Serena Rakar

Contemporary antithrombotic strategies in patients with acute coronary syndrome admitted to cardiac care units in Italy: The EYESHOT Study

Background: Several new antithrombotic therapies have emerged for the treatment of acute coronary syndrome (ACS). We sought to assess contemporary patterns of antithrombotic therapies use in patients with ACS. Methods and results: EYESHOT (EmploYEd antithrombotic therapies in patients with acute coronary Syndromes HOspitalized in iTalian cardiac care units) was a nationwide, prospective registry aimed to evaluate antithrombotic strategies employed in patients admitted to intensive cardiac care units (CCUs) for an ACS in Italy. Over a three-week period, 203 CCUs enrolled 2585 consecutive patients: 41.2% with ST-elevation myocardial infarction (STEMI) and 58.8% with non-ST elevation ACS (NSTE-ACS). During hospitalisation, low-molecular-weight heparins, aspirin, and clopidogrel were the most commonly used antithrombotic therapies. Among patients treated with percutaneous coronary intervention (PCI, n=1755), any crossover of heparin therapy occurred in 30.8% of cases, while switching from one P2Y12 inhibitor to another occurred in 3.6% of cases in the CathLab and in 14.2% before discharge. Of the 790 patients who did not receive revascularisation, switching of a P2Y12 inhibitor occurred in 5.7% of cases. At discharge, a new P2Y12 inhibitor (ticagrelor or prasugrel) in association with aspirin was prescribed in 59.5% of STEMI and 33.9% of NSTE-ACS patients: the most powerful predictor for prescription was PCI (odds ratio (OR) 6.18; 95% confidence interval (CI) 4.76–8.01; p<0.0001), whereas age ≥75 years was strongly associated with clopidogrel use (OR 0.28; 95% CI 0.22–0.36; p<0.0001). Conclusions: The EYESHOT registry shows the current pattern of antithrombotic treatments for ACS patients admitted to Italian CCUs and provides insights which may help to improve the clinical care of such patients.

Contrast-induced nephropathy in patients undergoing primary percutaneous coronary intervention without acute left ventricular ejection fraction impairment.

The prognostic relevance of direct contrast toxicity in patients treated with primary percutaneous coronary intervention remains unclear, owing to the confounding hemodynamic effect of acute left ventricular ejection fraction (LVEF) impairment on kidney function estimation. In the present study, 644 consecutive patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention were prospectively enrolled. Contrast-induced nephropathy (CIN) was defined as an increase in serum creatinine >25% or a decrease in the estimated glomerular filtration rate (eGFR) <25% from baseline in the first 72 hours. The primary end point of the study was major adverse cardiovascular events at 1 year (composite of death, myocardial infarction, target lesion revascularization, and bleeding). Among the global population, the interaction between the LVEF and eGFR at admission to define CIN was statistically significant (p <0.001). When only the 385 patients without acute LVEF impairment (i.e., those with LVEF ≥40%) were considered, 27 (7%) developed postprocedural CIN that was associated with increased major adverse cardiovascular events rate at 1 year of clinical follow-up (38% vs 9%; p <0.001). On adjusted Cox multivariate analysis, CIN was an independent predictor of worse outcomes, both when defined according to creatinine (hazard ratio 3.81, 95% confidence interval 1.71 to 8.48, p = 0.001) or eGFR (hazard ratio 3.77, 95% confidence interval 1.53 to 9.28, p = 0.004) variations. In conclusion, in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention, LVEF has a significant interaction with eGFR. When only patients without acute LVEF impairment were considered, CIN confirmed its negative prognostic effect on the 1-year clinical outcomes.

Management of patients with patent foramen ovale and cryptogenic stroke: a collaborative, multidisciplinary, position paper: executive summary.

Objectives: To organize a common approach on the management of patent foramen ovale (PFO) and cryptogenic stroke that may be shared by different specialists. Background: The management of PFO related to cryptogenic stroke is controversial, despite an increase in interventional closure procedures. Methods: A consensus statement was developed by approaching Italian national cardiological, neurological, and hematological scientific societies. Task force members were identified by the president and/or the boards of each relevant scientific society or working group, as appropriate. Drafts were outlined by specific task force working groups. To obtain a widespread consensus, these drafts were merged and distributed to the scientific societies for local evaluation and revision by as many experts as possible. The ensuing final draft, merging all the revisions, was reviewed by the task force and finally approved by scientific societies. Results: Definitions of transient ischemic attack and both symptomatic and asymptomatic cryptogenic strokes were specified. A diagnostic workout was identified for patients with candidate event(s) and patient foramen ovale to define the probable pathogenesis of clinical events and to describe individual PFO characteristics. Further recommendations were provided regarding medical and interventional therapy considering individual risk factors of recurrence. Finally, follow‐up evaluation was appraised. Conclusions: Available data provided the basis for a shared approach to management of cryptogenic ischemic cerebral events and PFO among different Italian scientific societies. Wider international initiatives on the topic are awaited.

