Cutting-Edge Techniques and Drugs for the Treatment of Pulmonary Embolism: Current Knowledge and Future Perspectives.

Pulmonary embolism (PE) is a potentially life-threatening condition requiring prompt diagnosis and treatment. Recent advances have led to the development of newer techniques and drugs aimed at improving PE management, reducing its associated morbidity and mortality and the complications related to anticoagulation. This review provides an overview of the current knowledge and future perspectives on PE treatment. Anticoagulation represents the first-line treatment of hemodynamically stable PE, direct oral anticoagulants being a safe and effective alternative to traditional anticoagulation: these drugs have a rapid onset of action, predictable pharmacokinetics, and low bleeding risk. Systemic fibrinolysis is suggested in patients with cardiac arrest, refractory hypotension, or shock due to PE. With this narrative review, we aim to assess the state of the art of newer techniques and drugs that could radically improve PE management in the near future: (i) mechanical thrombectomy and pulmonary embolectomy are promising techniques reserved to patients with massive PE and contraindications or failure to systemic thrombolysis; (ii) catheter-directed thrombolysis is a minimally invasive approach that can be suggested for the treatment of massive or submassive PE, but the lack of large, randomized controlled trials represents a limitation to widespread use; (iii) novel pharmacological approaches, by agents inhibiting thrombin-activatable fibrinolysis inhibitor, factor Xia, and the complement cascade, are currently under investigation to improve PE-related outcomes in specific settings.

Clusters of Comorbidities in the Short-Term Prognosis of Acute Heart Failure among Elderly Patients: A Retrospective Cohort Study.

Background and Objectives: Elderly patients affected by acute heart failure (AHF) often show different patterns of comorbidities. In this paper, we aimed to evaluate how chronic comorbidities cluster and which pattern of comorbidities is more strongly related to in-hospital death in AHF. Materials and Methods: All patients admitted for AHF to an Internal Medicine Department (01/2015−01/2019) were retrospectively evaluated; the main outcome of this study was in-hospital death during an admission for AHF; age, sex, the Charlson comorbidity index (CCI), and 17 different chronic pathologies were investigated; the association between the comorbidities was studied with Pearson's bivariate test, considering a level of p ≤ 0.10 significant, and considering p < 0.05 strongly significant. Thus, we identified the clusters of comorbidities associated with the main outcome and tested the CCI and each cluster against in-hospital death with logistic regression analysis, assessing the accuracy of the prediction with ROC curve analysis. Results: A total of 459 consecutive patients (age: 83.9 ± 8.02 years; males: 56.6%). A total of 55 (12%) subjects reached the main outcome; the CCI and 16 clusters of comorbidities emerged as being associated with in-hospital death from AHF. Of these, CCI and six clusters showed an accurate prediction of in-hospital death. Conclusions: Both the CCI and specific clusters of comorbidities are associated with in-hospital death from AHF among elderly patients. Specific phenotypes show a greater association with a worse short-term prognosis than a more generic scale, such as the CCI.

Implementation of EHMRG Risk Model in an Italian Population of Elderly Patients with Acute Heart Failure.

Acute heart failure (AHF) is a cardiac emergency with an increasing incidence, especially among elderly patients. The Emergency Heart failure Mortality Risk Grade (EHMRG) has been validated to assess the 7-days AHF mortality risk, suggesting the management of patients admitted to an emergency department (ED). EHMRG has never been implemented in Italian ED nor among elderly patients. We aimed to assess EHMRG score accuracy in predicting in-hospital death in a retrospective cohort of elderly subjects admitted for AHF from the ED to an Internal Medicine Department. We enrolled, in a 24-months timeframe, all the patients admitted to an Internal Medicine Department from ED for AHF. We calculated the EHMRG score, subdividing patients into six categories, and assessing in-hospital mortality and length of stay. We evaluated EHMRG accuracy with ROC curve analysis and survival with Kaplan−Meier and Cox models. We collected 439 subjects, with 45 in-hospital deaths (10.3%), observing a significant increase of in-hospital death along with EHMRG class, from 0% (class 1) to 7.7% (class 5b; p < 0.0001). EHMRG was fairly accurate in the whole cohort (AUC: 0.75; 95%CI: 0.68−0.83; p < 0.0001), with the best cutoff observed at >103 (Se: 71.1%; Sp: 72.8%; LR+: 2.62; LR-: 0.40; PPV: 23.0%; NPV: 95.7%), but performed better considering the events in the first seven days of admission (AUC: 0.83; 95%; CI: 0.75−0.91; p < 0.0001). In light of our observations, EHMRG can be useful also for the Italian emergency system to predict the risk of short-term mortality for AHF among elderly patients. EHMRG performance was better in the first seven days but remained acceptable when considering the whole period of hospitalization.

