bluuebunny/crossref_metadata_2025_split huggingface dataset:
AORTIC REGURGITATION INDEX IDENTIFIES SIGNIFICANT AORTIC REGURGITATION DURING IMPELLA SUPPORT FOR CARDIOGENIC SHOCK
Authors: Baldetti L , Alessandro B , Colombi R , Romagnolo D , Festi M , Peveri B , Frias A , Gramegna M , Sacchi S , Cianfanelli L , Pazzanese V , Ajello S , Scandroglio A 
Published: May 2024

Abstract

Background
Aortic regurgitation (AR) significantly hampers the unloading effect and the antegrade flow enhancement expected from the micro–axial flow pump Impella (Abiomed, Danvers). To date, no dedicated hemodynamic index is available to inform on the severity of AR during Impella support.

Methods
We included 100 patients receiving Impella support for CS with invasive hemodynamic assessment with pulmonary artery catheter (PAC). PAC measures were obtained 48 hours after Impella support initiation. AR grading was performed by either trans–thoracic or trans–esophageal echocardiography in the following strata: 0–none; 1–mild; 2–moderate; 3–moderate–severe; 4–severe. Study cohort was dichotomized according to AR severity≥2+. Several relevant hemodynamic indexes were validated against echocardiographic AR assessment to identify those mostly associated with significant AR (AR severity≥2+), including: AR index [ARI, calculated as (diastolic arterial pressure – pulmonary artery wedge pressure)/systolic arterial pressure, abbreviated in (DAP–PAWP)/SAP], diastolic pulse pressure (DPP, calculated as DAP–PAWP), MAP–adjuster ARI [ARIMAP calculated as (diastolic arterial pressure – pulmonary artery wedge pressure)/mean arterial pressure, abbreviated in (DAP–PAWP)/MAP)].

Results
Significant AR (≥2+) was found in 31% patients. Patients with AR≥2+ had higher values of pulmonary artery wedge pressure (PAWP) after 48 hours from support initiation [15 (12, 21) vs 12 (10, 16) mmHg; p&lt;0.021]. Several invasive hemodynamic indexes differentiated AR≥2+ vs AR&lt;2 patients, including: ARI [0.42 (0.36, 0.51) vs 0.50 (0.44, 0.61); p&lt;0.001], DPP [47 (37, 58) vs 57 (48.00, 68) mmHg; p=0.003] and ARIMAP [0.62 (0.54, 0.70) vs 0.70 (0.64, 0.75); p=0.005] (Figure 1). ARI demonstrated the strongest association and the greatest accuracy in identifying AR≥2+ (area under the curve 0.73; 95%CI: 0.61–0.85; p=0.002). The threshold of ARI 0.39 had excellent specificity (88.0%) and moderate sensitivity (62.9%), Figure 2.

Conclusions
The easy–to–use ARI metric [(DAP–PAWP)/SAP] accurately identifies patients with significant AR during Impella support, at the optimal cutoff of ARI 0.39. This index may be complementary to echocardiography in the assessment of AR during Impella support.
POOR GLYCEMIC CONTROL IS ASSOCIATED WITH ELEVATED LEVELS OF CIRCULATING AMYLOID BETA 1–40 IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION
Authors: Aleksova A , Fluca A , Pani B , Derin A , D‘Errico S , Pierri A , Sinagra G , Janjusevic M 
Published: May 2024

Abstract

Background
Recent evidence correlates Alzheimer‘s disease (AD) and diabetes mellitus (DM), through the involvement of reduced insulin–like growth factor (IGF–1). In acute myocardial infarction (AMI), low IGF–1 levels are correlated with a high risk of mortality and re–infarction. However, the DM–amyloid 1–40 (Aβ1–40) association in patients with coronary artery disease (CAD) remains unexplored.