Management of patients with patent foramen ovale and cryptogenic stroke: A collaborative, multidisciplinary, position paper

Objectives: To organize a common approach on the management of patent foramen ovale (PFO) and cryptogenic stroke that may be shared by different specialists. Background: The management of PFO related to cryptogenic stroke is controversial, despite an increase in interventional closure procedures. Methods: A consensus statement was developed by approaching Italian national cardiological, neurological, and hematological scientific societies. Task force members were identified by the president and/or the boards of each relevant scientific society or working group, as appropriate. Drafts were outlined by specific task force working groups. To obtain a widespread consensus, these drafts were merged and distributed to the scientific societies for local evaluation and revision by as many experts as possible. The ensuing final draft, merging all the revisions, was reviewed by the task force and finally approved by scientific societies. Results: Definitions of transient ischemic attack and both symptomatic and asymptomatic cryptogenic strokes were specified. A diagnostic workout was identified for patients with candidate event(s) and patient foramen ovale to define the probable pathogenesis of clinical events and to describe individual PFO characteristics. Further recommendations were provided regarding medical and interventional therapy considering individual risk factors of recurrence. Finally, follow‐up evaluation was appraised. Conclusions: Available data provided the basis for a shared approach to management of cryptogenic ischemic cerebral events and PFO among different Italian scientific societies. Wider international initiatives on the topic are awaited.

Nonpredictive value of fibrosis in dilated cardiomyopathy treated with metoprolol

Therapy with β-adrenergic blocking agents has been advocated as a potential useful approach in heart failure. Recent studies suggest that histologic parameters may be helpful in assessing the effectiveness of β-blocker treatment in dilated cardiomyopathy (DCM). In order to predict the response to β-blockers in DCM, fibrous tissue was evaluated at endomyocardial biopsy (EMB) in 45 patients (pts) with a mean left ventricular ejection fraction of 0.28 ± 0.07, who were successively long-term treated with metoprolol (M) (mean dosage 138 ±26 mg/die). EMB was performed from left (n = 32) or right (n = 13) ventricle by means of a Kings bioptome or the Cordis adaptation of this instrument. Quantification of fibrous tissue was performed at 9 × magnification and with a computerized morphometric system. Qualitative evaluation at light microscopy distinguished four types of fibrosis: pericellular, perivascular, focal, and endocardial. Volume fraction of fibrous tissue ranged from 1.3 to 35.5% (mean 12.1 ± 9.3%) and was not significantly correlated with any clinical variable considered. After 24 ± 12 months of treatment, 25 pts were considered improved (group A), whereas the remaining 20 pts were considered not improved (group B), according to criteria based on ejection fraction, left ventricular end-diastolic diameter, filling pattern at Doppler-Echocardiography, cardiothoracic ratio, NYHA functional class, and exercise duration at ergometric test. Volume fraction of fibrous tissue did not differ significantly between the two groups (group A = 12.1 ± 9.1%; group B = 11.3 ± 9.6%;p = NS). Dominant pericellular type of fibrosis was equally distributed between the two groups (group A = 9 25 pts, 36%; group B = 10 20 pts, 50%), whereas a perivascular and/or focal replacement fibrosis was more frequent in group A (group A = 10 20 pts, 50%; group B = 2 20 pts, 10%; p = .05, OR 5.55 at univariate analysis). At multivariate analysis mean aortic blood pressure was the only variable discriminating the two groups; the type of fibrosis, although not statistically significant, maintained a high value of odds-ratio (5.23). In conclusion, extent of total fibrosis assessed by EMB may range widely in patients with DCM, is not correlated with the most important clinical variables, and is not predictive of long-term response to β-blocker treatment. Otherwise, prevalent perivascular and/or focal replacement fibrosis could be associated with a higher probability of improvement after long-term β-blocker treatment.

