bluuebunny/crossref_metadata_2025_split huggingface dataset:
85 Diuretics trajectories in dilated cardiomyopathy
Authors: Nuzzi Vincenzo , Cannatà Antonio , Manca Paolo , Gregorio Caterina , Barbati Giulia , Stolfo Davide , Merlo Marco , Sinagra Gianfranco 
Published: December 2021

Abstract

Aims
Diuretics in heart failure (HF) are commended to relieve symptoms at lowest dosage effective. Dilated cardiomyopathy (DCM) is a particular HF setting with several variables that may influence disease trajectory. We aimed to assess the long-term use of diuretics in DCM, the possibility of withdrawal and to explore the prognostic correlations.

Methods and results
All consecutive DCM patients enrolled from 1990 to 2018 were considered eligible. All the patients had available the information about the furosemide-equivalent dose at baseline and at follow-up evaluation within 24 months. Patients were categorized in stable (diuretic dose variation &lt;50%), increasers (diuretics dose increase ≥50% or initiation of diuretic therapy), and decreasers (diuretics dose decrease ≥50% or never prescribed diuretics in the 24-months observation period). The prognostic role of the diuretics trajectory group was assessed with Kaplan Meier analysis and with a time-dependent multivariable model. The outcome measure was a composite of all-cause death/heart transplantation/HF hospitalization (ACD/HTx/HFH). 908 patients were included [mean age 50 ± 16, 70% male sex, 24% NYHA class III or IV, mean left ventricular ejection fraction (LVEF) 31 ± 9%, 66% treated with diuretics at baseline]. The furosemide-equivalent dose at enrolment had a linear association with the risk of outcome. Compared to other groups, decreaser patients were younger, had less HF symptoms, higher LVEF and more dilated left atrium. Decreasers had a lower prescription rate of diuretics and less frequent indication to renin-angiotensin inhibitors and mineralocorticoid receptors antagonists. Over a median follow-up of 122 (62–195) months decreasers had the lowest incidence of outcome, followed by stable, while increasers had the worst outcome (P &lt; 0.001). After adjustment for other prognosticators, compared to stable patients, decreasers had a reduced risk of ACD/HTx/HFH [HR: 0.497 (95% CI: 0.337–0.731)] while increasers had the highest risk of adverse outcome [HR: 2.027 (95% CI: 1.254–3.276)]. Similarly, amongst patients taking diuretics at baseline, the diuretics withdrawal was in independent outcome predictor. The only multivariable predictors of diuretics withdrawal were younger age and lower furosemide-equivalent dose at enrolment.

Conclusions
In DCM patients the diuretics dose at baseline is a strong prognosticator. Diuretics dose reduction or its withdrawal provides a prognostic benefit on hard outcome. Diuretics tapering in selected patients should be considered in the short-term follow-up to improve DCM prognosis.
279 Medical treatment with ARNI may reduce indications for primary prevention of sudden cardiac death in heart failure with reduced ejection fraction: insights from discover-ARNI, a multicentre Italian register
Authors: Pastore Maria Concetta , Mandoli Giulia Elena , Giannoni Alberto , Benfari Giovanni , Dini Frank Lloyd , Rosa Gianmarco , Pugliese Nicola Riccardo , Taddei Claudia , Correale Michele , Brunetti Natale Daniele , Magnesa Michele , Carluccio Erberto , Mengoni Anna , Guaricci Andrea Igoren , Piscitelli Laura , Citro Rodolfo , Ciccarelli Michele , Novo Giuseppina , Corrado Egle , Pasquini Annalisa , Loria Valentina , Carli Giuseppe De , Degiovanni Anna , Patti Giuseppe , Santoro Ciro , Moderato Luca , Cicoira Mariantonietta , Canepa Marco , Malagoli Alessandro , Emdin Michele , Cameli Matteo 
Published: December 2021

Abstract

Aims
This sub-study deriving from a multicentre Italian register (DISCOVER-ARNI) investigated whether sacubitril/valsartan in adjunction of optimal medical therapy (OMT) could reduce the rate of implantable cardioverter-defibrillator(ICD) indications for primary prevention in heart failure with reduced ejection fraction (HFrEF) according to European guidelines indications, and its potential predictors.

