bluuebunny/crossref_metadata_2025 huggingface dataset:
PRIMARY RESULTS FROM APOLLO–B OPEN–LABEL EXTENSION STUDY OF PATISIRAN IN PATIENTS WITH TRANSTHYRETIN CARDIAC AMYLOIDOSIS
Authors: Longhi (on Behalf Of) S , Mauer M , Berk J , Hanna M , Gillmore J , Vellosa–schwartzmann P , Lairez O , Hatano M , Cho H , Van Der Meer P , White M , Yureneva E , Sweetser M , Jay P , Vest J , Fontana M
Published: May 2024

Introduction

The Phase 3, placebo–controlled APOLLO–B study (NCT03997383) is evaluating the efficacy and safety of patisiran in patients (pts) with ATTR cardiac amyloidosis in a 12–month (M) double–blind (DB) period followed by an open–label extension (OLE) period when all pts receive patisiran. During the DB period, patisiran demonstrated statistically significant differences vs placebo in change from baseline (CFB) to M12 in 6–minute walk test (6MWT) and KCCQ–OS, and nominal significance in NT–proBNP and troponin I. Patisiran preserved functional capacity, health status and quality of life (QoL), while placebo was associated with steady worsening. Here, we describe data of the APOLLO–B OLE period.

Methods

Eligible pts (18–85 yrs) had echocardiographic evidence of cardiac amyloidosis and either ATTR amyloid detected in tissue biopsy or diagnosed by nonbiopsy criteria. Medical history of heart failure (HF) due to ATTR amyloidosis with ≥1 prior HF hospitalization or current clinical evidence of HF was required. Pts were randomized 1:1 to patisiran 0.3 mg/kg or placebo every 3 weeks for 12M. All pts completing the 12M DB period were eligible to receive patisiran in the OLE for up to 36M. Assessments in the OLE include CFB in 6MWT, KCCQ–OS, NT–proBNP, and troponin I, among other endpoints.

Results

At baseline, 359 pts (placebo, n=178; patisiran, n=181) received study drug in DB period: median (range) age, 76.0 (41, 85) yrs; male, 89%; wtATTR, 80%; receiving tafamidis, 25%. Of these, 334 (93%) pts entered the OLE. Preliminary data show that CFB to M18 in the patisiran arm were similar to results at M12 for 6MWT, KCCQ–OS, NT–proBNP, and troponin I. In the placebo arm, patisiran initiation was associated with a slower rate of worsening (6MWT) or relative stability (KCCQ–OS, NT–proBNP, troponin I) in each endpoint from M12 to M18 vs DB period. Differences between patisiran and placebo groups at M12 persisted at M18 (Table). Patisiran demonstrated an acceptable safety profile with no new safety concerns.

Conclusions

Preservation of functional capacity, health status and QoL by patisiran has been observed to date to be sustained through 18M of treatment in pts with ATTR cardiac amyloidosis. Placebo–treated pts initiating patisiran at M12 appear to show stabilization in these endpoints at M18. Early treatment initiation is important, as differences across evaluated endpoints persisted between patisiran and placebo arms after placebo–treated pts initiated patisiran.
GENDER DIFFERENCES IN PREDICTORS OF PRIMARY VENTRICULAR FIBRILLATION: RESULTS OF THE PREDESTINATION STUDY
Authors: Peano V , Angelini F , Baldi E , Camporotondo R , Pietrangiolillo F , Cipriani A , Lichelli L , Cerea P , Cacciavillani L , Boccuzzi G , Petitti E , D‘Acunto G , Caputo M , Auricchio A , Torchio M , Gnecchi M , Crotti L , Schwartz P , De Ferrari G , Dusi V
Published: May 2024

Introduction

Few studies evaluated risk factors for ventricular fibrillation (VF) before reperfusion during a first acute myocardial infarction (AMI). Important parameters such as blood potassium levels (K+), blood pressure (BP) and heart rate (HR) at presentation were not always considered. Furthermore, the potential for gender differences has never been investigated.

Objectives

To evaluate the presence of gender differences in predictors of primary VF development in the PREDESTINATION (PRimary vEntricular fibrillation and suDden dEath during a firST myocardial iNfArcTION) population.

