bluuebunny/crossref_metadata_2025 huggingface dataset:
CARDIONEUROABLATION: CASE SERIES
Authors: Valenti N , Di Monaco A , Romanazzi I , Quadrini F , Vitulano N , Troisi F , Grimaldi M
Published: May 2024

The aim of our prospective

Non–randomized study was to evaluate the efficacy and safety of Cardioneuroablation (CNA) in patients with recurrent cardioinhibitory vaso–vagal syncope (VVS) or functional bradyarrhythmias. From September 2022 to June 2023, a total of 10 ablation procedures were performed on 10 patients who met the inclusion criteria (30% female, mean age 51.9 years, range 19–81 years). In 5 cases the CNA was guided by HFS with documentation of vagal response, while in the other 5 cases it was performed with an anatomical approach. In 3 cases the ablation was performed only on the GPs of the right atrium, while in the remaining 70% of cases biatrial lesions were performed.

As regards the acute endpoints, we observed an increase in sinus heart, a shortening of the PQ interval, a reduction in TRNSc, a shortening of the AH interval and an increase in PW. During follow–up, a single patient, due to persistence of symptoms and bradyarrhythmic disorder, underwent definitive pacemaker implantation. No other patient had a recurrence of syncope and all reported being persistently asymptomatic. As regards the secondary endpoints, we highlighted a persistence of the increase in the minimum and average heart rate, a shortening of the PQ interval, a reduction in time and frequency domain parameters in the HRV analysis on the Holter ECG performed at follow–up. An increasing trend was also highlighted for maximum heart rate, although not significant. There were no significant changes in the QTc interval and no patient developed arrhythmic episodes.

Discussion

Cardioneuroablation is a relatively recent and still developing technique that aims to promote persistent cardiac vagal denervation through endocardial ablation of parasympathetic ganglia. In our prospective study of patients without structural heart disease suffering from recurrent cardioinhibitory VVS or symptomatic functional bradyarrhythmias, CNA was effective in reducing the syncopal burden and other symptoms complained of by patients before the procedure, and safety (only one case of pericardial effusion that did not require any therapy; low rate of exposure to ionizing radiation; not any increase in arrhythmic risk related to a prevalent sympathetic activity; no patient reported discomfort in feeling an average higher heart rate), with a notable improvement in the quality of life.
REPOLARIZATION GRADIENT CAUSES LOCAL DEPOLARIZATION ABNORMALITIES IN BRUGADA SYNDROME
Authors: Garibaldi S , Tirabasso D , Latrofa S , Hartwig V , Nesti M , Panchetti L , Mirizzi G , Startari U , Morelli M , Passino C , Emdin M , Piacenti M , Giannoni A , Rossi A
Published: May 2024

Background

Transmural voltage gradient in RVOT induces ECG–phenotype in Brugada syndrome(BrS). Moreover,RVOT depolarization abnormalities have been described as contributors to BrS phenotype and arrhythmogenesis.

Purpose

To investigate the effect of ajmaline administration on J–elevation of RVOT unipolar signals in BrS patients. Moreover,we wanted to assess whether ajmaline–induced unipolar J–point elevation variations induced local depolarization abnormalities.

Methods

21 BrS patients with spontaneous type–1 ECG pattern were enrolled. Due to the absence of BrS ECG pattern at the study, patients underwent RV endocardial mapping with the CARTO3 system, before (PRE) and after (POST) ajmaline administration. The data were exported from CARTO and converted into Matlab format using OpenEP. J–elevation for each point was calculated as the amplitude of the unipolar signal at J wave with respect to baseline. Activation time (AT) of each point was defined as the difference between local depolarization (minimum dV/dt of the unipolar signal) and surface ECG depolarization(time of the minimum signal on V2). With an automatic algorithm, corresponding PRE and POST points were selected. The difference between POST and PRE of each parameter was calculated to obtain the differential values delta–J and delta–AT. Differential values were then interpolated on the mesh of each subject to obtain 3D maps. The deltaJ map was divided into four intervals based on quartiles. We then selected a ROI ‘IN‘ on a region with the greatest deltaJ variation, and a second ROI ‘OUT‘ on the zone of lowest variation. The same ROIs were applied to the deltaAT map. The mean value of the respective differential parameters was extracted in each ROI.

Results

Greatest delta–J values were found in the RVOT/anterior wall. delta–J in the ROI ‘IN‘ was greater than in the ROI ‘OUT‘ (1.68 [1.11–2.28] vs 0.56 [0.38–0.93] mV, p<0.001). delta–AT in the ROI ‘IN’ was greater than in the ROI ‘OUT’ (27.96 [20.39–44.89] vs 7.62 [4.24–16.69] ms, p<0.001). A good correlation was found between delta–J and delta–AT, considering the data for the two ROIs together (Spearman R coefficient=0.71, p<0.001). Conclusions: Our study shows that the repolarization gradient, evaluated by localized delta–J increase in RVOT, justifies BrS ECG phenotype and local depolarization abnormalities. A strong correlation was present in these RVOT areas between J–elevation variation and slow conducting zones.
LONG–TERM OUTCOMES FOLLOWING TRANSVENOUS LEAD EXTRACTION: DATA FROM A TERTIARY REFERRAL CENTER
Authors: Calvi E , Arabia G , Cerini M , Falco R , Bellicini M , Curnis A
Published: May 2024

Transvenous lead extraction (TLE) has been established as a procedure with a satisfactory safety and efficacy profile in both intraoperative and short–term postoperative setting. However, data on long–term outcomes are limited.

The purpose of this study was to evaluate long–term outcomes and prognostic factors in patients who underwent TLE. Patients with a cardiac implantable electronic device (CIED) who underwent TLE between 2014 and 2016 were included in a retrospective analysis. The primary outcome was a composite of all–cause mortality and repeated TLE procedure, stratified based on the indication for CIED infection or reasons other than infection. Secondary outcomes included the individual components of the primary outcome. A total of 191 patients were included in the analysis, with 50% (n=96) undergoing TLE due to CIED–related infection. Complete procedural success was achieved in 189 patients (99%), with no major acute complications.

