The role of sodium-glucose co-transporter 2 inhibitors in myocardial infarction: available evidence and future perspectives.

There is an unmet need for new treatment options for patients with acute myocardial infarction (AMI) as progress in patients' outcomes has plateaued over the past 15 years. Sodium-glucose co-transporter 2 (SGLT2) inhibitors have demonstrated cardio-renal benefits in various disease states, encompassing diabetes mellitus, chronic kidney disease, and heart failure. Experimental studies further support their use in AMI, demonstrating beneficial effects in animal models by reducing infarct size and mitigating adverse cardiac remodelling. Recently, two clinical trials have been published thus paving the way for a new field to explore. This paper briefly outlines the available evidence and future perspectives regarding the use of SGLT2 inhibitors in this clinical scenario.

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.

Advanced heart failure: from definitions to therapeutic options.

Advanced heart failure (AHF) represents an ominous stage of heart failure (HF), where the expected prognosis remains poor regardless of the improvement in medical knowledge. In this review, we summarize the definition, prognosis, physiopathology, and clinical/therapeutic management of the disease, focusing on the fast and timely referral of the patient to the AHF facilities. We provide an insight of the diagnostic and therapeutic 'work up' performed in an Italian AHF hub, implying a deep phenotypical patients characterization in order to evaluate candidacy to the therapeutic gold standards as heart transplantation (HTx) and left ventricular assist device (LVAD).

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.

Intra-aortic Balloon Pump for Acute-on-Chronic Heart Failure Complicated by Cardiogenic Shock.

The intra-aortic balloon pump (IABP) is widely implanted as temporary mechanical circulatory support for cardiogenic shock (CS). However, its use is declining following the results of the IABP-SHOCK II trial, which failed to show a clinical benefit of the IABP in acute coronary syndrome (ACS)-related CS. Acute-on-chronic heart failure has become an increasingly recognized, distinct cause of CS (HF-CS). The pathophysiology of HF-CS differs from that of ACS-CS because it typically represents the progression from a state of congestion (with relatively preserved cardiac output) to a low-output state with hypoperfusion. The IABP is a volume-displacement pump that promotes forward flow from a high-capacitance reservoir to low-capacitance vessels, improving peripheral perfusion and decreasing left ventricular afterload in the setting of high filling pressures. The IABP can improve ventricular-vascular coupling and, therefore, myocardial energetics. Additionally, many patients with HF-CS are candidates for cardiac replacement therapies (left ventricular assist device or heart transplantation) and, therefore, may benefit from a bridge strategy that stabilizes the hemodynamics and end-organ function in preparation for more durable therapies. Notably, the new United Network for Organ Sharing donor heart allocation system has recently prioritized patients on IABP support. This review describes the role of IABP in the treatment of HF-CS. It also briefly discusses new strategies for vascular access as well as fully implantable versions for longer duration of support.

Early intra-aortic balloon pump in acute decompensated heart failure complicated by cardiogenic shock: Rationale and design of the randomized Altshock-2 trial.

BACKGROUND: Cardiogenic shock (CS) is a systemic disorder associated with dismal short-term prognosis. Given its time-dependent nature, mechanical circulatory support may improve survival. Intra-aortic balloon pump (IABP) had gained widespread use because of the easiness to implant and the low rate of complications; however, a randomized trial failed to demonstrate benefit on mortality in the setting of acute myocardial infarction. Acute decompensated heart failure with cardiogenic shock (ADHF-CS) represents a growing resource-intensive scenario with scant data and indications on the best management. However, a few data suggest a potential benefit of IABP in this setting. We present the design of a study aimed at addressing this research gap. METHODS AND DESIGN: The Altshock-2 trial is a prospective, randomized, multicenter, open-label study with blinded adjudicated evaluation of outcomes. Patients with ADHF-CS will be randomized to early IABP implantation or to vasoactive treatments. The primary end point will be 60 days patients' survival or successful bridge to heart replacement therapy. The key secondary end point will be 60-day overall survival; 60-day need for renal replacement therapy; in-hospital maximum inotropic score, maximum duration of inotropic/vasopressor therapy, and maximum sequential organ failure assessment score. Safety end points will be in-hospital occurrence of bleeding events (Bleeding Academic Research Consortium >3), vascular access complications and systemic (noncerebral) embolism. The sample size for the study is 200 patients. IMPLICATIONS: The Altshock-2 trial will provide evidence on whether IABP should be implanted early in ADHF-CS patients to improve their clinical outcomes.

Ten golden rules for reforestation to optimize carbon sequestration, biodiversity recovery and livelihood benefits.

