From statistical inference to machine learning: A paradigm shift in contemporary cardiovascular pharmacotherapy.

AIMS: Heart failure with reduced ejection fraction (HFrEF) poses significant challenges for clinicians and researchers, owing to its multifaceted aetiology and complex treatment regimens. In light of this, artificial intelligence methods offer an innovative approach to identifying relationships within complex clinical datasets. Our study aims to explore the potential for machine learning algorithms to provide deeper insights into datasets of HFrEF patients. METHODS: To this end, we analysed a cohort of 386 HFrEF patients who had been initiated on sodium-glucose co-transporter-2 inhibitor treatment and had completed a minimum of a 6-month follow-up. RESULTS: In traditional frequentist statistical analyses, patients receiving the highest doses of beta-blockers (BBs) (chi-square test, P = .036) and those newly initiated on sacubitril-valsartan (chi-square test, P = .023) showed better outcomes. However, none of these pharmacological features stood out as independent predictors of improved outcomes in the Cox proportional hazards model. In contrast, when employing eXtreme Gradient Boosting (XGBoost) algorithms in conjunction with the data using Shapley additive explanations (SHAP), we identified several models with significant predictive power. The XGBoost algorithm inherently accommodates non-linear distribution, multicollinearity and confounding. Within this framework, pharmacological categories like 'newly initiated treatment with sacubitril/valsartan' and 'BB dose escalation' emerged as strong predictors of long-term outcomes. CONCLUSIONS: In this manuscript, we not only emphasize the strengths of this machine learning approach but also discuss its potential limitations and the risk of identifying statistically significant yet clinically irrelevant predictors.

Enterobacter cloacae septicemia in a triple-cannula extracorporeal membrane oxygenation circulatory support treated with Seraph-100 Microbind affinity blood filter.

Bloodstream infections (BSI) are frequently encountered during extracorporeal membrane oxygenation (ECMO) support. Once septicemia is observed, treatment should be rapid, adequate, and multifaceted, particularly in advanced ECMO configurations. We report on a case of a 60-year-old male patient with acute-on-chronic heart failure due to ischemic cardiomyopathy. The treatment was complicated by cardiogenic shock requiring veno-arterial ECMO support, and, due to persistent pulmonary congestion, an upgrade with an additional left-atrial drainage cannula. After seven days of ECMO support, septicemia with shock ensued. Ex iuvantibus antibiotic treatment was started promptly. We wanted to minimize the likelihood of bacterial biofilm build-up requiring an exchange of the ECMO circuit and cannula, which was expected to be challenging. Therefore, we added a Seraph-100 Microbind affinity blood filter (providing blood purification with the potential for rapid bacterial clearance) to the ECMO circuit. Initial blood cultures tested positive for Enterobacter cloacae. Following a course of Seraph-100 treatment, bacteremia, septicemia, and shock resolved. There was no need for a circuit or cannula exchange. The additional eleven days of ECMO support were uneventful. The patient was successfully bridged to long-term mechanical circulatory support. We believe that the synergistic effect of early implementation of both broad-spectrum antibiotic treatment and blood purification with the potential for rapid bacterial clearance (such as the one provided with the Seraph-100 Microbind affinity blood filter) is crucial in BSI in patients receiving advanced ECMO.

The impact of earthquakes on the frequency and prognosis of the most common emergency cardiac conditions.

AIM: To assess whether the number of patients with a cardiac chief complaint and their characteristics differed between before and after two major earthquakes that struck Croatia in 2020. METHODS: We collected data on all visits of patients with a cardiac chief complaint examined in the emergency departments of six hospitals nearest to the epicenters. Patients seen during the 7 days before the earthquake were compared with those seen on the day and during the 6 days after the earthquake. RESULTS: Patients seen after the earthquake were younger (68 [59-79] vs 72.5 [65-80]; P<0.001) and less frequently had cardiovascular disease (32.9% vs 42.8%; P<0.001). This group less frequently had the primary diagnosis of acute myocardial infarction (AMI) (15.6% vs 21.9%; P=0.005), heart failure (9.3% vs 19.4%; P<0.001), dysregulated hypertension (13.9% vs 19.4%; P=0.01), but more frequently had non-anginal chest discomfort (28.8% vs 18.0%; P<0.001). In a subgroup analysis of patients seen in hospitals located within 20 km from the epicenter, significantly more patients seen after the earthquake compared with those seen before the earthquake presented with AMI (14.5% vs 22.8%; P=0.028), acute elevation of blood pressure (10% vs 21.8%, P=0.001), and paroxysmal arrhythmias treated with electrocardioversion (0.9% vs 4.5%, P=0.022). CONCLUSION: After two moderately strong earthquakes, hospitals within 20 km from the epicenter saw a significant increase in acute cardiac conditions such as elevated blood pressure, AMI, and cardioverted arrhythmias. Eventually, these earthquakes had no impact on the outcomes of the studied population.

