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Acute pulmonary embolism (PE) is characterized by a large heterogeneity of clinical presentation and disease course. We investigate whether different symptom PE phenotypes in hemodynamically stable PE could be associated with 30-day mortality risk. Hemodynamically stable patients from the multicentre, prospective Italian Pulmonary Embolism Registry (IPER) (September 2006-August 2010) presenting the most common four clinical phenotypes ( 24 h onset dyspnoea, chest pain, pleuritic pain and phlebitis) at admission were included and compared to those who were asymptomatic at admission. Overall, 1365 (mean age 68.7 ± 15.3 years, 609 males) were evaluated. Recent onset dyspnoea ( 24 h), chest pain, pleuritic pain and phlebitis were observed in 28.4%, 19.7%, 12.9% and 25.2%, respectively while asymptomatic patients represented the remaining 13.6% of cases. PE presenting with recent dyspnoea onset and chest pain had a lower 30-day overall survival (log-rank p = 0.01 and p 0.001, respectively). By contrast, there were no significant differences when comparing patients with pleuritic pain or phlebitis (log-rank p = 0.2). Similar findings were confirmed at the Cox multivariate regression analysis which indicated a higher mortality risk in patients with chest pain [HR 3.21, 95% CI 2.16-4.78, p 0.001] or recent dyspnoea [HR 2.12, 95% CI 1.22-3.87, p = 0.002] independent of age, heart rate, presence of right ventricular dysfunction, positive cardiac troponin and administration of systemic thrombolysis. Hemodynamically stable PE patients presenting with chest pain or recent onset dyspnoea had a lower 30-day survival compared to those asymptomatic or presenting pleuritic or phlebitis pain.Trial registry ClinicalTrials.gov; No: NCT01604538).

Aims We assess the prognostic role of mean arterial pressure (MAP) for 48 h clinical deterioration in intermediate-high risk pulmonary embolism (PE) patients after admission. Methods and results A post hoc analysis of intermediate-high-risk PE and intermediate-low-risk PE patients enrolled in the Italian Pulmonary Embolism Registry (IPER) (Trial registry: ClinicalTrials.gov; No.: NCT01604538) was performed. Clinical deterioration within 48 h was defined as patient worsening from a stable to an unstable haemodynamic condition, need of catecholamine infusion, endotracheal intubation, or cardiopulmonary resuscitation. Of 450 intermediate-high risk PE patients (mean age 71.4 ± 13.8 years, 298 males), 40 (8.8%) experienced clinical deterioration within 48 h from admission. Receiver operating characteristic analysis established the optimal cut-off value for MAP, as a predictor of 48 h clinical deterioration, ≤81.5 mmHg [area under curve (AUC) of 0.77 ± 0.3] with sensitivity, specificity, positive predictive value, and negative predictive value were 77.5, 95.0, 63.2, and 97.7%, respectively. Multivariate Cox regression analysis showed that independent risk factors for 48 h clinical deterioration were age [hazard ratio (HR): 1.26, 95% confidence interval (CI): 1.19–1.28, P < 0.0001], history of heart failure (HR: 1.76, 95% CI: 1.72–1.81, P < 0.0001), simplified Pulmonary Embolism Severity Index (HR: 1.52, 95% CI: 1.49–1.58, P = 0.001), systemic thrombolysis (HR: 0.54, 95% CI: 0.30–0.65, P < 0.0001), and a MAP of ≤81.5 mmHg at admission (HR: 3.25, 95% CI: 1.89–5.21, P < 0.0001). The deteriorating group had a significantly higher risk of 30-day mortality (HR: 2.61, 95% CI: 2.54–2.66, P < 0.0001) compared with the non-deteriorating group. Conclusion The mean arterial pressure appears to be a useful, bedside, and non-invasive prognostic tool potentially capable of promptly identifying intermediate-high risk PE patients at higher risk of 48 h clinical deterioration.

BACKGROUND: The prevalence and prognostic implications of acute cardiac injury (ACI), as a complication of coronavirus disease 2019 (COVID-19), remain unclear. OBJECTIVES: We conducted a systematic review and meta-analysis to investigate the relationship between ACI and mortality risk in COVID-19 patients. METHODS: Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed in abstracting data and assessing validity. We searched MEDLINE, Scopus and Web of Science to locate all articles published up to 10 April 2020 reporting data of COVID-19 survivors and nonsurvivors developing ACI as a complication of the infection. Quality assessment was performed using the Newcastle-Ottawa quality assessment scale. Data were pooled using the Mantel-Haenszel random effects models with odds ratio as the effect measure with the related 95% confidence interval. Statistical heterogeneity between groups was measured using the Higgins I statistic. RESULTS: Eight studies, enrolling 1686 patients (mean age 59.5 years), met the inclusion criteria and were included in the final analysis. Data regarding the outcome of patients complicated with ACI were available for 1615 patients. Of these, 387 (23.9%) experienced ACIs as COVID-19 complications during the hospitalization. The incidence of ACI was significantly higher among non survivors when compared with survivors (61.6 vs. 6.7%, P 

The aim of the present review is to analyze the clinical characteristics of patients with acute pulmonary embolism (PE) which seizures were the first clinical manifestation of the disease. After screening 258 articles in PubMed, Scopus, Cochrane Library, and Google Scholar databases, we identified 16 case reports meeting the inclusion criteria. The mean age of the population was 48.4 ± 19.8 years (9 males and 7 females). About three of four patients (68.7%) were hemodynamically stable at admission, having a systolic blood pressure > 90 mmHg. Intriguingly, the doubt of acute PE was based on clinical suspicion or on instrumental findings in 62.5% and 18.7% of patients, respectively. In 3 subjects (18.7%), the acute cardiovascular disease was not suspected. Half of patients had an unremarkable previous medical history while neurological comorbidities were present in 4 patients (25.0%). During seizures, a transient loss of consciousness (TLOC) was reported in 6 cases. Seizures were retrospectively classified according to the 2017 ILAE classification, whenever possible. A focal and generalized onset was reported in 37.5% and 50% of cases, respectively, in 12.5% of patient’s data that were insufficient to classify the events. The mean number of seizure episodes in the population enrolled was 2.0 ± 1.1. Mortality rate was 54.5% but one investigation did not report the patient’s outcome. The relationship between seizures and acute PE is probably underrecognized. Identifying patients that have a high probability of acute PE is fundamental to avoid any treatment delay and ameliorate their outcomes.