After a median follow–up of 6.5 years, the presence of infection at the time of TLE was associated with significantly lower event–free survival (67% vs. 83% in the non–infection group, adjusted hazard ratio [aHR] 1.97, 95% confidence interval [CI] 1.02–3.81, p = 0.04). The all–cause mortality rate was higher in the infected group (30% vs. 10%, p < 0.01). Conversely, the rate of repeated TLE did not differ significantly between the two groups (4% vs. 7%, p = 0.62). Among patients undergoing TLE due to infection, the presence of vegetations on leads or valvular apparatus (aHR 2.56; 95%CI 1.17–5.63, p = 0.02) and positive blood cultures (aHR 2.64; 95%CI 1.04–6.70, p = 0.04) were independently correlated with the primary outcome. Subgroup analysis based on gender revealed that female patients had a higher risk of minor intraprocedural and periprocedural complications (17.2% vs. 2.5%, p < 0.01), but no differences in long–term outcomes. Patients undergoing TLE for CIED–related infection demonstrate a high risk of long–term mortality. Systemic infection, indicated by vegetations and positive blood cultures, is associated with a worse prognosis, independent of the procedural complexity and success. Female patients exhibit an increased risk of minor intraprocedural and periprocedural complications.
FEASIBILITY AND MICRO–COSTING ANALYSIS OF A SAME–DAY DISCHARGE PROTOCOL FOR CATHETER ABLATION OF ATRIAL FIBRILLATION: A PILOT STUDY USING CRYOBALLOON ABLATION
Authors: Sgarito G , Conti S
Published: May 2024

Background

Catheter ablation (CA) is a well–established treatment for atrial fibrillation (AF). Due to the ageing population, increasing prevalence of AF risk factors, improving detection methods for AF, and broadening indications for ablation, CA for AF is the most common resource–consuming ablation procedure, strongly impacting waiting list times and healthcare costs. The combination of these factors and limited bed availability led to development of a same–day discharge (SDD) protocol with acceptable efficacy and safety outcomes. Due to the COVID–19 outbreak, we started the SDD pilot project to reduce patient hospital stays and time spent on the waiting list.

Objective

We aimed to assess our day–case service‘s overall effectiveness and safety. Furthermore, we aimed to evaluate the health–economic impact of a routine adoption of day–case AF ablation.

Methods

Patients with symptomatic and drug–refractory PAF or early Pe–AF scheduled for de–novo ablation were included in the study protocol if they had the following clinical and non–clinical criteria for an SDD protocol: 1–Clinical factors: a) stable anticoagulation, b) No history of bleeding, c) No systolic heart failure, d) No history of pulmonary disease, e) No interventional procedure within 60 days, f) BMI <35, g) CHA DS –VASc ≤3, h) non–severely dilated left atrium, i) age <65 years old; 2–Non–clinical factors: a) home residence within 50 km, or if more, with an emergency department (ER) reachable within 30 minutes, b) home assistance to the patients the same day of the procedure.

Results

Fifty–two patients were included in the SDD protocol and underwent PVI with the Arctic Front Advance cryoballoon ablation catheter. Patients were admitted to a cardiac short–stay unit on the day of ablation at 7 am. SDD procedures were carried out in conscious sedation without the presence of an anesthesiologist. After ablation, the patient was admitted to the recovery area for at least 6 hours. Postprocedural echocardiography was performed to rule out pericardial effusion. The bed occupancy cost reduction was 493€/procedure with the SDD protocol (2415€ vs. 1921€). No minor or major complications were observed in the SDD protocol.

Conclusion

The adoption of an optimized path would lead to a reduction in the length of hospital stays, optimization of beds, a reduction in waiting lists, an accelerating patient access to care and a reduction in patient management costs by optimizing the consumption of resources.
RELATIVE SURVIVAL AFTER ADULT CARDIAC SURGERY IN ITALY
Authors: Rosato S , Biancari F , D‘Errigo P , Manno V , Cuomo M , Duranti G , Baglio G
Published: May 2024

Background

Although adult cardiac surgery maintains an important role in the management of severe heart diseases also in the current era of constant technological advancements of transcatheter procedures, data on life expectancy of cardiac surgery patients is scarce.in particular, there is a lack of data on relative survival of frequently performed isolated cardiac surgery procedures.

In this study we estimated the observed 10–year survival in cardiac surgery patients, the expected survival from age– and sex–adjusted general population and the relative survival from a nationwide administrative registry.

Methods

This is an observational study from a nationwide administrative registry including all adult patients who underwent cardiac surgery from January 2010 to December 2020, in Italy.

Patients died within 90 days from the procedure have been excluded from this analysis. Age and sex adjusted relative survival of 90–day survivors was estimated using the Hakulinen and Tenkkanen’s method. A relative survival of 1.0 implies that the observed survival is the same as the expected survival in the age– and sex– matched general population.

Results

Data on 394445 consecutive adult patients survived 90 days after cardiac surgery have been analyzed. 10–year survival was 58.0% (95%CI 57.8–58.3), the expected survival was 70.1%, and the relative survival was 0.83 (95%CI 0.82–0.83). Patients who underwent surgical repair of the mitral valve and aortic valve had relative survival of 0.96 and 0.92, respectively, which means that the observed survival was close to the expected survival of the matched general population. Isolated coronary artery bypass grafting had a relative survival of 0.88. Surgical replacement of the heart valves had a relative survival below 0.80. Poor results with relative survival <0.70 were observed after complex cardiac surgery. Relative survival was below 0.60 in patients who underwent double or triple valve surgery combined with coronary surgery.