Unusual pattern of inferior vena cava thrombosis after veno-arterial extracorporeal membrane oxygenation: a report of two cases.

We report two cases of inferior vena cava (IVC) thrombosis after the retrieval of veno-arterial extracorporeal membrane oxygenation cannulas. In both patients, the venous cannula tips were placed in the upper half of the right atrium, enabling adequate blood drainage. During support, uneventful periods of IVC collapse were detected. After decannulation, thrombotic formations resembling a mold of the venous cannula were detected in both patients. Whether the IVC collapse caused IVC thrombosis during VA-ECMO support remains to be determined in further trials.

The influence of therapeutic hypothermia on the outcomes of cardiac arrest survivors: a retrospective cohort study.

AIM: To determine whether therapeutic hypothermia (TH) improves survival and neurological outcomes in out-of-hospital cardiac arrest (OHCA) survivors. METHODS: This retrospective cohort study enrolled patients treated for OHCA with a return of spontaneous circulation admitted to the Cardiac Intensive Care Unit from October 2000 until March 2019. Data were collected from medical archives. Propensity score matching was used. The primary endpoint was death during hospital stay and secondary endpoint was cerebral performance category (CPC) score at discharge. RESULTS: Out of 152 patients included in the study, 58 (38.7%) underwent TH treatment. After matching (which left 70 patients in the analysis), death during hospital stay occurred less often in TH group (28.6% vs 57.1%, P=0.029), while the difference in CPC score was not significant. Cox proportional hazards model showed the predictors of death during hospital stay to be TH (hazard ratio [HR] 0.29, 95% confidence interval [CI] 0.13-0.68, P=0.004), initial Glasgow Coma Scale score of 3 (HR 7.55, 95% CI 1.44-39.63, P=0.017), and heart failure (HR 2.35, 95% CI 1.02-5.34, P=0.045). TH was not an independent predictor of CPC score. Mann-Whitney U test and linear regression model showed that TH was associated with higher gain in GCS. CONCLUSION: TH was associated with better survival and certain variables suggesting improved neurological outcomes, suggesting that TH is a vital treatment option for comatose OHCA survivors.

Importance of acute cardiac care registries at the national level.

Improving organization and patient care quality in intensive care units is increasingly important as intensive care unit diagnostic and therapeutic procedures account for a growing proportion of hospital services. We identified the lack of comprehensive national and international registries available in the contemporary literature. This paper aims to describe and analyze cardiac intensive care unit (CICU) network at the national level in Croatia and its comparison with more developed countries. Thirty-four representatives from all Croatian acute hospitals (response rate of 100%) filled in a web based questionnaire on CICU organization and competence during September and October 2016. Organization and available technical procedures for health care in general, and especially in very expensive CICU treatment, highly depends on gross domestic product (GDP) per capita. That is why one could expect that Croatia, with the second lowest GDP among European Union countries and 4.7 CICU per million inhabitants will have worse results in this field in comparison with most of these countries. Results such as one nurse responsible for a mean of 2.7 CICU patients, 52% of cardiologists among physicians during working hours but 37% during night shifts, 24/7 transesophageal echocardiography in only 26.5% of CICUs, one-third without therapeutic hypothermia, and 23.5% without extracorporeal membrane oxygenation treatment are some of these results, revealing much room for improvement. This representative, nationwide sample of Croatian CICUs also demonstrated considerable variation of key elements of structures with respect to hospital size, academic status and financial issues, as well as a trend towards current guidelines. This kind of investigation is very important for proposing standards, reimbursement master plan, or quality assessment of the national health system.

Plasminogen activator inhibitor-1 activity and long-term outcome in patients with ST-elevation myocardial infarction treated with primary percutaneous coronary intervention: a prospective cohort study.

