[Venoarterial extracorporeal membrane oxygenation: from evidence to clinical practice]. / Il supporto della circolazione extracorporea nelle emergenze cardiologiche: evidenze scientifiche e pratica clinica.

Mortality for cardiogenic shock is still high despite optimal pharmacological therapy. Therefore, active mechanical circulatory support devices are increasingly used; venoarterial extracorporeal membrane oxygenation (VA-ECMO) enables full circulatory and respiratory support. However, recent data show that in patients with infarct-related shock unselected early use of VA-ECMO does not improve survival and is associated with major bleeding and peripheral ischemic complications. Nowadays, waiting for the results of definitive randomized controlled trials, the main indication for ECMO utilization is in selected patients with cardiac arrest, in those with shock for advanced heart failure refractory to conventional therapy, in those with fulminant myocarditis, in patients candidate for heart transplant or ventricular assistance, especially in presence of respiratory insufficiency and severe biventricular dysfunction. An important recommendation is its utilization in specialized, high-volume centers in the setting of hub and spoke hospitals.

Cangrelor in a challenging scenario of concomitant ischaemic stroke, pulmonary embolism, and ST-elevation myocardial infarction: a case report.

Background: Antithrombotic therapy in acute patients with both high ischaemic and bleeding risks remains challenging. Case summary: We presented a challenging case involving a 48-year-old man referred to our hospital for headache and a left superior quadrantanopia. A CT scan revealed a right inferior occipital lobe ischaemic stroke. During the hospital stay, the patients developed pulmonary embolism (PE), and ST-elevation myocardial infarction (STEMI). A triple antithrombotic therapy was indicated, but the patient presented with high bleeding (anaemia, active malignancy, ischaemic stroke) and ischaemic (ischaemic stroke, PE, and superimposed STEMI) risks. In this critical acute setting, prolonged cangrelor infusion of reduced dosage, coupled with aspirin and enoxaparin, proved an effective and safe antithrombotic approach. Discussion: Prolonged cangrelor bridging at a reduced dose of 0.75 µg/kg/min may represent an effective and safe option in acute patients requiring P2Y12 inhibition and presenting both high ischaemic and high bleeding risks.

Beneficial Effects of IABP in Anterior Myocardial Infarction Complicated by Cardiogenic Shock.

Background and Objectives. Recent guidelines have downgraded the routine use of the intra-aortic balloon pump (IABP) in patients with cardiogenic shock (CS) due to ST-elevation myocardial infarction (STEMI). Despite this, its use in clinical practice remains high. The aim of this study was to evaluate the prognostic impact of the IABP in patients with STEMI complicated by CS undergoing primary PCI (pPCI), focusing on patients with anterior MI in whom a major benefit has been previously hypothesized. Materials and Methods. We enrolled 2958 consecutive patients undergoing pPCI for STEMI in our department from 2005 to 2018. Propensity score matching and mortality analysis were performed. Results. CS occurred in 246 patients (8.3%); among these patients, 145 (60%) had anterior AMI. In the propensity-matched analysis, the use of the IABP was associated with a lower 30-day mortality (39.3% vs. 60.9%, p = 0.032) in the subgroup of patients with anterior STEMI. Conversely, in the whole group of CS patients and in the subgroup of patients with non-anterior STEMI, IABP use did not have a significant impact on mortality. Conclusions. The use of the IABP in cases of STEMI complicated by CS was found to improve survival in patients with anterior infarction. Prospective studies are needed before abandoning or markedly limiting the use of the IABP in this clinical setting.

Differences between cardiogenic shock related to acute decompensated heart failure and acute myocardial infarction.