Conclusions

The present findings provide a picture of the real expectation in terms of late survival of patients after adult cardiac surgery. This information can be useful for a throughout discussion with patients and their relatives on the benefits and risks associated with surgery, and it may be relevant in the decision–making process and in planning tertiary prevention.
MINIMALLY INVASIVE TRANS–AXILLARY VERSUS FULL STERNOTOMY MITRAL VALVE REPAIR: A PROPENSITY SCORE–MATCHED ANALYSIS ON MID–TERM OUTCOMES
Authors: Bifulco O , Malvindi P , Berretta P , Brugiatelli L , Cefarelli M , Alfonsi J , D‘Alfonso A , Zingaro C , Di Eusanio M
Published: May 2024

Minimally invasive cardiac surgery is an established approach for the treatment of heart valve pathologies and is associated with excellent technical and early postoperative outcomes. Data from medium– and long–term longitudinal evaluation of patients who underwent mitral valve repair (MVr) through transaxillary approach (TAxA) are still lacking. The aim of this study is to investigate mid–term results in patients who underwent TAxA MVr. Prospectively collected data of patients who underwent first–time MVr for MV regurgitation between 2017 and 2022, were reviewed. A total of 308 patients received TAxA, while in 220 cases, traditional full sternotomy (FS) was performed. Concomitant aortic and coronary artery bypass grafting (CABG) procedures, infective endocarditis or urgent operations were excluded. A propensity match (PS) analysis was used to overcome preoperative differences between the populations. Follow–up data were retrieved from outpatients’ clinic, telephone calls and municipal administration records. After PS–matching, two well–balanced cohorts of 171 patients were analysed. The overall 30–day mortality rate was 0.6% in both cohorts. No statistical difference in postoperative complications was reported. TAxA cohort experienced earlier postoperative extubation (p < 0.001) with a higher rate of extubation performed in the operating theatre (p < 0.001), shorter intensive care unit (ICU) stay (p < 0.001), and reduced hospitalization with 51% of patients discharged home (p < 0.001). Estimated survival at 5 years was 98.8% in TAxA vs. 93.6% in FS cohort (Log rank p = 0.15). The cumulative incidence of reoperation was 2.6% and 4.4% at 5 years, respectively, in TAxA and FS cohorts (Gray test p = 0.49). TAxA approach for MVr was associated with low rates of in–hospital mortality and major postoperative complications being furthermore associated with shorter mechanical ventilation time, shorter ICU stay and reduced hospitalization with a higher rate of patients able to be discharged home. At mid–term, TAxA was associated with excellent survival and low rate of MV reoperation.
NOVEL INTEGRATED IMAGING PARAMETERS FOR RISK STRATIFICATION OF ATRIAL FIBRILLATION IN PATIENTS WITH HYPERTROPHIC CARDIOMYOPATHY
Authors: Parisi F , La Franca E , Giovanni G , Bellavia D , Pistelli L , Zito C , Carerj S , Cipriani M
Published: May 2024

Background

Atrial fibrillation (AF) impacts prognosis of hypertrophic cardiomyopathy (HCM) by promoting progressive heart failure (HF) and increasing risk of stroke. Over the past years, several indexes and methods to predict AF among HCM patients have been proposed. However, they are limited by a lack of accuracy. Aims of our study was to evaluate the role of new echocardiographic parameters in predicting new onset of AF and to validate them by cardiac magnetic resonance (CMR).

Methods and Results

We analyzed clinical and imaging data of 141 HCM patients in sinus rhythm who underwent first evaluation at our center (51.2 ± 17.3 years, mean follow up 5.3 ± 3 years). Main parameters analyzed were left atrium (LA) end–diastolic volume (LAV min), end–systolic volume (LAVmax), LA ejection fraction (LAEF), left atrioventricular coupling index (LACI), and LA diameter (LAD). LACI was defined by the LAVmin divided by the LV end–diastolic volume (LVEDV); this parameter was assessed in previous studies as a good detector of early atrial remodeling and impaired LV compliance. 35 patients developed new–onset AF (after a mean period of 4 ± 3.2 years). At the baseline evaluation, LACI, LAD, and LAVmin showed to be significantly greater in patients who developed AF compared to patients who did not. At CMR, LACI >44% accurately predicted new–onset AF (sensitivity 85%, specificity 70%; AUC 0.81). LACI by ETT showed similar accuracy (AUC 0.75) and was superior to that shown by LAD (AUC 0.71) (Figure 1). Patients who did not develop AF had significantly higher LAEF at ETT (49.3 ± 11% vs 37 ± 9.6%; p < 0.0001). CMR analysis confirmed this result. LAEF >43% was a good predictor of AF free survival (log rank<0.001). Conversely, at a multivariate analysis, LAFE <43% by ETT was independently associated with AF occurrence (OR 4.5, 95% CI 1.4–13.7) (Figure 2). 11 patients experienced death or heart transplant (HTx). Higher values of LACI and LAVmin and lower values of LAEF were found to be associated the composite outcome of death or HTx. LACI>60% predicted the composite of death or HTx with good accuracy (AUC 0.74) (Figure 3).

Conclusions

LACI and LAEF showed to improve accuracy in predicting the new onset of AF in HCM patients without severe LA dilatation (LAD>45mm). Higher LACI and Lower LAEF (namely <43%) identify patients at higher risk of new onset AF, and, therefore, worthy of a more strict follow–up.
CORONARY FLOW AT REST AND CLINICAL OUTCOMES IN DILATED CARDIOMYOPATHY
Authors: Roccabruna A , Portolan L , Bonvicini E , Ciceri L , Pilan M , Springhetti P , Fabroni M , Piccoli A , Setti M , Benfari G , Scarsini R , Ribichini F
Published: May 2024

Background/Objectives

Reduced coronary flow reserve (CFR) was described in dilated cardiomyopathy (DCM). To match increased metabolic demand from the myocardium, resting coronary flow (rCF) increases with CFR consumption. Whether an increased rCF causing a reduction of CFR is associated with worse clinical outcomes in DCM remains debated. RCF is inversely correlated to the resting mean transit time (mtt) required for blood to pass through the coronary artery (rCF=1/mtt). A reliable surrogate of mtt is the ratio n frames/frame rate where n frames are the number of frames required for the dye to reach standard distal landmarks of coronary arteries during invasive coronary angiography (ICA) and frame rate is the frame rate acquisition. We aim to assess the prognostic role of rCF evaluated at the ICA performed as standard clinical practice at the time of diagnosis at long–term follow–up in DCM.

