ventricular remodelling, and safety events, assessed in-hospital and at 12 months' follow-up. The results of current phase II studies will help define the safety/efficacy profile of Epo for patients with STEMI.

Incidence, determinants, and prognostic value of reverse left ventricular remodelling after primary percutaneous coronary intervention: results of the Acute Myocardial Infarction Contrast Imaging (AMICI) multicenter study.

AIMS: Few data are available on the extent and prognostic value of reverse left ventricular remodelling (r-LVR) after ST-elevation acute myocardial infarction (STEMI). We sought to evaluate incidence, major determinants, and long-term clinical significance of r-LVR in a group of STEMI patients treated with primary percutaneous coronary intervention (PPCI). In particular, the role of preserved microvascular flow within the infarct zone in inducing r-LVR has been investigated. METHODS AND RESULTS: Serial echocardiograms (2DE) and myocardial contrast study were obtained within 24 h of coronary recanalization (T1) and at pre-discharge (T2) in 110 reperfused STEMI patients. Follow-up 2DE was scheduled after 6 months (T3). Two-year clinical follow-up was obtained. Reverse remodelling was defined as a reduction >10% in LV end-systolic volume (LVESV) at 6 months follow-up. r-LVR occurred in 39% of study population. At multivariable analysis, independent predictors of r-LVR were an effective microvascular reflow within the infarct zone, the in-hospital improvement of myocardial perfusion, an initial large LVESV, and a short time to reperfusion. Cox analysis identified r-LVR as the only independent predictor of 2-year event-free survival. Combined events rate was significantly higher among patients without compared to those with r-LVR (log-rank test P < 0.05). CONCLUSION: r-LVR frequently occurs in STEMI patients treated with PPCI and it is an important predictor of favourable long-term outcome. A preserved microvascular perfusion within the infarct zone is the major determinant of r-LVR.