Aim and Methods
To study Aβ1–40 concentrations based on glycaemic status, identify predictors of its levels, and assess the relationship between this peptide and IGF–1, we collected blood samples from 630 AMI patients on admission. Patients were classified into three groups based on haemoglobin A1c (HbA1c) levels: group 1 (189 patients without DM, HbA1c&lt;39 mmol/mol), group 2 (270 patients with pre–DM, HbA1c 39–48 mmol/mol), and group 3 (171 patients with DM, HbA1c&gt;48 mmol/mol).

Results
The cohort, mostly male (73.5%), had a mean age of 66.33 (11.28) years. Among them, 74.85% presented with ST–elevation myocardial infarction (STEMI), and 25.2% had a history of previous ischemic events. Median Aβ1–40 levels were 85.75 [53.85–128.67] pg/ml. Aβ1–40 positively correlated with age, tumor necrosis factor–alpha, HbA1c, HOMA–IR index, and TyG index. No significant correlation was observed between Aβ1–40 and IGF–1. Aβ1–40 levels increased from group 1 to group 3 (72.42 [48.79–109.26] pg/ml vs. 86.25 [53.4–125.54] pg/ml vs. 103.56 [61.78–46.31] pg/ml, respectively, p&lt;0.001). Although not statistically significant, DM patients tended to have lower IGF–1 values compared to those without DM, while pre–DM patients had the lowest values, suggesting poorer glycaemic control (groups 1, 2, and 3: 575.3 [326.75–864.75] pg/ml vs. 519.25 [294.08–800.48] pg/ml vs. 528.3 [216.2–836.6] pg/ml). At logistic regression analysis, high levels of Aβ1–40 were predicted by older age, worse left ventricular systolic function, higher HOMA–IR index, higher levels of HbA1c, and poorer glomerular filtration rate (GFR), corrected by vitamin D. Conversely, lower levels of IGF–1 were predicted by older age, higher TyG index, higher HbA1c, low vitamin D levels, and compromised GFR.

Conclusions
Given the established link between Aβ1–40 and mortality in AMI patients, improved glycaemic control could reduce the levels of this peptide, counteract its pro–inflammatory properties and improve prognosis. Further investigations are needed to clarify the complex relationship between Aβ1–40 and IGF–1.
ROLE OF RIGHT VENTRICULAR MYOCARDIAL WORK IN THE STRATIFICATION OF PATIENTS AFFECTED BY ADVANCED HEART FAILURE
Authors: Manca P , Rugiano G , Nuzzi V , Mulè M , Carvelli A , Cannata S , Fontana A , Cipriani M 
Published: May 2024

Abstract

Background
Currently adopted echocardiographic parameters for the evaluation of right ventricle (RV) are all loading sensitive and their reliability remains poor. RV myocardial work (RVMW) emerged as an innovative non–invasive diagnostic tool that incorporates strain pressure loops and potentially overcomes the aforementioned limitation. No previous studies assessed the variations of RVMW depending on the hemodynamic setting. Aim of the study: To evaluate the different values of RVMW in patients affected by advanced heart failure (AHF) with and without pulmonary hypertension (PH) at right heart catheterization (RHC) and their variations in patients with baseline PH who subsequently achieved PH reversibility.

