Prognostic Role of Tricuspid Annular Plane Systolic Excursion to Systolic Pulmonary Artery Pressure Ratio for the Identification of Early Clinical Deterioration in Intermediate-High-Risk Pulmonary Embolism Patients.

The ratio of tricuspid annular plane systolic excursion (TAPSE) to echocardiographically measured systolic pulmonary artery pressure (PASP) has been proposed as a surrogate of RV-arterial coupling. In this analysis, we assess the prognostic role of TAPSE/PASP for early clinical deterioration and short-term mortality in an often clinically challenging population of intermediate-high-risk patients with pulmonary embolism (PE). A post hoc analysis of intermediate-high-risk patients with PE enrolled in the Italian Pulmonary Embolism Registry (ClinicalTrials.gov: NCT01604538) was performed. All patients underwent transthoracic echocardiography at admission. The primary and secondary outcomes were clinical deterioration within 48 hours from admission and 30-day all-cause mortality, respectively. In 422 intermediate-high-risk patients with PE (mean age 71.2 ± 5.3 years, 238 men), 37 (8.7%) experienced clinical deterioration within 48 hours of admission. The 30-day mortality rate was 6.6% (n = 28). The receiver operating characteristic analysis established 0.33 as the optimal cut-off value for the TAPSE/PASP in predicting 48-hour clinical deterioration (area under the curve 0.79 ± 0.1). The sensitivity, specificity, positive predictive value, and negative predictive value were 81%, 88.5%, 40.5%, and 97.9%, respectively. The multivariate Cox regression analysis showed that a TAPSE/PASP ≤0.33 was an independent predictor of 48-hour clinical deterioration (hazard ratio 2.06, 95% confidence interval 1.98 to 2.11, p <0.0001) and 30-day mortality (hazard ratio 2.28, 95% confidence interval 2.25 to 2.33, p <0.001). TAPSE/PASP shows promise as a noninvasive prognostic predictor to identify intermediate-high-risk patients with PE at a higher risk of early clinical deterioration and short-term mortality.

Prognostic impact of the e-TAPSE ratio in intermediate-high risk pulmonary embolism patients.

We assess the prognostic role of a new index (Age-T index), based on age and the tricuspid annular plane systolic excursion (TAPSE) for the estimation of 30-day mortality and risk of 48-h clinical deterioration since admission, in intermediate-high risk Pulmonary Embolism (PE) patients. A post-hoc analysis of intermediate-high risk PE patients enrolled in the Italian Pulmonary Embolism Registry (IPER) (Trial registry: ClinicalTrials.gov; No.: NCT01604538) was performed. The Age-T index was calculated as the ratio between age and TAPSE. The primary outcome was the 30-day mortality risk while the risk of clinical deterioration within 48 h in the same patients was chosen as the secondary outcome. Among 450 intermediate-high risk PE patients (mean age 71.4 ± 13.8 years, 298 males), 40 (8.8%) experienced clinical deterioration within 48 h since admission and 32 (7.1%) died within 30-day. Receiver operating characteristic analysis established ≥ 4.9 as the optimal cut-off value for the Age-T index in predicting 30-day mortality (AUC of 0.76 ± 0.1). Sensitivity, specificity, PPV and NPV were 81.2, 85.6, 30.2 and 98.3%, respectively. Multivariate Cox regression analysis showed that an Age-T index ≥ 4.9 predicts 30-day mortality (HR: 3.24, 95% CI: 1.58-4.96, p < 0.001) and was also associated with a significantly higher risk of 48-h clinical deterioration (HR: 2.02, 95% CI 1.96-2.08, p < 0.0001) in intermediate-high risk PE patients. Age-T Index appears as a useful, bed-side and non-invasive prognostic tool to identify intermediate-high risk PE patients at higher risk of death and/or 48-h clinical deterioration.

Prognostic role of different temporal patterns of dyspnoea onset in patients with acute pulmonary embolism.

