Cardiogenic Shock Integrated PHenotyping for Event Reduction: A Pilot Metabolomics Analysis.

Cardiogenic shock (CS) portends a dismal prognosis if hypoperfusion triggers uncontrolled inflammatory and metabolic derangements. We sought to investigate metabolomic profiles and temporal changes in IL6, Ang-2, and markers of glycocalyx perturbation from admission to discharge in eighteen patients with heart failure complicated by CS (HF-CS). Biological samples were collected from 18 consecutive HF-CS patients at admission (T0), 48 h after admission (T1), and at discharge (T2). ELISA analytical techniques and targeted metabolomics were performed Seven patients (44%) died at in-hospital follow-up. Among the survivors, IL-6 and kynurenine were significantly reduced at discharge compared to baseline. Conversely, the amino acids arginine, threonine, glycine, lysine, and asparagine; the biogenic amine putrescine; multiple sphingolipids; and glycerophospholipids were significantly increased. Patients with HF-CS have a metabolomic fingerprint that might allow for tailored treatment strategies for the patients' recovery or stabilization.

Sacubitril/Valsartan in "Field Practice" Patients with Advanced Heart Failure: A Monocentric Italian Experience.

Patients with advanced heart failure (HF) experience a continuous decline in quality of life and have a very poor prognosis. Moreover, due to numerous comorbidities present in these patients, transplantation and left ventricular assist devices are usually impracticable in clinical practice. In this challenging setting, administration of inotropic agents may be the only possible therapy; however, this treatment requires frequent hospitalizations. Our hypothesis is that sacubitril/valsartan, given its marked efficacy and manageability, can be safely used in clinical practice in this setting, potentially reducing hospitalizations and the need for inotropic support. We report here our experience in a small series of patients with advanced HF treated with sacubitril/valsartan.

Organ perfusion pressure at admission and clinical outcomes in patients hospitalized for acute heart failure.

AIMS: Hypoperfusion portends adverse outcomes in acute heart failure (AHF). The gradient between end-organ inflow and outflow pressures may more closely reflect hypoperfusion than mean arterial pressure (MAP) alone. The aim of this study was to investigate organ perfusion pressure (OPP), calculated as MAP minus central venous pressure (CVP), as a prognostic marker in AHF. METHODS AND RESULTS: The Sodium NItroPrusside Treatment in Acute Heart Failure (SNIP)-AHF study was a multicentre retrospective cohort study of 200 consecutive patients hospitalized for AHF treated with sodium nitroprusside. Only patients with both MAP and invasive CVP data available from the SNIP-AHF cohort were included in this analysis. The primary endpoint was to assess OPP as a predictor of worsening heart failure (WHF), defined as the worsening of signs and symptoms of heart failure leading to intensification of therapy at 48 h. One hundred and forty-six patients fulfilling the inclusion criteria were included [mean age: 61.1 ± 13.5 years, 32 (21.9%) females; mean body mass index: 26.2 ± 11.7 kg/m2; mean left ventricular ejection fraction: 23.8%±11.4%, mean MAP: 80.2 ± 13.2 mmHg, and mean CVP: 14.0 ± 6.1 mmHg]. WHF occurred in 14 (9.6%) patients. At multivariable models including hemodynamic variables (OPP, shock index, and CVP), OPP at admission was the best predictor of WHF at 48 h [OR 0.91 (95% confidence interval 0.86-0.96), P-value = 0.001] with an optimal cut-off value of 67.5 mmHg (specificity 47.3%, sensitivity 100%, and AUC 0.784 ± 0.054). In multivariable models, including univariable significant parameters available at first bedside assessment, namely New York Heart Association functional class, OPP, shock index, CVP, and left ventricular end-diastolic diameter, OPP consistently and significantly predicted WHF at 48 h. CONCLUSION: In this retrospective analysis on patients hospitalized for AHF treated with sodium nitroprusside, on-admission OPP significantly predicted WHF at 48 h with high sensitivity.

Non-ST-elevation acute coronary syndrome in chronic kidney disease: prognostic implication of an early invasive strategy.