AIMS: The present analysis from the multicentre prospective Altshock-2 registry aims to better define clinical features, in-hospital course, and management of cardiogenic shock complicating acutely decompensated heart failure (ADHF-CS) as compared with that complicating acute myocardial infarction (AMI-CS). METHODS AND RESULTS: All patients with AMI-CS or ADHF-CS enrolled in the Altshock-2 registry between March 2020 and February 2022 were selected. The primary objective was the characterization of ADHF-CS patients as compared with AMI-CS. In-hospital length of stay and mortality were secondary endpoints. One-hundred-ninety of the 238 CS patients enrolled in the aforementioned period were considered for the present analysis: 101 AMI-CS (80% ST-elevated myocardial infarction and 20% non-ST-elevated myocardial infarction) and 89 ADHF-CS. As compared with AMI-CS, ADHF-CS patients were younger [63 (IQR 59-76) vs. 67 (IQR 54-73) years, P = 0.01], but presented with higher creatinine [1.6 (IQR 1.0-2.6) vs. 1.2 (IQR 1.0-1.4) mg/dL, P < 0.001], bilirubin [1.3 (IQR 0.9-2.3) vs. 0.6 (IQR 0.4-1.1) mg/dL, P = 0.01], and central venous pressure values [14 mmHg (IQR 8-12) vs. 10 mmHg (IQR 7-14),P = 0.01]. Norepinephrine was the most common catecholamine used in AMI-CS (79.3%), whereas epinephrine was used more commonly in ADHF-CS (65.5%); 75.8% vs. 46.6% received a temporary mechanical support in AMI-CS and ADHF-CS, respectively (P < 0.001). Length of hospital stay was longer in the latter [28 (IQR 13-48) vs. 17 (IQR 9-29) days, P = 0.001]. Heart replacement therapies were more frequently used in the ADHF-CS group (heart transplantation 13.5% vs. 0% and left ventricular assist device 11% vs. 2%, P < 0.01 and 0.01, respectively). In-hospital mortality was 41.1% (38.6% AMI-CS vs. 43.8% ADHF-CS, P = 0.5). CONCLUSIONS: ADHF-CS is characterized by a higher prevalence of end-organ and biventricular dysfunction at presentation, a longer hospital length of stay, and higher need of heart replacement therapies when compared with AMI-CS. In-hospital mortality was similar between the two aetiologies. Our data warrant development of new management protocols focused on CS aetiology.

Cardiac magnetic resonance predictors of left ventricular remodelling following acute ST elevation myocardial infarction: The VavirimS study.

BACKGROUND: Left ventricular (LV) remodelling (REM) ensuing after ST-elevation myocardial infarction (STEMI), has typically been studied by echocardiography, which has limitations, or cardiac magnetic resonance (CMR) in early phase that may overestimate infarct size (IS) due to tissue edema and stunning. This prospective, multicenter study investigated LV-REM performing CMR in the subacute phase, and 6 months after STEMI. METHODS AND RESULTS: patients with first STEMI undergoing successful primary angioplasty were consecutively enrolled. CMR was done at 30-days and 6-months. Primary endpoint was prevalence at 6 months of LV-REM [≥12% increase in LV end-diastolic volume index (LV-REMEDV)]; LV-REM by end-systolic volume index increase ≥12% (LV-REMESV) was also calculated. Of 325 patients enrolled, 193 with a full set of research-quality CMR images were analyzed. LV-REMEDV and LV-REMESV were present in 36/193 (19%) and 34/193 (18%) patients, respectively. At follow up, LV ejection fraction (EF) improved in patients with or without LV-REMEDV, whilst it decreased in those with LV-REMESV (p < 0.001 for interaction). Considering predictors of LV-REM, IS in the highest tertile was clearly separated from the two lower tertiles. In LV-REMEDV, the highest tertile was associated with significantly higher LV-EDV, LV-ESV, and lower EF. CONCLUSIONS: In a contemporary cohort of STEMI patients studied by CMR, prevalence of LV-REMEDV was lower than previously reported. Importantly, our data indicate that LV-REMEDV might not be "adverse" per se, but rather "compensatory", being associated with LV-EF improvement at follow-up. Conversely, LV-REMESV might be an "adverse" phenomenon associated with decreased LV-EF, driven by IS.

Heart rate control and haemodynamic improvement with ivabradine in cardiogenic shock patient on mechanical circulatory support.

