bluuebunny/crossref_metadata_2025 huggingface dataset:
682 Cardioncology: is it time to spread the need for dedicated management?
Authors: Magnesa Michele , Casavecchia Grazia , Barone Roberta , Riccardo Mariolina , Corbo Delia , Brunetti Natale Daniele
Published: December 2021

Case report

A 56-year-old man affected by micromolecular multiple myeloma was treated by several cycles of different chemotherapy drugs from September 2015 to December 2020. The chemotherapy regimen included 4-cycle first-line therapy with Bortezomib, Thalidomide, and Dexamethasone; 19-cycle second-line therapy with Carfilzomib, Revlimid, and Dexamethasone; 8-cycle third-line therapy with Daratumumab, Revlimid, and Dexamethasone; finally, he was started on therapy with Pomalidomide and Endoxan. During the various treatments, the patient did not follow a dedicated cardiological follow-up programme. In November 2020, he was hospitalized in the Intensive Care Unit for acute pulmonary oedema and subsequently discharged with a diagnosis of mild left ventricular systolic dysfunction (LVEF 50%). One month later, due to the worsening of dyspnoea, the patient was finally referred to our Cardioncology Unit for the medical assessment. The echocardiographic examination revealed a global and severe left ventricular dysfunction (FE 40%) with significant reduction in left ventricular global longitudinal strain (GLS −10%). For these reasons, we referred the patient to coronary angiography.

Conclusions

This case report wants to underline how important a dedicated cardiological follow-up is in patients undergoing chemotherapy drugs, especially if used at high doses and for many cycles.
12 Sex-related differential susceptibility to ponatinib-induced cardiotoxicity and its relationship to modulation of notch signalling in a muine model
Authors: Madonna Rosalinda , Pieragostino Damiana , Cufaro Maria Concetta , Del Boccio Piero , Pucci Angela , Mattii Letizia , Doria Vanessa , Dessalvi Christian Cadeddu , Zucchi Riccardo , Mercuro Giuseppe , De Caterina Raffaele
Published: December 2021

Aims

Ponatinib (PON), a tyrosine kinase inhibitor approved in chronic myeloid leukaemia, has proven cardiovascular toxicity. Although sex is a risk factor for PON-induced cardiotoxicity in humans, little is known about its mechanisms, in general, and sex-related mechanisms in particular. To determine the mechanisms of sex-related PON-induced cardiotoxicity and identify potential rescue strategies in a murine model.

Methods

Twenty-four-month-old male and female C57B5 mice were treated with 3 mg/kg/day of PON or vehicle via oral gavage for 28 days, with/without siRNA-Notch1 or siRNA-scrambled via tail vein every 3 days.

Results

PON + scrambled siRNA-treated male mice had a higher number of TUNEL-positive cells, a higher percentage of senescence-associated β-galactosidase positive senescent cardiac areas, as well as a lower reactivity degree for the survival marker Bmi1 than female counterparts. Proteomics analysis of cardiac tissue showed upstream activation of nitric oxide synthase (NOS) type 2, downstream activation of cell death and production of reactive oxygen species in PON + scrambled siRNA- compared to vehicle or PON + Notch1 siRNA-treated male mice. Upstream analysis showed beta-estradiol activation, while downstream analysis showed activation of cell survival and inhibition of cell death in PON + scrambled siRNA compared to vehicle-treated female mice. PON + scrambled siRNA-treated mice also showed a down-regulation of cardiac actin, which was more marked in male; as well as vessel density, which was more marked in female mice. Female hearts showed a greater extent of cardiac fibrosis than male counterparts at baseline, with no significant changes after PON treatment. In contrast, PON + scrambled siRNA-treated mice had less fibrosis than vehicle or PON + Notch1-siRNA-treated mice. Left ventricular systolic dysfunction shown in PON + scrambled siRNA-treated male mice and—to a lesser extent—by female mice was similarly reversed in both PON + Notch1-siRNA-treated male and female mice (Table 1).

Conclusions

We found a sex-related differential susceptibility and Notch1 modulation in PON-induced cardiotoxicity. This can improve our understanding of sex-related differences and help identify biomarkers in PON cardiotoxicity.
54 Sacubitril–valsartan (LCZ 696) improves longitudinal strain and ejection fraction in preclinical models treated with doxorubicin through NLRP3, MyD88, and pro-fibrotic chemokines
Authors: Quagliariello Vincenzo , Buccolo Simona , Iovine Martina , Maurea Fabrizio , Rea Domenica , Barbieri Antonio , Maurea Nicola
Published: December 2021

Aims

Doxorubicin-mediated adverse cardiovascular events are among the leading causes of morbidity and mortality in breast cancer patients. Sacubitril–valsartan (LCZ 696) is a combination drug, made up of neprilysin inhibitor sacubitril and angiotensin II receptor blocker valsartan, used for the treatment of heart failure in patients with a reduced ejection fraction. We hypothesized that LCZ 696, administered during doxorubicin, could improve cardiac function and cardiac inflammation in preclinical models.

Methods

Human Foetal cardiomyocytes (HFC cell line) were exposed to subclinical concentration of doxorubicin (200 nM) alone or in combination with LCZ-696 (100 mM) for 72 h. After the incubation period, we performed the following tests: cell viability, apoptosis and necrosis; expression of malondialdehyde and 4-hydroxynonenal and concentration of intracellular Ca2+. Moreover, pro-inflammatory studied were also performed (activation of NLRP3 inflammasome; expression of TLR4/MyD88; mTORC1 Fox01/3a; NF-κB). C57Bl/6 mice were untreated (Sham, n = 6) or treated for 10 days with doxorubicin i.p. at 2.17 mg/kg (DOXO, n = 6), LCZ-696 at 60 mg/kg (LCZ, n = 6) or doxorubicin combined to LCZ-696 (DOXO-LCZ, n = 6). Ejection fraction, radial and longitudinal strain were analysed through transthoracic echocardiography (Vevo 2100). Cardiac tissue expression of NLRP3 inflammasome, Myd88, NF-kB, and 13 chemokines (IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-12, IL17-α, IL-18, IFN-γ, TNF-α, G-CSF, and GM-CSF) were quantified.