BACKGROUND: The optimal timing of PCI for NSTE-ACS with CKD is unclear. The aim of our study was to assess whether early percutaneous coronary intervention (PCI) (within 24 hours from admission) is associated with improved in-hospital (mortality or acute kidney injury) and long-term events (composite of mortality, myocardial infarction, stroke and bleeding events) in patients with non-ST-elevation acute coronary syndromes (NSTE-ACS) with chronic kidney disease (CKD). METHODS: We retrospectively studied NSTE-ACS patients who underwent PCI in large tertiary centers. CKD was defined as estimated glomerular filtration rate (eGFR)<60 mL/min/1.73 m2. A propensity score for the likelihood of an early invasive strategy was calculated. Relative risks (RR) and adjusted hazard ratios (HR) were estimated for in-hospital and follow-up events. RESULTS: We included 821 patients, mean age was 69±12 years; 492 (60%) received an early PCI, and 273 (33%) had an eGFR <60. Median follow-up was 391 days. At univariate analysis, early treatment was associated with significantly lower in-hospital and follow-up events. However, after adjustment for major prognostic factors, there was no significant association with both in-hospital (RR=1.06; 95% CI 0.83-1.36) and follow-up events (RR=1.07; 95% CI 0.83-1.37). When the association was assessed in strata of CKD, lack of statistically significant association was confirmed, even if a trend emerged in patients with preserved renal function both on primary outcome (RR=0.47, 95% 0.18-1.22) and time to secondary outcome (HR=0.62, 95% CI 0.36-1.08). CONCLUSIONS: In conclusion in a cohort of NSTE-ACS patients, an early invasive strategy does not independently affect prognosis.

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.

Systemic leak capillary syndrome with myocardial involvement and cardiogenic shock: a case report.

Background: Systemic capillary leak syndrome (SCLS) is a potentially fatal disorder characterized by relapses of hypovolemic shock episodes. Case Summary: We present a case of a 58-year-old man who presented to the Emergency Department with a history of recurrent episodes of syncope in the last hours. A few days before medical contact the patient complained of sore throat, fever, and flu-like symptoms. He was initially admitted with a diagnosis of suspected myopericarditis. Forty-eight hours later, the haemodynamic status suddenly deteriorated to a mixed cardiogenic and shock; an endomyocardial biopsy showed localized inflammatory infiltrates and areas of necrosis of cardiomyocytes with positive viral search for parvovirus B19 (PVB19), therefore the patient was treated with methylprednisolone pulses. Based on the concurrent presence of the typical triad of hypotension, hypoalbuminaemia, and haemoconcentration we suspected systemic leak capillary syndrome potentially triggered by the PVB19 infection with acute myocarditis. The clinical conditions further deteriorated with rhabdomyolysis and acute kidney injury: we started continuous veno-venous haemofiltration adding a cytokines adsorber. In the following hours, we observed a significant clinical improvement. The patient was discharged 1 month later and 5 months after discharge he experienced a new attack of SCLS, this time without myocardial involvement and with prompt symptoms resolution. Conclusion: Systemic capillary leak syndrome is a potentially fatal disorder: early recognition of this entity and prompt initiation of supportive therapy are warranted, therefore, it is paramount that an emergency physician thinks of SCLS in patients with signs of cardiogenic shock and the classical triad of hypotension, hypoalbuminia, and haemoconcentration.

Effect of landiolol in patients with tachyarrhythmias and acute decompensated heart failure (ADHF): a case series.

Tachycardia and rapid tachyarrhythmias are common in acute clinical settings and may hasten the deterioration of haemodynamics in patients with acute decompensated heart failure (ADHF), treated with inotropes. The concomitant use of a short-acting ß1-selective beta-blocker, such as landiolol, could rapidly and safely restore an adequate heart rate without any negative inotropic effect. We present a case series of five patients with left ventricular dysfunction, admitted to our Intensive Cardiac Care Unit with ADHF deteriorated to cardiogenic shock, treated with a combination of landiolol and inotropes. Landiolol was effective in terms of rate control and haemodynamics optimization, enabling de-escalation of catecholamine dosing in all patients. The infusion was always well tolerated without hypotension. In conclusion, a continuous infusion of a low dose of landiolol (3-16 mcg/kg/min) to manage tachycardia and ventricular or supraventricular tachyarrhythmias in haemodynamically unstable patients may be considered.

Percutaneous Coronary Revascularization after Out-of-Hospital Cardiac Arrest: A Review of the Literature and a Case Series.

Out-of-hospital cardiac arrest (OHCA) is still associated with high mortality and severe complications, despite major treatment advances in this field. Ischemic heart disease is a common cause of OHCA, and current guidelines clearly recommend performing immediate coronary angiography (CAG) in patients whose post-resuscitation electrocardiogram shows ST-segment elevation (STE). Contrarily, the optimal approach and the advantage of early revascularization in cases of no STE is less clear, and decisions are often based on the individual experience of the center. Numerous studies have been conducted on this topic and have provided contradictory evidence; however, more recently, results from several randomized clinical trials have suggested that performing early CAG has no impact on overall survival in patients without STE.