We systematically review the potential role of left atrial (LA) size, evaluated at computed tomography angiography (CTA) in patients with acute pulmonary embolism (PE), as a new parameter of PE severity. A literature search based on PubMed (MEDLINE), Scopus, Cochrane library and Google Scholar databases was performed to locate previous published investigations reporting data on the severity of acute PE based on the evaluation of LA size (either volume, diameter or area). Six studies, corresponding to a total of 990 patients, published between 2012 and 2019 were included into the analysis. The severity of acute PE, in terms of hemodynamic impairment, increases with the reduction of the LA volume and a significant negative correlation was observed between the pulmonary artery obstruction index (PAOI) and the LA area. Similarly, the longest left-to-right as well as the anteroposterior diameters of the LA had a significant positive correlation with the PAOI index for both the measurement. The LA volume significantly decreased with the increasing of the PAOI index. Moreover, a lower LA volume was observed in those subjects with a saddle PE appearing as the best single parameter able to discriminate between patients having or not a saddle acute PE. Intriguingly, PE patients died within 30 days from the acute event had a significant small LA volume compared to survivors. Data obtained from the current medical literature seem to suggest that the evaluation of LA size evaluation could be a new parameter of PE severity. Further and larger prospective studies are needed to confirm preliminary findings.

The use of inferior vena cava (IVC) filters is recommended in patients with acute pulmonary embolism (PE) who have absolute contraindications to anticoagulant drugs and/or in those subjects with recurrent PE despite treated with an adequate anticoagulant regimen. During the last 2 decades, some investigations have demonstrated that the use of IVC filters in high-risk PE patients, treated or not with systemic thrombolysis, was able to reduce the short-term mortality rate if inserted early after the acute event. The aim of the present review is to analyze the use of IVC filters in high-risk PE patients enrolled in prospective multicenter registries between 1990 and 2018. After screening 3542 article in PubMed, Scopus, Cochrane library and Goggle Scholar databases, we identified four registry studies meeting the inclusion criteria. In a prospective cohort of 39,056 patients, 1387 (3.5%) were hemodynamically unstable at admission. Among them, IVC filters were used only in 2.7% of cases. Conversely, IVC filters were inserted in 3.8% of hemodynamically stable patients. Over the years, a fluctuating trend in the use of IVC filters was observed. In the absence of randomized controlled trial on this issue, which would be difficult, if not impossible to realize, data obtained from the medical literature seem to suggest that IVC filters could represent a valid adjunctive therapy in hemodynamically unstable PE patients, able to prevent further hemodynamic deterioration. Further and larger subgroup analyses, obtained both by prospective and retrospective studies, are necessary to clarify this therapeutic approach.

Highlights • Acute pulmonary embolism (PE) is a frequent complication of COVID-19 infection. • The in-hospital incidence of acute PE among COVID-19 patients is higher in ICU patients. • Computed tomography angiography (CTPA) is infrequently performed., Background Acute pulmonary embolism (PE) has been described as a frequent and prognostically relevant complication of COVID-19 infection. Aim We performed a systematic review and meta-analysis of the in-hospital incidence of acute PE among COVID-19 patients based on studies published within four months of COVID-19 outbreak. Material and Methods Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed in abstracting data and assessing validity. We searched Medline, Scopus and Web of Science to locate all articles published up to August 1, 2020 reporting the incidence of acute PE (or lung thrombosis) in COVID-19 patients. The pooled in-hospital incidence of acute PE among COVID-19 patients was calculated using a random effects model and presenting the related 95% confidence interval (CI). Statistical heterogeneity was measured using the Higgins I2 statistic. Results We analysed data from 7178 COVID-19 patients [mean age 60.4 years] included in twenty-three studies. Among patients hospitalized in general wards and intensive care unit (ICU), the pooled in-hospital incidence of PE (or lung thrombosis) was 14.7% of cases (95% CI: 9.9–21.3%, I2=95.0%, p

Data regarding pulmonary embolism (PE)-related mortality in Italy are scarce. We assessed PE-related mortality and its time trend in Italy by using the World Health Organization (WHO) Mortality Database.The vital registration data of Italy from the WHO Mortality Database were analyzed for the period between 2003 and 2015, and compared with time trends in Southern Europe. Death was defined as PE-related when classified with specific codes for PE or limb vein thrombosis listed as the primary cause of death. This coding was based on the International Classification of Diseases, tenth revision.Overall, 28 647 PE-related deaths (10 178 men and 18 469 women) were recorded between 2003 and 2015. The observed age-standardized annual PE-related mortality rates were 2.5 per 100 000 men and 2.8 per 100 000 women. Moreover, PE-related mortality increased with age with a seemingly exponential distribution. Joinpoint regression analysis demonstrated a statistically significant linear decrease in age-standardized PE-related mortality of -0.21 (95% confidence interval -0.27; -0.15) and -0.22 (95% confidence interval -0.28; -0.16) deaths per 100 000 population for men and women, respectively.The Italian age-adjusted mortality rates appeared lower compared to overall Southern Europe, despite a similar decreasing trend over time.

The temporal window for the administration of systemic thrombolysis (ST) in acute pulmonary embolism (PE) has not yet been clarified. We assessed the relationship between short-term cardiovascular (CV) mortality and time of ST administration.Among 394 consecutive patients admitted between January 2010 and June 2017 with a confirmed PE, we retrospectively review the clinical and instrumental data of those labelled as high-risk PE (n = 76, 41 males, mean aged 64.7 ± 9.1 years old).A receiving operating curve (ROC) analysis established the optimal temporal threshold for the administration of the ST, in respect to the 30-day CV mortality at 8.5 h from the symptom onset (Area under Curve 0.79 ± 0.6, 95% CI 0.73-0.86, p 0.0001). Mantel-Cox analysis showed that there was a significant difference in the distribution of survival between patients treated within 8.5 h from the beginning of symptoms onset to those treated after 8.6 h [log rank (Mantel-Cox) chi-square 9.68 p = 0.002]. Cox-regression analysis demonstrated that the administration of ST after 8.6 h from the symptom's onset was an independent predictor of 30-day CV mortality in high-risk PE patients (HR 7.81, 95% CI 1.84-33.05, p = 0.005), independently from the occurrence of major bleeding events (HR 5.89, 95% CI 1.38-25.13, p = 0.01), previous CAD (HR 3.31, 95CI 1.07-10.231. p = 0.03), RV/LV ratio after 2 h from the administration ST 1 (HR (12.91, 95% CI 3.04-54.77, p = 0.001) and PAH at discharge (HR 3.86, 95% CI 2.22-4.68, p = 0.002).ST administered within 8.5 h from symptoms onset may be associated with a reduced 30-day CV mortality in high-risk PE patients.

