bluuebunny/crossref_metadata_2025 huggingface dataset:
120 Safety and efficacy of renal artery denervation for uncontrolled-resistant hypertension in a high risk population with CKD: the Verona real-world experience
Authors: Fezzi Simone , Castaldi Gianluca , Widmann Maddalena , Marin Federico , Ruzzarin Alessandro , Tavella Domenico , Ribichini Flavio
Published: December 2021

Aims

To evaluate the safety and the efficacy of catheter-based radiofrequency renal sympathetic denervation (RSD) in a daily practice population of patients with uncontrolled resistant hypertension on top of medical therapy.

Methods and results

Consecutive unselected patients with uncontrolled resistant hypertension undergoing RSD were enrolled. Office and ambulatory blood pressure (BP) monitoring were collected at baseline and 3, 6, and 12 months after RSD. Efficacy was assessed also in patients with an estimated glomerular filtration rate below 45 ml/min/1.73 m2. Patients were defined responders to RSD if systolic BP decreased by at least 5 mmHg at ambulatory BP or by 10 mmHg at office BP at the last follow-up available. Fifty-four patients with multiple comorbidities underwent RSD for uncontrolled-resistant hypertension from 2012 to 2021. Baseline office and ambulatory BP was 161.0/87.2 ± 24.1/15.6 mmHg and 155.4/87.5 ± 19.3/14.6 mmHg, respectively. At 12-month follow-up a significant reduction of office and ambulatory systolic BP, respectively by − 15.66 ± 29.73 mmHg (P < 0.01) and by − 11.3 ± 23.1 mmHg (P < 0.05), was noticed. BP reduction at 12-month follow-up among patients with eGFR <45 ml/min was similar to that obtained in patients with higher eGFR. Among patients treated before July 2020 with available follow-up (45/54) 36 patients (80%) were classified as responders. Combined hypertension, higher ambulatory systolic BP and lower E/E’ at baseline emerged as predictors of success of RSD at univariate analysis. Among responders and non-responders, the average medication number showed no significant difference at baseline and during follow-up. No major complications were observed and renal function was stable up to 12 months, even in patients with lowest eGFR at baseline.

Conclusions

RSD is safe and feasible in patients with uncontrolled resistant hypertension on top of medical therapy, even in a high-risk CKD population with multiple comorbidities, with a significant reduction of systolic BP and a trend of reduction of the diastolic BP up to 12 months. 775 Figure
256 Impact of physiologically diffuse vs. focal pattern of coronary disease on quantitative flow reserve diagnostic accuracy
Authors: Scarsini Roberto , Fezzi Simone , Pesarini Gabriele , Sole Paolo Alberto Del , Mammone Concetta , Marcoli Michele , Venturi Gabriele , Tavella Domenico , Pighi Michele , Ribichini Flavio
Published: December 2021

Aims

Fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) disagree in ∼20% of intermediate coronary lesions. The physiological pattern of disease has a significant influence on FFR-iFR discordance. However, if the pattern of disease (diffuse vs. focal) impacts on QFR accuracy and on its agreement with FFR and iFR remains unknown.

Methods and results

194 unselected patients with 224 intermediate coronary lesions were investigated with iFR, FFR and QFR. The physiological pattern of disease was independently assessed with iFR Scout pullback in all the cases by two expert interventional cardiologists who were blinded to the clinical presentation, patient characteristics, coronary angiography and QFR results. A predominantly physiologically focal pattern was observed in 81 (36.2%) lesions, whereas a predominantly physiologically diffuse was observed in 143 (63.8%) cases. QFR demonstrated a significant correlation (r = 0.581, P < 0.001) and a substantial agreement with iFR, both in diffuse (AUC = 0.798) and in focal (AUC = 0.812) pattern of disease. Disagreement between QFR and iFR was observed in 51 (22.8%) lesions, consisting of iFR+/QFR − (64.7%) and iFR−/QFR + (35.3%). Notably, the physiological pattern of disease was the only variable significantly associated with iFR/QFR disagreement. In particular, coronary lesions with iFR+/QFR− demonstrated a significantly higher prevalence of predominantly physiologically diffuse pattern of disease compared with the subgroup with iFR−/QFR + [81.3% (26 of 32) vs. 55.6% (10 of 18); P = 0.012]. QFR virtual pullback demonstrated an excellent agreement (83.9%) with iFR Scout pullback in classifying the physiological pattern of disease.

Conclusions

QFR has a good diagnostic accuracy in assessing myocardial ischemia independently of the pattern of coronary disease. However, the physiological pattern of disease has an influence on the QFR/IFR disagreement, which occurs in ∼20% of the cases. The QFR virtual pullback correctly defined the physiological pattern of disease in the majority of the cases using the iFR pullback as reference.
214 Covered stent in a chest trauma: congenital coronary arterial fistula or traumatic coronary perforation?
Authors: Marsico Fabio , Carpinella Gerardo , Scalise Martina , Esposito Mafalda , Furbatto Fulvio , D’Andrea Davide , Serino Federica , Ziviello Francesca , Rumolo Salvatore , Bitello Carlo , Crispo Salvatore , Mauro Ciro
Published: December 2021

Aims

Coronary arterial fistula consists in a communication between a coronary artery and a cardiac cavity. It is tipically a congenital condition, but it can also be a result of invasive cardiac procedure. Although chest truama generally evolve to massive pericardial effusion, in some cases it can determine also a coronary perforation, with a consequent coronary arterial fistula.