Results

LCZ-696 exerts cardioprotective effects, enhancing cell viability of 48–54.6% compared to only doxorubicin-treated cells (P < 0.001 for all); LCZ 696 decreased NLRP3, MyD88 and NF-kB expression in cardiac cells. In preclinical study, LCZ 696 improved significantly the EF and prevented the reduction of radial and longitudinal strain after 10 days of treatment with doxorubicin. A reduced expression of NLRP3, MyD88 and NF-kB in cardiac tissues was seen in DOXO-LCZ group compared to DOXO mice (P < 0.001). Cardiac expression of IL-1β, IL-6, TNF-α, G-CSF and GM-CSF were significantly reduced after treatment with LCZ-696 indicating anti-inflammatory properties.

Conclusions

LCZ-696 exerts direct beneficial effects in cardiomyocytes exposed to doxorubicin. In preclinical models, LCZ-696 reduced inflammation and cytokine expression involved in doxorubicin-mediated cardiotoxicity.
88 Differential cardiotoxicity of immune checkpoint inhibitors involves damps fibronectin-EDA, calgranulin, galectine-3, and associated nlrp3 inflammasome-interleukins pathway in preclinical models
Authors: Quagliariello Vincenzo , Mauro Annabella Di , Scognamiglio Giosuè , Cipullo Ciro , Passariello Margherita , Barbieri Antonio , De Lorenzo Claudia , Di Bonito Maurizio , Maurea Nicola
Published: December 2021

Aims

Several strategies based on immune checkpoint inhibitors (ICIs) have been developed or are under investigation for cancer therapy, opening to advantages in cancer outcomes. However, several ICIs-induced side effects emerged in these patients, especially a rare but clinically significant cardiotoxicity with high rate of mortality. We analysed the differential vasculo and cardiotoxicity of Pembrolizumab, Nivolumab and Ipilimumab in preclinical models highlighting on the molecular pathways involved.

Methods

C57 female mice were treated with Ipilimumab, Pembrolizumab or Nivolumab (15 mg/kg) through intraperitoneal injection for 10 days. Before and after treatments, analysis of fractional shortening, ejection fraction, radial and longitudinal strain was performed through 2D-echocardiography (Vevo 2100, Visual Sonics Fujfilm). Fibrosis, necrosis, hypertrophy and vascular/myocardial NF-kB expression were analysed through Immunohistochemistry (IHC). DAMPs, NLRP3, MyD88, p65/NF-kB and 12 cytokines have been analysed in murine myocardium and in cardiomyocytes co-incubated with hPBMC.

Results

In preclinical models, treatment with Nivolumab leads to increased vascular and myocardial NF-kB expression without affecting fibrosis unlike Ipilimumab which also increases cardiac collagen production. Pembrolizumab increased myocardial hypertrophy and fibrosis in cardiac tissues with a strong vascular NF-kB expression. All tested ICIs increased DAMPs, NLRP3 inflammasome-IL1β-IL18 axis and only Pembrolizumab increased significantly the MyD88 expression vs. untreated mice.

Conclusions

In preclinical models, Pembrolizumab exerts the most relevant cardiotoxicity compared to Nivolumab and Ipilimumab, increasing immune infiltration in the myocardium and vascular inflammation. All tested ICIs increased DAMPs, NLRP3/IL-1β and MyD88 expression, leading to pro-inflammatory cytokine storm in heart tissues.
504 Comparison of cardiovascular risk scores to predict anthracycline-induced cardiotoxicity in early breast cancer patients
Authors: Solfanelli Giorgio , Bianchini Giulia , Petrungaro Mattia , Reale Simone , Lanza Oreste , Ferrera Armando , Tini Giacomo , Piras Marta , Pellegrini Patrizia , Tocci Giuliano , Battistoni Allegra , Volpe Massimo
Published: December 2021

Aims

Cardiovascular (CV) toxicities related to chemotherapy have been reported with increasing frequency. Thus, latest cardio-oncology guidelines focused on the importance of a baseline CV risk assessment before starting a potentially cardiotoxic regimen, in order to identify individuals at greater risk of developing CV toxicities and to prevent them. Despite these recommendations, there are still no validated systems to predict cardiotoxicity risk in oncological patients. The aim of the present study was to compare the average risk assessed by conventional CV risk scores (SCORE, QRISK2, ASCVD) and two recently developed cardiotoxicity risk scores (Baseline cardiovascular risk stratification proformas, Multivariable prediction model for major adverse cardiovascular events after early stage breast cancer) in a cohort of 41 (100% female; mean age 52.9 ± 11) early breast cancer (EBC) patients treated with epirubicin and to investigate the relationship between CV and cardiotoxicity risk and the rate of CV outcome, defined as biomarkers (high sensibility Troponin I and BNP) increase during the follow-up.

Results

A baseline CV risk assessment was performed in all patients before starting chemotherapy according to prespecified scores, showing a higher mean CV risk in our cohort compared to general population. Most patients were at low risk of developing cardiotoxicity according to prespecified scores. During the follow-up (mean 221 ± 75 days), the primary outcome occurred in 9.8% (n = 4). The average CV risk scores of patients developing the primary outcome were higher than the controls according to both conventional and cardiotoxicity risk scores (Figure 1). The QRISK2 achieved the best ratio cases average score/controls average score (r = 3) and the ROC curve confirmed QRISK2 as the best CV risk score to predict the outcome in our cohort, reaching the highest sensitivity and specificity (Figure 2).

