Transitioning to Palliative Care in an Italian Cardiac Intensive Care Unit Network.

BACKGROUND: Recent data indicate that end-of-life management for patients affected by acute decompensated heart failure in cardiac intensive care units is aggressive, with late or no engagement of palliative care teams. OBJECTIVE: To assess current palliative care and end-of-life practices in a contemporary Italian multicenter registry of patients with cardiogenic shock due to acute decompensated heart failure. METHODS: A survey-based approach was used to collect data on palliative care and end-of-life management practices. The AltShock-2 registry enrolled patients with cardiogenic shock from 12 participating centers. A subset of 153 patients with cardiogenic shock due to acute decompensated heart failure enrolled between March 2020 and March 2023 was analyzed, with a focus on early engagement of palliative care teams and deactivation of implantable cardioverter-defibrillators (ICDs). RESULTS: "Do not resuscitate" orders were documented in patient records in only 5 of 12 centers (42%). Palliative care teams were engaged for 21 of 153 enrolled patients (13.7%). Among the 51 patients with ICDs, 6 of 17 patients who died (35%) had defibrillator deactivation. Of the 17 patients who died, 13 died in the hospital and 4 died within 6 months after discharge; 1 patient had ICD deactivation supported by palliative care services at home. CONCLUSIONS: Therapy-limiting practices, including ICD deactivation, are not routine in the Italian centers participating in this study. The results emphasize the importance of integrating palliative care as a simultaneous process with intensive care to address the unmet needs of these patients and their families.

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.

SCAI stage reclassification at 24 h predicts outcome of cardiogenic shock: Insights from the Altshock-2 registry.

BACKGROUND: Cardiogenic shock (CS) includes several phenotypes with heterogenous hemodynamic features. Timely prognostication is warranted to identify patients requiring treatment escalation. We explored the association of the updated Society for Cardiovascular Angiography and Interventions (SCAI) stages classification with in-hospital mortality using a prospective national registry. METHODS: Between March 2020 and February 2022 the Altshock-2 Registry has included 237 patients with CS of all etiologies at 11 Italian Centers. Patients were classified according to their admission SCAI stage (assigned prospectively and independently updated according to the recently released version). In-hospital mortality was evaluated for association with both admission and 24-h SCAI stages. RESULTS: The overall in-hospital mortality was 38%. Of the 237 patients included and staged according to the updated SCAI classification, 20 (8%) had SCAI shock stage B, 131 (55%) SCAI stage C, 61 (26%) SCAI stage D and 25 (11%) SCAI stage E. In-hospital mortality stratified according to the SCAI classification at 24 h was 18% for patients in SCAI stage B, 27% for SCAI stage C, 63% for SCAI stage D and 100% for SCAI stage E. Both the revised SCAI stages on admission and at 24 h were associated with in-hospital mortality, but the classification potential slightly increased at 24-h. After adjusting for age, sex, lactate level, eGFR, CVP, inotropic score and mechanical circulatory support [MCS], SCAI classification at 24 h was an independent predictor of in-hospital mortality. CONCLUSIONS: In the Altshock-2 registry the utility of SCAI shock stages to identify risk of in-hospital mortality increased at 24 h after admission. Escalation of treatment (either pharmacological or with MCS) should be tailored to achieve prompt clinical improvement within the first 24 h after admission. Registration: http://www. CLINICALTRIALS: gov; Unique identifier: NCT04295252.

The effect of COVID-19 epidemic on vital signs in hospitalized patients: a pre-post heat-map study from a large teaching hospital.