Patients and Methods

PREDESTINATION is a prospective, multicenter, case–control study (matching 1:2 for sex and age) enrolling patients between 18 and 80 years of age with a first AMI, complicated (cases) or not (controls) by primary VF.

Results

1622 patients were analyzed (average 59 years, 83% male, 35% cases). Comparing male vs female cases, women were older, with lower BMI and lower potassium levels at presentation (3.6 ±0.6 vs 3.8±0.6 mEq/L, p=0.02); they also had a greater prevalence of first degree family history of sudden death (SD), of depression, of physical inactivity, of higher (3–4) TIMI flow in the culprit artery before reperfusion and of VF as first symptom of the AMI (27% vs 15%, p=0.03). The multivariable analysis (logistic regression) performed on the entire population and then only in males identified 9 independent predictors of primary VF, of which 7 risk factors (atrial fibrillation, first K+ ≤3.5 mEq/L, HR ≥90 bpm, family history of SD, anterior site of the AMI, known hypercholesterolemia, physical inactivity) and two protective factors (known diabetes mellitus and higher systolic BP at presentation). Only 2 factors were confirmed in women: first K+≤3.5 (OR 3, 95% CI 1.6–5.8, p<0.001) and systolic BP (OR 0.98 per mmHg, 95% CI 0.97–0.99, p=0.02); depression showed a trend for significance. The dose–response correlation coefficient between kaliemia and the probability of primary VF was much more negative in women than in man (figure).

Conclusions

The current analysis identified gender differences between cases of primary VF. Only 2 independent predictors of primary VF were found in the female population, with a strong significance of hypokalemia and a much stronger dose–response relationship than in males. These findings aim to start to fill the gap in knowledge of gender specific risk factors for primary VF.
DIAGNOSTIC CRITERIA FOR NON–DILATED LEFT VENTRICULAR CARDIOMYOPATHY WITH PROGNOSTIC SIGNIFICANCE
Authors: Aimo A , Gueli I , Alderotti B , Todiere G , Grigoratos C , Modena M , Botto N , Vittorini S , Vergaro G , Giannoni A , Castiglione V , Clemente A , De Gori C , Passino C , Cademartiri F , Aquaro G , Emdin M , Barison A
Published: May 2024

Background

Non–dilated left ventricular cardiomyopathy (NDLVC) is a novel diagnostic entity defined as non–ischemic LV scarring or fatty replacement regardless of the presence of global or regional wall motion abnormalities, or isolated global LV hypokinesia without scarring. While the absence of LV dilation and systolic dysfunction are implicit, no cut–offs were proposed.

Methods

All patients undergoing cardiac magnetic resonance (CMR) examination at a tertiary referral center from 2012 to 2022 and meeting the definition of NDLVC were evaluated. The primary endpoint was a composite of cardiac death, sustained ventricular tachycardia (VT) or ventricular fibrillation, appropriate defibrillator intervention; the secondary endpoint included also non–sustained VT.

Results

The cohort included 262 patients, with 176 men (67%) and a median age of 55 years (interquartile range 44–64 years). Patients without moderate (n=243, 93%) or severe LV dilation (n=249, 95%) had a longer survival free from both endpoints. The 50% LVEF threshold identified patients with different outcomes, whereas the 55% and 60% cut–offs did not. LVEF ≥50% and no severe LV dilation predicted a better outcome independent of percent LGE in the LV, the number of LV segments with LGE, LV fibro–fatty replacement, or right ventricular involvement. LVEF ≥50% and no severe LV dilation retained an independent prognostic value even in patients with LV LGE (80% of the whole cohort).

Conclusions

Excluding severe LV dilation (LVEDVi >129 mL/m2 in men and >116 mL/m2 in women) and LV dysfunction (LVEF <50%) could enhance the prognostic utility of the NDLVC definition.
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

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<0.021]. Several invasive hemodynamic indexes differentiated AR≥2+ vs AR<2 patients, including: ARI [0.42 (0.36, 0.51) vs 0.50 (0.44, 0.61); p<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

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<39 mmol/mol), group 2 (270 patients with pre–DM, HbA1c 39–48 mmol/mol), and group 3 (171 patients with DM, HbA1c>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<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

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

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

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

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

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

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

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.
TRANSIENT VENTRICULAR ARRHYTHMIAS DURING EXERCISE TEST TRIGGERED BY IRON DEFICIENCY ANAEMIA
Authors: Di Virgilio E , Basile P , Forastefano B , Totaro M , Falagario A , Carella M , Falco G , Ciccone M , Cicolini G , Guaricci A
Published: May 2024

Introduction

The onset of ventricular arrhythmias (VAs) during an exercise test (ET) is a common finding in asymptomatic middle–aged individuals. However, their clinical significance is uncertain, especially in absence of myocardial ischaemia or structural heart disease (SHD). VAs from the right ventricular outflow tract (RVOT) are the most common in a structurally normal heart and they can be exacerbated by several triggers.