Syncope and pre-syncope are well-known symptoms of acute pulmonary embolism (PE). However, data about their impact on short-term mortality are scant. We assess the short-term mortality (30-day) for all-causes in PE patients admitted with syncope or with pre-syncope, according their hemodynamic status at admission.Patients from the prospective Italian Pulmonary Embolism Registry (IPER) were included in the study. At admission, subjects were stratified according to 2008 ESC guidelines (as high- and non-high-risk patients).Among the 1716 patients with confirmed acute PE, syncope or pre-syncope was the initial manifestation of the disease in 458 (26.6%) patients. Short-term mortality (30-day) for all causes were significantly higher in patients with syncope/presyncope (42.5% vs 6.2%, p 0.0001) while PE patients with presyncope demonstrated a worst short-term outcome, in terms of mortality for all-causes, when compared to those subjects with syncope at admission (47.2% vs 37.4%, p = 0.03). A statistically significant difference in survival between pre-syncope and syncope was observed only in hemodynamically unstable patients [log rank p = 0.036]. Cox regression analysis confirmed that pre-syncope resulted an independent predictor of 30-day mortality in hemodynamically unstable patients at admission (HR 2.13, 95% CI 1.08-4.22, p = 0.029), independently from right ventricular dysfunction (RVD) (HR 6.23, 95% CI 3.05-12.71, p 0.0001), age (HR 1.03, 95% CI 1.00-1.06, p = 0.023) and thrombolysis (HR 2.27, 95% CI 1.11-4.66, p = 0.025).PE patients with syncope/presyncope had a higher 30-day mortality for all-causes as well as patients with presyncope had a worst short-term outcome when compared to PE patients with syncope. Moreover, hemodynamically unstable patients with presyncope had a worst prognosis independently from the presence of RVD, age, positive cTn and thrombolytic treatment.

Background Several electrocardiographic (ECG) abnormalities have been described in patients with acute pulmonary embolism (PE), with discordant reportings about their prognostic value. Methods Consecutive patients with echocardiography performed within 48 h from admission and ECG at presentation, were included in this analysis. The primary study outcome was in-hospital death for high-risk patients and in-hospital death or clinical deterioration for intermediate-risk patients. As secondary outcomes, the associations among ECG abnormalities and both right ventricular dysfunction at echocardiography and baseline troponin elevation were considered. Results 1194 patients were included in this analysis: 13.8% of patients were at high risk of early death, 61.7% were at intermediate risk and 24.5% were at low risk. ECG signs of RV strain showed a continuously decreasing prevalence from high-risk to intermediate-risk and low-risk patients. Differently, the prevalence of T- wave inversion was similar in high and intermediate-risk patients. In high-risk-patients, Qr pattern in lead V1 was the only ECG abnormality associated with in-hospital mortality, but this sign was detected in only 15.9% of this risk category; the presence of at least one ECG abnormality was not associated with the risk of in-hospital death. In not high-risk patients, the presence of at least one ECG abnormality was significantly associated with RVD and this association was confirmed for each individual ECG abnormality. Similar results were obtained as regards the baseline troponin elevation in 816 patients. Conclusions Among the electrocardiographic signs of RV strain/ischemia, Qr pattern in lead V1 was the only ECG abnormality associated with in-hospital mortality in high-risk patients. In not high-risk patients the demonstrated association among baseline ECG signs of RV strain/ischemia and RV dysfunction at echocardiography or troponin elevation highlights the need for early further investigations in patients with such ECG abnormalities.

Available studies have already identified age, heart rate (HR) and systolic blood pressure (SBP) as strong predictors of early mortality in acute pulmonary embolism (PE).One-hundred-seventy patients, with acute PE confirmed on computed tomography angiography (CTA) were enrolled. Thrombolysis In Myocardial Infarction (TIMI) risk index (TRI) was calculated using the formula [heart rate (HR) x (AGE/102)/ systolic blood pressure (SBP)]. Study outcomes were 30-day mortality and/or clinical deterioration.Receiver operating characteristics (ROC) curve revealed that a TRI ≥45 was highly specific for both outcomes (AUC 0.91, 95% CI 0.83-0.98, p0.0001) with a positive predictive value (PPV) and negative predictive value (NPV) of 8.3 and 96% for 30-day mortality while PPV and NPV for 30-day mortality and/or clinical deterioration were 21.1 and 98.2%, respectively. Multivariate regression analysis showed that TRI ≥45 was an independent predictor of 30-day mortality (O.R. 22.24, 95% CI 2.54-194.10, p=0.005) independently from positive cTnI and RVD (O.R. 9.57, 95% CI 1.88-48.78, p=0.007; OR 24.99, 95% CI 2.84-219.48, p=0.004). Similarly, 30-day mortality and/or clinical deterioration was predicted by TRI ≥45 (O.R. 11.57, 95% CI 2.36-56.63, p=0.003) and thrombolysis (3.83, 95% CI 1.04-14.09, p=0.043), independently from age, RVD and positive cTnI. Cox regression analysis confirmed the role of TRI as independent predictor for both outcomes. Mantel-Cox analysis showed that after 30-day follow-up there was a statistically significant difference in the distribution of survival between patients with and without TRI ≥45 [log rank (Mantel-Cox) chi-square 17.04, p0.0001].Thrombolysis In Myocardial Infarction (TIMI) risk index (TRI) predicted both 30-days mortality (all-causes) and/or clinical deterioration in patients with acute PE.

Acute pulmonary embolism (PE) is the third cause of cardiovascular (CV) mortality. We evaluated a new risk index, named Age-Mean Arterial Pressure Index (AMAPI), to predict 30-day CV mortality in patients with acute PE. Data of 209 patients (44.0% male and 56.0% female, mean age 70.58 ± 14.14 years) with confirmed acute PE were retrospectively analysed. AMAPI was calculated as the ratio between age and mean arterial pressure (MAP), which was defined as [systolic blood pressure + (2 × diastolic blood pressure)]/3. To test AMAPI accuracy, a comparison with shock index (SI) and simplified pulmonary embolism severity index (sPESI) was performed. Patients were divided in two groups according their hemodynamic stability, or not, at admission. 30-day mortality rate, in all cases for CV events, was 10.5% (n = 22). Hemodynamically unstable patients had a higher AMAPI compare to those without hypotension at admission (1.28 ± 0.39 vs 0.78 ± 0.27, p