Methods and results

A 22-year-old male patient, with no cardiovascular history, was admitted after a road accident, reporting pelvis break, 17 costal break, and sternal break, with consequent chest pain. On admission the patient had a heart rate of 100 b.p.m. and a blood pressure of 130/80 mmHg. Elettrocardiogram (ECG) reported ST elevation in antero-septal derivations (V1–V4). Echocardiogram showed a global left ventricular (LV) ejection fraction of 55%, with an apical-septal akinesia, with a minimal anterior pericardial effusion, not emodinamically significant. So, an emergency coronary angiography was performed, showing a fistula of the distal segment of the left anterior discendent coronary (LAD). In this case there were two possible options, a previously unknown congenital coronary arterial fistula, or a traumatic coronary perforation, determining a coronary arterial fistula. Considering the possibility of a traumatic coronary perforation, with the consequent risk of rapid pericardial effusion worsening, the decision was to perform percutaneous coronary intervention (PCI) with a covered stent (Biotronik Papyrus 2.5 × 20 mm, 8 atm), with a good final result, with total occlusion of fistula.

Conclusions

At 1 month follow-up, the patient was asymptomatic for dyspnoea or chest pain, with a heart rate of 70 b.p.m. and a blood pressure of 130/80 mmHg. ECG showed no anomalies in ST-T tract.
262 An attractive endovascular strategy for combined—aneurysmal and stenotic—coronary artery disease
Authors: Vendrametto Fauzia , Pierri Alessandro , Barbisan Davide , Piazza Rita , Pavan Daniela , Sinagra Gianfranco
Published: December 2021

In patients undergoing coronary angiography the coexistence of aneurysmal and stenotic lesions in adjacent segments of the same epicardial vessel is uncommon. We describe a rare case of single-vessel coronary artery disease (CAD) in a 70-year-old male, presenting with progressive effort-induced angina of 3-months’ evolution. The coronary angiogram revealed a critical calcified stenosis in the context of diffuse ectasia affecting the right coronary artery (RCA). Our report focuses on a complex revascularization procedure using the self-expandable Carotid Wallstent. Highlighting the importance of a multidisciplinary approach, we provide an original and effective endovascular solution for an unusual pathological angiographic finding, which could be of potential interest for interventional cardiologists.
651 Prevention of contrast induced nephropathy with urine alkalinization: the final results of the TEATE study
Authors: Molisana Michela , Lombardi Marco , Genovesi Eugenio , Innocentiis Carlo De , Limbruno Ugo , Misuraca Leonardo , Moretti Luciano , Vito Luca Di , Renda Giulia , Zimarino Marco , Nicola Marta Di , Caterina Raffaele De
Published: December 2021

Aims

Contrast-induced acute kidney injury (CI-AKI) after coronary angiography and percutaneous interventions (PCI) impacts on hospitalization duration and mortality. Pre-procedural hydration is the sole strategy currently recommended for preventing CI-AKI. The role of sodium bicarbonate (SB) although attractive, since urine alkalinization suppresses the production of reactive oxygen species, is still controversial, and the optimal dosing to attain adequate urine alkalinization is still undefined. The PrevenTion of contrast-inducEd nephropathy with urine alkalinization (TEATE) study was a prospective 3-centre 3-arm single-blind randomized controlled trial testing the hypothesis that adequate urine alkalinization is associated with CI-AKI prevention. Secondary endpoints were the efficacy of SB vs. saline in achieving adequate urine alkalinization and reducing the incidence of CI-AKI compared with saline.

Methods and results

Patients candidate to coronary angiography and/or PCI with moderate-to-severe chronic kidney disease [eGFR of 15–60 ml/min/1.73 m2, by the Modification of Diet in Renal Disease Study equation (MDRD)] were randomly assigned to saline hydration (control), oral SB or i.v. SB. The study protocol was registered (ClinicalTrials.gov NCT02980003). We evaluated urinary pH at the time of hospitalization, immediately before coronary angiography and 24–48 h after angiography. According to urine pH immediately before the procedure, patients were divided in two groups above or below a pH cut-off of 6. We enrolled a total of 241 patients: 81 were randomly assigned to the control group, 82 to i.v. SB and 78 to oral SB. Patients achieving a urinary pH > 6 before angiography had a lower incidence of CI-AKI (46%) than patients with urinary pH ≤ 6 (54%) [OR = 0.48 (95% CI: 0.25–0.9), P = 0.023]. The number of patients with urine pH > 6 was higher in both the i.v. (71%) and the oral SB (65%) groups compared to the hydration-only group (44%, P = 0.004). We found however no difference in the incidence of CI-AKI in the three treatment arms (20% in hydration alone, 21% in oral SB group and 22% in i.v. SB group) (P = 0.94). Subgroup analyses according to basal urine pH and eGFR ranges failed to identify statistically significant differences in the development of CI-AKI according to treatment allocation.

Conclusions

Urinary pH before the administration of contrast medium is an inverse correlate of CI-AKI incidence, and SB is superior to hydration alone in achieving urinary alkalinization. Since, however, SB did not reduce the incidence of CI-AKI, we conclude that urinary pH is a marker and not a mediator of CI-AKI.
712 In-stent restenosis: how optical coherence tomography can make the difference
Authors: Ricci Sara , De Candia Gianfranco , Cadeddu Mauro , Lai Giorgio , Secchi Sara , Aste Francesca , Meloni Luigi , Montisci Roberta
Published: December 2021

Aims

Patient male, 38 years old, affected by hypercholesterolaemia, carotid atherosclerosis, in 2014 NSTEMI (bivascular coronary artery disease treated by angioplasty and implantation of a medicated stent in the ostial and proximal tract of the right coronary artery). In September 2021 the patient went to the emergency room of our hospital for chest pain, that comes during physical exertion, with a spontaneous regression. We performed blood tests that showed phase rise of the Hs-TNI (>25 000 ng/dl). The ECG showed lateral sub-endocardial ischemia and the transthoracic echocardiogram a slight reduction in ejection fraction with hypochinesia of the inferior and inferior-lateral wall. After collegial discussion, it was decided to perform a coronary angiography.