Methods

This is a retrospective analysis of a prospective cohort of patients with idiopathic DCM under medical management enrolled in the Verona Heart Failure registry between 01/2012 and 12/2022. RCF was evaluated at the ICA performed at the time of diagnosis as 1/(n frames/frame rate). The primary endpoint was a composite of cardiovascular death, rehospitalization for heart failure, resuscitated cardiac arrest, hemodynamically unstable ventricular arrhythmias, implanted cardiac defibrillator intervention and cardiac transplantation due to advanced heart failure.

Results

110 patients were enrolled in the final cohort. 15 patients (13.6%) suffered the primary endpoint at a median follow–up time of 42 months (IQR 18–71). At the ROC curve analysis rCF predicts the primary endpoint at a cut–off of 2.32 with an AUC of 0.728 (0.599–0.858, p=0.005) with sensitivity, specificity, negative and positive predictive value of 73.3%, 69.5%, 94.3% and 27.5% respectively. Patients suffering the primary endpoint tended to be older (66 years [60–74] vs 59 years [51–69], p=0.060) and were characterized by an increased rCF (3 [1.87–3.75] vs 1.87 [1.36–2.5]). Patients with rCF<2.32 suffered the primary endpoint more frequently when compared to those with rCF≥2.32 (27.5% vs 5.7%, log rank test p=0.007).

Conclusions

Increased rCF leading to a consumption of CFR is associated with worse clinical outcomes at long term follow–up in idiopathic DCM. Whether coronary microvascular dysfunction can play a prognostic role in this setting remains to be explored by proper prospective studies.
HYPERTROPHIC CARDIOMYOPATHY AND MYBPC3 VARIANT - A CLINICAL CASE
Authors: Bianco M , Nangeroni G , Biolè C , Garello L , Giachino D , Chinaglia A
Published: May 2024

Introduction

Hypertrophic cardiomyopathy is a primary pathology of the cardiac muscle. Sarcomeric forms of hypertrophic cardiomyopathy (HCM) often have autosomal dominant transmission. A pathogenetic or likely pathogenetic mutation affecting genes encoding sarcomeric proteins is present in 30-60% of cases. In this study, we present a case of a family affected by hypertrophic cardiomyopathy with a mutation classified as of uncertain significance in the MYBPC3 gene.

Clinical Case

Mr. AA, 74 years old, attended the cardiomyopathy outpatient clinic of our hospital in June 2021 due to worsening heart failure with an hypertrophic phenotype. His medical history reported an increase in the thickness of the interventricular septum (IVS) since 1985. In 2015, the patient underwent pacemaker implantation for symptomatic 2:1 atrioventricular block associated with syncope and complete left bundle branch block. Since 2016, he had paroxysmal atrial fibrillation complicated by an ischemic stroke in 2019 with subtherapeutic INR. Cardiac magnetic resonance imaging (MRI) or genetic evaluation had never been performed. During the visit, the patient reported that his sister (AG, 73 years old) had undergone tests due to diffuse negative T waves findings in a previous ECG, revealing the presence of a long myocardial bridge of the left anterior descending artery (LAD). No family history of sudden cardiac death was reported. The echocardiogram of AA showed LV hypertrophy (septal wall thickness/posterior wall thickness 18/15 mm, respectively) with an ejection fraction of 36%. Suspecting sarcomeric HCM, a genetic test (TruSight One Expanded Illumina) was performed, revealing two variants of uncertain significance in heterozygosity in the CACNA1C - Calcium Voltage-Gated Channel Subunit Alpha1 C gene (c.2460G>C p.(Lys820Asn)) and MYBPC3 gene (c.2030C>T p.(Pro677Leu)). After a few months, AG presented MRI results suggestive of HCM apical variant (Figure 1). The genetic consultant recommended family screening, and the pedigree is shown in Figure 2. All carriers of the CACNA1C mutation had a negative phenotype. AG's son, IF, 56 years old, carriers of MYBPC3 mutation, presented an MRI compatible with early-stage HCM (Figure 3). His son, carriers of MYBPC3 mutation as well, is now awaiting a cardiac MRI.

Conclusions

In the family presented here, the MYBPC3 variant (c.2030C>T p.(Pro677Leu)) appears to be correlated with the development of sarcomeric hypertrophic cardiomyopathy. Registry studies with a large sample size are desirable to accurately classify variants of uncertain significance, which are becoming more common due to the widespread use of genetic tests.
PROGNOSTIC VALUE MEAN PULMONARY ARTERIAL PRESSURE AND PULMONARY VASCULAR RESISTANCE IN PATIENTS WITH PULMONARY ARTERIAL HYPERTENSION AT FOLLOW–UP
Authors: Dardi F , Salvi M , Guarino D , Ballerini A , Cennerazzo F , Bertozzi R , Donato F , Manes A , Palazzini M , Galiè N
Published: May 2024

Background

Hemodynamic variables related to right ventricular (RV) function have consistently been associated with survival in pulmonary arterial hypertension (PAH). New PAH treatments, however, seems to improve RV coupling reducing RV afterload [e.g. mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance (PVR)], but without increasing cardiac output. The prognostic role of a mPAP <35 mmHg at follow–up and PVR values <5 WU in prevalent patients have been described.

Objective

The aim of this work was to define the prognostic role of a mPAP <35 mmHg and PVR <5 WU in patients with idiopathic, hereditary, drug–induced PAH (I/H/D–PAH) and PAH associated with connective tissue disease (CTD–PAH) or congenital heart disease (CHD–PAH) at follow–up after first–line treatment strategy.