Methods and Results
All patients with AHF who underwent RHC and echocardiography within 24h at Istituto Mediterraneo per I Trapianti e Terapie ad Alta Specializzazione (ISMETT) since 01/05/2023 were prospectively enrolled. Patients with baseline documented PH who achieved PH reversibility at RHC underwent a second echcocardiographic assessment under the same hemodynamic conditions. The following components of RVMW were analysed: 1) RV global work index (RVGWI); 2) RV global constructive work (RVGCW); 3) RV global wasted work (RVGWW); 4) RV global work efficiency (RVGWE). Overall, 41 patients were enrolled (16 without PH and 25 with PH). Patients with PH had a higher RVGWI (341±133mmHg% vs 207±104mHg%; p=0.002) and RVGCW (450±153mmHg% vs 294±114mmHg%; p=0.001) compared to those without, while RVGWE did not differ in the two groups (80 ±10mmHg% vs 80 ±15mmHg%; p=0.92). A trend toward a higher RVGWW in patients with PH was observed (89±54mmHg% vs 59 ±66mmHg%; p=0.12). Among the 25 patients with PH, 10 were tested for PH reversibility and this was achieved in 9/10 (90%). RVGWI and RVGCW significantly dropped once PH reversibility was achieved (respectively from 393 ±185mmHg% to 241±67mmHg; p=0.008 and from 435±127mmHg% to 268±67mmHg%; p=0.048). Interestingly, RVGWE remained almost unchanged (from 81±11mmHg% to 79±9mmHg%; p=0.661) while there was a nearly significant trend in RWGWW decrease (from 65±20mmHg% to 41 ±22mmg%; p=0.076).

Conclusions
Patients affected by AHF and PH have significantly higher RVGWI and RWGCW compared to those without. However, RVGWE is similar between the groups and does not vary depending the hemodynamic setting, potentially identifying this parameter as the most reliable one in patients with AHF.
COMBINATORIAL IMMUNE CHECKPOINT BLOCKADE INCREASES MYOCARDIAL SECRETION OF H–FABP, NT–PRO–BNP, NLRP–3 INFLAMMASOME, INTERLEUKIN–1Β AND INTERLEUKIN–6: BIOCHEMICAL IMPLICATIONS IN CARDIO–IMMUNO–ONCOLOGY
Authors: Quagliariello V , Iovine M , Palma G , Bruzzese F , Luciano A , Giacobbe I , Giordano V , Barbato F , Arianna R , Izzo F , Bisceglia I , Maurea F , Canale M , Inno A , Maurea N 
Published: May 2024

Abstract

Background
Immune checkpoint blockade have become an integral part of oncology in recent years. Monoclonal antibodies against CTLA–4 or PD–1 or PDL–1 are the most studied ICIs in randomized clinical trials, however, more recently, an anti–LAG3 monoclonal antibody, Relatlimab, has been approved by FDA for combinatorial treatment with Nivolumab for metastatic melanoma. Moreover, anti PD–L1 blocking agent Atezolizumab is actually under study in association with Ipilimumab as innovative thearpy for metastatic lung cancer. Myocarditis, vasculitis and endothelitis are rarely observed in these patients on monotherapy, however new combination therapies and the use of new targets in immunotherapy could expose patients to more adverse cardiovascular events.

Purpose
In this study, we highlighted the cardiotoxic properties of new Combinatorial immune checkpoint blockade therapies.

Methods
Human cardiomyocytes co–cultured with human peripheral blood lymphocytes (hPBMCs) were exposed to monotherapy and combinatorial ICIs (PD–L1 and CTLA–4 or PD–1 and LAG–3 blocking agents, at 100 nM) for 48 h. After treatments, cardiac cell lysis and secretion of biomarkers of cardiotoxicity (H–FABP, NT–Pro–BNP), NLRP3–inflammasome and Interleukin 1 and 6 were determined through colorimetric and enzymatic assays.

Results
Both combinations of immune checkpoint inhibitors exert more potent cardiotoxic side effects compared to monotherapies against human cardiac cells co–cultured with human lymphocytes. LDH release from cardiac cells was 43% higher in PD–L1/CTLA–4 blocking agents, and 35.7% higher in PD–1/LAG–3 blocking agents compared to monotherapies. NT–Pro–BNP and H–FABP, were also strongly increased in combination therapy with respect to monotherapies. NLRP3, IL–6 and IL–1β levels were also increased by PDL–1/CTLA–4 and PD–1/LAG–3 combined blocking agents compared to untreated cells and monotherapies.