Methods and results

The coronary angiography showed the left coronary artery free from stenosis, with a collateral circle towards the right coronary; the right coronary showed an ostial and proximal critical in-stent restenosis with patency of the stent in the middle segment, total occlusion of the distal segment. It was decided to treat the right coronary. A guide wire was pushed into to the right coronary with difficulty and, after recanalization of the vessel, an optical coherence tomography (OCT) was performed. The OCT pointed out a homogeneous widespread neointima into the stent and an extraluminal fibrous-calcified plaque in the ostial proximal segment, which caused likely the stent under-expansion and then the stent fracture. We proceeded with angioplasty and stent implantation of the distal lesion. Due to the mechanism underlying critical in-stent restenosis (fracture of the stent) of the ostial proximal segment, we first proceed with a pre-dilatation of the lesion and then with a stent in stent implantation. Post-dilatation with a non-compliant balloon at high atm. Eventually, we found out a detail not visible before due to the ostial stenosis: the protrusion of some millimeters of the previously implanted stent in the ascending aorta; this was the cause of the difficulty in advancing the angioplasty material throughout the procedure. As a result, we had no complications.

Conclusions

Intracoronary imaging has stronger evidences to guide the percutaneous revascularization, especially for in-stent restenosis. Evaluation by OCT can highlight the mechanism of in-stent restenosis (biological causes/mechanical causes) and consequently it can guide the most appropriate method to perform percutaneous revascularization.
612 Comparison of two self-expandable supra-annular bioprosthesis: a propensity score-matched analysis
Authors: Sticchi Alessandro , Gallo Francesco , Marzo Vincenzo De , Won-keun Kim , 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

Limited data reported the comparison of bioprostheses for transcatheter aortic valve implantation (TAVI) among devices of supra-annular design. The aim of this study is to compare the clinical outcomes of the ACURATE neo and Evolut R/PRO valves for TAVI in a propensity score-matched analysis (PSM).

Methods and results

We performed a propensity score-matched analysis equalizing almost all the patient’s risk factors, anatomical and procedural characteristics, and assessing the predictive value of the remaining features. Our data were derived from a large, real-world, contemporary, multicentre, international, retrospective registry of 3862 consecutive patients undergoing TAVI using two different self-expandable supra-annular valves (Medtronic Evolut R/PRO and Boston ACURATE neo). We reached a matched population of 713 couples for each device group with a medium follow-up of 456.5 days. In the comparison of the clinical outcomes between the Evolut and the ACURATE patients, no difference occurred in mortality (9.8% vs. 9.0%, P = 0.650), heart failure hospitalization (9.6% vs. 6.0%, P = 0.076), myocardial infarction (0.7% vs. 0.4%, P = 0.718), stroke (2.4% vs. 1.4%, P = 0.239), major bleeding (3.3% vs. 3.4%, P = 1.000), vascular complications (13.7% vs. 10.9%, P = 0.126), endocarditis (1.1% vs. 0.6%, P = 0.568), sepsis (0.9% vs. 0.5%, P = 0.605), acute kidney injury (0.9% vs. 0.5%, P = 0.605), and new left bundle branch block (17% vs. 13.5%, P = 0.187). The only outcome with a significant difference between the groups was the need of pacemaker implantation in favour of the ACURATE valve (5.3% vs. 12.9% for the Evolut, P < 0.001).

Conclusions

In our PSM cohort, the comparison between the Evolut and the ACURATE valve showed no significant differences in the multiple outcomes evaluated, except for the rate of new pacemaker implantation. This data confirmed the recent literature, but it needs further dedicated investigation using the following devices generations.
374 Volume of contrast to creatinine clearance ratio predicts early mortality and AKI after TAVI
Authors: Venturi Gabriele , Scarsini Roberto , Pighi Michele , Sole Paolo Alberto Del , Mainardi Andrea , Ribichini Flavio
Published: December 2021

Aims

The volume of contrast to creatinine clearance ratio (CV/CrCl) is a useful indicator of the risk of acute kidney injury (AKI) in patients undergoing percutaneous interventional procedures. Association between CV/CrCl and adverse outcome after transcatheter aortic valve implantation (TAVI) was suggested but it is not well established.

Methods and results

A large retrospective multicentre cohort of 1381 patients treated with TAVI was analysed to assess the association between CV/CrCl and the risk of AKI and mortality at 90 days and one year after TAVI. Patients receiving renal replacement therapy at the time of TAVI were excluded. CV/CrCl was associated with the risk of AKI and 90 days mortality after TAVI after adjustment for age, sex, diabetes, baseline left ventricular function, baseline chronic kidney disease (CKD), previous myocardial infarction and peripheral vascular disease (HR: 1.16, 95% CI: 1.09–1.22, P < 0.0001). Importantly, CV/CrCl was associated with the adverse outcome independently from the presence of baseline CKD (p for interaction = 0.22). CV/CrCl was independently associated with the individual components of the composite primary outcome including AKI (OR: 1.18, 95% CI: 1.08–1.28, P < 0.0001) and 90 days mortality (HR: 1.90, 95% CI: 1.01–3.60, P = 0.047) after TAVI. AKI (HR: 1.94, 95% CI: 1.21–3.11, P = 0.006) but not CV/CrCl was associated with the risk of 1-year mortality after TAVI.