ST-elevation myocardial infarction with reduced left ventricular ejection fraction: Insights into persisting left ventricular dysfunction. A pPCI-registry analysis

Primary percutaneous coronary intervention (pPCI) largely reduced the rate of left ventricular (LV) dysfunction after ST-segment elevation acute myocardial infarction (STEMI). Though LV recovery begins early following revascularization, the optimal timing for re-assessment of LV function is still unclear. We sought to assess the proportion and timing of LV recovery in STEMI patients presenting with LV dysfunction treated by pPCI and to identify possible early predictors of adverse LV remodeling. STEMI patients with LV ejection fraction (LVEF ≤40%) at presentation treated by pPCI from 2007 to 2013 were included whether they had an available 3-step LVEF assessment (<24h post-pPCI, discharge and follow-up). Primary endpoint was LVEF ≤35% at follow-up. At a median time of 3months, 43 out of 154 patients (28%) had LVEF ≤35%. In patients with persistent LV dysfunction, LVEF was lower at admission and increased less during hospitalization (from 31±6 to 35±4% Vs 35±5 to 43±8% for patients with 3-months LVEF >35%, p<0.001). Independent predictors of 3-months LVEF ≤35% were creatinine at admission, peak troponin I and LVEF. Of note, LVEF re-assessment at discharge (median time 6days, IQR 4-9) showed an increased accuracy to predict 3-months LV dysfunction compared to LVEF at admission (AUC 0.80, 95% CI 0.72-0.88 vs AUC 0.69, 95% CI 0.58-0.79 respectively, p=0.03). In most of patients presenting with STEMI and LV dysfunction, a significant LV recovery can be observed early following pPCI. LVEF measurement at discharge indeed emerged as the best indicator of late persistence of severe LV dysfunction.

Predicting device failure after percutaneous repair of functional mitral regurgitation in advanced heart failure: Implications for patient selection

BACKGROUND Patients with heart failure (HF) and severe symptomatic functional mitral regurgitation (FMR) may benefit from MitraClip implantation. With increasing numbers of patients being treated the success of procedure becomes a key issue. We sought to investigate the pre-procedural predictors of device failure in patients with advanced HF treated with MitraClip. METHODS From April 2012 to November 2016, 76 patients with poor functional class (NYHA class III-IV) and severe left ventricular (LV) remodeling underwent MitraClip implantation at University Hospitals of Trieste and Bologna (Italy). Device failure was assessed according to MVARC criteria. Patients were subsequently followed to additionally assess the patient success after 12months. RESULTS Mean age was 67±12years, the mean Log-EuroSCORE was 23.4±16.5%, and the mean LV end-diastolic volume index and ejection fraction (EF) were 112±33ml/m2 and 30.6±8.9%, respectively. At short-term evaluation, device failure was observed in 22 (29%) patients. Univariate predictors of device failure were LVEF, LV and left atrial volumes and anteroposterior mitral annulus diameter. Annulus dimension (OR 1.153, 95% CI 1.002-1.327, p=0.043) and LV end-diastolic volume (OR 1.024, 95% CI 1.000-1.049, p=0.049) were the only variables independently associated with the risk of device failure at the multivariate model. CONCLUSIONS Pre-procedural anteroposterior mitral annulus diameter accurately predicted the risk of device failure after MitraClip in the setting of advanced HF. Its assessment might aid the selection of the best candidates to percutaneous correction of FMR.

Impact of abciximab on prognosis in diabetic patients undergoing primary percutaneous coronary intervention.

Background The impact of diabetes in patients with acute myocardial infarction (AMI) treated with primary percutaneous coronary intervention (PCI) is unclear. The benefit of abciximab in this subset of patients remains controversial. Methods and results Three hundred and twenty-seven consecutive and unselected patients with acute AMI treated with primary PCI were included in our single-center retrospective registry, 103 diabetic (31%) and 224 nondiabetic (69%). Abciximab was given at the physicians discretion. Diabetic patients were older (mean age 68.5 ± 11 vs. 65 ± 12 years; P = 0.009), had an increased prevalence of hypertension (73 vs. 54%; P = 0.001), a decreased prevalence of smoking (31 vs. 45%; P = 0.02), a longer duration of symptoms before hospital admission (190 vs. 143 min; P = 0.031), and a higher number of stents implanted (1.4 vs. 1.2; P = 0.04). Other clinical and angiographic characteristics were comparable in the two groups. Diabetic patients had a higher incidence of the combined end-point of death and reinfarction rate at 30 days (18 vs. 10%; P = 0.04) compared to nondiabetic patients. Abciximab treatment was associated with a lower in-hospital (23.8 vs. 5%; P = 0.005) and 30-day (23.8 vs. 6.6%; P = 0.012) mortality, and a lower incidence of death and reinfarction at 30 days (33.3 vs. 9.8%; P = 0.003) in diabetic patients. In nondiabetic patients, abciximab was not associated with improved outcome measures. Advanced Killip class (III and IV) and abciximab were found to be independently associated with 30-day death or myocardial infarction [respectively, odds ratio (OR) 6.075, 95% confidence interval (CI) 1.59–23.218, P = 0.008 and OR 0.177, 95% CI 0.034–0.938, P = 0.042] in the propensity score-matched populations of diabetic patients. Advanced Killip class and thrombolysis in myocardial infarction score index were found to be independently associated with 30-day death or myocardial infarction (respectively, OR 6.607, 95% CI 1.5–29.106, P = 0.013 and OR 1.094 95% CI 1.042–1.148, P < 0.001) in the propensity score-matched populations of nondiabetic patients. Conclusions In our registry diabetic patients treated with primary PCI for AMI had a worse in-hospital and 30-day outcome than nondiabetic patients. Adjunct pharmacologic treatment with abciximab was associated to a better prognosis only in diabetic patients.