Venous thromboembolism (VTE), including pulmonary embolism and deep venous thrombosis, is the third most common cause of cardiovascular death. The management of the acute phase of VTE has already been described in several guidelines. However, the management of the follow-up (FU) of these patients has been poorly defined. This consensus document, created by the Italian cardiologists, wants to clarify this issue using the currently available evidence in VTE. Clinical and instrumental data acquired during the acute phase of the disease are the cornerstone for planning the FU. Acquired or congenital thrombophilic disorders could be identified in apparently unprovoked VTE during the FU. In other cases, an occult cancer could be discovered after a VTE. The main targets of the post-acute management are to prevent recurrence of VTE and to identify the patients who can develop a chronic thromboembolic pulmonary hypertension. Knowledge of pathophysiology and therapeutic approaches is fundamental to decide the most appropriate long-term treatment. Moreover, prognostic stratification during the FU should be constantly updated on the basis of the new evidence acquired. Currently, the cornerstone of VTE treatment is represented by both the oral and the parenteral anticoagulation. Novel oral anticoagulants should be an interesting alternative in the long-term treatment.

Acute pulmonary embolism (PE) still represents the third leading cause of cardiovascular mortality in developed countries. In this regard, the last European guidelines offer important suggestions on the management of the disease in daily clinical practice but, at the same time, they do not take into account the feasibility of the recommendations according to the local available resources, including the presence or lack of adequate healthcare facilities (cardiological intensive care unit, cath-lab) or specialists (cardiologist available on a 24 h basis, interventional cardiologist, cardiac surgeon, etc.) all over the day. In the real clinical practice, those recommendations should be adapted to the local available resources. The aim of this document is to provide some suggestions regarding the diagnosis and treatment of acute PE, according to the possible available resources in different local circumstances.

Hemodynamically unstable pulmonary embolism (PE) represents a complex and life-threatening event with a highly variable course and poor prognosis in the short-term period. Despite an immediate reperfusion treatment is recommended in these patients, previous investigations have reported a lower use of systemic thrombolysis (ST). The aim of the present review is to assess and describe the real use of ST in hemodynamically unstable patients with acute PE enrolled in prospective—multicenter registries between the 1990 and 2018. Over that period, 1216 articles were identified in Pubmed. After excluding the duplicates obtained using the different searching MeSH (n = 703), 513 articles were screened and then excluded for not meeting inclusion criteria due the article type, design of the study or no English language. As result, 13 articles were assessed for eligibility and carefully reviewed. Finally, five studies met the inclusion criteria and were included in the analysis. The identified study registries enrolled prospectively 41364 consecutive patients with acute PE between the 1993 and the 2016. Among these, 2168 (5.2%) were hemodynamically unstable at presentation. ST was administered in 29.7% (n = 645) of patients while catheter-direct treatment (CDT) was used only in 1.4% (n = 32) of cases. Conversely, surgical pulmonary embolectomy (SPE) was adopted as reperfusion treatment in 39 patients (1.7%). Intriguingly, the 68% of patients not received a reperfusion treatment despite they were hemodynamically unstable at admission. Despite the internationals guidelines recommendations, a prompt reperfusion is performed only in one on three hemodynamically unstable patients with acute PE.

Reperfusion in acute pulmonary embolism (PE) by percutaneous techniques is a valid therapeutic option when there is a formal contraindication to or failure of thrombolysis. In the last years, an increasing number of patients with acute PE have been treated with these techniques.In order to obtain a map of current availability and use of percutaneous techniques in PE, on behalf of the ANMCO Pulmonary Circulation Area, 56 Italian interventional cardiology and radiology departments, equipped with technology for percutaneous embolectomy, were invited to participate in a national survey. Questionnaires were e-mailed to each department from April to May 2015.Thirty-one out of 56 centers (54.8% in the North, 9.7% in the Center and 35.5% in the South of Italy) answered to the questionnaire. Percutaneous techniques were available in 90% of the cardiology departments involved, reporting also a good experience with their use in PE (77.4%). Only two responders were interventional radiology departments. AngioJet(®) and EkoSonic Endovascular System(®) (64.7% and 19.4%, respectively) were the most common devices used. Overall, in 2014, 62 patients were treated with percutaneous techniques, mainly in the North of the country. With regard to local diagnostic and therapeutic protocols, 61.3% of respondents reported owning one. Great interest was provided by participants in adhering to this national multicenter registry.Our results show the interest of Italian cardiology departments about percutaneous techniques as a therapeutic option for acute PE. Percutaneous techniques are largely available but still underused in routine clinical practice.

Background Registries are essential to obtain information on the whole spectrum of patients with pulmonary embolism (PE). The aim of the Italian Pulmonary Embolism Registry (IPER) is to report on demographics, clinical features, management, and outcomes of patients diagnosed with PE in everyday clinical practice. Methods Patients with confirmed acute PE were enrolled in a web-based registry, in Cardiology, Emergency or Internal Medicine Departments in 47 hospitals in Italy. Results Overall, 1716 patients were included, mean age 70 ± 15 years, (14% of the patients were 75 year old); 57% of female gender and 11.7% hemodynamically unstable at presentation/diagnosis. D-dimer was performed in 1358 patients (80%). Computerized tomographic pulmonary angiogram (CT) was used for diagnosis in the majority of the patients (82.1%), followed by perfusion lung scan (8.6%). Thrombolytic agents were used in 185 (10.8%) patients, percutaneous thrombectomy in 14 (0.8%) and surgery in 2 (0.1%). One hundred sixteen patients died while in-hospital (6.7%), 68 (3.9%) due to PE. Death or clinical deterioration occurred in 138 patients (8.0%). All-cause mortality was 31.8% in hemodynamically unstable patients and 3.4% in hemodynamically stable patients; the corresponding PE-related deaths were 23.3% and 1.4% respectively. Age > 75 (HR 1.50, 95% CI 1.01-2.25), immobilization > 3 days before diagnosis of PE (HR 2.54, 95% CI 1.72-3.77) and hemodynamic impairment (HR 6.38, 95% CI 4.26-9.57) were independent predictors for in-hospital death. Conclusions Patients with PE have a considerable risk of death during the hospital stay, PE being the most common cause of early mortality.

We report the case of a 35-year-old man who developed a massive pulmonary embolism (PE) after spine surgery. After an accidental axial fall, the patient developed a spinal epidural hematoma (SHE). Because major trauma, recent surgery and known bleeding risk are considered absolute contraindications to systemic thrombolysis, the patient was treated with catheter-directed therapy (CDT). CDT remains a useful treatment in massive PE, especially when systemic thrombolysis is contraindicated or has failed.