Conclusions

CV/CrCl is associated with excess renal damage and early mortality after TAVI. Procedural strategies to minimize the CV/CrCl during TAVI may improve early clinical outcomes in patients undergoing TAVI.
479 Safety and effectiveness of left atrial appendage occlusion in patients with chronic kidney disease
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

Left atrial appendage occlusion (LAAO) might be particularly attractive in chronic kidney disease (CKD) patients, owing to a high thromboembolic risk and an even higher risk of bleeding. We sought to evaluate the safety and effectiveness of LAAO in CKD patients.

Methods and results

A total of 1238 patients undergoing LAAO at six centres were enrolled. On the basis of kidney function, as assessed via the CKD-EPI formula, patients were classified in two groups. Group1 had a GFR value ≤60 ml/min/1.73 m2 (CKD stages 3a-b, 4, and 5), whereas Group2 had a function >60 ml/min/1.73 m2 (CKD stages 1 and 2). Predicted annual rates of TE or major bleeding events were compared to the annualized observed risk of the two populations. Compared to Group 2 (n = 720, 47.5% males), patients in Group 1 (n = 518, 86.5% males) were older (mean age: 78 ± 8 vs. 75 ± 8, P < 0.001), and were at higher risk (CHA2DS2-VASc: 4.7 ± 1.4 vs. 4.4 ± 1.4; HAS-BLED: 3.8 ± 1.1 vs. 3.2 ± 1.0; P < 0.001 for both). Procedural complications (within 7 days) were observed in 3.1% of patients in Group1 and 4.6% of those in Group2 (P = 0.18); of them, major procedural adverse events occurred in 10 patients of Group1 [1.9%; four gastrointestinal (GI) bleedings, four tamponades, one myocardial infarction, one retroperitoneal hematoma] and in 15 (2.1%; seven pericardial tamponades, five retroperitoneal hematomas, two strokes, and one GI bleeding) of Group2 (P = 0.84). During a mean follow-up of 11.5 ± 7 months (1183 pt/years), 10 stroke/TIA (1.9%) and 25 major bleeding events (4.8%; 18 GI and 7 intracranial) were observed in Group1. Rate of TE events was not statistically different between groups (1.9% vs. 2.6%; P = 0.41); major bleedings had a significantly higher incidence in Group 1 (4.8% vs. 2.4%, P = 0.02). Based on the estimated annual TE risk according to the CHA2DS2-VASc score (4.76% in Group1 and 4.51% in Group 2), the % risk reduction after LAAO was 57.5% and 38.8%, respectively. Based on the estimated annual major bleeding risk based on the HAS-BLED score (7.31% in Group1 and 5.39% in Group2), the % bleeding risk reduction was 30.9% and 54.2%.

Conclusions

LAAO is a safe and effective approach in CKD patients. Given the increased risk of bleeding and contraindications to oral anticoagulation, CKD patients might be good candidates for LAA occlusion.
628 Long-term clinical impact of permanent pacemaker implantation in patients undergoing transcatheter aortic valve intervention: a systematic review and meta-analysis
Authors: Zito Andrea , Princi Giuseppe , Lombardi Marco , Mario Domenico D’A , Vergallo Rocco , Aurigemma Cristina , Romagnoli Enrico , Pelargonio Gemma , Bruno Piergiorgio , Trani Carlo , Burzotta Francesco , Crea Filippo
Published: December 2021

Aims

As compared with surgery, transcatheter aortic valve implantation (TAVI) is associated with increased need for permanent pacemaker implantation (PPMI). The clinical impact of PPMI post-TAVI has not been fully established. To assess by an updated meta-analysis the clinical outcomes related to PPMI after TAVI at long-term (≥12 months) follow-up (LTF).

Methods and results

A comprehensive literature research was performed on PubMed and EMBASE. The primary endpoint was all-cause death. Secondary endpoints were rehospitalization for heart failure, stroke, and myocardial infarction. A subgroup analysis was performed according to Society of Thoracic Surgeon—Predicted Risk of Mortality (STS-PROM) score. A total of 31 studies were identified, providing data on 51 069 patients. The mean duration of follow-up was 22 months. At LTF, PPMI post-TAVI was associated with a higher risk of all-cause death [22.9% vs. 19.6%; risk ratio (RR), 1.18, 95% confidence interval (CI), 1.10–1.25; P < 0.001] and rehospitalization for heart failure (16.6% vs. 15.1%; RR, 1.32; 95% CI, 1.13–1.52; P < 0.001). In contrast, risks of stroke and myocardial infarction were not affected. Among the 20 studies that reported surgical risk, the association between PPMI and LTF all-cause death risk was statistically significant only in studies enrolling patients with high STS-PROM score (RR, 1.25; 95% CI, 1.12–1.40), although there was a similar trend in those at medium and low-risk.

Conclusions

Patients necessitating PPMI after TAVI have higher long-term risk of all-cause death and rehospitalization for heart failure as compared to those who do not receive PPMI. Thus, strategies aimed at reducing need for PPMI might improve survival after TAVI.
333 Phrenic nerve neuropathy discovered with cardiopulmonary exercise test in long-COVID-19 syndrome
Authors: Masè Marco , Carriere Cosimo , Tavcar Irena , Sinagra Gianfranco
Published: December 2021