Methods

treatment naïve PAH patients were assessed at 1st follow–up (3–6 months after starting PAH–specific therapy; 1st F–UP) with right heart catheterization. The primary outcome was all–cause death. Analyses were performed using Kaplan Meier curves and comparisons were done with Log–rank test. Cox regression analysis was used to find the predictive value of mPAP and PVR at bivariate analysis. Data are expressed as median (IQR).

Results

794 patients with PAH were enrolled (54% I/H/D, 28% CTD, 18% CHD) and 706 have a complete re–evaluation 4 (3–6) months after starting first–line treatment. Death occurred in 54% of patients over a median follow–up duration of 5.8 (2.4–11) years. Survival curves according to a cut–off value of 35 mmHg for mPAP and 5 WU for PVR are shown in the Figure. Patients with PVR <5 WU and mPAP ≤35 mmHg have a better prognosis than patients with PVR ≥5 WU (independently from mPAP; p–values <0.02) but have the same prognosis of patients with PVR <5 WU and mPAP >35 mmHg (p–value= 0.666). Patients with PVR <5 WU and mPAP >35 mmHg have a better prognosis than patients with PVR ≥5 WU and mPAP >35 mmHg (p–value= 0.031) and a trend toward a better prognosis than patients with PVR ≥5 WU and mPAP ≤35 mmHg (p–value= 0.06). Patients with PVR ≥5 WU have the same prognosis independently from mPAP (p–value= 0.683). In a bivariate Cox regression analysis only PVR <5 WU predict prognosis [HR (95%CI)= 0.61 (0.44–0.84); p–value= 0.002] while a mPAP <35mmHg is not prognostic [HR (95%CI)= 1.00 (0.72–1.40); p–value= 0.991].

Conclusions

mPAP <35 mmHg does not further discriminate the survival over a cut–off value of 5 WU of PVR.
BASELINE SHOCK INDEX–CREATININE CLEARANCE AS A PREDICTOR OF LONG–TERM MORTALITY AFTER ACS. RESULTS FROM 24 YEARS OF FOLLOW–UP OF THE ABC STUDY ON HEART DISEASE
Authors: Mahmoud H , Berton G , Palmieri R , Cavuto F , Cordiano R , Merotto D , Dario M , Dal Bo A , Bagato F
Published: May 2024

Background

Shock index (SI), defined as heart rate divided by systolic blood pressure, is a useful simple predictor of long–term mortality after acute myocardial infarction.

Purpose

To assess the utilization of the SI updated version that includes renal function (Shock Index–Creatinine Clearance (SI–C)) to predict long–term mortality after ACS.

Methods

This preliminary analysis included 589 patients with ACS admitted to three Italian hospitals and discharged alive. Baseline clinical and laboratory data were collected within the first 7 days of hospitalization and SI–C was calculated as (SI×100)–estimated CCr. Patients were prospectively followed for 24 years or until death.

Results

Virtually all patients completed the follow–up, representing 7066 person–years. Patients‘ mean age was 66±12 years, 70% were males and 482(82%) had died during follow–up. Compared to those who survived, deceased patients were significantly different in many clinical features. They also showed significantly higher SI–C values ( –11± 25 vs. –36±23, p<0.0001). The predictive value of SI–C for 24–year mortality was very good (area under the curve= 0.783, 95% CI: 0.738–0.827, p<0.001). The cumulative risk was significantly higher in the upper SI–C tertile (log–rank = 162.1, p < 0.001). Unadjusted Cox regression survival analysis showed that the SI–C score was significantly associated with long–term global mortality (HR: 2.1, 95%CI 1.8–2.3, p<0.0001). A fully adjusted model revealed the same results.

Conclusion

Baseline SI–C seems to be an effective independent predictor of long–term global mortality after ACS. It may have potential as a novel and simple early risk stratification tool for ACS patients including long–term outcomes.
IMPACT OF HEAT–NOT–BURN CIGARETTE PASSIVE SMOKING ON CHILDREN‘S OXIDATIVE STRESS, ENDOTHELIAL AND PLATELET FUNCTION
Authors: Maggio E , Carnevale R , Pannunzio A , Cinicola B , Palumbo I , Bartimoccia S , Nocella C , Cammisotto V , Violi F , Biondi–Zoccai G , Frati G , Zicari A , Loffredo L
Published: May 2024

Growing global use of heat–not–burn cigarettes (HNBC) prompts investigation. Prior studies assessed HNBC‘s effects on cardiovascular health, revealing heightened oxidative stress, platelet activation, and endothelial dysfunction. However, limited understanding exists regarding passive smoking‘s impact on children exposed to HNBC.

This study aims to assess levels of oxidative stress, endothelial and platelet function among children exposed to passive smoke from HNBC, traditional tobacco (TT) cigarettes and unexposed subjects. Seventy–eight children (2–18 years) were divided into three groups: HNBC passive smokers (n=26), TT cigarette exposed (n=26), and control (CNT) group (n=26, unexposed).

Oxidative stress was evaluated by serum NADPH oxidase–2 (NOX2) activity, assessed by soluble Nox2–derived peptide (sNOX2–dp), isoprostanes, hydrogen peroxide (H2O2) production, hydrogen break–down activity (HBA) and NO bioavailability. Endothelial function was assessed by brachial flow–mediated dilation (FMD). Platelet function was evaluated by soluble CD40 ligand (sCD40L), soluble P–selectin (sP–selectin) and thrombus formation by T–TAS analysis. Passive smoking–exposed children (both HNBC and TT) exhibited significantly increased serum sNOX2–dp, isoprostanes, H2O2, sCD40L sP–selectin and thrombus formation versus controls. Conversely, exposed children displayed reduced brachial FMD and serum NO bioavailability. No significant differences were found between children exposed to passive smoking of HNBC vs TT.