The Lombardy SARS-CoV-2 outbreak in February 2020 represented the beginning of COVID-19 epidemic in Italy. Hospitals were flooded by thousands of patients with bilateral pneumonia and severe respiratory, and vital sign derangements compared to the standard hospital population. We propose a new visual analysis technique using heat maps to describe the impact of COVID-19 epidemic on vital sign anomalies in hospitalized patients. We conducted an electronic health record study, including all confirmed COVID-19 patients hospitalized from February 21st, 2020 to April 21st, 2020 as cases, and all non-COVID-19 patients hospitalized in the same wards from January 1st, 2018 to December 31st, 2018. All data on temperature, peripheral oxygen saturation, respiratory rate, arterial blood pressure, and heart rate were retrieved. Derangement of vital signs was defined according to predefined thresholds. 470 COVID-19 patients and 9241 controls were included. Cases were older than controls, with a median age of 79 vs 76 years in non survivors (p = < 0.002). Gender was not associated with mortality. Overall mortality in COVID-19 hospitalized patients was 18%, ranging from 1.4% in patients below 65 years to about 30% in patients over 65 years. Heat maps analysis demonstrated that COVID-19 patients had an increased frequency in episodes of compromised respiratory rate, acute desaturation, and fever. COVID-19 epidemic profoundly affected the incidence of severe derangements in vital signs in a large academic hospital. We validated heat maps as a method to analyze the clinical stability of hospitalized patients. This method may help to improve resource allocation according to patient characteristics.

Impella 5.0 support before, during, and after surgical ventriculoplasty following acute myocardial infarction in the COVID-19 era: a case report.

BACKGROUND: Left ventricular (LV) aneurysms complicate anterior myocardial infarctions (MIs) in 8-15% of cases. In case of associated LV dysfunction, rapidly evolving heart failure may follow, and urgent surgery becomes life-saving. CASE SUMMARY: Following an acute anterior MI treated by percutaneous coronary intervention, which resulted in apical hypokinesis, depressed LV function, and moderate mitral regurgitation, a 70-year-old male patient kept in contact with our cardiology department through phone calls. Over 6 weeks, the patient's conditions worsened. For fear of contracting COVID-19, he refused to attend to the Emergency Room. Conditions did not improve despite medical therapy adjustments, and he was admitted to hospital following a syncope. Computed tomography scan revealed pneumonia, and he was placed in a 'grey' ward while waiting for nose-swab results for COVID-19. A rapid escalation of treatment was necessary as conditions did not improve with low-dose inotropes, and he required invasive ventilation. An Impella 5.0 was implanted as support prior to surgery, was maintained during the procedure and as a means of weaning off extracorporeal circulation. Surgery was successful and Impella 5.0 was removed on postoperative Day 5. DISCUSSION: To date, Impella use in cardiothoracic surgery has been described in case of ventricular septal rupture or as a bridge to permanent LV assist device. In our case, Impella 5.0 was implanted, used as a bridge to surgery, and as postoperative support in a patient with evolving cardiogenic shock due to LV aneurysm and depressed LV ejection fraction following acute MI, in the difficult setting of the COVID-19 pandemic.

[Percutaneous mitral valve repair in acute mitral regurgitation]. / Plastica mitralica transcatetere per il trattamento dell'insufficienza mitralica acuta.

Acute mitral regurgitation is a life-threatening pathology. Nowadays, percutaneous mitral valve repair with the MitraClip device offers, in selected patients, a safe and effective therapeutic alternative to open surgery. Hereby, we report the case of an 82-year-old woman with lateral ST-elevation myocardial infarction determining severe acute mitral regurgitation, who was treated with an urgent MitraClip procedure. Moreover, we discuss echocardiographic assessment of acute mitral regurgitation and we review available literature and possible management of this complex scenario.

Italian Multicenter Registry of Bare Metal Stent Use in Modern Percutaneous Coronary Intervention Era (AMARCORD): A multicenter observational study.