Corona virus disease of 2019 (COVID19) is an ongoing global pandemic caused by SARS-CoV-2 virus. COVID-19 typically involves the respiratory tract with a wide spectrum of disease severity. Long-Covid19 syndrome refers to a series of symptoms that sometimes persist after COVID-19 infection. We describe a case of unilateral phrenic nerve palsy in a young woman with Long-COVID-19 syndrome. a 28-year-old woman admitted for COVID-19 presented persistent exertional dyspnoea. All the examinations performed were normal. At Cardiopulmonary exercise test (CPET) however, the ventilation plot was characterized by a lack of increase of the tidal volume compensated with a premature and continuous rise in respiratory frequency. Suspecting a ventilation abnormality, an electroneurography of the diaphragmatic nerves was conducted showing a right phrenic nerve palsy. Long-COVID-19 syndrome is a growing entity in clinical practice and dyspnoea is one of the most common symptoms. In this setting, phrenic nerve palsy should be ruled out, especially in patients with unexplained dyspnoea. CPET is a complete technique that assesses both pulmonary and cardiac performance. Since it might give important clues in the recognition of the cause of persistent symptoms after COVID-19 it should be extensively performed in these patients.
127 SARS-CoV-2 pandemic: post-lockdown subclinic cardiovascular events detected by 12-leads electrocardiogram at Emergency Department
Authors: Parato Vito Maurizio , D’Agostino Simone , Marcelli Stefano , Petrelli Giuseppina
Published: December 2021

Aims

Few data are available regarding changes in mitral regurgitation (MR) severity with guideline-directed medical therapy (GDMT) in heart failure (HF). We evaluated the evolution and impact of MR after GDMT in the BIOlogy Study to TAilored Treatment in Chronic Heart Failure (BIOSTAT-CHF).

Methods and results

A retrospective post hoc analysis was performed on HF patients from BIOSTAT-CHF with available data on MR status at baseline and at 9-month follow-up after GRMT optimization. The primary endpoint was a composite of all-cause death or HF hospitalization. Among 1022 patients with data at both time-points, 462 (45.2%) had moderate-severe MR at baseline and 360 (35.2%) had it at 9-month follow-up. Regression of moderate–severe MR from baseline to 9 months occurred in 192/462 patients (41.6%) and worsening from baseline to moderate–severe MR at 9 months occurred in 90/560 patients (16.1%). The presence of moderate–severe MR at 9 months, independent from baseline severity, was associated with an increased risk of the primary endpoint [unadjusted hazard ratio (HR), 2.03; 95% confidence interval (CI), 1.57–2.63; P < 0.001], also after adjusting for the BIOSTAT-CHF risk-prediction model (adjusted HR, 1.85; 95% CI, 1.43–2.39; P < 0.001). Younger age, LVEF ≥50% and treatment with higher ACEi/ARB doses were associated with a lower likelihood of moderate–severe MR at 9 months, whereas older age was the only predictor of worsening MR.

Conclusions

Among patients with HF undergoing GDMT optimization, ACEi/ARB up-titration and HFpEF were associated with MR improvement, and the presence of moderate–severe MR after GRMT was associated with worse outcome.
183 Small nucleolar RNA SNORD3A: a potential new biomarker and molecular player in heart failure
Authors: Paolillo Roberta , Schiattarella Giacomo Gabriele , D'Apice Stefania , Holley Christopher , Corte Alessandro Della , Bancone Ciro , Perrino Cinzia , Esposito Giovanni
Published: December 2021

Aims

Despite optimal therapy, heart failure (HF) remains a relentless and deadly disease. Given the relative inaccessibility of myocardial human tissues, identification of circulating biomarkers mirroring myocardial pathological signalling pathways, especially in peripheral blood mononuclear cells (PBMC) is expected to be extremely relevant. Small Nucleolar RNAs (snoRNAs) have been shown to play important roles in various cellular physiological processes. However, the connection between snoRNAs and pathological dysfunction in the heart or peripheral blood mononuclear cells (PBMC) is still poorly understood. To identify novel circulating PBMC biomarkers linked to myocardial dysfunction and HF.

Methods

Myocardial left ventricle (LV) samples and PBMC were obtained from patients affected by ischaemic HF (HF, n = 13) undergoing heart transplantation and control donors (CD, n = 7) and analysed by RNA sequencing analysis (RNASeq). SNORD3A expression levels in the different groups were evaluated by quantitative real-time PCR. HF was induced in 8-week-old wild type C57BL/6 mice by transverse aortic constriction (TAC). Sham-operated mice (sham) were used as controls. After 12-week-TAC (12w) or sham operation, mice were anesthetized, cardiac function was analysed by echocardiography, and cardiac/PBMC samples were collected after sacrifice. In order to test the role of SNORD3A in cardiomyocyte hypoxia, H9C2 cardiomyoblasts were transfected with SNORD3A-targeted antisense oligonucleotides (ASO) and cell survival was analysed.

Results

RNASeq analysis identified a small set of genes differentially expressed in the heart and PBMC from HF patients. Among these, SNORD3A was up-regulated in cardiac and PBMC samples from HF patients compared to CD (Figure 1A). Similarly, in murine HF induced by 12w TAC, SNORD3A levels were increased by rtPCR, both in the heart and PBMC (Figure 1B). SNORD3A expression levels were also significantly increased in H9C2 cells exposed to in vitro hypoxia (Figure 1C). Interestingly, H9C2 transfection with SNORD3A-specific ASO significantly reduced hypoxia-induced SNORD3A up-regulation and reduced hypoxia-induced cell death (Figure 1D).

Conclusions

In this study, we identify SNORD3A as a novel possible biomarker in human HF, similarly up-regulated in the heart and PBMC, induced by hypoxia in vitro and modulating cell survival.
138 Exercise haemodynamics in heart failure with preserved ejection fraction: a systematic review and meta-analysis
Authors: Baratto Claudia , Caravita Sergio , Soranna Davide , Dewachter Céline , Bondue Antoine , Zambon Antonella , Badano Luigi P. , Parati Gianfranco , Vachiéry Jean-Luc
Published: December 2021

Aims

Exercise right heart catheterization (RHC) is considered the gold-standard test to diagnose heart failure with preserved ejection fraction (HFpEF). However, exercise RHC is an insufficiently standardized technique, and current haemodynamic thresholds to define HFpEF are not universally accepted. We sought to describe the exercise haemodynamics profile of HFpEF cohorts reported in literature, as compared with control subjects.