AIMS: Dyspnoea is a well known symptom of acute pulmonary embolism (PE). We assess the prognostic role of different patterns of dyspnoea onset regarding in-hospital mortality, clinical deterioration and the composite of the outcomes in PE patients, according to their haemodynamic status at admission. METHODS: Patients from the prospective Italian Pulmonary Embolism Registry (IPER) were included in the study. At admission, patients were stratified, according to their haemodynamic status, as high- (haemodynamically unstable) and non-high-risk (haemodynamically stable) patients. RESULTS: Overall, 1623 consecutive patients (mean age 70.2 ±â€Š15.2 years, 696 males), with confirmed acute PE, were evaluated for the features of dyspnoea. Among these, 1353 (83.3%) experienced dyspnoea at admission. No significant differences were observed regarding in-hospital mortality and the composite outcome of in-hospital mortality and clinical deterioration between patients with and without dyspnoea. However, in non-high-risk patients, clinical deterioration was more frequently observed when dyspnoea was present compared with absence of dyspnoea ( P  = 0.002). Multivariate Cox regression analyses showed that non-high-risk patients had an increased risk of clinical deterioration when experiencing dyspnoea within 24 h [hazard ratio (HR): 1.57, 95% confidence interval (CI): 1.49-1.65, P  < 0.0001] and between 25 h and 7 days before admission (HR: 1.66, 95% CI: 1.58-1.77, P  < 0.0001), independently of age, sex, right ventricular dysfunction, positive cardiac troponin and thrombolysis. CONCLUSIONS: Non-high-risk PE patients experiencing dyspnoea within 7 days before hospitalization had a higher risk of clinical deterioration compared with those without and, therefore, they may require more aggressive management.

Mean arterial pressure predicts 48 h clinical deterioration in intermediate-high risk patients with acute pulmonary embolism.

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.

Impact of clinical profile at admission on the outcomes in patients hospitalized for acute pulmonary embolism: data from the IPER Registry.

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).

Incidence of acute pulmonary embolism in COVID-19 patients: Systematic review and meta-analysis.

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<0.0001) and 23.4% (95% CI:16.7-31.8%, I2=88.7%, p<0.0001), respectively. Segmental/sub-segmental pulmonary arteries were more frequently involved compared to main/lobar arteries (6.8% vs18.8%, p<0.001). Computer tomography pulmonary angiogram (CTPA) was used only in 35.3% of patients with COVID-19 infection across six studies. CONCLUSIONS: The in-hospital incidence of acute PE among COVID-19 patients is higher in ICU patients compared to those hospitalized in general wards. CTPA was rarely used suggesting a potential underestimation of PE cases.

Incidence and mortality risk in coronavirus disease 2019 patients complicated by acute cardiac injury: systematic review and meta-analysis.

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 < 0.0001). The pooled analysis confirmed a significantly increased risk of death in COVID-19 patients complicated with ACI during the disease (odds ratio: 21.6, 95% confidence interval: 8.6-54.4, P < 0.0001, I = 82%). CONCLUSION: Development of ACI during COVID-19 significantly increases the risk of death during the infection.

[An update on pulmonary embolism-related mortality in Italy (2003-2015)]. / Aggiornamento sui dati relativi alla mortalità da embolia polmonare in Italia (2003-2015).

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: The Italian age-adjusted mortality rates appeared lower compared to overall Southern Europe, despite a similar decreasing trend over time.

[Diagnostic and therapeutic models for the management of acute pulmonary embolism: an issue of local available resources]. / Modelli diagnostici e terapeutici nel trattamento dell'embolia polmonare acuta: una questione di risorse locali.

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.

Seizures as the first clinical manifestation of acute pulmonary embolism: an underestimate issue in neurocritical care.

BACKGROUND: 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. METHODS: After screening 258 articles in PubMed, Scopus, Cochrane Library, and Google Scholar databases, we identified 16 case reports meeting the inclusion criteria. RESULTS: 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. CONCLUSIONS: 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.

Left atrial size measured on CT pulmonary angiography: another parameter of pulmonary embolism severity? A systematic review.

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.

Inferior Vena Cava Filters in Hemodynamically Unstable Patients with Acute Pulmonary Embolism: How Often are They Used? Data from Multicenter Prospective Registries on Acute Pulmonary Embolism.

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.

Thrombolysis in hemodynamically unstable patients: still underused: a review based on multicenter prospective registries on acute pulmonary embolism.

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.

Systemic thrombolysis in haemodynamically unstable pulmonary embolism: The earlier the better?

INTRODUCTION: 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. MATERIAL AND METHODS: 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 ±â€¯9.1 years old). RESULTS: 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 ±â€¯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, 95& CI 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). CONCLUSIONS: ST administered within 8.5 h from symptoms onset may be associated with a reduced 30-day CV mortality in high-risk PE patients.