Methods and results
In this observational study, consecutive patients with HFrEF eligible for sacubitril/valsartan from 13 Italian centres were included. Lack of follow-up or speckle tracking data represented exclusion criteria. Demographic, clinical, biochemical and echocardiographic data were collected at baseline and after 6 months of therapy. Of 351 patients, 225 (64%) were ICD carriers and 126 (36%) were not ICD carriers (of whom 13 had not indication) at baseline. After 6 months of sacubitril/valsartan, among 113 non-ICD carriers despite having baseline left ventricular (LV)EF ≤ 35% and New York Heart Association (NYHA) class = II–III, 69(60%) did not show ICD indications; 44(40%) still fulfilled ICD criteria (Figure 1). Age, atrial fibrillation, mitral regurgitation&gt;moderate, left atrial volume index (LAVi), and LV global longitudinal strain (GLS) significantly varied between the groups. With ROC curves, age ≥ 75 years, LAVi ≥ 42 ml/m2 and LV GLS ≥ −8.3% were associated with ICD indications persistence (AUC = 0.65, 0.68, and 0.68, respectively). With univariate and multivariate analysis, age and LV GLS emerged as the only significant predictors of ICD indications at follow-up.

Conclusions
Sacubitril/valsartan provided early improvement of NYHA class and LVEF, reducing the possible number of implanted ICD for primary prevention in HFrEF. Baseline advanced age and reduced LV GLS were markers of ICD indication despite OMT. Early therapy with sacubitril/valsartan may save infective/haemorrhagic risks and unnecessary costs deriving from ICDs.
393 Long-term prognostic value of haemodynamic determinants of right ventricular pulsatile afterload in patients with advanced heart failure
Authors: Rubino Francesca , Scarsini Roberto , Piccoli Anna , Biagio Livio San , Tropea Ilaria , Onorati Francesco , Faggian Giuseppe , Pighi Michele , Tavella Domenico , Mammone Concetta , Ribichini Flavio 
Published: December 2021

Abstract

Aims
Right ventricular (RV) dysfunction demonstrated a strong impact on survival of patients with advanced heart failure with reduced ejection fraction (HFrEF). Increased RV afterload is associated with poor prognosis in patients with HF. To examine the prognostic relevance of RV pulsatile afterload parameters, in particular pulmonary artery compliance (PAC), elastance (PAE), and pulsatile index (PAPi) in a large cohort of patients with advanced HFrEF evaluated for heart transplantation (HT).

Methods and results
149 patients with HFrEF enlisted for HT were evaluated with right heart catheterization (RHT) and echocardiography and were followed until death or any censoring events including HT, left ventricular assist device (LVAD), and hospitalization for acute heart failure (HHF). Cox regression and ROC-curve analysis were used to test the prognostic value of RV pulsatile afterload determinants. During a mean observation time of 500 ± 424 days, the primary endpoint occurred in 29 (19.5%) patients. The mean age was 56.6 ± 10.1 years and 85.2% were male. The most frequent etiology of HF was ischaemic cardiomyopathy (52.3%). Mean LV ejection fraction was 25.7 ± 10.2%. Patients who met the primary endpoint were significantly older and with worse haemodynamic profile than event-free survivors. In particular, the primary endpoint occurred in patients with lower PAC (1.8 ± 0.8 vs. 2.7 ± 2.0, P = 0.01), higher mean pulmonary arterial pressure (mPAP) (33.5 ± 11.3 vs. 29.3 ± 11.0, P = 0.05), PVR (3.0 ± 1.6 vs. 2.6 ± 2.0, P = 0.09), and PEA (1.12 ± 0.5 vs. 0.98 ± 0.6, P = 0.04). A significant increased risk of adverse outcome was observed in patients with PAC &lt;1.9 ml/mmHg (HR: 3, 95% CI: 1.3–6, P = 0.007), PEA &gt; 0.9 mmHg/ml (HR: 2.5, 95% CI: 1.1–5.2, P = 0.02) and mPAP ≥25 mmHg (HR: 3.0, 95% CI: 1.0–7.5, P = 0.03). The predictive value of PAC was superior compared with PVR (AUC comparison, P = 0.019) and PAPi (P = 0.03). Conversely, PAC presented similar prognostic accuracy compared with mPAP (P = 0.51) and PEA (P = 0.19). Moreover, PAC demonstrated incremental prognostic value compared with the cardiac index (P = 0.02), whereas mPAP and PAE did not.