Left Ventricular Unloading in Acute on Chronic Heart Failure: From Statements to Clinical Practice.

Cardiogenic shock remains a deadly complication of acute on chronic decompensated heart failure (ADHF-CS). Despite its increasing prevalence, it is incompletely understood and therefore often misdiagnosed in the early phase. Precise diagnosis of the underlying cause of CS is fundamental for undertaking the correct therapeutic strategy. Temporary mechanical circulatory support (tMCS) is the mainstay of management: identifying and selecting optimal patients through understanding of the hemodynamics and a prompt profiling and timing, is key for success. A recent statement from the American Heart Association provided pragmatic suggestions on tMCS device selection, escalation, and weaning strategies. However, several areas of uncertainty still remain in clinical practice. Accordingly, we present an overview of the main pitfalls that can occur during patients' management with tMCS through a clinical case. This case illustrates the strict interdependency between left ventricular unloading and right ventricular dysfunction in the case of low filling pressures. Moreover, it further illustrates the pivotal role of stepwise escalation of therapy in a patient with an ADHF-CS and its peculiarities as compared to other forms of acute heart failure.

Sodium nitroprusside in acute heart failure: A multicenter historic cohort study.

AIMS: Despite evidence of hemodynamic benefit of sodium nitroprusside (SNP) treatment for acute heart failure (AHF), there are limited data about its efficacy and safety. This study aimed to assess the effectiveness and safety of SNP treatment, to explore the impact of N-terminal pro-B natriuretic peptide (NT-proBNP) reduction on clinical endpoints and to identify possible predictors of clinical response. METHODS AND RESULTS: Multicenter retrospective cohort study of 200 patients consecutively admitted for AHF in 2 Italian Centers. Primary endpoint was the reduction of NT-proBNP levels ≥25% from baseline values within 48 h from the onset of SNP infusion. Secondary and safety endpoints included all-cause mortality, rehospitalization for HF at 1, 3 and 6 months, length of hospital stay (LOS) and severe hypotension. 131 (66%) patients experienced a NT-proBNP reduction ≥25% within 48 h from treatment onset, irrespective of initial systolic blood pressure (SBP). Left ventricular end diastolic diameter (LVEDD) was the only independent predictor of treatment efficacy. Patients who achieved the primary endpoint (i.e., 'responders') had lower LOS (median 15 [IQR:10-27] vs 19 [IQR:12-35] days, p-value = 0.033) and a lower incidence of all-cause mortality and rehospitalization for HF at 1 and 3 months compared to "non responders" (p-value <0.050). Severe hypotension was observed in 10 (5%) patients, without any adverse clinical consequence. CONCLUSION: SNP is a safe and effective treatment of AHF, particularly in patients with dilated left ventricle. Reduced NT-proBNP levels in response to SNP is associated to shorter LOS and lower risk of 1- and 3-month re-hospitalizations for HF. CLINICAL TRIAL REGISTRATION: http://www. CLINICALTRIALS: gov. Unique identifier: NCT05027360.

Cardiovascular injuries and SARS-COV-2 infection: focus on elderly people.

The novel coronavirus disease (COVID-19) has hit the healthcare system worldwide. The risk of severe infection and mortality increases with advancing age, especially in subjects with comorbidities such as cardiovascular disease, hypertension, diabetes, obesity and cancer. Moreover, cardiovascular complications such as myocardial injury, heart failure and thromboembolism are frequently observed in COVID-19 cases, and several biomarkers (troponin, NTproBNP and D-Dimer) have been identified as prognostic indicators of disease severity and worst outcome. Currently, there is no specific therapy against SARS-CoV-2, although many medications are under investigation. The aim of this review will be to explore the intertwined relationship between COVID-19 disease and the cardiovascular system, focusing on elderly population. The available supportive treatments along with the related concerns in elderly patients, due to their comorbidities and polypharmacotherapy, will be explored.

Covid and Cardiovascular Diseases: Direct and Indirect Damages and Future Perspective.

SARS-CoV-2 infection determines a disease that predominantly affects lungs. However the cytokines storms, determined by the huge immune response to the infection, could affect also other organs and apparatus such as heart and vessels. Beyond the acute inflammation itself also hypercoagulative status has been linked to SARSCoV-2 infection and this surely relates to the increase seen in prevalence of pulmonary embolism and myocardial infarction. A number of cardiac abnormalities and pathologies have been observed, with special attention to cardiac arrhythmias and myocardial involvement. Furthermore, indirect damages determined by the reduction in acute and chronic cardiovascular care, results in a strong mortality and morbidity outcomes in cardiological patients. In this review we will summarise current knowledge on both direct and indirect cardiovascular damages determined by the SARS-CoV-2 pandemia.