Intracardiac echocardiography (ICE) is a widespread approach in many cardiovascular procedures in which it has the potential to reduce the fluoroscopy time and patients radiation exposure. We sought to assess the patient radiation exposure during transcatheter closure of interatrial communications with and without ICE-guidance.In a prospective consecutive series of 25 consecutive patients who underwent transcatheter closure of interatrial communications between May and October 2005 with (15 patients) and without (10 patients) ICE-guidance in a single secondary care referral centre, we measured the dose-area product (DAP), the fluoroscopy dose-area product (FDAP), the total dose-area product (TDAP), and the mean procedural time.In patients underwent ICE-guided transcatheter closure procedure the mean fluoroscopy time, the mean DAP, mean FDAP, and mean TDAP resulted significantly lower than in control patients: 2.0 +/- 0.21 (range 1.6-2.2) versus 5.05 +/- 0.54 (range 4.2-5.8) minutes (P0.001) , 13.72 +/- 9.03 (range 11.36-14.63) versus 21.95 +/- 6.93 (range 20.90-23.93) Gycm2 (P0.001), 8.25 +/- 1.22 (range 6.60-9.50) versus 20.15 +/- 8.83 (range 18.90-20.93) Gycm2 (P0.001), and 29.33 +/- 1.51(range 27.16-31.00) versus 32.61 +/- 2.53 (range 29.20-35.55) Gycm2 (P0.01). On the contrary, the mean procedural time, was significantly higher in ICE-guided transcatheter closure patients: 30.2 +/- 2.45 (range 23-40) versus 24.5 +/- 2.45 (range 24-31) minutes (P = 0.03).The radiation exposure during ICE-guided transcatheter closure of interatrial communications in this group of patients was quite lower than that reported in literature for such procedures and compared favourably with radiation exposure of patients in whom the intervention was performed without ICE guidance.

Endovascular management of peripheral vascular disease before cardiac surgery is still debated. We sought to present our preliminary experience of endovascular stent placement in patients scheduled for urgent cardiac surgery.Between November 2003 and August 2005, 20 patients scheduled for urgent coronary surgery (13 males, mean age 72.5+/-5.3 years) underwent endovascular repair of PVD on the basis of clinical and angiographic indications. Aspirin (100 mg/day) plus low molecular weight heparin (nadroparin calcium) 100 IU/kg/12 h for urgent coronary surgical revascularization was administered after the procedure.Endovascular stenting has been performed in four clinical settings: renal artery stenting prior to coronary surgery (nine patients) to decrease the impact of extracorporeal circulation on an impaired renal function, iliac artery artery angioplasty and stenting (eight patients) in order to facilitate aortic balloon pump insertion after surgery, subclavian artery angioplasty and stenting propedeutical to arterial conduits bypass surgery (one patient), carotid artery stenting before coronary surgery (two patients). All patients underwent successful endovascular repair followed by cardiac surgery. At a mean follow-up of 12+/-4.6 months all patients are alive and without evident thrombosis or restenosis of the implanted vascular stents.Endovascular treatment of PVD in patients scheduled for urgent coronary surgery may be effective, relatively safe and lasting in spite of low dose antiplatelet regimen.

Aims A large number of descriptive data on patients with acute myocardial infarction are based on clinical trials and registries on non consecutive patients: these data may give only a partial picture on treatment delay, patient characteristics, treatment and outcome of acute myocardial infarction in the real world. Methods and results The BLITZ survey prospectively enrolled all of the patients with acute myocardial infarction admitted in 296 (87%) Italian Coronary Care Units from 15–29 October 2001. Data on treatment delay, therapeutic strategies, duration of hospitalization and 30-day outcome were collected. One thousand nine hundred and fifty-nine consecutive patients (mean age 67±12 years, 70% males) were enrolled, 65% with ST-segment elevation (STEMI), 30% with no ST-segment elevation (NSTEMI) and 5% with undetermined ECG. The median delay between symptom onset and hospital arrival was 2h and 9min with 76% of patients hospitalized within the sixth hour (26% within the first hour, 48% within the second). The median delay from hospital arrival to reperfusion therapy in STEMI was 45min (IQR 26–85) for thrombolysis (50% of the patients) and 85 min (IQR 60–135) for primary angioplasty (15% of the patients). Coronary angiography was performed during hospital stay in 46% of the patients (STEMI 48%, NSTEMI 43%, undetermined AMI 35%), coronary angioplasty in 25% (STEMI 26%, NSTEMI 15%, undetermined AMI 13%) and coronary bypass in 1.4% (1%, 2.2% and 1% respectively). Twenty-two percent of the patients admitted to hospitals without cath-lab were transferred to a tertiary care hospital for invasive procedures. The overall median hospital stay was 10 days (IQR 7–12, STEMI 10, NSTEMI 9, undeterminedAMI 11) and was not significantly different between hospitals with or without cath-lab (respectively, 9 and 10 days, P =0.38). After discharge and up to 30 days, coronaryangiography was performed in 11% (STEMI 11%, NSTEMI 11%, undetermined MI 9%), angioplasty in 10% (STEMI 10%, NSTEMI 11%, undetermined MI 7%), bypass surgery in 7% (STEMI 5%, NSTEMI 11%, undetermined AMI 7%). The in-hospital and 30-day case fatality rates were 7.4% and 9.4%, respectively (7.5% and 9.5% for STEMI, 5.2% and 7.1% for NSTEMI, 18.2% and 21.2% for undetermined MI). Conclusions Patients with acute myocardial infarction admitted to the Italian CCUs, are older than those represented in clinical trials. A high proportion of these cases has the chance to receive early reperfusion therapy. Short-term mortality is lower than expected for patients with STEMI, but higher than reported for NSTEMI.

The aim of the present study was to compare the ambulatory blood pressure levels in mild (stage 1) hypertensive women using oral contraceptives and respective values in nonusers of oral contraceptives with similar office blood pressure. The study group consisted of 24 mild hypertensive patients taking low dosage estrogen-progestogen oral contraceptives. Seventy women of similar age and body mass index who had never used oral contraceptives served as a control group. Both daytime and nighttime systolic blood pressure values were significantly higher in oral contraceptive users. There was an average 8.3 mm Hg difference (95% confidence interval, 3.0 to 13.7 mm Hg; P = .003) for the daytime and 6.1 mm Hg difference (95% confidence interval, 0.4 to 11.8 mm Hg; P = .04) for the nighttime. No significant differences in ambulatory diastolic blood pressure between the two groups were found. These data provide evidence that hypertensive oral contraceptive users with the same office blood pressure as that in hypertensive noncontraceptive users have a significantly higher ambulatory systolic blood pressure. Our results support the opinion that alternative methods of contraception should be considered for hypertensive women in place of oral contraceptives.