Case Report

An asymptomatic 53–year–old woman without cardiovascular risk factors and good functional status was referred for a cardiologic evaluation before uterine polypectomy. Laboratory exams showed moderate iron deficiency anaemia (IDA), due to uterine chronic blood loss, treated with iron sulfate and folic acid. The ECG pointed out a QS aspect in leads V1–V3. A preserved regional and global systolic function and a mild concentric hypertrophy of the left ventricle (LV) were observed at the transthoracic echocardiogram. The ET with echocardiography, according to the Bruce protocol, was interrupted due to physical exhaustion, reaching the theoretical maximum heart rate, in absence of ischaemic repolarization alterations and a normal segmental wall kinetic with a preserved contractile reserve of the LV. However, after the first minute of recovery, multiple monomorphic non–sustained ventricular tachycardias (NSVT) originating from the RVOT were observed. In the following minutes their frequency reduced with the onset of isolated premature ventricular contractions (PVCs), terminating with a single polymorphic NSVT of 3 beats. During both exercise and recovery, were observed occasional runs of atrial tachycardia. A significant coronary artery disease was ruled out by coronary angiography (CA). Subsequently, a contrast–enhanced Cardiac Magnetic Resonance revealed a mid–wall late gadolinium enhancement in the basal segment of the inferior wall. The patient underwent uterine polypectomy without complications, restoring haemoglobin (Hb) values during the following months. Subsequently, Holter ECG and ET did not revealed VAs. Thus, the patient resumed moderate aerobic physical activity without any adverse arrhythmic events.

Discussion

The RVOT VAs are commonly idiopathic and triggered by several factors. CA and CMR may provide additional information during the diagnostic algorithm. IDA may promote VAs after exercise in predisposed patients without SHD, requiring a prompt restoration of Hb and iron levels.
VENTRICULAR ARRHYTHMIA EVENTS IN PATIENTS WITH IMPLANTABLE CARDIOVERTER–DEFIBRILLATOR BEFORE AND AFTER THE TREATMENT WITH SODIUM–GLUCOSE CO–TRANSPORTER 2 INHIBITORS
Authors: Vecchi A , Giannotti Santoro M , Pasanisi E , Talini E , Lapira F , Puccioni E , Menegato A
Published: May 2024

Background

Role of sodium–glucose co–transporter 2 inhibitors (SGLT2i) in the treatment of chronic heart failure is increasing. However, some case series described appropriate shocks from ICD in patients following the initiations of SGLT2i and a larger analysis is not present in the literature.

Methods

The aim of this study is to investigate the rate of ventricular arrhythmic burden and appropriate anti–tachycardia therapy from ICD before and after the initiation of SGLT2i therapy. A retrospective single–center analysis was performed, comparing ventricular events from home monitoring reports 3 months before and 3 months after SGLT2i therapy treatment.

Results

Seventeen patients were enrolled in the study. The baseline clinical e therapy characteristics of patients are shown in the table. Ten patients (59%) had mono cameral or dual cameral ICD and 7 had implantable cardiac resynchronization therapy (CRT) defibrillators.During the 3 months before SGLT2i treatment, 4/17 patients had nun–sustained ventricular tachycardia (NSVT) vs 8/17 (23% vs 47%, P value 0.23) patients with NSTV after the treatment. Seven patients (41%) had an increase in the rate of NSVT events (with a patient with 28 NSVT after treatment vs 0 before treatment). No patients had anti–tachycardia therapy in the 3 months before treatment, while during the 3 months after the SGLT2i treatment, 1 patient had a ventricular tachycardia treated with anti–tachycardia pacing (110 days after the beginning of the treatment) and 2 patients had a ventricular tachycardia treated with appropriate shock (2 and 25 days after the beginning of SGLT2i treatment).