Conclusions

In a cohort of young patients affected by EBC the mean CV risk is higher than the general young female population according to traditional CV risk scores. Moreover, patients developing the primary outcome during the Follow-up were those at higher CV risk and high risk of cardio toxicity. Surprisingly the best score to predict the incidence of outcome was the QRISK2, confirming the crucial role of baseline CV risk in cancer patients.
234 Echocardiographic visualization of retroaortic anomalous coronary artery
Authors: Bruno Noemi , Ferrari Ilaria , Pelliccia Francesco , Gaudio Carlo , Monzo Luca
Published: December 2021

A 65-year-old female was admitted to our hospital for sudden onset of typical chest pain at rest lasting few minutes. Her medical background included systemic hypertension, type 2 diabetes, dyslipidaemia, and mild obesity. Upon arrival in the emergency room, the electrocardiogram didn’t reveal signs of acute myocardial ischaemia and serial cardiac troponin T measurements were persistently negative. A transthoracic echocardiogram (TTE) was performed, showing mild ventricular hypertrophy, no regional wall motion abnormalities, and a preserved left ventricular ejection fraction. A highly echogenic tubular structure, located slightly on the atrial side of the atrioventricular groove was noted in multiple apical views. Its tubular shape was suggestive of a vascular structure, but its location was atypical for a normal vessel; indeed its persistence in more than an echocardiographic plane excluded an artefact. According to patient’s clinical history and her high cardiovascular risk profile she was referred for coronary angiography, demonstrating no critical stenosis but an anomalous aortic origin of a coronary artery (AAOCA) from the inappropriate sinus of Valsalva: the left main coronary artery (LMCA) arose from the right coronary cusp and then took a caudal posterior loop running posterior to the aortic root. In light of these findings we could associate the tubular structure seen at TTE to the retroaortic course of LMCA, a finding recently described as retroaortic anomalous coronary (RAC) sign. Among AAOCA, the retroaortic course of the LMCA is an uncommon diagnosis in adults, and its association with a single coronary origin is extremely rare. Although it has been usually considered a benign clinical entity, it is associated with an increased risk in morbidity and mortality during valve surgery. The presence of RAC sign at TTE was demonstrated to be highly suggestive of an anomalous coronary artery (specificity 93.9%) and strongly associated with retroaortic LMCA course at computed tomography angiography. 234 Figure B
710 Advanced echocardiographic analysis to identify cardiac toxicity after TKI exposure in patients with CML
Authors: Parlavecchio Antonio , Caminiti Rodolfo , Vetta Giampaolo , Pelaggi Giuseppe , Lofrumento Francesca , Vinciguerra Paolo , Parisi Francesca , Demurtas Elisabetta , Licordari Roberto , Cusma Maurizio , Manganaro Roberta , Micari Antonio , Di Bella Gianluca , Zito Concetta , Carerj Scipione
Published: December 2021

Aims

Worsening of cardiac function with increased arrhythmic risk is common in cancer patients undergoing chemotherapy. Impaired LV global longitudinal strain (GLS) in these patients despite preserved ejection fraction is a common issue. Recently, myocardial work by speckle-tracking echocardiography has been used to overcome GLS limitations in various conditions, but little is known about its usefulness in the detection of cardiac toxicity. Moreover, left atrial (LA) toxicity may occur early in the course of cancer therapy. The main aim of the study was to assess the cardiotoxic effects of tyrosine kinase inhibitors (TKIs) on patients with Philadelphia chromosome-positive chronic myeloid leukaemia (Ph+ CML) by using novel echocardiographic tools as myocardial work and atrial strain analysis.

Methods and results

We retrospectively enrolled Ph+ CML patients treated with TKIs followed at the cardio-oncology outpatient clinic of our hospital from December 2018 to March 2019 who underwent clinical evaluation with ECG and echocardiogram (TTE) before and after 1 year of treatment with TKIs. Healthy subjects were enrolled in the control group matched for gender, age and cardiovascular risk factors. Myocardial work was derived from the strain-pressure relation, integrating in its calculation the non-invasive arterial pressure. LA longitudinal strain (reservoir, conduit, and booster) was obtained from an optimized apical 4-chamber view of the LA. The study recruited 32 patients in Ph+ CML group and 32 healthy controls. 39% of patients were treated with Imatinib, 29.3% with Nilotinib, 4.9% with Dasatinib and 4.9% with Ponatinib. Main results are detailed in Table 1. At 1-year follow-up there was a significant reduction compared to baseline in global constructive work (2555.22 ± 564.33 vs. 2119.31 ± 700.19; P = 0.0001), global work efficiency (96.13 ± 1.90 vs. 94.00 ± 2.96; P = 0.002), and global work index (2340.75 ± 579.57 vs. 1938.46 ± 680.23; P = 0.001), and a non-significant reduction in global wasted work (P = 0.393). Regarding left atrial strain analysis at the 1-year follow-up there was a statistically significant reduction in LA contractile strain (booster= 14.63 ± 1.408 vs. 12.38 ± 1.581; P = 0.018). LA contractile strain reduction was also observed in the comparison with controls (12.38 ± 2.99 vs. 14.91 ± 3.09; P = 0.009). Any other significant difference was detected between baseline and FU TTE data in the Ph+ CML group.

Conclusions

New imaging methods for the study of cardiotoxicity provide an additional tool for early prediction of potential adverse effects of antineoplastic drugs. TKIs therapy leads to an impairment of atrial contractility, which can be detected by atrial strain e myocardial work analysis.
314 Automated left atrial volume measurement by two-dimensional speckle-tracking echocardiograpy. Feasibility, accuracy, and reproducibility
Authors: Florescu Diana Ruxandra , Badano Luigi Paolo , Tomaselli Michele , Torlasco Camilla , Tartea Georgica , Florescu Cristina , Volpato Valentina , Parati Gianfranco , Muraru Denisa
Published: December 2021

Aims

A by-product of left atrial (LA) strain analysis is the automated measurement of LA maximal volume (LAVmax), which may decrease the time of echocardiography reporting, and increase the reproducibility of the LAVmax measurement. However, the automated measurement of LAVmax by two-dimensional speckle-tracking analysis (2DSTE) has never been validated. Accordingly, we sought to: (i) assess the feasibility of automated LAVmax measurement by 2DSTE; (ii) compare the automated LAVmax by 2DSTE with conventional two-dimensional (2DE) biplane and three-dimensional echocardiography (3DE) measurements; and (iii) evaluate the accuracy and reproducibility of the three echocardiography techniques.