Multivariable regression linked sNOX2 (standardized coefﬁcient β:–0.284; SE: 0.040; p=0.01) and H2O2 (standardized coefﬁcient β:–0.243; SE: 0.0; p=0.02) as independent predictors of FMD, and isoprostanes (standardized coefﬁcient β:0.388; SE: 0.022; p<0.001) and serum cotinine (standardized coefﬁcient β:0.270; SE: 0.048; p=0.01) with sNOX2–dp levels.

Exposure to HNBC smoke heightened oxidative stress, endothelial dysfunction, platelet activation, and thrombus formation in children. Findings suggest avenues for interventions to curb childhood passive smoking exposure.
SEX DIFFERENCES IN CLINICAL CHARACTERISTICS AND OUTCOMES OF PATIENTS UNDERGOING CATHETER–DIRECTED TREATMENTS FOR HIGH RISK AND INTERMEDIATE–HIGH RISK ACUTE PULMONARY EMBOLISM. DO WE NEED SEX–SPECIFIC CONSIDERATIONS IN THE MANAGEMENT OF ACUTE PE?
Authors: Morosato M , Russo F , Iannaccone M , Colombo C , Adamo M , Galli M , Boccuzzi G , Bossi I , Nicolò C , Ferri L , Giuliano C , Rampoldi A , De Nittis G , Montorfano M , Oliva F , Chieffo A , Sacco A
Published: May 2024

Background

Acute pulmonary embolism (PE) is a common disease associated with a high mortality rate. Catheter–Directed Treatments (CDTs) could address some unsolved issues in high and intermediate–high risk PE patients evolving towards hemodynamic deterioration when systemic thrombolysis (ST) is contraindicated or fails. Few data in literature suggest that female patients hospitalized for PE experience adverse clinical outcomes as compared with their male counterparts. However, whether there is a specific impact of sex on CDTs outcomes in PE within real–world clinical settings remains unexplored.

Methods

This is a multicenter retrospective study including patients admitted in five Italian Centers, who underwent CDTs for high and intermediate–high risk PE, as defined by ESC Guidelines. In–hospital and one–year clinical outcomes were evaluated using medical records and follow–up assessments. Bleeding events were defined according to the Bleeding Academic Research Consortium (BARC) criteria.

Results

A total of 191 patients were included, 101 women (52.9%) and 90 men (47.1%). High risk PE was diagnosed in 56 (29%) patients, while intermediate–high risk PE was diagnosed in 135 (71%). Of these, 132 (69%) were treated by ultrasound–assisted thrombolysis (USAT), with negligible sex disparity between treatment modalities. Notably, female patients presented more frequently with cardiac arrest (11% vs. 2.6%, p = 0.03), had lower prevalence of absolute contraindications to ST (23% vs. 42%, p = 0.004) and history of recent major surgery (8.9% vs. 22%, p = 0.01). Female patients had a trend towards higher procedural–related complications (17% versus 9%, OR 2.07 95%CI 0.87–5.33, p=0.11), higher in–hospital mortality rate (20% versus 8.9%, OR 2.53 95%C.I. 1.09–6.41, p=0.038) and higher likelihood of bleeding events (22% versus 10%, OR 2.54 95%CI 1.13–6.14, p=0.029). At 1 year follow–up, female sex was associated with higher all–cause mortality (29.1% versus 12.7%, HR 2.50 95%CI 1.15–5.43, p=0.022). Multivariate regression analysis identified female sex, diagnosis of high–risk PE and a history of neoplasia as independent predictors of 1–year all–cause mortality.

Conclusions

In our experience, female patients undergoing CDTs for acute PE showed worse clinical presentation, higher procedural–related complications, and poorer outcomes than males. In our opinion this sex disparity underscores the need for sex–specific considerations in acute PE management strategies.
SOLUBLE GUANYLATE CYCLASE ACTIVATOR VERICIGUAT PREVENTS ANTHRACYCLINE–MEDIATED CARDIOTOXICITY AND SARCOPENIA THROUGH NO–SGC–CGMP–NLRP3 PATHWAY: POTENTIAL APPLICATION IN CANCER PATIENTS
Authors: Quagliariello V , Iovine M , Giacobbe I , Giordano V , Arianna R , Barbato M , Izzo F , Maurea F , Bisceglia I , Paccone A , Inno A , Maurea N
Published: May 2024

Background

Anthracycline–induced cardiomyopathies and sarcopenia are frequently seen in cancer patients, affecting their overall survival and quality of life; therefore, new cardioprotective strategies are needed in cardioncology. Vericiguat is a new oral guanylate cyclase activator that reduces heart failure hospitalizations or cardiovascular death through improvement of smooth muscle cell relaxation and reduction of myocardial fibrosis and inflammation. In this study, we highlight on the potential cardioprotective properties of vericiguat against anthracycline.mediated cardiotoxicity and sarcopenia.

Methods

Human cardiomyocytes (AC–16 cells) and Primary Skeletal Muscle Cells (HSkMC cells) were exposed for 48h to doxorubicin (DOXO) at 0,3 and 1 µM or Vericiguat at 10–7,10–5,10–3 mM or both in combination. Mithocondrial cell viability, LDH and Citocrome C release were performed to study cytoprotective properties. TUNEL assay, cGMP and NLRP–3, Myd–88 intracellular levels were quantified through colorimetric and selective ELISA methods. IL–1β, IL–6, IL–8, CXCL–2, TGF–β and IL–18 were also analyzed in cardiac and muscle cell lysates after treatments.

Results

Vericiguat exerts a significant cytoprotective and anti–apoptotic effect in cardiac and muscle cell lines during exposure to DOXO. A drastic increase in cGMP expression and reduction in NLRP–3, Myd–88 levels were also seen in Vericiguat–DOXO groups vs DOXO groups (p<0.001). Pro–inflammatory and cytotoxic cytokines were also downregulated after Vericiguat treatment during DOXO exposure.