Improving the EHMRG Prognostic Evaluation of Acute Heart Failure with TAPSE/PASp: A Sequential Approach.

The Emergency Heart Failure Mortality Risk Grade (EHMRG) can predict short-term mortality in patients admitted for acute heart failure (AHF) in the emergency department (ED). This paper aimed to evaluate if TAPSE/PASp, an echocardiographic marker of ventricular desynchronization, can improve in-hospital death prediction in patients at moderate-to-high risk, according to EHMRG score classification. From 1 January 2018 to 30 December 2019, we retrospectively enrolled all the consecutive subjects admitted to our Internal Medicine Department for AHF from the ED. We performed bedside echocardiography within the first 24 h of admission. We evaluated EHMRG and NYHA in the ED, days of admission in Internal Medicine, and in-hospital mortality. We assessed cutoffs with ROC curve analysis and survival with Kaplan-Meier and Cox regression. We obtained a cohort of 439 subjects; 10.3% underwent in-hospital death. Patients with normal TAPSE/PASp in EHMRG Classes 4, 5a, and 5b had higher survival rates (100%, 100%, and 94.3%, respectively), while subjects with pathologic TAPSE/PASp had lower survival rates (81.8%, 78.3%, and 43.4%, respectively) (p < 0.0001, log-rank test). TAPSE/PASp, an echocardiographic marker of ventricular desynchronization, can further stratify the risk of in-hospital death evaluated by EHMRG.

Chronic Respiratory Diseases and Neurodegenerative Disorders: A Primer for the Practicing Clinician.

Chronic respiratory disorders represent a world epidemic. Their incidence and prevalence in the world population is increasing, and especially among elderly subjects, they are commonly associated with other pathologies, often generating a status of high clinical complexity. Neurology, internal medicine, and pneumology specialists should be aware of the common background of these disorders in order to treat correctly the patient's comorbid state and optimize the treatment considering potential overlaps. In this review, we aimed to focus on the relationships between chronic respiratory disorders and chronic neurodegenerative diseases at different levels; we review the shared risk factors and the interactions between disorders, the indications to explore respiratory function in neurodegenerative diseases, pathology-pathology and drug-pathology interactions in patients affected by both chronic neurologic and respiratory diseases.

Clinical Method Applied to Focused Ultrasound: The Case of Wells' Score and Echocardiography in the Emergency Department: A Systematic Review and a Meta-Analysis.

Background and Objectives: bedside cardiac ultrasound is a widely adopted method in Emergency Departments (ED) for extending physical examination and refining clinical diagnosis. However, in the setting of hemodynamically-stable pulmonary embolism, the diagnostic role of echocardiography is still the subject of debate. In light of its high specificity and low sensitivity, some authors suggest that echocardiographic signs of right ventricle overload could be used to rule-in pulmonary embolism. In this study, we aimed to clarify the diagnostic role of echocardiographic signs of right ventricle overload in the setting of hemodynamically-stable pulmonary embolism in the ED. Materials and Methods: we performed a systematic review of literature in PubMed, Web of Science and Cochrane databases, considering the echocardiographic signs for the diagnosis of pulmonary embolism in the ED. Studies considering unstable or shocked patients were excluded. Papers enrolling hemodynamically stable subjects were selected. We performed a diagnostic test accuracy meta-analysis for each sign, and then performed a critical evaluation according to pretest probability, assessed with Wells' score for pulmonary embolism. Results: 10 studies were finally included. We observed a good specificity and a low sensitivity of each echocardiographic sign of right ventricle overload. However, once stratified by the Wells' score, the post-test probability only increased among high-risk patients. Conclusions: signs of echocardiographic right ventricle overload should not be used to modify the clinical behavior in low- and intermediate- risk patients according to Wells' score classification. Among high-risk patients, however, echocardiographic signs could help a physician in detecting patients with the highest probability of pulmonary embolism, necessitating a confirmation by computed tomography with pulmonary angiography. However, a focused cardiac and thoracic ultrasound investigation is useful for the differential diagnosis of dyspnea and chest pain in the ED.