Documento di posizione multidisciplinare sulla gestione del forame ovale pervio in presenza di ischemia cerebrale criptogenica – versione 2013

There is no generally accepted consensus on the management of patent foramen ovale (PFO) in the presence of cryptogenic cerebral ischemia, because of the lack of conclusive evidence. The aim of this position paper was to develop and promote a joint approach based on available data that may be shared by different specialists, while waiting for definite results from randomized controlled trials. A position statement was produced involving the major national scientific societies. The task force members were nominated by the presidents and/or executive boards of each society or working group, as appropriate, based on their previous work in relevant topic areas. Specific task force working groups prepared the drafts. In order to achieve maximum agreement, these drafts were merged and distributed to the scientific societies for local evaluation. The ensuing final draft, merging all the revisions, was reviewed by the task force and finally approved by all scientific societies. The following issues were addressed: definitions of transient ischemic attack (TIA) and both symptomatic and asymptomatic cryptogenic stroke; formulation of a diagnostic workup for patients with clinical event(s) and PFO; recommendations regarding medical and interventional treatment options considering individual risk factors based on the three available randomized trials and other observational studies; recommendations regarding requirements for operators and centers in Italy; definition of a follow-up evaluation protocol. In conclusion, available data provided the basis for the first multi-society position paper on the management of cryptogenic stroke/TIA and PFO.There is no generally accepted consensus on the management of patent foramen ovale (PFO) in the presence of cryptogenic cerebral ischemia, because of the lack of conclusive evidence. The aim of this position paper was to develop and promote a joint approach based on available data that may be shared by different specialists, while waiting for definite results from randomized controlled trials. A position statement was produced involving the major national scientific societies. The task force members were nominated by the presidents and/or executive boards of each society or working group, as appropriate, based on their previous work in relevant topic areas. Specific task force working groups prepared the drafts. In order to achieve maximum agreement, these drafts were merged and distributed to the scientific societies for local evaluation. The ensuing final draft, merging all the revisions, was reviewed by the task force and finally approved by all scientific societies. The following issues were addressed: definitions of transient ischemic attack (TIA) and both symptomatic and asymptomatic cryptogenic stroke; formulation of a diagnostic workup for patients with clinical event(s) and PFO; recommendations regarding medical and interventional treatment options considering individual risk factors based on the three available randomized trials and other observational studies; recommendations regarding requirements for operators and centers in Italy; definition of a follow-up evaluation protocol. In conclusion, available data provided the basis for the first multi-society position paper on the management of cryptogenic stroke/TIA and PFO.

Contrast induced nephropathy: a new predictive model based on pre procedural glycemia and glomerular filtration rate

Aims: The risk of contrast induced nephropathy (CIN) is predicted by the already proposed formula of the ratio of contrast volume to glomerular filtration rate (GFR). Recent data from literature undescore that the incidence of CIN is significantly influenced by admission glycemia. Therefore, our aim was to identify a predictive model of CIN based on the quantity of contrast used during pPCI, known independent predictors of CIN, and pre procedural glycemia. Methods and results: 679 STEMI patients treated with primary PCI (pPCI) were enrolled in our prospective study. CIN was defined as an absolute serum creatinine increase ≥0.3 mg/dl after procedure. Admission hyperglycemia was defined as glucose levels >198 mg/dl. Medium volume of contrast (CV) we used ranged from 30 to 700 ml. We observed a significant increase in the incidence of CIN with the increase of the CV/GFR ratio which was in turn influenced by admission hyperglycemia. We therefore created a model of CIN prediction based on CV, GFR and admission glycemia. This model results from the product of admission glycemia and CV/GFR × 100. We then confronted our model with previously proposed models for prediction of CIN in pPCI patients (model 1: CV/GFR >3.7; model 2: CV/{[5 × weigth (kg)]/serum creatinin (mg/dl)} >1) obtaining better AUC with ROC analisys (AUC 0.72 vs 0.63, p<0.001 with model 1, AUC 0.72 vs 0,59, p<0.001 with model 2). At multivariate analisys a value of 4.2 was the best indipendent predictor of CIN. Conclusions: Our CIN risk model based on CV and admission glycemia was more accurate than the existing models. This model can be useful before pPCI to identify the safe quantity of contrast to use, and after pPCi to identify the subgroup of patients at higher risk of CIN.