Methods and results

LAVmax (34–197 ml) were obtained from 198/210 (feasibility 94%) consecutive patients with various cardiac diseases (median age 67 years, 126 men) by 2DSTE, 2DE, and 3DE. 2DE and 2DSTE measurements resulted in similar LAVmax values (bias = 1.5 ml, limits of agreement, LOA ± 7.5 ml), and slightly underestimated 3DE LAVmax (biases = −5 ml, LOA ± 17 ml, and −6 ml, LOA ± 16 ml, respectively). LAVmax by 2DSTE and 2DE were strongly correlated to those obtained by cardiac magnetic resonance (CMR) (r = 0.946, and r = 0.935, respectively; P < 0.001). However, LAVmax obtained by 2DSTE (bias = −9.5 ml, LOA ± 16 ml) and 2DE (bias = −8 ml, LOA ± 17 ml) were significantly smaller than those measured by CMR. Conversely, 3DE LAVmax were similar to CMR (bias = −2 ml, LOA ± 10 ml). Excellent intra- and inter-observer intraclass correlations were found for 3DE (0.995 and 0.995), 2DE (0.990 and 0.988), and 2DSTE (0.990 and 0.989).

Conclusions

Automated LAVmax measurement by 2DSTE is highly feasible, highly reproducible, and provided similar values to conventional 2DE calculations in consecutive patients with a wide range of LAVmax.
310 Ruptured sinus of Valsalva aneurysm as a rare cause of sisto-diastolic murmur: role of multimodality imaging in diagnosis and surgical planning
Authors: De Luca Antonio , Fiocco Alessandro , Restivo Luca , Poletti Angela , Faganello Giorgio , Bussani Rossana , Sinagra Gianfranco
Published: December 2021

A 27-year-old man had an incidental finding of sisto-diastolic murmur during a screening medical evaluation. Transthoracic and subsequent transesophageal echocardiography revealed a saccular enlargement of non-coronary (NC) sinus of Valsalva. The aneurysm extended into the right atrium (RA) and presented a large wall discontinuity, with continuous sisto-diastolic flow from the aorta to the right atrium. Computed tomography confirmed the findings and excluded other associated abnormalities. The patient underwent urgent surgical intervention. Intraoperatively, findings reported a floppy and cribrose saccular aneurysm sprouting from the NC sinus inside the RA. The correction turned out to be very challenging due to the close connection between the aneurysmal wall and the tricuspid valve (TV) and aortic valve (AV) annuli. The aortic NC sinus was excised and replaced with a Dacron patch. Damaging of the TV septal leaflet required repair through a consolidating suture involving the septal leaflet of TV and the corresponding annular insertion. AV replacement was also needed due to damage of the AV NC cusp. No complications occurred during the postoperative stay. Histopathology revealed severe atrophy of muscular and elastic fibres of the aortic wall, elastic fiber fragmentation, replacement fibrosis and extensive deposition of mucopolysaccharides.

Sinus of Valsalva aneurysm (SoVA) is a rare condition characterized by an enlargement of the aortic root between the aortic valve and the sinotubular junction. SoVA can be either congenital, as a consequence of weakness of the elastic lamina, or acquired, due to infective, degenerative, or traumatic conditions. A prevalence of 0.09% was described in autopsy series and males are more frequently affected. Acute rupture of SoVA requires emergent surgery because of acute life-threatening haemodynamic instability. Congenital and chronic ruptured SoVA could be asymptomatic. Nevertheless, such incidental finding requires urgent surgical correction due to the possibility of unexpected further rupture, generating massive left-right shunt. The close relationship with nearby anatomical structures is a major issue which should be taken into account. In this perspective multimodality imaging is of paramount importance, allowing for a fine surgical planning and avoidance of complications.
122 Exercise stress echocardiography in paediatric and adolescent patients: what is the role?
Authors: Avesani Martina , Calvo Giacomo , Sabatino Jolanda , Sirico Domenico , Castaldi Biagio , Reffo Elena , Cerutti Alessia , Biffanti Roberta , Borrelli Nunzia , Piccinelli Enrico , Fraisse Alain , Padalino Massimo , Vida Vladimiro , Di Salvo Giovanni
Published: December 2021

Aims

To describe the current application of exercise stress echocardiography (ESE) in our Paediatric Cardiology Departments.

Methods and results

Baseline and under stress symptoms, vital parameters, ECG, and echocardiograms from patients who underwent ESE in our centres, were retrospectively analysed and compared, as well as clinical management plans formulated based on ESEs results. Forty-five patients from Centre 1 (median age 16 years), including 87% of patients with congenital heart diseases (CHDs), and 20 patients from Centre 2 (median age 11 years), mainly tested to rule out myocardial ischemia, were included. Among patients from Centre 1, 28 had previously been treated surgically, 6 percutaneously, and 11 were under follow-up. Indications for ESE/patients’ native diagnosis are illustrated in the picture. Centre 1: Exercise was maximal in 17 patients, with 2 of them having symptoms at the peak of exercise. It was stopped beforehand in 28 patients because of dyspnoea (3) and muscle fatigue (25). No arrhythmia was detected. ESE was considered as positive in 14 patients; after that, 3 patients underwent percutaneous interventions, 2 underwent cardiac surgery, 3 received indication for cardiac catheterization, 4 for advanced cardiac imaging, and 2 for exercise restriction and medical therapy. Centre 2: 15 patients (75%) completed the exercise, and none of them developed symptoms. In the remaining 25%, exercise was stopped because of muscle exhaustion. No arrhythmia was detected, and all the ESEs were negative. Comparing the cohorts, no differences in terms of ejection fraction were noticed at rest and under stress. Patients in cohort 1 were older (P = 0.002), they achieved lower average maximal heart rate (P = 0.0001), performed less lasting exercise (P = 0.05), and ESE was maximal less frequently (P = 0.005). Lastly, they had significant changes in clinical decisions (P = 0.004).