Methods and results

We performed a systematic literature review until December 2020. Studies reporting pulmonary artery wedge pressure (PAWP) at rest and peak exercise were extracted. Summary estimates of all haemodynamic variables were evaluated, stratified according to body position (supine/upright exercise), and the PAWP/cardiac output (CO) slope during exercise was extrapolated. Twenty-eight studies were identified, providing data for 2230 HFpEF patients and 706 controls. At peak exercise, patients with HFpEF achieved higher PAWP [30 (29–31) vs. 16 (15–17) mmHg, P < 0.001] and mean right atrial pressure (P < 0.001) than controls. These differences persisted after adjustment for age, sex, body mass index, body position. However, peak PAWP values were highly heterogeneous among the cohorts, with a relative overlap with controls. PAWP/CO slope was steeper in HFpEF than in controls [3.81 (3.24–4.38) vs. 0.91 (0.24–1.58) mmHg/l/min, P < 0.001], even after adjustment for covariates (P = 0.020) (Figure).

Conclusions

The haemodynamic profile of HFpEF patients is consistent across studies and characterized by a higher left and right filling pressure at rest, magnified by physical exercise. Our analysis strongly suggests that PAWP/CO slope might allow for a more consistent identification of HFpEF, irrespective of body position. This variable likely overcomes the shortcomings of an isolated peak PAWP measurement, allowing for a more univocal identification of HFpEF in patients with unexplained dyspnoea.
347 From arterial hypertension to left ventricular hypertrophy and heart failure: role of cardiopulmonary exercise testing in heart failure with preserved ejection fraction
Authors: Borsi Leonardo , Lazzeroni Davide , Moderato Luca , Centorbi Claudio Stefano , Bini Matteo , Magnani Giulia , Brambilla Lorenzo , Piepoli Massimo , Cabassi Aderville , Ardissino Diego , Coruzzi Paolo , Niccoli Giampaolo
Published: December 2021

Aims

Arterial hypertension (AHT) represents the leading cause of heart failure (HF). A complex cardiovascular (CV) continuum of events leads to the progression from AHT to left ventricular hypertrophy (LVH), the hallmark of hypertensive heart (HH), towards heart failure with preserved ejection fraction (HFpEF) or reduced ejection fraction (HFrEF). Cardiopulmonary exercise testing (CPET) represents an important tool to evaluate HF patients (both with HFpEF and HFrEF) allowing quantification of functional capacity and mechanisms of dyspnoea as well as providing prognostic markers.

To

investigate CPET responses in AHT patients at various stages of disease progression from AHT to LVH and HF with preserved and reduced ejection fraction.

Methods and results

From a CPET registry of 1.397 consecutive subjects, 92 patients were selected (matched according to age, gender, BMI, CV risk factors, beta-blockers) and divided into four groups: 23 AHT patients without LVH, 23 HH patients, 23 HFpEF patients and 23 HFrEF. HFrEF were defined according to LV-EF values while HFpEF were defined according to the presence of NYHA Class ≥2 and HFA-PEFF Score. Mean age was 65 ± 10 years, mean BMI was 28.5 ± 5, male gender was prevalent 83% and 33% had diabetes. Both HFpEF and HFrEF showed lower cardiorespiratory fitness (peak VO2; P < 0.001), cardiovascular efficiency (VO2/Watt slope: P < 0.001), oxygen pulse (VO2/HR: P < 0.001), cardiac output (P < 0.001) and stroke volume (P < 0.001) at peak as well as lower chronotropic response (P < 0.001), ventilatory efficiency (VE/VCO2 slope: P < 0.001), and heart rate recovery (HRR: P = 0.004) compared with both AHT and HH groups. Interestingly, no differences between HFpEF and HFrEF have been found in all CPET data except for chronotropic response (using Tanaka equation), lower in HFpEF (37.5 ± 16.5 vs. 53.5 ± 20.5; P < 0.001) and ventilatory efficiency, lower in HFrEF (VE/VCO2 slope: 32 ± 5 vs. 37 ± 10; P < 0.001). Finally, adding functional capacity (peak VO2) data to ESC Criteria an improvement in HFpEF diagnosis accuracy was found, with 82% sensitivity and 90% specificity (AUC: 859—95% CI: 754–963; P < 0.0001).

Conclusions

Despite the intrinsic differences in ejection fraction, both HFpEF and HFrEF shares similar cardiopulmonary mechanisms and cardiovascular responses to exercise. CPET may represent a useful tool in order to identify and stratify hypertensive heart patients with HFpEF with high diagnostic accuracy.
270 Prediction of congestive state and prognosis in acute and chronic heart failure: the association between NT-proBNP and left atrial strain
Authors: Pastore Maria Concetta , Mandoli Giulia Elena , Ghionzoli Nicolò , D’Ascenzi Flavio , Cavigli Luna , Carrucola Chiara , Lisi Matteo , Focardi Marta , Valente Serafina , Patti Giuseppe , Mondillo Sergio , Cameli Matteo
Published: December 2021

Aims

In acute and chronic heart failure (HF), the relief of congestion is one of the pivotal elements to improve patient’s quality of life and prognosis. N-terminal pro-brain natriuretic peptide (NT-proBNP) is a well-known marker of cardiovascular (CV) congestion in HF, although with limited specificity. Peak atrial longitudinal strain (PALS) by speckle tracking echocardiography is emerging as an index of left ventricular (LV) filling pressure and prognosis in HF, however, its role as a marker of congestion should be further elucidated. The aim of our study was to determine the association between NT-proBNP and PALS in patients acute and chronic HF.