AIM: To determine the relationship between plasminogen activator inhibitor-1 (PAI-1) activity rise during the first 24 hours of ST-elevation myocardial infarction (STEMI) treatment and death after 5 years. METHODS: From May 1, 2009 to March 23, 2010, 87 STEMI patients treated with primary percutaneous coronary intervention (PCI) at the Sestre Milosrdnice University Hospital Center were consecutively enrolled in prospective single-center cohort study. PAI-1 activity was determined on admission and 24 hours later. The primary end-point was death after 5 years. The predictive value of PAI-1 activity variables as biomarkers of death was assessed using receiver operating characteristic (ROC) curve, independent predictors of death were assessed using multivariate Cox regression, and covariates independently related to higher PAI-1 activity rise were assessed using linear regression. RESULTS: Two patients died during the hospital treatment and 11 during the follow-up. PAI-1 activity rise had the largest area under curve (0.748) for predicting death rate (optimal cut-off point 3.7 U/mL, sensitivity 53.8%, specificity 90.5%). Patients with PAI-1 activity rise higher than 3.7 U/mL had significantly higher mortality (P<0.001). Kaplan-Meier survival curve diverged within the first year after STEMI. Independent predictors of death were PAI-1 rise and final Thrombolysis in Myocardial Infarction flow. PAI-1 activity rise was independently related to heart failure, thrombus aspiration, and body weight. CONCLUSION: PAI-1 activity rise higher than 3.7 U/mL is associated with higher 5-year death rate in STEMI patients treated with primary PCI.

Percutaneous Coronary Intervention for Left Main Chronic Total Occlusion: Unprotected or Protected Case?

A 60-year-old male with chronic obstructive pulmonary disease and active smoking was admitted for positive treadmill test. He reported exertional chest pain 4 months ago; however, since then he had been symptom free. Echocardiography showed severe anteroseptal and mild inferoposterior hypokinesia, preserved wall thickness and moderately reduced left-ventricular ejection fraction. Coronary angiography revealed non-calcified chronic total occlusion (CTO) of the left main (LM) with microchannel toward the left circumflex artery (Cx). Oligosymptomatic or asymptomatic patients with unprotected LM-CTO are rarely encountered.

Impella for the Management of Ventricular Septal Defect Complicating Acute Myocardial Infarction: A European Multicenter Registry.

Ventricular septal defect (VSD) is a rare but severe complication of myocardial infarction (MI). Temporary mechanical circulatory support (MCS) can be used as a bridge to VSD closure, heart transplantation, or ventricular assist device. We describe the use of Impella device in this context based on a multicenter European retrospective registry (17 centers responded). Twenty-eight post-MI VSD patients were included (Impella device were 2.5 for 1 patient, CP for 20, 5.0 for 5, and unknown for 2). All patients were in cardiogenic shock with multiple organ failure (SAPS II 41 [interquantile range {IQR} = 27-53], lactate 4.0 ± 3.5 mmol/L) and catecholamine support (dobutamine 55% and norepinephrine 96%). Additional temporary MCS was used in 14 patients (50%), mainly extracorporeal life support (ECLS) (n = 9, 32%). Severe bleedings were frequent (50%). In-hospital and 1 year mortalities were 75%. Ventricular septal defect management was surgical for 36% of patients, percutaneous for 21%, and conservative for 43%. Only surgically managed patients survived (70% in-hospital survival). Type and combination of temporary MCS used were not associated with mortality (Impella alone or in combination with intra-aortic balloon pump [IABP] or ECLS, p = 0.84). Impella use in patients with post-MI VSD is feasible but larger prospective registries are necessary to further elucidate potential benefits of left ventricular unloading in this setting.

Does shifting to professional emergency department staffing affect the decision for chest radiography?