Conclusion
Data of the present study, although in vitro, indicate that combinatorial immune checkpoint blockade, induce a pro– inflammatory phenotype, thus indicating that these therapies should be closely monitored by the multidisciplinary team consisting of oncologists, cardiologists and immunologists.
A RARE COMPLICATION OF LEAD EXTRACTION: THE A–V FISTULA
Authors: Gianmarco A , Cerini M , Calvi E , Falco R , Curnis A 
Published: May 2024

Abstract
We describe the case of a 59 years–old male patient with dilated idiopathic cardiomiopathy (left ventricle ejection fraction 20%), type 2 diabetes mellitus, arterial hypertension, atrial fibrillation, dyslipidemia, chronic kidney disease. The patient underwent the implantation of a bicameral implantable cardioverter defibrillator (ICD) for primary prevention in 2002, with subsequent upgrading to a cardiac resynchronization therapy defibrillator (CRT–D) in January 2021.
The patient came to our Hospital for pocket erosion in October 2021, after an unsuccessful course of antibiotic therapy with clarithromycin. During hospitalization, we found positive blood cultures for Staphylococcus aureus. The ECOTEE showed a 1 cm filamentous mobile mass adhering to the right ventricular lead, compatible with vegetation. Before lead extraction, a venous angiography was performed, showing patency of the anonymous–subclavian–right caval venous axis and total occlusion of the left axis with collateral circulation. At October 20th 2021 transvenous lead extraction (TLE) was performed. The coronary sinus lead was manually removed. During the extraction of the passive fixation dual–coil right ventricular lead (using powered mechanical sheaths and laser sheaths), profuse bleeding started following sheath removal. The angiography showed an arteriovenous fistula between the subclavian vein and the left internal mammary artery. The patient remained hemodynamically stable, with no signs of hemothorax. The lead extraction procedure was halted. The fistula closed spontaneously and embolization was not required. Two computed tomography scans (CT) were performed, revealing spontaneous closure of the fistula without further complication. The patient was continuously monitored at in our cardiac intensive care unit (CICU) without any further complications. On November 23rd a complete lead extraction was performed without complications. On December 18th the patient was implanted with a new CRT–D device from the right side. No complication occurred. The patient was discharged 48h later in good general conditions.
The junction between the left brachiocephalic vein and the superior vena cava is a high–risk region during lead extraction. Venous laceration with hemodynamic collapse is the most severe complication arising in this region, but arteriovenous fistula formation after excimer laser extraction also has been reported as a rare complication.
THE THOUSAND FACES OF LAMINOPATHIES: FROM MUSCLE TO CONDUCTION SYSTEM
Authors: Freschini M , Notaristefano F , Zingarini G , Del Pinto M , Broccatelli A , Castellani C , D‘Ammando M , Riccini C , Coiro S , Grikstaite E , Giuranna M , Pesce F , Russo G , Del Papa M , Catania F , Cavallini C 
Published: May 2024

Abstract

Introduction
LMNA–related cardiomyopathy may manifest itself with a variable degree of left ventricular dysfunction, progressive conduction system disease which mainly involve atrioventricular node, atrial and ventricular tachyarrhythmias.

Clinical Case
Woman, 46 years old, admitted to the emergency department for angina and subsequent syncope while she was driving. In anamnesis evidence of symptomatic bradycardia. A previous 24h ECG–Holter showed persistent junctional rhythm in absence of significant pauses. At ECG evidence of junctional rhythm, HR 42 bpm. At echocardiogram there was preserved biventricular systolic function. Midly increased HS–Tn. For the submitted clinic and symptomatic bradycardia in anamnesis, exercise test was performed which was positive for symptoms (chest oppression) and severe chronotropic incompetence. Subsequent coronary angiography showed normal coronary arteries. Then the patient underwent to head–up tilt test that resulted negative for syncope but positive for symptoms and chronotropic incompetence. On suspicion of conduction system pathology a "bedside" SETE was performed that showed SSS (TRNSc 900 msec – fig.1) and an AV conduction disturbance (BAV I° with a persistent 400 msec long PR after isoprenaline iv – fig.2). To clarify the conduction system pathology genesis, cardiac–MRI was recommended (but declined) and genetic testing was done, which identified a pathogenetic mutation of LMNA–gene. Therefore, the patient underwent to dual–chamber PMK implantation and was included in a course of close follow–up in order to diagnose early myocardial involvement or ventricular tachyarrhythmias whose make necessary an up–grading to ICD.