Methods and results

Patients hospitalized for de-novo or recurrent acute HF and patients with chronic HF referred to our echo-labs for follow-up evaluation were included in this retrospective study. Patients with missing data, previous cardiac surgery, heart transplant and/or left ventricular assist device implantation, non-feasible speckle tracking analysis were excluded. Clinical characteristics, laboratory examinations, transthoracic echocardiography data were collected. Speckle tracking analysis was performed offline on the echocardiographic records. Follow up data were obtained via electronical records or phone-calls. The primary clinical endpoint was a combination of all-cause death and HF hospitalization.

The overall study cohort included 388 patients (172 with chronic HF and 216 with chronic HF). Mean age was 65 ± 12, 37% were female. Most patients had reduced LV systolic function (mean LV ejection fraction = 30 ± 10%; mean LV global longitudinal strain = −8.3 ± 3.9%). Patients with acute HF presented higher values of NT-proBNP than those with chronic HF [median (interquartile range) = 6039 (2989–13 535) pg/ml vs. 544 (200–1533) pg/ml] and lower global PALS =10.4 (6.3–16.45)% vs. 15.6 (10.6–21)%. Global PALS showed a significant inverse correlation with NT-proBNP both in acute and chronic HF (all P < 0.001) and to be a significant predictor of NT-proBNP with linear regression analysis (R2 = 0.2; P < 0.001). During a median follow-up of 1 year, 98 patients reached the combined endpoint (49 all-cause deaths, 16 CV deaths, 62 HF hospitalizations). With ROC curves, both NT-proBNP and global PALS showed to be good predictors of the combined endpoint (AUC = 0.87and 0.82, respectively, Figure 1).

Conclusions

Global PALS is associated with NT-proBNP in acute and chronic HF and may be used as additional index of congestion to optimize therapeutic management in these patients. Both global PALS and NT-proBNP confirmed to be accurate prognostic markers in HF.
115 Prognostic significance of iron deficiency status in chronic inflammatory cardiomyopathy
Authors: Peretto Giovanni , Sala Simone , Camaschella Clara
Published: December 2021

Aims

Iron deficiency (ID) and associated anaemia (IDA) represent major comorbidities in chronic diseases. However, their prevalence and prognostic significance have never been investigated in chronic inflammatory cardiomyopathy (CIC).

Methods and results

This is a single-centre, prospective study, on consecutive adult patients with CIC (symptom onset > 3 months, endomyocardial biopsy-proven chronic myocarditis) undergoing iron status assessment (enrollment: January 2014–January 2019). ID was defined as either serum ferritin < 100 µg/l or transferrin saturation < 20%. IDA was defined as haemoglobin < 12 g/dl in women, < 13 g/dl in men. The primary endpoint was the occurrence of heart failure events (HFE) and/or arrhythmic events (AE). The study cohort is composed by 219 CIC patients (mean age 46 ± 15 y, 71% males, mean LVEF 50 ± 14%). Diagnosis was furtherly supported by cardiac magnetic resonance in 194 cases (89%). Baseline characteristics of patients with IDA (n = 48), ID (n = 70), and non-ID controls (n = 101) were largely comparable. We found that median in-hospital stay length was 13 days (IQR: 6–20) in IDA patients vs. 8 (IQR: 5–11) in the remaining groups (P = 0.002), and was inversely correlated with haemoglobin values on admission. By 3.9 ± 1.8 year prospective follow-up, events occurred in 86 patients (39%). For the composite endpoint, the only factors associated with events were ID status (HR: 6.3, 95% CI: 2.1–19.5, P = 0.001) and male gender (HR: 5.4, 95% CI: 1.2–24.9, P = 0.030). In detail, HFE occurred in 48 patients (40/118 IDA or ID vs. 8/101 controls, P < 0.001), and AE in 51 (34/118 IDA or ID vs. 17/101 controls, P = 0.039). All cardiac deaths (n = 7) occurred in ID or IDA patients (P = 0.016; n = 1 and 6, respectively).

Conclusions

ID and IDA are common among CIC patients, and may bare a negative prognostic value. Our findings suggest a careful evaluation of haemoglobin levels and iron status, and call for further investigation on both pathophysiological and prognostic implications of ID and IDA among CIC patients.
8 Acute pulmonary embolism or paroxysmal atrial fibrillation in patients with heart failure and preserved ejection fraction: prognostic implications
Authors: Tufano Nicola , Turris Salvatore De
Published: December 2021

Aims

Heart failure with preserved ejection fraction (HFpEF) is a growing public health problem. Its prevalence among heart failure patients increases over time, accounting for at least 50% of all hospital admissions for HF. Nevertheless, no single guideline exists for diagnosis or treatment for HFpEF, and older age or comorbidities are additional factors that confuse etiology and complicate prognosis. Moreover, there are few data regarding the consequences of HFpEF on other recurrent pathologies.

To assess the prognostic impact of a pre-existing HFpEF on patients ospidalized for intercurrent episodes of atrial fibrillation (AF) or acute pulmonary embolism (PE).

Methods and results

We performed a retrospective evaluation of 222 patients, consecutively hospitalized in our unit of Cardiology with a diagnosis of paroxysmal AF or acute PE, from January 2017 to December 2020. We recruited exclusively patients with normal cardiac function and HFpEF patients. Heart failure with reduced FEVS patients were excluded from the study. We have described for each patient the demographic and clinical characteristics, comorbidities, instrumental test results, and clinical outcomes. In order to assess, for each group, the relationship between patient characteristics and clinical outcomes, the Chi-square test or alternatively the Pearson–Spearman correlation coefficients were calculated.