Pulmonary hypertension is characterized by an increase in pulmonary vascular resistance and premature death. Echocardiography is useful in the screening of patients with suspected pulmonary hypertension by estimation of the systolic regurgitant tricuspid flow velocity according to the simplified Bernoulli equation. On this basis, the survey INCIPIT was created aiming at evaluating the frequency of suspected pulmonary hypertension among Italian patients.From November 10 to 29, 2008, echo laboratories were invited to report on a special electronic file the number of echocardiographic examinations performed and the number of those showing a peak tricuspid regurgitant flow velocityor = 3 m/s.123 echo labs participated in the study. 21 483 echocardiograms were evaluated from 110 centers (58, 17 and 35 in North, Center and South Italy, respectively); 1410 (6.6%) exams showed a systolic regurgitant flow velocityor = 3 m/s (median value 3.3 and interquartile range 0.46). Patients were predominantly female (female to male ratio 734/676), with a mean age of 71.8 +/- 11.8 years, median body mass index of 25.7 kg/m2 (interquartile range 5.5). Overall, 21.4% patients had no symptoms, 48.7% had dyspnea, 11.2% had asthenia, 3.9% had chest pain, and 7.4% had dyspnea and asthenia. Among the 1410 patients with a tricuspid regurgitant flow velocityor = 3 m/s, 52.62% had left heart disease, 7.52% lung disease, 1.35% chronic thromboembolic pulmonary hypertension, 0.92% collagen disease, 0.43% congenital heart disease, 0.14% liver disease, 0.07% HIV, 26.45% more than one disease, and 10.5% presented suspected pulmonary hypertension of unknown cause.In the Italian echo labs, the occurrence of suspected pulmonary hypertension is not uncommon. Cardiologists should be encouraged to refer patients with suspected pulmonary hypertension of unknown origin to specialized centers in order to define the cause of pulmonary hypertension and to institute the appropriate therapy.

Background.The effect of alteplase versus heparin in pulmonary embolism has not been studied extensively with serial pulmonary angiograms. Objectives.The aim of this randomized, open trial was to evaluate the efficacy and safety of alteplase followed by heparin, versus heparin alone, in 30 patients with angiographically documented pulmonary embolism. Methods.Twenty patients were allocated randomly to a 2-h infusion of alteplase (10 mg bolus, then 90 mg over 2 h) followed by heparin; the other 16 patients were given intravenous heparin at a continuous infusion rate of 1,750 IU/h. Results.The vascular obstruction, assessed by the Miller index at pulmonary angiography, decreased significantly in alteplasetreated patients (p < 0.01) from a baseline of 28.3 ± 2.9 to a value of 24.8 ± 5.2 2 h after the start of infusion; in the heparin group there was no change (from 25.3 ± 5.3 to 25.2 ± 5.4). Mean pulmonary artery pressure decreased significantly from a baseline of 30.2 ± 7.8 mm Hg to 21.4 ± 6.7 in the alteplase group and increased in the heparin group (from 22.3 ± 10.5 to 24.8 ± 11.2 mm Hg). For a subset of patients, lung scans were performed at baseline and on days 7 and 30. There were no differences between the two groups in the follow-up lung scans, but there were significant decreases from the baseline values. Bleeding occurred in 14 of 20 alteplase-treated patients and in 6 of 16 in the heparin group (p = NS). There were three major bleeding episodes in the alteplase group and two in the heparin group. Two patients died after fibrinolysis (one of acute renal failure after cardiac tamponade and one of cardiac arrest after cerebral hemorrhage) and one patient in the heparin group died of recurrent pulmonary embolism. Conclusions.Alteplase resulted in a greater and faster improvement of the angiographic and hemodynamic variables compared with heparin. However, the high frequency of bleeding observed with alteplase in this trial suggests that patients should be carefully selected before thrombolytic therapy is given.

In the era of evidence-based medicine, the monitoring of the adherence to the guidelines is fundamental, in order to verify the diagnostic and therapeutic processes. Informatic paperless databases allow a higher data quality, lower costs and timely analysis with overall advantages over the traditional surveys. The RUTA project (acronym of Triveneto Registry of ANMCO CCUs) was designed in 1999, aiming at creating an informatic network among the coronary care units of a large Italian region, for a permanent survey of patients admitted for acute myocardial infarction. Information ranges from the pre-hospital phase to discharge, including all relevant clinical and management variables. The database uses DBMS Personal Oracle and Power-Builder as user interface, on Windows platform. Anonymous data are sent to a central server.

We conducted a genome-wide association study testing single nucleotide polymorphisms (SNPs) and copy number variants (CNVs) for association with early-onset myocardial infarction in 2,967 cases and 3,075 controls. We carried out replication in an independent sample with an effective sample size of up to 19,492. SNPs at nine loci reached genome-wide significance: three are newly identified (21q22 near MRPS6-SLC5A3-KCNE2, 6p24 in PHACTR1 and 2q33 in WDR12) and six replicated prior observations1, 2, 3, 4 (9p21, 1p13 near CELSR2-PSRC1-SORT1, 10q11 near CXCL12, 1q41 in MIA3, 19p13 near LDLR and 1p32 near PCSK9). We tested 554 common copy number polymorphisms (>1% allele frequency) and none met the pre-specified threshold for replication (P < 10-3). We identified 8,065 rare CNVs but did not detect a greater CNV burden in cases compared to controls, in genes compared to the genome as a whole, or at any individual locus. SNPs at nine loci were reproducibly associated with myocardial infarction, but tests of common and rare CNVs failed to identify additional associations with myocardial infarction risk.