Urgent solutions to global climate change are needed. Ambitious tree-planting initiatives, many already underway, aim to sequester enormous quantities of carbon to partly compensate for anthropogenic CO2 emissions, which are a major cause of rising global temperatures. However, tree planting that is poorly planned and executed could actually increase CO2 emissions and have long-term, deleterious impacts on biodiversity, landscapes and livelihoods. Here, we highlight the main environmental risks of large-scale tree planting and propose 10 golden rules, based on some of the most recent ecological research, to implement forest ecosystem restoration that maximizes rates of both carbon sequestration and biodiversity recovery while improving livelihoods. These are as follows: (1) Protect existing forest first; (2) Work together (involving all stakeholders); (3) Aim to maximize biodiversity recovery to meet multiple goals; (4) Select appropriate areas for restoration; (5) Use natural regeneration wherever possible; (6) Select species to maximize biodiversity; (7) Use resilient plant material (with appropriate genetic variability and provenance); (8) Plan ahead for infrastructure, capacity and seed supply; (9) Learn by doing (using an adaptive management approach); and (10) Make it pay (ensuring the economic sustainability of the project). We focus on the design of long-term strategies to tackle the climate and biodiversity crises and support livelihood needs. We emphasize the role of local communities as sources of indigenous knowledge, and the benefits they could derive from successful reforestation that restores ecosystem functioning and delivers a diverse range of forest products and services. While there is no simple and universal recipe for forest restoration, it is crucial to build upon the currently growing public and private interest in this topic, to ensure interventions provide effective, long-term carbon sinks and maximize benefits for biodiversity and people.

Recurrent stent thrombosis in a patient with acute coronary syndrome and ischemic colitis: between life-threatening thrombosis and life-threatening bleeding.

Complete blood count should always be considered to tailor diagnosis and appropriate management in patients with acute ischemic heart disease. We present a challenging case of recurrent acute coronary syndrome, in the context of very high thrombotic risk due to concomitant inflammatory disease. Although no general guidelines exist for the switch between antiplatelet agents, particularly in the acute setting, in specific cases, the availability of different orally- and i.v.-acting agents and platelet function tests may allow to discriminate among multiple possible mechanisms of drug failure or side effects in the individual patient.

Acute myocardial infarction complicating ischemic stroke: is there room for cangrelor?

Acute myocardial infarction (AMI) complicating ischemic stroke is a well known and undertreated event. A conservative management is not infrequent in these settings, due to the fear of hemorrhagic complications related to antithrombotic therapy. Notably, an invasive approach with a primary percutaneous coronary intervention (PCI) has been shown to be associated with a lower in-hospital mortality in patients with concomitant ischemic stroke and AMI. The optimal antiplatelet regimen in these cases has been not clearly defined, yet. We report two cases of patients with AMI complicating ischemic stroke, successfully treated with cangrelor infusion, which was started during PCI and maintained up to 48 h at bridge therapy dosage (0.75 mcg/kg/min). Both patients underwent successful PCI in the acute phase, and neither ischemic nor hemorrhagic complications occurred during in-hospital stay.

Protracted aortic valve closure during peripheral veno-arterial extracorporeal life support: is intra-aortic balloon pump an effective solution?

BACKGROUND: Left ventricular (LV) afterload increase with protracted aortic valve (AV) closure may represent a complication of veno-arterial extracorporeal membrane oxygenation (V-A ECMO). The aim of the present study was to assess the effects of an intra-aortic balloon pump (IABP) to overcome such a hemodynamic shortcoming in patients submitted to peripheral V-A ECMO. METHODS: Among 184 adult patients who were treated with peripheral V-A ECMO support at Medical University Center Maastricht Hospital between 2007 and 2018, patients submitted to IABP implant for protracted AV closure after V-A ECMO implant were retrospectively identified. All clinical and hemodynamic data, including echocardiographic monitoring, were collected and analyzed. RESULTS: During the study period, 10 subjects (mean age 60 years old, 80% males) underwent IABP implant after peripheral V-A ECMO positioning due to the diagnosis of protracted AV closure and inefficient LV unloading as assessed by echocardiography and an absence of pulsation in the arterial pressure wave. Recovery of blood pressure pulsatility and enhanced LV unloading were observed in 8 patients after IABP placement, with no significant differences in the main hemodynamic parameters, inotropic therapy or in the ECMO flow (p=0.48). The weaning rate in this patient subgroup (mean ECMO duration 8 days), however, was only 10%, with another patient finally transplanted, leading to a 20% survival-to-hospital discharge. CONCLUSION: IABP placement was an effective solution in order to reverse the protracted AV closure and impaired LV unloading observed during peripheral V-A ECMO support. However, the impact on the weaning rate and survival needs further investigations.

Management of cardiogenic shock in acute decompensated chronic heart failure: The ALTSHOCK phase II clinical trial.