The 222 patients studied had an average age of 73.7 years (min. 27, max: 94). 68 AF patients had pre-existing HFpEF, whereas AF patients without HF were 77. Patients with pre-existing HFpEF and newly-onset AF had a more advanced age (76.7 y vs. 72.9 y), and greater comorbidity (meanly 4 vs. 3) rather than AF patients without HFpEF. Moreover, percentage of converting arrhythmia were significantly higher in AF patients without HFpEF. Patients with acute PE and pre-existing HFpEF were 44, whereas PE patients without HF were 33. Acute PE patients with pre-existing HFpEF had older age, a prevalence for female sex, more comorbidities, an average longer hospitalizations, but no significantly different rates of severe complications (ictus, haemorrhagies, needs for ventilation, pulmonary infarction or deaths) rather than PE patients without HFpEF.

Conclusions

The patients with AF or PE and concomitant HFpEF that were hospitalized from January 2017 to December 2020, showed an average longer hospitalization, a lower percentage of converting arrhythmia, probably due to the older age and the greater comorbidity.
727 Circadian variations of platelet reactivity on Clopidogrel in patients treated with elective percutaneous coronary intervention
Authors: Circhetta Simone , Mangiacapra Fabio , Viscusi Michele Mattia , Paolucci Luca , De Luca Roberta , Nusca Annunziata , Melfi Rosetta , Ricottini Elisabetta , Ussia Gian Paolo , Grigioni Francesco
Published: December 2021

Aims

The potential diurnal variations of platelet reactivity in patients on clopidogrel treated with elective percutaneous coronary intervention (PCI) for stable coronary artery disease (CAD) are currently unknown.

Methods and results

We prospectively enrolled 15 patients with stable CAD treated PCI and on clopidogrel therapy for at least eight days. All patients received their maintenance 75-mg clopidogrel dose at 8 AM. Platelet reactivity was assessed with the Verifynow P2Y12 assay at three different time points (10 AM, 6 PM, and 6 AM). Platelet reactivity is expressed as P2Y12 reaction units (PRU) and PRU thresholds ≥208 and ≥240 were used to define high platelet reactivity (HPR). A significant heterogeneity in diurnal levels of platelet reactivity was found (P = 0.0004), with a peak occurring at the 6 AM assessment. In addition, at the 6 AM evaluation patients showed the highest prevalence of HPR (53.3% of patients with PRU ≥240, 66.7% of patients with PRU ≥208).

Conclusions

Platelet reactivity in patients with stable CAD treated with PCI and taking clopidogrel in the morning follows a circadian rhythm, thus suggesting that platelet inhibition may not be constant and sufficient throughout the day. Whether an evening or a bis in die administration of clopidogrel may result in a constant and more reliable antiplatelet inhibition, should be investigated in dedicated studies.
246 Air pollution and coronary plaque vulnerability and instability: an optical coherence tomography study
Authors: Montone Rocco Antonio , Camilli Massimiliano , Russo Michele , Vecchia Giulia La , Iannaccone Giulia , Rinaldi Riccardo , Gurgoglione Filippo , Crea Filippo , Niccoli Giampaolo
Published: December 2021

Aims

Air pollution is an emerging key player in determining the residual risk of coronary events. However, pathophysiological mechanisms linking air pollution and coronary events have been not adequately investigated. We aimed at assessing the relationship between exposure to air pollutants and mechanisms of coronary instability evaluated by optical coherence tomography (OCT) in patients with acute coronary syndrome (ACS).

Methods and results

ACS patients undergoing OCT imaging were retrospectively selected. Mechanism of culprit lesion instability was classified as plaque rupture (PR) or intact fibrous cap (IFC) by OCT, and the presence of macrophage infiltrates (MØI) and thin-cap fibroatheroma (TCFA) at the culprit site was also assessed. Based on each case’s home address, exposure to several pollutants was evaluated, including particulate matter 2.5 (PM2.5), particulate matter 10 (PM10), and carbon monoxide (CO). Only patients with >2 years of available data on air pollution exposure prior to ACS were enrolled. We included 126 patients [median age 67.0 years (55.5–76.0), 97 (77.0%) male]. Sixty-six patients (52.4%) had PR as mechanism of plaque instability. Patients with PR were exposed to significantly higher PM2.5 levels compared to IFC, and PM2.5 was independently associated with PR [odds ratio per unit = 1.194, 95% CI: (1.036–1.377), P = 0.015]. Moreover, exposure to higher levels of PM2.5 was independently associated with the presence of TCFA and of MØI at the culprit site. Interestingly, PM2.5, PM10, and CO levels were positively and significantly correlated with serum levels of C-reactive protein. ROC curves were constructed to assess the ability of PM2.5 to predict the presence of plaque rupture, TCFA or MØI. The AUC for PM2.5 to predict plaque rupture was 0.62 (95% CI: 0.52–0.71, P = 0.018), for TCFA was 0.71 (95% CI: 0.61–0.80, P <0.001) and for MØI was 0.80 (95% CI: 0.71–0.88, P <0.001). Using a PM2.5 cut-off value of 13.40 μg/m3, the sensitivity and specificity for MØI were 81% and 66%, respectively.

Conclusions

We provide novel insights into the missing link between air pollution and increased risk of coronary events. In particular, exposure to higher concentrations of air pollutants is a risk factor for vulnerable plaque features and for plaque rupture as mechanism of coronary instability mediated by systemic and local plaque inflammation. Of importance, the thresholds of air pollutants that predicted the presence of vulnerable plaque features are far lower than commonly accepted safety thresholds used to start preventive measures for public health, suggesting that further efforts are needed in order to reduce the adverse effects on the cardiovascular system.