Conclusions

In paediatric cardiology, particularly in children with CHDs, ESE is a promising technique and could influence significantly clinical management plans.
45 Experience of 5 years of balloon pulmonary angioplasty in a single centre: safety and short-term results
Authors: Guarino Daniele , Palazzini Massimiliano , Saia Francesco , Dardi Fabio , Taglieri Nevio , De Lorenzis Alessandro , Ballerini Alberto , Rotunno Mariangela , Magnani Ilenia , Donato Federico , Bertozzi Riccardo , Marrozzini Cinzia , Manes Alessandra , Galiè Nazzareno
Published: December 2021

Aims

Balloon pulmonary angioplasty (BPA) has recently been developed as a treatment strategy for chronic thromboembolic pulmonary hypertension (CTEPH) but efficacy and technical safety have to be established. We examine the effects of BPA on patients with inoperable disease or residual pulmonary hypertension (PH) after pulmonary endarterectomy (PEA).

Methods and results

From 2015 to 2020 we enrolled symptomatic inoperable CTEPH patients and patients with residual PH after PEA. At baseline and 3 months after last BPA session patients underwent clinical evaluation, 6-min walking distance (6MWD), and right heart catheterization. Friedman test with Bonferroni post-hoc pairwise analysis was used. Fifty patients [male 42%, median age 68 (51–74) years, 42 inoperable, and 8 with residual PH after PEA] were treated for a total of 156 sessions (median 2 sessions/patient); during each session we treated 2.3 (2.2–2.7) vessels. Results are shown in the Table. Forty-nine patients were treated with medical therapy before BPA (19 with combination therapy). Five pulmonary artery dissection and two haemoptysis with clinical impairment were documented during the procedures; 37 patients had lung injury (radiographic opacity with/without haemoptysis and/or hypoxaemia), none had renal dysfunction, 7 patients had access site complications. Seven patients died during follow-up (none within 30 days from the procedure) because of sepsis (1), heart failure (1), cancer (2), arrhythmic storm (2), and sudden death in patients with severe coronary atherosclerosis (1).

Conclusions

BPA is a safe and effective treatment able to improve symptoms and haemodynamic profile. 45 Table 16MWD, six minute walking distanceCI, cardiac index; mPAP, mean pulmonary arterial pressure; PAC, pulmonary arterial compliance; PVR, pulmonary vascular resistance; RAP, right atrial pressure; SvO2, mixed venous oxygen saturation; WHO-FC, World Health Organization functional class.
53 Exercise oxygen kinetic in hypertrophic cardiomyopathy: results from a multicentre cardiopulmonary exercise testing study
Authors: Mapelli Massimo , Romani Simona , Magrì Damiano , Merlo Marco , Cittar Marco , Masé Marco , Muratori Manuela , Gallo Giovanna , Sclafani Matteo , Carriere Cosimo , Zaffalon Denise , Salvioni Elisabetta , Mattavelli Irene , Vignati Carlo , De Martino Fabiana , Rovai Sara , Autore Camillo , Sinagra Gianfranco , Agostoni Piergiuseppe
Published: December 2021

Aims

Reduced cardiac output (CO) has been considered crucial in symptoms’ genesis in hypertrophic cardiomyopathy (HCM). We evaluated the cardiopulmonary exercise testing (CPET) response in HCM focusing on parameters strongly associated with stroke volume (SV) and cardiac output (CO), such as oxygen uptake (VO2) and O2-pulse, considering both their absolute values and temporal behaviour during physical exercise.

Methods and results

We enrolled 312 non-end stage HCM patients, divided according to left ventricle outflow tract obstruction (LVOTO) at rest or during Valsalva manoeuver (72% with LVOTO < 30; 10% between 30 and 49; and 18% ≥50 mmHg). Peak VO2 (percent of predicted), O2-pulse, and ventilation to carbon dioxide production (VE/VCO2) slope did not change across LVOTO groups. Ninety-six (31%) HCM patients presented an abnormal O2-pulse temporal behaviour, irrespective of LVOTO values. These patients showed lower peak systolic pressure, workload (106 ± 45 vs. 130 ± 49 W), VO2 (74 ± 17% vs. 80 ± 20%) and O2-pulse (12 [9–14] vs. 14 [11–17]ml/beat), with higher VE/VCO2 slope (28 [25–31] vs. 27 [24–31]) (P < 0.005 for all). Only two patients had an abnormal VO2/work slope.

Conclusions

None of CPET parameters, either as absolute values or dynamic relationships, were associated with LVOTO. Differently, an abnormal O2-pulse exercise behaviour, which is strongly related to inadequate SV during exercise, correlates with reduced functional capacity (peak and anaerobic threshold VO2 and workload) and increased VE/VCO2 slope, helping identifying more advanced disease irrespectively of LVOTO. Adding O2-pulse kinetics evaluation to standard CPET could lead to a potential incremental benefit in terms of HCM prognostic stratification and, then, therapeutic management.
732 TEE role in patients selection for transcatheter edge to edge tricuspid repair
Authors: Filippis Aurelio De , Nobile Edoardo , Paolucci Luca , Vitez Luka , Bono Maria Caterina , Carpenito Myriam , Cammalleri Valeria , Mega Simona , Nusca Annunziata , Grigioni Francesco , Ussia Gian Paolo
Published: December 2021

Aims

The natural history of tricuspid valve (TV) regurgitation is characterized by dismal prognosis and high in-hospital mortality when treated with isolated TV surgery. Although the anatomy and the imaging of the TV are very challenging, the edge-to-edge repair with the TriClip (Abbott Vascular, Santa Clara, CA) showed promising results. We report preliminary results of our experience with the TriClip System in a cohort of ‘real life’ patients with functional tricuspid regurgitation (TR).