Conclusions

Vericiguat significantly reduced cardiotoxic effects and sarcopenia induced by DOXO therapy though enhancement of cGMP levels and reduction of NLRP–3/Myd–88/cytokines pathways. These findings provide a framework for future studies aiming to assess vericiguat for the therapeutic targeting of anthracycline–mediated cardiotoxicity and sarcopenia.
A CASE OF RIGHT HEART FAILURE: WHEN IT IS NOT PULMONARY EMBOLISM
Authors: Tadiello E , Zimelli E , Urbani G , Hinna Danesi T , Reghellin D , Bilato C
Published: May 2024

A 66–year–old patient, showing exertional dyspnea and atypical chest pain, came to our attention with instrumental findings at echocardiogram of right ventricular failure and was hospitalized due to worsening signs and symptoms of right heart failure. Signs of right ventricular strain and the McGinn–White sign (S1Q3T3 pattern) were seen on the ECG, leading to the suspicion of pulmonary thromboembolism (PE). Pulmonary CT angiography confirmed bilateral PE involving the main pulmonary artery. Oral anticoagulant therapy was initiated with initial partial benefit and relief of symptoms. However, after four weeks, the patient was readmitted for severe heart failure and signs of low cardiac output. Echocardiography showed the presence of a conspicuous, mobile, isoechoic mass occupying most of the main pulmonary artery, suggesting thrombosis. The patient underwent urgent surgical thromboendoarterectomy extended to the third segmental left branches and to the second segmental right branches of the pulmonary artery; a severe pulmonary valve regurgitation was observed and therefore the valve was replaced with a Edwards–Magna pericardial bioprosthetic valve. ECMO (Extracorporeal Membrane Oxygenation) was initiated due to haemodinac instability. In the postoperative period, the severe heart failure worsened, unresponsive to pharmacological treatments and mechanical support, leading to the patient passing away in the following days. Unexpectedly, histological analysis of the surgical specimen revealed neoplastic cells with vascular/endothelial differentiation; fluorescence in situ hybridization (FISH) detected the MDM2 gene (cfr.23–F–00275), involved in the p53 protein regulation mechanisms, which is consistent with a diagnosis of angiosarcoma. Pulmonary–artery angiosarcomas are extremely rare (few anecdotical cases are described in literature) and resemble the CT–signs and clinical features of PE, seriously delaying the diagnosis. They are usually associated with a worse prognosis than PE, one and a half months survival time when inoperable. Radical surgery, associated with thirty six and a half months survival time, is often unfeasible because of locally advanced disease or metastatic disease already present at diagnosis. The main differences with PE are the more proximal and almost–occluding involvement of the pulmonary artery, the absence of peripheral vein thrombosis and the absence of response to anticoagulant therapy.
TWO LEADS IN ONE CORONARY SINUS: A RARE CASE OF TRANSVENOUS LEAD EXTRACTION
Authors: Arabia G , Cerini M , Calvi E , Falco R , Bellicini M , Nicolai A , Curnis A
Published: May 2024

Device–related infection remains a potentially fatal complication in patients with cardiac implantable electronic devices (CIEDs). Current guidelines recommend complete system extraction in such cases. Moreover, lead extraction of multiple leads implanted in the same CS tributary can be challenging. We describe a case of 71–year–old male with dilated cardiomyopathy. He underwent an implantable cardioverter defibrillator (ICD) implantation in secondary prevention in the year 2005, after a previous cardiac arrest. Subsequently, an upgrading to a cardiac resynchronization therapy defibrillator (CRT–D) in 2018 was performed with a unipolar coronary sinus lead implanted in an anterolateral branch of the coronary sinus (CS). Two months a new active fixation lead was implanted in CS for an elevated impedance of the previous CS catheter. In February 2022, the patient presented signs of pocket infection and was referred to our center for transvenous lead extraction (TLE). For the coronary sinus leads, a locking stylet was first positioned in each lead, then mechanical sheaths were advanced over the passive lead and subsequently on the active lead. Afterwards, a hand–powered mechanical sheath was advanced sequentially over each lead up to the coronary sinus ostium. Contrast injection through the sheath revealed extensive fibrosis of the CS ostium. Midline sternotomy was done and through a right atrial incision, the proximal parts of the CS leads were externalized. A 7.5 Fr mechanical dilator sheath was then advanced over the passive lead, allowing the removal of both the CS leads. Upon resolution of the infection, a new CRT–D device was implanted with two leads in the right ventricle (one in the right ventricular apex, and the other on the interventricular septum), following a multisite right ventricular pacing approach. We present the first case in literature to undergo lead extraction of two leads in the same coronary coronary sinus. The presence of two leads induced extensive fibrosis inside the CS. A combination with surgical approach was needed in order to avoid any possible tear of the coronary sinus. The unusual implantation of more than one lead in the same CS tributary can increase the procedural risk when the need for extraction arises. In that case, a surgical approach combined with the utilization of transvenous lead extaction tools can provide a way to extract the leads with minimal surgical manipulation.
WHEN AND WHERE DOES A CARRIER OF HEREDITARY TRANSTHYRETIN AMYLOIDOSIS (ILE88LEU) SHOW THE FIRST SIGNS OF THE DISEASE? DIAGNOSTIC CHALLENGES OF A NOT ONLY CARDIOGENIC MUTATION
Authors: Brugiatelli L , Vagnarelli F , Lofiego C , Capodaglio I , Patani F , Tofoni P , Maurizi K , Pietrucci F , Schicchi N , Tortora G , Lupidi F , Burroni L , Dello Russo A , Perna G
Published: May 2024