Conclusion

This small retrospective analysis showed an increase in ventricular arrhythmic events in the 3 months after the initiation of SGLT2i. These data prospect the need for a larger analysis for a stronger statistical correlation.
SYNCOPE OF UNCERTAIN NATURE
Authors: Perfetti S , Greco G , Mandunzio D , Citarelli G , Zaccaro S , Pedio E , Caldarola P
Published: May 2024

A 59 year–old male without relevant past medical history presented to our hospital because of an episode of chest pain followed by a syncope during driving, completely resolved once arrived at the ED. He complained of other chest pain episodes in the last past weeks. During hospitalization he has been asympthomatic and physical examination was unremarkable. ECG showed q waves in inferior leads and a Brugada pattern type 2. Cardiac enzymes were normal. Echocardiography showed akinesis of medio–basal inferior wall with slight reduction of EF (50%). Coronary angiography demonstrated a total occlusion of RCA and a 50% stenosis of LCA, treated with PCI and DES implantation. A following ECG revealed a spontaneous Brugada pattern type 1. This element let us reevaluate his past syncope nature. Electrophysiologists were consulted and the patient was deemed to be at low risk for sudden cardiac death. No ICD was indicated and a loop recorder was implanted. He underwent genetic test for Brugada syndrome, still pending at the moment. Brugada syndrome is a congenital electrical disorder associated with a high risk of ventricular arrhythmias and sudden cardiac death. Cardiac sodium channel gene SCN5A mutations represent the most frequent genetic variant, also associated with other cardiac disorders, but other potentially pathogenic variants have been reported. Brugada syndrome is diagnosed in patients with a spontaneous type 1 ECG pattern, characterized by J point elevation of > 2 mV with coved ST elevation and T wave inversion in at least one right precordial ECG lead, V1 or V2, positioned in the second, third or fourth intercostal spaces. This is an unusual case of incidental evidence of Brugada pattern type 1 after coronary revascularization. According to latest guidelines, our patient, due to his unexplained syncope nature, was deemed to loop recorder implantation (IIA Class). Actually his syncope could be due to the total occlusion of RCA or an arrythmia correlated to Brugada syndrome. Only loop recorder monitoring and genetic test results will help us in our patient’s management and to consider the possibility of ICD implantation.
CARDIONEUROABLATION IN A YOUNG PATIENT WITH A THIRD–DEGREE ATRIO–VENTRICULAR BLOCK
Authors: Valenti N , Di Monaco A , Romanazzi I , Vitulano N , Quadrini F , Troisi F , Grimaldi M
Published: May 2024

Clinical Case

The clinical case focuses on a 19–year–old women with a non–congenital third degree atrio–ventricular block (AVB), symptomatic for dyspnoea for mild efforts, with structurally normal heart, no other comorbidities and no medications taken. Both the exercise stress test and the atropine test documented a sinus tachycardia at 190 bpm with a 2:1 AVB and a narrow QRS, and 1:1 AV conduction until a sinus rate of 90 bpm. She underwent CNA procedure, targeted the inferior paraseptal ganglionated plexus (IPSGP), both the right and left atrial sides, with gradual improvement of impulse conduction. After the procedure, we observed a persistence of only first degree AVB (PQ interval 260 msec) and a complete regression of symptoms, persistent at 6–month follow–up.

Conclusions

A strategy of modulation of ganglionated plexi by endocardial ablation is conceivable for the treatment of pathological conditions due to parasympathetic hyperactivity. Patients with functional atrioventricular block (FAVB), even without organic damage to the conduction system, often present disabling symptoms with a significant reduction in quality of life. Treatment with drugs and/or pacemakers has given poor results; pacemaker implantation is not well accepted and is accompanied by significant psychological discomfort, as well as carrying a risk of infection and long–term ventricular desynchronization. The absence of an organic disease as well as a presumed benign course of the disease make the decision more difficult. Current guidelines recommend the implantation of a definitive pacemaker in patients with paroxysmal or permanent third degree AVB, regardless of symptoms. Although not yet included in current guidelines, the CNA procedure could be used in the future to treat AV node dysfunctions in young subjects with a dominant functional component.
DIFFERENT INTRAOPERATIVE TRANSIT TIME FLOW MEASUREMENT DOES NOT AFFECT EARLY OUTCOME IN FEMALE AND MALE GENDER AFTER CABG
Authors: Nardi P , Labriola V , Calogera P , Altieri C , Buioni D , Scognamiglio M , Salvati A , Ruvolo G
Published: May 2024