Methods and results

From January to September 2021, 30 consecutive patients with severe TR has been screened, 8 underwent transcatheter TriClip repair. The anatomical feasibility was established according to a complete transesophageal echocardiogram (TEE) and a dedicated CT scan for the right cardiac chambers. All the echocardiographic projections focused on right ventricle were used during the procedure, with the aim of optimizing the visualization of the catheters and device with respect to the anatomical structures of the tricuspid valve complex. The procedure was conducted under general anesthesia, guided by TEE and fluoroscopy. In-hospital and 30-day clinical and echocardiographic outcomes were recorded. The annulus septo-lateral diameter was enlarged in all cases, and functional TR was present in all patients. In two patients, the pacemaker lead interfered with leaflets coaptation. TR jet was predominantly central. The implant and procedural success were achieved in all cases, implanting one device in five patients and two in three patients. The final TR grade was 2+ in four patients and and 1+ in the others. All patients were extubated in the catheterization laboratory. There were no procedural or in-hospital adverse events. At 30-day follow-up, we observed significant improvement in clinical and echocardiographic outcomes.

Conclusions

In our experience, 26% of screened patients were selected for the procedure. Favourable anatomical findings for the TV edge-to-edge repair were the following: moderate leaflet tethering (coaptation depth <10 mm); large annulus but with small coaptation gap (<7 mm); antero-septal or postero-septal jet location; commissural jet; small right ventricular dimensions; pacemaker lead with no leaflet tethering. The best transcatheter approach consists of obliterating the antero-septal coaptation rim for a more favourable angle between the inferior vena cava and valvular plane. High-quality TEE imaging during the procedure is required for obtaining procedural success. Patient selection and tricuspid valve anatomy characterization with TEE and cardiac CT scan is critical for procedural success and clinical improvements.
114 Impact of left ventricular ejection fraction on procedural and long-term outcomes of bifurcation percutaneous coronary intervention
Authors: Gallone Guglielmo , Bruno Francesc , Filippo Ovidio De , Cerrato Enrico , Muscoli Saverio , Trabattoni Daniela , Mario Carlo Di , Doronzo Mattia , Conrotto Federico , Escaned Javier , Koo Bon-kwon , D’Ascenzo Fabrizio , Ferrari Gaetano Maria De
Published: December 2021

Aims

Longitudinal systolic function may integrate information on aortic stenosis (AS) natural history and cardiac comorbidities with potential prognostic implications. We explored the impact of tissue Doppler imaging (TDI)-derived longitudinal systolic function defined by the peak systolic average of lateral and septal mitral annular velocities (average S’) among symptomatic patients with severe AS undergoing transcatheter aortic valve implantation (TAVI).

Methods and results

297 unselected patients with severe AS undergoing TAVI from January 2017 to December 2018 at three European centres, with available average S′ at preprocedural echocardiography were retrospectively included. The primary endpoint was the Kaplan Meier estimate of all-cause mortality. After a median 18 months (IQR 12–18) follow-up, 36 (12.1%) patients died. Average S′ was associated with all-cause mortality (per 1 cm/s decrease: HR: 1.29, 95% CI: 1.03–1.60, P = 0.025), with a best cut-off of 6.5 cm/s. Patients with average S′ <6.5 cm/s (55.2% of the study population) presented characteristics of more advanced left ventricular remodelling and functional impairment along with higher burden of cardiac comorbidities, and experienced higher all-cause mortality (17.6% vs. 7.5%, P = 0.007) also when adjusted for in-study outcome predictors (adj-HR: 3.33, 95% CI: 1.25–8.90, P = 0.016). Results were consistent among patients with preserved ejection fraction, normal-flow AS, high-gradient AS and in those without left ventricular hypertrophy.

Conclusions

Longitudinal systolic function assessed by average S’ is independently associated with long-term all-cause mortality among unselected patients with symptomatic severe AS undergoing TAVI. In this population, an average S′ below 6.5 cm/s best defines clinically meaningful reduced longitudinal systolic function and may aid clinical risk stratification.
143 Incidence, predictors, and clinical impact of transient left bundle branch block in patients undergoing transcatheter aortic valve implantation
Authors: Leone Attilio , Franzone Anna , Avvedimento Marisa , Piccolo Raffaele , Angellotti Domenico , Mariani Andrea , Castiello Domenico Simone , Ilardi Federica , Manzo Rachele , Iapicca Cristina , Serafino Luigi Di , Cirillo Plinio , Esposito Giovanni
Published: December 2021

Aims

This study aims to evaluate the incidence and prognostic impact of transient left bundle branch block (LBBB) in patients undergoing transcatheter aortic valve implantation (TAVI) with balloon-expandable or self-expanding valves. Clinical, echocardiographic and electrocardiographic predictors of transient LBBB were also investigated.

Methods and results

197 patients treated with TAVI at Federico II University hospital, Naples, Italy were enrolled. Electrocardiograms (ECGs) were obtained before and after TAVI procedure, at discharge and at 30-day follow-up. ECGs were anonymously digitalized and analysed by five cardiologists. Transient LBBB was defined as LBBB regressed within 30 days after procedure. All ECGs for each patient were analysed by the same cardiologist. The primary endpoint of the study was all-cause mortality and permanent pacemaker implantation (PPI) at 1-month after TAVI. Secondary endpoints included cerebrovascular accidents, acute myocardial infarction, vascular complications, acute kidney injury, endocarditis, and re-hospitalization for all causes. Out of 197 patients enrolled, 54 (27.4%) developed transient LBBB. Among patients with transient LBBB, 70.4% were female. Mean age was higher in transient LBBB group compared with control group (81.0 ± 6.4 years, vs. 78. 6 ± 6.5 years; P = 0.022). From logistic analysis, peak transvalvular gradient (OR: 1.01, 95% CI: 0.93–1.00; P < 0.034) and left ventricular ejection fraction (LVEF) (OR: 0.96, 95% CI: 0.93–0.99, P < 0.012) were identified as predictive factors of transient LBBB. No differences between the two studied groups were observed in primary and secondary endpoints (all-cause mortality: 1.9% vs. 0.7%; P = 0.46; PPI: 9.6% vs. 12%; P = 0.80).