SOFA and qSOFA usefulness for in-hospital death prediction of elderly patients admitted for suspected infection in internal medicine.

PURPOSE: To reduce intensive care unit overcrowding and optimize resources, elderly patients affected by suspected infection with declining clinical conditions could be managed in internal medicine departments with stepdown beds. However, commonly used prognostic scores, as Sequential Organ Failure Assessment (SOFA) or quick SOFA (qSOFA) have never been studied in this specific setting. The aim of this study was to evaluate the role and the accuracy of SOFA and qSOFA as prognostic scores in a population of elderly patients with suspected infection admitted to stepdown beds of two internal medicine departments. METHODS: Elderly patients admitted from the emergency department in the stepdown beds of two different internal medicine departments for suspected infection were assessed with SOFA and qSOFA scores at the admission. All patients were treated according to current guidelines. Age, sex, comorbidities, Charlson comorbidity index, SOFA and qSOFA were assessed. In-hospital death and length of hospital admission were also recorded. RESULTS: 390 subjects were enrolled. In-hospital death occurred in 144 (36.9%) patients; we observed that both SOFA (HR 1.189; 95% CI 1.128-1.253; p < 0.0001) and qSOFA (HR 1.803; 95% CI 1.503-2.164; p < 0.0001) scores were independently associated with an increased risk of in-hospital death. However, the accuracy of both SOFA (AUC: 0.686; 95% CI 0.637-0.732; p < 0.0001) and qSOFA (AUC: 0.680; 95% CI 0.641-0.735; p < 0.0001) in predicting in-hospital death was low in this population. CONCLUSION: Elderly patients admitted to stepdown beds for suspected infection experience a high rate of in-hospital death; both SOFA and qSOFA scores can be useful to identify a group of patients who can benefit from admission to an intermediate care environment, however their accuracy is low.

CHA2DS2-VASc score predicts atrial fibrillation recurrence after cardioversion: Systematic review and individual patient pooled meta-analysis.

BACKGROUND: Despite progresses in the treatment of the thromboembolic risk related to atrial fibrillation (AF), the management of recurrences remains a challenge. HYPOTHESIS: To assess if congestive heart failure or left ventricular systolic dysfunction (CHA2 DS2 -VASc) score is predictive of early arrhythmia recurrence after AF cardioversion. METHODS: Systematic review and individual patient pooled meta-analysis following Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. INCLUSION CRITERIA: observational trials in patients with AF undergoing cardioversion, available data on recurrence of AF and available data on CHA2 DS2 -VASc score. Clinical studies of interest were retrieved by PubMed, Cochrane Library, and Biomed Central. Seven authors were contacted for joining the patient level meta-analysis, and three shared data regarding anthropometric measurements, risk factors, major comorbidities, and CHA2 DS2 -VASc score. The primary outcome was the recurrence of AF after cardioversion in patients free from antiarrhythmic prophylaxis. Univariate and multivariate logistic regression was performed. RESULTS: Overall, we collect data of 2889 patients: 61% were male, 50% with hypertension, 12% with diabetes, and 23% with history of ischemic heart disease. The median CHA2DS2-VASc score was 2.. At the multivariate analysis, chronic kidney disease (odds ratio [OR] 1.94; 95% confidence interval [CI] 1.12-3.27; P = 0.01), peripheral artery disease (OR 1.65; 95% CI 1.23-2.19; P < 0,0001), previous use of beta blockers (OR 1.5; 95% CI 1.19-1.88; P < 0.0001), and CHA2DS2-VASc score > 2 (OR 1.37; 95% CI 1.1-1.68; P = 0.002) were independent predictors of early recurrence of AF. CONCLUSIONS: CHA2DS2-VASc score predicts early recurrence of AF in the first 30 days after electrical or pharmacological cardioversion. Protocol registration PROSPERO (CRD42017075107).

Serum Uric Acid, Kidney Function and Acute Ischemic Stroke Outcomes in Elderly Patients: A Single-Cohort, Perspective Study.