Conclusions
Impaired haemodynamic RV parameters are associated with worse survival in patients with advanced HFrEF. Pulsatile RV afterload indices should be considered in the evaluation of patients enlisted for HT. PAC demonstrated an independent prognostic value in this highly selected cohort of patients awaiting HT.
545 Cardiac protection by pirfenidone after myocardial infarction: a bioinformatic analysis
Authors: Aimo Alberto , Iborra-Egea Oriol , Martini Nicola , Galvez-Monton Carolina , Burchielli Silvia , Panichella Giorgia , Passino Claudio , Emdin Michele , Bayes-Genis Antoni 
Published: December 2021

Abstract

Aims
Left ventricular (LV) remodelling after myocardial infarction (MI) is promoted by an intense fibrotic response, which could be targeted by an anti-fibrotic drug such as pirfenidone.

Methods and results
We explored the relationship between protein modulation by pirfenidone and post-MI remodelling, based on publicly available molecular information and transcriptomic data from a swine model of MI. We also compared the effects of pirfenidone and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEi/ARB), mineralocorticoid receptor blockers (MRA) and beta-blockers. We identified six causative motives of post-MI remodelling (cardiomyocyte cell death, impaired myocyte contractility, extracellular matrix remodelling and fibrosis, hypertrophy, renin–angiotensin–aldosterone system activation, and inflammation), 4 pirfenidone targets and 21 bioflags (indirect effectors). When considering both targets and bioflags, pirfenidone showed a broad relationship encompassing all six motives. p38γ-MAPK12 blockade inhibits cardiomyocyte apoptosis, cardiomyocyte hypertrophy and inflammation. Furthermore, pirfenidone can modulate extracellular matrix remodelling and cardiac fibrosis by targeting the TGFβ1-SMAD2/3 pathway and other effector proteins such as matrix metalloproteases 2 and 14, PDGFA/B, and IGF1, which promote myocardial fibrosis, cardiomyocyte hypertrophy and impaired contractility. All the gold standard drugs were found to be important for specific clinical motives, but pirfenidone had a more widespread action on the molecular pathways active in the post-MI setting.

Conclusions
A bioinformatic approach allowed to identify several possible mechanisms of action of pirfenidone with beneficial effects in the post-MI LV remodelling, and suggests additional effects over guideline-recommended therapies. These findings support clinical studies evaluating the beneficial effects of pirfenidone in patients with MI.
766 Distal embolization protection systems. A rare complication
Authors: Aste Francesca , De Candia Gianfranco , Lai Giorgio , Cadeddu Mauro , Secchi Sara , Pettinau Antonio , Ricci Sara Jane , Meloni Luigi , Montisci Roberta 
Published: December 2021

Abstract

Aims
The no reflow phenomenon is a not rare complication that occurs in up to 30% of patients with acute coronary syndrome undergoing myocardial reperfusion by percutaneous coronary intervention. The use of coronary artery thrombus aspiration or distal embolization protection systems has reduced the risk of distal embolization and no-reflow phenomenon.