Discussion
The patient presented an unusual form of LMNA–related cardiomyopathy which clinical presentation included only symptomatic sick sinus syndrome for syncope; the absence of other clinical manifestations made diagnosis complex. This showed how important is sometimes to look for the mechanism behind a common disorder such as bradycardia in young patients with no apparent cardiovascular risk factors, also considering genetic testing in suspected cases.

Conclusion
This is a rare case of LMNA–related cardiomiopathy whose peculiarity is in the pathology of the conduction system, with a greater involvement of sinus node than atrioventricular node. This phenotype showed an unusual clinical presentation with an initial absence of cardiac muscle involvement.
DENGUE MYOCARDITIS IN A DECEASED PATIENT WITH POSTMORTEM POSITIVE DENGUE SEROLOGY
Authors: Petrone A , Minopoli T , Di Mario C 
Published: May 2024

Abstract
Dengue, a viral illness, is spread through the bite of an infected female arthropod and is mostly found in tropical and subtropical areas. The disease can present in various forms: from silent, asymptomatic cases to the more recognizable dengue fever. In its severe manifestations, it can progress to hemorrhagic dengue or the more critical dengue shock syndrome. Additionally, there are uncommon presentations (known as expanded dengue syndrome) that include myocarditis. Here, we present the case of a 50–year–old woman with a medical history of undifferentiated connective tissue disorder and breast carcinoma. Following a trip to Thailand in November 2023, she exhibited a three–day fever. She was admitted emergency department (DEA) on November 11 with syncopal episodes, nausea, vomiting, hypotension, peripheral hypoperfusion, and lactic acidosis. An ECG displayed QS patterns in V1–V3, and echocardiography indicated global hypokinesia (FE: 20%), a 5 mm pericardial effusion, and a non–collapsible IVC of 21 mm. In the suspicion of infective myocarditis, we performed serology testing for several viruses. Upon transfer to the intensive care unit (CICU), she presented with severe metabolic acidosis secondary to cardiogenic shock. Interventions included an intra–aortic balloon pump (IABP) and vasopressor support. Despite these measures, her condition deteriorated, necessitating extracorporeal membrane oxygenation (ECMO) initiation. Although intensive management, her clinical status did not improve. Serial laboratory analyses indicated ongoing multiorgan dysfunction. Unfortunately, the patient‘s condition worsened, culminating in her demise on November 13. The serology analysis results, available after the patient‘s death, revealed an infection caused by dengue virus.
In this case, we highlight a rare presentation of dengue virus infection leading to myocarditis. Despite aggressive therapeutic interventions, including ECMO support, the patient‘s condition deteriorated rapidly, underscoring the severity of dengue myocarditis. The delayed diagnosis emphasizes the importance of increased clinical vigilance in endemic areas, especially when encountering unusual cardiac presentations in patients with recent travel histories to dengue–endemic regions.
OPTIMAL MANAGEMENT OF A PATIENT WITH STEMI COMPLICATED BY REFRACTORY CARDIOGENIC SHOCK THROUGH SUCCESSFUL COLLABORATION BETWEEN SPOKE AND HUB CENTERS
Authors: Valenti G , Monello A , Rusticali G , Losi L , Bolognesi G , Aschieri D 
Published: May 2024