OBJECTIVES: We aimed to evaluate the use of bare metal stent (BMS) implantation in current percutaneous coronary intervention (PCI) era, focusing on indications for use and clinical outcomes. BACKGROUND: Limited data on BMS usage in current clinical practice are available. METHODS: All patients who underwent PCI with at least one BMS implantation in 18 Italian centers from January 1, 2013 to December 31, 2017, were included in our registry. Rates of BMS use and reasons for BMS implantations were reported for the overall study period and for each year. Primary outcomes were mortality, bleeding (Bleeding Academic Research Consortium-BARC and Thrombolysis in Myocardial Infarction-TIMI non-CABG definitions), and major adverse cardiac events (MACE) defined as the composite of all-cause and cardiac death, any myocardial infarction, target vessel revascularization, or any stent thrombosis. RESULTS: Among 58,879 patients undergoing PCI in the study period, 2,117 (3.6%) patients (mean age 73 years, 69.7% males, 73.3% acute coronary syndrome) were treated with BMS implantation (2,353 treated lesions). The rate of BMS implantation progressively decreased from 10.1% (2013) to 0.3% (2017). Main reasons for BMS implantation were: ST-elevation myocardial infarction (STEMI) (23.1%), advanced age (24.4%), and physician's perception of high-bleeding risk (34.0%). At a mean follow-up of 2.2 ± 1.5 years, all-cause and cardiac mortality were 25.6 and 12.7%, respectively; MACE rate was 35.3%, any bleeding rate was 13.0% (BARC 3-5 bleeding 6.3%, TIMI non-CABG major bleeding 6.1%). CONCLUSION: In a large, contemporary, real-world, multicenter registry, BMS use progressively reduced over the last 5 years. Main reasons for BMS implantation were STEMI, advanced age, and physician's perception of high-bleeding risk. High rates of mortality and MACE were observed in this real-world high-risk population.

MitraClip Treatment for Severe Mitral Regurgitation Due to Chordae Rupture Following Impella CP Support in a Patient With Severe Aortic Stenosis.

We report the case of an 85-year-old man with severe aortic stenosis who underwent high-risk percutaneous coronary intervention with Impella CP support. Unfortunately, the device caused mitral chordae tendineae rupture leading to severe mitral regurgitation. The patient underwent a staged fully percutaneous treatment with transcatheter aortic valve replacement followed by elective Mitraclip therapy. Echocardiographic monitoring is of paramount importance during Impella insertion and removal in order to avoid and deal with mitral damage. Mitraclip therapy is a feasible rescue therapy for severe mitral regurgitation due to chordae rupture in patients at high risk for surgery.

Lower dose direct oral anticoagulants and improved survival: A combined analysis in patients with established atherosclerosis.

BACKGROUND: Antithrombotic/anticoagulation effects of direct oral anticoagulants (DOACs) are dose-dependent. However, recent observations suggest that administering lower dose DOACs may better protect against all-cause mortality. We investigated whether, in patients with established atherosclerosis, DOAC dose selection would affect the risk of all-cause mortality. METHODS: We performed a structured literature research for controlled trials allowing random assignment to a lower dose DOAC, a higher dose DOAC, or control therapy in patients with established atherosclerosis. Pooled risk ratios (RRs) of all-cause mortality in lower and higher dose DOACs versus control therapy were estimated using a random-effect model. RESULTS: Atherosclerosis manifested as acute coronary syndrome (n=17,220), stable coronary (CAD) and/or peripheral artery disease (PAD) (n=27,395) or CAD associated with atrial fibrillation (n=4,510). Antithrombotic doses of rivaroxaban (2.5 mg or 5.0 mg BID) or dabigatran (50 mg, 75 mg, 110 mg, or 150 mg, BID) were tested in three trials versus single or dual antiplatelet control therapy, whereas anticoagulation doses of edoxaban (30 mg or 60 OD) were tested versus warfarin in one trial. Compared to control, patients receiving lower dose (RR 0.80, 95% CI 0.73-0.89, p<0.0001, I²=0%), but not those receiving higher dose DOACs (RR 0.95, 95% CI 0.87-1.05, p=0.3074, I²=0%), had a significant reduction of all-cause mortality. Benefit from lower dose DOACs remained after sensitivity analysis or direct comparison with higher dose DOACs (RR 0.84, 95% CI 0.76-0.93, p=0.0009, I²=0%). CONCLUSIONS: Within antithrombotic/anticoagulation regimens of DOAC administration, selection of lower dose appears to protect from all-cause mortality in patients with established atherosclerosis.