AIMS: Cardiogenic shock (CS) is a life-threatening condition due to primary cardiac dysfunction. First-line therapy involves drug administration (including inotropes and/or vasopressors) up to mechanical circulatory support. Tachycardia is a frequent compensatory mechanism in response to hypotension and low cardiac output or a side effect related to inotropic drugs. Ivabradine selectively acts on the IKf channel in the sinoatrial node to reduce sinus heart rate without affecting inotropism. Its use, in small non-randomized series of patients with CS without mechanical circulatory support, was safe and well tolerated. METHODS AND RESULTS: We present the use of ivabradine in six patients with CS undertaking veno-arterial extracorporeal membrane oxygenation (VA-ECMO) and a matched cohort of selected patients with similar features who did not receive ivabradine. Data regarding haemodynamic and echocardiographic monitoring, oxygenation, renal function, mechanical circulatory support, inotropes, and vasopressors doses were collected before (t0), at 12 (t1), 24 (t2), and 48 (t3) h after ivabradine administration. Ivabradine administration led to a significant heart rate reduction of 20.83 [95% confidence interval (CI) -27.2 to -14.4] b.p.m. (<0.01). Echo-derived left ventricular native stroke volume (SV) significantly increased by +7.83 (95% CI 4.74-10.93) mL (P < 0.001) with a parallel reduction of VA-ECMO support [-170 (95% CI -225.05 to -114.95)]. Noradrenaline was down-titrated over the observation period in all patients (P = 0.016). CONCLUSION: A significant reduction in heart rate was observed after ivabradine administration. This was associated with a native ventricular SV improvement allowing the reduction of extracorporeal flow support and vasopressors administration.

Machine learning for prediction of in-hospital mortality in coronavirus disease 2019 patients: results from an Italian multicenter study.

BACKGROUND: Several risk factors have been identified to predict worse outcomes in patients affected by SARS-CoV-2 infection. Machine learning algorithms represent a novel approach to identifying a prediction model with a good discriminatory capacity to be easily used in clinical practice. The aim of this study was to obtain a risk score for in-hospital mortality in patients with coronavirus disease infection (COVID-19) based on a limited number of features collected at hospital admission. METHODS AND RESULTS: We studied an Italian cohort of consecutive adult Caucasian patients with laboratory-confirmed COVID-19 who were hospitalized in 13 cardiology units during Spring 2020. The Lasso procedure was used to select the most relevant covariates. The dataset was randomly divided into a training set containing 80% of the data, used for estimating the model, and a test set with the remaining 20%. A Random Forest modeled in-hospital mortality with the selected set of covariates: its accuracy was measured by means of the ROC curve, obtaining AUC, sensitivity, specificity and related 95% confidence interval (CI). This model was then compared with the one obtained by the Gradient Boosting Machine (GBM) and with logistic regression. Finally, to understand if each model has the same performance in the training and test set, the two AUCs were compared using the DeLong's test. Among 701 patients enrolled (mean age 67.2 ±â€Š13.2 years, 69.5% male individuals), 165 (23.5%) died during a median hospitalization of 15 (IQR, 9-24) days. Variables selected by the Lasso procedure were: age, oxygen saturation, PaO2/FiO2, creatinine clearance and elevated troponin. Compared with those who survived, deceased patients were older, had a lower blood oxygenation, lower creatinine clearance levels and higher prevalence of elevated troponin (all P < 0.001). The best performance out of the samples was provided by Random Forest with an AUC of 0.78 (95% CI: 0.68-0.88) and a sensitivity of 0.88 (95% CI: 0.58-1.00). Moreover, Random Forest was the unique model that provided similar performance in sample and out of sample (DeLong test P = 0.78). CONCLUSION: In a large COVID-19 population, we showed that a customizable machine learning-based score derived from clinical variables is feasible and effective for the prediction of in-hospital mortality.

Sex-related differences in patients with coronavirus disease 2019: results of the Cardio-COVID-Italy multicentre study.