Chronic kidney disease and hyperuricemia have been associated to an increased risk and a worse prognosis in acute ischemic stroke. Several mechanisms, including platelet dysfunction, coagulation disorders, endothelial dysfunction, inflammation, and an increased risk of atrial fibrillation could be implicated. The role of serum uric acid in this setting is still object of debate. We enrolled all the consecutive patients admitted to our department for acute ischemic stroke. Cox regression analysis was used to evaluate the risk of in-hospital death considering serum uric acid levels and all the comorbidities. In the overall sample, hyperuricemia was independently associated to an increased risk of in-hospital mortality. This effect was stronger in patients with chronic kidney disease while, in the group of patients with normal renal function, the relationship between hyperuricemia and increased stroke mortality was not confirmed. Hyperuricemia could be associated to higher in-hospital mortality for ischemic stroke among elderly patients when affected by kidney disease. Survival does not seem to be affected by hyperuricemia in patients with normal kidney function.

Charlson comorbidity index as a predictor of in-hospital death in acute ischemic stroke among very old patients: a single-cohort perspective study.

Chronic diseases are increasing worldwide. Association of two or more chronic conditions is related with poor health status and reduced life expectancy, particularly among elderly patients. Comorbidities represent a risk factor for adverse events in several critical illnesses. We aimed to evaluate if elderly patients are affected by multiple chronic pathologies, assessed by Charlson comorbidity index (CCI), showed a reduced in-hospital survival after ischemic stroke. In a 3-year period, we evaluated all the subjects admitted to our internal medicine department for ischemic stroke. Age, sex, NIHSS score and all the comorbidities were recorded. Days of hospitalization, hospital-related infections and in-hospital mortality were also assessed. For each patient, we evaluated CCI, obtaining four classes: group 1 (CCI: 2-3), group 2 (CCI: 4-5), group 3 (CCI: 6-7) and group 4 (CCI: ≥8). Survival was evaluated with Kaplan-Meier and Cox regression analyses. The complete model considered in-hospital death as the main outcome, days of hospitalization as the time variable and CCI as the main predictor, adjusting for NIHSS, sex and nosocomial infections. Patients in CCI group 3 and 4 had an increased risk of in-hospital mortality, independently of NIHSS, sex and nosocomial infections. Elderly patients with multiple comorbidities have higher risk of in-hospital death when affected by ischemic stroke.

CHA2DS2-VASc in the prediction of early atrial fibrillation relapses after electrical or pharmacological cardioversion.

BACKGROUND: In hemodynamically stable patients, mortality and morbidity related to atrial fibrillation are mainly due to cardioembolic disorder. No difference in the survival rate and incidence of embolic events has been described in patients undergoing rhythm or rate control if the latter is combined with an appropriate anticoagulant therapy. CHA2DS2-VASc is a score that allows clinicians to stratify embolic risk in patients affected by nonvalvular atrial fibrillation. Each item can be involved in triggering and maintaining atrial fibrillation. Thus, we hypothesized that CHA2DS2-VASc may help to predict early recurrences after cardioversion. METHODS: A total of 319 consecutive patients, admitted to our emergency department or hemodynamically stable persistent atrial fibrillation, were enrolled and treated with electrical or pharmacological sinus rhythm restoration. Outcome was defined as recurrence of atrial fibrillation 5 days after cardioversion. Predicted probability of sinus rhythm stability was assessed with an ordinal regression model using CHA2DS2-VASc as an independent variable. RESULTS: The model showed a progressive decrease in the predicted probability of sinus rhythm stability after electrical or pharmacological cardioversion along with an increase in the CHA2DS2-VASc score. A logarithmic relationship was the best-fit trend among CHA2DS2-VASc ranks and the predicted probability of sinus rhythm stability in patients undergoing both electrical and pharmacological cardioversion (r(2) = 0.98, P < 0.05 for electrical cardioversion; r(2) = 0.91, P < 0.05 for pharmacological cardioversion). CONCLUSION: Our preliminary results suggest that CHA2DS2-VASc score could be useful in evaluating the risk of early recurrence of atrial fibrillation after cardioversion. This information may have implications for disease monitoring and treatment strategies in clinical practice.