To evaluate the prevalence of severe right atrial conduction delay in patients with sinus node dysfunction (SND) and atrial fibrillation (AF) and the effects of pacing in the right atrial appendage (RAA) and in the inter-atrial septum (IAS).Forty-two patients (15 male, 72 +/- 7 years) underwent electrophysiologic study to measure the difference between the conduction time from RAA to coronary sinus ostium during stimulation at 600 ms and after extrastimulus (DeltaCTos). Patients were classified as group A if DeltaCTos60 ms and group B if60 ms. Each Group was randomized to RAA/IAS pacing and algorithms ON/OFF.Fifteen patients (36%, group A) had DeltaCTos = 76 +/- 11 ms and 27 patients (64%, group B) had DeltaCTos = 36 +/- 20 ms. Twenty-two patients were paced at the RAA and 20 at the IAS. During the study, no AF recurrences were reported in 11 of 42 (26%) patients, independently of RAA or IAS pacing. Patients from group A and RAA pacing had 0.79 +/- 0.81 episodes of AF/day during DDD, which increased to 1.52 +/- 1.41 episodes of AF/day during DDDR + Alg (P = 0.046). Those with IAS pacing had 0.5 +/- 0.24 episodes of AF/day during DDD, which decreased to 0.06 +/- 0.08 episodes of AF/day during DDDR + Alg (P = 0.06). In group B, no differences were reported between pacing sites and pacing modes.Severe right atrial conduction delay is present in one-third of patients with SND and AF: continuous pacing at the IAS is superior to RAA for AF recurrences. In patients without severe conduction delay, no differences between pacing site or mode were observed.

Background: Implantation procedures for cardiac resynchronization therapy (CRT) remain challenging with regard to coronary sinus (CS) cannulation and left ventricular (LV) lead positioning. Technologic advances in catheter design may facilitate CS cannulation and LV lead placement. Aims: To evaluate two different telescoping dual-catheter systems, RAPIDO Guiding Catheter System (Group R) and RAPIDO ADVANCE Guiding Catheter System (Group A) (Guidant Inc., St. Paul, MN, USA), during implantation of a CRT device. Methods: Seventy-four consecutive patients randomly received a CRT device using the R or A system. Results: An LV lead was successfully implanted in 74 patients (100%). (1) Median times for CS cannulation in groups R and A were 0.3 minutes (range from 0.05 to 14 minutes) and 0.5 minutes (range from 0.05 to 9 minutes), respectively (P = NS). (2) Median times for LV lead placement were 8 minutes (range from 0.8 to 100 minutes) and 3.5 minutes (range from 0.25 to 30 minutes), respectively, for groups R and A (P = 0.032). (3) Median total fluoroscopy times were 12.33 minutes (range from 5 to 70 minutes) and 14.33 minutes (range from 6 to 53 minutes) for groups R and A, respectively (P = NS). (4) Median procedural times for CRT implantation were 80 minutes (range from 40 to 200 minutes) and 75 minutes (range from 45 to 180 minutes) (P = NS) in groups R and A, respectively. There were no major complications. Conclusion: CS cannulation and LV lead placement with a telescopic dual-catheter system is a safe and feasible approach that may reduce fluoroscopy and overall CRT implantation times. Our observations suggest that the RAPIDO ADVANCE System is faster than the RAPIDO System in terms of median time for LV lead positioning.

Increasing clinical evidence shows that conventional right ventricular pacing is detrimental to left ventricular function. Recent studies in canines [1] showed that right ventricular apical (RVA) pacing causes abnormal contraction patterns due to abnormal activation of the left ventricle during RVA pacing compared to normal sinus rhythm. Moreover, these studies gave evidence that sustained RVA pacing is associated with histological and structural changes that cause left ventricular function to deteriorate. In humans, shortand long-term studies [2, 3] have confirmed the adverse effects of RVA pacing. A theoretical pacing system that could preserve the normal Purkinje activation should be considered the ideal pacing approach, because the ventricular dyssynchrony would be prevented and the normal activation pattern maintained. However, the traditional pacing tools do not allow an easy approach to the His bundle, and therefore few clinical reports of this pacing mode exist in the literature. Deshmukh et al. [4, 5] reported the results of direct His-bundle pacing (DHBP) in patients with chronic heart failure and atrial fibrillation who were candidates for ablate-and-pace strategy because of a rapid and pharmacologically uncontrolled ventricular rate. According to Deshmukh et al., the criteria for verification of the DHBP were the following: (1) recording of His bundle potential with the permanent pacing lead; (2) pace-ventricular interval equal to His-ventricular interval ± 15 ms; (3) paced QRS morphology and duration equal to the intrinsic QRS in all 12 ECG leads. Twelve out of 18 patients in the first study and 39 out of 54 patients in the second study were successfully paced. In a long-term follow-up (42 months) the

Purpose To report the combined use of percutaneous aspiration thrombectomy and rheolytic thrombectomy in the setting of extensive inferior vena cava (IVC) thrombosis and filter occlusion. Case report A 28-year-old paraplegic man with a vena cava filter in situ for previous deep vein thrombosis (DVT) was referred to our center for evaluation of dyspnea and right leg edema and swelling. Computed tomography excluded a pulmonary embolism and revealed severe, massive DVT of both iliac veins and the IVC, including the vena cava filter. Percutaneous aspiration thrombectomy was attempted because intravenous heparin therapy was ineffective, and moderate anemia contraindicated regional thrombolysis. Several passes of a guiding catheter proximally and distally to the filter, with suction provided by a 50-mL syringe, achieved minimal IVC recanalization. Subsequently, a 6-F AngioJet catheter was passed via the guiding catheter through the filter, the IVC, and both iliac veins, obtaining a satisfactory result. The patient was discharged after 7 days and did very well at 6-month follow-up, with no recurrent DVT. Conclusion This case demonstrates the usefulness of combined percutaneous aspiration and rheolytic thrombectomy in treating extensive IVC thrombosis and occluded IVC filters, especially when thrombolytic therapy cannot be used.

Background: These days no codified multidisciplinary protocol has been reported to manage all the different patent foramen ovale (PFO)-mediated syndromes. We sought to propose a multidisciplinary program of diagnosis, treatment, and follow-up of all PFO-mediated syndromes based on an in-hospital multidisciplinary task force and to review the activities during the first year. Methods: From September 2004, we organized in our hospital, a 600-bed tertiary hospital, a management program for PFO-mediated syndromes based on a task force composed of cardiologists, neurologists, and internists. Different levels of protocols were created in order to cover diagnosis, treatment, and follow-up of PFO-mediated syndromes. We reviewed the activity of our program in the first year up to September 2005. Results: Thirty-five patients (23 female, mean age 65 ± 24 years) were evaluated for suspected PFO-mediated syndromes: 20 for cryptogenic stroke, 2 for peripheral and coronary embolisms, 3 for platypnea-orthodeoxia, 9 for emicrania with aura, and 1 with hypoxiemia during neurosurgical intervention in the posterior cranial fossa. Diagnosis of PFO was confirmed in 25 patients. According to the multidisciplinary protocols, 15 patients failed to meet the requirements for transcatheter closure and were left in medical therapy whereas 11 patients (7 patients with PFO, 2 with multiperforated ASD, and 2 with a secundum ASD) underwent transcatheter closure. After a mean follow-up of 10.8 ± 4.9 months, no recurrent PFO syndromes were noted in patients treated with devices. Conclusion: The first year of our multidisciplinary program allowed a reasonable and potentially successful approach for correctly identifying patients with PFO-mediated syndromes until randomized studies are completed.