Background

Intraoperative transit time flow measurement (TTFM) of left internal thoracic (L–ITA) and saphenous vein (SV) grafts (SVG) can improve graft patency and, consequently, clinical outcome in patients undergoing coronary artery bypass grafting (CABG). We have investigate if there were differences in female and male gender on TTFM –flow (mL/min) and pulsatility index (PI)– measured at the weaning form cardio–pulmonary bypass after CABG and early results. We started to use TTFM on September 2022.

Methods

Between September 2022 and September 2023, TTFM was performed in 101 patients (21 females, 80 males) undergoing CABG, isolated (n=75) or in association with other procedures (n=26).

Results

No significant differences were observed in age (66.2±11 vs 66.9±9 years; P=0.81), Euroscore–2 (4.2±3 vs 3.8±3; P=0.24), left ventricular ejection fraction (54±8 vs 52±9; P=0.08). Associated procedures were more frequently performed in females (47.6% vs 20%; P<0.05). Left anterior descending artery (1.4±0.2 vs 1.6±0.2 mm; P=0.001), first obtuse marginal branch (1.3±0.2 vs 1.5±0.3 mm; P<0.05), right posterior artery (1.2±0.2 vs 1.4±0.3 mm; P<0.05) diameters were smaller in females. TTFM flow of L–ITA or SV grafts on the left anterior descending artery (28±9 vs 38±18 mL/min; P<0.05), first obtuse marginal branch (27±15 vs 42±28 mL/min; P<0.05), right posterior descending artery (29±11 vs 36±19 mL/min; P>0.5) was lower in females. No PI values differences were observed in the coronary arteries territories (3.9±0.8 vs 3.7±0.9; 3.8±0.5 vs 3.9±1; 3.5±0.9 vs 3.3±1) (P>0.5). There were no operative mortality and major cardio–vascular complications; postoperative respiratory failure occurred in three males.

Conclusions

As compared with their male counterpart, the lower values of L–ITA and SV grafts flow observed in females can be related to the smaller diameter of coronary arteries rather than to their vascular resistance. However, the reduced graft flow observed in female gender does not affect early outcomes.
RIGHT AXILLARY MINI–THORACOTOMY FOR MINIMALLY INVASIVE MITRAL SURGERY: A 5–YEAR SINGLE–CENTER EXPERIENCE
Authors: Greco C , Mangia F , Zaccaria S , Casali G , Paraninfi A , Nicolardi S
Published: May 2024

Objectives

To report early– and long–term outcomes of patients undergoing minimally invasive mitral surgery (MIMS) through right axillary mini–thoracotomy (RAMT) over a 5–year period.

Methods

From July 2016 to December 2021, a total of 172 patients underwent MIMS through RAMT at “Vito Fazzi” Hospital.

Results

Mitral valve diseases were degenerative (62.8%), rheumatic (13.9%), functional (13.4%), Barlow (5.2%), and endocarditis (4.7%) mitral disease. Mitral valve repair was performed in 142 patients (82.5%) and 30 (17.5%) had mitral replacement. Repair techniques included neochordae implantation (53.5%), isolated annuloplasty (28.9%), leaflet resection (11.3%), sliding plasty (4.9%) and Alfieri procedure (0.7%). Furthermore, in 29 patients (16,8%) concomitant procedures were associated. All cardiac procedures were performed under direct vision and without using thoracoscopes. Mean length of skin incision under the armpit (fig 1) was 5.7 ± 1.3 cm. Of note, conversion to median sternotomy occurred only in 2 (1.2%) cases. Stroke incidence was 0.9% and in–hospital mortality 0.5%. Overall survival and freedom from reoperation at 5 years were 91.5% and 99.1%, respectively (fig 2).