Abstract
Male, 51 y–o. STEMI (5/4/23) → PCIp on proximal LAD without procedural complications. Post–procedure BP 120/30 mmHg, HR 85 bpm. Critical stenoses remained on Circumflex (CFx)–Marginal Obtuse (MO).In the post–procedure observation, the patient experienced two episodes of Ventricular Fibrillation (VF),treated with DC–Shock, and cardiogenic shock,prompting urgent coronary angiography.The decision was made for ultrasound–guided right femoral arterial access and pre–procedural implantation of Impella CP smart–assist device in the left ventricle.During coronary angiography, hyperacute stent thrombosis in the proximal LAD was observed.Manual thrombus aspiration followed by Angiojet Spiroflex thromboaspiration partially improved flow (TIMI 1).Due to evidence of critical stenosis (likely plaque shift),a DES was implanted in the ostio–proximal segment of the LAD.Revascularization was completed on the MO and CFx–MO axis. TIMI 3 flow achieved.Echocardiographic control confirmed proper Impella CP placement,estimated LVEF10%,normal right sections.Impella CP flow 3.9 L/min post–procedure.Due to acute pulmonary edema during the procedure,the patient was sedated,intubated,and transferred to the ICU.On April 6, 2023, refractory cardiogenic shock persisted despite circulatory support with Impella and adrenaline 0.25
CRITICALLY ILL INTENSIVE CARE UNIT PATIENT WITH AN UNUSUAL EKG
Authors: Munaretto L , Della Mattia A , Marson G , Pellis T , Sinagra G , Pavan D 
Published: May 2024

Abstract

Case Description
A 64–year–old male with a history of paroxysmal atrial fibrillation, alcohol abuse, and tonic–clonic epileptic seizures post traumatic brain injury, treated with Valproic acid, was admitted unconscious. In the ICU, a comatose state from crush syndrome–induced oligo–anuric AKI necessitated sedation. Upon sedation discontinuation, a tonic–clonic seizure occurred. Deep sedation was reintroduced for burst suppression using Propofol and Valproic acid, with dosage adjusted based on serial monitoring of Valproate levels, reaching Propofol levels up to 3.6 mg/kg/h extended during the entire duration of hospitalization. Initially hypertensive, there was a worsening of the general condition with hemodynamic instability and the need for incremental dosage of vasopressor support with Norepinephrine and Vasopressin. The subsequent night episodes of non–sustained ventricular tachycardia (TVNS) occurred, followed by in–hospital cardiac arrest due to pulseless ventricular tachycardia (PTV) treated with DC shock with immediate return of spontaneous circulation (ROSC) and a shift to wide QRS complex atrial fibrillation (AF) and repolarization changes compatible with a coved–shaped type pattern (Fig.1). Hemodynamic instability persisted leading to progressive evolution towards refractory hypotension until cardiac arrest (ACC) and subsequent death.

Discussion
The incidence of Propofol Infusion Syndrome (PRIS) is unknown but carries a 18–30% mortality rate. Critical illness, especially neurological injury, may predispose to PRIS triggered by Propofol, dose, and duration dependent (≥4 mg/kg/hr for ≥48 hours). PRIS results from mitochondrial dysfunction, inhibiting Carnitine Palmitoyl Transferase I (CPT I), disrupting fatty acid beta–oxidation, leading to reduced ATP levels, and systemic fatty acid accumulation. Stress exacerbates a metabolic shift to free fatty acids, intensified by inotropic and vasopressor drugs, causing arrhythmias and systemic and myocardic necrosis. PRIS manifests as metabolic acidosis, severe rhabdomyolysis, AKI, and hyperkalemia. Myocardial injury is evident in ECG changes, including a Brugada–like pattern and coved–type ST–segment elevations, arrhythmias, and cardiovascular collapse. Timely recognition is crucial, and management involves Propofol discontinuation, hemodynamic support, hemodialysis, and, in refractory cases, ExtraCorporeal Membrane Oxygenation (ECMO). Prevention is paramount.