INTRODUCTION: The role of sex compared to comorbidities and other prognostic variables in patients with coronavirus disease (COVID-19) is unclear. METHODS: This is a retrospective observational study on patients with COVID-19 infection, referred to 13 cardiology units. The primary objective was to assess the difference in risk of death between the sexes. The secondary objective was to explore sex-based heterogeneity in the association between demographic, clinical and laboratory variables, and patients' risk of death. RESULTS: Seven hundred and one patients were included: 214 (30.5%) women and 487 (69.5%) men. During a median follow-up of 15 days, deaths occurred in 39 (18.2%) women and 126 (25.9%) men. In a multivariable Cox regression model, men had a nonsignificantly higher risk of death vs. women (P = 0.07).The risk of death was more than double in men with a low lymphocytes count as compared with men with a high lymphocytes count [overall survival hazard ratio (OS-HR) 2.56, 95% confidence interval (CI) 1.72-3.81]. In contrast, lymphocytes count was not related to death in women (P = 0.03).Platelets count was associated with better outcome in men (OS-HR for increase of 50 × 103 units: 0.88 95% CI 0.78-1.00) but not in women. The strength of association between higher PaO2/FiO2 ratio and lower risk of death was larger in women (OS-HR for increase of 50 mmHg/%: 0.72, 95% CI 0.59-0.89) vs. men (OS-HR: 0.88, 95% CI 0.80-0.98; P = 0.05). CONCLUSIONS: Patients' sex is a relevant variable that should be taken into account when evaluating risk of death from COVID-19. There is a sex-based heterogeneity in the association between baseline variables and patients' risk of death.

Combined Role of Troponin and Natriuretic Peptides Measurements in Patients With Covid-19 (from the Cardio-COVID-Italy Multicenter Study).

Data concerning the combined prognostic role of natriuretic peptide (NP) and troponin in patients with COVID-19 are lacking. The aim of the study is to evaluate the combined prognostic value of NPs and troponin in hospitalized COVID-19 patients. From March 1, 2020 to April 9, 2020, consecutive patients with COVID-19 and available data on cardiac biomarkers at admission were recruited. Patients admitted for acute coronary syndrome were excluded. Troponin levels were defined as elevated when greater than the 99th percentile of normal values. NPs were considered elevated if above the limit for ruling in acute heart failure (HF). A total of 341 patients were included in this study, mean age 68 ± 13 years, 72% were men. During a median follow-up period of 14 days, 81 patients (24%) died. In the Cox regression analysis, patients with elevated both NPs and troponin levels had higher risk of death compared with those with normal levels of both (hazard ratio 2.94; 95% confidence interval 1.31 to 6.64; p = 0.009), and this remained significant after adjustment for age, gender, oxygen saturation, HF history, and chronic kidney disease. Interestingly, NPs provided risk stratification also in patients with normal troponin values (hazard ratio 2.86; 95% confidence interval 1.21 to 6.72; p = 0.016 with high NPs levels). These data show the combined prognostic role of troponin and NPs in COVID-19 patients. NPs value may be helpful in identifying patients with a worse prognosis among those with normal troponin values. Further, NPs' cut-point used for diagnosis of acute HF has a predictive role in patients with COVID-19.

Barriers associated with emergency medical service activation in patients with ST-segment elevation acute coronary syndromes.

Many ST-segment elevation acute coronary syndrome (STEACS) patients fail to activate the Emergency Medical System (EMS), with possible dramatic consequences. Prior studies focusing on barriers to EMS activation included patients with any acute coronary syndrome (ACS) without representation of southern European populations. We aimed to investigate the barriers to EMS call for patients diagnosed for STEACS in Italy. A prospective, single-center, survey administered to all patients treated with primary percutaneous coronary intervention for STEACS in a tertiary hospital in northern Italy from 01/06/2018 to 31/05/2020. The questionnaire was filled out by 293 patients. Of these, 191 (65.2%) activated the EMS after symptoms onset. The main reasons for failing to contact EMS were the perception that the symptoms were unrelated to an important health problem (45.5%) and that a private vehicle is faster than EMS to reach the hospital (34.7%). Patients who called a private doctor after symptoms onset did not call EMS more frequently than those who did not and 30% of the patients who did not call the EMS would still act in the same way if a new episode occurred. Previous history of cardiovascular disease was the only predictor of EMS call. Information campaigns are urgently needed to increase EMS activation in case of suspected STEACS and should be primary focused on patients without cardiovascular history, on the misperception that a private vehicle is faster than EMS activation, and on the fact that cardiac arrest occurs early and may be prevented by EMS activation.