Conclusions

RAMT access for MIMS is a safe and reproducible approach associated with low mortality and morbidity, the possibility to perform complex mitral surgery under direct vision, high rate of mitral valve repair, and excellent late results. Importantly, limited skin incision under the armpit provided excellent aesthetic results.
MECHANICAL HEART VALVES AND ORAL ANTICOAGULATION: A SURVEY OF THE ITALIAN SOCIETY OF CARDIAC SURGERY
Authors: Santarpino G , Di Mauro M , De Feo M , Menicanti L , Paparella D , Mastroroberto P , Speziale G , Pollari F , Mauro M , Torella M , Coscioni E , Barili F , Cardetta F , Parolari A
Published: May 2024

In the latest European guidelines for the management of valvular heart disease, mechanical valve prostheses maintain a strategic role, particularly for certain patient subsets and age groups. Despite the high number of devices implanted in clinical practice, particularly in non–European and North American regions, current scientific literature and debate seem to suggest a limited use of mechanical heart valves. The cardiac surgery community seems to be highly interested in biological and transcatheter valve prostheses but less interested in mechanical heart valves, including possible strategies for self–management of anticoagulation therapy. In this respect, the Italian Society of Cardiac Surgery (SICCH), in particular the Italian Group of Research for Outcome in Cardiac Surgery (GIROC), has promoted a survey among its members to stimulate the interest in this topic and express their opinion on this issue that, due to the prevalence of the affected population and the new treatment options for improving patient’s quality of life, should be more appraised and debated in the cardiac surgery community. The recorded results, obtained on the answers to 111 questionnaires, seem to divide the specialists into "pros" and "contras" on a useful tool for the entire cardiac surgery community. For this reason, SICCH proposes in conclusion to declare its unified and institutional opinion on this topic.
HAEMODYNAMIC FORCES ANALYSIS IN PATIENTS WITH PARAVALVULAR REGURGITATION AFTER TAVR: A PROPENSITY–SCORE MATCHED RETROSPECTIVE STUDY
Authors: Scudeler L , Alessandro V , Miccoli D , Mascaretti D , Airale L , De Ferrari G , Alunni G
Published: May 2024

Background

Paravalvular regurgitation (PVR) after TAVR is a frequent complication, but its direct quantification and grading with conventional echocardiography is still limited by several factors. LV remodeling has still a role in the evaluation of PVR and its pathophysiology. Hemodynamic forces (HDF) analysis has emerged as a new tool to evaluate LV cardiac function in addiction to ejection fraction (EF) and global longitudinal strain (GLS). Aim of the study: To evaluate the difference in pre– and post–TAVR HDF in patients with preserved EF, using a propensity–matched analysis comparing patients with more than mild PVR to patients with mild or no PVR. Medis Ultrasound Suite software has been used for the estimation of HDF in order to differentiate earlier LV function modification between the two groups and its relationship with clinical outcomes.

Material and Methods

25 patients from two European high–volume centers with more than mild PVR and coupled pre– and post–TAVR echocardiographic evaluation available for HDF analysis were retrospectively included, paired 1:2 with 50 patients, matched for characteristics that may influence HDF analysis and with mild or none PVR. Clinical outcome was a composite of heart failure (HF) valve–related hospitalization and worsening HF at 1 year.

Results

No significative differences were found at baseline clinical and echocardiography evaluation between the two groups: median age was 83 years, mean LVEF was 61%. Post–procedural echocardiographic evaluation was performed at 34 days after TAVR (IQR 5 – 50). Patients with significant PVR had higher LV end–diastolic volume (p = 0.044), lower endocardial GLS (p = 0.07) and lower LV diastolic apex–base longitudinal forces (LVD Apex–Base) (p = 0.045). The difference between LVD Apex–base pre– and post–TAVR was significantly lower in the significant PVR group (–0.8 vs 0.3%, p = 0.021). At Cox regression analysis, LV longitudinal force (LVLF) Ratio turned out to be predictive of clinical outcome (HR 1.11, 95CI 1.02 – 1.20, p = 0.017) in the overall population.

Conclusion

HDF analysis seems to be superior to conventional echocardiographic values of left ventricular cardiac function to detect the early effects of LV volume overload in patients with significant PVR after TAVR. Furthermore, in the overall population, LVLF Ratio predicts clinical outcomes and could be a promising new index to better evaluate the development of heart failure in patients with AS undergoing TAVR.