Conclusions

Peak transvalvular gradient and LVEF predict onset of transient LBBB, a common conduction disturbance after TAVI. Onset of transient LBBB does not correlate with worse clinical outcomes at 30 days.
349 Left atrial appendage closure with the II generation ultraseal device: an international registry. The ligate study
Authors: Liccardo Gaetano , Pivato Carlo A , Sanz-sanchez Jorge , Pelloni Elisa , Pudjak Krzysztof , Xuareb Robert G , Gonzalez Ignacio Cruz , Pisano Francesco , Tarantini Giuseppe , Cook Stephane , Regazzoli Damiano , Reimers Bernhard , Condorelli Gianluigi , Bragato Renato Maria , Stefanini Giulio G , Pagnotta Paolo
Published: December 2021

Aims

Left atrial appendage (LAA) occlusion with first generation Ultraseal device (Cardia, Eagan, Minnesota) has been shown to be a feasible therapeutic option in patients with non-valvular atrial fibrillation (NVAF). However, there is a paucity of data regarding the novel Ultraseal device. To assess feasibility and safety of second generation LAA closure Ultraseal device in patients with NVAF.

Methods and results

All patients with NVAF undergoing second generation Ultraseal device implantation between February 2018 and September 2020 were included in a multicentre international registry. Periprocedural and post-discharge events were collected up to 6-months follow-up. Primary efficacy endpoints of interest were device success and technical success; primary safety endpoint was in-hospital major adverse events occurrence. A total of 52 patients were included: mean age 75 ± 8, 69.2% male, mean HAS-BLED 3 ± 1. The device was successfully implanted in all patients. Technical success was achieved in 51 patients (98.0%). In-hospital major adverse event occurred in three patients (5.8%). The incidence of 6-months all-cause death and major bleeding was 11.6% and 2.1%, respectively. No strokes, transient ischaemic attacks, systemic embolisms or device embolization were reported.

Conclusions

Second generation Ultraseal Device implantation was associated with high procedural success rate and a low incidence of peri-procedural complications. Larger studies with longer follow-up are warranted to evaluate the safety and the efficacy of this device, especially at medium and long term follow-up.
369 Mono-orifice mitral valve after transcatehter repair with mitraclip system
Authors: Montalto Claudio , Mandurino-mirizzi Alessandro , Munafò Andrea Raffaele , Frassica Romina , Crimi Gabriele
Published: December 2021

A 70 years old male with non-ischaemic dilated cardiomyopathy (left ventricular end-diastolic volume, LVEDV, 200 mL), reduced left ventricular ejection fraction (LVEF, 30%) and worsening dyspnoea was screened for transcatheter repair of severe mitral regurgitation (MR). Baseline echocardiogram showed marked symmetrical bi-leaflet tethering with a symmetrical central jet. Etiology was predominantly functional with organic features including partial flail scallop (A1) and a ruptured second order chorda (Figure 1A). Pre-operative strategy was to deploy a single MitraClip NT in the central position. After correct deployment of the first clip, we observed a remarkable reduction of regurgitant jets in the lateral position accompanied by a complete holosystolic lack of leaflet coaptation in the medial orifice which caused significant residual regurgitation. (Figure 1B) MitraClip deployment in the commissural position is associated with technical challenges, including limited maneuvering, risk of chordae rupture and inability to retrieve the device if entangled. (1) Therefore, after careful crossing of the medial neo-orifice and rapid positioning a second MitraClip NT was implanted medial to the first device in the commissural position (Figure 2). As a result, the medial orifice was obliterated resulting in an atypical mono-orifice morphology which resembles a commissural edge-to-edge plasty. Anterograde flow was normal (G med 2.5 mmHg) and the trivial residual jet of MR was lateral to the two clips implanted. At 1-year follow-up the patient was asymptomatic (NYHA functional class I) with a stable mild MR and no change in anterograde gradients; positive remodelling of the left ventricle (LVEDP: −48 ml) and increased LVEF (+8%) were observed. 369 Figure 1.
734 Have I lost my large rupture cavity? The fingerprint of atherosclerotic plaque healing detected by serial optical coherence tomography imaging
Authors: Ricchiuto Alfredo , Vergallo Rocco , Lombardi Marco , Maino Alessandro , Bianchini Emiliano , Buonpane Angela , D’Ascenzo Domenico , Romagnoli Enrico , Leone Antonio Maria , Aurigemma Cristina , Burzotta Francesco , Trani Carlo , Crea Filippo
Published: December 2021

A 64-year-old man, prior smoker, with a history of paroxysmal atrial fibrillation was referred to our hospital due to worsening dyspnoea, progressively worsening angina, and a positive stress EKG testing. Coronary angiography (CAG) showed an angiographically intermediate stenosis of the mid left anterior descending (LAD) artery and a focal, complex lesion of the distal right coronary artery (RCA) (Figure 1A and B, red arrow). Treatment of the LAD stenosis was deferred based on a negative fractional flow reserve value (i.e. 0.85). Optical coherence tomography (OCT) imaging (ILUMIEN OPTIS, Abbott Vascular, Santa Clara, CA) was performed to better characterize the RCA lesion, which disclosed a ruptured thin-cap fibroatheroma (TCFA) with a large ‘empty’ cavity (Figure 1C–G, red arrows) and overlying ‘layered’ tissue (Figure 1H, white arrowheads). Based on these OCT findings, suggestive of initial plaque healing, and on a large residual lumen dimension (i.e. minimum lumen area, MLA, at the rupture site: 7.7 mm2), this lesion was not treated with percutaneous coronary intervention. The patient was discharged on aspirin, edoxaban, metoprolol, rosuvastatin, and ezetimibe, and remained clinically stable for more than 1 year. Due to angina recurrence, a new CAG was performed 18 months after the first admission, revealing a progression of the mid LAD stenosis that was treated with a 2.5/28 mm drug-eluting stent, and an improvement of the RCA lesion angiographic appearance (smooth contour) (Figure 1A′–B′). RCA OCT imaging was repeated demonstrating a complete healing of the large rupture cavity with all the hallmarks of the reparative process (Figure 1C′–H′): (1) re-established fibrous cap integrity and smooth vessel lumen profile; (2) thickening of the fibrous cap and reduction of lipid burden (i.e., transformation of TCFA into thick-cap fibroatheroma, ThCFA); (3) replacement of the ‘empty’ cavity with new ‘granulation tissue’; (4) initial calcification of the plaque; (5) heterogeneous signal-rich layers with distinct optical-signal intensity (layered, ‘onion-like’ pattern); and (6) mild lumen narrowing (MLA at the rupture site: 6.9 mm2).
607 Comparison of incidence and predictors of new left bundle branch block and permanent pacemaker implantation in a large multicentre contemporary TAVI registry using the Evolut R/pro system vs. the accurate neo valve
Authors: Sticchi Alessandro , Gallo Francesco , Marzo Vincenzo De , Won-keun Kim , Khokhar Arif A , Zeus Tobias , Toggweiler Stefan , Marco Federico De , Reimers Bernhard , Nombela-franco Luis , Barbanti Marco , Brugaletta Salvatore , Piva Tommaso , Rodes-cabau Josep , Porto Italo , Colombo Antonio , Giannini Francesco
Published: December 2021