Methods and results
We describe the case of a 77 year old female suffering from hypertension presented at our emergency department for inferior STEMI. An urgent coronary angiography was performed, showing a three-vessel coronary artery disease with right coronary artery sub-occluded in the middle segment (culprit lesion), with a voluminous endoluminal minus image, as intracoronary thrombosis. Before performing the coronary angioplasty, a Spider FX3 filter was placed on the distal segment of the right coronary artery; thrombus aspiration was performed, which was ineffective, then angioplasty and Zotarolimus eluting stent implantation in the mid segment of the right coronary artery. After stent implantation, an image of minus was highlighted inside the basket of the filter, as a migrated and incarcerated thrombotic formation; then, the filter was removed. During the removal of the filter, longitudinal crush of the distal portion of the stent is caused, with limitation of the downstream flow, in the absence of haemodynamic instability. The stent was recrossed with Fielder XT guidewire supported by Turnpike LP Microcatheter. Multiple dilations werenperformed with semi-compliant and non-compliant increasing-caliber balloons and then Zotarolimus eluting stent implantation, in partial overlap with the distal portion of the previously implanted stent, with TIMI flow 3. The echocardiogram showed a normal global systolic function, with alterations in regional kinetics. On the 6th day, angioplasty and Zotarolimus eluting stent implantation was performed on the mid-proximal segment of the left anterior descending artery. During the hospitalization the patient was stable and has been discharged in good condition on the ninth day.

Conclusions
The interest of this case is the evidence of a rare complication related to the use of distal embolization protection system, probably due to an incomplete closure of the filter before removal, due to the high amount of thrombotic material inside it. The rapid recrossing of the stent after the longitudinal crush, the angioplasty and the second stent implantation, led to a quick flow restoration, without haemodynamic and clinical consequences on the patient's outcome.
658 Impairment of strain reserve extends to remote myocardium in the sub-acute phase of ST-elevation myocardial infarction
Authors: Diana Giovanni , Manfredonia Laura , Filice Monica , Ravenna Emanuele , Ingrasciotta Gessica , Ruscio Eleonora , Graziani Francesca , Lombardo Antonella , Lanza Gaetano Antonio , Crea Filippo , Locorotondo Gabriella 
Published: December 2021

Abstract

Aims
In ST-elevation myocardial infarction (STEMI), subtle tissutal changes in remote myocardium predict long-term left ventricular (LV) remodelling and prognosis, independently of infarct size and microvascular obstruction. Whether there is a subclinical dysfunction of remote myocardium, detectable by longitudinal strain (LS) at echocardiography, and whether it varies in different locations of STEMI and with adenosine (ADO) challenge, is still unknown.

Methods and results
Fifty-three patients (age 65 ± 12.5 years, 44 male, 20 anterior and 33 non-anterior, P = 0.01) underwent rest/stress echocardiography at 7 ± 2 days after successfully treated STEMI, and at 6-months follow-up. Global LS (GLS), ischaemic and remote LS (iLS and rLS) were analysed in anterior and non-anterior STEMI. Both at rest and at follow-up, GLS was stratified by ejection fraction (EF) into three groups: EF &lt; 40%, 40–49%, and ≥50%. Normal subjects, undergoing ADO stress echo, represented controls. Anterior STEMI showed lower GLS than controls (P &lt; 0.001) and non-anterior STEMI (P &lt; 0.001). ADO increased GLS in controls (P = 0.05), but neither in anterior nor in non-anterior STEMI, GLS changed during ADO stress, although significantly improved at follow-up (P &lt; 0.001 and P = 0.002, respectively). In anterior STEMI, rLS was comparable to iLS at rest, during stress and at follow-up (P = ns), while in non-anterior STEMI rLS was higher than iLS throughout the study (P &lt; 0.001). Patients with EF &lt; 40% and 40–49% had similar values of GLS, iLS, and rLS, which were, both at rest and at follow-up, lower than those of patients with EF ≥ 50% (P &lt; 0.001).