Introduction: Much clinical evidence has shown that right ventricular (RV) apical pacing is detrimental to left ventricular function. Preservation of the use of the His-Purkinje (H-P) system may be ideal in heart block that is restricted to the AV node, but may be of no benefit when H-P disease exists. Aim: To investigate the feasibility of direct His-bundle pacing (DHBP) using a new system consisting of a steerable catheter and a new 4.1 F screw-in lead. Method: Between May and December 2004, 26 patients (19 male, mean age: 77 ± 5 years) with a standard pacemaker (PM) indication and preserved His-bundle conduction were enrolled and DHBP was attempted. Results: DHBP was achieved in 24 patients (92%); two patients were paced in the His area, but the paced QRS morphology and duration were different from the native QRS. The mean time for lead positioning was 19 ± 17 minutes, the mean fluoroscopy time was 11 ± 8 minutes, and the total procedure time (skin-to-skin including positioning of a quadripolar diagnostic catheter for His recording) was 75 ± 18 minutes. In DHBP pacing, the acute pacing threshold was 2.3 ± 1.0 V at a pulse duration of 0.5 msec, and the sensed potentials were 2.9 ± 2.0 mV. At a 3-month follow-up examination, the same QRS duration and morphology recorded on implantation were observed in all patients. The pacing threshold was 2.8 ± 1.4 V, and sensed potentials were 2.5 ± 1.8 mV; the sensing configuration was changed from bipolar to unipolar in 6 patients to resolve undersensing issues. No major complications were observed. Conclusions: This feasibility study shows that DHBP can be accomplished with a new system consisting of a steerable catheter and an active fixation lead in 92% of the patients in whom it was attempted.

We report the case of a massive embolism of atheromatous material during stenting of a tight renal artery stenosis, which was prevented by using a distal embolic protection device and aggressive aspiration of the blood through a guiding catheter. A 72-year-old man who was referred to our institution for coronary artery disease treated with coronary angioplasty underwent renal angiography which revealed a tight stenosis (99%) located at the ostium of the right renal artery extending for 15 mm into the main tract. The diameter of the artery was estimated to be 5.5 cm in the main tract, and the plaque had a soft appearance complicated by the presence of a thrombus (persistence of contrast agent in the plaque on selective renal angiography). Renal artery Doppler ultrasound and renal scintigraphy confirmed the need for renal revascularization. An embolus protection device (FilterWire EZ, Boston Scientific, Natick, MA, USA) was successfully opened distally to the stenosis after gentle predilation. After stent deployment (Genesis 5.5×18 mm, Cordis, J&J Medical, Miami Lakes, FL, USA), aggressive aspiration of the blood through the guiding catheter was performed. A large amount of embolic material with macroscopic particles was retrieved into the basket of the embolic protection device and in the blood aspirated with the guiding catheter. Good functional results were obtained on Doppler analysis of intrarenal blood flow, with a resistive index of 70. Despite the fact that the extensive use of embolic protection devices in renal artery stenting is still under discussion, this technique may be advisable in selected cases with favorable anatomy and high embolic risk, especially in patients with complex and hazy lesions.

The authors assessed the prevalence of pulmonary arterial hypertension (PAH) in patients with hyperthyroidism and evaluated the response to treatment of the thyrotoxicosis. They assessed the pulmonary artery systolic pressure (PASP) at rest (estimated by echocardiography) in 23 consecutive patients diagnosed with hyperthyroidism due to Graves’ disease or toxic multinodular goiter. Twelve of 23 patients (52%) did not show antithyroglobulin and antithyroperoxidase antibodies. Seventeen patients were followed up for at least 9 months after achieving a stable euthyroid status. Fifteen (65%) patients demonstrated PAH at admission. Four patients were lost to follow-up; therefore they were able to evaluate 17 patients serially with echocardiography. Sixteen patients normalized their PASP value: 13 after methimazole, 2 after total thyroidectomy, and 1 after 131I treatment. In 1 patient no significant change in PASP was observed. This patient experienced an acute myocardial reinfarction during follow-up. They found a higher prevalence than that previously reported in observational studies. In addition, they demonstrated that the PAH reverses after correction of hyperthyroidism. Elevated PASP at rest on echocardiography may be considered a frequent finding of thyrotoxicosis. Moreover, the data seem not to support an autoimmune pathogenesis for PAH.

A 68-year-old hypertensive man was admitted to our center for a non-ST-elevation acute coronary syndrome with normal troponin value. The clinical history was remarkable for enabliting pain of the left upper arm. After a positive stress test, the patient was scheduled for coronary angiography. The coronary angiography revealed severe 3-vessel coronary artery disease and a slight impairment of left ventricular function. …

BACKGROUND: Acute myocardial infarction (AMI) is rare among young women. The search for unknown risk factors is warranted. Endothelial protein C receptor (EPCR) is largely present at the endothelial surface of large arteries. No studies about association of anti-EPCR autoantibodies (anti-EPCR) with AMI are available. METHODS: Plasma IgA, IgM and IgG anti-EPCR levels were measured by enzyme-linked immunosorbent assay in 165 women younger than 45 years who survived a first AMI and 165 healthy women, matched by age and geographical origin. RESULTS: Using the 90th percentile of IgA anti-EPCR in the control group, IgA anti-EPCR were independently associated with AMI after adjustment for cardiovascular risk factors (OR 5.1; 95% CI 1.7-15.6; P = 0.004). The risk apparently conferred by IgA anti-EPCR increased dose-dependently (P for trend =0.0002). IgM anti-EPCR were less consistently associated with AMI: a significant increase in the risk was found when women above the 90th percentile were compared with those in the lowest quartile (OR 3.6; 95% CI 1.2-11.5; P = 0.03). IgG anti-EPCR were similar in patients and controls. A total of 145 patients underwent coronary arteriography. IgA or IgM anti-EPCR were not different among patients with different degrees of atherosclerotic lesion (anova, P = 0.77 and 0.24, respectively). CONCLUSIONS: High levels of IgA and, to a lesser extent, IgM anti-EPCR, are associated with AMI in young women.