Early detection of elevated cardiac biomarkers to optimise risk stratification in patients with COVID-19.

OBJECTIVE: Risk stratification is crucial to optimise treatment strategies in patients with COVID-19. We aimed to evaluate the impact on mortality of an early assessment of cardiac biomarkers in patients with COVID-19. METHODS: Humanitas Clinical and Research Hospital (Rozzano-Milan, Lombardy, Italy) is a tertiary centre that has been converted to the management of COVID-19. Patients with confirmed COVID-19 were entered in a dedicated database for cohort observational analyses. Outcomes were stratified according to elevated levels (ie, above the upper level of normal) of high-sensitivity cardiac troponin I (hs-TnI), B-type natriuretic peptide (BNP) or both measured within 24 hours after hospital admission. The primary outcome was all-cause mortality. RESULTS: A total of 397 consecutive patients with COVID-19 were included up to 1 April 2020. At the time of hospital admission, 208 patients (52.4%) had normal values for cardiac biomarkers, 90 (22.7%) had elevated both hs-TnI and BNP, 59 (14.9%) had elevated only BNP and 40 (10.1%) had elevated only hs-TnI. The rate of mortality was higher in patients with elevated hs-TnI (22.5%, OR 4.35, 95% CI 1.72 to 11.04), BNP (33.9%, OR 7.37, 95% CI 3.53 to 16.75) or both (55.6%, OR 18.75, 95% CI 9.32 to 37.71) as compared with those without elevated cardiac biomarkers (6.25%). A multivariate analysis identified concomitant elevation of both hs-TnI and BNP as a strong independent predictor of all-cause mortality (OR 3.24, 95% CI 1.06 to 9.93). CONCLUSIONS: An early detection of elevated hs-TnI and BNP predicts mortality in patients with COVID-19. Cardiac biomarkers should be systematically assessed in patients with COVID-19 at the time of hospital admission in order to optimise risk stratification.

Contribution of genome-wide association studies to scientific research: a pragmatic approach to evaluate their impact.

The factual value of genome-wide association studies (GWAS) for the understanding of multifactorial diseases is a matter of intense debate. Practical consequences for the development of more effective therapies do not seem to be around the corner. Here we propose a pragmatic and objective evaluation of how much new biology is arising from these studies, with particular attention to the information that can help prioritize therapeutic targets. We chose multiple sclerosis (MS) as a paradigm disease and assumed that, in pre-GWAS candidate-gene studies, the knowledge behind the choice of each gene reflected the understanding of the disease prior to the advent of GWAS. Importantly, this knowledge was based mainly on non-genetic, phenotypic grounds. We performed single-gene and pathway-oriented comparisons of old and new knowledge in MS by confronting an unbiased list of candidate genes in pre-GWAS association studies with those genes exceeding the genome-wide significance threshold in GWAS published from 2007 on. At the single gene level, the majority (94 out of 125) of GWAS-discovered variants had never been contemplated as plausible candidates in pre-GWAS association studies. The 31 genes that were present in both pre- and post-GWAS lists may be of particular interest in that they represent disease-associated variants whose pathogenetic relevance is supported at the phenotypic level (i.e. the phenotypic information that steered their selection as candidate genes in pre-GWAS association studies). As such they represent attractive therapeutic targets. Interestingly, our analysis shows that some of these variants are targets of pharmacologically active compounds, including drugs that are already registered for human use. Compared with the above single-gene analysis, at the pathway level GWAS results appear more coherent with previous knowledge, reinforcing some of the current views on MS pathogenesis and related therapeutic research. This study presents a pragmatic approach that helps interpret and exploit GWAS knowledge.