Conclusions
In the subacute phase, anterior STEMI shows the worst impairment of LS in both ischaemic and remote regions. Strain reserve to ADO is absent in remote myocardium, as well as in ischaemic zone, regardless of MI location. Global, ischaemic and remote LS may improve at follow-up.
243 Mental health status and sexual habits in young patient after acute coronary syndrome
Authors: Nicolò Claudio , Franzino Marco , Pistelli Lorenzo , De Sanctis Giulia , Parisi Francesca , Migliorato Alessandro , Grimaldi Patrizia , Crea Pasquale , Luzza Francesco , Carerj Scipione , Di Bella Gianluca , Costa Francesco , Micari Antonio 
Published: December 2021

Abstract

Aims
Acute coronary syndrome (ACS) has a huge potential impact on patients’ life, and little is known on the long-term effect on mental health in young patients.

Methods and results
We included consecutive young patients (≤45 years at presentation) with ACS referred from October 2013 until March 2021 to our clinic. Physical and mental status was evaluated through the standardized SF12 scale for physical (PCS) and mental status (MCS). Depression and perceived stress were evaluated with the patient health questionnaire 9 (PHQ9) and perceived stress scale (PSS). A total of 91 patients have been included and followed for a median of 40 months. History of anxiety or depression at baseline was reported in 1.1% and 2.2%, respectively. Physical and mental health status was impaired in 65.8% and 42.1% of patients, respectively (Figure). Predictors of poorer physical health were lower LVEF, WMSI, and multivessel disease. Predictors of poorer mental health were age and nuisance bleeding during follow-up. Mild/moderate depression was reported in 47.3%. Moderate/high stress was reported in 78.1%. 37.1% patients affirmed that their career trajectory worsened after the event and 37.8% declared a reduction of income. 53.8% declared mild to significant changes in their sexual activity, while 83.8% declared to have received no advises on sexual activity from their Doctor.

Conclusions
In conclusion, ACS is a dramatic event with a significant impact on young patients’ life at a physical, mental, and social level. Measures of social/psychological support in the aftermath of the event merit consideration in future research.
401 Myocardial viability and ischaemia assessment in chronic coronary total occlusions according to collaterals distribution: a retrospective analysis
Authors: Pinto Giuseppe , Chiarito Mauro , Liccardo Gaetano , Baggio Sara , Bacci Elodi , Gasparini Gabriele , Francone Marco , Stefanini Giulio , Condorelli Gianluigi , Monti Lorenzo 
Published: December 2021

Abstract

Aims
Whether CTO-PCI (chronic total occlusions—percutaneous coronary intervention) offers clinical benefit over optimal medical therapy is still a matter of debate. Viability and ischaemia assessment could improve selection of candidates to PCI. Traditionally, well-developed collaterals are considered a marker of myocardial viability in CTO territory. Current literature offers few data concerning the relationship between viability/ischaemia and collaterals distribution.

Methods and results
We retrospectively analysed the Cardiovascular Magnetic Resonance (CMR) studies and coronary angiographies of patients with at least one CTO referred at Humanitas Research Hospital between June 2009 and September 2020. We included 131 patients who underwent CMR with LGE assessment; of them, 111 (85%) underwent stress-CMR with adenosine. AHA segments (16 segment/patient for a total of 2096 segment assessed) were assessed on three short axis projection and scored for WMSI on cine images, for the presence of ischaemia on first pass perfusion, and for viability on LGE images. Viability was defined as LGE transmurality ≤50% and WMSI (wall motion score index) &gt;1. Patients were divided in three groups according to collaterals distribution at coronary angiography:
Patients with TD collaterals were more likely to have viable segments in the CTO-territory (90% of the segments in TD, 76% in WD, and 71% in PD, coeff. 0.107, P &lt; 0.001). No statistically significant differences were found between groups as regard the amount of ischaemic segments (61% of the segments in TD, 65% in WD, and 60% in PD, P = 0.189).