Acute kidney injury and in-hospital mortality in patients with ST-elevation myocardial infarction of different age groups.

BACKGROUND: Acute kidney injury (AKI) is a well-known complication of ST-elevation acute myocardial infarction (STEMI) with an adverse impact on prognosis. Since AKI develops more frequently in elderly patients, we hypothesized that its higher incidence in older STEMI patients might explain their increased in-hospital mortality. We assessed the relationship between AKI and in-hospital mortality in patients with STEMI of different age groups. METHODS: We retrospectively evaluated 5136 STEMI patients treated with primary percutaneous coronary intervention (pPCI). We defined AKI as ≥0.5 mg/dl creatinine increase in the first 72 h. Patients were grouped according to age (<75 [n = 4040] or ≥ 75 [n = 1096] years). The primary endpoint was in-hospital mortality. RESULTS: The incidence of AKI was 7%. It was 4.6% in patients <75 years and 15.1% in those ≥75 years (P < 0.0001). The overall in-hospital mortality was 4%. It was 2.6% and 8.5% in patients younger and older than 75 years, respectively (P < 0.0001). It was higher in AKI than in non-AKI patients, both in the overall population (27% vs. 2%) and in the two age groups (25% vs. 2% and 29% vs. 5% in younger and older patients, respectively; P < 0.0001). The adjusted odds ratio of in-hospital mortality associated with AKI progressively decreased in parallel with increasing age decades (from 24.7 [95% CI 11.2-54.1] in patients <65 years to 3.9 [95% CI 1.6-9.7] in those >85 years). CONCLUSIONS: In STEMI patients treated with pPCI, AKI incidence and in-hospital mortality steadily increase with age. However, the prognostic impact of AKI is progressively reduced as age increases.

The prognostic value of serial troponin measurements in patients admitted for COVID-19.

AIMS: Myocardial injury (MI) in coronavirus disease-19 (COVID-19) is quite prevalent at admission and affects prognosis. Little is known about troponin trajectories and their prognostic role. We aimed to describe the early in-hospital evolution of MI and its prognostic impact. METHODS AND RESULTS: We performed an analysis from an Italian multicentre study enrolling COVID-19 patients, hospitalized from 1 March to 9 April 2020. MI was defined as increased troponin level. The first troponin was tested within 24 h from admission, the second one between 24 and 48 h. Elevated troponin was defined as values above the 99th percentile of normal values. Patients were divided in four groups: normal, normal then elevated, elevated then normal, and elevated. The outcome was in-hospital death. The study population included 197 patients; 41% had normal troponin at both evaluations, 44% had elevated troponin at both assessments, 8% had normal then elevated troponin, and 7% had elevated then normal troponin. During hospitalization, 49 (25%) patients died. Patients with incident MI, with persistent MI, and with MI only at admission had a higher risk of death compared with those with normal troponin at both evaluations (P < 0.001). At multivariable analysis, patients with normal troponin at admission and MI injury on Day 2 had the highest mortality risk (hazard ratio 3.78, 95% confidence interval 1.10-13.09, P = 0.035). CONCLUSIONS: In patients admitted for COVID-19, re-test MI on Day 2 provides a prognostic value. A non-negligible proportion of patients with incident MI on Day 2 is identified at high risk of death only by the second measurement.

Implications of atrial fibrillation on the clinical course and outcomes of hospitalized COVID-19 patients: results of the Cardio-COVID-Italy multicentre study.