Aims

Conduction disorders and permanent pacemaker implantation (PPI) continue to be an important issue in patients who undergo transcatheter aortic valve implantation (TAVI). The aim of this study was to investigate the incidence and clinical outcomes of new left bundle branch block (LBBB) and PPI after TAVI in a comparison between two self-expandable supra-annular transcatheter valves.

Methods and results

We report the data from an international, retrospective registry including 3862 consecutive patients who underwent TAVI with two self-expanding transcatheter heart valves (Medtronic Evolut R/PRO and Boston ACURATE neo). Patients with pre-existing left or right bundle branch block, any atrioventricular blocks or previous pacemaker implantation were excluded. Finally, we performed a propensity score matched analysis (PSM) to match the patients and overcome pre-procedural differences reaching 427 couples. New-onset Left Bundle Branch Block (LBBB) occurred with a rate of 13.1% (56/427) in the ACURATE group and 18.7% (80/427) in the Evolut group (P = 0.031). The incidence of new permanent pacemaker implantation was 16.4% (70/427) in the Evolut group and 6.8% (29/427) in the ACURATE group, respectively (P < 0.001). In the multivariate regression analysis, we found the valve recapture [odds ratio (OR): 4.66, 95% confidence interval (CI): 1.08–23.75, P = 0.042] as significant predictors for LBBB, and male sex (OR: 1.59, CI: 1.03–2.46, P = 0.036), ACURATE valve (OR: 0.34, CI: 0.20–0.57, P < 0.001) and post-procedure LBBB (OR: 4.38, CI: 2.78–6.85, P < 0.001) for PPI.

Conclusions

In our large multi-centre contemporary cohort of patients, new LBBB and PPI occurred more frequently in patients following TAVI with Evolut R/PRO vs. ACURATE valve. However, the choice of the valve seemed to influence only the rate of pacemaker implantation and not the incidence of new LBBB. Further data is required to clarify the impact of valve design on conduction abnormalities.
475 Is left atrial appendage device compression rate a predictor of incomplete occlusion in patients undergoing watchman device implantation?
Authors: Magnocavallo Michele , Rocca Domenico Giovanni Della , Lavalle Carlo , Chimenti Cristina , Carola Gianni , Mohanty Sanghamitra , Trivedi Chintan , Bassiouny Mohamed , Al-Ahmad Amin , Burkhardt David J , Gallinghouse Joseph G , Sanchez Javier E , Horton Rodney P , Natale Andrea
Published: December 2021

Aims

Transesophageal echocardiography (TEE) is a standard peri-procedural imaging modality in patients undergoing percutaneous left atrial appendage (LAA) occlusion. An accurate device sizing is pivotal to assess stability and achieve successful closure. In this prospective study, we sought to evaluate the correlation between Watchman device compression rates (DCRs) and risk of incomplete LAA occlusion at follow-up in patients undergoing Watchman device implantation.

Methods and results

Two-dimensional TEE via a commercially available transducer (Vivid, Philips) was performed during the procedure and within 3 months after the procedure. LAA size, morphology, and DCRs [(original device size—size after deployment)/original device size; %] were assessed in a mid-oesophageal view at 0°, 45°, 90° and 135°, according to company recommendations. Residual leaks ≥ 3 mm were classified as significant. Between 2016 and 2018, 116 patients underwent LAA occlusion with a Watchman device at our institution. The mean age was 74 ± 9 years and 60.4% (n = 70) were males. The average CHA2DS2-VASc and HAS-BLED scores were 4.7 ± 1.7 and 2.5 ± 1.1, respectively. The final device size was 21 mm in 11 (9.5%) patients, 24 mm in 28 (24.1), 27 mm in 27 (23.3%), 30 mm in 26 (22.4%), and 33 mm in 24 (20.7). At follow-up TEE, 16 (13.8%) patients were found to have a significant (≥3 mm) residual leak. The average DCRs measured at different angles in patients with and without leak were not significantly different (24 ± 8% vs. 26 ± 7% at 0°, P = 0.47; 23 ± 9% vs. 25 ± 7% at 45°, P = 0.58; 23 ± 8% vs. 23 ± 6% at 90°, P = 0.61; 22 ± 8% vs. 21 ± 7% at 135°, P = 0.61). At receiver operating characteristic (ROC) analysis, the areas under the curve to discriminate between patients with/without leak were 0.58, 0.57, 0.55, and 0.46 for DCRs measured at 0°, 45°, 90°, and 135° angles.

Conclusions

Peri-procedural assessment of DCRs does not appear to be an accurate method to predict LAA complete occlusion in patients undergoing Watchman device implantation.