Determinants of Functional Improvement After Cardiac Rehabilitation in Acute Coronary Syndrome.

INTRODUCTION: Cardiac rehabilitation (CR) is an effective tool for secondary prevention after acute coronary syndrome (ACS). AIM: Aim of our study was to find the significant determinants of exercise capacity (evaluated with the six-minute walking test-6-MWT) and functional improvement in patients undergoing CR after an ACS. METHODS: The study group included 298 patients (mean age 61.6 ± 10.2 years; males 80.2%) who, after ACS, were enrolled in CR program at Niguarda Hospital in Milan from 2015 to 2018. For all patients, we collected anamnestic, clinical and instrumental cardiological data. All patients performed a 6-MWT at the beginning (6-MWT-1) and at the end (6-MWT-2) of CR program. Δ meters were used to represent functional improvement. RESULTS: Multiple linear regression models were carried out for 6-MWT-1, 6-MWT-2, Δ meters and % Δ meters. Standardized regression coefficients showed that age (ß = - 0.237; p < 0.001), BMI (ß = - 0.116; p = 0.006) and heart rate (ß = - 0.082; p = 0.040) were determinants of exercise capacity (6MWT-1 and 2), whereas age (ß = -.231; p = 0.004), sex (ß = - 0.187; p = 0.008) and BMI (ß = - 0.164; p = 0.022) were determinants of functional improvement (Δ meters). CONCLUSIONS: Our data showed that functional improvement after CR in ACS patients is mainly related to non-cardiological variables. Instead it is related to intrinsic factors, both modifiable (BMI) and non-modifiable (age, sex).

Vascular Aging and Disease of the Large Vessels: Role of Inflammation.

Structural and functional arterial properties commonly impair with aging process. These effects on vasculature could act at many levels from microcirculation to large vessels. Above normal aging process classic cardio-vascular risk factors (hypertension, diabetes mellitus, dyslipidemia, etc.) accelerate the physiological process leading to premature structural and functional alterations that has also been termed early vascular aging. Target organ damage evaluation could be clinically important since these alterations precede by many years' cardiovascular events and so their assessment can predict the onset of more serious and costly events giving the opportunity to prevent CV events by earlier therapeutic intervention. This review will focus on large artery functional properties and particularly on the role of inflammation on the aortic stiffening process.

Effects of extracorporeal cardiopulmonary resuscitation on neurological and cardiac outcome after ischaemic refractory cardiac arrest.

BACKGROUND: Extracorporeal cardiopulmonary resuscitation is increasingly recognised as a rescue therapy for refractory cardiac arrest, nevertheless data are scanty about its effects on neurologic and cardiac outcome. The aim of this study is to compare clinical outcome in patients with cardiac arrest of ischaemic origin (i.e. critical coronary plaque during angiography) and return of spontaneous circulation during conventional cardiopulmonary resuscitation vs refractory cardiac arrest patients needing extracorporeal cardiopulmonary resuscitation. Moreover, we tried to identify predictors of survival after successful cardiopulmonary resuscitation. METHODS: We enrolled 148 patients with ischaemic cardiac arrest admitted to our hospital from 2011-2015. We compared clinical characteristics, cardiac arrest features, neurological and echocardiographic data obtained after return of spontaneous circulation (within 24 h, 15 days and six months). RESULTS: Patients in the extracorporeal cardiopulmonary resuscitation group ( n=63, 43%) were younger (59±9 vs 63±8 year-old, p=0.02) with lower incidence of atherosclerosis risk factors than those with conventional cardiopulmonary resuscitation. In the extracorporeal cardiopulmonary resuscitation group, left ventricular ejection fraction was lower than conventional cardiopulmonary resuscitation at early echocardiography (19±16% vs 37±11 p<0.01). Survivors in both groups showed similar left ventricular ejection fraction 15 days and 4-6 months after cardiac arrest (46±8% vs 49±10, 47±11% vs 45±13%, p not significant for both), despite a major extent and duration of cardiac ischaemia in extracorporeal cardiopulmonary resuscitation patients. At multivariate analysis, the total cardiac arrest time was the only independent predictor of survival. CONCLUSIONS: Extracorporeal cardiopulmonary resuscitation patients are younger and have less comorbidities than conventional cardiopulmonary resuscitation, but they have worse survival and lower early left ventricular ejection fraction. Survivors after extracorporeal cardiopulmonary resuscitation have a neurological outcome and recovery of heart function comparable to subjects with return of spontaneous circulation. Total cardiac arrest time is the only predictor of survival after cardiopulmonary resuscitation in both groups.