BACKGROUND: The study aims to determine whether shifting to professional emergency department (ED) teams leads to a higher rate of radiologic workup. METHODS: We retrospectively analyzed a total of 2,000 patients presenting to the ED of a tertiary teaching hospital in two time periods: group 1 (G1) comprised 1,000 consecutive patients enrolled from December 21, 2012 to January 5, 2013 (all patients were examined by an internal medicine specialist); group 2 (G2) comprised 1,000 consecutive patients enrolled from December 21, 2018 to January 3, 2019 (all patients were examined by an emergency physician). RESULTS: The chest X-ray (CXR) was performed in 40.6% of all patients. There was no difference in the frequency of CXR (38.9% in G1 vs. 42.3% in G2, P=0.152). More CXRs were performed in G2 patients older than 65 years, in female patients older than 65 years, in patients presenting during the evening and night shifts or off-hours, in patients with a history of malignancy, in patients with gastrointestinal bleeding, and in patients with bradycardia, but fewer in patients presenting with arrhythmia. No difference in the rates of pathological CXR was found (47.3% in G1 vs. 52.2% in G2, P=0.186). Compared with G2, higher sensitivity and specificity were obtained for the binary logistic regression model predicting pathological findings in G1. CONCLUSIONS: Shifting to professional ED teams does not increase radiologic workup. By implementing deliberate usage of ultrasound, some self-governing procedures, case-oriented investigations, and center-specific recommendations, unnecessary radiologic workup can be avoided. Professional ED teams could lead to a higher standard of emergency care.

[Antithrombotic therapy in the treatment of STEMI and NSTEMI patients]. / Antitrombotska terapija u lijecenju bolesnika s infarktom miokarda s elevacijom i bez elevacije ST segmenta.

By establishing the Croatian network of primary PCI more patients can now be treated by this method every year. Nevertheless, therapeutic success depends on appropriate, i.e. complete antithrombotic therapy. On the other hand, about half of inhabitants of Croatia have not yet been covered with primary PCI network. Aspirin has an established role in antithrombotic therapy, demonstrated in numerous clinical studies. Thienopirydines, especially clopidogrel, have improved the outcome of interventional cardiology. GP IIb/IIIa receptor inhibitors, despite their high price, pave their way into our daily practice. Heparin is an essential part of therapy for almost all acute coronary syndrome scenarios, but the role of low-molecular heparins is yet to be clarified. Fibrinolytic therapy still "saves lifes". By improving new fibrinolytics, they have become easier to use, entail less side effects and are more efficient.

[Lung function in children residentially exposed to asbestos]. / Plucna funkcija djece rezidencijalno izlozene azbestu.

Impairment of respiratory function is one of the most sensitive indicators used in the evaluation of the effects of air pollution on human health. We compared predicted values of flow-volume curve according to Knudson and the spirometry results in 81 healthy children; 40 girls and 41 boy, aged (10.69 +/- 2.24) years. We also measured the transfer factor of the lungs for carbon monoxide (TLCO) using the single-breath method and compared the results with reference values by Cotes. Patients were selected randomly among pre-school and elementary school children from the Split area, who were residentially exposed to asbestos. Children with atopic diseases, family history of atopy, history of severe respiratory diseases, and history of smoking were excluded from study. We found a statistically significant difference in FVC (p < 0.0001) from normal values according to Knudson, but when expressed in the percentage of the Knudson values, this difference was not significant (p > 0.05). No statistically significant difference was found for FEV1, FEF75, FEF50, FEF25, and FEV1/FVC. TLCO reached (107.37 +/- 20.50)% of normal values according to Cotes, and was not significantly different. At this point, it is hard to predict the consequences of exposure to low levels of asbestos in childhood, because it takes a long time for complications such as neoplasms, pulmonary fibrosis, or respiratory insufficiency to develop.

Plasminogen activator inhibitor 1 in acute coronary syndromes.

Plasminogen activator inhibitor 1 (PAI-1) is the main regulator of endogenous fibrinolysis, overriding the impact of other constituents of fibrinolysis. In plasma, it can be found in three forms: active, latent and inactive. There are numerous commercially available tests, analysing the activity of PAI-1 or the antigen level, with variable correlations between the two. PAI-1 has been extensively studied regarding incidence and outcomes of acute coronary syndromes, and showed positive association with both in numerous studies. Higher PAI-1 has been associated with worse short- and long-term outcomes. Studies are more consistent in the primary percutaneous coronary intervention era. Higher rise of PAI-1 within the first 24 h of acute myocardial infarction has been linked to some of its high-risk features. The circadian pattern of PAI-1 kinetics has been previously described, and the mechanisms behind this phenomenon and its impact on the incidence of acute coronary syndromes are well known. Further investigations are needed to test the safety and efficacy of PAI-1 as a pharmacological target in cardiovascular diseases.