We present the case of a 58–year–old man with a familiar history (mother affected) positive for ATTR–v (Ile88Leu) amyloidosis. The mother initially had a pure cardiac phenotype and was firstly treated with tafamidis, but progression of the disease to the nervous system warranted a switch to patisiran. Our patient carried the Ile88Leu mutation and had a medical history notable for surgically treated left carpal tunnel syndrome (CTS) and untreated right CTS. Furthermore, he was affected by systemic arterial hypertension and was a habitual smoker. He has been followed at our Institution since 2018. His first echocardiogram showed normal left ventricular ejection fraction (LVEF 65%), mild hypertrophy (anterior septum: 12 mm), and borderline values of GLS (– 16%) without any specific pattern. Further exams were executed: Bone scintigraphy (BS): negative (Perugini score 0); Coronary artery ct scan: moderate stenosis of proximal LAD; Neurologic evaluation: no signs of peripheral neuropathy. The clinical picture remained unaltered in 2020 and 2021. However, during November 2022 the patient developed atrial fibrillation (AF) and presented to the ED for dyspnea and palpitations. Electrical cardioversion was performed with success but subsequent recurrences warranted AF ablation in April 2023. At that moment, the patient was re–evaluated. Basal ECG did not show any significant alteration (FIg.1)This time, echocardiogram showed mild worsening of hypertrophy (13 mm septum), GLS – 16% with apical sparing pattern, no other major variations (Fig.2). BS was repeated and revealed grade 1 Perugini score (Fig.3). Hence, a series of clinical question arose: Should we begin a specific treatment or is the disease in an excessively early stage that does not warrant treatment? Is AF linked to concomitant arterial hypertension or might it be an early marker of disease? We questioned the usefulness of endomyocardial biopsy in this specific setting. In this case, we repeated electromyography that showed mild axonal sensitive–motor polyneuropathy. Finally, we concluded for initial signs of systemic amyloidosis ATTR–v (Ile88Leu) type with mixed phenotype (neurological+cardiac). The neurological involvement allowed us to start a gene–silencer (Patisiran). In conclusion, a periodic neurological evaluation is necessary and has crucial therapeutic implications in all genotypes. Indeed, there is increasing evidence that Ile88Leu is a not only cardiogenic mutation.
DON’T FORGET ABOUT CARDIAC AMYLOIDOSIS: WHEN RED FLAGS MATTER
Authors: Pedio E , Colucci C , Falagario A , Mannarini A , De Michele L , D‘Agostino C
Published: May 2024

Case Report

A 78–year–old man came to our attention for worsening dyspnea, asthenia and frequent lipothymic episodes in the last few weeks. Nothing remarkable was reported in anamnesis except for periodic cardiological check–ups ascribed to hypertensive heart disease and moderate aortic stenosis. Other cardiovascular risk factors were obesity, previous smoking habits and dyslipidemia. A recent 24–hours ECG monitoring revealed slow permanent atrial fibrillation (AF) with 3–seconds pauses, frequent premature ventricular complexes (PVCs) and some PVCs couplets. On arrival, NT–proBNP was elevated (2952 pg/mL), while ECG showed AF with a heart rate of 50/m and low voltages in peripheral leads. Transthoracic echocardiogram revealed a biatrial dilatation, a severe left ventricular (LV) concentric hypertrophy with a preserved LV ejection fraction (EF) and a moderate aortic stenosis. In addition, a restrictive LV filling pattern, a decreased longitudinal myocardial contraction and an apical sparing of longitudinal strain were reported. Invasive coronary angiography was performed with evidence of normal coronary arteries. Given the echocardiographic suspicion of amyloidosis, a 99mTc–Hydroxymethylene diphosphonate (HMDP) scintigraphy was performed, showing a moderate cardiac uptake and an attenuated bone uptake (Perugini Score 2). Serum and urine immunofixation resulted negative. Genetic testing did not find any mutations in Transthyretin (TTR) gene. Therefore, the diagnosis of TTR wild–type amyloidosis was made. Before discharge, putting it all together, we opted to implant a leadless pacemaker in order to protect the patient from life–threatening bradyarrhythmias.

Discussion

Although it is currently considered rare, there is growing evidence that cardiac amyloidosis may be more common than once thought. First of all, it should be investigated in HFpEF–patients (heart failure with preserved EF) with LV hypertrophy. Despite several red flags (low QRS voltages, conduction disorders, elevated NT–proBNP, severe LV hypertrophy and aortic stenosis) and various medical consultations, our patient had to wait 4 years or more to be diagnosed with cardiac amyloidosis. Inevitably, a diagnostic delay means loss of time in treatment initiation. Earlier diagnosis would enable us to improve our patients’ survival and heart failure hospitalization. Awareness alone is not enough, we must be right on target too.
COMPARISON BETWEEN DIFFERENT TRANSRADIAL ARTERY HEMOSTASIS PROTOCOLS IN LIGURIAN CARDIOLOGIES
Authors: Lorenzo P , Corona M
Published: May 2024

Background

Transradial artery access (TRA) for coronary angiography and percutaneous coronary intervention is associated with lower bleeding and vascular complications than transfemoral artery access. In our hospital, TRA is widely used and hemostasis is usually achieved using TRBand device. We used to remove the device in about 10 hours according to our protocol.

Aims

The aim of this study is to describe and compare different TRA hemostasis protocols in order to understand if a shorter protocol could be more effective.

Methods

This is an observational study performed in all Hospitals of our region (Liguria). All Cardiology Departments were included in this analysis. We requested to all to self–refer: a) which radial hemostasis device was used; b) which deflation protocol (DP) was used. c) If they usually report and analyze adverse events. Adverse events are described as: bleeding, hematoma, ecchymosis, skin damage, local infection, pseudoaneurysm, or artery occlusion. RESULTS In Liguria there are 9 Cardiology Departments with Cath Lab (CL); 8 of them accepted to participate. All the Cath Labs use the TRBAND device but the deflation protocols are very different. 5 Cath Labs follows the DP suggested by the manufacturer. Only 2 CL adopted different DP if and higher dose of heparin was administered. Only one report bleedings or any delete in the DP. None analyze periodically the incidence of adverse events.

Conclusions

There are different methods to achieve radial hemostasis furthermore with the same device different deflating protocols are used. Further studies are necessary to evaluate the best DP. Regular audits must be strongly suggested in all Cardiology Departments in order to monitorate and improve the adverse events.