Conclusions
The presence of myocardial viability is slightly associated with the degree of coronary collateralization at coronary angiography while the amount of ischaemia is not. Stress CMR should be considered in CTO patients before a reopening attempt.
418 Titin mutations and female sex characterize dilated cardiomyopathy in the elderly
Authors: Cannata Antonio , Merlo Marco , Dal Ferro Matteo , Manca Paolo , Paldino Alessia , Barbati Giulia , Graw Sharon , Bromage Daniel , Johnson Renee , Roy Darius , Gigli Marta , Stolfo Davide , Abbate Antonio , Parkih Victoria , Ashley Euan , Lakdawala Neal , Carr-White Gerry , Fatkin Diane , Mcdonagh Theresa , Taylor Matthew , Mestroni Luisa , Sinagra Gianfranco 
Published: December 2021

Abstract

Aims
Dilated cardiomyopathy (DCM) is frequently caused by genetic factors. Studies identifying deleterious rare variants have predominantly focused on early-onset cases, and little is known about the genetic underpinnings of the growing numbers of patients with DCM who are diagnosed after 60 years of age (i.e. late-onset DCM). The aim is to investigate the prevalence, type, and prognostic impact of disease-associated rare variants in late-onset DCM patients.

Methods and results
We analysed a population of late-onset DCM patients who had undergone genetic testing in seven international tertiary referral centres worldwide. A positive genotype was defined as the presence of ‘pathogenic’ or ‘likely pathogenic’ (P/LP) variants. The study outcome was all-cause mortality. 184 patients over age 60 years (56% females, mean age 67 ± 6 years, mean left ventricular ejection fraction 32 ± 10%) were studied. Sixty-six patients (36%) were carriers of a P/LP variant. Titin truncating variants (TTNtv) were the most prevalent (present in 25% of the total population and accounting for 69% of all genotype-positive patients). During a median follow-up of 42 months (interquartile range: 10–115), 23 patients (13%) died; 17 of these (25%) were carriers of P/LP variants while six patients (5.1%) were genotype-negative (P &lt; 0.001).

Conclusions
In the largest series worldwide, to date, of patients with late-onset DCM, we found a high prevalence of female sex and a high genetic mutation burden, largely due to TTNtv. Patients with a positive genetic test had higher mortality than genotype-negative patients. These findings support the extended use of genetic testing also in the elderly.
415 Correlation between tissue abnormalities and myocardial deformation indices in arrhythmogenic cardiomyopathy: a pilot study
Authors: De Luca Antonio , Cappelletto Chiara , Perotto Maria , Stolfo Davide , Merlo Marco , Sinagra Gianfranco 
Published: December 2021

Abstract

Aims
To evaluate the correlation between cardiac magnetic resonance (CMR) tissue abnormalities and impairment of myocardial deformation indices in patients with definite diagnosis of arrhythmogenic cardiomyopathy (AC).

Methods and results
41 AC Patients with available CMR study were enrolled. Myocardial deformation indices (i.e. global longitudinal strain -GLS-; global circumferential strain -GCS-; global radial strain -GRS-) for both ventricles were calculated using feature tracking analysis. Quantification of tissue abnormalities (i.e. late gadolinium enhancement -LGE- extension expressed as percentage of total ventricular mass) was performed. Spearman’s rho correlation was evaluated. Mean age was 44 ± 13 years and 26 (63%) patients were male. Mean left ventricular (LV) ejection fraction (EF) was 54 ± 10% and mean right ventricular (RV) EF was 49 ± 12%. Median LV LGE extension was 8.9% (1.05–21) and median RV LGE extension was 0 (0–6.92). All myocardial deformation indices were moderately associated with LGE extension (for LV 3D GLS Spearman’s Rho 0.423, P 0.016; 2D GCS Spearman’s Rho 0.388, P 0.028; 3D GCS 0.362, P 0.042; 2D GRS Spearman’s Rho −0.417, P 0.018; 3D GRS −0.396, P 0.025; for RV 2D GLS Spearman’s Rho 0.385, P 0.030; RV GCS Spearman’s Rho 0.450, P 0.010; RV GRS Spearman’s Rho −0.459, P 0.008).

Conclusions
All myocardial deformation indices showed a moderate association with LGE extension in a cohort of patients with definite AC. Further studies are needed to validate this observation and understand its implications.