Management of acute decompensated heart failure patients presenting with cardiogenic shock (CS) is not straightforward, as few data are available from clinical trials. Stabilization before left ventricle assist device (LVAD) or heart transplantation (HTx) is strongly advocated, as patients undergoing LVAD implant or HTx in critical status have worse outcomes. This was a multicenter phase II study with a Simon 2-stage design, including 24 consecutive patients treated with low-moderate epinephrine doses, whose refractory CS prompted implantation of intra-aortic balloon pump (IABP) which was subsequently upgraded with peripheral venoarterial extracorporeal membrane oxygenation. At admission, patients had severe left ventricular dysfunction and overt CS, 7 patients could be managed only with inotropic therapy, and 16 patients were transitioned to IABP and 1 to IABP and venoarterial extracorporeal membrane oxygenation; the median duration of epinephrine therapy was 7 days (interquartile range 6-15), and the median dose was 0.08 µg/kg/min (interquartile range 0.05-0.1); 21 patients (87.5%) survived at 60 days (primary outcome); among them, 13 (61.9%) underwent LVAD implantation, 2 (9.5%) underwent HTx, and 6 (28.6%) improved on medical treatment, indicating that early and intensive treatment of CS in chronic advanced heart failure patients with low-dose epinephrine and timely short-term mechanical circulatory support leads to satisfactory outcomes.

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.

The VENERE Study: EffectiVenEss of a Rehabilitation Treatment With Nordic Walking in ObEse or OveRweight Diabetic PatiEnts With Cardiovascular Disease.

Background: Nordic walking (NW) has several potential benefits for individuals with cardiovascular (CV) disease, type 2 diabetes, and obesity and/or overweight. NW improves cardiovascular health, including exercise capacity and blood pressure control. NW enhances glycemic control and insulin sensitivity in diabetes, and aids in weight management and body composition improvement. NW offers additional advantages, such as improvement in muscular strength, joint mobility, physical activity levels, and psychological well-being. Methods: This open-label study with 3 arms will aim to evaluate the efficacy, safety, and adherence to exercise prescription in obese and/or overweight diabetic patients with CV complications. The primary objective will be to assess the CV performance of participants after a 6-month and a 12-month follow-up period, following a 3-month NW intervention, compared with standard rehabilitation, and with cardiological counseling (control group) training lasting 3 months. Results: The results of the study will provide valuable insights into the comparative effectiveness of a NW intervention vs standard rehabilitation and control group training in improving CV performance in obese and/or overweight diabetic patients with CV complications. Additionally, safety and adherence data will help inform the feasibility and sustainability of the exercise prescription over an extended period. Conclusions: These findings may have implications for the development of tailored exercise programs for this specific patient population, with the aim of optimizing CV health outcomes. Clinical Trials Registration: NCT05987410.

Contexte: La marche nordique offre plusieurs bienfaits potentiels aux personnes atteintes d'une maladie cardiovasculaire (CV), de diabète de type 2, de surpoids ou d'obésité. Elle améliore la santé cardiovasculaire, notamment l'endurance à l'effort et la régulation de la pression artérielle, en plus de favoriser l'équilibre glycémique et d'accroître la sensibilité à l'insuline chez les personnes diabétiques. Elle facilite également la gestion du poids et l'amélioration de la composition corporelle. Par ailleurs, la marche nordique présente d'autres avantages, comme l'augmentation de la force musculaire, de la mobilité articulaire, du niveau d'activité physique et du bien-être psychologique. Méthodologie: Cette étude ouverte à 3 groupes vise à évaluer l'efficacité, la sécurité et l'observance des exercices prescrits chez des sujets diabétiques obèses ou en surpoids présentant des complications CV. Le principal objectif consistera à évaluer la performance CV des participants au cours d'une période de suivi de 6 et 12 mois après un programme de marche nordique de 3 mois, comparativement à un programme de réadaptation standard et à un programme d'encadrement en soins CV (groupe témoin) de 3 mois. Résultats: Les résultats de l'étude fourniront de précieux renseignements sur l'efficacité d'un programme de marche rapide comparativement à un programme de réadaptation standard et à un programme d'encadrement (groupe témoin) pour améliorer la performance CV chez des sujets diabétiques obèses ou en surpoids présentant des complications CV. Les données relatives à la sécurité et à l'observance permettront également d'évaluer la faisabilité et la viabilité de la prescription d'exercices sur une longue période. Conclusions: Ces résultats pourraient s'avérer utiles dans l'élaboration de programmes d'exercices spécifiquement conçus pour cette population de patients, afin d'optimiser les résultats en santé CV. Numéro d'inscription de l'essai clinique: NCT05987410.

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.