AIMS: To assess the clinical relevance of a history of atrial fibrillation (AF) in hospitalized patients with coronavirus disease 2019 (COVID-19). METHODS AND RESULTS: We enrolled 696 consecutive patients (mean age 67.4 ± 13.2 years, 69.7% males) admitted for COVID-19 in 13 Italian cardiology centres between 1 March and 9 April 2020. One hundred and six patients (15%) had a history of AF and the median hospitalization length was 14 days (interquartile range 9-24). Patients with a history of AF were older and with a higher burden of cardiovascular risk factors. Compared to patients without AF, they showed a higher rate of in-hospital death (38.7% vs. 20.8%; P < 0.001). History of AF was associated with an increased risk of death after adjustment for clinical confounders related to COVID-19 severity and cardiovascular comorbidities, including history of heart failure (HF) and increased plasma troponin [adjusted hazard ratio (HR): 1.73; 95% confidence interval (CI) 1.06-2.84; P = 0.029]. Patients with a history of AF also had more in-hospital clinical events including new-onset AF (36.8% vs. 7.9%; P < 0.001), acute HF (25.3% vs. 6.3%; P < 0.001), and multiorgan failure (13.9% vs. 5.8%; P = 0.010). The association between AF and worse outcome was not modified by previous or concomitant use of anticoagulants or steroid therapy (P for interaction >0.05 for both) and was not related to stroke or bleeding events. CONCLUSION: Among hospitalized patients with COVID-19, a history of AF contributes to worse clinical course with a higher mortality and in-hospital events including new-onset AF, acute HF, and multiorgan failure. The mortality risk remains significant after adjustment for variables associated with COVID-19 severity and comorbidities.

Determinants of the protective effect of glucocorticoids on mortality in hospitalized patients with COVID-19: Insights from the Cardio-COVID-Italy multicenter study.

BACKGROUND: Glucocorticoid therapy has emerged as an effective therapeutic option in hospitalized patients with coronavirus disease 2019 (COVID-19). This study aimed to focus on the impact of relevant clinical and laboratory factors on the protective effect of glucocorticoids on mortality. METHODS: A sub-analysis was performed of the multicenter Cardio-COVID-Italy registry, enrolling consecutive patients with COVID-19 admitted to 13 Italian cardiology units between 01 March 2020 and 09 April 2020. The primary endpoint was in-hospital mortality. RESULTS: A total of 706 COVID-19 patients were included (349 treated with glucocorticoids, 357 not treated with glucocorticoids). After adjustment for relevant covariates, use of glucocorticoids was associated with a lower risk of in-hospital mortality (adjusted HR 0.44; 95% CI 0.26-0.72; p = 0.001). A significant interaction was observed between the protective effect of glucocorticoids on mortality and PaO2/FiO2 ratio on admission (p = 0.042), oxygen saturation on admission (p = 0.017), and peak CRP (0.023). Such protective effects of glucocorticoids were mainly observed in patients with lower PaO2/FiO2 ratio (<300), lower oxygen saturation (<90%), and higher CRP (>100 mg/L). CONCLUSIONS: The protective effects of glucocorticoids on mortality in COVID-19 were more evident among patients with worse respiratory parameters and higher systemic inflammation.

Elevated serum uric acid is a predictor of contrast associated acute kidney injury in patient with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention.

BACKGROUND: Contrast associated-acute kidney injury (CA-AKI) has been associated with adverse outcomes after ST-segment elevation myocardial infarction (STEMI). However, early markers of CA-AKI are still needed to improve risk stratification. We investigated the association between elevated serum uric acid (eSUA) and CA-AKI in patients with STEMI treated with primary percutaneous coronary intervention (pPCI). METHODS AND RESULTS: Serum creatinine (Scr) was measured at admission and 24, 48 and 72 h after pPCI. CA-AKI was defined as an increase of 25% (CA-AKI 25%) or 0.5 mg/dl (CA-AKI 0.5) of Scr level above the baseline after 48 h following contrast administration. Multivariable analyses to investigate CA-AKI predictors were performed by binary logistic regression and multivariable backward logistic regression model. In the 3023 patients considered, CA-AKI was more frequent among patients with eSUA as compared with patients with normal SUA levels, considering both CA-AKI definitions (CA-AKI25%: 20.8% vs 16.2%, p < 0.012; CA-AKI 0.5: 10.1% vs 5.8%, p < 0.001). The association between eSUA and CA-AKI was confirmed at multivariable analyses (CA-AKI 25%: odd ratio 1.32, 95% CI 1.03-1.69, p = 0.027; CA-AKI 0.5: odd ratio 1.76, 95% CI 1.11-2.79, p = 0.016). CONCLUSION: Elevated serum uric acid is associated with CA-AKI after reperfusion in patients with STEMI treated with pPCI.